Frequency of the dawn phenomenon in type 2 diabetes: implications for diabetes therapy.

This study was designed to assess the frequency of the dawn phenomenon in patients with type 2 diabetes. A secondary aim was to examine the influence of varying treatment regimens on the frequency of the dawn phenomenon. The dawn phenomenon was defined as a rise in plasma glucose levels of > or = 0.5 mmol/L (10 mg/dL) between 0500 and 0900 h occurring after a growth hormone surge of > or = 5 microg/L. Sixteen subjects (six men, 10 women) with type 2 diabetes were studied overnight on their current mode of therapy in the General Clinical Research Center. Additionally, six of these subjects were restudied in random order after each of the following three therapeutic regimens: (1) 6 weeks of glipizide, (2) 6 weeks of bedtime NPH insulin, and (3) 3 days of intensive insulin therapy with multiple injections of regular insulin followed by assessment during overnight intravenous infusion of insulin. Thus, a total of 34 overnight studies were performed under various treatment conditions to provide an approximate frequency of the dawn phenomenon in type 2 diabetes. Blood was drawn every 30 min between midnight and 0800 h for measurement of glucose, insulin, C-peptide, and growth hormone levels. Additional counterregulatory hormone levels were determined during 24 of the studies, and the integrity of growth hormone secretion in response to insulin-induced hypoglycemia was assessed in 12 of the 16 patients. The subjects were aged 51 +/- 15 years with a body mass index of 31 +/- 5 kg/m(2) and a mean glycosylated hemoglobin of 8.1 +/- 1.2%. The dawn phenomenon occurred in only one of 34 (3%) studies. Moreover, the four different treatment regimens did not affect the frequency of occurrence of the dawn phenomenon. Ten of the 12 patients tested failed to secrete growth hormone in response to insulin-induced hypoglycemia. These data suggest that the dawn phenomenon is unusual in type 2 diabetes. Previously reported high prevalence rates in studies using similar sample size may be attributable to a Biostator-induced artifact. Decisions regarding therapies for type 2 diabetes should not be based on the assumption that the dawn phenomenon routinely causes early morning hyperglycemia.

[1]  R. Rizza,et al.  Physiological concentrations of growth hormone exert insulin-like and insulin antagonistic effects on both hepatic and extrahepatic tissues in man. , 1981, The Journal of clinical endocrinology and metabolism.

[2]  Alberto Maran,et al.  Continuous subcutaneous glucose monitoring in diabetic patients: a multicenter analysis. , 2002, Diabetes care.

[3]  M. Rendell,et al.  The Dawn Phenomenon, an Early Morning Glucose Rise: Implications for Diabetic Intraday Blood Glucose Variation , 1981, Diabetes Care.

[4]  Importance of growth hormone for blood glucose regulation following insulin-induced nocturnal hypoglycemia in insulin-dependent diabetes mellitus. , 2009, Acta medica Scandinavica.

[5]  D. Owens,et al.  The dawn phenomenon and diabetes control in treated NIDDM and IDDM patients. , 1992, Diabetes research and clinical practice.

[6]  P. Cryer,et al.  Failure of nocturnal hypoglycemia to cause fasting hyperglycemia in patients with insulin-dependent diabetes mellitus. , 1987, The New England journal of medicine.

[7]  H. Orskov,et al.  Metabolic effects of growth hormone in humans. , 1995, Metabolism: clinical and experimental.

[8]  F. Casanueva,et al.  Growth hormone (GH) response to GH-releasing peptide-6 and GH-releasing hormone in normal-weight and overweight patients with non-insulin-dependent diabetes mellitus. , 1999, Metabolism: clinical and experimental.

[9]  J. Gerich,et al.  Prevention of the Dawn phenomenon (early morning hyperglycemia) in insulin-dependent diabetes mellitus by bedtime intranasal administration of a long-acting somatostatin analog. , 1988, Metabolism: clinical and experimental.

[10]  G. Boden,et al.  Evidence for a circadian rhythm of insulin secretion. , 1996, The American journal of physiology.

[11]  B. Beaufrère,et al.  Dawn phenomenon in Type 1 (insulin-dependent) diabetic adolescents: influence of nocturnal growth hormone secretion , 1988, Diabetologia.

[12]  W. Blackard,et al.  Pump-induced Insulin Aggregation: A Problem with the Biostator , 1985, Diabetes.

[13]  Philip Raskin,et al.  The Somogyi phenomenon. Sacred cow or bull? , 1984, Archives of internal medicine.

[14]  P. Brunetti,et al.  Nocturnal spikes of growth hormone secretion cause the dawn phenomenon in Type 1 (insulin-dependent) diabetes mellitus by decreasing hepatic (and extrahepatic) sensitivity to insulin in the absence of insulin waning , 2004, Diabetologia.

[15]  I. Hirsch,et al.  Failure of Nocturnal Hypoglycemia to Cause Daytime Hyperglycemia in Patients With IDDM , 1990, Diabetes Care.

[16]  P. Cryer,et al.  External and internal standards in the single-isotope derivative (radioenzymatic) measurement of plasma norepinephrine and epinephrine. , 1985, The Journal of laboratory and clinical medicine.

[17]  K. Reschke,et al.  Circadian Variation of Insulin Requirement in Insulin Dependent Diabetes Mellitus The Relationship between Circadian Change in Insulin Demand and Diurnal Patterns of Growth Hormone, Cortisol and Glucagon during Euglycemia , 1995, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[18]  T. M. Hayes,et al.  Dawn Phenomenon: Its Frequency in Non-Insulin-Dependent Diabetic Patients on Conventional Therapy , 1987, Diabetes Care.

[19]  D. Dunger,et al.  The Dawn Phenomenon Is Related To Overnight Growth Hormone Release In Adolescent Diabetics , 1990, Clinical endocrinology.

[20]  T. M. Hayes,et al.  Non-insulin-dependent diabetic patients (NIDDMs) do not demonstrate the dawn phenomenon at presentation. , 1988, Diabetes research and clinical practice.

[21]  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.

[22]  P. Cryer,et al.  Absence of the dawn phenomenon and abnormal lipolysis in Type 1 (insulin-dependent) diabetic patients with chronic growth hormone deficiency , 1992, Diabetologia.

[23]  N. Møller,et al.  Effects of growth hormone on glucose metabolism. , 1991, Hormone research.

[24]  G. Schernthaner,et al.  Dawn Phenomenon and Somogyi Effect in IDDM , 1989, Diabetes Care.

[25]  P. Brunetti,et al.  Studies on overnight insulin requirements and metabolic clearance rate of insulin in normal and diabetic man: relevance to the pathogenesis of the dawn phenomenon , 1986, Diabetologia.

[26]  W. Kerner,et al.  Studies on the pathogenesis of the dawn phenomenon in insulin-dependent diabetic patients. , 1984, Metabolism: clinical and experimental.

[27]  E. Ritz,et al.  Abnormal pulsatile secretion of growth hormone in non‐insulin‐dependent diabetes mellitus , 1997, Clinical endocrinology.

[28]  M. Bajaj,et al.  Effect of Glycemic Control on Glucose Counterregulation During Hypoglycemia in NIDDM , 1998, Diabetes Care.

[29]  P. Cryer,et al.  Sequence of events during development of the dawn phenomenon in insulin-dependent diabetes mellitus. , 1985, Metabolism: clinical and experimental.

[30]  G. Bolli,et al.  The "dawn phenomenon"--a common occurrence in both non-insulin-dependent and insulin-dependent diabetes mellitus. , 1984, The New England journal of medicine.

[31]  S. Amemiya,et al.  Role of IGF Binding Protein- 1 in the Dawn Phenomenon and Glycemic Control in Children and Adolescents With IDDM , 1997, Diabetes Care.