EARLIER APPEARANCE OF IMPAIRED INSULIN-SECRETION THAN OF VISCERAL ADIPOSITY IN THE PATHOGENESIS OF NIDDM - 5-YEAR FOLLOW-UP OF INITIALLY NONDIABETIC JAPANESE-AMERICAN MEN

OBJECTIVE - To identify risk factors for development of non-insulin-de pendent diabetes mellitus (NIDDM) during a 5-year longitudinal follow- up of second-generation Japanese-American (Nisei) men. RESEARCH DESIGN AND METHODS - For 5 years, 137 initially nondiabetic Nisei men were f ollowed with 75-g oral glucose tolerance tests at the initial visit an d at 2.5- and 5-year follow-up visits. Body fat distribution was asses sed by computed tomography (CT) and body mass index (BMI) calculated a t each visit. Fasting insulin and C-peptide, the increment of insulin and C-peptide at 30 min after the oral glucose load, intra-abdominal a nd total subcutaneous fat by CT, and BMI were compared between those w ho remained nondiabetic (non-DM) and those who had developed NIDDM at 2.5 years (DM-A) and 5 years (DM-B). RESULTS - At baseline, the DM-A g roup had significantly increased intra-abdominal fat, elevated lasting plasma C-peptide, and lower C-peptide response at 30 min after oral g lucose. At the 2.5-year follow-up, this group had markedly increased f asting plasma insulin and decreased 30-min insulin and C-peptide respo nse to oral glucose. The DM-B group also had significantly lower insul in response at 30 min alter oral glucose at baseline but no significan t difference in intra-abdominal fat or lasting plasma insulin and C-pe ptide levels. When this group developed NIDDM by 5-year follow-up, how ever, an increase of intra-abdominal fat was found superimposed on the pre-existing lower insulin response. Fasting plasma insulin and C-pep tide remained low. CONCLUSION - In DM-A, lower 30-min insulin response to oral glucose (an indicator of beta-cell lesion) and increased intr a-abdominal fat and lasting C-peptide (indicators of insulin resistanc e) were the risk factors related to the development of NIDDM. DM-B sub jects had a lower 30-min insulin response to oral glucose at baseline and increased intra-abdominal fat at 5 years, when they were found to have NIDDM. Thus, both insulin resistance and impaired beta-cell funct ion contribute to the development of NIDDM in Japanese-Americans, and impaired beta-cell function may be present earlier than visceral adipo sity in some who subsequently develop NIDDM.