Diabetic peripheral neuropathy is an abnormality of the nervous system in diabetics which results in a loss of sensation in the feet and the legs. The exact cause of peripheral neuropathy in diabetics is not clearly understood, but many theories exist. One popular theory is based on the loss of small vessel blood flow to the nerves, which impairs the nerves and results in nerve dysfunction. A new study, published online in the journal Diabetes, found that elevated triglycerides were associated with the progression of diabetic neuropathy (1). Researchers at the University of Michigan and Wayne State University evaluated 427 diabetic patients with neuropathy. The sural nerve, which travels on the outside of the leg down to the foot, was used to measure fiber density, the nerve signal speed and vibration threshold. After one year, those individuals with high triglycerides at baseline had significant progression of their neuropathy in comparison to those with normal triglyceride levels at baseline. The duration of diabetes, active treatment of diabetes or body mass index were not associated with neuropathy progression. The authors concluded that triglyceride levels are an active predictor of neuropathy progression in diabetics.

The authors stated that the study findings reinforced the link between cardiovascular disease and peripheral neuropathy. Triglycerides are a type of fat the body uses to store energy. When food consumed exceeds calories exerted, the body stores the excess calories in fat cells as triglycerides. Triglycerides are part of the blood lipid panel used to evaluate cardiovascular disease risk. Elevated triglycerides are a well-known cardiovascular disease risk factor.

The idea that lipids are associated with small blood vessel disease (microangiopathy) is not new. Previous studies have found associations between high levels of triglycerides in the blood and microangiopathy in diabetics (2). The lack of blood flow to the nerves, as a result of microangiopathy, causes changes within the nerves (demyelination and axonal degeneration) and results in nerve dysfunction. Microangiopathy causes the blood vessel lining to thicken which results in a narrowing of the vessel lumen, reducing blood flow (3). Without adequate blood flow, the nerves undergo changes, which ultimately result in nerve dysfunction. This recent research reinforces the link between small blood vessel disease and diabetic peripheral neuropathy.

1. Wiggin TD et al. Elevated Triglycerides Correlate with Progression of Diabetic Neuropathy. Diabetes published online, May 1, 2009, as db08-1771.

2. Eckel RH et al. Plasma lipids and microangiopathy in insulin-dependent diabetes mellitus. Diabetes Care. 1981 Jul-Aug;4(4):447-53.

3. Powell HC. Microangiopathy in human diabetic neuropathy. Acta Neuropathologica. Volume 68, Number 4 / December, 1985.

A novel fixed-dose combination tablet of repaglinide plus metformin provides comparable glycemic control to a rosiglitazone plus metformin tablet, show results from a phase III study.

Combining oral agents into fixed-dose combination tablets offers potential increased convenience for patients and increased compliance with therapy.

Philip Raskin (University of Texas Southwestern Medical Center, Dallas, Texas, USA) and colleagues compared the efficacy and safety of the recently-approved repaglinide/metformin fixed-dose combination tablet with an existing rosiglitazone/metformin formulation.

In the 26-week study, 561 individuals with Type 2 diabetes not adequately controlled with mono- or dual oral antidiabetes medication were randomized in a 1:1:1 fashion to a repaglinide/metformin fixed-dose combination tablet either twice, or three times daily, or a rosiglitazone/metformin fixed-dose combination tablet twice daily.

The study was designed to test primarily whether treatment with the repaglinide/metformin single-tablet combination is noninferior to treatment with a rosiglitazone/metformin tablet as measured by changes in glycated hemoglobin (HbA1c), and secondly that treatment with repaglinide/metformin twice daily is noninferior to three times daily treatment.

“The repaglinide/metformin fixed-dose combination was shown here to be noninferior to rosiglitazone/metformin,” report the authors in the journal Diabetes, Obesity and Metabolism.

Final changes in HbA1c were not significantly different between the repaglinide/metformin and the rosiglitazone/metformin treatment arms, although reductions were observed earlier with repaglinide/metformin.

In contrast, rosiglitazone/metformin showed significantly greater reductions in fasting plasma glucose at weeks 18 and 26 than repaglinide/metformin.

The authors attribute this observation to the mechanisms of action of the two compounds. An insulin sensitizer such as rosiglitazone is more likely to improve fasting plasma glucose levels, whereas an insulin secretagogue such as repaglinide taken at mealtime is more likely to improve postprandial glucose excursions.

Rosiglitazone/metformin had a mostly adverse effect on lipid profiles. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol all increased in this group, while the same parameters all decreased or were essentially unchanged during treatment with repaglinide/metformin.

As expected, hypoglycemic episodes were more frequent with repaglinide/metformin than rosiglitazone/metformin (38.8% vs 10.2%, respectively), although there were no episodes of severe hypoglycemia.

In the rosiglitazone/metformin group, peripheral edema was reported in 6.5% of individuals, but in only 2.1% of individuals in the repaglinide/metformin group. Overall adverse event profiles were comparable between treatment groups.

“This new repaglinide/metformin fixed-dose combination twice daily had efficacy comparable to that of the rosiglitazone/metformin fixed-dose combination twice daily currently in clinical use,” conclude the authors.

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

Free abstract

Time spent taking part in moderate and vigorous physical activity (MVPA) improves indicators of insulin resistance independently of time spent sedentary, taking part in light-intensity activity, and TV viewing, report researchers in the journal Diabetes Care.

Low levels of physical activity are associated with insulin resistance, which is an independent predictor for Type 2 diabetes even in people with normal glucose levels.

Ulf Ekelund (University of Cambridge, UK) and colleagues examined whether time spent sedentary, at light-intensity activity, at MVPA, and TV viewing predict future insulin resistance in people at high risk for Type 2 diabetes.

This information is important as while existing guidelines on physical activity emphasize the importance of MVPA, they do not consider the potential harmful effects of sedentary living.

The researchers measured physical activity and anthropometric and metabolic variables at baseline and after 1 year of follow-up in 192 individuals with a family history of Type 2 diabetes taking part in the ProActive UK trial.

As it is difficult to accurately capture light-intensity activity or total sedentary behavior by questionnaire, physical activity was measured objectively by accelerometry. Insulin resistance was expressed as fasting insulin and the homeostasis model assessment score (HOMA-IR).

The authors report that baseline MVPA was a significant predictor of fasting insulin at follow-up and that the association approached significance for HOMA-IR, independently of time spent sedentary or involved in light-intensity activity, gender, age, smoking status, waist circumference, and self-reported TV viewing.

Time spent sedentary and at light-intensity activity were not significantly associated with insulin resistance.

The authors also found that change in MVPA was significantly and inversely related to the change in fasting insulin and the HOMA score after adjustment for baseline characteristics, TV viewing, and follow-up time.

In addition, an increase in MVPA over 1 year was associated with improved insulin sensitivity.

“These results highlight the importance of promoting moderate-intensity activity such as brisk walking to improve insulin sensitivity and other metabolic risk factors and to prevent Type 2 diabetes, at least in individuals with a high risk of developing this disease,” conclude the authors.

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

Free abstract