CORE CURRICULUM IN NEPHROLOGY Diabetes and the Kidney Andrew S. O’Connor, DO, MPH, and Jeffrey R. Schelling, MD DIABETES Definitions ● Metabolic disorder of multiple causes char- acterized by chronic hyperglycemia and disorders of carbohydrate, fat, and protein metabolism ● Results from defects in insulin secretion (type 1), insulin action (type 2), or combina- tion of these factors ● World Health Organization and American Diabetes Association diagnostic criteria:  Fasting plasma glucose 126 mg/dL (7.0 mmol/L) or fasting whole-blood glucose level 110 mg/dL (6.1 mmol/ L), or a  2-hour post–glucose-load plasma glu- cose 200 mg/dL (11.1 mmol/L; 180 mg/dL [10.0 mmol/L] if whole blood), or a  Random plasma glucose 200 mg/dL (11.1 mmol/L) on 1 occasion  “Prediabetic” stage: fasting plasma glu- cose between 100 and 126 mg/dL (5.6 and 7.0 mmol/L) increasingly recognized as risk factor for end-organ complications; evidence supports lifestyle interventions to prevent or delay onset of diabetes Incidence ● 18.2 million people in United States have diabetes (National Health and Nutrition Examination Survey 1999 to 2000), and up to one third of these cases are undiagnosed ● Approximately 1 in 400 to 500 children and adolescents have type 1 diabetes ● With increases in obesity rates in adoles- cents, type 2 diabetes becoming common, especially in minority groups ● 8.7% of adults have diabetes; rate increases to 18% of adults aged 60 years ● By 2030, anticipate 366 million cases of type 2 diabetes worldwide and 30 million US cases Risk Factors for Development Type 1 diabetes ● Defined by autoimmunity; autoantigens in- clude islet-cell proteins, glutamic acid decar- boxylase, insulin, and proinsulin ● Viral infections may initiate a poorly under- stood immune response, which induces -cell damage ● Genetics/family history:  Lifetime risk for 1 monozygotic twin is 20% to 30% if the other has diabetes  18 different risk alleles have been identified Type 2 diabetes ● Environment:  Most patients are overweight or obese, suggesting role for environmental fac- tors, especially “Westernization” of diet with highly processed foods high in fat and simple sugars ● Genetics/family history:  High degrees of concordance within fami- lies and between twins  Single gene mutations have been identi- fied for multiple mature-onset diabetes of the young (MODY) phenotypes ADDITIONAL READING 1. Diabetes Prevention Program Research Group: Reduc- tion in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393-403, 2002 From the Rammelkamp Center for Education and Re- search, Department of Medicine, Case Western Reserve University, Cleveland, OH. Received February 18, 2005; accepted in revised form May 12, 2005. Originally published online as doi:10.1053/j.ajkd.2005.05.032 on August 22, 2005. Address reprint requests to Jeffrey R. Schelling, MD, Rammelkamp Center for Education and Research, Depart- ment of Medicine, Case Western Reserve University, 2500 MetroHealth Dr, Cleveland, OH 44109. E-mail: jeffrey. schelling@case.edu © 2005 by the National Kidney Foundation, Inc. 0272-6386/05/4604-0025$30.00/0 doi:10.1053/j.ajkd.2005.05.032 American Journal of Kidney Diseases, Vol 46, No 4 (October), 2005: pp 766-773 766