Metabolite ratios as potential biomarkers for type 2 diabetes:a DIRECT study

Aims/hypothesis Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes. Methods We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case–control studies of prevalent (n = 4925) and incident (n = 4277) diabetes. The data were analysed using regression models with adjustment for potential confounders. Results There were dynamic changes in metabolite levels in response to the different secretagogues. Furthermore, several fasting pairwise metabolite ratios were associated with one or multiple clamp-derived measures of insulin secretion (all p Conclusion/interpretation In this study we have shown that the Val_PC ae C32:2 metabolite ratio is associated with an increased risk of type 2 diabetes and measures of insulin secretion and resistance. The observed effects were stronger than that of the individual metabolites and independent of known risk factors.</p

Traditional risk factors for essential hypertension: analysis of their specific combinations in the EPIC-Potsdam cohort

Appropriate interventions might improve the prevention of essential hypertension. This requires a comprehensive view of modifiable lifestyle factors (MLFs) distribution and effect. To determine how six MLFs (general adiposity, abdominal adiposity, alcohol consumption, smoking, diet, physical inactivity) for risk of hypertension are distributed and how their combinations affect the risk, a prospective study cohort of 11,923 healthy participants from the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam Study was used. Of these, 1,635 developed hypertension during a mean follow-up of 10.3 years. Mutually exclusive combinations, clustering and interactions of MLFs were then investigated stratifying by sex, Hazard Ratios (HRs) and Population Attributable Risks (PARs%) were calculated. General adiposity alone was sufficient to increase the risk of hypertension (HR = 1.86, PAR% 3.36), and in this cohort it played a major role in enhancing the risk of hypertension, together with smoking and physical inactivity. MLFs had a different impact and a different modulation of risk in women and men, and they showed a remarkable tendency to occur in specific patterns with higher prevalence than expected. This indication can help to promote a holistic approach through multifactorial preventive strategies addressing more than a factor at a time. For prevention of hypertension addressing adiposity together with smoking, promoting at the same time physical activity should be the first choice

Effects of acarbose treatment on markers of insulin sensitivity and systemic inflammation

Background: This study assessed the effect of postprandial glucose reduction by acarbose on insulin sensitivity and biomarkers of systemic inflammation. Methods: This was a single-center, double-blind, randomized, placebo-controlled, crossover study <40 weeks in duration, involving 66 subjects with varying degrees of glucose tolerance. Eligible patients completed a 3-week run-in period and were randomized to receive either 100 mg of acarbose three times daily followed by placebo, or vice versa, lasting 12 weeks each with a 12-week washout between interventions. Liquid meal challenges and hyperinsulinemic-euglycemic glucose clamp were performed at weeks 0, 12, 24, and 36. Results: Fasting proinsulin levels and proinsulin-to-adiponectin ratios but not fasting adiponectin levels were significantly lower during acarbose versus placebo treatment. Clamp-derived insulin sensitivity index and body weight were unchanged by the intervention. Levels of fasting insulin, fasting glucose, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1 beta were comparable between treatments. In the liquid meal challenge tests, postprandial glucose and insulin responses were significantly lower during acarbose versus placebo treatment. The effects of acarbose on the reduction of fasting proinsulin was most pronounced in subjects with impaired fasting glucose/impaired glucose tolerance (n = 24). Conclusions: Reduction of the glycemic load by acarbose decreased fasting levels of proinsulin but had no effect on adiponectin and whole-body insulin sensitivity as well as biomarkers reflecting inflammation. The preventive effects of acarbose on type 2 diabetes mellitus and cardiovascular risk need further investigation and cannot be explained by changes of insulin resistance and inflammatory biomarkers

Hepatic insulin clearance is closely related to metabolic syndrome components

OBJECTIVE Insulin clearance is decreased in type 2 diabetes mellitus (T2DM) for unknown reasons. Subjects with metabolic syndrome are hyperinsulinemic and have an increased risk of T2DM. We aimed to investigate the relationship between hepatic insulin clearance (HIC) and different components of metabolic syndrome and tested the hypothesis that HIC may predict the risk of metabolic syndrome. RESEARCH DESIGN AND METHODS Individuals without diabetes from the Metabolic Syndrome Berlin Brandenburg (MeSyBePo) study (800 subjects with the baseline examination and 189 subjects from the MeSyBePo recall study) underwent an oral glucose tolerance test (OGTT) with assessment of insulin secretion (insulin secretion rate [ISR]) and insulin sensitivity. Two indices of HIC were calculated. RESULTS Both HIC indices showed lower values in subjects with metabolic syndrome (P < 0.001) at baseline. HIC indices correlate inversely with waist circumference, diastolic blood pressure, fasting glucose, triglycerides, and OGTT-derived insulin secretion index. During a mean follow-up of 5.1 ± 0.9 years, 47 individuals developed metabolic syndrome and 33 subjects progressed to impaired glucose metabolism. Both indices of HIC showed a trend of an association with increased risk of metabolic syndrome (HICC-peptide odds ratio 1.13 [95% CI 0.97–1.31], P = 0.12, and HICISR 1.38 [0.88–2.17], P = 0.16) and impaired glucose metabolism (HICC-peptide 1.12 [0.92–1.36], P = 0.26, and HICISR 1.31 [0.74–2.33] P = 0.36), although point estimates reached no statistical significance. CONCLUSIONS HIC was associated with different components of metabolic syndrome and markers of insulin secretion and insulin sensitivity. Decreased HIC may represent a novel pathophysiological mechanism of the metabolic syndrome, which may be used additionally for early identification of high-risk subjects