Holistic Approach to Glycemic control
HOLISTIC APPROACH TO GLYCEMIC CONTROL
Ralph A. DeFronzo, M.D., Professor of Medicine, Chief, Diabetes Division, University of Texas Health Science Center, San Antonio, TX
Ten years ago, our concept of the pathogenesis of type 2 diabetes was quite simple. We recognised that there was underlying moderate-severe insulin resistance affecting muscle and the liver, and this, coupled with beta cell failure, formed the classical triumvirate (1). The insulin resistance in muscle primarily was responsible for the excessive postprandially rise in plasma glucose concentration, while insulin resistance in the liver, in combination with accelerated gluconeogenesis, resulted in an excessive rate of hepatic glucose production which led to an increase in the fasting plasma glucose concentration (2-4). In response to the insulin resistance, the beta cell initially is able to compensate, by appropriately increasing its secretion of insulin to maintain normal glucose homeostasis (1,5,6). However, with time declining beta cell function results first in postprandial hyperglycaemia and subsequently a rise in the fasting plasma glucose concentration and ultimately the onset of frank diabetes (5,7-9). The relative contributions of beta cell failure and insulin resistance to the diabetic state vary between different ethnic populations (10). However diabetes does not become manifest until beta cell failure leads to a failure to compensate for the insulin resistance(1,11).
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