Mitochondrial mutation m.3243A>G associates with insulin resistance in non-diabetic carriers

Aim This case–control study aimed to examine impairments in glucose metabolism in non-diabetic carriers of the mitochondrial mutation m.3243A>G by evaluating insulin secretion capacity and sensitivity. Methods Glucose metabolism was investigated in 23 non-diabetic m.3243A>G carriers and age-, sex- and BMI-matched healthy controls with an extended 4-h oral glucose tolerance test (OGTT). Insulin sensitivity index and acute insulin response were estimated on the basis of the OGTT. This was accompanied by examination of body composition by dual-energy X-ray absorptiometry (DXA), maximum aerobic capacity and a Recent Physical Activity Questionnaire (RPAQ). Results Fasting p-glucose, s-insulin and s-c-peptide levels did not differ between m.3243A>G carriers and controls. Insulin sensitivity index (BIGTT-S1) was significantly lower in the m.3243A>G carriers, but there was no difference in the acute insulin response between groups. P-lactate levels were higher in carriers throughout the OGTT. VO2max, but not BMI, waist and hip circumferences, lean and fat body mass%, MET or grip strength, was lower in mutation carriers. BIGTT-S1 remained lower in mutation carriers after adjustment for multiple confounding factors including VO2max in regression analyses. Conclusions Glucose metabolism in m.3243A>G carriers was characterized by reduced insulin sensitivity, which could represent the earliest phase in the pathogenesis of m.3243A>G-associated diabetes.

Two nights of recovery sleep restores the dynamic lipemic response, but not the reduction of insulin sensitivity, induced by five nights of sleep restriction

Chronic inadequate sleep is associated with increased risk of cardiometabolic diseases. The mechanisms involved are poorly understood but involve changes in insulin sensitivity, including within adipose tissue. The aim of this study was to assess the effects of sleep restriction on nonesterified fatty acid (NEFA) suppression profiles in response to an intravenous glucose tolerance test (IVGTT) and to assess whether 2 nights of recovery sleep (a “weekend”) is sufficient to restore metabolic health. We hypothesized that sleep restriction impairs both glucose and lipid metabolism, specifically adipocyte insulin sensitivity, and the dynamic lipemic response of adipocyte NEFA release during an IVGTT. Fifteen healthy men completed an inpatient study of 3 baseline nights (10 h of time in bed/night), followed by 5 nights of 5 h of time in bed/night and 2 recovery nights (10 h of time in bed/night). IVGTTs were performed on the final day of each condition. Reductions in insulin sensitivity without a compensatory change in acute insulin response to glucose were consistent with prior studies (insulin sensitivity P = 0.002; acute insulin response to glucose P = 0.23). The disposition index was suppressed by sleep restriction and did not recover after recovery sleep ( P < 0.0001 and P = 0.01, respectively). Fasting NEFAs were not different from baseline in either the restriction or recovery conditions. NEFA rebound was significantly suppressed by sleep restriction ( P = 0.01) but returned to baseline values after recovery sleep. Our study indicates that sleep restriction impacts NEFA metabolism and demonstrates that 2 nights of recovery sleep may not be adequate to restore glycemic health.

Fasting Plasma Glucose Indicates Reversibility of the Acute Insulin Response after Short-Term Intensive Insulin Therapy in Patients with Various Duration of Type 2 Diabetes

Recovery of acute insulin response (AIR) is shown to be associated with long-term outcomes of patients with early type 2 diabetes treated with short-term intensive insulin therapy (SIIT). However, the complexity of measuring an AIR limits its utility in a real-world clinical setting. The aim of the study was to assess fasting indicators that may estimate recovery of the AIR after SIIT. We enrolled 62 patients with type 2 diabetes mellitus (T2DM) of varying disease duration who had poor glycemic control. Participants were treated with SIIT using insulin pumps to achieve near normoglycemia for 7 days. The AIR before and after the therapy were measured by intravenous glucose tolerance tests. After the therapy, AIR increased from −16.7 (−117.4, 52.4) pmol/L·min to 178.7 (31.8, 390.7) pmol/L·min (P<0.001) while hyperglycemia was alleviated; this improvement was observed in all disease duration categories. AIR was almost absent when fasting plasma glucose (FPG) > 10 mmol/L, while both AIR (R=−0.53, P<0.001) and its improvement from baseline (△AIR, R=−0.52, P<0.001) were negatively associated with FPG after SIIT when FPG < 10 mmol/L. In multivariate analyses, FPG after SIIT and baseline fasting C peptide were independent indicators of both AIR after the therapy and ∆AIR; HDL-C after the therapy also predicted AIR after the therapy. We concluded that recovery of the AIR could be obtained in T2DM patients of varying disease duration by SIIT and it could be conveniently estimated using posttreatment fasting plasma glucose and other fasting indicators.

Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial

ABSTRACT Background Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned. Objective The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables. Design We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group). Methods The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period. Results Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of −17.7% (−29.3% to −1.0%) in comparison to −2.8% (−30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350–1040 mU · L-1· min) to 671 mU · L-1· min (376–1010 mU · L-1· min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence. Conclusions Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. This trial was registered at www.clinicaltrials.gov as NCT02589002.

Cardiorespiratory Fitness and Adiposity as Determinants of Metabolic Health—Pooled Analysis of Two Twin Cohorts

Context: The joint effects of cardiorespiratory fitness (CRF) and body composition on metabolic health are not well known. Objective: To examine the associations of CRF, fat-free mass index (FFMI), and fat mass index (FMI) with metabolic health in individual twins and controlling for genetic and shared environmental effects by studying monozygotic intrapair differences. Design, Setting, and Participants: Two cross-sectional samples of healthy adult monozygotic and dizygotic twins were drawn from population-based Danish and Finnish national twin registries (n = 996 and n = 309). Main Measures: CRF was defined as VO2max divided by fat-free mass. Insulin sensitivity and acute insulin response indices were derived from an oral glucose tolerance test. A continuous metabolic syndrome score was calculated. Visceral and liver fat were measured in the Finnish sample. Associations were analyzed separately in both cohorts with multivariate linear regression and aggregated with meta-analytic methods. Results: Insulin sensitivity, acute insulin response, metabolic syndrome score, visceral, and liver fat amount had strong and statistically significant associations with FMI (|β| 0.53 to 0.79), whereas their associations with CRF and FFMI were at most weak (|β| 0.02 to 0.15). The results of the monozygotic intrapair differences analysis showed the same pattern. Conclusions: Although FMI is strongly associated with worsening of metabolic health traits, even after controlling for genetic and shared environmental factors, there was little evidence for the effects of CRF or FFMI on metabolic health. This suggests that changing FMI rather than CRF or FFMI may affect metabolic health irrespective of genetic or early environmental determinants.

The effect of a home-based strength training program on type 2 diabetes risk in obese Latino boys

Objective: To determine the effects of a home-based strength training (HBST) intervention on insulin sensitivity (SI), compensatory acute insulin response and β-cell function, body composition measures, and maximum strength in obese Latino boys. Methods: A total of 26 obese Latino males aged between 14 and 18 years were randomized to either a twice-weekly (n=15) or a control group (C; n=15) for 16 weeks. HBST for 16 weeks, composed of two 1-h sessions per week. Outcome measures were assessed pre-and post-intervention/control condition and included SI, acute insulin response to glucose (AIR) and disposition index (DI), fasting glucose, 2-h glucose, body composition using waist-hip circumferences, body mass index (BMI), dual energy X-ray absorptiometry (DEXA) scan, blood pressure, and strength by 1-repetition maximum. A repeated measures GLM was used to assess differences in changes in outcome measures, between the C and the HBST groups. Results: There were no significant overall intervention effects on any of the outcome variables (p<0.05). Conclusion: These results suggest that an HBST does not improve SI, maximal strength or decrease adiposity in obese Latino boys.