Risk Factors for Type 2 Diabetes: Lessons Learned from Japanese Americans in Seattle

Abstract

Migrant Japanese populations in both the United States and Brazil have for a long time shown a higher prevalence of type 2 diabetes than in native Japanese, suggesting an interaction of lifestyle and genetic predisposition in the etiology of type 2 diabetes. The overall objective of the Seattle Japanese American Community Diabetes Study was to learn more about the etiology and pathogenesis of type 2 diabetes in Japanese Americans. This metabolically based epidemiologic study included extensive assessments of insulin sensitivity, insulin response, and adiposity with the latter including measurements of body fat distribution by both anthropometry and computed tomography. Because of this, the importance of visceral adiposity as a risk factor for abnormal glucose tolerance, hypertension, coronary heart disease, and the metabolic syndrome was demonstrated. In conjunction with an examination of diet and physical activity patterns, the result was a clearer understanding of the etiology and pathogenesis of type 2 diabetes in Japanese Americans. Wepropose that a lifestyle that fosters increased weight gain, especially in the visceral adipose depot, promotes the development of insulin resistance which in turn exposes an underlying reduced beta-cell reserve in susceptible individuals, resulting in glucose intolerance and eventually in many the development of diabetes. We have shown that it may be possible to delay or prevent the development of diabetes through dietary and exercise interventions in individuals identified as having impaired glucose tolerance. The lessons learned from studying migrant Japanese in Seattle may in many ways be applicable to other populations of Asian origin.

Figure 1

The overarching hypothesis for the Seattle Japanese American Community Diabetes Study was that nature and nurture interacted in the development of type 2 diabetes.

Figure 2

Mean blood glucose levels with 3‐h oral glucose tolerance test were not significantly different between diabetic men in Tokyo (n = 26) and Seattle (n = 68).

Figure 3

Mean plasma insulin levels with 3‐h oral glucose tolerance test were significantly higher (P < 0.006) in diabetic men in Seattle (n = 68) than in Tokyo (n = 26). Comparison of insulin assays between Seattle and Tokyo showed an excellent correlation (r = 0.885, P < 0.001) with Seattle levels tending to be slightly, but not significantly, lower than in Tokyo.

Figure 4

Diabetic Nisei men tended to have greater intra‐abdominal fat area by computed tomography (CT) than normal glucose tolerance (NGT) Nisei men. Two representative abdominal CT scans with low and high intra‐abdominal fat areas are shown at the bottom with intra‐abdominal fat colored white.

Figure 5

The mean 2‐h plasma glucose levels at 5 years of follow up in Nisei men who were impaired glucose tolerance at baseline were progressively higher as level of risk increased and were higher in those with a family history (hx) of diabetes. The trend with level of risk was significant (P < 0.05) in those with a family history of diabetes. Low risk: low dietary animal fat and protein plus high physical activity; intermediate risk: low dietary animal fat and protein and low physical activity or high dietary animal fat and protein and high physical activity; high risk: high dietary animal fat and protein and low physical activity.

Figure 6

Lifestyle intervention significantly reduced overall adiposity as measured by (a) bodyweight and (b) underwater weighing at 6 and 24 months compared with control. Lifestyle intervention also significantly reduced (c) intra‐abdominal fat (IAF) area at 6 and 24 months and (d) waist circumference at 24 months compared with control. P‐values for control vs intervention group comparisons are shown above the bars.

Figure 7

Lifestyle intervention significantly improved (a) insulin sensitivity at 6 and 24 months compared with control, but had no effect upon (b) beta‐cell function. P‐values for control vs intervention group comparisons are shown above the bars. AIRg, acute insulin response to glucose.