Beta cell function, hepatic insulin clearance, and insulin sensitivity in South Asian and Nordic women after gestational diabetes mellitus

South Asians have higher risk of type 2 diabetes after gestational diabetes mellitus (GDM) than Nordic women; however the mechanisms behind this difference remain unclear. We investigated insulin sensitivity, beta cell function, and hepatic insulin clearance, in 179 South Asian and 108 Nordic women ∼17 months after GDM (mean age 35.3 years and BMI 29.1 kg/m2), via an oral glucose tolerance test using deconvolution of C-peptide kinetics. 31% of South Asian and 53% of Nordic participants were normoglycemic at the time of measurement. South Asian women had higher area under the curve (AUC) for glucose, pre-hepatic insulin, peripheral insulin, and lower levels of insulin sensitivity, disposition index, and fasting hepatic insulin clearance compared with Nordic women. In the group with prediabetes or diabetes, South Asian women displayed similar AUC for glucose and pre-hepatic insulin, but higher AUC for peripheral insulin, and lower levels of disposition index, and fasting hepatic insulin clearance compared with Nordic women. The waist-to-height ratio mediated ∼25-40% of the ethnic differences in insulin sensitivity in normoglycemic women. Overall, our novel data showed that normoglycemic South Asian women after GDM displayed lower insulin secretion for a given insulin resistance, and lower hepatic insulin clearance compared with Nordic women. South Asian women are at high risk of developing type 2 diabetes after GDM, and preventive efforts should be prioritized

High prevalence and significant ethnic differences in actionable HbA 1C after gestational diabetes mellitus in women living in Norway

Background: The type 2 diabetes risk after gestational diabetes mellitus (GDM) is twice as high in South Asian compared to European women. Current guidelines differ regarding which test to use as a screening-tool post-GDM. We aimed to identify ethnic differences in the prevalence rates and early predictors for actionable HbA1c (defined as prediabetes and diabetes) short time after GDM. Methods: This cross-sectional study, enrolling South Asian and Nordic women 1–3 years after a diagnosis of GDM, was undertaken at three hospitals in Norway. We performed a clinical and laboratory evaluation including an oral glucose tolerance test (OGTT). Medical records were used to retrieve data during pregnancy. Prediabetes was classified with HbA1c alone or combined with OGTT glucose measurements according to the WHO, WHO-IEC, and ADA criteria (fasting plasma glucose (FPG) 6.1–6.9 mmol/L, FPG 6.1–6.9 mmol/L and/or HbA1c 42-47 mmol/mol (6.0-6.4%), and FPG 5.6–6.9 mmol/L and/or HbA1c 39-47 mmol/mol (5.7-6.4%)). Ethnic differences in prevalence and predictors of glucose deterioration were assed by χ2 (Pearson) tests and logistic regression models. Results: We included 163 South Asian and 108 Nordic women. Actionable HbA1c levels were highly prevalent and more so among South Asian than Nordic women (WHO-IEC-HbA1c: 25.8% vs. 6.5% (p ≤ 0.001), ADA-HbA1c: 58.3% vs. 22.2% (p ≤ 0.001)). Although adding OGTT-data gave higher combined prevalence rates of prediabetes and diabetes (WHO: 65.6% vs. 47.2% (p ≤ 0.05), WHO-IEC: 70.6% vs. 47.2% (p ≤ 0.001), ADA: 87.8% vs. 65.7% (p ≤ 0.001)), the excess risk in the South Asian women was best captured by the HbA1c. Important predictors for glucose deterioration after GDM were: South Asian ethnicity, GDM before the index pregnancy, use of glucose-lowering drugs in pregnancy, higher age, and higher in-pregnancy fasting glucose levels. Conclusions: In women with GDM 1–3 year previously, we found high prevalence and significant ethnic differences in actionable ADA-HbA1c levels, with South Asian ethnicity, GDM before the index pregnancy, and the use of glucose-lowering drugs in pregnancy as the most important risk factors. This study reinforces the importance of annual screening—preferably with HbA1c measurements—to facilitate early intervention after GDM

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

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Effects of prebiotics on postprandial GLP-1, GLP-2 and glucose regulation in patients with type 2 diabetes: A randomised, double-blind, placebo-controlled crossover trial

Aims We aimed to investigate the effect of prebiotic inulin-type fructans (ITF) versus a control supplement on postprandial levels of glucagon-like peptide-1 and -2 (GLP-1 and -2), glucose and insulin in people with type 2 diabetes. Methods Adult men and women with type 2 diabetes were randomised in a double-blind, placebo-controlled crossover study. The study participants received 16 g/d ITF and 16 g/d control supplement (maltodextrin) for 6 weeks each in two phases separated by a 4-week washout. A standardised mixed-meal test was performed before and after each intake period. The primary end point was changes in the GLP-1 response, and secondary end points were GLP-2, glucose and insulin responses. Data were analysed using mixed-model analysis. Results A total of 29 participants were included in the study. Differences between and within the two treatments in estimated area under the curves were not significant. Yet, the predicted means for meal-induced GLP-1 response in plasma showed a 4.8% decline after the prebiotic treatment and an 8.6% increase after the control treatment (difference in changes between the treatments, p < 0.001). Fasting or postprandial glucose, insulin or GLP-2 levels were not changed. Conclusions Our findings do not support that ITF improve incretin responses or glucose regulations in this population. Clinicaltrials.gov (NCT02569684)

Subsarcolemmal lipid droplet responses to a combined endurance and strength exercise intervention

Muscle lipid stores and insulin sensitivity have a recognized association although the mechanism remains unclear. We investigated how a 12‐week supervised combined endurance and strength exercise intervention influenced muscle lipid stores in sedentary overweight dysglycemic subjects and normal weight control subjects (n = 18). Muscle lipid stores were measured by magnetic resonance spectroscopy (MRS), electron microscopy (EM) point counting, and direct EM lipid droplet measurements of subsarcolemmal (SS) and intramyofibrillar (IMF) regions, and indirectly, by deep sequencing and real‐time PCR of mRNA of lipid droplet‐associated proteins. Insulin sensitivity and VO2max increased significantly in both groups after 12 weeks of training. Muscle lipid stores were reduced according to MRS at baseline before and after the intervention, whereas EM point counting showed no change in LD stores post exercise, indicating a reduction in muscle adipocytes. Large‐scale EM quantification of LD parameters of the subsarcolemmal LD population demonstrated reductions in LD density and LD diameters. Lipid droplet volume in the subsarcolemmal LD population was reduced by ~80%, in both groups, while IMF LD volume was unchanged. Interestingly, the lipid droplet diameter (n = 10 958) distribution was skewed, with a lack of small diameter lipid droplets (smaller than ~200 nm), both in the SS and IMF regions. Our results show that the SS LD lipid store was sensitive to training, whereas the dominant IMF LD lipid store was not. Thus, net muscle lipid stores can be an insufficient measure for the effects of training

Understanding mechanisms behind unwanted health behaviours in Nordic and South Asian women and how they affect their gestational diabetes follow-ups: A qualitative study

Aims: The type 2 diabetes risk following gestational diabetes mellitus (GDM) is high, particularly among South Asian women in Western countries. Our study aimed to advance the knowledge regarding the mechanisms behind suboptimal follow-up in the Nordic and South Asian women with previous GDM by comparing (1) their experiences, (2) health and disease perceptions and (3) barriers to and facilitators of health-promoting behaviours. Methods: This qualitative study was conducted in three hospital outpatient clinics in Norway, comprising six focus group interviews with 28 women 1–3 years after a pregnancy with GDM. The participants were purposively sampled and grouped according to their ethnicity. The data were analysed using thematic analysis, and a theoretical approach was applied to support the analysis and discuss the study's findings. Results: Five main themes were identified: lack of resilience, emotional distress, ‘caught between a rock and a hard place’, postpartum abandonment and insufficient guidance. The key determinants of the maintenance of unwanted health behaviours after GDM were consistent across the ethnic groups. Although the importance of a culturally sensitive approach was emphasised, it appeared secondary to the need for a more organised public healthcare during and after GDM. Conclusions: Women's real-life constraints, combined with the inadequate healthcare-service implementation, could explain the non-adherence to the lifestyle-changes guidelines essential for preventing diabetes post-GDM. We suggest promoting specific coping strategies and changing the healthcare service approach rather than relying on women's capacity to initiate the necessary changes

Understanding mechanisms behind unwanted health behaviours in Nordic and South Asian women and how they affect their gestational diabetes follow-ups: A qualitative study

Aims The type 2 diabetes risk following gestational diabetes mellitus (GDM) is high, particularly among South Asian women in Western countries. Our study aimed to advance the knowledge regarding the mechanisms behind suboptimal follow-up in the Nordic and South Asian women with previous GDM by comparing (1) their experiences, (2) health and disease perceptions and (3) barriers to and facilitators of health-promoting behaviours. Methods This qualitative study was conducted in three hospital outpatient clinics in Norway, comprising six focus group interviews with 28 women 1–3 years after a pregnancy with GDM. The participants were purposively sampled and grouped according to their ethnicity. The data were analysed using thematic analysis, and a theoretical approach was applied to support the analysis and discuss the study's findings. Results Five main themes were identified: lack of resilience, emotional distress, ‘caught between a rock and a hard place’, postpartum abandonment and insufficient guidance. The key determinants of the maintenance of unwanted health behaviours after GDM were consistent across the ethnic groups. Although the importance of a culturally sensitive approach was emphasised, it appeared secondary to the need for a more organised public healthcare during and after GDM. Conclusions Women's real-life constraints, combined with the inadequate healthcare-service implementation, could explain the non-adherence to the lifestyle-changes guidelines essential for preventing diabetes post-GDM. We suggest promoting specific coping strategies and changing the healthcare service approach rather than relying on women's capacity to initiate the necessary changes

SKELETAL MUSCLE PHOSPHATIDYLCHOLINE AND PHOSPHATIDYLETHANOLAMINE ARE RESPONSIVE TO EXERCISE AND RELATED TO INSULIN SENSITIVITY IN HUMANS

Introduction: Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) composition in skeletal muscle has been linked to insulin sensitivity.Aim: To evaluate relationships between skeletal muscle PC:PE ratio, physical exercise and insulin sensitivity in humans.Materials and Methods: PC and PE were measured in m. vastus lateralis biopsies obtained from subjects examined in different studies with different degrees of insulin sensitivity: type 2 diabetes (n=13), impaired glucose metabolism and untrained (n=13), impaired glucose metabolism and trained (n=13), obesity (n=13), untrained normal weight controls (n=13), trained normal weight controls (n=13) and endurance trained athletes (n=6). From a subset of the subjects (MyoGlu; n=26) biopsies were obtained at rest, immediately after 45 min of cycle ergometer at 70% maximum oxygen uptake, and 2 h post-exercise, before as well as after 12 weeks of combined endurance- and strength-exercise intervention. Insulin sensitivity was measured by euglycemic hyperinsulinemic clamp. In addition, several measures of physical fitness were obtained, global RNA-sequencing was performed on the biopsies, and mitochondria and lipid droplets were quantified using point counting on electron microscopic images.Results: Skeletal muscle PC:PE ratio was highest in the type 2 diabetic group and gradually lower in groups with increasing insulin sensitivity. The lowest ratio was observed among endurance athletes. Twelve weeks of exercise intervention enhanced skeletal muscle levels of PC by ~21% and PE by ~42%, and reduced the PC:PE ratio by ~16%; a reduction in the PC:PE ratio predicted increased insulin sensitivity (β=-1.6, P<0.001). Transcriptomic analyses indicated that enzymes involved in PC and PE synthesis may explain the increased levels of PC and PE and the reduction in the PC:PE ratio after 12 weeks of exercise. The PC:PE ratio also correlated with mRNA expression of genes related to insulin receptor, Akt/PkB and mTORC1 signaling, and to the fraction of lipid droplets and mitochondria within skeletal muscle cells. Mitochondrial volume was increased from 3.4-5.7% after 12 weeks of exercise intervention.Conclusion: Skeletal muscle PC:PE ratio is inversely related to insulin sensitivity. The molecular link between skeletal muscle PC:PE ratio and insulin sensitivity probably involves several mechanisms including, but not limited to, mitochondrial function