Type 2 diabetes treatment approaches

Ralph DeFronzo (San Antonio, TX) suggested an interesting set of approaches to the treatment of type 2 diabetes. DeFronzo noted that the natural history of type 2 diabetes involves a reduction in insulin sensitivity during the progression from lean to obese with normal tolerance, and that the subsequent progression to impaired glucose tolerance (IGT) is associated with a further decrease in insulin sensitivity and a relative deficiency in insulin secretory function. As IGT progresses to diabetes, insulin secretion decreases without a further worsening in insulin sensitivity. DeFronzo presented studies of normal glucose-tolerant, impaired glucose-tolerant, and type 2 diabetic individuals that demonstrated an increase in the absolute rate of glucose-induced insulin secretion during the progression from normal to varying degrees of IGT, with insulin secretion subsequently decreasing progressively with worsening degrees of diabetes. Examining the ratio of insulin secretion to insulin resistance (the disposition index), DeFronzo showed that the logarithm of insulin secretion/insulin resistance is inversely proportional to the log of the 2-h glucose, and that with advanced degrees of IGT, ∼80% of insulin secretory capacity is lost, implying that insulin deficiency begins well before the onset of diabetes as currently defined. He cited an autopsy study showing that by the time elevations occur in fasting glucose, there is a 50% loss of β-cell mass, with a further decrease in β-cell volume with progression to diabetes (1).

The Diabetes Prevention Program further raises concern about the clinical implications of the term “pre-diabetes,” as the program found a 7.9% prevalence of diabetic retinopathy among individuals with IGT. At the time of diabetes diagnosis, 12.6% had retinopathy, although the mean A1C was only 6.1%. Peripheral neuropathy also …