The present study is a late installment of results of a large survey, inaugurated in the early 1980s, that called attention to links between hyperinsulinemia, insulin resistance, dysglycemia, hypertension, obesity, and hyperlipidemia (1
). Basal insulin was the strongest predictor for progression to type 2 diabetes over 24 years. Whereas ethnicity and higher values of basal insulin, triglycerides, BMI, blood pressure, fasting glucose, and male sex were each predictive of dysglycemia 24 years later, in the multiple regression model, the most statistically significant risk factor was basal insulin, reinforcing its importance as a chief component and perhaps a dominant factor in the development of type 2 diabetes.
Possible shortcomings of our study include remoteness of the outcome assessment from the baseline measurement causing inadequate information on medications, lifestyle changes, and time of onset of dysglycemia. Survival bias may affect the estimated links between basal hyperinsulinemia and dysglycemia, most likely attenuating them. A single baseline measurement of BMI has probably increased the magnitude of the association between obesity and the outcome of dysglycemia.
Our study has several strengths: the definition of normoglycemia was based on both fasting and 2-h postload glucose values, leaving our sample unconfounded by dysglycemia at baseline. The long follow-up period of 24 years, as well as the advanced age of subjects at follow-up, allowed us to report actual rates of dysglycemia. Finally, our cohort is of a well-chosen sample randomly selected from a national population registry, representative of the population with an equal number of men and women.
In our cohort, association between fasting plasma glucose and basal plasma insulin was weak with a correlation coefficient of 0.1 but was still statistically significant (P = 0.02), likely because of the large sample size. This suggests that, in this group of normoglycemic subjects, in the basal state, the absolute glucose value has a limited effect on basal insulin level. We conclude that in subjects with normoglycemia, basal insulin in the upper quintile confers an increased risk for the development of glucose dysmetabolism. We suggest that in “normal” subjects, fasting glucose and basal insulin are markers of different pathways to an overlapping group of disease processes.
Marked hyperinsulinemia is a common characteristic of several ethnic groups with a high prevalence of diabetes, including Mexican Americans (7
), Pacific Islanders (8
), Native Americans (9
), and African Americans (10
), even at an early age (10
). Identifying individuals whose glucose tolerance will most likely progress over the years to dysglycemia would be of great public health benefit. Thus, a basal insulin measurement may turn out to be a useful adjunct in at-risk individuals with normal or near-normal glycemia. We provide here long-term epidemiological evidence that hyperinsulinemia in the basal state may relate to the root cause of type 2 diabetes. The increasing prevalence of hyperinsulinemia, particularly among groups such as young adults and non-Hispanic white women (15
), in light of our findings, is alarming.