Undiagnosed diabetes based on HbA 1c by socioeconomic status and healthcare consumption in the Tromsø Study 1994-2016

Introduction - We aimed to investigate whether the proportion of undiagnosed diabetes varies by socioeconomic status and healthcare consumption, in a Norwegian population screened with glycated hemoglobin (HbA1c). Research - design and methods In this cohort study, we studied age-standardized diabetes prevalence using data from men and women aged 40–89 years participating in four surveys of the Tromsø Study with available data on HbA1c and self-reported diabetes: 1994–1995 (n=6720), 2001 (n=5831), 2007–2008 (n=11 987), and 2015–2016 (n=20 170). We defined undiagnosed diabetes as HbA1c ≥6.5% (48 mmol/mol) and no self-reported diabetes. We studied the association of education, income and contact with a general practitioner on undiagnosed diabetes and estimated adjusted prevalence ratio (aPR) from multivariable adjusted (age, sex, body mass index) log-binomial regression. Results - Higher education was associated with lower prevalence of diagnosed and undiagnosed diabetes. Those with secondary and tertiary education had lower prevalence of undiagnosed diabetes (aPR for tertiary vs primary: 0.54, 95% CI: 0.44 to 0.66). Undiagnosed as a proportion of all diabetes was also significantly lower in those with tertiary education (aPR:0.78, 95% CI: 0.65 to 0.93). Household income was also negatively associated with prevalence of undiagnosed diabetes. Across the surveys, approximately 80% of those with undiagnosed diabetes had been in contact with a general practitioner the last year, similar to those without diabetes. Conclusions - Undiagnosed diabetes was lower among participants with higher education. The hypothesis that those with undiagnosed diabetes had been less in contact with a general practitioner was not supported

LIGHT/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro

Published version. Source at http://dx.doi.org/10.1007/s00125-016-4036-y Aims/hypothesis: Activation of inflammatory pathways is involved in the pathogenesis of type 2 diabetes mellitus. On the basis of its role in vascular inflammation and in metabolic disorders, we hypothesised that the TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) could be involved in the pathogenesis of type 2 diabetes mellitus. Methods: Plasma levels of LIGHT were measured in two cohorts of type 2 diabetes mellitus patients (191 Italian and 40 Norwegian). Human pancreatic islet cells and arterial endothelial cells were used to explore regulation and relevant effects of LIGHT in vitro. Results: Our major findings were: (1) in both diabetic cohorts, plasma levels of LIGHT were significantly raised compared with sex- and age-matched healthy controls (n = 32); (2) enhanced release from activated platelets seems to be an important contributor to the raised LIGHT levels in type 2 diabetes mellitus; (3) in human pancreatic islet cells, inflammatory cytokines increased the release of LIGHT and upregulated mRNA and protein levels of the LIGHT receptors lymphotoxin β receptor (LTβR) and TNF receptor superfamily member 14 (HVEM/TNFRSF14); (4) in these cells, LIGHT attenuated the insulin release in response to high glucose at least partly via pro-apoptotic effects; and (5) in human arterial endothelial cells, glucose boosted inflammatory response to LIGHT, accompanied by an upregulation of mRNA levels of HVEM (also known as TNFRSF14) and LTβR (also known as LTBR). Conclusions/interpretation: Our findings show that patients with type 2 diabetes mellitus are characterised by increased plasma LIGHT levels. Our in vitro findings suggest that LIGHT may contribute to the progression of type 2 diabetes mellitus by attenuating insulin secretion in pancreatic islet cells and by contributing to vascular inflammation

Single-centre, triple-blinded, randomised, 1-year, parallel-group, superiority study to compare the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on remission of type 2 diabetes and β-cell function in subjects with morbid obesity: a protocol for the Obesity surgery in Tønsberg (Oseberg) study

publishedVersio

Characteristics of Glucose Metabolism in Nordic and South Asian Subjects with Type 2 Diabetes

Background: Insulin resistance and type 2 diabetes are more prevalent in people of South Asian ethnicity than in people of Western European origin. To investigate the source of these differences, we compared insulin sensitivity, insulin secretion, glucose and lipid metabolism in South Asian and Nordic subjects with type 2 diabetes. Methods: Forty-three Nordic and 19 South Asian subjects with type 2 diabetes were examined with intra-venous glucose tolerance test, euglycemic clamp including measurement of endogenous glucose production, indirect calorimetry measuring glucose and lipid oxidation, and dual x-ray absorptiometry measuring body composition. Results: Despite younger mean ± SD age (49.7±9.4 vs 58.3±8.3 years, p = 0.001), subjects of South Asian ethnicity had the same diabetes duration (9.3±5.5 vs 9.6±7.0 years, p = 0.86), significantly higher median [inter-quartile range] HbA1c (8.5 [1.6] vs 7.3 [1.6] %, p = 0.024) and lower BMI (28.7±4.0 vs 33.2±4.7 kg/m2, p<0.001). The South Asian group exhibited significantly higher basal endogenous glucose production (19.1 [9.1] vs 14.4 [6.8] µmol/kgFFM⋅min, p = 0.003). There were no significant differences between the groups in total glucose disposal (39.1620.4 vs 39.2617.6 µmol/kgFFM⋅min, p = 0.99) or first phase insulin secretion (AUC0–8 min: 220 [302] vs 124 [275] pM, p = 0.35). In South Asian subjects there was a tendency towards positive correlations between endogenous glucose production and resting and clamp energy expenditure. Conclusions: Subjects of South Asian ethnicity with type 2 diabetes, despite being younger and leaner, had higher basal endogenous glucose production, indicating higher hepatic insulin resistance, and a trend towards higher use of carbohydrates as fasting energy substrate compared to Nordic subjects. These findings may contribute to the understanding of the observed differences in prevalence of type 2 diabetes between the ethnic groups

Description of patients.

<p>Data are presented as number (percentage) or as mean ± standard deviation. <i>p</i>-values from <i>^a</i>Student's t-test or <i>^b</i>Chi square test. OAD: oral antidiabetic agent, GLP-1: Glucagon-like peptid 1 analogue. Microalb.: microalbuminuria. Other complications include ophthalmopathy, neuropathy, diabetic foot, sexual dysfunction and periodontal disease. NOR = Nordic, SA = South Asians.</p

Basal and Clamp Indirect Calorimetry.

<p>Data are presented as mean ± standard deviation or median [inter-quartile range]. <i>p</i>-values from Student’s <i>t</i>-tests or Mann-Whitney U tests as appropriate. NOR: Nordic, SA: South Asians, FFM: fat free mass, REE: resting energy expenditure, EE_clamp: energy expenditure during clamp, RQ: respiratory quotient, ΔRQ: change in respiratory quotient from basal to clamp conditions.</p

Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight

Aims/hypothesis Obesity and insulin resistance may be associated with altered expression and secretion of adipokines. Physical activity can markedly improve insulin sensitivity, but the association with adipokines remains largely unknown. In this study, we examined the effects of physical activity on the subcutaneous white adipose tissue (scWAT) secretome and its relationship to insulin sensitivity. Methods As reported previously, we enrolled 26 sedentary, middle-aged men (13 dysglycaemic and overweight; 13 normoglycaemic and of healthy weight) into a 12 week, supervised, intensive physical exercise intervention that included two endurance and two resistance sessions each week. Insulin sensitivity was measured as the glucose infusion rate from a euglycaemic–hyperinsulinaemic clamp. In our previous study, we measured maximum oxygen uptake, upper- and lower-body strength and a range of circulating biomarkers, and quantified adipose tissue depots using MRI and magnetic resonance spectroscopy. We have now performed global mRNA sequencing, microarrays and RT-PCR of scWAT and skeletal muscle biopsies, and quantified selected plasma adipokines by ELISA. Results Insulin sensitivity increased similarly in both dysglycaemic (45%) and normoglycaemic (38%) men after 12 weeks of exercise, as reported previously. mRNA sequencing of scWAT revealed 90 transcripts that responded to exercise in dysglycaemic men, whereas only marginal changes were observed in normoglycaemic men. These results were validated using microarrays and RT-PCR. A total of 62 out of 90 transcripts encoded secreted proteins. Overall, 17 transcripts were upregulated and 73 transcripts were downregulated. Downregulated transcripts included several macrophage markers, and were associated with inflammatory and immune-related pathways. Levels of these immune-related transcripts were enhanced in dysglycaemic men vs normoglycaemic men at baseline, but were normalised after the exercise intervention. Principal component and correlation analyses revealed inverse correlations between levels of these immune-related transcripts and insulin sensitivity at baseline, after the intervention, and for the change between baseline and after the intervention. In addition, levels of these transcripts at baseline could predict exercise-induced improvements in insulin sensitivity. Adipokine levels in scWAT (but not in skeletal muscle) were significantly correlated with corresponding plasma adipokine concentrations, as exemplified by leptin, high-molecular-weight adiponectin and secreted frizzled-related protein 4 (SFRP4). SFRP4 mRNA was the most exercise-responsive transcript in scWAT from dysglycaemic men, and plasma SFRP4 concentrations were reduced in dysglycaemic men, but not in normoglycaemic men, after 12 weeks of exercise. Conclusions/interpretation This study indicates that scWAT may be an important mediator of exercise-induced improvements in insulin sensitivity, especially in overweight dysglycaemic individuals at increased risk of developing type 2 diabetes

Vitamin D, Gestational Diabetes, and Measures of Glucose Metabolism in a Population-Based Multiethnic Cohort

Objective. We explored associations between maternal 25-hydroxyvitamin D (25(OH)D) status during pregnancy and gestational diabetes (GDM) and other measures of glucose metabolism. Methods. We analysed 25(OH)D at 15 and 28 gestational weeks (GW) in 745 multiethnic pregnant women attending antenatal care units in Oslo, Norway, between 2008 and 2010. GDM was diagnosed with a 75 g oral glucose tolerance test at 28 GW. Separate regression analyses were performed to investigate associations between 25(OH)D and GDM and measures of glucose metabolism. Results. A higher proportion of ethnic minority women had GDM () and low 25(OH)D () compared to Europeans. In logistic regression analyses, 25(OH)D < 50 nmol/L was associated with GDM after adjusting for age, parity, education, and season (OR 1.6; 95% CI 1.1–2.2). After additional adjustments for variables reflecting fat mass (skinfolds or BMI) and ethnicity, the association disappeared with ethnicity having a much stronger effect than the adiposity variables. We got similar results exploring effects on other measures of glucose metabolism and when change in 25(OH)D from inclusion to 28 GW was taken into account. Conclusions. Vitamin D deficiency was not associated with GDM or glucose metabolism in a multiethnic population-based study, after adjustments for confounding factors, in particular ethnicity

Changes in bone quality after Roux-en-Y gastric bypass: A prospective cohort study in subjects with and without type 2 diabetes

Background Obesity and type 2 diabetes (T2D) are associated with an increased risk of skeletal fractures despite a normal areal bone mineral density (aBMD) and low bone turnover, possibly due to reduced bone material strength. Roux-en-Y gastric bypass (RYGB) enables a substantial and persistent weight loss and resolution of obesity related comorbidities such as T2D. However, the procedure induces a decrease in aBMD and increased bone turnover and fracture rate. To our knowledge, changes in bone material strength after RYGB have not been explored. This study aimed to evaluate changes in factors influencing bone quality; bone material strength, aBMD and bone turnover markers, in a population with morbid obesity undergoing RYGB and whether these changes differed in participants with and without T2D. We also sought to assess factors associated with bone material strength and bone mineral density in obese subjects before and after RYGB. Methods We examined 34 participants before and one year after RYGB, of whom 13 had T2D. Bone material strength index (BMSi) was evaluated by impact microindentation, aBMD and body composition by Dual energy X-ray absorptiometry, levels of bone turnover markers and calciotropic hormones were estimated from fasting serum samples. Participants with and without T2D were comparable before surgery, with the exception of glycosylated hemoglobin (HbA1c). Results Preoperatively, BMSi was inversely associated with BMI, βunadjusted -1.1 (-1.9 to -0.28), R2 = 0.19, p = 0.010, and this association remained significant after adjusting for age and gender. After RYGB the participants had lost a mean ± SD of 33.9 ± 10.9 kg, 48.7 ± 14.2 % of total body fat, increased physical activity, unchanged vitamin D levels, and all but one of the 13 participants with T2D were in diabetes remission. BMSi increased from 78.1 ± 8.5 preoperatively to 82.0 ± 6.4 one year after RYGB, corresponding to an increase of 4.0 ± 9.8 in absolute units or 6.3 ± 14.0 %, p = 0.037. The increase was comparable in participants with and without T2D. In subjects with T2D, a larger decrease in HbA1c was associated with a larger increase in BMSi βunadjusted -9.2 (-16.5 to -1.9), R2 = 0.47, p = 0.019. Bone turnover markers (CTX-1 and PINP) increased by 195.1 ± 133.5 % and 109.5 ± 70.6 %, respectively. aBMD decreased by 3.9 ± 5.5 % in the lumbar spine, 8.2 ± 4.6 % in the femoral neck, 11.6 ± 4.9 % in total hip and 9.4 ± 3.8 % in total body. Conclusion Our findings indicate that bone material strength improves despite an increase in bone turnover and a decrease in aBMD one year after RYGB. Trends were statistically comparable in participants with and without T2D. However, improved glucose control was associated with improved bone material strength in participants with T2D