Insulin and its role in chronic kidney disease

The body’s resistance to the actions of insulin (type II diabetes defect) results in compensatory increased production and secretion by the pancreas and leads to hyperinsulinemia in order to maintain euglycemia. When insulin secretion cannot be increased adequately (type I diabetes defect) to overcome insulin resistance in maintaining glucose homeostasis, hyperglycemia and glucose intolerance ensues. Insulin resistance and glucose intolerance has been well recognized in patients with advanced chronic kidney diseases (CKD). The etiology may involve uremic toxins from protein catabolism, vitamin D deficiency, metabolic acidosis, anemia, poor physical fitness, inflammation, and cachexia. Glucose and insulin abnormalities in nondiabetic CKD patients are implicated in the pathogenesis of hyperlipidemia and may represent important risk factors for accelerated atherosclerosis in these patients. Insulin secretion inadequacy has been associated with growth retardation in adolescents with CKD. Normal adolescents demonstrate an increase in insulin secretion as they go into puberty. It seems that the puberty growth spurt in adolescents both with normal health and renal failure may require increased insulin secretion as one of its hormonal requirements. Finally, insulin resistance has been associated with CKD. Whether insulin resistance is an antecedent of CKD or a consequence of impaired kidney function has been a subject of debate. The goal of this review was to provide an update of the literature on insulin pathophysiology in CKD, current understanding of its mechanisms, and epidemiological association of insulin resistance and CKD. Supported by a Mid-Career Research Development Award K24 DK59574 and U01 DK-03–012 from the National Institute of Health to RHM.