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The peptides ghrelin and leptin circulate in blood and participate in energy homeostasis, feeding behavior, and regulation of body weight (1-3). Ghrelin is predominantly produced by the stomach, whereas leptin [...], The gastric peptide ghrelin augments and the adipocyte-derived hormone leptin reduces appetite and food intake. In the central nervous system, insulin directly decreases hunger sensation but could also act indirectly by modulating ghrelin and leptin secretion. This study examines dose-dependent effects of insulin on plasma ghrelin and leptin concentrations during hyperinsulinemic (1, 2, and 4 mU * [kg.sup.-1] * [min.sup.-1])-euglycemic clamp tests in six nondiabetic (control subjects) and six type 2 diabetic patients. Type 2 diabetic patients were studied before and after prolonged (12-h and 67-h) variable intravenous insulin treatment aiming at near-normoglycemia (115 ± 4 mg/dl). Nondiabetic subjects were also studied during saline infusion, which did not affect ghrelin but decreased leptin by 19 ± 6% (P < 0.03). In control subjects, plasma ghrelin decreased at all clamp steps (-17 ± 1, -27 ± 6, and -33 ± 4%, respectively; P < 0.006 vs. baseline), whereas leptin increased by 35 ± 11% (P < 0.05). In type 2 diabetic patients without insulin treatment, ghrelin decreased by 18 ± 7% (P < 0.05) only after 4 mU * [kg.sup.-1] * [min.sup.-1] insulin infusion and leptin increased by 19 ± 6% (P < 0.05). After prolonged insulin treatment and near-normoglycemia, ghrelin and leptin remained unchanged in type 2 diabetic patients during the clamps. In conclusion, insulin reduces plasma ghrelin in nondiabetic patients and, to a lesser extent, in type 2 diabetic patients before insulin therapy. These findings indicate an indirect effect of insulin via ghrelin on the suppression of hunger sensation and appetite.

Gestational diabetes mellitus (GDM) is a frequent metabolic complication during pregnancy that does not completely normalize after delivery (1-3). Women with a history of previous gestational diabetes (pGDM) are often [...], Women with previous gestational diabetes (pGDM) are frequently insulin-resistant, which could relate to intramyocellular lipid content (IMCL). IMCL were measured with ¹H nuclear magnetic resonance spectroscopy in soleus (IMCL-S) and tibialis-anterior muscles (IMCL-T) of 39 pGDM (32 ± 2 years, waist-to-hip ratio 0.81 ± 0.01) and 22 women with normal glucose tolerance (NGT; 31 ± 1 years, 0.76 ± 0.02) at 4-6 months after delivery. Body fat mass (BFM) was assessed from bioimpedance analysis, insulin sensitivity index ([S.sub.I]), and glucose effectiveness ([S.sub.G]) from insulin-modified frequently sampled glucose tolerance tests, pGDM exhibited 45% increased BFM, 35% reduced [S.sub.I] and [S.sub.G] (P < 0.05), and 40% (P < 0.05) and 55% (P < 0.005) higher IMCL-S and IMCL-T, respectively. IMCL related to body fat (BFM P < 0.005, leptin P < 0.03), but only IMCL-T correlated (P < 0.03) with [S.sub.I] and glucose tolerance index independent of BMI. Insulin-resistant pGDM (n = 17) had higher IMCL-S (+66%) and IMCL-T (+86%) than NGT and insulin-sensitive pGDM (+28%). IMCL were also higher (P < 0.005, P = 0.05) in insulin-sensitive pGDM requiring insulin treatment during pregnancy and inversely related to the gestational week of GDM diagnosis. Thus, IMCL-T reflects insulin sensitivity, whereas IMCL-S relates to obesity. IMCL could serve as an additional parameter of increased diabetes risk because it identifies insulin-resistant pGDM and those who were diagnosed earlier and/or required insulin during pregnancy.