Clinical Briefs

By Louis Kuritzky, MD

Weight Loss in Type 2 Diabetes

Most subjects with type 2 diabetes (DM2) are overweight. There is abundant support for the diverse benefits of weight loss in DM2, including improved insulin resistance, lipid profiles, and blood pressure, to name but a few. Unfortunately, weight loss is a very daunting challenge for most DM2 patients, often complicated by the fact that some hypoglycemic pharmacotherapies tend to induce weight gain.

In DM2, besides traditional weight loss programs, little information has been shared regarding novel dietary approaches, such as meal replacement programs (MRP) or repetitive low-calorie diets, especially in combination with pharmacotherapy.

This trial involved overweight or obese DM2 subjects (n = 61), all of whom, after calculation of daily basal energy requirement, received advice on a traditional reduced calorie diet (500-1000 Kcal reduction daily) plus exercise (recommended 30 minutes thrice weekly). Those randomized to the combination therapy received, in addition, sibutramine 10-15 mg/d and replacement meals (consisting of 900-1300 Kcal/d of meal shakes or bars, administered as 220 Kcal 4-6 times daily). Subjects were instructed to use meal replacements as their sole nutrition for 1 week every 2 months, and use the meal replacement products (calories = 340) to substitute for a single meal each day during the non-low-calorie MRP weeks.

At 1 year, weight loss in the com bined treatment group was greater than the standard treatment group, including a 6.4% decline from baseline body weight. This intensive regimen provid ed greater effect upon weight loss and A1C than some prior trials. Long-term maintenance of weight reduction has remained an elusive goal, and whether study subjects could maintain these favorable changes for a greater duration is unknown.

Redmon JB, et al. Diabetes Care. 2003;26:2505-2511.

Dalteparin and Chronic Foot Ulcers in Diabetics with PAD

The increasing prevalence of type 2 diabetes (DM2) will be likely accompanied by an increase of late-onset diabetic complications, such as chronic foot ulcers (CFU). One of the limiting factors in healing CFU is the microcirculatory impairment found in DM2.

Consecutive DM2 patients with CFU (n = 87) were randomly assigned in a double-blind fashion to dalteparin 5000 units SQ daily (or a similar volume of saline). Treatment continued until the ulcer healed, or up to 6 months. Traditional ulcer care by appropriate consultants was provided to all patients. There were 2 patients withdrawn from the study, one because of a bleeding event and one because of superficial skin necrosis at the injection sites (although concomitant insulin administration at the same sites complicates attributing etiology).

The number of patients with com pletely healed ulcers or markedly reduced ulcer size was much superior in the dalteparin group (29 vs 20 patients). The number of amputations in the dal teparin group was also substantially lower (2 vs 8). Dalteparin may be considered in addition to traditional thera pies for foot ulcers in DM2 patients with peripheral arterial occlusive disease.

Kalani M, et al. Diabetes Care. 2003;26:2575-2580.

Pioglitazone and LDL in Nondiabetic Hypertensives

The role of LDL in development of arteriosclerotic disease is well established. In some patient groups, especially diabetics, the type of LDL appears to be as (or more) important than the absolute amount of LDL. That is, small dense LDL (SDLDL), which is disproportionately present in type 2 diabetics (and especially when diabetes control is poor), is associated with a marked increased cardiovascular risk.

Hypertension is sometimes described as a syndrome, rather than a single physical finding, because of its frequent concomitance with dyslipidemia, insulin resistance, and obesity. As among diabetics, SDLDL is disproportionately present in hypertension. Although pioglitazone (PIO) is typically considered as a hypoglycemic agent, it has previously been shown to reduce SDLDL levels as well. Whether this beneficial effect might also occur with hypertensive, nondiabetic subjects was the object of inquiry in this trial.

Patients with hypertension (n = 60) were randomized to PIO 45 mg/d or placebo for 16 weeks. At the end of that time, patients on PIO enjoyed a decline of 22% in SDLDL levels, with no demonstrable effect on total triglycerides, LDL, or HDL. Glitazones appear to act through the peroxisome proliferators-activated receptor-gamma (PPAR-gamma) and may ultimately have a role in correcting or improving dyslipidemia associated with both diabetes and hypertension.

Winkler K, et al. Diabetes Care. 2003;26:2588-2594.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.