In this unique longitudinal study (Whitehall II cohort), the authors characterized the trajectories of fasting and 2-hour postload glucose and of indices of insulin sensitivity and insulin secretion before the onset of type 2 diabetes. Over a median follow-up period of 9.7 years, 505 new cases of type 2 diabetes were diagnosed out of the 6536 participants. Multilevel models adjusted for age, sex and ethnicity revealed that metabolic measures had linear trends in the non diabetic group, except for insulin secretion. However, in the diabetic group, a linear increase in fasting glucose was followed by a steeper slope (from 5.79 mmol/L to 7.40 mmol/l), 3 years before the diagnosis of type 2 diabetes. Accordingly, 2-hour postload glucose increased rapidly during this period (from 7.60 mmol/L to 11.90 mmol/l). Insulin sensitivity (HOMA) decreased linearly in both groups but with a steeper slope in the diabetic group, 5 years before type 2 diabetes diagnosis. Insulin secretion (HOMA β-cell function) also increased between year 4 and 3 before the diagnosis of type 2 diabetes (from 85.0% to 92.6%) and then decreased (62.4%). Thus, these changes in plasma glucose concentrations, insulin sensitivity and insulin secretion 3 to 6 years before the onset of type 2 diabetes diagnosis may represent important opportunities for screening and prevention. The authors also hypothesized that prevention may be more effective during those years than during the prediabetes stage to delay the onset of type 2 diabetes. In their comment, Matthews DR and Levy JC expressed their doubt about sensitivity of screening diabetic individuals 3 or 4 years ahead but they commend the investigators for the uniqueness of their study which clearly shows the variation in β;-cell function (increase and then decrease) which precedes the exponential increase in glycemia leading to the diagnosis of type 2 diabetes.
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