Risk of symptomatic gallstones in women with severe obesity.

Although obesity is a well-recognized risk factor for gallstones, the excess risks associated with higher levels of obesity and recent weight change are poorly quantified. We evaluated these issues in the Nurses' Health Study. Among 90,302 women aged 34-59 y at baseline followed from 1980 to 1988, 2122 cases of newly diagnosed symptomatic gallstones occurred during 607,104 person-years of follow-up. From 1980 to 1986, 488 cases of newly diagnosed unremoved gallstones were documented. We observed a striking monotonic increase in gallstone disease risk with obesity; women with a body mass index (BMI) greater than 45 kg/m2 had a sevenfold excess risk compared with those whose BMI was less than 24 kg/m2. Women with a BMI greater than 30 kg/m2 had a yearly gallstone incidence of greater than 1% and those with a BMI greater than or equal to 45 kg/m2 had a rate of approximately 2%/y. Recent weight loss was associated with a modestly increased risk after adjustment for BMI before weight loss. Current smoking was an independent risk factor; women smoking greater than or equal to 35 cigarettes/d had a relative risk of 1.5 (95% CI 1.2-1.9).

Dietary predictors of symptom-associated gallstones in middle-aged women.

In 1980, 88,837 women aged 34-59 y completed a semiquantitative food frequency questionnaire and were followed for 4 y. Four hundred thirty-three women reported a cholecystectomy for recent cholecystitis, and 179 reported unremoved, newly symptomatic gallstones diagnosed by ultrasound or x ray. Among the 59,306 women with Quetelet's index of relative weight less than 25 kg/m2, inverse associations were observed between intakes of vegetable fat and vegetable protein and the risk of reportedly symptomatic gallastones, after adjusting for age, Quetelet's index in 1980, weight change between 1976 and 1980, energy intake, and alcohol intake. The relative risk in the highest quintile of vegetable fat intake, as compared with the lowest quintile, was 0.6 [95% confidence interval (CI), 0.4-0.9], and the corresponding relative risk for vegetable protein intake was 0.7 (95% CI, 0.6-0.9). No significant associations were found with energy-adjusted intakes of cholesterol, animal fat, animal protein, carbohydrate, or sucrose.

MELAS syndrome with mitochondrial tRNA(Leu)(UUR) mutation: correlation of clinical state, nerve conduction, and muscle 31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin.

We report a patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes treated with riboflavin and nicotinamide for 18 months, during which time previously frequent encephalopathic spells ceased. To confirm clinical benefit, we withdrew treatment and monitored response with muscle 31P magnetic resonance spectroscopy (MRS) and sural nerve conduction studies. Of three prospectively chosen MRS variables, two changed coincidentally with clinical end points; phosphocreatine (PCr)/adenosine triphosphate recovery rates fell in parallel with sural nerve sensory amplitudes, and a drop in muscle bioenergetic efficiency (relationship of inorganic phosphate/PCr to the accelerating force of contracting muscle) coincided with development of encephalopathy. Investigations revealed a deficiency of respiratory complex I and mutation of the mitochondrial tRNA(Leu)(UUR). We suggest that a defective cellular energy state in mitochondrial disease may be partially treatable and that changes seen in appropriate muscle spectroscopy studies may parallel improvement in brain and peripheral nerve function.

Weight, diet, and the risk of symptomatic gallstones in middle-aged women.

To assess the risk factors for symptomatic gallstones, 88,837 women in the Nurses' Health Study cohort (age range, 34 to 59 years) were followed for four years after completing a detailed questionnaire about food and alcohol intake in 1980. A total of 433 cholecystectomies and 179 cases of newly symptomatic, unremoved gallstones, diagnosed by ultrasonographic examination or x-ray films, were reported during the four-year follow-up. The age-adjusted relative risk for very obese women, who had a Quetelet index of relative weight (weight in kilograms divided by the square of the height in meters) of more than 32 kg per square meter, was 6.0 (95 percent confidence interval, 4.0 to 9.0), as compared with women whose relative weight was less than 20 kg per square meter. For slightly overweight women (relative weight, 24 to 24.9 kg per square meter), the relative risk was 1.7 (95 percent confidence interval, 1.1 to 2.7). Overall, we observed a roughly linear relation between relative weight and the risk of gallstones. Among the 59,306 women whose relative weight was less than 25 kg per square meter, a high energy intake (greater than 8200 J per day), as compared with a low energy intake (less than 4730 J per day), was associated with an increased incidence of symptomatic gallstones (relative risk, 2.1; 95 percent confidence interval, 1.4 to 3.3), and an alcohol intake of at least 5 g per day was associated with a decreased incidence as compared with abstention (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.8). Parity did not appear to be an important risk factor after an adjustment was made for relative weight. These data support a strong association between obesity and symptomatic gallstones and suggest that even moderate overweight may increase the risk.