Impaired Fasting Glucose and Body Mass Index as Determinants of Mortality in ALLHAT: Is the Obesity Paradox Real?

Emerging literature suggests that obesity may be "protective" against mortality and cardiovascular outcomes, while dysglycemia may worsen outcomes regardless of obesity. The authors measured the association of weight, smoking, and glycemia with mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Among 5423 ALLHAT participants without established diabetes or cardiovascular disease, 3980 (73%) had normal fasting glucose and 1443 (27%) had impaired fasting glucose (IFG) levels at study entry. After a median of 4.9 years follow-up, 554 (10%) had died (37% cardiovascular). IFG was associated with higher all-cause mortality (adjusted hazard ratio HR, 1.23; 95% confidence interval CI, 1.02-1.50), while obesity was associated with lower all-cause mortality (adjusted HR, 0.76; 95% CI, 0.60-0.96). However, after excluding underweight individuals (body mass index BMI <22 kg/m(2) ) and smokers, neither obesity nor IFG was associated with all-cause mortality corrected. Although obesity appeared protective against mortality, this association was not significant in never-smokers or after exclusion of BMI <22 kg/m(2) . The obesity paradox may result from confounding by a sicker, underweight referent population and smoking.