Diabetic status of patients with leprosy in Kuwait.

OBJECTIVE: The aim of this study was to screen for diabetes mellitus in leprosy patients to elucidate whether leprosy infection may play a role in the pathogenesis of diabetes mellitus in this population. SUBJECTS AND METHODS: Thirty patients of different ages and of both sexes with various types of leprosy were included in this study. In addition, 15 healthy individuals of comparable age and sex who had no family history of diabetes mellitus were identified as controls. In both groups, determinations of fasting and postprandial blood sugar, an oral glucose tolerance test (OGTT), measures of fasting serum insulin and pro-inflammatory cytokine tumor necrosis factor alpha (TNFα), as well as calculations using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), were carried out. RESULT: Approximately 13.3% of the leprosy patients were diabetic, and 37.7% were in pre-diabetic. The highest incidences of diabetes and pre-diabetes were in lepromatous leprosy (10% and 20%, respectively); a lower incidence of pre-diabetes (6.6%) was observed in tuberculoid leprosy; and the lowest incidence of diabetes (0.0%) was noted in borderline leprosy patients. Although normal healthy persons were not diabetic (0%), 20% were pre-diabetic. CONCLUSION: This study revealed that the incidence of diabetes was higher in the leprosy patients than in the control group. As a result, we recommend that all leprosy patients should be screened for diabetes.

Dual regulation of muscle glycogen synthase during exercise by activation and compartmentalization.

Glycogen synthase (GS) is considered the rate-limiting enzyme in glycogenesis but still today there is a lack of understanding on its regulation. We have previously shown phosphorylation-dependent GS intracellular redistribution at the start of glycogen re-synthesis in rabbit skeletal muscle (Prats, C., Cadefau, J. A., Cussó, R., Qvortrup, K., Nielsen, J. N., Wojtaszewki, J. F., Wojtaszewki, J. F., Hardie, D. G., Stewart, G., Hansen, B. F., and Ploug, T. (2005) J. Biol. Chem. 280, 23165-23172). In the present study we investigate the regulation of human muscle GS activity by glycogen, exercise, and insulin. Using immunocytochemistry we investigate the existence and relevance of GS intracellular compartmentalization during exercise and during glycogen re-synthesis. The results show that GS intrinsic activity is strongly dependent on glycogen levels and that such regulation involves associated dephosphorylation at sites 2+2a, 3a, and 3a + 3b. Furthermore, we report the existence of several glycogen metabolism regulatory mechanisms based on GS intracellular compartmentalization. After exhausting exercise, epinephrine-induced protein kinase A activation leads to GS site 1b phosphorylation targeting the enzyme to intramyofibrillar glycogen particles, which are preferentially used during muscle contraction. On the other hand, when phosphorylated at sites 2+2a, GS is preferentially associated with subsarcolemmal and intermyofibrillar glycogen particles. Finally, we verify the existence in human vastus lateralis muscle of the previously reported mechanism of glycogen metabolism regulation in rabbit tibialis anterior muscle. After overnight low muscle glycogen level and/or in response to exhausting exercise-induced glycogenolysis, GS is associated with spherical structures at the I-band of sarcomeres.

Long term effects of oral vitamin E supplement in type II diabetic patients.

This triple-blind, placebo-controlled clinical trial was conducted to determine the effect of the vitamin E on fasting blood sugar (FBS), serum insulin, and glycated hemoglobin (GHb) in type 11 diabetic patients (NIDDM). A total of 100 patients, with no complications, aged 20-60 years old were chosen from those consulting the Isfahan Social Security Service Diabetes Clinic and divided randomly into two treated and placebo groups, and matched for age, sex, level of education, and occupation. The treated and placebo groups were given vitamin E tablets (200 IU/day) and placebo respectively. Serum vitamin E, total cholesterol (TC), triglycerides (TG), FBS, insulin, and GHb were measured at the beginning and at the end of the study (a period of 27 weeks); FBS, GHb and insulin levels were also determined several times during the period. Blood lipids and FBS were measured using the ELAN 2000 autoanalyzer at the Isfahan Cardiovascular Research Center, while for measuring insulin the enzyme-linked immunosorbent assay (ELISA) method was used; GHb was determined calorimetrically (thiobarbituric acid), and for vitamin E measurements the Hansen and Warwick method was used, by which the vitamin E was determined fluorometrically. The findings of this study show no effect of vitamin E supplementation in the patients: GHb did not change appreciably, FBS was reduced nonsignificantly (-4.3% in the treated group vs. -14.0% in the placebo group, p < 0.05). In the case of insulin, no increase was seen; instead, a decrease was observed (slightly more than 17% in the two groups, p = 0.15). No changes were observed in the levels of blood lipids. It was concluded that a daily vitamin E supplement of 200 IU for a period of 27 weeks does not affect insulin, GHb, or FBS in type II diabetic patients. However, since this antioxidant vitamin is beneficial in other ways in these patients, it would seem justified to recommend its use. Certainly, more extensive research is necessary to draw definite conclusions.

Release mechanism of insulin encapsulated in trehalose ester derivative microparticles delivered via inhalation.

The aim of this study was to evaluate properties of amorphous oligosaccharide ester derivative (OED) microparticles in order to determine drug release mechanisms in the lung. Trehalose OEDs with a wide range of properties were synthesised using conventional methods. The interaction of spray dried amorphous microparticles (2-3 microm) with water was investigated using attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) and dynamic vapour sorption (DVS). The in vivo performance of insulin/OED microparticles was assessed using a modified Higuchi kinetic model. A modified Hansen solvent parameter approach was used to analyse the interactions with water and in vivo trends. In water or high humidity, OED powders absorb water, lose relaxation energy and crystallise. The delay of the onset of crystallisation depends on the OED and the amount of water present. Crystallisation follows first order Arrhenius kinetics and release of insulin from OED microparticles closely matches the degree of crystallisation. The induction period depends on dispersive interactions between the OED and water while crystallisation is governed by polarity and hydrogen bonding. Drug release from OED microparticles is, therefore, controlled by crystallisation of the matrix on contact with water. The pulmonary environment was found to resemble one of high humidity rather than a liquid medium.

Comparison of the effects of a monounsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects.

OBJECTIVE: Recent studies have demonstrated beneficial metabolic effects of dietary monounsaturated fatty acids (MUFA) in Type-2 diabetes mellitus (Type-2 DM). The question arises if dietary MUFA also has desirable effects on risk markers in subjects with high risk of developing Type-2 DM. SETTING: University department of endocrinology. SUBJECTS: Sixteen healthy, first-degree relatives (six men, 10 women, age (mean+/-s.d.): 35+/-2 years) with normal oral glucose tolerance tests. INTERVENTIONS: Randomised study with two 4-week treatment periods with either a carbohydrate-rich (CHO) diet (55 E% carbohydrate, 30 E% fat, 15 E% protein) or a diet rich in olive oil [MUFA 40 E% fat (25 E% as MUFA), 45 E% carbohydrate, 15 E% protein]. The periods were divided by a 4-week wash-out period. RESULTS: Similar lowering effects on total cholesterol, low density lipoprotein (LDL)-cholesterol, triglyceride and apoB levels were seen after the two diets. Slightly higher levels of high-density lipoprotein (HDL)-cholesterol (1.4+/-0.4 vs 1.3+/-0.4 mmol/l, P<0. 0001) and apoA-1 (1.2+/-0.3 vs 1.1+/-0.3 mmol/l, P<0.05) were found in the MUFA-diet. Furthermore, the insulin sensitivity, as assessed by Bergman's minimal model, and the first response insulin areas were similar, as were the 24-h blood pressures and the von Willebrand Factor (vWF) levels. CONCLUSIONS: Isocaloric diets rich in MUFA or rich in carbohydrate, respectively, seem to have similar effects on cardiovascular risk factors in persons at high risk of developing Type-2 DM. A potential risk, however, on body weight of high-fat diets should be kept in mind. SPONSORSHIP: This study was supported by grants from the Danish Diabetes Association, Institute of Clinical Experimental Research, Aarhus University, The Danish Heart Foundation, The Danish Medical Research Council, Velux Foundation, Poul and Erna Sehested Hansens Foundation, Mogens Svarre Mogensens Foundation.