Insulin resistant phenotype is associated with high serum leptin levels inoffspring of patients with non-insulin-dependent diabetes mellitus

Objective: To investigate whether there are differences in serum leptin lev els between the offspring of non-insulin-dependent diabetes mellitus (NIDDM ) patients representing different phenotypes of NIDDM, and furthermore to i nvestigate the role of different fat tissue (subcutaneous fat area (SCFAT) and intra-abdominal fat area (IAFAT)) and insulin sensitivity on serum lept in levels, Design: Twenty non-diabetic offspring of NIDDM patients with insulin secret ion deficient phenotype (IS-group), 18 non-diabetic offspring of NIDDM pati ents with insulin resistant phenotype (IR-group) and 14 healthy control sub jects without a family history of diabetes were studied. Methods: Serum leptin le levels were measured by RIA. SCFAT and IAFAT were measured by computed tomography! the total fat mass (TFM) by bioelectrical impedance and the whole body glucose uptake (WBGU) by the euglycemic hyperi nsulinemic clamp technique, Results: Subjects of the control group (P = 0.003) and the IS-group (P<0.00 1) had lower serum leptin levels than subjects of the IR-group even after a djustment for gender (P<0.001), TFM (P = 0.009), fasting plasma insulin (P= 0.003) and for IAFAT (P<0.001). The differences weakened after adjustments for SCFAT (P = 0.028) or WBGU (P = 0.040) and disappeared after adjustment for both SCFAT and WBGU (P = 0.058). In the stepwise multiple regression an alyses SCFAT,WBGU and gender explained 58% of the variation of serum leptin levels whereas IAFAT failed to be a significant determinant of serum lepti n levels, Conclusions: The higher serum leptin levels in the IR-group was markedly, b ut not solely explained by lower rates of WBGU and higher SCFAT. SCFAT was shown to be a more important determinant of serum leptin levels than IAFAT among these study groups.