Treating postprandial hyperglycemia does not appear to delay progression of early type 2 diabetes: The Early Diabetes Intervention Program

OBJECTIVE - Postprandial hyperglycemia characterizes early type 2 diabetes. We investigated whether ameliorating postprandial hyperglycemia with acarbose would prevent or delay progression of diabetes, defined as progression to frank fasting hyperglycemia, in subjects with early diabetes (fasting plasma glucose [FPG] <140 mg/dl and 2-h plasma glucose ≥ 200 mg/dl). RESEARCH DESIGN AND METHODS - Two hundred nineteen subjects with early diabetes were randomly assigned to 100 mg acarbose t.i.d. or identical placebo and followed for 5 years or until they reached the primary outcome (two consecutive quarterly FPG measurements of ≥ 140 mg/dl). Secondary outcomes included measures of glycemia (meal tolerance tests, HbA_1c, annual oral glucose tolerance tests [OGTTs]), measures of insulin resistance (homeostasis model assessment [HOMA] of insulin resistance and insulin sensitivity index from hyperglycemic clamps), and secondary measures of β-cell function (HOMA-β, early- and late-phase insulin secretion, and proinsulin-to-insulin ratio). RESULTS - Acarbose significantly reduced postprandial hyperglycemia. However, there was no difference in the cumulative rate of frank fasting hyperglycemia (29% with acarbose and 34% with placebo; P = 0.65 for survival analysis). There were no significant differences between groups in OGTT values, measures of insulin resistance, or secondary measures of β-cell function. In a post hoc analysis of subjects with initial FPG <126 mg/dl, acarbose reduced the rate of development of FPG ≥ 126 mg/dl (27 vs. 50%; P = 0.04). CONCLUSIONS - Ameliorating postprandial hyperglycemia did not appear to delay progression of early type 2 diabetes. Factors other than postprandial hyperglycemia may be greater determinants of progression of diabetes. Alternatively, once FPG exceeds 126 mg/dl, β-cell failure may no longer be remediable.