Hypoglycemia in Type 1 and Type 2 Diabetes: Physiology, Pathophysiology, and Management

IN BRIEF The threat and incidence of hypoglycemia is the major limiting factor in intensive glycemic control for both type 1 and type 2 diabetes. This article reviews the physiology of the normal counterregulatory responses to hypoglycemia and the deficient counterregulatory defenses that occur in patients with diabetes. Treatment paradigms for establishing good glycemic control while limiting hypoglycemia are also discussed.

[1]  P. Cryer.  Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. , 2005, Diabetes.

[2]  B. Frier,et al.  Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. , 2005, Diabetes care.

[3]  S. Davis,et al.  Effects of glycemic control on target organ responses to epinephrine in type 1 diabetes. , 2005, American journal of physiology. Endocrinology and metabolism.

[4]  P. Donnan,et al.  Frequency and predictors of hypoglycaemia in Type 1 and insulin‐treated Type 2 diabetes: a population‐based study , 2005, Diabetic medicine : a journal of the British Diabetic Association.

[5]  P. Cryer,et al.  Hypoglycemia in type 2 diabetes. , 2004, The Medical clinics of North America.

[6]  P. Cryer.  Diverse causes of hypoglycemia-associated autonomic failure in diabetes. , 2004, The New England journal of medicine.

[7]  I. Gabriely,et al.  Hypoglycemia in diabetes: common, often unrecognized. , 2004, Cleveland Clinic journal of medicine.

[8]  A. Ertl,et al.  Estrogen blunts neuroendocrine and metabolic responses to hypoglycemia. , 2003, Diabetes.

[9]  P. Cryer,et al.  Hypoglycemia in diabetes. , 2003, Diabetes care.

[10]  S. Davis,et al.  Hypoglycemia associated autonomic failure , 2002, Clinical Autonomic Research.

[11]  P. Cryer,et al.  Hypoglycemia-associated autonomic failure in advanced type 2 diabetes. , 2002, Diabetes.

[12]  I. Deary,et al.  Symptoms of hypoglycaemia in people with diabetes , 2001, Diabetic medicine : a journal of the British Diabetic Association.

[13]  B. D. de Galan,et al.  Glucose counterregulation in Type 2 diabetes mellitus , 2001, Diabetic medicine : a journal of the British Diabetic Association.

[14]  M. Stumvoll,et al.  Avoidance of Hypoglycemia Restores Hypoglycemia Awareness by Increasing -Adrenergic Sensitivity in Type 1 Diabetes , 2001, Annals of Internal Medicine.

[15]  S. Davis,et al.  Effects of morning hypoglycemia on neuroendocrine and metabolic responses to subsequent afternoon hypoglycemia in normal man. , 2001, The Journal of clinical endocrinology and metabolism.

[16]  A. Hattersley,et al.  Hypoglycaemic counter-regulation at normal blood glucose concentrations in patients with well controlled type-2 diabetes , 2000, The Lancet.

[17]  I. Hirsch,et al.  Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes. , 2000, Diabetes care.

[18]  S. Heller,et al.  Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. U.K. Lispro Study Group. , 1999, Diabetes care.

[19]  P. Cryer,et al.  Reduced beta-adrenergic sensitivity in patients with type 1 diabetes and hypoglycemia unawareness. , 1998, Diabetes care.

[20]  I. Mühlhauser,et al.  Risk factors of severe hypoglycaemia in adult patients with Type I diabetes – a prospective population based study , 1998, Diabetologia.

[21]  R. Holman,et al.  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. , 1998 .

[22]  I. Deary,et al.  Perceived symptoms of hypoglycaemia in elderly Type 2 diabetic patients treated with insulin , 1998, Diabetic medicine : a journal of the British Diabetic Association.

[23]  I. Macdonald,et al.  Effects of Glycemic Control on Protective Responses Against Hypoglycemia in Type 2 Diabetes , 1998, Diabetes Care.

[24]  W. Ray,et al.  Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. , 1997, Archives of internal medicine.

[25]  S. Davis,et al.  Effects of Differing Antecedent Hypoglycemia on Subsequent Counterregulation in Normal Humans , 1997, Diabetes.

[26]  P. Cryer.  Hypoglycemia: Pathophysiology, Diagnosis, and Treatment , 1997 .

[27]  I. Cranston,et al.  Altered Hierarchy of Protective Responses Against Severe Hypoglycemia in Normal Aging in Healthy Men , 1997, Diabetes Care.

[28]  Hypoglycemia in the Diabetes Control and Complications Trial , 1997, Diabetes.

[29]  P. Cryer,et al.  Reversal of Hypoglycemia Unawareness, But Not Defective Glucose Counterregulation, in IDDM , 1994, Diabetes.

[30]  P. Brunetti,et al.  Relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycaemia in male and female humans , 1994, Diabetologia.

[31]  A. Maran,et al.  Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes , 1994, The Lancet.

[32]  H. Tuokko,et al.  Altered responses to hypoglycemia of healthy elderly people. , 1994, The Journal of clinical endocrinology and metabolism.

[33]  H. Tuokko,et al.  Counterregulatory Hormone Responses to Hypoglycemia in the Elderly Patient with Diabetes , 1994, Diabetes.

[34]  T. Jones,et al.  Gender influences counterregulatory hormone responses to hypoglycemia. , 1993, Metabolism: clinical and experimental.

[35]  A. Cherrington,et al.  The effects of insulin on the counterregulatory response to equivalent hypoglycemia in patients with insulin-dependent diabetes mellitus. , 1993, The Journal of clinical endocrinology and metabolism.

[36]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[37]  A. Maran,et al.  Gender differences in counterregulation to hypoglycaemia , 1993, Diabetologia.

[38]  B. Frier,et al.  Frequency and Symptoms of Hypoglycaemia Experienced by Patients with Type 2 Diabetes Treated with Insulin , 1993, Diabetic medicine : a journal of the British Diabetic Association.

[39]  P. Cryer,et al.  Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. Recent antecedent hypoglycemia reduces autonomic responses to, symptoms of, and defense against subsequent hypoglycemia. , 1993, The Journal of clinical investigation.

[40]  P. Cryer,et al.  Reduced Neuroendocrine and Symptomatic Responses to Subsequent Hypoglycemia After 1 Episode of Hypoglycemia in Nondiabetic Humans , 1991, Diabetes.

[41]  W. Tamborlane,et al.  Effect of Intensive Insulin Therapy on Glycemic Thresholds for Counterregulatory Hormone Release , 1988, Diabetes.

[42]  P. Cryer,et al.  Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics. , 1988, The New England journal of medicine.

[43]  P. Cryer,et al.  Identification of type I diabetic patients at increased risk for hypoglycemia during intensive therapy. , 1983, The New England journal of medicine.

[44]  L. Sayadi,et al.  Abstract , 1897, Journal of the Neurological Sciences.

[45]  P. De Feo,et al.  The dawn phenomenon in Type 1 (insulin-dependent) diabetes mellitus: magnitude, frequency, variability, and dependency on glucose counterregulation and insulin sensitivity , 2004, Diabetologia.

[46]  P. Cryer,et al.  Negotiating the Barrier of Hypoglycemia in Diabetes , 2002 .

[47]  Ukpds,et al.  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes , 2002 .

[48]  P. Cryer.  Hypoglycemia risk reduction in type 1 diabetes. , 2001, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[49]  S. Davis,et al.  Hypoglycemic counterregulatory responses differ between men and women with type 1 diabetes. , 2000, Diabetes.

[50]  C. Mathews,et al.  Reevaluation of the major histocompatibility complex genes of the NOD-progenitor CTS/Shi strain. , 2000, Diabetes.

[51]  P. Cryer.  Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. , 1998, Advances in pharmacology.