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Objective: Injected volume and subcutaneous adipose tissue blood flow (ATBF) affect insulin absorption. Pharmacokinetics of short-acting insulin analogs were established by assessing injection of small doses in lean subjects, healthy or with type 1 diabetes. In obese patients, however, daily dosages are larger and ATBF is decreased. This study assessed the kinetics of a short-acting insulin analog in obese subjects with type 2 diabetes.Research Design and Methods: Euglycemic clamps after subcutaneous lispro injections were performed. Six healthy control subjects received 10 units. Seven obese (BMI 38.3 ± 7.0 kg/m(2)) subjects with type 2 diabetes received 10, 30, and 50 units. Plasma lispro was measured by specific radioimmunoassay and ATBF by the (133)Xe-washout technique.Results: ATBF was 64% lower in subjects with type 2 diabetes than in control subjects. After 10 units injection, time to lispro plasma peak (T(max)) was similar (48.3 vs. 55.7 min; control subjects versus type 2 diabetic subjects), although maximal concentration (C(max))/dose was 41% lower in subjects with type 2 diabetes, with lower and delayed maximal glucose infusion rate (GIR(max): 9.0 vs. 0.6 mg/kg/min, P < 0.0001, 69 vs. 130 min, P < 0.0001, respectively). After 30- and 50-unit injections, T(max) (88.6 and 130.0 min, respectively) and time to GIR(max) (175 and 245 min) were further delayed and dose related (r(2) = 0.51, P = 0.0004 and r(2) = 0.76, P < 0.0001, respectively).Conclusions: Absorption and hypoglycemic action of increasing dosages of lispro are critically delayed in obese subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Oral 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid was used to determine whether an increase in cardiac dietary fatty acid (DFA) metabolism in impaired glucose tolerance (IGT) is different in men and women. Myocardial DFA partitioning after 6 h was higher in IGT versus control subjects (P = 0.006) in both men (2.14 [95% CI 1.70-2.18] vs. 1.28 standard uptake value [SUV] units [0.80-1.76]) and women (1.95 [1.57-2.33] vs. 1.64 SUV units [1.32-1.96]) without difference between sexes. Myocardial DFA fractional uptake (Ki) between time 90 and 120 min postprandially was also higher in IGT versus control subjects (P < 0.001) in men (0.063 [0.032-0.095] vs. 0.016 min(-1) [0.007-0.025]) and women (0.050 [0.024-0.077] vs. 0.030 min(-1) [0.013-0.047]) without significant sex difference. Men had higher net myocardial DFA uptake between time 90 and 120 min driven by higher chylomicron-triglyceride (TG) levels. IGT-associated increased cardiac DFA partitioning was directly related to obesity in women, whereas it was associated with IGT per se in men. We conclude that early cardiac DFA uptake is higher in men driven by change in postprandial chylomicron-TG level but that increase in 6-h postprandial cardiac DFA partitioning nevertheless occurs with IGT both in men and women., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Evidence suggests that some actions of insulin are effected by inositolphosphoglycan (IPG) mediators. We hypothesize that a deficiency in D-chiro-inositol (DCI) and/or a DCI-containing IPG (DCI-IPG) may contribute to insulin resistance in humans., Research Design and Methods: To assess this possibility in polycystic ovary syndrome (PCOS), we determined insulin sensitivity (Si by frequently sampled intravenous glucose tolerance test), plasma and urinary DCI and myo-inositol (MYO) levels (by gas chromatography/mass spectrometry), and the release of insulin and DCI-IPG during the oral glucose tolerance test (area under the curve [AUC]) in 23 women with PCOS and 26 normal women., Results: Women with PCOS were heavier than control subjects (P = 0.002 for BMI), but also had decreased Si (P < 0.001) and increased AUC(insulin) (P < 0.001) compared with normal women, even when corrected for BMI. The urinary clearance of DCI (uCl(DCI)) was increased almost sixfold in PCOS compared with normal women (P = 0.001), but not MYO clearance (P = 0.10). uCl(DCI) correlated inversely with Si when all women were analyzed together (n = 49, r = -0.50, P < 0.001) and was one of the three best independent parameters predicting Si. Finally, the ratio of AUC(DCI-IPG) to AUC(insulin) was decreased threefold in women with PCOS (P < 0.001)., Conclusions: uCl(DCI) is inversely correlated with insulin sensitivity in women and is a strong independent predictor of insulin resistance in multivariate models. PCOS, which is characterized by insulin resistance, is associated with a selective increase in uCl(DCI) and impaired DCI-IPG release in response to insulin. These findings are consistent with a defect in tissue availability or utilization of DCI in PCOS that may contribute to the insulin resistance of the syndrome.