A Giancaterini

L-Carnitine Improves Glucose Disposal in Type 2 Diabetic Patients

OBJECTIVE Aim of the present study is to evaluate the effects of L-carnitine on insulin-mediated glucose uptake and oxidation in type II diabetic patients and compare the results with those in healthy controls. DESIGN Fifteen type II diabetic patients and 20 healthy volunteers underwent a short-term (2 hours) euglycemic hyperinsulinemic clamp with simultaneous constant infusion of L-carnitine (0.28 micromole/kg bw/minute) or saline solution. Respiratory gas exchange was measured by an open-circuit ventilated hood system. Plasma glucose, insulin, non-esterified fatty acids (NEFA) and lactate levels were analyzed. Nitrogen urinary excretion was calculated to evaluate protein oxidation. RESULTS Whole body glucose uptake was significantly (p<0.001) higher with L-carnitine than with saline solution in the two groups investigated (48.66+/-4.73 without carnitine and 52.75+/-5.19 micromoles/kg(ffm)/minute with carnitine in healthy controls, and 35.90+/-5.00 vs. 38.90+/-5.16 micromoles/kg(ffm)/minute in diabetic patients). Glucose oxidation significantly increased only in the diabetic group (17.61+/-3.33 vs. 16.45+/-2.95 micromoles/kg(ffm)/minute, p<0.001). On the contrary, glucose storage increased in both groups (controls: 26.36+/-3.25 vs. 22.79+/-3.46 micromoles/kg(ffm)/minute, p<0.001; diabetics: 21.28+/-3.18 vs. 19.66+/-3.04 micromoles/kg(ffm)/minute, p<0.001). In type II diabetic patients, plasma lactate significantly decreased during L-carnitine infusion compared to saline, going from the basal period to the end-clamp period (0.028+/-0.0191 without carnitine and 0.0759+/-0.0329 with carnitine, p<0.0003). CONCLUSIONS L-carnitine constant infusion improves insulin sensitivity in insulin resistant diabetic patients; a significant effect on whole body insulin-mediated glucose uptake is also observed in normal subjects. In diabetics, glucose, taken up by the tissues, appears to be promptly utilized as fuel since glucose oxidation is increased during L-carnitine administration. The significantly reduced plasma levels of lactate suggest that this effect might be exerted through the activation of pyruvate dehydrogenase, whose activity is depressed in the insulin resistant status.

Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery

One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease (CHD) risk. A cross-sectional study was designed to randomly assign 79 morbidly obese subjects (27 men and 52 women; age: 30-45 years) either to a diet protocol (20 kcal per kg fat-free mass (FFM); 55% carbohydrates, 30% fat, and 15% proteins) or to malabsorptive surgery (biliopancreatic diversion). Fatness parameters, measured by dual-energy X-ray absorptiometry, lipid profile, insulin, leptin, sex steroid hormones and sex hormone-binding globulin (SHBG) levels were compared at baseline and 1 year after the beginning of the study. The data showed that plasma SHBG levels, but not testosterone levels, correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women. Total leptin levels were significantly lower (P<0.0001) in post-BPD subjects of both sexes compared to dietary treated obese subjects. The logarithm of plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG, but not insulin levels, were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients. The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness. Finally, in obese patients, SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis.

Computing DIT from energy expenditure measures in a respiratory chamber: a direct modeling method

The possibility of computing Diet Induced Thermogenesis (DIT) is an important feature of metabolic investigations. However, methodological problems have affected the determination of DIT in the indirect calorimetric chamber. DIT has been commonly estimated by regressing energy expenditure on a measure of physical activity. Although used for many years as the only feasible approach to calculate DIT in a respiratory chamber, this traditional method has been criticized because of an apparent underestimation of the DIT, but no alternative method has been suggested so far. The present work proposes to estimate DIT directly by means of a mathematical model. This approach also allows to simultaneously estimate other parameters, namely resting energy expenditure (REE), physical activity (PA) and physical exercise (PE).

Effects of propyonil- l -carnitine topical irrigation in distal ulcerative colitis: a preliminary report

infliximab infusion 4 wk prior and her first infusion 6 wk prior. The patient delivered a baby prematurely at wk 24 of conception with a birth weight of 681 g. The neonate had intracerebral and intrapulmonary bleeding, was disconnected from the life support system on day 3, and died shortly thereafter. Despite a repeat infusion of infliximab the patient continued to be symptomatic; colonoscopy showed a narrowed area in the left colon but almost near normal mucosa all the way to the cecum, and surgical removal of the strictured colonic segment alone was accomplished. The patient was in clinical remission at 5-wk follow-up after surgery. She conceived when her IBD was active, which could have been the reason for the adverse outcome of her pregnancy. But she was also on several agents that could potentially have impacted her pregnancy outcome, one of which was infliximab. There have been several published reports on pregnancy outcome in IBD patients exposed to conventional agents (2) but none on it in those exposed to infliximab. As of May, 2000, the company had data on 27 women who were exposed to infliximab during the first trimester of pregnancy or immediately prior (D. Klumpe, Centocor, personal communication). One woman underwent an elective abortion for personal reasons, and there were three reports of miscarriages, though two of these were based on patient reports only. Six babies were born, five at full term and the sixth at week 37. In addition, another patient who was contemplating infliximab infusion during a second pregnancy had delivered a child with tetralogy of Fallot 15 months prior after a first trimester exposure to infliximab; the child underwent surgical correction and was doing well. Whether infliximab has any effect on male spermatogenesis is completely unknown, though patients have raised this question with their physicians. There are published reports on thalidomide, a potent inhibitor of TNF-a production that is potentially teratogenic; several mechanisms for the teratogenicity have been proposed (3). The major teratogenic effect of thalidomide is on the limbs, ears, and eyes, but duodenal fistulae, neural tube abnormalities, and midline hemangiomas have been reported (4). Thalidomide decreases TNFa production by accelerating the degradation of the messenger RNA that codes for the protein, whereas infliximab acts as both a cytokine carrier and as a TNF antagonist, with the end result being that TNF is rendered biologically inactive. It is not certain if infliximab could potentially have any teratogenic effects, but it is imperative that practitioners continue to report to the company details on pregnancy outcomes in those patients who are exposed to infliximab during or just before conception.