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Background: Volatile anesthetics impair insulin secretion and glucose utilization; however, the precise mechanism of action that underlies these effects is unknown. The authors hypothesized that isoflurane inhibits glucose-induced inhibition of adenosine triphosphate-sensitive potassium channel activity in pancreatic beta cells, which could result in impaired insulin secretion and glucose tolerance., Methods: Intravenous glucose tolerance tests were performed on 28 male Japanese White rabbits anesthetized with sodium pentobarbital. Glibenclamide (50 microg/kg + 33.5 microg x kg x h) or vehicle was administered 75 min before intravenous administration of 0.6 g/kg glucose. Half of the animals (n = 7) in the vehicle and glibenclamide groups received isoflurane at 1.0 minimum alveolar concentration 30 min before administration of glucose, and the other half received a vehicle control. Hemodynamics, blood glucose, and plasma insulin were measured. A cell-attached patch clamp configuration was used to record single channel currents in the pancreas from male Swiss-Webster mice., Results: Isoflurane alone or a combination of isoflurane and glibenclamide inhibited the insulinogenic index to a greater extent than in the vehicle and glibenclamide groups. In the patch clamp experiments, channel activity was significantly decreased as the glucose concentration was increased from 0 to 10 mm. The subsequent application of 0.5 mm isoflurane reversed the effects of glucose on channel activity., Conclusion: These results show that isoflurane impairs insulin secretion and glucose utilization. The mechanism of action responsible for these effects may involve a decrease in glucose-induced inhibition of adenosine triphosphate-sensitive potassium channel activity in pancreatic beta cells.

Background: Recent studies reported that intraoperative hyperglycemia is an independent risk factor for mortality and morbidity related to surgery. Volatile anesthetics, such as sevoflurane, impair glucose use, suggesting their possible contributions to intraoperative hyperglycemia. However, the effects of IV anesthetics, such as propofol, on glucose metabolism are poorly understood. Thus, we compared the effects of sevoflurane and propofol on glucose metabolism under aerobic conditions in fed rats., Methods: We first examined changes in blood glucose levels in rats undergoing sigmoid colostomy under sevoflurane, sevoflurane/buprenorphine, propofol, and propofol/buprenorphine anesthesia. We then examined changes in blood glucose levels after glucose administration using awake rats, rats under sevoflurane anesthesia, and rats under propofol anesthesia., Results: Blood glucose levels increased markedly after sigmoid colostomy under sevoflurane anesthesia; the marked increases could not be prevented by the coadministration of buprenorphine. Under propofol anesthesia, blood glucose levels did not change after sigmoid colostomy at the highest dose, but increased slightly at the lowest and intermediate doses; the slight increases were completely prevented by the coadministration of buprenorphine. Whereas changes in blood glucose levels after glucose administration in rats under sevoflurane anesthesia were significantly greater than those in awake rats, the changes in rats under propofol anesthesia were similar to those in awake rats., Conclusions: During surgery, hyperglycemia was observed under sevoflurane and sevoflurane/buprenorphine anesthesia, but blood glucose levels were relatively stable under propofol and propofol/buprenorphine anesthesia. Whereas sevoflurane exaggerates glucose intolerance, propofol has no significant effects on glucose tolerance. We speculate that this feature of propofol contributes, at least in part, to the stable glucose metabolism during surgery observed in this study. The results of this study confirm the marked difference in the effects of sevoflurane and propofol on glucose metabolism.

Objective: To estimate whether 17alpha-hydroxyprogesterone caproate treatment in pregnancy increases the frequency of abnormal glucose screening and gestational diabetes mellitus (GDM)., Methods: This is a retrospective cohort study of women treated with weekly 17alpha-hydroxyprogesterone caproate. Women with pregestational diabetes and multiple gestations were excluded. 17alpha-hydroxyprogesterone caproate-exposed women were randomly matched with three unexposed controls by maternal age and prepregnancy body mass index (BMI). The main outcomes were an abnormal 1-hour 50-g glucose screen (at least 135 mg/dL) and GDM (a 1-hour 50-g glucose screen of at least 200 mg/dL or two or more abnormal values on a 3-hour 100-g oral glucose tolerance test)., Results: A total of 110 17alpha-hydroxyprogesterone caproate-exposed women were matched with 330 controls. Maternal race between exposed women and controls was similar (46% compared with 39% African American, 17% compared with 18% Hispanic, 36% compared with 40% white, P=.57). Abnormal 1-hour glucose screens were more frequent in the 17alpha-hydroxyprogesterone group (23.6% compared with 11.2%, P<.001), as was the diagnosis of GDM (10.9% compared with 3.6%, P=.003). 17alpha-hydroxyprogesterone caproate remained independently associated with the diagnosis of GDM (odds ratio 3.3, 95% confidence interval 1.3-8.1) in a conditional multiple logistic regression analysis controlling for maternal race, age, BMI, and parity., Conclusion: Women receiving weekly intramuscular 17alpha-hydroxyprogesterone caproate have more frequent abnormal glucose testing and gestational diabetes compared with unexposed controls. These results are consistent with published data regarding the effect of progesterone on insulin resistance., Level of Evidence: II.

Sirolimus (SRL) has been shown to improve long-term graft survival in several calcineurin inhibitor avoidance/minimization protocols. Although SRL has been suggested to reduce the progression of chronic renal graft damage and to prevent the development of neoplasia, two of the most prominent challenges in the field of transplantation, its use is significantly limited by an extremely high incidence of side effects. Some of the side effects are directly linked to the antiproliferative action of SRL, whereas the mechanisms underlying most of the undesired effects of the drug are still far from being clarified. Nevertheless, there is an increasing body of evidence linking most these drug-associated events to SRL dose. In addition, it is now possible to identify well-defined risk factors for most of these effects. Thus, to limit SRL-related side effects the two golden rules are (1) accurate selection of patients to be treated and (2) avoidance of high SRL doses.

Background: Protease inhibitor therapy in human immunodeficiency virus (HIV)-infected adults has been associated with onset or aggravation of glucose intolerance. We report a case of a pregnant HIV-infected woman receiving highly active antiretroviral therapy who developed acute onset of severe insulin resistance during treatment for preterm labor., Case: A 26-year-old multigravida with HIV infection treated with highly active antiretroviral therapy presented in preterm labor. During treatment, including corticosteroids for fetal lung maturity, severe hyperglycemia and ketonemia suggestive of diabetic ketoacidosis were detected. Aggressive intravenous fluid and insulin therapy was necessary to correct hyperglycemia., Conclusion: We found that HIV-positive pregnant women receiving highly active antiretroviral therapy may be at increased risk for development of glucose intolerance. The use of medications that impair glucose tolerance, for example, corticosteroids, may have a synergistic effect in aggravating insulin resistance. Additional screening for glucose intolerance later in the third trimester should be considered in these patients.

Objectives: To evaluate metabolic abnormalities, beta-cell function, lipid profile and vascular risk factors in HIV patients on protease inhibitors (PI)., Design: Prospective cross-sectional study., Methods: Thirty-eight HIV-1-infected patients receiving at least one PI were compared with 17 PI-naive HIV patients in an oral glucose tolerance test (OGTT). Serum glucose, insulin, proinsulin, and C-peptide were determined. The fasting lipid pattern was analysed using electrophoresis and the assessment of apolipoproteins including lipoprotein (a). Fibrinogen, homocysteine, and anticardiolipin antibodies were also assessed., Results: Twenty-seven (71%) of the PI-treated group had detectable hyperlipidaemia. Isolated hypertriglyceridaemia was present in 12 patients (44%), two (7%) of them had type V and 10 (37%) subjects had type IV hyperlipidaemia (Frederickson classification). Type IIb hyperlipidaemia defined as an increase of both very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) was found in 10 (36%) subjects, and five (18%) patients presented with isolated hypercholesterolaemia (type IIa). PI treatment was associated with significant higher fasting cholesterol, triglycerides, LDL and VLDL levels. Apolipoprotein B and E concentrations were significantly increased in patients receiving PI. Elevated concentrations of lipoprotein (a) (> 30 mg/dl) were detected in six (16%) of the hyperlipidaemic patients on PI. Eighteen (46%) patients on PI had impaired oral glucose tolerance and five (13%) had diabetes. Although four (24%) of the PI-naive patients were glucose intolerant, none had diabetes. Fasting concentrations and secretion response of insulin, proinsulin, and C-peptide to glucose ingestion was significantly increased in the PI-treated group suggesting a beta-cell dysfunction in addition to peripheral insulin resistance. Beta-cell abnormalities were associated with the abnormal lipid pattern and PI treatment., Conclusion: Combination drug regimens including PI are accompanied by impaired glucose tolerance, hyperproinsulinaemia as an indicator for beta-cell dysfunction, and lipid abnormalities proved to be significant risk factors for coronary heart disease. Moreover, PI may have an impact on the processing of proinsulin to insulin.