Orally administered VSL#3 prevents autoimmune diabetes and induces immunomodulation by a reduction in insulitis severity. Our results provide a sound rationale for future clinical trials of the primary prevention of type 1 diabetes by oral VSL#3 administration.

OBJECTIVE -To compare pharmacokinetics and pharmacodynamics of insulin analogs glargine and detemir, 24 subjects with type 1 diabetes (aged 38 Ϯ 10 years, BMI 22.4 Ϯ 1.6 kg/m 2 , and A1C 7.2 Ϯ 0.7%) were studied after a 2-week treatment with either glargine or detemir once daily (randomized, double-blind, crossover study).RESEARCH DESIGN AND METHODS -Plasma glucose was clamped at 100 mg/dl for 24 h after subcutaneous injection of 0.35 unit/kg. The primary end point was end of action (time at which plasma glucose was Ͼ150 mg/dl).RESULTS -With glargine, plasma glucose remained at 103 Ϯ 3.6 mg/dl up to 24 h, and all subjects completed the study. Plasma glucose increased progressively after 16 h with detemir, and only eight subjects (33%) completed the study with plasma glucose Ͻ180 mg/dl. Glucose infusion rate (GIR) was similar with detemir and glargine for 12 h, after which it decreased more rapidly with detemir (P Ͻ 0.001). Estimated total insulin activity (GIR area under the curve [AUC] 0 -end of GIR ) was 1,412 Ϯ 662 and 915 Ϯ 225 mg/kg (glargine vs. detemir, P Ͻ 0.05), with median time of end of action at 24 and 17.5 h (glargine vs. detemir, P Ͻ 0.001). The antilipolytic action of detemir was lower than that of glargine (AUC free fatty acids 0 -24 h 11 Ϯ 1.7 vs. 8 Ϯ 2.8 mmol/l, respectively, P Ͻ 0.001).CONCLUSIONS -Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h.

OBJECTIVETo compare the pharmacokinetics and pharmacodynamics of NPH, glargine, and detemir insulins in type 2 diabetic subjects.RESEARCH DESIGN AND METHODSThis study used a single-blind, three-way, cross-over design. A total of 18 type 2 diabetic subjects underwent a euglycemic clamp for 32 h after a subcutaneous injection of 0.4 units/kg at 2200 h of either NPH, glargine, or detemir after 1 week of bedtime treatment with each insulin.RESULTSThe glucose infusion rate area under the curve0–32 h was greater for glargine than for detemir and NPH (1,538 ± 688; 1,081 ± 785; and 1,170 ± 703 mg/kg, respectively; P < 0.05). Glargine suppressed endogenous glucose production more than detemir (P < 0.05) and similarly to NPH (P = 0.16). Glucagon, C-peptide, free fatty acids, and β-hydroxy-butyrate were more suppressed with glargine than detemir. All 18 subjects completed the glargine study, but two subjects on NPH and three on detemir interrupted the study because of plasma glucose >150 mg/dL.CONCLUSIONSCompared with NPH and detemir, glargine provided greater metabolic activity and superior glucose control for up to 32 h.

The combined measurement of autoantibodies and markers of ovarian reserve (as inhibin B and AMH) may permit to identify women with POI due to steroid cell autoimmunity with a preserved proportion of primordial and primary follicles. In the future the development of techniques of in-vitro folliculogenesis may permit new treatment strategies for women with SCA-POI-related infertility.

Two thirds of women with recent-onset SCA-POI had normal AMH concentrations. Women with SCA-POI, differently from those with iPOI, present a preserved ovarian follicle pool for several years after diagnosis of ovarian insufficiency.