Cocoa Flavanol Supplementation and the Effect on Insulin Resistance in Females Who Are Overweight or Obese: A Randomized, Placebo-Controlled Trial

There is interest in the impact that dietary interventions can have on preventing the transition from insulin resistance to type 2 diabetes, including a suggestion that the bioactive components of cocoa may enhance fasting insulin sensitivity. However, a role for cocoa flavanols (CF) in reducing insulin resistance in the insulin-stimulated state, an important risk factor for cardiovascular disease, is unresolved. This study investigated whether CF consumption improved whole-body insulin-mediated glucose uptake (‘M’) in females with overweight/obesity, using a randomized, double-blinded, placebo-controlled, parallel-group design. Thirty-two premenopausal females (19–49 years; 27–35 kg·m−2) with elevated HOMA-IR (HOMA-IR >1.5) supplemented their habitual diet with two servings/day of a high-flavanol cocoa drink (HFC; 609 mg CF/serving; n = 16) or low-flavanol cocoa drink (LFC; 13 mg CF/serving; n = 16) for 4 weeks. Assessment of HOMA-IR and ‘M’ during a 3-h, 60 mIU insulin·m−2·min−1 euglycemic clamp was performed before and after the intervention. Data are the mean (SD). Changes to HOMA-IR (HFC −0.003 (0.57); LFC −0.0402 (0.86)) and ‘M’ (HFC 0.99 (7.62); LFC –1.32 (4.88) µmol·kg−1·min−1) after the intervention were not different between groups. Four weeks’ consumption of ~1.2 g CF/day did not improve indices of fasting insulin sensitivity or insulin-mediated glucose uptake. A recommendation for dietary supplementation with cocoa flavanols to improve glycemic control is therefore not established

Fish oil omega-3 fatty acids partially prevent lipid-induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation

Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic–hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater following n6PUFA compared with Control and n3PUFA, suggesting that mitochondrial lipid overload was responsible for the lower insulin action observed. Despite these favourable metabolic effects of n3PUFA, accumulation of total muscle acylcarnitine was not attenuated when compared with n6PUFA. These findings demonstrate that n3PUFA exert beneficial effects on insulin-stimulated skeletal muscle glucose storage and oxidation independently of total acylcarnitine accumulation, which does not always reflect mitochondrial lipid overload

Investigation of the haemodynamic effects of exenatide in healthy male subjects

AIMS In clinical studies of glucagon-like peptide-1 (GLP-1) agonists used in the management of patients with type 2 diabetes, there is often a small accompanying fall in blood pressure. The mechanism underlying this effect is not known, although exenatide, a GLP-1 mimetic, has acute regional vasodilator properties in rats. We have therefore studied the haemodynamic effects of exenatide in healthy male volunteers. METHODS We compared the effects of a single 10μg subcutaneous injection of exenatide with placebo in a double-blind, randomized, crossover study. For 2h after dosing, haemodynamic measurements were made using a Finometer, venous occlusion plethysmography and Doppler ultrasound. The urine sodium:creatinine excretion ratio was determined. RESULTS At the end of the study when exenatide was compared with placebo, heart rate had risen by a mean of 8.2 (95% CI 4.2, 12.2, P < 0.01) beatsmin-1, cardiac output by a mean of 1.2 (95% CI 0.42, 20.3, P < 0.05) lmin-1 and total peripheral resistance had fallen by 120 (95% CI -8, -233, P < 0.05) dynscm-5.There were no differences in blood pressure. The urinary sodium:creatinine ratio was increased by mean 12.4 (95% CI 4.6, 20.2, P < 0.05) mmolmmol-1 when exenatide was compared with placebo. CONCLUSIONS Exenatide has significant haemodynamic effects in healthy volunteers. The results of this study are consistent with exenatide having both vasodilator and natriuretic properties. The vascular changes may contribute to the hypotensive effect of exenatide when used chronically in patients with diabetes. © 2012 The British Pharmacological Society

Safety and effectiveness of do-it-yourself artificial pancreas system compared with continuous subcutaneous insulin infusions in combination with free style libre in people with type 1 diabetes

Aims: The use of do-it-yourself artificial pancreas systems (DIYAPS) among people with type 1 diabetes is increasing. At present, it is unclear how DIYAPS compares with other technologies such as FreeStyle Libre (FSL) and continuous subcutaneous insulin infusion (CSII). The aim of this analysis is to compare safety, effectiveness and quality-of-life outcomes of DIYAPS use with the addition of FSL to CSII. Method: Data from two large UK hospitals were extracted from the Association of British Clinical Diabetologists (ABCD) DIYAPS and FSL audits. Outcomes included HbA1c, glucose TBR (time-below-range), TIR (time-in-range), Diabetes Distress Score (DDS), and Gold hypoglycaemia score. Any adverse events were noted. Changes at follow-up were assessed using paired t-tests and ANOVA in Stata; TIR/TBR at follow-up assessed using unpaired t-tests; chi-square tests assessed the change in frequency of health utilisation (e.g. hospital admissions). Results: DIYAPS (n=35) and FSL+CSII (n=149) users, with median follow-up duration of 1.4 (IQR 0.8–2.1) and 1.3 (IQR 0.7–1.8) years, respectively, were included. HbA1c with DIYAPS use changed by −10mmol/mol [0.9%] (p<0.001, 95% CI 5, 14 [0.5, 1.3%]) significantly lower (p<0.001) than in the FSL+CSII group −3mmol/mol [0.25%] (p<0.001, 95% CI 1, 4 [0.1, 0.4%]). TIR was higher and TBR was lower in the DIYAPS group. Adverse events were rare in both groups and no significant differences were observed in the frequency of healthcare utilisation. Conclusion: DIYAPS use was associated with a lower HbA1c levels, higher TIR and lower TBR compared with FSL+CSII. There was no significant increase in adverse events, although this should be interpreted cautiously given the low numbers of users. Full results from the ABCD DIYAPS audit are awaited