Abstract
Hypoglycemia is the limiting factor in the glycemic management of diabetes because it generally precludes maintenance of euglycemia. Improving glycemic control while minimizing hypoglycemia in type 1 diabetes mellitus (T1DM) and advanced type 2 diabetes (T2DM) involves both application of the principles of aggressive therapy—patient education and empowerment, frequent self-monitoring of blood glucose, flexible insulin regimens, individualized glycemic goals, and ongoing professional guidance and support—and implementation of hypoglycemia risk reduction.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
The 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.
Reichard P, Nilsson B-Y, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 1993;329: 304–309.
The United Kingdom Prospective Diabetes Study Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998;352: 837–853.
Cryer PE. Hypoglycemia. Pathophysiology, Diagnosis and Treatment. Oxford University Press, New York, 1997.
Cryer PE. Hypoglycemia is the limiting factor in the management of diabetes. Diabetes/Metab Res Rev 1999;15: 42–46.
The Diabetes Control and Complications Trial Research Group. Epidemiology of severe hypoglycemia in the Diabetes Control and Complications Trial. Am J Med 1991;90: 450–459.
The Diabetes Control and Complications Trial Research Group. Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes 1997;46: 271–286
Reichard P, Berglund B, Britz A, Cars I, Nilsson BY, Rosenqvist U. Intensified conventional insulin treatment retards the microvascular complications of insulin-dependent diabetes mellitus: The Stockholm Diabetes Intervention Study after 5 years. J Intern Med 1990;230: 101–108.
The United Kingdom Prospective Diabetes Study Group. A 6-year, randomized, controlled trial cornparing sulfonylurea, insulin and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med 1998;128: 165–175.
Egger M, Davey Smith G, Stettler C, Diem P. Risk of adverse effects of intensified treatment in insulin-dependent diabetes mellitus: A meta-analysis. Diabet Med 1997;14: 919–928.
Laing SP, Swerdlow AJ, Slater SD, Bothat JL, Burden AC, Waugh NR, et al. The British Diabetic Association Cohort Study. II. Cause-specific mortality in patients with insulin-treated diabetes mellitus. Diabet Med 1999;16: 466–471.
Hepburn DA, MacLeod KM, Pell ACH, Scougal IJ, Frier BM. Frequency and symptoms of hypoglycemia experienced by patients with type 2 diabetes treated with insulin. Diabet Med 1993;10: 231–237.
Stumvoll M, Meyer C, Mitrakou A, Nadkarni V, Gerich J. Renal glucose production and utilization: new asnects in humans. Diabetologia 1997;40: 749–757.
Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest 1987;79: 777–781.
Mitrakou A, Ryan C, Veneman T, Mokan M, Jensen T, Kiss I, et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms and cerebral dysfunction. Am J Physiol 1991;260: E67-E74.
Fanelli C, Pampanelli S, Epifano L, Rambotti AM, Ciofetta M, Modarelli F, et al. Relative roles of insulin and hypoglycemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycemia in male and female humans. Diabetologia 1994;37: 797–807.
Boyle PJ, Cryer PE. Growth hormone, cortisol, or both are involved in defense against, but are not critical to recovery from, prolonged hypoglycemia in humans. Am J Physiol 1991;260: E395–E402.
Amiel SA, Simonson DC, Sherwin RS, Lauritano AA, Tamborlane WV. Exaggerated epinephrine responses to hypoglycemia in normal and insulin-dependent diabetic children. J Pediatr 1987;110: 832–837.
Jones TW, Boulware SD, Kraemer DT, Caprio S, Sherwin RS, Tamborlane WV. Independent effects of youth and poor diabetes control on responses to hypoglycemia in children. Diabetes 1991;40: 358–363.
Jones TW, Borg WP, Boulware SD, McCarthy G, Sherwin RS, Tamborlane WV. Enhanced adrenomedullary response and increased susceptibility to neuroglycopenia: mechanisms underlying the adverse effects of sugar ingestion in healthy children. J Pediatr 1995;126: 171–177.
Amiel, SA, Maran A, Powrie, JK, Umpleby AM, Macdonald IA. Gender differences in counterregulation to hypoglycemia. Diabetologia 1993;36: 460–464.
Davis SN, Cherrington AD, Goldstein RE, Jacobs J, Price L. Effects of insulin on counterregulatory response to equivalent hypoglycemia in normal females. Am J Physiol 1993;265: E680–E689.
Fanelli C, Pampanelli S. Epifano L, Rambotti AM, Ciofetta M, Modarelli F, 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. Diabetologia 1994;37: 797–807.
Davis S, Shavers C, Costa F. Differential gender related neuroendocrine responses to hypoglycemia are due to alterations in CNS drive and not glycemic thresholds. Diabetes 1997;46: 17A (abstract).
Towler DA, Havlin CE, Craft S, Cryer P. Mechanisms of awareness of hypoglycemia: Perception of neurogenic (predominantly cholinergic) rather than neuroglycopenic symptoms. Diabetes 1993;42: 1791–1798.
Boyle PJ, Schwartz NS, Shah SD, Clutter WE, Cryer PE. Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics. N Engl J Med 1988;318: 1487–1492.
Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV. Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release. Diabetes 1988;37: 901–907.
Mitrakou A, Fanelli C, Veneman T, Perriello G, Platanisoto D, Rambotti A, et al. Reversibility of hypoglycemia unawareness in patients with an insulinoma. N Engl J Med 1993;329: 834–839.
Fukuda M, Tanaka A, Tahara Y, Ikegami H, Yamamoto Y, Kumahara Y, et al. Correlation between minimal secretory capacity of pancreatic β-cells and stability of diabetic control. Diabetes 1988;37: 81–88.
Mühlhauser I, Overmann H, Bender R, Bott U, Berger M. Risk factors for severe hypoglycaemia in adult patients with type 1 diabetes-a prospective population based study. Diabetologia 1997;41: 1274–1282.
Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH. Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science 1973;182: 171–173.
Bolli G, De Feo P, Compagnucci P, Cartechini MG, Angeletti G, Santeusanio F, et al. Abnormal glucose counterregulation after subcutaneous insulin in insulin dependent diabetes mellitus: interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion. Diabetes 1983;32: 134–141.
Boden G, Reichard GA Jr, Hoeldtke RD, Rezvani I, Owen OE. Severe insulin-induced hypoglycemia associated with deficiencies in the release of counterregulatory hormones. N Engl J Med 1981;305: 1200–1205.
Hirsch BR, Shamoon H. Defective epinephrine and growth hormone responses in type 1 diabetes are stimulus specific. Diabetes 1987;36: 20–26.
Dagogo-Jack SE, Craft S, Cryer PE. Hypoglycemia-associated autonomic failure in insulin dependent diabetes mellitus. J Clin Invest 1993;91: 819–828.
Heller SR, Cryer PE. Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after one episode of hypoglycemia in nondiabetic humans. Diabetes 1991;40: 223–226.
Davis MR, Shamoon H. Counterregulatory adaptation to recurrent hypoglycemia in normal humans. J Clin Endocrinol Metab 1991;73: 995–1001.
Widom B, Simonson DC. Intermittent hypoglycemia impairs glucose counterregulation. Diabetes 1992;41: 1597–1602.
Veneman T, Mitrakou A, Mokan M, Cryer P, Gerich J. Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia. Diabetes 1993;42: 1233–1237.
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.
Davis MR, Mellman M, Shamoon H. Further defects in counterregulatory responses induced by recurrent hypoglycemia in IDDM. Diabetes 1992;41: 1335–1340.
Lingenfelser T, Renn W, Sommerwerck U, Jung ME, Buettner UW, Zaiser-Kaschel H, et al. Compromised hormonal counterregulation, symptom awareness, and neurophysiological function after recurrent short-term episodes of insulin-induced hypoglycemia in IDDM patients. Diabetes 1993;42: 610–618.
Bottini P, Boschetti E, Pampanelli S, Ciofetta M, Del Sindaco P, Scionti L, et al. Contribution of autonomic neuropathy to reduced plasma adrenaline responses to hypoglycemia in IDDM: evidence for a nonselective defect. Diabetes 1997;46: 814–823.
Meyer C, Grobmann R, Mitrakou A, Mahler R, Veneman T, Gerich J, et al. Effects of autonomic neuropathy on counterregulation and awareness of hypoglycemia in type 1 diabetic patients. Diabetes Care 1998;21: 1960–1966.
White NH, Skor D, Cryer PE, Bier DM, Levandoski L, Santiago JV. Identification of type 1 diabetic patients at increased risk for hypoglycemia during intensive therapy. N Engl J Med 1983;308: 485–491.
Bolli GG, De Feo P, De Cosmo S, Perriello G, Ventura MM, Masssi-Benedetti M, et al. A reliable and reproducible test for adequate glucose counterregulation in type 1 diabetes. Diabetes 1984;33: 732–737.
Gold AE, MacLeod KM, Frier BM. Frequency of severe hypoglycemia in patients with type 1 diabetes with impaired awareness of hypoglycemia. Diabetes Care 1994;17: 697–703.
Cryer PE. Iatrogenic hypoglycemia as a cause of hypoglycemia-associated autonomic failure in IDDM: a vicious cycle. Diabetes 1992;41: 255–260.
Hvidberg A, Fanelli CG, Hershey TG, Terkamp C, Craft S, Cryer PE. Impact of recent antecedent hypoglycemia on hypoglycemic cognitive dysfunction in nondiabetic humans. Diabetes 1996;45: 1030–1036.
Ovalle F, Fanelli CG, Paramore DS, Hershey T, Craft S, Cryer PE. Brief twice weekly episodes of hypoglycemia reduce detection of clinical hypoglycemia in type 1 diabetes mellitus. Diabetes 1998;47: 1472–1479.
Fanelli CG, Paramore DS, Hershey T, Terkamp C, Ovalle F, Craft S, et al. Impact of nocturnal hypoglycemia on hypoglycemic cognitive dysfunction in type 1 diabetes mellitus. Diabetes 1998;47: 1920–1927.
Dagogo-Jack S, Rattarasarn C, Cryer PE. Reversal of hypoglycemia unawareness, but not defective glucose counterregulation, in IDDM. Diabetes 1994;43: 1426–1434.
Fanelli CG, Pampanelli S, Epifano L, Rambotti AM, Vincenzo AD, Modarelli F, et al. Long-term recovery from unawareness, deficient counterregulation and lack of cognitive dysfunction during hypoglycemia following institution of rational intensive therapy in IDDM. Diabetologia 1994;37: 1265–1276.
Cranston I, Lomas J, Maran A, Macdonald I, Amiel S. Restoration of hypoglycemia unawareness in patients with long duration insulin-dependent diabetes mellitus. Lancet 1994;344: 283–287.
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.
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.
Boyle PJ, Nagy RJ, O’Connor AM, Kempers SF, Yeo RA, Qualls C. Adaptation in brain glucose uptake following recurrent hypoglycemia. Proc Natl Acad Sci USA 1994;91: 9352–9356.
Boyle PJ, Kempers SF, O’Connor AM, Nagy RJ. Brain glucose uptake and unawareness of hypoglycemia in patients with insulin dependent diabetes mellitus. N Engl J Med 1995;333: 1726–1731.
Segel S, Fanelli C, Dence C, Markham J, Videen T, Paramore D, et al. Blood-to-brain glucose transport is not increased following hypoglycemia. Diabetes 2001;50: 1911–1917.
Paramore DS, Fanelli CG, Shah SD, Cryer PE. Hypoglycemia per se stimulates sympathetic neural as well as adrenomedullary activity but, unlike the adrenomedullary response, the forearm sympathetic neural responses is not reduced following recent hypoglycemia. Diabetes 1999;48: 1429–1436.
Berlin I, Grimaldi A, Payan C, Sachon C, Bosquet F, Thervet F, et al. Hypoglycemic symptoms and decreased β-adrenergic sensitivity in insulin dependent diabetic patients. Diabetes Care 1987;10: 742–747.
Korytkowski M, Mokan M, Veneman T, Mitrakou A, Cryer P, Gerich JE. Reduced β-adrenergic sensitivity in insulin dependent diabetic patients. Diabetes Care 1998;21: 1939–1943.
Fritsche A, Stumvoll M, Grüb M, Sieslack S, Renn W, Schmülling R-M, et al. Effect of hypoglycemia on β-adrenergic sensitivity in normal and type 1 diabetic subjects. Diabetes Care 1998;21: 1505–1510.
Fritsche A, Stumvoll M, Häring H-U, Gerich JE. Reversal of hypoglycemia unawareness in a longterm type 1 diabetic patient by improvement of β-adrenergic sensitivity after prevention of hypoglycemia. J Clin Endocrinol Metab 2000;85: 523–525.
Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay IR, et al., for the UKPDS Group. Autoantibodies to islet cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. Lancet 1997;350: 1288–1293.
Segel SA, Paramore DS, Cryer PE. Defective glucose counterregulation in type 2 diabetes. Diabetes 2000;49: A131 (abstract).
Perriello G, De Feo P, Torlone E, Fanelli C, Santeusanio F, Brunetti P, et al. The dawn phenomenon in type 1 (insulin dependent) diabetes mellitus: magnitude, frequency, variability, and dependence on glucose counterregulation and insulin sensitivity. Diabetes 1991;34: 21–28.
Jones TW, Porter P, Sherwin RS, Davis EA, O’Leary P, Frazer F, et al. Decreased epinephrine responses to hypoglycemia during sleep. N Engl J Med 1998;338: 1657–1662.
Heller SR, Amiel SA, Mansell P, the U.K. Lispro Study Group. Effect of the fast acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. Diabetes Care 1999;22: 1607–1611.
Ratner RE, Hirsch IB, Neifing JL, Garg SK, Mecca TE, Wilson CA, for the U.S. Study Group of Insulin Glargine in Type 1 Diabetes. Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. Diabetes Care 2000;23: 639–643.
Saleh TY, Cryer PE. Alanine and terbutaline in the prevention of nocturnal hypoglycemia in IDDM. Diabetes Care 1997;20: 1231–1236.
Ververs MTC, Rouwé C, Smit GPA. Complex carbohydrates in the prevention of nocturnal hypoglycaemia in diabetic children. Eur J Clin Nutr 1993;47: 268–273.
Kaufman FR, Devgan S. Use of uncooked cornstarch to avert nocturnal hypoglycemia in children and adolescents with type 1 diabetes. J Diabetes Complications 1996;10: 84–87.
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-B52.
Cryer PE. Hypoglycemia: the limiting factor in the management of IDDM: Diabetes 1994;43: 1378–1379.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Cryer, P.E. (2003). Prevention and Correction of Hypoglycemia. In: Sperling, M.A. (eds) Type 1 Diabetes. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-310-1_7
Download citation
DOI: https://doi.org/10.1007/978-1-59259-310-1_7
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-258-2
Online ISBN: 978-1-59259-310-1
eBook Packages: Springer Book Archive