Hypoglycaemia in Clinical Diabetes

76 FREQUENCY, CAUSES AND RISK FACTORS• Hypoglycaemia occurs when there is an imbalance between insulin-mediated glucosedisposal and glucose influx into the circulation from the liver and exogenous carbohydrate.Typical precipitants include patient error in insulin dosage, alcohol andexercise.• Plasma concentrations of exogenous insulin cannot decline in response to falling bloodglucose and the time action profiles of current insulins do not accurately mimic the normalphysiological variation in insulin. In a high proportion of cases, no underlying precipitantof a given episode of hypoglycaemia can be identified.• The DCCT and other intervention studies have provided substantial information of theepidemiology of severe hypoglycaemia, but individuals participating in such studies maynot be representative of the wider population who have type 1 diabetes.• A major determinant of increased risk of severe hypoglycaemia is Hypoglycaemia-Associated Autonomic Failure, which is a consequence of exposure to recurrent episodesof hypoglycaemia. This is a feature of individuals with long-standing diabetes, intensiveinsulin therapy and strict glycaemic control.• Recent data suggest that there may be specific genetic factors that predispose to anincreased risk of hypoglycaemia.REFERENCESAirey CM, Williams DRR, Martin PG, Bennett CMT, Spoor PA (2000). Hypoglycaemia induced byexogenous insulin – ‘human’ and animal insulin compared. Diabetic Medicine 17: 416–32.Allen C, LeClaire T, Palta M, Daniels K, Meredith M, D’Alessio DJ, for the Wisconsin DiabetesRegistry Project (2001). Risk factors for frequent and severe hypoglycemia in type 1 diabetes.Diabetes Care 24: 1878–81.American Diabetes Association Workgroup on Hypoglycemia (2005). Defining and Reporting Hypoglycemiain Diabetes. Diabetes Care 28: 1245–9.Anderson JH, Brunelle RL, Koivisto VA, Pfutzner A, Trautmann ME, Vignati L, DiMarchi R, TheMulticenter Insulin Lispro Study Group (1997). Reduction of postprandial hyperglycemia andfrequency of hypoglycemia in IDDM patients on insulin-analog treatment. Diabetes 46: 265–70.Arky RA, Veverbrants E, Abramson EA (1968). Irreversible hypoglycemia. A complication of alcoholand insulin. Journal of the American Medical Association 206: 575–8.Avogaro A, Beltramello P, Gnudi L, Maran A, Valerio A, Miola M et al. (1993). Alcohol intakeimpairs glucose counterregulation during acute insulin-induced hypoglycemia in IDDM patients.Evidence for a critical role of free fatty acids. Diabetes 42: 1626–34.Bacatselos SO, Karamitsos DT, Kourtoglou GI, Zambulis CX, Yovos JG, Vyzantiadis AT (1995).Hypoglycaemia unawareness in type 1 diabetic patients under conventional insulin treatment.Diabetes Nutrition and Metabolism 8: 267–75.Banarer S, Cryer PE (2003). Sleep-related hypoglycemia-associated autonomic failure in type 1diabetes. Diabetes 52: 1195–1203.Bode BW, Schwartz S, Stubbs HA, Block JE (2005). Glycemic characteristics in continuously monitoredpatients with type 1 and type 2 diabetes. Normative values. Diabetes Care 28: 2361–6.Bolli G, De Feo P, Compagnucci P, Cartechini MG, Angeletti G, Santeusanio F et al. (1983).Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. Interaction of antiinsulinantibodies and impaired glucagon and epinephrine secretion. Diabetes 32: 134–41.