These cases arouse concern that fenfluramine-phentermine therapy may be associated with valvular heart disease. Candidates for fenfluramine-phentermine therapy should be informed about serious potential adverse effects, including pulmonary hypertension and valvular heart disease.

Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men. IntroductionA predominantly upper-body fat distribution is an important risk factor for the metabolic complications of obesity (1), especially when it is associated with increased intra-abdominal fat (2). Several metabolic abnormalities associated with upper-body obesity can be reproduced by excess FFAs, including insulin resistance with respect to muscle glucose uptake (3) and endogenous glucose production (4) and increased VLDL triglyceride production (5). Increased delivery of FFAs to the liver may be responsible for some of these abnormalities (6, 7). Visceral adipocytes are more lipolytically active than subcutaneous adipocytes in vitro (8, 9), suggesting that the association between greater amounts of visceral fat and the metabolic complications of obesity may reflect excess FFAs originating from visceral adipose tissue lipolysis (6, 7). These FFAs are released directly into the portal vein, exposing the liver to more FFAs than would be predicted from systemic FFA availability data. Thus, enlarged visceral fat stores could increase the proportion of hepatic FFA delivery coming from visceral, as opposed to systemic, sources.The relationship between visceral fat and splanchnic FFA kinetics has not been assessed in humans. We previously reported a slight, but nonsignificant increase in splanchnic FFA (palmitate) release in upper-body obese women compared with lower-body obese and nonobese women (10). Visceral fat was not measured, however, and we did not include women with the full range of obesity-related metabolic abnormalities (10) in whom more significant disturbances of FFA metabolism might be expected. In addition, men were not studied, and obese ...

Trial data available to date are unable to demonstrate a statistically significant reduction in mortality and cardiovascular risk associated with vitamin D. The quality of the available evidence is low to moderate at best.

Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men. IntroductionA predominantly upper-body fat distribution is an important risk factor for the metabolic complications of obesity (1), especially when it is associated with increased intra-abdominal fat (2). Several metabolic abnormalities associated with upper-body obesity can be reproduced by excess FFAs, including insulin resistance with respect to muscle glucose uptake (3) and endogenous glucose production (4) and increased VLDL triglyceride production (5). Increased delivery of FFAs to the liver may be responsible for some of these abnormalities (6, 7). Visceral adipocytes are more lipolytically active than subcutaneous adipocytes in vitro (8, 9), suggesting that the association between greater amounts of visceral fat and the metabolic complications of obesity may reflect excess FFAs originating from visceral adipose tissue lipolysis (6, 7). These FFAs are released directly into the portal vein, exposing the liver to more FFAs than would be predicted from systemic FFA availability data. Thus, enlarged visceral fat stores could increase the proportion of hepatic FFA delivery coming from visceral, as opposed to systemic, sources.The relationship between visceral fat and splanchnic FFA kinetics has not been assessed in humans. We previously reported a slight, but nonsignificant increase in splanchnic FFA (palmitate) release in upper-body obese women compared with lower-body obese and nonobese women (10). Visceral fat was not measured, however, and we did not include women with the full range of obesity-related metabolic abnormalities (10) in whom more significant disturbances of FFA metabolism might be expected. In addition, men were not studied, and obese ...

Vitamin D combined with calcium reduces the risk of falls. The reduction in studies without calcium coadministration did not reach statistical significance. The majority of the evidence is derived from trials enrolling elderly women.