Hypoglycemia, hypoglycemia unawareness and counterregulation in children and adolescents with type 1 diabetes mellitus

Journal of Pediatric Endocrinology and Metabolism

Volumn 18, Issue 9, 2005, Pages 831-841

  Böber, Ece ^b   Büyükgebiz, Atilla ^b   Verrotti, Alberto ^a   Chiarelli, Francesco ^a  

^a UNIVERSITY OF CHIETI   (Italy)

^b DOKUZ EYLUL UNIVERSITY   (Turkey)

Author keywords

Children; Hypoglycemia; Type 1 diabetes mellitus

Indexed keywords

GLUCOSE; HEMOGLOBIN A1C; INSULIN; INSULIN ASPART; INSULIN DETEMIR; INSULIN GLARGINE; INSULIN LISPRO;

ADOLESCENT; CHILD; CLINICAL FEATURE; DIET SUPPLEMENTATION; DISEASE SEVERITY; DOSE RESPONSE; EXERCISE; GLUCOSE BLOOD LEVEL; HORMONAL REGULATION; HORMONE RESPONSE; HUMAN; HYPOGLYCEMIA; INSULIN RELEASE; JUVENILE DIABETES MELLITUS; LEARNING DISORDER; METABOLIC REGULATION; MORBIDITY; PATHOPHYSIOLOGY; RECURRENCE RISK; REVIEW; RISK ASSESSMENT; RISK FACTOR; TREATMENT INDICATION;

EID: 27844542180     PISSN: 0334018X     EISSN: None     Source Type: Journal    
DOI: 10.1515/JPEM.2005.18.9.831     Document Type: Review

References (97)

1. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977-986.
2. Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. J Pediatr 1994; 125: 177-188.
3. Davis EA, Keating B, Byrne GC, Russell M, Jones TW. Hypoglycemia: incidence and clinical predictors in a large population-based sample of children and adolescents with IDDM. Diabetes Care 1997; 20: 22-25.
4. Lteif AN, Schwenk WF II. Type 1 diabetes mellitus in early childhood: glycemic control and associated risk of hypoglycemic reactions. Mayo Clin Proc 1999; 74: 211-216.
5. Rewers A, Chase HP, Mackenzie T, Walravens P, Roback M, Rewers M, Hamman RF, Klingensmith G. Predictors of acute complications in children with type 1 diabetes. JAMA 2002; 287: 2511-2518.
6. Bolli GB. Counterregulatory mechanisms to insulin-induced hypoglycemia in humans: relevance to the problem of intensive treatment of IDDM. J Pediatr Endocrinol Metab 1998; 11 (Suppl 1): 103-115.
7. Banarer S, McGregor VP, Cryer PE. Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response. Diabetes 2002; 51: 958-965.
8. Ahern J, Tamborlane W. Practical strategies for avoiding hypoglycaemia in patients with IDDM. Diabetes Rev Int 1996; 5: 6-9.
9. Fukuda M, Tanaka A, Tahara Y, Ikegami H, Yamamato Y, Kumahara Y, Shima K. Correlation between minimal secretory capacity of pancreatic β-cells and stability of diabetic control. Diabetes 1988; 37: 81-88.
10. Borg MA, Borg WP, Tamborlane WV, Brines ML, Shulman GI, Sherwin RS. Chronic hypoglycemia and diabetes impair counterregulation induced by localized 2-deoxyglucose perfusion of the ventromedial hypothalamus in rats. Diabetes 1999; 48: 584-587.
11. Hepburn DA, Patrick AW, Brash HM, Thomson I, Frier BM. Hypoglycaemia unawareness in type 1 diabetes: a lower plasma glucose is required to stimulate sympathoadrenal activation. Diabet Med 1991; 8: 934-945.
12. Amiel SA, Tamborlane WV, Simonson DC, Sherwin RS. Defective glucose counterregulation after strict glycaemic control of insulin-dependent diabetes mellitus. N Engl J Med 1987; 316: 1376-1383.
13. Simonson DC, Tamborlane WV, DeFronzo RA, Sherwin RS. Intensive insulin therapy reduces counterregulatory hormone responses to hypoglycaemia in patients with type I diabetes. Ann Intern Med 1985; 103: 184-190.
14. Bjorgaas M, Vik T, Sand T, Birkeland K, Sager G, Vea H, Jorde R. Counterregulatory hormone and symptom responses to hypoglycaemia in diabetic children. Diabet Med 1997; 14: 433-441.
15. Davis SN, Shavers C, Costa F, Mosqueda-Garcia R. Role of cortisol in the pathogenesis of deficient counterregulation after antecedent hypoglycemia in normal humans. J Clin Invest 1996; 98: 680-691.
16. Rattarasarn C, Dagogo-Jack S, Zachwieja JJ, Cryer PE. Hypoglycemia-induced autonomic failure in IDDM is specific for stimulus of hypoglycemia and is not attributable to prior autonomic activation. Diabetes 1994; 43: 809-818.
17. Dagogo-Jack SE, Craft S, Cryer PE. Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. Recent antecedent hypoglycemia reduces autonomic responses to, symptoms of, and defense against subsequent hypoglycemia. J Clin Invest 1993; 91: 819-828.
18. Cryer PE. Hypoglycemia-associated autonomic failure in diabetes. Am J Physiol Endocrinol Metab 2001; 281: E1115-E1121.
19. Davis SN, Shavers C, Mosqueda-Garcia R, Costa F. Effects of differing antecedent hypoglycemia on subsequent counterregulation in normal humans. Diabetes 1997; 46: 1328-1335.
20. Davis SN, Mann S, Galasetti P, Neill RA, Tate D, Ertl AC, Costa F. Effects of differing durations of antecedent hypoglycemia on counterregulatory responses to subsequent hypoglycemia in normal humans. Diabetes 2000; 49: 1897-1903.
21. McGregor VP, Banarer S, Cryer PE. Elevated endogenous cortisol reduces autonomic neuroendocrine and symptom responses to subsequent hypoglycemia. Am J Physiol Endocrinol Metab 2002; 282: E770-E772.
22. McGregor VP, Greiwe JS, Banarer S, Cryer PE. Limited impact of vigorous exercise on defenses against hypoglycemia: relevance to hypoglycemia-associated autonomic failure. Diabetes 2002; 51: 1485-1492.
23. Sandoval DA, Ping L, Neill AR, Morrey S, Davis SN. Cortisol acts through central mechanisms to blunt counterregulatory responses to hypoglycemia in conscious rats. Diabetes 2003; 52: 2198-2204.
24. Davis SN, Shavers C, Davis B, Costa F. Prevention of an increase in plasma cortisol during hypoglycemia preserves subsequent counterregulatory responses. J Clin Invest 1997; 100: 429-438.
25. Raju B, McGregor VP, Cryer PE. Cortisol elevations comparable to those that occur during hypoglycemia do not cause hypoglycemia-associated autonomic failure. Diabetes 2003; 52: 2083-2089.
26. Porter BA, Keating B, Byrne G, Jones TW. Incidence and predictive criteria of nocturnal hypoglycemia in young children with insulin dependent diabetes mellitus. J Pediatr 1997; 130: 366-372.
27. Beregszàszi M, Tubiana-Rufi N, Benali K, Noël M, Bloch J, Czernichow P. Nocturnal hypoglycemia in children and adolescents with insulin-dependent diabetes mellitus: prevalence and risk fictors. J Pediatr 1997; 131: 27-33.
28. Lopez MJ, Oyarzabal M, Barrio R, Hermoso F, Lopez JP, Rodriquez M, Blasco L, Gastaldo E. Nocturnal hypoglycemia in IDDM patients younger than 18 years. Diabetic Med 1997; 14: 772-777.
29. Matyka KA, Crawford C, Wiggs L, Dunger DB, Stores G. Alterations in sleep physiology in young children with insulin dependent diabetes mellitus: relationship to nocturnal hypoglycemia. J Pediatr 2000; 137: 233-238.
30. Matyka KA, Wiggs L, Pramming S, Stores G, Dunger DB. Cognitive function and mood after profound nocturnal hypoglycaemia in prepubertal children with conventional insulin treatment for diabetes. Arch Dis Child 1999; 81: 138-142.
31. 13C magnetic resonance spectroscopy, in young children with type 1 diabetes mellitus. Diabet Med 2001; 18: 659-662.
32. Matyka KA, Crowne EC, Havel PJ, MacDonald IA, Matthews D, Dunger DB. Counterregulation during spontaneous nocturnal hypoglycemia in prepubertal children with type 1 diabetes. Diabetes Care 1999; 22: 1144-1150.
33. Jones TW, Porter P, Sherwin RS, Davis EA, O'Leary P, Frazer F, Byrne G, Stick S, Tamborlane WV. Decreased epinephrine responses to hypoglycemia during sleep. N Engl J Med 1998; 338: 1657-1662.
34. Bendtson I, Rosenfalck AM, Binder C. Nocturnal versus diurnal hormonal counterregulation to hypoglycemia in type 1 (insulin-dependent) diabetic patients. Acta Endocrinol (Copenh) 1993; 128: 109-115.
35. Diabetes Control and Complications Trial Research Group. Effects of intensive diabetes therapy on neuropsychological function in adults in the Diabetes Control and Complications Trial. Ann Intern Med 1996; 124: 379-388.
36. Reichard P, Berglund B, Britz A, Levander S, Rosenqvist U. Hypoglycemic episodes during intensified insulin treatment: increased frequency, but no effect on cognitive function. J Intern Med 1991; 229: 9-16.
37. Reichard P, Pihl M, Rosenqvist U, Sule J. Complications in IDDM are caused by elevated blood glucose level: the Stockholm Diabetes Intervention Study (SIDS) at 10-year follow-up. Diabetologia 1996; 39: 1483-1486
38. Ryan C, Vega A, Drash A. Cognitive deficits in adolescents who developed diabetes in early life. Pediatrics 1985; 75: 921-927.
39. Hershey T, Bhargava N, Sadler M, White NH, Craft S. Conventional versus intensive diabetes therapy in children with type 1 diabetes: effect on memory and motor speed. Diabetes Care 1999; 22: 1239-1241.
40. Rovet JF, Ehrlich RM. The effect of hypoglycemic seizures on cognitive function in children with diabetes: a 7-year prospective study. J Pediatr 1999; 134: 392-394.
41. Bjorgaas M, Gimse R, Vik T, Sand T. Cognitive function in type 1 diabetic children with and without episodes of severe hypoglycaemia. Acta Paediatr 1997; 86: 148-153.
42. Wredling R, Levander S, Adamson U, Lins PE. Permanent neuropsychological impairment after recurrent episodes of severe hypoglycaemia in man. Diabetologia 1990; 33: 152-157.
43. Gschwend S, Ryan C, Atchinson J, Arslanian S, Becker D. Effects of acute hypoglycemia on mental efficiency and counterregulatory hormones in adolescents with insulin-dependent diabetes mellitus. J Pediatr 1995; 126: 178-184.
44. Ryan C, Longstreet C, Morrow L. The effects of diabetes mellitus on the school attendance and school achievement of adolescents. Child Care Health Dev 1985; 11: 229-240.
45. Cryer P, Fisher J, Shamoon H. Hypoglycemia. Diabetes Care 1994; 17: 734-755.
46. McCrimmon RJ, Gold AE, Deary IJ, Kelnar CJH, Frier BM. Symptoms of hypoglycemia in children with IDDM. Diabetes Care 1995; 18: 858-861.
47. Schneider S, Beyer J, Sarnighausen HE, Burchert D, Kann P, Kustner H, Kunt T. Comparison of hypoglycemia perception and hormonal counterregulation in controlled hypoglycemia. A contribution to the diagnosis of hypoglycemia unawareness syndrome in type 1 diabetic patients. Dtsch Med Wochenschr 2000; 125: 177-181 (Abst).
48. Damacco F, Torelli C, Frezza E, Piccino E, Tansella F. Problems of hypoglycemia arising in children and adolescents with insulin-dependent diabetes mellitus. J Pediatr Endocrinol Metab 1998; 11 (Suppl 1): 167-176.
49. Shehadeh N, Kassem J, Tchaban I, Ravid S, Shahar E, Naveh T, Etzioni A. High incidence of hypoglycemic episodes with neurologic manifestations in children with insulin dependent diabetes mellitus. J Pediatr Endocrinol Metab 1998; 11 (Suppl 1): 183-187.
50. Gold AE, Marshall SM. Cortical blindness and cerebral infarction associated with severe hypoglycaemia. Diabetes Care 1996; 19: 1001-1003.
51. Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990-1996. Arch Dis Child 1999; 81: 318-323.
52. Bhatia V, Wolfsdorf JI. Severe hypoglycemia in youth with msulin-dependent diabetes mellitus: frequency and causative factors. Pediatrics 1991; 88: 1187-1193.
53. Clarke WL, Gonder-Frederick L, Cox DJ. The frequency of severe hypoglycaemia in children with insulin-dependent diabetes mellitus. Horm Res 1996; 45 (Suppl 1): 48-52.
54. The Diabetes Control and Complication Trial Research Group. Hypoglycemia in the Diabetes Control and Complication Trial. Diabetes 1997; 46: 271-286.
55. Nordfeldt S, Ludvigsson J. Severe hypoglycemia in children with IDDM. A prospective population study, 1992-1994. Diabetes Care 1997; 20: 497-503.
56. Chiarelli F, Verrotti A, Catino M, Sabatino G, Pinelli L. Hypoglycaemia in. children with type 1 diabetes mellitus. Acta Paediatr 1999; 88 (Suppl 427): 31-34.
57. Nordfeldt S, Ludvigsson J. Adverse events in intensively treated children and adolescents with type 1 diabetes. Acta Paediatr 1999; 88: 1184-1193.
58. Lopez MJ, Oyarzabal M, Rodriquez M, Barrio R, Hermoso F, Blasco L. Study Group of Infantile Diabetes of the Spanish Paediatric Endocrinology Society. Severe hypoglycemia in Spanish diabetic children and adolescents. J Pediatr Endocrinol Metab 1999; 12: 85-87.
59. Ludvigsson J, Nordfeldt S. Hypoglycaemia during intensified insulin therapy of children and adolescents. J Pediatr Endocrinol Metab 1998; 11 (Suppl 1): 159-166.
60. Davis EA, Keating B, Byrne GC, Russell M, Jones TW. Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus. Arch Dis Child 1998; 78: 111-115.
61. Tabak AG, Tamas G, Zgribor J, Wilson R, Becker D, Kerenyi Z, Orchard TJ. Targets and reality: a comparison of health care indicators in the U.S. (Pittsburgh Epidemiology of Diabetes Complications Study) and Hungary (DiabCare Hungary). Diabetes Care 2000; 23: 1284-1289.
62. Mortensen HB, Hougaard P. Comparison of metabolic control in a cross-sectional study of 2873 children and adolescents with IDDM from 18 countries. The Hvidøre Study Group on Childhood Diabetes. Diabetes Care 1997; 20: 714-720.
63. Bergada I, Suissa S, Dufresne J, Schiffrin A. Severe hypoglycemia in IDDM children. Diabetes Care 1989; 12: 239-244.
64. Fanelli C, Epifano L, Rambotti AM, Pampanelli S, Di Vincenzo A, Modarelli F, Lepore M, Annibale B, Ciofetta M, Bottini P, Parcellati F, Scionti L, Santeusiano F, Brunetti P, Bolli GB. Meticulous prevention of hypoglycemia (near-) normalizes magnitude and glycemic thresholds of neuroendocrine responses to, symptoms of, and cognitive function during hypoglycemia in intensively treated patients with IDDM of short duration. Diabetes 1993; 42: 1683-1689.
65. The DCCT Research Group. Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial. Am J Med 1991; 90: 451-459.
66. Fanelli C, Pampanelli S, Epifano L, Rambotti AM, Di Vincenzo A, Modarelli F, Ciofetta M, Lepore M, Annibale B, Torlone E, Perriello G, De Feo P, Santeusiano F, Brunetti P, Bolli GB. Long term recovery from unawareness, deficient counterregulation and lack of cognitive dysfunction during hypoglycaemia, following institution of a rational, intensive insulin therapy in IDDM. Diabetologia 1994; 37: 1265-1276.
67. Cranston I, Lomas J, Maran A, Macdonald I, Amiel SA. Restoration of hypoglycaemia awareness in patients with long duration insulin dependent diabetes. Lancet 1994; 344: 283-287.
68. Fritsche A, Stumwoll M, Haring HU, Gerich JE. Reversal of hypoglycemia unawareness in a long term type 1 diabetic patient by improvement of beta-adrenergic sensitivity after prevention of hypoglycemia. J Clin Endocrinol Metab 2000; 85: 523-525.
69. Fanelli C, Pampanelli S, Lalli C, Del Sincado P, Ciofetta M, Lepore M, Porcellati F, Bottini P, Di Vincenzo A, Brunetti P, Bolli GB. Long-term intensive therapy of IDDM patients with clinically overt autonomic neuropathy: effects on awareness of, and counterregulation to hypoglycemia. Diabetes 1997; 46: 1172-1181.
70. Dagogo-Jack S, Rattarasarn C, Cryer PE. Reversal of hypoglycemia unawareness, but not defective glucose counterregulation, in IDDM. Diabetes 1994; 43: 1426-1434.
71. Chalon S, Berlin I, Sachon C, Bosquet F, Grimaldi A. Propranolol in hypoglycaemia unawareness. Diabetes Metab 1999; 25: 23-26.
72. Bolli GB. How to ameliorate the problem of hypoglycemia in intensive as well as nonintensive treatment of type 1 diabetes. Diabetes Care 1999; 22 (Suppl 2): B43-52.
73. Ludvigsson J, Bolli GB. Intensive insulin treatment in diabetic children. Diabetes Nutr Metab 2001; 14: 292-304.
74. Stocks AE. Insulin lispro: experience in a private practice setting. Med J Aust 1999; 170; 364-367.
75. Chase HP, Lockspesier T, Peery B, Shepherd M, MacKenzie T, Anderson J, Garg SK. The impact of the Diabetes Control and Complications Trial and humalog insulin on glycohemoglobin levels and severe hypoglycemia in type 1 diabetes. Diabetes Care 2001; 24: 430-434.
76. Mohn A, Matyka KA, Harris DA, Ross KM, Edge JA, Dunger DB. Lispro or regular insulin for multiple injection therapy in adolescence. Differences in free insulin and glucose levels overnight. Diabetes Care 1999; 22: 27-32.
77. Home PD, Lindolm A, Hylleberg B, Round P, for the U.K. Insulin Aspart Study Group. Improved glycemic control with insulin aspart. A multicenter randomized double-blind crossover trial in type 1 diabetic patients. Diabetes Care 1998; 21: 1904-1909.
78. Raskin P, Guthrie RA, Leiter L, Riis A, Jovanovic L. Use of insulin aspart, a fast-acting insulin analog, as the mealtime insulin in the management of patients with type 1 diabetes. Diabetes Care 2000; 23: 583-588.
79. Rosenstock J, Park G, Zimmerman J, U.S. Insulin Glargine (HOE901) Type 1 Diabetes Investigator Group. Basal insulin glargine (HOE901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. Diabetes Care 2000; 23: 1137-1142.
80. Russell-Jones D, Simpson R, Hylleberg B, Draeger E, Bolinder J. Effects on QD insulin detemir on neutral protamine Hagedorn on blood glucose control in patients with type 1 diabetes mellitus using a basal-bolus regimen. Clin Ther 2004; 26: 724-736.
81. Bade BW, Sabbah HT, Gross TM, Frederickson LP, Davidson PC. Diabetes management in the new millennium using insulin pump therapy. Diabetes Metab Res Rev 2002; 18 (Suppl 1): S14-20.
82. 1c with low risk of hypoglycemia. J Pediatr Endocrinol Metab 2003; 16: 393-399.
83. 1c levels across all age groups. Pediatr Diabetes 2002; 3: 10-15.
84. Litton J, Rice A, Friedman N, Oden J, Lee MM, Freemark M. Insulin pump therapy in toddlers and preschool children with type 1 diabetes mellitus. J Pediatr 2002; 141: 490-495.
85. Weissberg-Benchell J, Antisdel-Lomaglio J, Seshadri R. Insulin pump therapy; a meta-analysis. Diabetes Care 2003; 26: 1079-1087.
86. Winiger G, Keller U, Laeger R, Girard J, Berger W. Protein content of the evening meal and nocturnal plasma glucose regulation in type I diabetic subjects. Horm Res 1995; 44: 101-104.
87. Kaufman FR, Devgan S. Use of uncooked cornstarch to avert nocturnal hypoglycemia in children and adolescents with type I diabetes. Diabetes Complications 1996; 10: 84-87.
88. Rami B, Zidek T, Schober E. Influence of a beta-glucan-enriched bedtime snack on nocturnal blood glucose levels in diabetic children. J Pediatr Gastroenterol Nutr 2001; 32: 34-36.
89. Levine BS, Anderson BJ, Butler DA, Antisdel JE, Brackett J, Laffel LM. Predictors of glycemic control and short term adverse outcomes in youth with type 1 diabetes. J Pediatr 2001; 139: 197-203.
90. Boland E, Monsod T, Delucia M, Brandt CA, Fernando S, Tamborlane WV. Limitations of conventional methods of self-monitoring of blood glucose. Diabetes Care 2001; 24: 1858-1862.
91. Schialfini R, Ciampalini P, Fierabracchi A, Spera S, Borrelli P, Bottazzo GF. The continuous glucose monitoring system (CGMS) in type 1 diabetic children is the way to reduce hypoglycemic risk. Diabetes Metab Res Rev 2002; 18: 324-329.
92. Kubiak T, Hermanns N, Schreckling HJ, Kulzer B, Haak T. Assessment of hypoglycemia awareness using continuous glucose monitoring. Diabet Med 2004; 21: 487-490.
93. Seidl R, Birnbacher R, Hauser E, Bernert G, Freilinger M, Schober P. Brainstem auditory evoked potentials and visually evoked potentials in young patients with IDDM. Diabetes Care 1996; 19: 1220-1224.
94. 1c, age at diagnosis and sex. Diabetologia 2002; 45: 108-114.
95. Grey M, Boland EA, Davidson M, Li J, Tamborlane WV. Coping skills training for youth with diabetes mellitus has long-lasting effects on metabolic control and quality of life. J Pediatr 2000; 137: 107-113.
96. Harris MA, Wysocki T, Sadler M, Wilkinson K, Harvey LM, Buckloh LM, Mauras N. Validation of a structured interview for the assessment of diabetes self-management. Diabetes Care 2000; 23: 1301-1304.
97. Hernandez CA, Bradish GI, Rodger NW, Rybansky SI. Self-awareness in diabetes: using body cues, circumstances and strategies. Diabetes Educ 1999; 25: 576-584.