Tapentadol ER (100 to 250 mg bid) was associated with better gastrointestinal tolerability than oxycodone HCl CR (20 to 50 mg bid) and provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year.
The regional distribution of body fat has repeatedly been found to be a significant and independent risk factor for cardiovascular disease in both obese men and women. To determine whether abnormalities in the lipid-lipoprotein profile and systolic and diastolic blood pressure are related to specific fat depots early in the course of obesity, we used magnetic resonance imaging to measure accurately intraabdominal and subcutaneous fat masses in 14 obese [body mass index (BMI; in kg/m2) 30 +/- 1.3] and 10 nonobese (BMI: 21 +/- 0.5) adolescent girls matched for age and Tanner stage of development. Intraabdominal and subcutaneous fat depots were two- to threefold greater in obese than in nonobese girls (P < 0.01). Total cholesterol, triacylglycerol, low-density-lipoprotein (LDL) cholesterol, basal insulin, and systolic and diastolic blood pressure were significantly higher in obese adolescent girls than in control subjects. In obese girls, intraabdominal fat but not BMI or waist-to-hip ratio was highly correlated with basal insulin (r = 0.55, P < 0.04), triacylglycerols (r = 0.53, P < 0.03), and high-density-lipoprotein (HDL) cholesterol (r = -0.54, P < 0.04). Femoral adipose tissue was inversely related to triacylglycerol (r = -0.51) and LDL cholesterol (r = -0.56, P < 0.05) concentrations in obese girls. The study indicates that early in the natural history of obese adolescent girls, cardiovascular risk factors are related to the amount of intraabdominal fat.
To establish whether alterations in insulin action and secretion and their relationship to body fat distribution occur early in the course of developing obesity, we studied 14 obese adolescent girls [13.2 +/- 0.7 yr, body mass index (BMI) 32 +/- 1.4], 16 nonobese young women (24.0 +/- 0.6 yr, BMI 21.0 +/- 0.9). Insulin action was assessed by a sequential two-step (8 and 40 mU,m-2.min-1) euglycemic insulin clamp in combination with [1-13C]glucose and indirect calorimetry. Insulin secretion was determined by the hyperglycemic clamp technique (6.9 mmol/l). Magnetic resonance imaging was used to quantify visceral and subcutaneous abdominal fat depots. In obese girls, an impairment in glucose disposal was present with both insulin doses; at the higher dose, rates of glucose uptake were reduced by 30% in nonobese girls (240 +/- 30 vs. 340 +/- 19 mg.m-2.min-1, P < 0.05) and by an additional 29% (170 +/- 17 mg.m-2.min-1, P < 0.05) in obese girls. Insulin infusion failed to stimulate glucose oxidation and to suppress lipid oxidation only in obese girls. Suppression of free fatty acid levels, but not hepatic glucose production, was decreased in obese girls compared with controls. Fasting and glucose-stimulated insulin responses were greater in obese than in nonobese adolescents, who, in turn, had greater responses than lean women. In obese girls, visceral fat, but neither waist-to-hip circumference ratio nor subcutaneous fat, was highly correlated with basal insulin secretion (r = 0.89, P < 0.001), stimulated insulin secretion (r = 0.61, P < 0.05), and insulin resistance (r = -0.87, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Compared with placebo, tapentadol ER 100-250 mg bid provided a statistically significant difference in the maintenance of a clinically important improvement in pain 1 , 2 and was well-tolerated by patients with painful DPN.
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