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Progression to Type 2 Diabetes Characterized by Moderate Then Rapid Glucose Increases

¹ Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona
² Department of Mathematics and Statistics, Arizona State University, Tempe, Arizona

Address correspondence and reprint requests to Dr. Clinton C. Mason, Diabetes Epidemiology and Clinical Research Section, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 1550 E. Indian School Rd., Phoenix, AZ 85014-4972. E-mail: masonclint{at}niddk.nih.gov

Abbreviations: GEM, glucose effects model; OGTT, oral glucose tolerance test; SSE, sum of squared error

OBJECTIVE—The transition of an individual from normoglycemia to diabetes has generally been thought to involve either moderate or rapid changes in glucose over time, although few studies have analyzed these changes. We sought to determine whether a general pattern of glucose change exists in most individuals who become diabetic.

RESEARCH DESIGN AND METHODS—We examined longitudinal data from Pima Indians who developed diabetes after several biennial examinations to characterize changes in 2-h plasma glucose. A distinct pattern of glucose change was apparent in the time course of most individuals, an initial linear trend followed by a steeper rise in glucose values. A model consisting of additive linear and exponential functions was hypothesized to account for this pattern and was tested for goodness of fit on 55 individuals who became diabetic after at least 10 previous examinations.

RESULTS—The combined linear and exponential model provided a significantly better fit than linear or exponential models alone in 40 of the 55 cases (P < 10^–38). Using this model, the timeframe over which glucose values rose suddenly was estimated, having a median time to onset of <4.5 years from the time at which the exponential effect had contributed a modest increase of 10 mg/dl to the initial linear trend.

CONCLUSIONS—We conclude that there are two distinct processes affecting glucose levels in most individuals who progress to type 2 diabetes and that the rapid glucose rise identified in these people may be an important period for physiologic and preventive research.

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