The effect of tramadol on the plasma glucose level of streptozotocin (STZ)-induced diabetic rats was investigated. A dose-dependent lowering of plasma glucose was seen in the fasting STZ-induced diabetic rats 30 min after intravenous injection of tramadol. This effect of tramadol was abolished by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid -receptors. However, response to tramadol was not changed in STZ-induced diabetic rats receiving p-chlorophenylalanine at a dose sufficient to deplete endogenous 5-hydroxytrptamine (5-HT). Therefore, mediation of 5-HT in this action of tramadol is ruled out. In isolated soleus muscle, tramadol enhanced the uptake of radioactive glucose in a concentration-dependent manner. The stimulatory effects of tramadol on glycogen synthesis were also seen in hepatocytes isolated from STZ-induced diabetic rats. The blockade of these actions by naloxone and naloxonazine indicated the mediation of opioid -receptors. The mRNA and protein levels of the subtype 4 form of glucose transporter in soleus muscle were increased after repeated treatments for 4 days with tramadol in STZ-induced diabetic rats. Moreover, similar repeated treatments with tramadol reversed the elevated mRNA and protein levels of phosphoenolpyruvate carboxykinase in the liver of STZinduced diabetic rats. These results suggest that activation of opioid -receptors by tramadol can increase the utilization of glucose and/or decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin. Diabetes 50: [2815][2816][2817][2818][2819][2820][2821] 2001 U nlike the analgesic effects of opioids, their effects on glucose metabolism in diabetes have received little attention. In diabetic patients, ␤-endorphin stimulates insulin secretion (1). Also, ␤-endorphin is known to be involved in plasma glucose homeostasis (2,3). Opioid receptors in the pancreas have been investigated for this regulation of plasma glucose (4,5). However, the effect of opioids on glucose homeostasis does not depend entirely on insulin. In our previous study (6), we found that ␤-endorphin is also responsible for the reduction of plasma glucose during cold exposure in streptozotocin (STZ)-induced diabetic rats, which were used as a type 1 diabetes model. Actually, injection of exogenous ␤-endorphin lowered plasma glucose in STZ-induced diabetic rats (6). Moreover, we demonstrated that loperamide, an agonist of opioid -receptors, could lower plasma glucose in STZ-induced diabetic rats (7). Thus, it has been shown that activation of opioid -receptors may produce a plasma glucose-lowering effect in diabetic rats lacking insulin. Clinically, tramadol has widely been used as an analgesic through activation of opioid -receptors (8 -11) and others (9). In the present study, we investigated the effect of tramadol on plasma glucose and characterized the role of opioid -receptors in the action of tramadol during the absence of insulin, both in vivo and in vitro. We also examined the influence of repeated treatmen...

A positive association exists between potentially inappropriate drug prescribing, as defined by the Beers criteria, and ADRs in first-visit elderly outpatients. Clinicians should be alert to the possibility of ADRs if a patient takes more than five drugs, has a history of ADRs, or exhibits poor compliance with prescribed drugs.

OBJECTIVE: To evaluate the inter-relationships of age-and menopause-related changes of general obesity and body fat distribution and their independent effects on cardiovascular risk factors. DESIGN: Cross-sectional study. SUBJECTS: One-hundred and thirty-six premenopausal and 193 postmenopausal Chinese women with body mass index (BMI)`30 kgam 2 . MEASUREMENTS: Anthropometric surrogates of general obesity (BMI, total body fat percentage) and central obesity (waist-to-hip ratio, centrality index) were measured. Blood pressure, 75 g oral glucose tolerance test, glycosylated hemoglobin A 1c and lipid pro®les were also measured. RESULTS: Signi®cant correlation coef®cients between age, general obesity, central obesity and cardiovascular disease risk factors were noted. Through the menopausal transition, the BMI and total body fat percentage were increased signi®cantly. After adjustments for age and BMI, the postmenopausal women showed higher android fat percentage, centrality index, glycosylated hemoglobin A 1c , serum concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol and atherogenic indices than the premenopausal women. In multiple stepwise regression models, age exerted independent effects on oral glucose tolerance test 2 h plasma glucose level, systolic and diastolic blood pressure, total cholesterol level, and LDL cholesterol. Menopause was an independent variable in relation to the changes of glycosylated hemoglobin A 1c , total and LDL cholesterol levels, triglyceride levels and atherogenic indices. The centrality index was the major independent variable of all the cardiovascular disease risk factors, except total and LDL cholesterol level. However, the variation of total body fat percentage had no independent effect on any cardiovascular disease risk factors. CONCLUSION: Through the aging and menopausal effects, women will increase total body fat content, favoring the central body fat distribution. Age, menopause and central obesity were all independent and signi®cant factors to the cardiovascular disease risk factors in Chinese women.

Background: Genetic variations of the human adiponectin gene are associated with metabolic phenotypes, including obesity, insulin sensitivity, and diabetes. However, these associations have not been examined in an elderly population. Objective: The objective of the study was to investigate whether the genetic variants of adiponectin are associated with any metabolic phenotype in the elderly. Design: In a population-based, case-control genetic association study, a total of 1438 subjects 65 y old were recruited from the community. The phenotypes of the metabolic syndrome (MetS) were measured. Four single-nucleotide polymorphisms (SNP) were genotyped by mass spectrometry. Results: The G allele of SNP276 in intron 2 was associated with a reduced risk of obesity, MetS, and diabetes mellitus. The GT genotype relative to the GG genotype had an age-and sex-adjusted odds ratio of 1.32 for obesity [body mass index (BMI; in kg/m 2 ) ͧ 25; P ҃ 0.014] and of 1.33 (P ҃ 0.011) and 1.47 (P ҃ 0.001) for MetS according to modified National Cholesterol Education Program and International Diabetes Federation criteria, respectively. The age-, sex-, and BMI-adjusted odds ratio of diabetes mellitus for the GT and TT genotypes relative to the GG genotype were 1.28 (P ҃ 0.042) and 1.72 (P ҃ 0.013), respectively, and there was an obvious dosage effect (P for trend ҃ 0.004). In linear regression after adjustment for age, sex, and BMI, the GT and TT genotypes were associated with fasting plasma glucose concentrations 5.2 and 11.1 mg/dL higher, respectively, than those of the GG genotype. Conclusions: Genetic variation of the adiponectin gene is associated with obesity, MetS, and diabetes mellitus in the elderly. The genetic effect on diabetes mellitus is partially independent of BMI. Am J Clin Nutr 2007;86:509 -13.