‘Glucose control-related’ and ‘non-glucose control-related’ effects of insulin on weight gain in newly insulin-treated type 2 diabetic patients

Abstract

Insulin use is common in type 2 diabetes and is frequently accompanied by weight gain, the composition of which is poorly understood. The present study evaluates insulin-induced body composition changes. Body weight and composition of thirty-two type 2 diabetic patients undergoing their first 12 months of insulin therapy were compared with those observed in thirty-two type 2 diabetic patients previously treated on insulin (minimum 1 year). Body composition was determined by simultaneous body water spaces (bioelectrical impedance analysis) and body density measurements. After 6 months, glycosylated Hb (HbA1c) significantly improved in the newly treated group (P,0·0001), but remained stable in those treated previously. HbA1c did not differ between 6 and 12 months in the two groups. Body weight significantly (P¼ 0·04) changed over 12 months in those newly treated only (þ2·8 kg), essentially comprising fatfree mass (P¼ 0·044). Fat mass remained unchanged (P¼ 0·85) as did total body water, while extracellular: total body water ratio tended to increase in those newly treated (P¼0·059). Weight changes correlated with HbA1c changes (R 2 0·134, P¼ 0·002) in the initial 6 months only. Insulin therapy leads to weight gain (2·8 kg), predominantly fat-free mass, over 12 months. After 6 months, newly treated patients continued gaining weight despite an unchanged HbA1c, suggesting the potential anabolic role of insulin in subsequent gains. Therefore, in the initial 6 months, weight gain can be attributed to a 'glucose controlrelated effect' and further gain appears to be due to a 'non-glucose control-related' effect of insulin treatment.

Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT)

“…Only one recently published trial, by Lane and colleagues, found a 5.3 kg weight loss after 24 weeks in 21 extremely obese (BMI 39.6 kg/m 2 ) patients with insulin-resistant type 2 diabetes [19]. The larger weight loss observed in the present study may be explained first by the fact that it was not designed with the intention to improve glycaemic control, as improvement in glycaemic control is usually associated with weight gain [5,8]. Second, liraglutide-induced insulin dose reductions were greater in our study than in others [17,19,23,[25][26][27], and the decrease in insulin dose was also a predictor of weight loss.…”

“…This is obviously undesirable in an already overweight population, and it may lead to aversion to the therapy and a further increase in insulin dose, and offset the beneficial effects of insulin [6]. Most insulin-induced weight gain, on average 2-6 kg, occurs within the first 9-12 months of insulin therapy [5,7,8]. Hence, a therapy that ameliorates pronounced weight gain when encountered within this time frame would be extremely desirable, but the best treatment strategy for this clinical problem is unclear.…”

Insulin Analogs: Impact on Treatment Success, Satisfaction, Quality of Life, and Adherence

“…7 The inherent anabolic activity of insulin on both adipose and muscle tissue may be responsible for prolonged periods of weight gain, even beyond the initial phase of "glucose control-related' weight gain, or re-gain. 88 So-called "defensive snacking" behaviors, driven by fears of hypoglycemia, can also contribute to weight gain in patients using insulin.…”

“…6,[87][88][89] Weight gain in type 2 patients occurs through increases in both fat and fat-free mass. 88,89 In the DCCT, even modest weight increases had a negative impact on lipid profiles and systolic blood pressure. 90 Similar findings in type 2 patients were noted in a report from the Swedish National Diabetes Register.…”

Resting energy expenditure is not increased in mildly hyperglycaemic obese diabetic patients

“…Percentage fat was calculated using a three-compartmental model (Siri, 1961), a model already validated in those with type 2 diabetes (Sallé et al 2005), which provides an assessment of percentage fat that is independent of FFM hydration:…”