Carbohydrate and insulin metabolism in chronic kidney disease
- Biff F Palmer, MD
Biff F Palmer, MD
- Professor of Internal Medicine
- University of Texas Southwestern Medical Center
- William L Henrich, MD, MACP
William L Henrich, MD, MACP
- Professor of Medicine
- President of the Health Science Center
- University of Texas Health Science Center School of Medicine
Uremia is typically associated with impaired glucose metabolism. Some patients have hyperglycemia in response to oral and intravenous glucose loads, while others are able to maintain normoglycemia by raising plasma insulin levels. Studies utilizing the euglycemic and hyperglycemic clamp techniques suggest that several disturbances in carbohydrate handling may be present. Tissue insensitivity to insulin is of primary importance, but alterations in insulin degradation and insulin secretion also may contribute [1-3]. The variable severity of these changes in individual patients explains the variable plasma levels of insulin and glucose that may be seen both fasting and following a glucose load.
This topic will review the changes in carbohydrate and insulin metabolism that occur in chronic kidney disease (CKD) and the clinical implications of these abnormalities in nondiabetics. The impact of these changes on the management of hyperglycemia in diabetic patients with end-stage renal disease (ESRD) is discussed separately. (See "Management of hyperglycemia in patients with type 2 diabetes and pre-dialysis chronic kidney disease or end-stage renal disease".)
NORMAL RENAL HANDLING OF INSULIN
The kidney plays a central role in the metabolism of insulin in normal subjects [1,2,4]. Insulin has a molecular weight of 6000 and is therefore freely filtered. Of the total renal insulin clearance, approximately 60 percent occurs by glomerular filtration and 40 percent by extraction from the peritubular vessels. Insulin in the tubular lumen enters proximal tubular cells by carrier-mediated endocytosis and is then transported into lysosomes, where it is metabolized to amino acids . The net effect is that <1 percent of filtered insulin appears in the final urine.
The renal clearance of insulin is 200 mL/min, significantly exceeding the normal glomerular filtration rate (GFR) of 120 mL/min due to the contribution of tubular secretion. From this rate of renal clearance, it can be calculated that 6 to 8 units of insulin are degraded by the kidney each day, which accounts for approximately 25 percent of the daily production of insulin by the pancreas. The contribution of renal metabolism is enhanced in diabetic subjects receiving exogenous insulin since injected insulin enters the systemic circulation directly, without first passing through the liver.
Impaired tissue sensitivity to insulin occurs in almost all uremic subjects and is largely responsible for the abnormal glucose metabolism seen in this setting [1-3]. Possible mechanisms that could account for the reduction in insulin-mediated glucose handling include: (1) increased hepatic gluconeogenesis that does not suppress normally following insulin; (2) reduced hepatic and/or skeletal muscle glucose uptake; and (3) impaired intracellular glucose metabolism due either to decreased oxidation to carbon dioxide and water or to diminished synthesis of glycogen.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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