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

Abstract

OBJECTIVE--To identify risk factors for development of non-insulin-dependent 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 followed with 75-g oral glucose tolerance tests at the initial visit and at 2.5- and 5-year follow-up visits. Body fat distribution was assessed by computed tomography (CT) and body mass index (BMI) calculated at each visit. Fasting insulin and C-peptide, the increment of insulin and C-peptide at 30 min after the oral glucose load, intra-abdominal and total subcutaneous fat by CT, and BMI were compared between those who 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 group had significantly increased intra-abdominal fat, elevated fasting plasma C-peptide, and lower C-peptide response at 30 min after oral glucose. At the 2.5-year follow-up, this group had markedly increased fasting plasma insulin and decreased 30-min insulin and C-peptide response to oral glucose. The DM-B group also had significantly lower insulin response at 30 min after oral glucose at baseline but no significant difference in intra-abdominal fat or fasting plasma insulin and C-peptide levels. When this group developed NIDDM by 5-year follow-up, however, an increase of intra-abdominal fat was found superimposed on the pre-existing lower insulin response. Fasting plasma insulin and C-peptide remained low. CONCLUSION--In DM-A, lower 30-min insulin response to oral glucose (an indicator of beta-cell lesion) and increased intra-abdominal fat and fasting C-peptide (indicators of insulin resistance) were the risk factors related to the development of NIDDM. DM-B subjects 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 function contribute to the development of NIDDM in Japanese-Americans, and impaired beta-cell function may be present earlier than visceral adiposity in some who subsequently develop NIDDM.

No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population

“…Supporting this hypothesis, the Japanese population, as an ethnic group, is thought to be more genetically prone to developing pancreatic b-cell dysfunction rather than insulin resistance (Chen et al 1995), although there has been debate about the relative importance of insulin resistance versus b-cell dysfunction in the development of T2D. On the other hand, populations with a high prevalence of the 121Q allele (African-Americans, Dominicans and South Asians) are reportedly more insulin resistant than Caucasians (Jensen et al 2002;.…”

Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study

“…The defect in insulin secretion in IGT individuals is most evident when the early (0-to 30-min) plasma insulin response following glucose ingestion is examined. Typically, the total insulin area under the curve following oral or intravenous glucose is normal or increased [1,2,3,8,10,17,18,23,24,25,26,40,41,42,43]. Similarly, it is not uncommon to observe an increased or "normal" plasma insulin response in T2DM patients with mild fasting hyperglycaemia (<7.8 mmol/l), although the early (0--30-min) insulin response is impaired [16,44].…”

Early disturbances in insulin secretion in the development of type 2 diabetes mellitus

“…Walker et al (1997) noted lower plasma insulin levels at 2 h after the OGTT in IGT subjects with a family history than in IGT subjects without a family history of diabetes, suggesting that families may have a genetic tendency to have lower beta cell function. Others have noted delayed insulin responses after an OGTT, with lower plasma insulin increases during the first 30 min in IGT as compared with controls, with subsequent hyperinsulinemia later on (Mitrakou et al, 1992;Chen et al, 1995). This has also been observed in AfricanAmericans with IGT (Osei et al, 1997).…”