Bedtime insulin/daytime glipizide. Effective therapy for sulfonylurea failures in NIDDM.

Bedtime insulin (BI)/daytime sulfonylurea (DSU) therapy was studied double-blind in 30 non-insulin-dependent diabetes mellitus subjects in whom sulfonylurea (SU) therapy had failed. Subjects were switched to glipizide for 2 months (phase I) to confirm failure (fasting plasma glucose [FPG] 12.0 +/- 0.4 mmol/l) and then randomly assigned into three groups: BI-DSU; BI-no DSU; and DSU-no BI. During phase II (3 months), the BI dose was fixed (20 U/1.73 m2, low-dose). In phase III (3 months), BI was titrated up (high-dose) to achieve good control or until hypoglycemic symptoms prevented further dose increases. In phase IV (6 months), 25 of the 30 original subjects received open-labeled, high-dose BI-DSU. Low-dose BI-DSU markedly reduced FPG (13.6 +/- 0.8 to 8.0 +/- 0.6 mmol/l, P < 0.001), mean 24-h glucose (P < 0.001), HbA1c (8.9 +/- 0.7 to 7.6 +/- 0.3%, P = 0.07), and basal hepatic glucose production (HGP) (P < 0.005). A positive correlation (r = 0.69, P < 0.05) between the declines in FPG and HGP was observed. Neither low-dose BI alone nor DSU alone reduced FPG, mean 24-h glucose, HbA1c, or basal HGP. High-dose (40 +/- 5 U/day) BI plus DSU further reduced the FPG (6.3 +/- 0.6 mmol/l), HbA1c (7.1 +/- 0.3%), mean 24-h plasma glucose, and basal HGP (all P < 0.05 vs. phase II).(ABSTRACT TRUNCATED AT 250 WORDS)

Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women.

In this study, total body fat content and fat topography were related to glucose metabolism in the basal and insulin-stimulated states in 18 nonobese and 18 obese premenopausal nondiabetic women. All subjects received a euglycemic insulin (20 mU.min-1.m2) clamp study in combination with [3-3H]-D-glucose infusion and indirect calorimetry to quantitate total body glucose uptake, glucose oxidation, and nonoxidative glucose disposal. Total body fat content was determined with tritiated water, whereas body fat distribution was estimated from the WHR, the STR, and the VSR (measured by magnetic resonance imaging). In the postabsorptive state, total body glucose utilization, glucose oxidation, and nonoxidative glucose disposal rates were similar in nonobese and obese women, whereas during the insulin clamp all three metabolic parameters were reduced significantly in the obese group. In nonobese women, total body fat content was related inversely to both total and nonoxidative glucose disposal during the insulin clamp, whereas no relationship was found between glucose metabolism (total, oxidative, and nonoxidative) and WHR, STR, or VSR. In contrast, in obese women, no relationship was observed between total body fat content and any measure of insulin-mediated glucose metabolism. However, both WHR and VSR were related inversely to total, oxidative, and nonoxidative glucose disposal rates during the insulin clamp. These results suggest that total body fat content and body fat topography are associated differently with insulin-mediated glucose metabolism in nonobese and obese women. In the nonobese women, total body fat mass appears to be a primary determinant of tissue sensitivity to insulin, whereas in obese women, body fat topography exerts a more dominant effect.

Ethanol feeding and thyroid hormone monodeiodination.

Adult male rats were placed on a 3 week regimen of ethanol (as 20% of total calories) in a nutritionally adequate diet, and controls were matched equicalorically without ethanol. Serum measurements of T4, T3, FT4, rT3, and TSH were performed in both the fed and the fasted state (18 hours). In the fed state, serum hormone measurements did not differ between control and ethanol-treated rats. Overnight fasting had a significant effect in decreasing serum T3 level in both experimental and control rats and in decreasing serum T4 level in ethanol-treated animals; FT4 and rT3 levels were not affected. Fasting also decreased in vitro hepatic T4 to T3 production to an equivalent degree in control and ethanol-treated rats, but did not alter hepatic T4 to rT3 production rates in control animals. In the fed state, hepatic rT3 neogenesis in animals given ethanol declined relative to the levels observed in control fed rats; fasting restored the depressed rT3 neogenesis to the levels noted in the fed state. Because decreased rT3 production in ethanol-treated rats in the fed state could not be explained on the basis of a change in 5'-deiodinase activity, it is suggested that ethanol administered with a nutritionally adequate diet may inhibit hepatic rT3 generation by inhibiting T4(5)-deiodinase.

Ethanol inhibition of pituitary-thyroid axis: an effect secondary to nutritional deficiency.

Ethanol as either 20% or 36% of total calories in a Lieber diet was administered to male rats. At these concentrations, ethanol consumption relative to body weight did not differ. Pair-fed controls were restricted to the amount of calories consumed by rats given ethanol. Under these conditions, a direct effect of ethanol on the hypothalamic-hypophyseal-thyroid axis could not be demonstrated. There were no differences between pair-fed control and ethanol treated rats in serum or pituitary TSH, TSH response to TRH, or T4 and T3 levels. On the other hand, in rats given ethanol as 36% of total calories ("36%" ethanol-treated), and in their pair-fed controls, a marked decrease in serum T4 levels occurred (25% and 30%), relative to the corresponding "20%" groups. The decreased T4 in the "36%" groups was associated with a pronounced fall in caloric intake, decreased serum TSH, and declines in adenohypophyseal and body weights -- all of which were of similar magnitude in experimental and control rats. Thus, inanition was probably the primary cause of reduced thyroid function in the "36%" groups. An interesting aspect of this change was the finding of no difference in serum T3 levels between pair-fed control and ethanol treated rats in the 36% and 20% groups despite the reduced T4 and caloric intake in 36% animals; the lack of decrease in T3 concentration in 36% animals may reflect augmented peripheral conversion of T4 to T3 or reduced T3 clearance.

Premenstrual syndrome: concerns, controversies, and treatment.

Premenstrual syndrome is of interest to health care professionals today because of media attention and large numbers of women who are concerned about their premenstrual symptoms. At the same time, there is a lack of consensus as to diagnostic criteria and specific treatment. There appears to be a relationship between mood disorders such as major depression and luteal phase symptoms. An approach to the diagnosis and treatment of the patient with premenstrual syndrome is described.