In people at high risk for developing diabetes, the use of metformin shows beneficial effects on cardiometabolic risk factors, post-hoc analysis shows.

Recent guidelines from international diabetes associations such as the International Diabetes Federation, the American Diabetes Association, and the European Association for the Study of Diabetes suggest that metformin may be a pharmacological complement to lifestyle measures for the prevention of Type 2 diabetes in high-risk individuals.

This prompted Annick Fontbonne (IRD Center, Montpellier, France) and co-workers to re-analyze data from BIGPRO1 (Biguanides and Prevention of the Risks in Obesity), a 1-year trial conducted in the early 1990s, which studied the effects of metformin versus placebo on clinical and metabolic parameters in 457 non-diabetic individuals with upper-body obesity.

The authors compared the changes in cardiometabolic risk factors between treatment groups in two subsets of trial participants consisting of 101 individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and 51 individuals who fulfilled the inclusion criteria for the Diabetes Prevention Program (DPP), a trial in which metformin was effective in delaying the onset of diabetes.

In the IFG/IGT subset, metformin was associated with a 14.1 mmHg reduction in systolic blood pressure at 1 year compared with a 2.0 mmHg reduction for placebo. Slight reductions were also observed for fasting plasma glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol in people receiving metformin, whereas these parameters increased in the placebo group.

The authors noted similar results in the subset of individuals with DPP criteria.

There were no significant differences between the treatment groups in a number of other cardiometabolic risk factors, such as weight, 2-hour post-load blood glucose, fasting and 2-hour post-load insulin, high-density lipoprotein cholesterol, triglycerides, and fibrinolytic markers.

The authors recognize that as a post-hoc analysis their results have limitations, and emphasize that lifestyle modifications are the primary objective of diabetes prevention in all at-risk individuals.

However, they say that, as one of only a few randomized controlled trials on the effects of metformin in non-diabetic individuals, these data support the use of metformin as a useful addition to lifestyle measures in the prevention of diabetes in at-risk individuals.

“Our present analysis suggests that metformin treatment in prediabetic individuals, compared with placebo, has no untoward effects on the cardiometabolic risk factors that are frequently encountered in such subjects and may even have beneficial effects on some of them,” Fontbonne and team conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Infection with Helicobacter pylori is associated with increased levels of fetuin A and associated insulin resistance, which may be evidence of a link with diabetes, say researchers.

“Among the various factors capable of inducing insulin resistance, the upregulation of ?2-Heremans Schmid glycoprotein, also known as human fetuin A, has been linked with impaired insulin sensitivity, glucose metabolism and, subsequently, the onset of diabetes mellitus,” explain Spyros Potamianos (University of Thessaly, Larissa, Greece) and colleagues.

Certain pathogens have been observed to increase levels of fetuin A. To investigate whether H. pylori is such an infection, the researchers measured levels of fetuin A and fasting insulin and glucose in 105 non-diabetic individuals who were undergoing esophagogastroduodenoscopy due to dyspeptic complaints.

As reported in the journal Diabetologia, 72 participants were found to be infected with H. pylori and 33 were not. In multivariate analysis (adjusted for age, gender, body mass index, lipids, and C-reactive protein), H. pylori-positive individuals had significantly higher levels of fetuin A (0.74 vs 0.57 g/l) and homeostasis model assessment of insulin resistance (2.6-2.8 vs 1.9-2.0) than those who were not infected.

However, fasting glucose concentrations were similar between the two groups.

Potamianos and team say that the “data from the present study are consistent with the notion that H. pylori infection may induce insulin resistance.”

However, they caution that “the present model cannot be regarded as final, since it was shaped based upon the findings of a study of a more or less observational nature.”

They conclude: “Further research is therefore required, preferably using a more ‘mechanistic’ approach so that the conclusions presented above may be verified, and perhaps expanded by the inclusion of other constituents, eg, adipokines, gastrin or somatostatin, before a widely accepted mechanism is completely established.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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The burden of rupture-prone atherosclerotic plaque increases with the duration of diabetes mellitus, a study using intravascular ultrasound (IVUS) has found.

The finding may explain, in part, why the risk for coronary heart disease rises with increasing duration of diabetes mellitus, say the researchers writing in the journal Circulation: Cardiovascular Interventions.

For the study, Steven Marso (University of Missouri, Kansas City, USA) and co-workers used IVUS and virtual histology to investigate the relationship between thin-cap fibroatheroma and diabetes duration.

Thin-cap fibroatheromatous plaques are characterized by a necrotic core, intraplaque hemorrhage, calcification, and a thin layer of connective tissue, and are particularly susceptible to rupture, explain the researchers.

The study participants were 54 diabetic individuals undergoing diagnostic coronary angiography, of whom 26 had been diagnosed with diabetes for less than 10 years and 28 had suffered from the disease for 10 year or longer.

Those with a longer duration of diabetes were older, less likely to have a history of tobacco use, had higher total cholesterol levels, and were more likely to be treated with insulin than those with a shorter duration of diabetes.

Furthermore, the total plaque burden was significantly greater in patients with a longer duration of diabetes, at 60.4% in those with diabetes for 10 or more years versus 50.2% for those with diabetes for less than 10 years.

The distribution of plaque phenotypes also differed by diabetes duration, with thin-cap fibroatheroma accounting for just 10.8% of plaques in those with diabetes for less than 10 years versus 54.4% of plaques in those with diabetes for 10 or more years. This difference was highly statistically significant and remained so after adjustment for multiple comparisons, clinical characteristics, and diabetes treatment.

Noting that thin-cap fibroatheroma is associated with an increased risk for coronary thrombosis and cardiovascular death, Marso et al conclude that not only the presence but also the duration of diabetes “contribute to high-risk atherosclerotic phenotypes.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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A combined risk allele score calculated from variants in four genes associated with fasting plasma glucose levels significantly predicts risk for Type 2 diabetes, show results from the Dutch New Hoorn Study.

“Several reports have shown that genetic variation in the genes for glucokinase (GCK), glucokinase regulatory protein (GCKR), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2) and melatonin receptor type 1B (MTNR1B) is associated with fasting plasma glucose,” say L ‘t Hart (Leiden University, The Netherlands) and colleagues.

In this study, the team tested 2361 non-diabetic individuals and 2628 individuals with Type 2 diabetes from the Dutch New Hoorn Study for the single nucleotide polymorphisms (SNPs) rs1799884 (GCK), rs1260326 (GCKR), rs560887 (G6PC2), and rs10830963 (MTNR1B).

They found that the GCK, G6PC2, and MTNR1B variants, but not the GCKR SNP, were significantly associated with fasting plasma glucose levels.

When these three SNPs were combined to form a risk allele score, fasting plasma glucose levels went up by 0.05 mmol/l per additional risk allele and glycated hemoglobin went up by around 0.03% per risk allele.

The most common risk allele score was four and therefore was used as a reference group. Individuals with less than three risk alleles had a 23% reduction in the risk for Type 2 diabetes, whereas those with more than five had a 2.05-fold increased risk for the condition.

Of note, age at diagnosis was significantly associated with the number of risk alleles present.

“To our knowledge, this is the first report showing that the analyzed loci have a combined effect on Type 2 diabetes susceptibility, although the contribution of each individual variant to the risk of Type 2 diabetes is very low or undetectable,” say ‘t Hart and team.

They conclude in the journal Diabetologia: “If replicated, our results imply that these loci not only influence fasting plasma glucose levels, probably through an altered set point for glucose at which an insulin response is elicited, but also jointly increase the risk of Type 2 diabetes and the age at diagnosis.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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