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  • 51.
    Marseglia, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Italian National Council Research (CNR), Italy.
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Rizzuto, Debora
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ferrari, Camilla
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Florence, Italy.
    Whisstock, Christine
    Brocco, Enrico
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Crepaldi, Gaetano
    Maggi, Stefania
    Cognitive functioning among patients with diabetic foot2014In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 28, no 6, p. 863-868Article in journal (Refereed)
    Abstract [en]

    Aims: Using diabetic foot (OF) as an indicator of severe diabetes, we aimed to investigate the cognitive profile of OF patients and the relations between cognitive functioning and both diabetes complications and comorbidities. Methods: Dementia-free patients with DF aged 30-90 (n = 153) were assessed through medical records and a cognitive battery. Information on diabetes complications and comorbidities was collected via interview; glycated hemoglobin (HbA1c) was tested. Data were analyzed using robust logistic or quantile regression adjusted for potential confounders. Results: The mean Mini-Mental Examination (MMSE) score of patients was 24.6 (SD = 3.6), and 40% had global cognitive dysfunction (MMSE <= 24). Among elderly patients (aged >= 65), MMSE impairment was related to amputation (OR 3.59, 95% CI 1.07-12.11). Episodic memory impairment was associated with foot amputation (OR 4.13, 95% CI 1.11-1528) and microvascular complications (OR 9.68, 95% CI 1.67-56.06). Further, elderly patients with HbA1c <7% had increased odds of psychomotor slowness (OR 7.75, 95% CI 1.55-38.73) and abstract reasoning impairment (OR 4.49, 95% CI: 1.15-17.46). However, such significant associations were not shown in adult patients aged <65. Conclusion: Amputation, microvascular diseases and glycemic control were associated with impaired global cognitive function and its domains among patients aged >= 65.

  • 52. Martins, Andressa J.
    et al.
    Isherwood, Cheryl M.
    Vasconcelos, Suleima P.
    Lowden, Arne
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute.
    Skene, Debra J.
    Moreno, Claudia R. C.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute. University of São Paulo, Brazil.
    The effect of urbanization on sleep, sleep/wake routine, and metabolic health of residents in the Amazon region of Brazil2020In: Chronobiology International, ISSN 0742-0528, E-ISSN 1525-6073, Vol. 37, no 9-10, p. 1335-1343Article in journal (Refereed)
    Abstract [en]

    Studying communities with different levels of urbanization may further the understanding of risk factors underlying metabolic diseases. The present study is unique by comprising detailed assessment of sleep and activity, biological rhythms, and metabolic factors of men from the same geographical location and place of birth that reside in different, rural vs. town, stages of urbanization. Sleep patterns, activity, and metabolic indicators in two groups (rural, n = 22 and town/urban, n = 20) of men residing in an Amazonian community (Xapuri, Acre, Brazil) were compared. Sociodemographic, anthropometric, and metabolic variables - fasting glucose, insulin resistance, triglycerides, total HDL cholesterol, LDL cholesterol, and VLDL cholesterol - were assessed. Sleep patterns, light exposure, and physical activity levels were additionally assessed by actigraphy, plus daily activities were recorded in diaries for 10 days. Town/urban dwellers were found to have significantly higher body weight, fasting glucose, insulin levels, and insulin resistance than rural dwellers, whereas triglycerides levels were similar. Town/Urban dwellers had shorter sleep duration (p< .01) and later sleep onset and offset times (p= .01). Our findings show an association between stage of urbanization and presence of risk factors for metabolic disorders, such as overweight, insulin resistance, increased glucose levels, short sleep duration, and less natural light exposure during work times.

  • 53. Merlin, Jon
    et al.
    Sato, Masaaki
    Chia, Ling Yeong
    Fahey, Richard
    Pakzad, Mohsen
    Nowell, Cameron J.
    Summers, Roger J.
    Bengtsson, Tore
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Evans, Bronwyn A.
    Hutchinson, Dana S.
    Rosiglitazone and a beta(3)-Adrenoceptor Agonist Are Both Required for Functional Browning of White Adipocytes in Culture2018In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 9, article id 249Article in journal (Refereed)
    Abstract [en]

    The recruitment of brite (or beige) adipocytes has been advocated as a means to combat obesity, due to their ability to phenotypically resemble brown adipocytes (BA). Lineage studies indicate that brite adipocytes are formed by differentiation of precursor cells or by direct conversion of existing white adipocytes, depending on the adipose depot examined. We have systematically compared the gene expression profile and a functional output (oxygen consumption) in mouse adipocytes cultured from two contrasting depots, namely interscapular brown adipose tissue, and inguinal white adipose tissue (iWAT), following treatment with a known browning agent, the peroxisome proliferator-activated receptor (PPAR gamma) activator rosiglitazone. Prototypical BA readily express uncoupling protein (UCP)1, and upstream regulators including the beta(3)-adrenoceptor and transcription factors involved in energy homeostasis. Adipocytes from inguinal WAT display maximal UCP1 expression and mitochondrial uncoupling only when treated with a combination of the PPAR. activator rosiglitazone and a beta(3)-adrenoceptor agonist. In conclusion, brite adipocytes are fully activated only when a browning agent (rosiglitazone) and a thermogenic agent (beta(3)-adrenoceptor agonist) are added in combination. The presence of rosiglitazone throughout the 7-day culture period partially masks the effects of beta(3)-adrenoceptor signaling in inguinal white adipocyte cultures, whereas including rosiglitazone only for the first 3 days promotes robust beta(3)-adrenoceptor expression and provides an improved window for detection of beta(3)-adrenoceptor responses.

  • 54. Mota, Maria Carliana
    et al.
    Mendes Silva, Catarina
    Tibiletti Balieiro, Laura Cristina
    Makin Fahmy, Walid
    Marqueze, Elaine Cristina
    de Castro Moreno, Claudia Roberta
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Stress Research Institute. University of São Paulo, Brazil.
    Crispim, Cibele Aparecida
    Social Jetlag Is Associated With Impaired Metabolic Control During a 1-Year Follow-Up2021In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 12, article id 702769Article in journal (Refereed)
    Abstract [en]

    Previous studies have identified social jetlag (SJL) as a risk factor for non-communicable chronic diseases (NCCDs), but its association with metabolic control over time is unclear in the literature. Therefore, we examined the influence of SJL on metabolic parameters and blood pressure (BP) in patients with NCCDs over a 1-year follow-up. This retrospective, longitudinal study included 625 individuals (age: 56.0 +12.0 years; 76% female) with NCCDs [type 2 diabetes mellitus (TD2), systemic arterial hypertension (SHA), obesity, or dyslipidemia]. SJL was calculated based on the absolute difference between mid-sleep time on weekends and weekdays. Current metabolic parameters and BP of the patients were compared with data from a year prior. Generalized estimating equations (GEE) and multiple linear regression analyses were used to examine the association among SJL, metabolic parameters, and BP. Multiple linear regression analyses adjusted for confounders showed that SJL was positively associated with the delta difference of fasting glucose (β = 0.11, p = 0.02) and triglyceride levels (β = 0.09, p = 0.04) among all subjects with NCCDs, and with fasting glucose (β = 0.30, p = 0.0001) and triglyceride levels (β = 0.22, p = 0.01) in the TD2 group. GEE analysis demonstrated an isolated effect of SJL on diastolic BP. High SJL impaired clinical and metabolic control in individuals with NCCDs, leading to a worse profile after a 1-year follow-up, particularly among type II diabetics.

  • 55.
    Nedergaard, Jan
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    von Essen, Gabriella
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cannon, Barbara
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Brown adipose tissue: can it keep us slim? A discussion of the evidence for and against the existence of diet-induced thermogenesis in mice and men2023In: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 378, no 1888, article id 20220220Article, review/survey (Refereed)
    Abstract [en]

    The issue under discussion here is whether a decrease in the degree of UCP1 activity (and brown adipose tissue activity in general) could be a cause of obesity in humans. This possibility principally requires the existence of the phenomenon of diet-induced thermogenesis. Obesity could be a consequence of a reduced functionality of diet-induced thermogenesis. Experiments in mice indicate that diet-induced thermogenesis exists and is dependent on the presence of UCP1 and thus of brown adipose tissue activity. Accordingly, many (but not all) experiments indicate that in the absence of UCP1, mice become obese. Whether similar mechanisms exist in humans is still unknown. A series of studies have indicated a correlation between obesity and low brown adipose tissue activity, but it may be so that the obesity itself may influence the estimates of brown adipose tissue activity (generally glucose uptake), partly explaining the relationship. Estimates of brown adipose tissue catabolizing activity would seem to indicate that it may possess a capacity sufficient to help maintain body weight, and obesity would thus be aggravated in its absence.

  • 56.
    Nässel, Dick R.
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Kubrak, Olga I.
    Stockholm University, Faculty of Science, Department of Zoology.
    Liu, Yiting
    Stockholm University, Faculty of Science, Department of Zoology.
    Luo, Jiangnan
    Stockholm University, Faculty of Science, Department of Zoology.
    Lushchak, Oleh V.
    Stockholm University, Faculty of Science, Department of Zoology.
    Factors that regulate insulin producing cells and their output in Drosophila2013In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 4, article id 252Article, review/survey (Refereed)
    Abstract [en]

    Insulin-like peptides (ILPs) and growth factors (IGFs) not only regulate development, growth, reproduction, metabolism, stress resistance, and lifespan, but also certain behaviors and cognitive functions. ILPs, IGFs, their tyrosine kinase receptors and downstream signaling components have been largely conserved over animal evolution. Eight ILPs have been identified in Drosophila (DILP1-8) and they display cell and stage-specific expression patterns. Only one insulin receptor, dInR, is known in Drosophila and most other invertebrates. Nevertheless, the different DILPs are independently regulated transcriptionally and appear to have distinct functions, although some functional redundancy has been revealed. This review summarizes what is known about regulation of production and release of DILPs in Drosophila with focus on insulin signaling in the daily life of the fly. Under what conditions are DILP-producing cells (IPCs) activated and which factors have been identified in control of IPC activity in larvae and adult flies? The brain IPCs that produce DILP2, 3 and 5 are indirectly targeted by DILP6 and a leptin-like factor from the fat body, as well as directly by a few neurotransmitters and neuropeptides. Serotonin, octopamine, GABA, short neuropeptide F (sNPF), corazonin and tachykinin-related peptide have been identified in Drosophila as regulators of IPCs. The GABAergic cells that inhibit IPCs and DILP release are in turn targeted by a leptin-like peptide (unpaired 2) from the fat body, and the IPC-stimulating corazonin/sNPF neurons may be targeted by gut-derived peptides. We also discuss physiological conditions under which IPC activity may be regulated, including nutritional states, stress and diapause induction.

  • 57.
    Nässel, Dick R.
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Williams, Michael J.
    Cholecystokinin-like peptide (DSK) in Drosophila, not only for satiety signaling2014In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 5, article id 219Article, review/survey (Refereed)
    Abstract [en]

    Cholecystokinin (CCK) signaling appears well conserved over evolution. In Drosophila, the CCK-like sulfakinins (DSKs) regulate aspects of gut function, satiety and food ingestion, hyperactivity and aggression, as well as escape-related locomotion and synaptic plasticity during neuromuscular junction development. Activity in the DSK-producing neurons is regulated by octopamine. We discuss mechanisms behind CCK function in satiety, aggression, and locomotion in some detail and highlight similarities to mammalian CCK signaling.

  • 58. Oliveira, A.J.
    et al.
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Lopes, C.S.
    Monteiro Ponce de Leon, A.
    The influence of social relationships on obesity: sex differences in a longitudinal study2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 8, p. 1540-1547Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the effect of five dimensions of social relationships on obesity and potential sex differences in these associations.

    Design and Methods: This study used longitudinal data from the Swedish Level of Living Surveys (LNU) in 1991 and 2000. The sample included 3,586 individuals. The dimensions of social relationships examined in this study include emotional support, frequency of visiting friends, marital status, marital status changes, and a Social Relationships Index (SRI). Obesity status was based on BMI (kg/m(2)) and calculated with self-reported measurements. The association between social relationships and the incidence of obesity after 9 years of follow-up was evaluated through Poisson regressions.Results: After controlling for confounders, we found that the lack of emotional support (RR = 1.98; 95% CI, 1.1-4.6) influenced the incidence of obesity among men. In addition, men with the lowest levels of SRI (RR = 2.22; 95% CI, 1.1-4.4) had an increased risk of being obese. Among women, SRI was not significantly associated with obesity. Women who changed their marital status from married to unmarried had lower risk of obesity (RR = 0.39; 95% CI, 0.2-0.9).

    Conclusions: This study provides evidence for the effect of social relationships on the incidence of obesity, with significant differences by sex.

  • 59.
    Olsson, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Grill, Valdemar
    Midthjell, Kristian
    Ahlbom, Anders
    Andersson, Tomas
    Carlsson, Sofia
    Mortality in Adult-Onset Autoimmune Diabetes Is Associated With Poor Glycemic Control Results from the HUNT Study2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 12, p. 3971-3978Article in journal (Refereed)
    Abstract [en]

    OBJECTIVEKnowledge on mortality in autoimmune diabetes with adult onset is limited. We compared mortality in adult-onset autoimmune diabetes and type 2 diabetes, taking into account metabolic risk factors, HbA(1c), lifestyle, and socioeconomic factors.RESEARCH DESIGN AND METHODSParticipants of the population-based HUNT2 Study (second survey of the Norwegian HelseUndersOkelsen i Nord-TrOndelag Study; n = 64,264) were followed up prospectively for mortality in the Cause of Death Registry (1995-2009). Diabetes with onset 35 years was classified as autoimmune diabetes in adults if anti-GAD was positive (n = 208) and as type 2 diabetes if anti-GAD was negative (n = 2,425). Hazard ratios (HRs) of mortality from all-causes, cardiovascular disease (CVD), and ischemic heart disease (IHD) were calculated using the Cox proportional hazards model.RESULTSPrevalence of the metabolic syndrome was lower in autoimmune diabetes than in type 2 diabetes (55 vs. 77%, P < 0.001). Still, autoimmune diabetes was associated with an increased risks of mortality from all-causes (HR 1.55 [95% CI 1.25-1.92]), CVD (1.87 [1.40-2.48]), and IHD (2.39 [1.57-3.64]), equally high as in type 2 diabetes in analyses where individuals without diabetes were used as the reference group. The increased risk was not explained by overweight, lifestyle, socioeconomic position, or presence of the metabolic syndrome. Excess mortality was primarily observed in individuals with elevated HbA(1c).CONCLUSIONSMortality in autoimmune diabetes was as high as in type 2 diabetes, despite a more favorable baseline metabolic risk profile. Excess risk was associated with poor glycemic control. The results from this study, the largest so far on mortality in autoimmune diabetes in adults, underscore the importance of optimal treatment modalities to improve survival in adult-onset autoimmune diabetes.

  • 60. Ost, Mario
    et al.
    Igual Gil, Carla
    Coleman, Verena
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Efstathiou, Sotirios
    Vidic, Veronika
    Weyers, Miriam
    Klaus, Susanne
    Muscle-derived GDF15 drives diurnal anorexia and systemic metabolic remodeling during mitochondrial stress2020In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 21, no 3, article id e48804Article in journal (Refereed)
    Abstract [en]

    Mitochondrial dysfunction promotes metabolic stress responses in a cell-autonomous as well as organismal manner. The wasting hormone growth differentiation factor 15 (GDF15) is recognized as a biomarker of mitochondrial disorders, but its pathophysiological function remains elusive. To test the hypothesis that GDF15 is fundamental to the metabolic stress response during mitochondrial dysfunction, we investigated transgenic mice (Ucp1-TG) with compromised muscle-specific mitochondrial OXPHOS capacity via respiratory uncoupling. Ucp1-TG mice show a skeletal muscle-specific induction and diurnal variation of GDF15 as a myokine. Remarkably, genetic loss of GDF15 in Ucp1-TG mice does not affect muscle wasting or transcriptional cell-autonomous stress response but promotes a progressive increase in body fat mass. Furthermore, muscle mitochondrial stress-induced systemic metabolic flexibility, insulin sensitivity, and white adipose tissue browning are fully abolished in the absence of GDF15. Mechanistically, we uncovered a GDF15-dependent daytime-restricted anorexia, whereas GDF15 is unable to suppress food intake at night. Altogether, our evidence suggests a novel diurnal action and key pathophysiological role of mitochondrial stress-induced GDF15 in the regulation of systemic energy metabolism.

  • 61. Ovchinnikov, Vladimir Y.
    et al.
    Kashina, Elena V.
    Mordvinov, Viatcheslav A.
    Fromm, Bastian
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    EV-transported microRNAs of Schistosoma mansoni and Fasciola hepatica: Potential targets in definitive hosts2020In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 85, article id 104528Article in journal (Refereed)
    Abstract [en]

    Trematodes are widespread parasitic flatworms that significantly affect mankind either directly as human parasites, or indirectly via the infection of livestock and the related economic damage. The two most important trematode taxa are the blood flukes Schistosoma and the liver flukes Fasciola, but detection and differentiation of these parasites remains a challenge. Recently, microRNAs (miRNAs) were described from extracellular vesicles (EV) for both parasites secreted into respective hosts. These molecules have been proposed as mediators of parasite-host communication, and potential biomarkers for the detection of parasitic infections from host blood. Our aim here was to study similarities and differences in the miRNA complements of Schistosoma mansoni and Fasciola hepatica, EV-load in particular, to predict their targets and potential functions in the parasite-host interaction. We reanalyzed the known miRNA complements of S. mansoni and F. hepatica and found 16 and 4 previously overlooked, but deeply conserved miRNAs, respectively, further moving their complements closer together. We found distinct miRNA enrichment patterns in EVs both showing high levels of flatworm miRNAs with potential for the detection of an infection from blood. Two miRNAs of the protostome specific MIR-71 and MIR-277 families were highly expressed in EVs and could, therefore, have potential as biomarkers for trematode infection. Curiously, we identified nucleotide differences in the sequence of Mir-277-P2 between S. mansoni and F. hepatica that hold great promise for the distinction of both parasites. To test whether the EV-miRNAs of S. mansoni and F. hepatica could be modulating the expression of host genes, we predicted miRNA targets in 321 human and cattle messenger RNAs that overlapped between both hosts. Of several predicted targets, wnt signaling pathway genes stood out and their suppression likely leads to changes in the glucose concentration in host blood and the reduction of inflammatory and immune responses.

  • 62. Pekkala, Timo
    et al.
    Hall, Anette
    Mangialasche, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden.
    Kemppainen, Nina
    Mecocci, Patrizia
    Ngandu, Tiia
    Rinne, Juha O.
    Soininen, Hilkka
    Tuomilehto, Jaakko
    Kivipelto, Miia
    Solomon, Alina
    Association of Peripheral Insulin Resistance and Other Markers of Type 2 Diabetes Mellitus with Brain Amyloid Deposition in Healthy Individuals at Risk of Dementia2020In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 76, no 4, p. 1243-1248Article in journal (Refereed)
    Abstract [en]

    We explored the association of type 2 diabetes related blood markers with brain amyloid accumulation on PiB-PET scans in 41 participants from the FINGER PET sub-study. We built logistic regression models for brain amyloid status with12 plasma markers of glucose and lipid metabolism, controlled for diabetes and APOE ɛ4 carrier status. Lower levels of insulin, insulin resistance index (HOMA-IR), C-peptide, and plasminogen activator (PAI-1) were associated with amyloid positive status, although the results were not significant after adjusting for multiple testing. None of the models found evidence for associations between amyloid status and fasting glucose or HbA1c.

  • 63. Pettersson-Klein, A. T.
    et al.
    Izadi, M.
    Ferreira, D. M. S.
    Cervenka, I.
    Correia, J. C.
    Martinez-Redondo, V.
    Southern, M.
    Cameron, M.
    Kamenecka, T.
    Agudelo, L. Z.
    Porsmyr-Palmertz, M.
    Martens, Ulf
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Lundgren, Bo
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Otrocka, M.
    Jenmalm-Jensen, A.
    Griffin, P. R.
    Ruas, J. L.
    Small molecule PGC-1 alpha 1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration2018In: Molecular metabolism, ISSN 2212-8778, Vol. 9, p. 28-42Article in journal (Refereed)
    Abstract [en]

    Objective: The peroxisome proliferator-activated receptor-gamma coactivator-1 alpha 1 (PGC-1 alpha 1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1 alpha 1 activation is potentially beneficial for systemic metabolism. Pharmacological PGC-1 alpha 1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-1 alpha 1 is a transcriptional coactivator with no known ligand-binding properties. While, PGC-1 alpha 1 activation is regulated by several mechanisms, protein stabilization is a crucial limiting step due to its short half-life under unstimulated conditions.

    Methods: We designed a cell-based high-throughput screening system to identify PGC-1 alpha 1 protein stabilizers. Positive hits were tested for their ability to induce endogenous PGC-1 alpha 1 protein accumulation and activate target gene expression in brown adipocytes. Select compounds were analyzed for their effects on global gene expression and cellular respiration in adipocytes.

    Results: Among 7,040 compounds screened, we highlight four small molecules with high activity as measured by: PGC-1 alpha 1 protein accumulation, target gene expression, and uncoupled mitochondrial respiration in brown adipocytes.

    Conclusions: We identify compounds that induce PGC-1 alpha 1 protein accumulation and show that this increases uncoupled respiration in brown adipocytes. This screening platform establishes the foundation for a new class of therapeutics with potential use in obesity and associated disorders.

  • 64. Qi, Xiuying
    et al.
    Sun, Jing
    Wang, Jing
    Wang, Peizhong Peter
    Xu, Zhongliang
    Murphy, Madonna
    Jia, Junting
    Wang, Jianhua
    Xie, Yun
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Prevalence and Correlates of Latent Autoimmune Diabetes in Adults in Tianjin, China A population-based cross-sectional study2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 1, p. 66-70Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Data on latent autoimmune diabetes in adults (LADA) from population-based studies are sparse. We sought to investigate the prevalence and correlates of LADA. RESEARCH DESIGN AND METHODS: A total of 8,109 participants, who were aged >= 15 years and living in Tianjin, China, were assessed to identify individuals with type 2 diabetes (American Diabetes Association Criteria, 1997) and further to detect patients with LADA. LADA was ascertained by 1) the presence of type 2 diabetes and age >= 35 years, 2) the lack of a requirement for insulin at least 6 months after the diagnosis of type 2 diabetes, and 3) serum GAD antibody positivity. Data were analyzed using multinomial logistic regression with adjustment for potential confounders. RESULTS: Of all participants, 498 (6.1%) were patients with type 2 diabetes. Of them, 46 (9.2%) were found to have LADA. The prevalence of LADA was 0.6% (46 of 8,109), and tended to increase with age up to 50-59 years in all participants. The odds ratios (95% CI) of LADA related to hypertension, family history of diabetes, waist-to-hip ratio >= 0.85, and major stressful events were 1.93 (1.02-3.65), 17.59 (9.08-34.06), 5.37 (2.31-12.49), and 4.09 (1.75-9.52), respectively. CONCLUSIONS: The prevalence of LADA is similar to 9% in patients with type 2 diabetes. Hypertension, family history of diabetes, central obesity, and major stressful events may be associated with the occurrence of LADA.

  • 65.
    Rinde, Mia
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Kupferschmidt, Natalia
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Iqbal, Muhammad Naeem
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Robert-Nicoud, Ghislaine
    Johnston, Eric V.
    Lindgren, Maria
    Bengtsson, Tore
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mesoporous silica with precisely controlled pores reduces food efficiency and suppresses weight gain in mice2020In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 15, no 2, p. 131-144Article in journal (Refereed)
    Abstract [en]

    Aim: Obesity is a risk factor for cardiovascular disease and diabetes. We aimed to elucidate the effects of distinct mesoporous silica particles (MSPs) supplemented in food on metabolic parameters in obesity. Materials & methods: MSPs with precisely controlled pore size were synthesized, characterized and compared with a control in a C57Bl/6 mouse diet-induced obesity model, studying weight, adiposity, metabolic regulation and food efficiency. Results: The most effective MSPs reduced adipose tissue formation to 6.5 +/- 0.5 g compared with 9.4 +/- 1.2 g, leptin levels nearly halved from 32.8 +/- 7.4 to 16.9 +/- 1.9 ng/ml and a 33% reduction of food efficiency. Control MSP showed no effects. Conclusion: Results demonstrate potential of distinct MSPs to improve metabolic risk factors. Further studies investigating mechanism of action and confirming human safety are needed.

  • 66. Robson-Doucette, Christine A.
    et al.
    Sultan, Sobia
    Allister, Emma M.
    Wikström, Jakob D.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Koshkin, Vasilij
    Bhatacharjee, Alpana
    Prentice, Kacey J.
    Sereda, Samuel B.
    Shirihai, Orian S.
    Wheeler, Michael B.
    beta-Cell Uncoupling Protein 2 Regulates Reactive Oxygen Species Production, Which Influences Both Insulin and Glucagon Secretion2011In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, no 11, p. 2710-2719Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-The role of uncoupling protein 2 (UCP2) in pancreatic beta-cells is highly debated, partly because of the broad tissue distribution of UCP2 and thus limitations of whole-body UCP2 knockout mouse models. To investigate the function of UCP2 in the beta-cell, beta-cell-specific UCP2 knockout mice (UCP2BKO) were generated and characterized. RESEARCH DESIGN AND METHODS-UCP2BKO mice were generated by crossing loxUCP2 mice with mice expressing rat insulin promoter-driven Cre recombinase. Several in vitro and in vivo parameters were measured, including respiration rate, mitochondrial membrane potential, islet ATP content, reactive oxygen species (ROS) levels, glucose-stimulated insulin secretion (GSIS), glucagon secretion, glucose and insulin tolerance, and plasma hormone levels. RESULTS-UCP2BKO beta-cells displayed mildly increased glucose-induced mitochondrial membrane hyperpolarization but unchanged rates of uncoupled respiration and islet ATP content. UCP2BKO islets had elevated intracellular ROS levels that associated with enhanced GSIS. Surprisingly, UCP2BKO mice were glucose-intolerant, showing greater alpha-cell area, higher islet glucagon content, and aberrant ROS-dependent glucagon secretion under high glucose conditions. CONCLUSIONS-Using a novel beta-cell-specific UCP2K0 mouse model, we have shed light on UCP2 function in primary beta-cells. UCP2 does not behave as a classical metabolic uncoupler in the beta-cell, but has a more prominent role in the regulation of intracellular ROS levels that contribute to GSIS amplification. In addition, beta-cell UCP2 contributes to the regulation of intraislet ROS signals that mediate changes in alpha-cell morphology and glucagon secretion. Diabetes 60:2710-2719, 2011

  • 67. Roos, Elin
    et al.
    Wärmländer, Sebastian K. T. S.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. UCLA, USA.
    Meyer, Jeremy
    Sholts, Sabrina B.
    Jarvet, Jüri
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. The National Institute of Chemical Physics and Biophysics, Estonia.
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Roos, Per M.
    Amyotrophic Lateral Sclerosis After Exposure to Manganese from Traditional Medicine Procedures in Kenya2021In: Biological Trace Element Research, ISSN 0163-4984, E-ISSN 1559-0720, Vol. 199, p. 3618-3624Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron loss and widespread muscular atrophy. Despite intensive investigations on genetic and environmental factors, the cause of ALS remains unknown. Recent data suggest a role for metal exposures in ALS causation. In this study we present a patient who developed ALS after a traditional medical procedure in Kenya. The procedure involved insertion of a black metal powder into several subcutaneous cuts in the lower back. Four months later, general muscle weakness developed. Clinical and electrophysiological examinations detected widespread denervation consistent with ALS. The patient died from respiratory failure less than a year after the procedure. Scanning electron microscopy and X-ray diffraction analyses identified the black powder as potassium permanganate (KMnO4). A causative relationship between the systemic exposure to KMnO4 and ALS development can be suspected, especially as manganese is a well-known neurotoxicant previously found to be elevated in cerebrospinal fluid from ALS patients. Manganese neurotoxicity and exposure routes conveying this toxicity deserve further attention.

  • 68.
    Sato, Masaaki
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Monash University, Australia.
    Dehvari, Nodi
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Öberg, Anette I.
    Dallner, Olof S.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. The Rockefeller University, USA.
    Sandström, Anna L.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Olsen, Jessica M.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Csikasz, Robert I.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Summers, Roger J.
    Hutchinson, Dana S.
    Bengtsson, Tore
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 12, p. 4115-4129Article in journal (Refereed)
    Abstract [en]

    There is an increasing worldwide epidemic of type 2 diabetes that poses major health problems. We have identified a novel physiological system that increases glucose uptake in skeletal muscle but not in white adipocytes. Activation of this system improves glucose tolerance in Goto-Kakizaki rats or mice fed a high-fat diet, which are established models for type 2 diabetes. The pathway involves activation of β2-adrenoceptors that increase cAMP levels and activate cAMP-dependent protein kinase, which phosphorylates mammalian target of rapamycin complex 2 (mTORC2) at S2481. The active mTORC2 causes translocation of GLUT4 to the plasma membrane and glucose uptake without the involvement of Akt or AS160. Stimulation of glucose uptake into skeletal muscle after activation of the sympathetic nervous system is likely to be of high physiological relevance because mTORC2 activation was observed at the cellular, tissue, and whole-animal level in rodent and human systems. This signaling pathway provides new opportunities for the treatment of type 2 diabetes.

  • 69. Scott, Robert A.
    et al.
    Scott, Laura J.
    Maegi, Reedik
    Marullo, Letizia
    Gaulton, Kyle J.
    Kaakinen, Marika
    Pervjakova, Natalia
    Pers, Tune H.
    Johnson, Andrew D.
    Eicher, John D.
    Jackson, Anne U.
    Ferreira, Teresa
    Lee, Yeji
    Ma, Clement
    Steinthorsdottir, Valgerdur
    Thorleifsson, Gudmar
    Qi, Lu
    Van Zuydam, Natalie R.
    Mahajan, Anubha
    Chen, Han
    Almgren, Peter
    Voight, Ben F.
    Grallert, Harald
    Mueller-Nurasyid, Martina
    Ried, Janina S.
    Rayner, Nigel W.
    Robertson, Neil
    Karssen, Lennart C.
    Van Leeuwen, Elisabeth M.
    Willems, Sara M.
    Fuchsberger, Christian
    Kwan, Phoenix
    Teslovich, Tanya M.
    Chanda, Pritam
    Li, Man
    Lu, Yingchang
    Dina, Christian
    Thuillier, Dorothee
    Yengo, Loic
    Jiang, Longda
    Sparso, Thomas
    Kestler, Hans A.
    Chheda, Himanshu
    Eisele, Lewin
    Gustafsson, Stefan
    Frånberg, Mattias
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA). Stockholm University, Science for Life Laboratory (SciLifeLab).
    Strawbridge, Rona J.
    Benediktsson, Rafn
    Hreidarsson, Astradur B.
    Kong, Augustine
    Sigurdsson, Gunnar
    Kerrison, Nicola D.
    Luan, Jian'an
    Liang, Liming
    Meitinger, Thomas
    Roden, Michael
    Thorand, Barbara
    Esko, Tonu
    Mihailov, Evelin
    Fox, Caroline
    Liu, Ching-Ti
    Rybin, Denis
    Isomaa, Bo
    Lyssenko, Valeriya
    Tuomi, Tiinamaija
    Couper, David J.
    Pankow, James S.
    Grarup, Niels
    Have, Christian T.
    Jorgensen, Marit E.
    Jorgensen, Torben
    Linneberg, Allan
    Cornelis, Marilyn C.
    Van Dam, Rob M.
    Hunter, David J.
    Kraft, Peter
    Sun, Qi
    Edkins, Sarah
    Owen, Katharine R.
    Perry, John R. B.
    Wood, Andrew R.
    Zeggini, Eleftheria
    Tajes-Fernandes, Juan
    Abecasis, Goncalo R.
    Bonnycastle, Lori L.
    Chines, Peter S.
    Stringham, Heather M.
    Koistinen, Heikki A.
    Kinnunen, Leena
    Sennblad, Bengt
    Muehleisen, Thomas W.
    Noethen, Markus M.
    Pechlivanis, Sonali
    Baldassarre, Damiano
    Gertow, Karl
    Humphries, Steve E.
    Tremoli, Elena
    Klopp, Norman
    Meyer, Julia
    Steinbach, Gerald
    Wennauer, Roman
    Eriksson, Johan G.
    Mannisto, Satu
    Peltonen, Leena
    Tikkanen, Emmi
    Charpentier, Guillaume
    Eury, Elodie
    Lobbens, Stephane
    Gigante, Bruna
    Leander, Karin
    McLeod, Olga
    Bottinger, Erwin P.
    Gottesman, Omri
    Ruderfer, Douglas
    Blueher, Matthias
    Kovacs, Peter
    Tonjes, Anke
    Maruthur, Nisa M.
    Scapoli, Chiara
    Erbel, Raimund
    Joeckel, Karl-Heinz
    Moebus, Susanne
    De Faire, Ulf
    Hamsten, Anders
    Stumvoll, Michael
    Deloukas, Panagiotis
    Donnelly, Peter J.
    Frayling, Timothy M.
    Hattersley, Andrew T.
    Ripatti, Samuli
    Salomaa, Veikko
    Pedersen, Nancy L.
    Boehm, Bernhard O.
    Bergman, Richard N.
    Collins, Francis S.
    Mohlke, Karen L.
    Tuomilehto, Jaakko
    Hansen, Torben
    Pedersen, Oluf
    Barroso, Ines
    Lannfelt, Lars
    Ingelsson, Erik
    Lind, Lars
    Lindgren, Cecilia M.
    Cauchi, Stephane
    Froguel, Philippe
    Loos, Ruth J. F.
    Balkau, Beverley
    Boeing, Heiner
    Franks, Paul W.
    Gurrea, Aurelio Barricarte
    Palli, Domenico
    Van der Schouw, Yvonne T.
    Altshuler, David
    Groop, Leif C.
    Langenberg, Claudia
    Wareham, Nicholas J.
    Sijbrands, Eric
    Van Duijn, Cornelia M.
    Florez, Jose C.
    Meigs, James B.
    Boerwinkle, Eric
    Gieger, Christian
    Strauch, Konstantin
    Metspalu, Andres
    Morris, Andrew D.
    Palmer, Colin N. A.
    Hu, Frank B.
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    Dupuis, Josee
    Morris, Andrew P.
    Boehnke, Michael
    McCarthy, Mark I.
    Prokopenko, Inga
    An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans2017In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, no 11, p. 2888-2902Article in journal (Refereed)
    Abstract [en]

    To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.

  • 70.
    Shang, Ying
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Vetrano, Davide Liborio
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Fondazione Policlinico “A. Gemelli” IRCC, Italy; Catholic University of Rome, Italy.
    Dove, Abigail
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Welmer, Anna-Karin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden; Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden.
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Not Only Diabetes but Also Prediabetes Leads to Functional Decline and Disability in Older Adults2021In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 44, no 3, p. 690-698Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Diabetes is linked to functional decline, but the impact of prediabetes on physical function is unknown. We aimed to examine and compare the impact of prediabetes and diabetes on physical function and disability progression and to explore whether cardiovascular diseases (CVDs) mediate these associations.

    RESEARCH DESIGN AND METHODS A cohort of 2,013 participants aged >= 60 from the Swedish National Study on Aging and Care in Kungsholmen, an ongoing population-based longitudinal study, was monitored for up to 12 years. Physical function was measured with chair stand (s) and walking speed (m/s) tests, and disability was measured by summing the numbers of impaired basic and instrumental activities of daily living. Diabetes was identified through medical examinations or clinical records, medication use, or glycated hemoglobin (HbA(1c)) >= 6.5%. Prediabetes was defined as HbA(1c) >= 5.7-6.4% in participants free of diabetes. CVDs were ascertained through clinical examinations and the National Patient Register. Data were analyzed using mixed-effect models and mediation models.

    RESULTS At baseline, 650 (32.3%) had prediabetes and 151 had diabetes (7.5%). In multiadjusted mixed-effect models, prediabetes was associated with an increased chair stand time (beta 0.33, 95% CI 0.05-0.61), a decreased walking speed (beta -0.006, 95% CI -0.010 to -0.002), and an accelerated disability progression (beta 0.05, 95% CI 0.01-0.08), even after controlling for the future development of diabetes. Diabetes led to faster functional decline than prediabetes. In mediation analyses, CVDs mediated 7.1%, 7.8%, and 20.9% of the associations between prediabetes and chair stand, walking speed, and disability progression, respectively.

    CONCLUSIONS Prediabetes, in addition to diabetes, is associated with faster functional decline and disability, independent of the future development of diabetes. This association may be in part mediated by CVDs.

  • 71.
    Shang, Ying
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Marseglia, Anna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Welmer, Anna-Karin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska University Hospital, Sweden.
    Wang, Rui
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Natural history of prediabetes in older adults from a population-based longitudinal study2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, no 3, p. 326-340Article in journal (Refereed)
    Abstract [en]

    Background. The natural history of prediabetes in older adults remains unknown.

    Objectives. To assess the rate at which prediabetes progresses to diabetes, leads to death or reverts to normoglycaemia in older adults and to identify prognostic factors related to different outcomes of prediabetes.

    Methods. In the Swedish National Study on Aging and Care-Kungsholmen, 2575 diabetes-free participants aged >= 60 years were examined at baseline and followed for up to 12 years. At each wave, diabetes was diagnosed via medical examination, antidiabetic drug use, medical records or glycated haemoglobin (HbA1c) >= 6.5%. Prediabetes was defined as HbA1c >= 5.7% and normoglycaemia as HbA1c <5.7% in diabetes-free participants. Data were analysed with multinomial logistic regression.

    Results. At baseline, 918 (36%) individuals had prediabetes. Of them, 204 (22%) reverted to normoglycaemia (3.4/100 person-years, 95% CI 5.6-12.3), 119 (13%) developed diabetes (2.0/100 person-years, 95% CI 1.7-2.4) and 215 (23%) died (13.0/100 person-years, 95% CI 11.4-14.9) during the 12-year follow-up. The rates of reversion, progression and mortality were higher in the first 6-year than in the second 6-year follow-up, albeit not statistically significant. Lower systolic blood pressure (SBP), absence of heart diseases and weight loss promoted the reversion from prediabetes to normoglycaemia, whilst obesity accelerated its progression to diabetes.

    Conclusions. During a 12-year follow-up, most of older adults with prediabetes remained stable or reverted to normoglycaemia, whereas only one-third developed diabetes or died. Lower SBP, no heart diseases and weight management may promote reversion to normoglycaemia, suggesting possible strategies for achieving normoglycaemia in older adults with prediabetes.

  • 72. Snoek, Frank J.
    et al.
    Anarte-Ortiz, Maria Teresa
    Anderbro, Therese
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Clinical psychology.
    Cyranka, Katarzyna
    Hendrieckx, Christel
    Hermanns, Norbert
    Indelicato, Liliana
    Mcguire, Brian E.
    Mocan, Andreia
    Nefs, Giesje
    Polonsky, William H.
    Stewart, Rose
    Vallis, Michael
    Roles and competencies of the clinical psychologist in adult diabetes care: A consensus report2024In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 41, no 5, article id e15312Article, review/survey (Refereed)
    Abstract [en]

    Aims: Psychological care is recognised as an integral part of quality diabetes care. We set out to describe the roles and competencies of the clinical psychologist as a member of the multidisciplinary adult diabetes care team, focused on secondary care.

    Methods: The authors are clinically experienced psychologists involved in adult diabetes care, from Australia, Europe and North America, and active members of the international psychosocial aspects of diabetes study group. Consensus was reached as a group on the roles and competencies of the clinical psychologist working in adult diabetes secondary care, building both on expert opinion and a selective review and discussion of the literature on psychological care in diabetes, clinical guidelines and competency frameworks.

    Results: The clinical psychologist fulfils multiple roles: (1) as a clinician (psychological assessment and therapy), (2) as advisor to the healthcare team (training, consulting), (3) as a communicator and promotor of person-centred care initiatives and (4) as a researcher. Four competencies that are key to successfully fulfilling the above-mentioned roles in a diabetes setting are as follows: (a) specialised knowledge, (b) teamwork and advice, (c) assessment, (d) psychotherapy (referred to as STAP framework).

    Conclusions: The roles and competencies of clinical psychologists working in diabetes extend beyond the requirements of most university and post-graduate curricula. There is a need for a comprehensive, accredited specialist post-graduate training for clinical psychologists working in diabetes care, building on the proposed STAP framework. This calls for a collaborative effort involving diabetes organisations, clinical psychology societies and diabetes psychology interest groups.

  • 73. Song, Fei
    et al.
    Bao, Cuiping
    Deng, Meiyu
    Xu, Hui
    Fan, Meijuan
    Paillard-Borg, Stephanie
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Qi, Xiuying
    The prevalence and determinants of hypothyroidism in hospitalized patients with type 2 diabetes mellitus2017In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 55, no 1, p. 188-194Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate the prevalence of hypothyroidism among hospitalized patients with type 2 diabetes mellitus and its related factors, and to assess the prevalence of macrovascular and microvascular diseases among type 2 diabetes mellitus inpatients with hypothyroidism and euthyroidism. A total of 1662 type 2 diabetes mellitus inpatients hospitalized at the Metabolic Diseases Hospital, Tianjin Medical University from 1 January 2008 to 1 March 2013 were included in this study. Information on demographic and anthropometric factors and additional variables related to hypothyroidism were collected from medical records. Prevalence rates were calculated and standardized using direct method based on the age-specific and sex-specific structure of all participants. Data were analyzed using binary logistic regression with adjustment for potential confounders. The prevalence of hypothyroidism among type 2 diabetes mellitus inpatients was 6.8 %, and 77.0% of the patients with hypothyroidism had subclinical hypothyroidism. The prevalence of hypothyroidism increased with age, and was higher in women (10.8 %) than in men (3.4 %). Older age (odds ratio, 1.74; 95% confidence interval, 1. 05 to 2.89), female gender (odds ratio, 2.02; 95% confidence interval, 1.05 to 3.87), and positive thyroid peroxidase antibody (odds ratio, 4.99; 95% confidence interval, 2.83 to 8.79) were associated with higher odds of hypothyroidism among type 2 diabetes mellitus inpatients. The type 2 diabetes mellitus inpatients with hypothyroidism had higher prevalence of cerebrovascular diseases than those with euthyroidism after adjustment for age and gender. The prevalence of hypothyroidism among type 2 diabetes mellitus inpatients was 6.8 %, and most patients had subclinical hypothyroidism. Older age, female gender, and positive thyroid peroxidase antibody could be indicators for detecting hypothyroidism in type 2 diabetes mellitus inpatients.

  • 74. Speakman, John R.
    et al.
    de Jong, Jasper M. A.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Yale School of Medicine, USA.
    Westerterp, Klaas R.
    Yamada, Yosuke
    Sagayama, Hiroyuki
    Kurpad, Anura
    Luke, Amy H.
    Pontzer, Herman
    Rodeheffer, Matthew S.
    Rood, Jennifer
    Schoeller, Dale A.
    Wong, William W.
    Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure2023In: Nature Metabolism, E-ISSN 2522-5812, Vol. 5, no 4, p. 579-588Article in journal (Refereed)
    Abstract [en]

    Obesity is caused by a prolonged positive energy balance. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor. 

  • 75. Stattin, Nouha Saleh
    et al.
    Kane, Kimberly
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm County Council, Sweden.
    Stenback, Marina
    Wajngot, Alexandre
    Seijboldt, Kaija
    Improving the structure of diabetes care in primary care: A pilot study2020In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 14, no 10, p. 33-39Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this pilot study was to determine whether glycemic control can be improved in patients with type 2 diabetes by implementing a workshop model to improve the structure of diabetes care at primary health care centers (PHCCs). Methods: The intervention consisted of 4 workshops at 12 PHCCs with HbA1c >70 mmol/mol (high HbA1c). Each PHCC could choose how many workshops they wished to attend and was to be represented by the manager, a diabetes nurse, and a GP. Participants analyzed the structure of diabetes care at their PHCC and developed an action plan to improve it. The percentage of patients with high HbA1c at baseline, 12, and 24 months was collected. Qualitative content analysis was also conducted. Results: All PHCCs reduced the percentage of patients with high HbA1c 12 months after the intervention, but not all maintained the reduction at 24 months. Participants experienced structuring diabetes care as central to reducing the percentage of patients with high HbA1c. Pillars of structured diabetes care included establishing routines, working in teams, and having and implementing an action plan. Conclusions: Working with the structure of diabetes care improved care structure and had a positive impact on HbA1c. To sustain the positive impact, PHCCs had to set long-term goals and regularly evaluate performance. 

  • 76. Sun, Zhuoyu
    et al.
    Wang, Shuqi
    Yang, Rongrong
    Li, Xuerui
    Yang, Yumeng
    Qi, Xiuying
    Ma, Yaomei
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, China; Tianjin Center for International Collaborative Research in Environment, Nutrition and Public Health, China.
    Gestational diabetes mellitus and risks of gynecologic cancers: Results from a nationwide Swedish twin study2021In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 162, no 1, p. 142-147Article in journal (Refereed)
    Abstract [en]

    Background: Type 2 diabetes has been associated with increased risk of gynecologic cancers, yet the effect of gestational diabetes mellitus (GDM) on gynecologic cancers is unclear.

    Objectives: To examine associations between GDM history and subsequent gynecologic cancers in parous women, and to explore whether gestational hypertension (GH) plays a role in the associations.

    Study design: The population-based cohort study included 15,941 individuals from the Swedish Twin Registry. The history of GDM and GH was ascertained based on self-reports. Incident cases of gynecologic cancers (including cancers of the cervix, uterus, ovaries and other female genitalia) were obtained from the National Patients Registry and the Swedish Cancer Registry. Generalized estimating equation models were applied to analyze associations between GDM and gynecologic cancers. Stratified analysis was used to explore whether associations between GDM and gynecologic cancers differed by GH. Additive and multiplicative interactions were calculated between GDM and GH.

    Results: Of all participants, 350 (2.2%) had GDM, and 1762 (11.1%) had incident gynecologic cancers. No statistically significant associations were found between GDM and risks of any gynecologic cancers. However, GDM was associated with an increased risk of ovarian cancer (OR = 5.29, 95% CI: 1.63–17.19) in women with GH. Interactions between GDM and GH were observed on the additive scale (Attributable proportion due to interaction: 0.86, 95% CI 0.42–1.30, P < 0.001).

    Conclusions: The associations between GDM and risks of gynecologic cancers were not evident, but the effect of GDM on the risk of ovarian cancer was modified by GH. Further validation in larger cohorts is warranted.

  • 77.
    Taloyan, Marina
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Saleh-Stattin, Nuha
    Johansson, Sven-Erik
    Agréus, Lars
    Wändell, Per
    Hypertriglyceridemic waist may explain ethnic differences in hypertension among patients with type 2 diabetes in Sweden2012In: BMC Research Notes, E-ISSN 1756-0500, Vol. 5, article id 474Article in journal (Refereed)
    Abstract [en]

    Background

    Hypertension is common among persons with type 2 diabetes. The aim of this study was to analyze the association between ethnicity and hypertension prevalence after adjusting for age, sex, Hba1c, total cholesterol, elevated triglycerides and hypertriglyceridemic waist. The study population consisted of 354 primary health care patients diagnosed with type 2 diabetes (173 Assyrians/Syrians and 181 Swedes) residing in Södertälje, Sweden. Unconditional logistic regression was used to analyze the data.

    Results

    Hypertension prevalence was higher among Swedes than Assyrians/Syrians, (77% versus 58%; p = 0.001). In the unadjusted logistic regression model, the odds ratio for hypertension in Swedes was twice as high than that in Assyrians/Syrians (OR = 2.44; 95% CI =1.54-3.86). In the age- and sex-adjusted model, odds ratio of hypertension was 2.25 (95% CI 1.41-3.60). After adjustments for total cholesterol was made, the odds ratio of hypertension decreased slightly to 1.73. When elevated triglycerides and hypertriglyceridemic waist were separately introduced, the odds ratio of hypertension was no longer significant between the ethnic groups (1.60 and 1.43 for triglycerides and hypertriglyceridemic waist respectively). In addition, advanced age – 60–69 years old (OR = 1.80, CI 95% 1.00-3.20) and ≥ 70 years old (OR = 2.88, CI 95% 1.40-5.93), elevated total cholesterol (OR = 1.48, CI 95% 1.12-1.95) and presents of hypertriglyceridemic waist (those with high WC and high TG) were significant confounding factors for the increased risk of hypertension independent of ethnicity.

    Conclusions

    The crude differences in prevalence of hypertension between the Swedes and Assyrians/Syrians in our study population with type 2 diabetes were no longer significant when adjusting for high triglycerides levels or the presence of hypertriglyceridemic waist.

  • 78.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Stressens endokrinologi2015In: Endokrinologi / [ed] Sigbritt Werner, Stockholm: Liber, 2015, 3, p. 389-394Chapter in book (Other academic)
  • 79. van Beek, Sten M. M.
    et al.
    Bruls, Yvonne M. H.
    Vanweert, Froukje
    Fealy, Ciarán E.
    Connell, Niels J.
    Schaart, Gert
    Moonen-Kornips, Esther
    Jörgensen, Johanna A.
    Vaz, Frédéric M.
    Smeets, Ellen T. H. C.
    Joris, Peter J.
    Gemmink, Anne
    Houtkooper, Riekelt H.
    Hesselink, Matthijs K. C.
    Bengtsson, Tore
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Havekes, Bas
    Schrauwen, Patrick
    Hoeks, Joris
    Effect of β2-agonist treatment on insulin-stimulated peripheral glucose disposal in healthy men in a randomised placebo-controlled trial2023In: Nature Communications, E-ISSN 2041-1723, Vol. 14, article id 173Article in journal (Refereed)
    Abstract [en]

    β2-agonist treatment improves skeletal muscle glucose uptake and whole-body glucose homeostasis in rodents, likely via mTORC2-mediated signalling. However, human data on this topic is virtually absent. We here investigate the effects of two-weeks treatment with the β2-agonist clenbuterol (40 µg/day) on glucose control as well as energy- and substrate metabolism in healthy young men (age: 18-30 years, BMI: 20-25 kg/m2) in a randomised, placebo-controlled, double-blinded, cross-over study (ClinicalTrials.gov-identifier: NCT03800290). Randomisation occurred by controlled randomisation and the final allocation sequence was seven (period 1: clenbuterol, period 2: placebo) to four (period 1: placebo, period 2: clenbuterol). The primary and secondary outcome were peripheral insulin-stimulated glucose disposal and skeletal muscle GLUT4 translocation, respectively. Primary analyses were performed on eleven participants. No serious adverse events were reported. The study was performed at Maastricht University, Maastricht, The Netherlands, between August 2019 and April 2021. Clenbuterol treatment improved peripheral insulin-stimulated glucose disposal by 13% (46.6 ± 3.5 versus 41.2 ± 2.7 µmol/kg/min, p = 0.032), whereas skeletal muscle GLUT4 translocation assessed in overnight fasted muscle biopsies remained unaffected. These results highlight the potential of β2-agonist treatment in improving skeletal muscle glucose uptake and underscore the therapeutic value of this pathway for the treatment of type 2 diabetes. However, given the well-known (cardiovascular) side-effects of systemic β2-agonist treatment, further exploration on the underlying mechanisms is needed to identify viable therapeutic targets.

  • 80. van Beek, Sten M. M.
    et al.
    Kalinovich, Anastasia
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Schaart, Gert
    Bengtsson, Tore
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Hoeks, Joris
    Prolonged b(2)-adrenergic agonist treatment improves glucose homeostasis in diet-induced obese UCP1(-/-) mice2021In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 320, no 3, p. E619-E628Article in journal (Refereed)
    Abstract [en]

    Prolonged supplementation with the b2-agonist clenbuterol improves glucose homeostasis in diabetic rodents, likely via b2-adreno-ceptor (b2-AR)-mediated effects in the skeletal muscle and liver. However, since rodents have, in contrast to—especially diabetic—humans, substantial quantities of brown adipose tissue (BAT) and clenbuterol has affinity to b1- and b3-ARs, the contribution of BAT tothese improvements is unclear. Therefore, we investigated clenbuterol-mediated improvements in glucose homeostasis in uncouplingprotein 1-deficient (UCP1/) mice, lacking thermogenic BAT, versus wild-type (WT) mice. Anesthetized WT and UCP1/C57Bl/6 micewere injected with saline or clenbuterol and whole body oxygen consumption was measured. Furthermore, male WT and UCP1/C57Bl/6 mice were subjected to 17-wk of chow feeding, high-fat feeding, or high-fat feeding with clenbuterol treatment betweenweeks 13 and 17. Body composition was measured weekly with MRI. Oral glucose tolerance and insulin tolerance tests were per-formed in week 15 and 17, respectively. Clenbuterol increased oxygen consumption approximately twofold in WT mice. This increasewas blunted in UCP1/mice, indicating clenbuterol-mediated activation of BAT thermogenesis. High-fat feeding induced diabeto-genic phenotypes in both genotypes. However, low-dose clenbuterol treatment for 2 wk significantly reduced fasting blood glucoseby 12.9% in WT and 14.8% in UCP1/mice. Clenbuterol treatment improved glucose and insulin tolerance in both genotypes com-pared with HFD controls and normalized to chow-fed control mice independent of body mass and composition alterations.Clenbuterol improved whole body glucose homeostasis independent of UCP1. Given the low human abundancy of BAT, b2-AR ago-nist treatment provides a potential novel route for glucose disposal in diabetic humans.

  • 81. Virgilio, Enrico
    et al.
    Trevisan, Caterina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Université Libre de Bruxelles, Belgium; University of Padua, Italy.
    Abbatecola, Angela
    Malara, Alba
    Palmieri, Annapina
    Fedele, Giorgio
    Stefanelli, Paola
    Leone, Pasqualina
    Schiavoni, Ilaria
    Maggi, Stefania
    Volpato, Stefano
    Incalzi, Raffaele Antonelli
    Onder, Graziano
    Diabetes Affects Antibody Response to SARS-CoV-2 Vaccination in Older Residents of Long-term Care Facilities: Data From the GeroCovid Vax Study2022In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 45, no 12, p. 2935-2942Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Type 2 diabetes may affect the humoral immune response after vaccination, but data concerning coronavirus disease 19 (COVID-19) vaccines are scarce. We evaluated the impact of diabetes on antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in older residents of long-term care facilities (LTCFs) and tested for differences according to antidiabetic treatment.

    RESEARCH DESIGN AND METHODS

    For this analysis, 555 older residents of LTCFs participating in the GeroCovid Vax study were included. SARS-CoV-2 trimeric S immunoglobulin G (anti-S IgG) concentrations using chemiluminescent assays were tested before the first dose and after 2 and 6 months. The impact of diabetes on anti-S IgG levels was evaluated using linear mixed models, which included the interaction between time and presence of diabetes. A second model also considered diabetes treatment: no insulin therapy (including dietary only or use of oral antidiabetic agents) and insulin therapy (alone or in combination with oral antidiabetic agents).

    RESULTS

    The mean age of the sample was 82.1 years, 68.1% were women, and 25.2% had diabetes. In linear mixed models, presence of diabetes was associated with lower anti-S IgG levels at 2 (β = −0.20; 95% CI −0.34, −0.06) and 6 months (β = −0.22; 95% CI −0.37, −0.07) after the first vaccine dose. Compared with those without diabetes, residents with diabetes not using insulin had lower IgG levels at 2- and 6-month assessments (β = −0.24; 95% CI −0.43, −0.05 and β = −0.30; 95% CI −0.50, −0.10, respectively), whereas no differences were observed for those using insulin.

    CONCLUSIONS

    Older residents of LTCFs with diabetes tended to have weaker antibody response to COVID-19 vaccination. Insulin treatment might buffer this effect and establish humoral immunity similar to that in individuals without diabetes.

  • 82. Virtue, Sam
    et al.
    Feldmann, Helena
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Christian, Mark
    Tan, Chong Yew
    Masoodi, Mojgan
    Dale, Martin
    Lelliott, Chris
    Burling, Keith
    Campbell, Mark
    Eguchi, Naomi
    Voshol, Peter
    Sethi, Jaswinder K.
    Parker, Malcolm
    Urade, Yoshihiro
    Griffin, Julian L.
    Cannon, Barbara
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Vidal-Puig, Antonio
    A New Role for Lipocalin Prostaglandin D Synthase in the Regulation of Brown Adipose Tissue Substrate Utilization2012In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 61, no 12, p. 3139-3147Article in journal (Refereed)
    Abstract [en]

    In this study, we define a new role for lipocalin prostaglandin D synthase (L-PGDS) in the control of metabolic fuel utilization by brown adipose tissue (BAT). We demonstrate that L-PGDS expression in BAT is positively correlated with BAT activity, upregulated by peroxisome proliferator activated receptor gamma coactivator 1 alpha or 1 beta and repressed by receptor-interacting protein 140. Under cold-acclimated conditions, mice lacking L-PGDS had elevated reliance on carbohydrate to provide fuel for thermogenesis and had increased expression of genes regulating glycolysis mid de novo lipogenesis in BAT. These transcriptional differences were associated with increased lipid content in BAT and a BAT lipid composition enriched with de novo synthesized lipids. Consistent with the concept that lack of L-PGDS increases glucose utilization, mice lacking L-PGDS had improved glucose tolerance after high-fat, feeding. The improved glucose tolerance appeared to be independent of changes in insulin sensitivity, as insulin levels during the glucose tolerance test and insulin, leptin, and adiponectin levels were unchanged. Moreover, L-PGDS knock-out mice exhibited increased expression of genes involved in thermogenesis and increased norepinephrine-stimulated glucose uptake to BAT, suggesting that sympathetically mediated changes in glucose uptake may have improved glucose tolerance. Taken together, these results suggest that L-PGDS plays an important role in the regulation of glucose utilization in vivo. Diabetes 61:3139-3147, 2012

  • 83.
    von Essen, Gabriella
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Lindsund, Erik
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cannon, Barbara
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nedergaard, Jan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Adaptive facultative diet-induced thermogenesis in wild-type but not in UCP1-ablated mice2017In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 313, no 5, p. E515-E527Article in journal (Refereed)
    Abstract [en]

    The significance of diet-induced thermogenesis (DIT) for metabolic control is still debated. Although obesogenic diets recruit UCP1 and adrenergically inducible thermogenesis, and although the absence of UCP1 may promote the development of obesity, no actual UCP1-related thermogenesis identifiable as diet-induced thermogenesis has to date been unambiguously demonstrated. Examining mice living at thermoneutrality, we have identified a process of facultative (directly elicited by acute eating), adaptive (magnitude develops over weeks on an obesogenic diet), and fully UCP1-dependent thermogenesis. We found no evidence for UCP1-independent diet-induced thermogenesis. The thermogenesis was proportional to the total amount of UCP1 protein in brown adipose tissue and was not dependent on any contribution of UCP1 in brite/beige adipose tissue, since no UCP1 protein was found there under these conditions. Total UCP1 protein amount developed proportionally to total body fat content. The physiological messenger linking obesity level and acute eating to increased thermogenesis is not known. Thus UCP1-dependent diet-induced thermogenesis limits obesity development during exposure to obesogenic diets but does not prevent obesity as such.

  • 84.
    Wallace, Matthew
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Khlat, Myriam
    Guillot, Michel
    Infant mortality among native-born children of immigrants in France, 2008-17: results from a socio-demographic panel survey2021In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 31, no 2, p. 326-333Article in journal (Refereed)
    Abstract [en]

    Background: Within Europe, France stands out as a major country that lacks recent and reliable evidence on how infant mortality levels vary among the native-born children of immigrants compared with the native-born children of two parents born in France. Methods: We used a nationally representative socio-demographic panel consisting of 296 400 births and 980 infant deaths for the period 2008-17. Children of immigrants were defined as being born to at least one parent born abroad and their infant mortality was compared with that of children born to two parents born in France. We first calculated infant mortality rates per 1000 live births. Then, using multi-level logit models, we calculated odds ratios of infant mortality in a series of models adjusting progressively for parental origins (M1), core demographic factors (M2), father's socio-professional category (M3) and area-level urbanicity and deprivation score (M4). Results: We documented a substantial amount of excess infant mortality among those children born to at least one parent from Eastern Europe, Northern Africa, Western Africa, Other Sub-Saharan Africa and the Americas, with variation among specific origin countries belonging to these groups. In most of these cases, the excess infant mortality levels persisted after adjusting for all individual-level and area-level factors. Conclusions: Our findings, which can directly inform national public health policy, reaffirm the persistence of longstanding inequality in infant mortality according to parental origins in France and add to a growing body of evidence documenting excess infant mortality among the children of immigrants in Europe.

  • 85. Wang, Jingya
    et al.
    Bai, Yang
    Zeng, Zihang
    Wang, Jun
    Wang, Ping
    Zhao, Yongai
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, People’s Republic of China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, People’s Republic of China.
    Zhu, Yun
    Qi, Xiuying
    Association between life-course cigarette smoking and metabolic syndrome: a discovery-replication strategy2022In: Diabetology & Metabolic Syndrome, E-ISSN 1758-5996, Vol. 14, no 1, article id 11Article in journal (Refereed)
    Abstract [en]

    Background: The relation between cigarette smoking and metabolic syndrome (MetS) remains unclear, and previous studies focusing on MetS are limited in sample size. We investigated the association between life-course smoking and MetS with independent discovery and replication samples.

    Methods: Preliminary analysis utilized data from an annual cross-sectional survey of 15,222 participants aged >= 60 years in Tianjin, China. Suggestive associations were followed-up in 8565 adults from the China Health and Nutrition Survey. MetS was identified according to the criteria of the Chinese Diabetes Society in 2013. Life-course smoking was assessed by a comprehensive smoking index (CSI), based on information on smoking intensity, duration, and time since cessation across life-course, collected through standard questionnaires. Participants were divided into four groups: non-smokers; and the tertiles of CSI in ever smokers. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between life-course smoking and MetS.

    Results: In the discovery sample, ORs of MetS were 2.01 (95%CI: 1.64-2.47) and 1.76 (95%CI: 1.44-2.16) for smokers in the highest and second tertile of CSI compared with never smokers. Potential interaction was shown for age, with increased ORs for MetS associated with smoking limited to individuals who aged < 70 years (P-interaction = 0.015). We were able to replicate the association between cigarette smoking and MetS in an independent adult sample (second tertile vs. never: OR = 1.30, 95%CI: 1.04-1.63). The interaction of smoking with age was also replicated.

    Conclusions: Life-course cigarette smoking is associated with an increased odds of MetS, especially among individuals who aged < 70 years.

  • 86. Wang, Pin
    et al.
    Li, Yuanjing
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Mingqi
    Song, Lin
    Dong, Yi
    Han, Xiaolei
    Tuomilehto, Jaakko
    Wang, Yongxiang
    Du, Yifeng
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Shandong Provincial Hospital, P.R. China.
    Comparing glycemic traits in defining diabetes among rural Chinese older adults2024In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 1, article id e0296694Article in journal (Refereed)
    Abstract [en]

    Background

    We sought to identify the optimal cut-off of glycated hemoglobin (HbA1c) for defining diabetes and to assess the agreements of fasting plasma glucose (FPG), fasting serum glucose (FSG), and HbA1c in defining diabetes among rural older adults in China.

    Methods

    This population-based cross-sectional study included 3547 participants (age ≥61 years, 57.8% women) from the Multidomain Interventions to Delay Dementia and Disability in Rural China from 2018–2019; of these, 3122 had no previously diagnosed diabetes. We identified the optimal cut-off of HbA1c against FPG ≥7.0 mmol/L for defining diabetes by using receiver operating characteristic curve and Youden index. The agreements of FPG, FSG, and HbA1c in defining diabetes were assessed using kappa statistics.

    Results

    Among participants without previously diagnosed diabetes (n = 3122), the optimal HbA1c cut-off for defining diabetes was 6.5% (48 mmol/mol), with the sensitivity of 88.9%, specificity of 93.7%, and Youden index of 0.825. The correlation coefficients were 0.845 between FPG and FSG, 0.574 between FPG and HbA1c, and 0.529 between FSG and HbA1c in the total sample (n = 3547). The kappa statistic for defining diabetes was 0.962 between FSG and FPG, and 0.812 between HbA1c and FPG.

    Conclusions

    The optimal cut-off of HbA1c for diagnosing diabetes against FPG >7.0 mmol/L is ≥6.5% in Chinese rural-dwelling older adults. The agreement in defining diabetes using FPG, FSG, and HbA1c is nearly perfect. These results have relevant implications for diabetes research and clinical practice among older adults in China.

  • 87. Wang, Zhida
    et al.
    Bao, Cuiping
    Su, Cheng
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Luo, Hongbin
    Chen, Liming
    Qi, Xiuying
    Association between diabetes or antidiabetic therapy and lung cancer: A meta-analysis2013In: Journal of Diabetes Investigation, ISSN 2040-1116, E-ISSN 2040-1124, Vol. 4, no 6, p. 659-666Article in journal (Refereed)
    Abstract [en]

    Aims/IntroductionDiabetes can increase the risk of cancers at several sites, but the association between diabetes and lung cancer remains unclear. We aimed to provide the quantitative estimates for the association between diabetes or antidiabetic treatment and lung cancer risk in the present meta-analysis. Materials and MethodsCohort studies were identified by searching the PubMed database (January 1960 through October 2012) and manually assessing the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. ResultsA total of 19 cohort studies were included in the present meta-analysis. Of these, 14 studies focused on the association between diabetes and lung cancer incidence, and seven studies focused on the association between antidiabetic treatment and lung cancer incidence. Compared with non-diabetic individuals, diabetic patients do not have an increased risk of lung cancer (RR=1.04, 95% CI 0.87-1.24). The association between diabetes and lung cancer remained not statistically significant in subgroup analysis stratified by study characteristics, study quality, diabetes ascertainment or important confounders. A null association between insulin or biguanides therapy and lung cancer risk was found. However, the diabetic patients receiving thiazolidinedione (TZD) treatment had a 20% reduced risk of lung cancer than those without TZD treatment. ConclusionsNo association between diabetes and lung cancer risk was found. However, TZD treatment might reduce lung cancer risk in diabetic patients.

  • 88. Wang, Zhida
    et al.
    Zhang, Jie
    Xu, Hui
    Chen, Liming
    Dove, Abigail
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Development and Validation of a Prevalence Model for Latent Autoimmune Diabetes in Adults (LADA) Among Patients First Diagnosed with Type 2 Diabetes Mellitus (T2DM)2021In: Medical Science Monitor, ISSN 1234-1010, E-ISSN 1643-3750, Vol. 27, article id e932725Article in journal (Refereed)
    Abstract [en]

    Background: We designed this study to develop and validate a prevalence model for latent autoimmune diabetes in adults (LADA) among people initially diagnosed with type 2 diabetes mellitus (T2DM).

    Material/Methods: The study recruited 930 patients aged 318 years who were diagnosed with T2DM within the past year. Demographic information, medical history, and clinical biochemistry records were collected. Logistic regression was used to develop a regression model to distinguish LADA from T2DM. Predictors of LADA were identified in a subgroup of patients (n=632) by univariate logistic regression analysis. From this we developed a prediction model using multivariate logistic regression analysis and tested its sensitivity and specificity among the remaining patients (n=298).

    Results: Among 930 recruited patients, 880 had T2DM (96.4%) and 50 had LADA (5.4%). Compared to T2DM patients, LADA patients had fewer surviving b cells and reduced insulin production. We identified age, ketosis, history of tobacco smoking, 1-hour plasma glucose (1hPG-AUC), and 2-hour C-peptide (2hCP-AUC) as the main predictive factors for LADA (P<0.05). Based on this, we developed a multivariable logistic regression model: Y=-8.249-0.035(X1)+1.755(X2)+1.008(X3)+0.321(X4)-0.126(X5), where Y is diabetes status (0=T2DM, 1=LADA), X1 is age, X2 is ketosis (1=no, 2=yes), X3 is history of tobacco smoking (1=no, 2=yes), X4 is 1hPG-AUC, and X5 is 2hCP-AUC. The model has high sensitivity (78.57%) and selectivity (67.96%).

    Conclusions: This model can be applied to people newly diagnosed with T2DM. When Y 30.0472, total autoantibody screening is recommended to assess LADA.

  • 89. Wijk, Ingrid
    et al.
    Amsberg, Susanne
    Andreassen Gleissman, Sissel
    Toft, Eva
    Anderbro, Therese
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Clinical psychology. Karolinska Institutet, Stockholm, Sweden.
    Johansson, Unn-Britt
    Living with Type 1 Diabetes as Experienced by Adults with Prolonged Elevated HbA1c: A Qualitative Study2023In: Diabetes Therapy, ISSN 1869-6953, E-ISSN 1869-6961, Vol. 14, p. 1673-1684Article in journal (Refereed)
    Abstract [en]

    Introduction: High HbA1c levels in type 1 diabetes (T1D) are associated with increased risk of micro- and macrovascular complications and severe diabetes distress. A more comprehensive understanding of the adult perspective of living with T1D can improve the quality of care. We aimed to describe experiences of living with T1D as an adult with prolonged elevated HbA1c.

    Methods: Thirteen adults with T1D and HbA1c > 60 mmol/mol (7.6%) for at least 1 year were individually interviewed via a digital platform. The interviews were transcribed verbatim and analyzed using qualitative content analysis.

    Results: The analysis identified an overarching theme, “a lifelong follower”, and generated two main categories describing study participants’ experience: constraining and manageable. Constraining experiences were explained in obligated control, loss of control, environmental impact, and consequences of diabetes. Manageable experiences were described in everyday life, approach to diabetes, and support in life. Diabetes knowledge in health care and in the general public, and individualized care were important factors in feeling understood, safe, and supported.

    Conclusions: The findings revealed the diverse experiences of adults with prolonged elevated HbA1c. Living with T1D, a lifelong non-chosen follower, could be perceived as constraining but manageable in different degrees. A person-centered care approach addressing both dimensions may be beneficial. Experiences of living with and managing diabetes are multifaceted and intertwined with life context and medical prerequisites.

  • 90. Wändell, Per E.
    et al.
    Gigane, Bruna
    Nixon Andreasson, Anna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Carlsson, Axel C.
    Gender Differences Regarding Novel Biomarkers and Metabolic Risk Factors in Metformin Treated Type 2 Diabetic Patients2012In: The Open Diabetes Journal, E-ISSN 1876-5246, Vol. 5, p. 13-19Article in journal (Refereed)
    Abstract [en]

    We aimed to analyze associations between adiponectin, ghrelin and leptin with anthropometric and metabolic markers in men and women with Metformin-treated type 2 diabetes (n=53), recruited from a trial of relaxation therapies. Anthropometrical measures and fasting blood samples were assessed on three occasions: at baseline, and after 10 and 24 weeks: BMI, waist, HbA1c, insulin, glucose, adiponectin, leptin, fasting ghrelin, high sensitivity C-reactive protein (CRP), tumor necrosis factor α (TNF- α) and interleukin 6 (IL-6). HOMA2ir and HOMA2s were calculated from fasting glucose and insulin, and adiponectin/leptin and adiponectin/HOMA2ir ratios were calculated. In men, higher leptin and lower adiponectin/leptin ratio correlated with insulin and insulin resistance, and in women lower ghrelin with insulin and insulin resistance. In multivariate linear regression, higher levels of leptin were associated with insulin resistance among men, but not among women. Among women, insulin resistance was associated with lower adiponectin/leptin ratio and ghrelin. Factor analysis showed that leptin in women was closely related to anthropometric variables, but in men both related to anthropometric and inflammatory variables. Gender differences could indicate different pathophysiologic mechanisms of insulin resistance and type 2 diabetes among men and women, where leptin possibly could be a better marker among men, and ghrelin among women.

  • 91.
    Xu, Weili
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Caracciolo, Barbara
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Winblad, Bengt
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Accelerated progression from mild cognitive impairment to dementia in people with diabetes2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 11, p. 2928-35Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The effect of diabetes on mild cognitive impairment (MCI) and its conversion to dementia remains controversial. We sought to examine whether diabetes and pre-diabetes are associated with MCI and accelerate the progression from MCI to dementia.

    RESEARCH DESIGN AND METHODS: In the Kungsholmen Project, 963 cognitively intact participants and 302 subjects with MCI (120 with amnestic MCI [aMCI] and 182 with other cognitive impairment no dementia [oCIND]) age ≥ 75 years were identified at baseline. The two cohorts were followed for 9 years to detect the incident MCI and dementia following international criteria. Diabetes was ascertained based on a medical examination, hypoglycemic medication use, and random blood glucose level ≥ 11.0 mmol/l. Pre-diabetes was defined as random blood glucose level of 7.8-11.0 mmol/l in diabetes-free participants. Data were analyzed using standard and time-dependent Cox proportional-hazards models.

    RESULTS: During the follow-up period, in the cognitively intact cohort, 182 people developed MCI (42 aMCI and 140 oCIND), and 212 developed dementia. In the MCI cohort, 155 subjects progressed to dementia, the multi-adjusted hazard ratio (95% CI) of dementia was 2.87 (1.30-6.34) for diabetes, and 4.96 (2.27-10.84) for pre-diabetes. In a Kaplan-Meier survival analysis, diabetes and pre-diabetes accelerated the progression from MCI to dementia by 3.18 years. Diabetes and pre-diabetes were neither cross-sectionally nor longitudinally associated with MCI.

    CONCLUSIONS: Diabetes and pre-diabetes substantially accelerate the progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI. The association of diabetes with the development of MCI is less evident in old people.

  • 92.
    Xu, Weili
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Xu, Zhongliang
    Jia, Junting
    Xie, Yun
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qi, Xiuying
    Detection of Prediabetes and Undiagnosed Type 2 Diabetes: A Large Population-Based Study2012In: Canadian Journal of Diabetes, ISSN 1499-2671, Vol. 36, no 3, p. 108-113Article in journal (Refereed)
    Abstract [en]

    Objective: Prediabetes and undiagnosed diabetes have been commonly ignored. We aimed to investigate the prevalence of prediabetes and undiagnosed type 2 diabetes mellitus, and to verify the hypothesis that vascular risk factors (VRFs) may indicate prediabetes and undiagnosed type 2 diabetes.

    Methods: A total of 7567 adults, who were 20 to 79 years of age, and living in Tianjin, China, participated in this study. Type 2 diabetes was assessed based on medical history, hypoglycemic drugs use, fasting plasma glucose level >= 7.0 mmol/L, or postprandial 2-hour plasma glucose level >= 11.1 mmol/L. Undiagnosed type 2 diabetes was defined among subjects with type 2 diabetes when neither a medical history of diabetes nor hypoglycemic drugs use was present. Prediabetes was ascertained as fasting plasma glucose level of 6.1 to 6.9 mmol/L, or postprandial 2-hour plasma glucose level of 7.8 to 11.0 mmol/L (WHO 1999) among diabetes-free participants. Data were analyzed using multinomial logistic regression with adjustment for potential confounders.

    Results: Of all participants, 655 (8.7%) had prediabetes, and 721 (9.5%) were patients with type 2 diabetes, including 321 (4.2%) undiagnosed type 2 diabetes accounting for 44.5% patients with diabetes. The prevalence of prediabetes and undiagnosed type 2 diabetes increased with age, and was higher in women than in men. In a fully adjusted multinomial logistic regression model, hypertension, overweight, obesity, central obesity, and family history of diabetes were significantly associated with prediabetes and undiagnosed diabetes, whereas physical inactivity was independently related to undiagnosed diabetes.

    Conclusion: The prevalence of prediabetes and undiagnosed diabetes is approximately 13%, and almost 45% of patients with diabetes are undiagnosed. VRFs, such as hypertension, high adiposity, and family history of diabetes can be indicators for detecting prediabetes and undiagnosed diabetes.

  • 93. Xu, Z.
    et al.
    Qi, X.
    Dahl, A. K.
    Xu, W.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Waist-to-height ratio is the best indicator for undiagnosed Type 2 diabetes2013In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 30, no 6, p. e201-E207Article in journal (Refereed)
    Abstract [en]

    Aims

    Early detection of diabetes is important for the prevention of diabetic complications. The best adiposity index for indicating Type 2 diabetes mellitus remains unclear. We aimed to identify the optimal adiposity measure among BMI, waist circumference, waist–hip ratio and waist-to-height ratio to indicate undiagnosed Type 2 diabetes and impaired fasting glucose in Chinese adults.

    Methods

    A total of 7567 participants aged 20–79 years were included in this study. Impaired fasting glucose was defined as a fasting plasma glucose level of 6.1–6.9 mmol/l in participants without diabetes. Undiagnosed Type 2 diabetes was identified as fasting plasma glucose ≥ 7.0 mmol/l when neither a history of diabetes nor use of hypoglycaemic drugs was present. Body weight, height, waist and hip circumferences were measured following standard procedures. Data were analysed using logistic regression and areas under the receiver operating characteristic curves.

    Results

    Of the 7567 participants, 536 were defined as having impaired fasting glucose and 690 were patients with Type 2 diabetes, including 290 (3.8%) persons with undiagnosed diabetes. In multivariate logistic regression, the odds ratios of waist-to-height ratio (≥ 0.5) were stronger than BMI (≥ 24 kg/m2), waist circumference (≥ 85 cm in men and ≥ 80 cm in women) and waist–hip ratio (≥ 0.85) for undiagnosed Type 2 diabetes and impaired fasting glucose. Among the four indices, waist-to-height ratio ≥ 0.5 showed the largest area under the receiver operating characteristic curve for diagnosing undiagnosed Type 2 diabetes (0.725, 95% CI 0.693–0.756) and impaired fasting glucose (0.662, 95% CI 0.638–0.687).

    Conclusions

    By comparison with BMI, waist circumference and waist–hip ratio, waist-to-height ratio ≥ 0.5 may be the best indicator for undiagnosed Type 2 diabetes and impaired fasting glucose.

  • 94. Yan, Xin
    et al.
    Wang, Zhen
    Westberg-Rasmussen, Sidse
    Tarbier, Marcel
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Rathjen, Thomas
    Tattikota, Sudhir G.
    Peck, Bailey C. E.
    Kanke, Matt
    Oxvig, Claus
    Frystyk, Jan
    Starup-Linde, Jakob
    Sethupathy, Praveen
    Friedländer, Marc R.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Gregersen, Søren
    Poy, Matthew N.
    Differential Impact of Glucose Administered Intravenously and Orally on Circulating miR-375 Levels in Human Subjects2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 10, p. 3749-3755Article in journal (Refereed)
    Abstract [en]

    Background

    To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however, their functional role in this compartment remains unclear.

    Objective

    The aim of this study was to determine whether systemic levels of miRNAs abundant in blood, including the neuroendocrine tissue-enriched miR-375, are altered in response to a glucose challenge.

    Design

    Twelve healthy males were recruited for an acute crossover study that consisted of two tests each following an 8-hour fasting period. An oral glucose tolerance test (OGTT) was performed, and blood samples were collected over a 3-hour period. Following a period of at least 1 week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood-collection protocol.

    Results

    The glucose response curve following the IIGI mimicked that obtained after the OGTT, but as expected, systemic insulin levels were lower during the IIGI compared with the OGTT (P < 0.05). miR-375 levels in circulation were increased only in response to an OGTT and not during an IIGI. In addition, the response to the OGTT also coincided with the transient increase of circulating glucagon-like peptide (GLP)-1, GLP-2, and glucose-dependent insulinotropic polypeptide.

    Conclusions

    The present findings show levels of miR-375 increase following administration of an OGTT and, in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play an important role in the abundance and function of this miRNA in the blood.

  • 95. Yang, Rongrong
    et al.
    Pedersen, Nancy L.
    Bao, Cuiping
    Xu, Weige
    Xu, Hui
    Song, Ruixue
    Qi, Xiuying
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, People’s Republic of China.
    Type 2 diabetes in midlife and risk of cerebrovascular disease in late life: a prospective nested case-control study in a nationwide Swedish twin cohort2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 8, p. 1403-1411Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis We aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association.

    Methods In this prospective nested case-control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40-59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset age >= 60 years. Generalised estimating equation (GEE) models were used to analyse unmatched case-control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case-control analyses in CBD-discordant twin pairs.

    Results Of all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs (95% CIs) of type 2 diabetes were 1.29 (1.03, 1.61) for cerebral infarction, 2.03 (1.20, 3.44) for occlusion of cerebral arteries, 0.52 (0.12, 2.21) for subarachnoid haemorrhage and 0.78 (0.45, 1.36) for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes-cerebral infarction association was 0.96 (0.51, 1.80). The differences in ORs from the GEE and co-twin control analyses were not statistically significant (p=0.780).

    Conclusions/interpretation Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes-cerebral infarction association, but further clarification is needed.

  • 96.
    Zandawala, Meet
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Tian, Shi
    Elphick, Maurice R.
    The evolution and nomenclature of GnRH-type and corazonin-type neuropeptide signaling systems2018In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 264, p. 64-77Article, review/survey (Refereed)
    Abstract [en]

    Gonadotropin-releasing hormone (GnRH) was first discovered in mammals on account of its effect in triggering pituitary release of gonadotropins and the importance of this discovery was recognized forty years ago in the award of the 1977 Nobel Prize for Physiology or Medicine. Investigation of the evolution of GnRH revealed that GnRH-type signaling systems occur throughout the chordates, including agnathans (e.g. lampreys) and urochordates (e.g. sea squirts). Furthermore, the discovery that adipokinetic hormone (AKH) is the ligand for a GnRH-type receptor in the arthropod Drosophila melanogaster provided evidence of the antiquity of GnRH-type signaling. However, the occurrence of other AKH-like peptides in arthropods, which include corazonin and AKH/corazonin-related peptide (ACP), has complicated efforts to reconstruct the evolutionary history of this family of related neuropeptides. Genome/transcriptome sequencing has revealed that both GnRH-type receptors and corazonin-type receptors occur in lophotrochozoan protostomes (annelids, mollusks) and in deuterostomian invertebrates (cephalochordates, hemichordates, echinoderms). Furthermore, peptides that act as ligands for GnRH-type and corazonin-type receptors have been identified in mollusks. However, what has been lacking is experimental evidence that distinct GnRH-type and corazonin-type peptide-receptor signaling pathways occur in deuterostomes. Importantly, we recently reported the identification of two neuropeptides that act as ligands for either a GnRH-type receptor or a corazonin-type receptor in an echinoderm species - the common European starfish Asterias rubens. Discovery of distinct GnRH-type and corazonin-type signaling pathways in this deuterostomian invertebrate has demonstrated for the first time that the evolutionarily origin of these paralogous systems can be traced to the common ancestor of protostomes and deuterostomes. Furthermore, lineage-specific losses of corazonin signaling (in vertebrates, urochordates and nematodes) and duplication of the GnRH signaling system in arthropods (giving rise to the AKH and ACP signaling systems) and quadruplication of the GnRH signaling system in vertebrates (followed by lineage-specific losses or duplications) accounts for the phylogenetic distribution of GnRH/corazonin-type peptide-receptor pathways in extant animals. Informed by these new insights, here we review the history of research on the evolution of GnRH/corazonin-type neuropeptide signaling. Furthermore, we propose a standardized nomenclature for GnRH/corazonin-type neuropeptides wherein peptides are either named GnRH or corazonin, with the exception of the paralogous GnRH-type peptides that have arisen by gene duplication in the arthropod lineage and which are referred to as AKH (or red pigment concentrating hormone, RCPH, in crustaceans) and ACP.

  • 97. Zhang, H.
    et al.
    Xu, W.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Dahl, A. K.
    Xu, Z.
    Wang, H-X
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qi, X.
    Relation of socio-economic status to impaired fasting glucose and Type2 diabetes: findings based on a large population-based cross-sectional study in Tianjin, China2013In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 30, no 5, p. e157-E162Article in journal (Refereed)
    Abstract [en]

    Aims Studies on the relationship between socio-economic status and Type2 diabetes mellitus in the Chinese population are sparse. We aimed to examine the relation of socio-economic status as represented by income, education and occupation to impaired fasting glucose, Type2 diabetes, and the control of Type2 diabetes in a large Chinese population. Methods This study included 7315 individuals who were aged 2079years and living in Tianjin, China. Impaired fasting glucose and Type2 diabetes were ascertained according to the 1999 World Health Organization criteria. Data were analysed using multinomial and binary logistic regression, with adjustment for potential confounders. Result Among all participants, 532 (7.3%) persons had impaired fasting glucose, 688 (9.4%) persons had Type2 diabetes, including 288 (3.9%) previously undiagnosed Type2 diabetes. In fully adjusted multinomial logistic regression, compared with higher income (2000 yuan, $243.3/month), lower income (<1000 yuan, $121.70/month) showed odds ratios (95% confidence intervals) of 3.31 (2.484.41) for impaired fasting glucose, 4.50 (3.076.61) for undiagnosed Type2 diabetes and 4.56 (3.206.48) for diagnosed Type2 diabetes. These results remained significant in the analysis stratified by education and occupation. Furthermore, persons who were retired were more likely to have impaired fasting glucose [odds ratio1.91 (1.402.45)], undiagnosed Type2 diabetes [odds ratio2.01) 1.402.89] and diagnosed Type2 diabetes [odds ratio3.02 (2.124.22)]. Among the patients with Type2 diabetes previously diagnosed, lower education (less than senior high school), non-manual work and unemployment were related to worse glycaemic control (fasting blood glucose level >8.5mmol/l). Conclusions Lower income and retirement are associated with increased odds of impaired fasting glucose and Type2 diabetes in Tianjin, China. Education and occupation may play a role in glycaemic control among patients with Type2 diabetes.

  • 98. Zhang, Qian
    et al.
    Delessa, Challa Tenagne
    Augustin, Robert
    Bakhti, Mostafa
    Colldén, Gustav
    Drucker, Daniel J.
    Feuchtinger, Annette
    Garcia Caceres, Cristina
    Grandl, Gerald
    Harger, Alexandra
    Herzig, Stephan
    Hofmann, Susanna
    Holleman, Cassie Lynn
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Kleinert, Maximilian
    Knerr, Patrick J.
    Kulaj, Konxhe
    Legutko, Beata
    Lickert, Heiko
    Liu, Xue
    Luippold, Gerd
    Lutter, Dominik
    Malogajski, Emilija
    Tarquis Medina, Marta
    Mowery, Stephanie A.
    Blutke, Andreas
    Perez-Tilve, Diego
    Salinno, Ciro
    Sehrer, Laura
    DiMarchi, Richard D.
    Tschöp, Matthias H.
    Stemmer, Kerstin
    Finan, Brian
    Wolfrum, Christian
    Müller, Timo D.
    The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling2021In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 33, no 4, p. 833-844Article in journal (Refereed)
    Abstract [en]

    Uncertainty exists as to whether the glucose-dependent insulinotropic polypeptide receptor (GIPR) should be activated or inhibited for the treatment of obesity. Gipr was recently demonstrated in hypothalamic feeding centers, but the physiological relevance of CNS Gipr remains unknown. Here we show that HFD-fed CNS-Gipr KO mice and humanized (h)GIPR knockin mice with CNS-hGIPR deletion show decreased body weight and improved glucose metabolism. In DIO mice, acute central and peripheral administration of acyl-GIP increases cFos neuronal activity in hypothalamic feeding centers, and this coincides with decreased body weight and food intake and improved glucose handling. Chronic central and peripheral administration of acyl-GIP lowers body weight and food intake in wild-type mice, but shows blunted/absent efficacy in CNS-Gipr KO mice. Also, the superior metabolic effect of GLP-1/GIP co-agonism relative to GLP-1 is extinguished in CNS-Gipr KO mice. Our data hence establish a key role of CNS Gipr for control of energy metabolism.

  • 99. Zhang, Zhenwen
    et al.
    Fang, Penghua
    He, Biao
    Guo, Lili
    Runesson, Johan
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Shi, Mingyi
    Zhu, Yan
    Bo, Ping
    Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats2016In: Journal of Diabetes Research, ISSN 2314-6745, E-ISSN 2314-6753, article id 9095648Article in journal (Refereed)
    Abstract [en]

    Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebroventricular administration of M617 on insulin sensitivity and insulin signaling were evaluated in adipose tissues of type 2 diabetic rats. The results showed that central injection of M617 significantly increased plasma adiponectin contents, glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, GLUT4 mRNA expression levels, GLUT4 contents in plasma membranes, and total cell membranes of the adipose cells but reduced the plasma C-reactive protein concentration in nondiabetic and diabetic rats. The ratios of GLUT4 contents were higher in plasma membranes to total cell membranes in both nondiabetic and diabetic M617 groups than each control. In addition, the central administration of M617 enhanced the ratios of pAkt/Akt and pAS160/AS160, but not phosphorylative cAMP response element-binding protein (pCREB)/CREB in the adipose cells of nondiabetic and diabetic rats. These results suggest that excitation of central galanin receptor 1 facilitates insulin sensitivity via activation of the Akt/AS160 signaling pathway in the fat cells of type 2 diabetic rats.

  • 100. Ziqubu, Khanyisani
    et al.
    Dludla, Phiwayinkosi V.
    Mabhida, Sihle E.
    Jack, Babalwa U.
    Keipert, Susanne
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Jastroch, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mazibuko-Mbeje, Sithandiwe E.
    Brown adipose tissue-derived metabolites and their role in regulating metabolism2024In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 150, article id 155709Article, review/survey (Refereed)
    Abstract [en]

    The discovery and rejuvenation of metabolically active brown adipose tissue (BAT) in adult humans have offered a new approach to treat obesity and metabolic diseases. Beyond its accomplished role in adaptive thermogenesis, BAT secretes signaling molecules known as “batokines”, which are instrumental in regulating whole-body metabolism via autocrine, paracrine, and endocrine action. In addition to the intrinsic BAT metabolite-oxidizing activity, the endocrine functions of these molecules may help to explain the association between BAT activity and a healthy systemic metabolic profile. Herein, we review the evidence that underscores the significance of BAT-derived metabolites, especially highlighting their role in controlling physiological and metabolic processes involving thermogenesis, substrate metabolism, and other essential biological processes. The conversation extends to their capacity to enhance energy expenditure and mitigate features of obesity and its related metabolic complications. Thus, metabolites derived from BAT may provide new avenues for the discovery of metabolic health-promoting drugs with far-reaching impacts. This review aims to dissect the complexities of the secretory role of BAT in modulating local and systemic metabolism in metabolic health and disease.

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