Effect of thiazolidinediones on body weight in patients with diabetes mellitus
Section snippets
Body fat distribution and insulin resistance
Although insulin resistance is associated with obesity, recent evidence suggests that insulin resistance is more closely related to the distribution of body fat rather than the overall fat mass.4, 5 Central obesity (fat around the waist) reflects an increase in intra-abdominal visceral fat. Data suggest that adipocytes in visceral fat are metabolically more active than in subcutaneous fat, releasing greater amounts of fat products such as free fatty acids (FFAs).6 Furthermore, because visceral
Effects of diabetes treatments on obesity
Many of the medications used to treat diabetes have been reported to cause weight gain, potentially causing distress to patients who are trying to lose weight. A variety of mechanisms contribute to this weight gain (Table 1). Severe hyperglycemia induces a catabolic state, and its correction leads to rebuilding of muscle and fat mass. This is particularly true with the use of insulin, whether exogenous or endogenous (i.e., stimulation by secretagogues). In addition, even mild degrees of
Mechanism of weight gain with thiazolidinediones
TZDs are ligands of peroxisome proliferator-activated receptor–γ (PPAR-γ), which is highly expressed in adipose tissue and plays an important role in the differentiation of adipocytes.26 The beneficial effects of TZDs on glucose metabolism are believed to be mediated by their binding to PPAR-γ, an activity likely to stimulate adipogenesis.27 The TZDs have a site-specific effect on differentiation of human preadipocytes; this effect is markedly enhanced in subcutaneous fat, with less effect in
Use of thiazolidinediones in obese patients
Clinical trials of TZDs have been conducted in a wide variety of patients with and without overt diabetes. Most of these trials included patients with moderate to severe obesity, and the mean body mass index (BMI) was approximately 30 to 35 in clinical trials conducted in the United States. Buch and coworkers45 reported their experience with the addition of rosiglitazone to insulin therapy for 24 weeks; their 8 subjects were massively obese patients (mean BMI, 42) with poorly controlled type 2
Weight loss/maintenance in patients treated with thiazolidinedione
Several strategies have been used to induce weight loss in patients with diabetes. The weight-loss agents sibutramine and orlistat have been studied as monotherapy and in combination with antidiabetic therapies in patients with type 2 diabetes. Such combinations cause weight loss while decreasing the need for insulin or secretagogue therapy46, 47, 48, 49, 50; however, these weight-loss agents have not been studied in combination with TZDs. Another option is use of low-calorie packaged or liquid
Summary
Obesity plays a pivotal role in the development of insulin resistance and is common in patients with type 2 diabetes. Strategies to manage body weight should be part of all diabetic treatment plans. However, through a variety of mechanisms, most medications used to treat diabetes tend to provoke weight gain, and this can be problematic for patients who are attempting to lose weight. Currently available data indicate that TZDs improve insulin sensitivity and cause a favorable redistribution of
Summary statements
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Weight gain occurs with most treatments for diabetes.
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Weight gain may be associated with TZDs, but it is not inevitable, and it can be controlled with dietary methods.
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TZDs improve insulin sensitivity and cause a favorable redistribution of fat.
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The combination of metformin with a TZD does not cause additional weight gain and may have an additive effect on insulin sensitivity.
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