FAMILIAL RELATIONSHIPS BETWEEN OBESITY AND NIDDM

Obesity and family history of diabetes are both risk factors for non-i nsulin-dependent diabetes mellitus (NIDDM), but it has been proposed t hat lean individuals with NIDDM have a greater load of diabetes suscep tibility genes. If this is the case, one might expect a high prevalenc e of NIDDM in relatives of diabetic individuals with a low body mass i ndex (BMI). Among Pima Indians participating in an epidemiological stu dy, prevalence of NIDDM was evaluated in relation to BMI of a diabetic parent or to the average parental BMI when both parents had diabetes in 1,535 offspring from 547 families. Prevalence of NIDDM was also eva luated in relation to BMI of a randomly selected index diabetic siblin g in 1,722 siblings from 721 families. NIDDM was diagnosed by an oral glucose tolerance test. Compared with offspring of diabetic parent(s) at the 25th percentile of BMI, the odds ratio (OR) for diabetes in off spring of diabetic parents at the 75th percentile was 0.6 (95% confide nce interval [CI] 0.5-0.7), adjusted for age, sex, BMI in offspring, n umber of diabetic parents, and age at onset of diabetes and sex of the diabetic parent(s). In the analysis according to BMI in a diabetic si bling, the corresponding OR was 0.8 (95% CI 0.6-0.9), Risk ratios were only modestly higher when the analysis was restricted to relatives of subjects whose BMI had been determined before the onset of diabetes. NIDDM in the presence of a low BMI is more strongly familial than that at a higher BMI. This may indicate that a greater load of familial de terminants of diabetes is present in leaner diabetic people, and it su ggests that these determinants are largely separate from those that re sult in familial aggregation of obesity.