NIDDM in Mexican-American families. Heterogeneity by age of onset

Heredity has long been known as a risk factor for non-insulin-dependent diabetes mellitus (NIDDM), but the mode of inheritance of NIDDM remains unclear. We examined the distribution of diabetes in 29 Mexican-American families ascertained on a diabetic proband.

Probands represented a random sample of diabetic Mexican Americans residing in low-income neighborhoods from San Antonio, TX. A total of 375 family members of these diabetic probands were examined, and diabetes was diagnosed according to the World Health Organization plasma glucose criteria.

The prevalence of diabetes decreased from 28.2% in first-degree relatives of the probands to 13.3% in second-degree relatives to 11.1% in third-degree relatives. When compared with Mexican Americans with no parental history of diabetes, this represents an excess of diabetes of 2.0-, 1.3-, and 1.1-fold in first-, second-, and third-degree relatives, respectively. Five of the 29 probands (17%) had an age of diabetes onset < 40 years. In the first-degree relatives of these early-onset probands, diabetes prevalence was 47.0% (16 of 34) compared with only 24.1% (34 of 141) in the first-degree relatives of the 24 late-onset probands. After adjustment for age, this excess represented a fivefold increase in the odds of diabetes among relatives of the early-onset probands compared with relatives of the late-onset probands (P < 0.001). Moreover, the 16 affected family members of the early-onset probands had a mean age of diabetes onset of 42.7 years compared with 49.9 years for the 34 affected members of the late-onset probands, although this difference was not statistically significant (P = 0.13).

NIDDM may be genetically heterogeneous in this Mexican-American population, with family members of early-onset diabetes patients being at higher risk for NIDDM than family members of late-onset diabetes patients.