Insulin-resistant patients with type 2 diabetes mellitus have higher serum leptin levels independently of body fat mass

Abstract

In obese people, an increase of plasma leptin levels is well-known and is seen as a consequence of the increased body fat mass. Moreover, a relationship between fasting concentrations of leptin and insulin has been described. Hyperinsulinemia is considered to be indicative of insulin resistance. We aimed at elucidating the interrelations between leptin, insulin and insulin resistance in type 2 diabetic patients. Under metabolic ward conditions, we investigated 21 moderately overweight men with type 2 diabetes. The patients had a mean age of 49.1 years, a mean body mass index (BMI) of 26.8 kg/m(2), and a mean diabetes duration of 82.5 months. All patients were treated with diet alone. We measured fasting leptin and insulin levels, body composition by determination of total body water, and insulin resistance by euglycemic hyperinsulinemic clamp technique. At univariate analysis, fasting leptin level significantly and positively correlated with BMI (r=0.49, p=0.02) and with fasting insulin (r=0.69, p=0.001), while it negatively correlated with the glucose disposal rate (r=-0.62, p=0.002). Furthermore, leptin was inversely correlated with HDL-cholesterol (r=-0.45, p=0.04). When excluding the influence of body fat mass or of BMI in partial correlation analysis, the correlations between leptin and insulin or insulin sensitivity remained significant. The relationship between insulin resistance (as measured directly in the clamp experiments) and leptin concentrations was also shown by subdividing the diabetic patients according to tertiles of insulin sensitivity. The highest fasting leptin levels were observed in those patients with the most expressed insulin resistance. Our data point to a functional relationship between insulin resistance and leptin concentrations in insulin-resistant type 2 diabetic men, independently of body composition. This relationship is believed to be mediated by insulin.

Diabetes and the risk of prostate cancer: the role of diabetes treatment and complications

“…For example, although men with insulin-resistant type 2 diabetes may initially have increased levels of endogenous insulin, IGF-1 and leptin, as the disease progresses to insulin deficiency (the stage where insulin may be added as a therapy), levels of these factors decrease. 10,17,18 Insulin and IGF-1 may be involved in prostate cancer development through stimulating cell growth and proliferation. 11,15 Other factors, such as circulating leptin, have also been implicated in the development and progression of prostate cancer.…”

Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance

“…While previous reports have indicated a relationship between leptin levels and insulin resistance, this relationship has been considered by some to be due to increased fat mass (21). Other investigators have demonstrated both in experimental animals and in human subjects that the association between insulin resistance and leptin levels may be independent of body fat mass (22,23). Leptin can also inhibit insulin-stimulated glucose uptake in cultured rat skeletal muscle cells (24).…”

IGF-1 and risk of additional breast cancer in the WHEL study

“…IGF1 is part of an inter-related metabolic system that includes insulin and two adipocytokines (leptin and adiponectin) that are closely related with insulin (Fischer et al 2002, Matsubara et al 2002, Stefan et al 2002, Wauters et al 2003. It has been shown that insulin has a role in breast cancer incidence through stimulation of proliferation of breast cancer cells (Milazzo et al 1992, Mayer et al 2008.…”