Skip to main content

Alterations in Fuel Metabolism in Critical Illness

Hypoglycemia

  • Chapter
Endocrinology of Critical Disease

Part of the book series: Contemporary Endocrinology ((COE,volume 4))

  • 117 Accesses

Abstract

Glucose has an essential function as the fundamental energy source for the brain. This critical fuel requirement creates a need for a consistently available and uninterrupted supply of glucose. Because of the crucial need for glucose, an intricate homeostatic system has evolved to assure adequate availability of glucose at all times: Postabsorptive (fasting) levels of plasma glucose are generally kept within the fairly narrow range of 60–100 mg/dL or 3.3–5.6 mM/L (1). This stability is maintained even under the disruptive circumstances of caloric deprivation and increased energy requirements, which occur with severe trauma, febrile illnesses, and other catabolic states. The maintenance of adequate serum glucose levels is, in fact, a paramount goal of the stress response, and the increased secretion of “stress hormones,” such as cortisol, catecholamines, and growth hormone, contributes to the provision of consistent glucose availability; if the system for glucoregulation is going to be off-target, it will err by promoting an elevation of glucose levels, rather than risking the potential catastrophe of an inadequate glucose supply. Thus, an elevation of the serum glucose level is the most common clinical disorder of glucose metabolism in critical illness, as discussed in detail in Chapter 10. However, some patients with critical illness will have a failure in the life-sustaining system for maintaining serum glucose levels; this inability to provide an adequate energy supply can lead to severe dysfunction of many organs, and it ultimately may cause the demise of the affected individual.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Service FJ. Hypoglycemic disorders. N Engl J Med 1995; 332: 1144–1152.

    Article  PubMed  CAS  Google Scholar 

  2. Service FJ. Hypoglycemia. Med Clin North Am 1995; 79: 1–8.

    PubMed  CAS  Google Scholar 

  3. Zeller J, Bougneres P. Hypoglycemia in infants. Trends Endocrinol Metab 1992; 3: 366–370.

    Article  PubMed  CAS  Google Scholar 

  4. Huang S, Phelps E, Hoffman E, et al. Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol 1981; 238: E69 — E82.

    Google Scholar 

  5. Haymond MW. Diarrhea, malnutrition, euglycemia, and fuel for thought. N Engl J Med 1990; 322: 1390–1391.

    Article  PubMed  CAS  Google Scholar 

  6. McCall AL. Effects of glucose deprivation on glucose metabolism in the central nervous system. In Frier BM, Fisher BM, eds. Hypoglycemia and Diabetes: Clinical and Physiological Aspects. Edward Arnold, London, 1993, pp. 56–71.

    Google Scholar 

  7. De Vivo DC, Trifiletti RR, Jacobson RI, et al. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 1991; 325: 703–709.

    Article  PubMed  Google Scholar 

  8. Lang CH, Dobrescu C. Sepsis-induced increased in glucose uptake by macrophage-rich tissues persist during hypoglycemia. Metabolism. 1991; 40: 585–593.

    Article  PubMed  CAS  Google Scholar 

  9. Takakura Y, Kuentzel SL, Raub TJ, et al. Hexose uptake in primary cultures of bovine brain microvessel endothelial cells. I. Basic characteristics and effects of D-glucose and insulin. Biochim Biophys Acta 1991; 1071: 1–10.

    Article  Google Scholar 

  10. Boado RJ, Pardridge WM. Glucose deprivation causes posttranscriptional enhancement of brain capillary endothelial glucose transporter gene expression via GLUT1 mRNA stabilization. J Neurochem 1993; 60: 2290–2296.

    Article  PubMed  CAS  Google Scholar 

  11. Koranyi L, Bourrey RE, James D, et al. Glucose transporter gene expression in rat brain: pretranslational changes associated with chronic insulin-induced hypoglycemia, fasting and diabetes. Mol Cell Neurosci 1991; 2: 244–252.

    Article  PubMed  CAS  Google Scholar 

  12. McCall AL, Fixman LB, Fleming N, et al. Chronic hypoglycemia increases brain glucose transport. Am J Physiol 1986; 251: E442 — E447.

    PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  Google Scholar 

  15. Cryer PE. Hypoglycemia begets hypoglycemia in IDDM. Diabetes 1993; 42: 1691–1693.

    PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Mitrakou A, Fanelli C, Veneman T, et al. Reversibility of unawareness of hypoglycemia in patients with insulinomas. N Engl J Med 1993; 329: 834–839.

    Article  PubMed  CAS  Google Scholar 

  18. Fanelli CG, Epifano L, Rambotti AM, et al. Meticulous prevention of hypoglycemia normalizes the glycemic threshold and magnitude of most neuroendocrine responses to, symptoms of, and cognitive function during hypoglycemia in intensively treated patients with short-term IDDM. Diabetes 1993; 42: 1683–1689.

    Article  PubMed  CAS  Google Scholar 

  19. Zhu PJ, Krnjevic K. Adenosine release is a major cause of failure of synaptic transmission during hypoglycemia in rat hippocampal slices. Neuroscience Letters. 1993; 155: 128–131.

    Article  PubMed  CAS  Google Scholar 

  20. Lins PE, Adamson H. Neurologic manifestations of hypoglycemia. In Frier BM, Fisher BM, eds. Hypoglycaemia and Diabetes: Clinical and Physiological Aspects. Edward Arnold, London, 1993, pp. 347–354.

    Google Scholar 

  21. Bendtson I. Neurophysiological changes of hypoglyceamia. In Frier BM, Fisher BM, eds. Hypoglycemia and Diabetes: Clinical and Physiological Aspects. Edward Arnold, London, 1993, pp. 72–79.

    Google Scholar 

  22. Odeh M, Oliven A. Hypoglycemia and bilateral cortical blindness. Diabetes Care. 1996; 19: 272–273.

    PubMed  CAS  Google Scholar 

  23. Langan SJ, Deary IJ, Hepburn DA, et al. Cumulative cognitive impairment following recurrent severe hypoglyceamia in adult patients with insulin-treated diabetes mellitus. Diabetologia 1991; 34: 337–344.

    Article  PubMed  CAS  Google Scholar 

  24. Deckert T, Poulsen JE, Larsen M. Prognosis of diabetics with diabetes onset before the age of thirty-one: I. Survival, causes of death, and complications. Diabetologia 1978; 14: 363–370.

    CAS  Google Scholar 

  25. Tunbridge WM. On behalf of the Medical Services Study Group and British Diabetic Association: Factors contributing to deaths of diabetics under fifty years of age. Lancet 1981; 2: 569–572.

    Article  PubMed  CAS  Google Scholar 

  26. Jaspan JB, Wollman RL, Bernstein L, et al. Hypoglycemic peripheral neuropathy in association with insulinoma: Implication of glucopenia rather than hyperinsulinism. Medicine 1982; 61: 33–44.

    Article  PubMed  CAS  Google Scholar 

  27. Buchanan BJ, Filkins JP. Hypoglycemic depression of RES function. Am J Physiol 1976; 231: 265–269.

    PubMed  CAS  Google Scholar 

  28. Strauch B, Felig P, Baxter J, Schimpff S. Hypothermia in hypoglycemia. JAMA 1969; 210: 345–346.

    Google Scholar 

  29. Maggs DG, Scott AR, MacDonald IA. Thermoregulatory responses to hyperinsulinemic hypoglycemia and euglycemia in humans. Am J Physiol 1994; 267: R1266 - R1272.

    PubMed  CAS  Google Scholar 

  30. Buchanan T, Cane P, Eng C, Sipos G, Lee C. Hypothermia is critical for survival during prolonged insulin-induced hypoglycemia in rats. Metabolism 1991; 40: 330–334.

    Article  PubMed  CAS  Google Scholar 

  31. Agardh C, Smith M, Siesjo B. The influence of hypothermia on hypoglycemia-induced brain damage in the rat. Acta Neuropathol 1992; 83: 379–385.

    Article  PubMed  CAS  Google Scholar 

  32. Comi RJ. Approach to acute hypoglycemia. Endocrinol Metab Clin North Am 1993; 22: 247–262.

    PubMed  CAS  Google Scholar 

  33. Comi RJ, Gorden P, Doppman JL, et al. Insulinoma. In Go VLW, ed. The Exocrine Pancreas. Raven, New York, 1986, pp. 745–761.

    Google Scholar 

  34. Kitabchi AE, Goodman RC. Hypoglycemia. Pathophysiology and diagnosis. Hosp Pract 1987; 22: 45–56, 59–60.

    Google Scholar 

  35. Fajans SS, Floyd JC Jr. Fasting hypoglycemia in adults. N Engl J Med. 1976; 294: 766–772.

    Article  PubMed  CAS  Google Scholar 

  36. Merimee TJ, Tyson JE. Stabilization of plasma glucose during fasting: normal variations in two separate studies. N Engl J Med. 291: 1275–1278.

    Google Scholar 

  37. Felig P, Lynch V. Starvation in human pregnancy: hypoglycemia, hypoinsulinemia and hyerketonemia. Science 1970; 170: 990–992.

    Article  PubMed  CAS  Google Scholar 

  38. Felig P, Cherif A, Minagawa A, et al. Hypoglycemia during prolonged exercise in normal men. N Engl J Med 1982; 306: 895–900.

    Article  PubMed  CAS  Google Scholar 

  39. Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic threshold for activation of glucose counter-regulatory systems are higher than the threshold for symptoms. J Clin Invest 1987; 79: 777–781.

    Article  PubMed  CAS  Google Scholar 

  40. Mitrakou A, Ryan C, Veneman T, et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. Am J Physiol 1991; 260: E67 - E74.

    PubMed  CAS  Google Scholar 

  41. Bolli GB, Fanelli CG. Unawareness of hypoglycemia. N Engl J Med 1995; 333: 1771–1772.

    Article  PubMed  CAS  Google Scholar 

  42. Cryer PE. Glucose counterregulation: the physiological mechanisms that prevent or correct hypoglycaemia. In: Frier BM, Fisher MB, eds. Hypoglycaemia and Diabetes: Clinical and Physiological Aspects. Edward Arnold, London, 1993, pp. 34–55.

    Google Scholar 

  43. Boyle PJ, Cryer PE. Growth hormone, cortisol, or both are involved in defense against, but are not critical to recovery from, prolonged hypoglycemia. Am J Physiol 1991; 260: E395 - E402.

    PubMed  CAS  Google Scholar 

  44. Borg WP, During MJ, Sherwin RS, Borg MA, Brines ML, Shulman GI. Ventromedial hypothalamic lesions in rats suppress counterregulatory responses to hypoglycemia. J Clin Invest 1994; 93: 1677–1682.

    Article  PubMed  CAS  Google Scholar 

  45. Hepburn DA, Deary IJ, Frier BM, Patrick AW, Quinn JD, Fisher BM. Symptoms of acute insulin-induced hypoglycemia in humans with and without IDDM: factor-analysis approach. Diabetes Care 1991; 14: 949–957.

    Article  PubMed  CAS  Google Scholar 

  46. Service FJ, Dale AJD, Elveback LR, Jiang NS. Insulinoma: clinical and diagnostic features of 60 consecutive cases. Mayo Clin Proc 1976; 51: 417–429.

    PubMed  CAS  Google Scholar 

  47. Blackman JD, Towle VL, Lewis GF, et al. Hypoglycemia thresholds for cognitive dysfunction in humans. Diabetes 1990; 39: 828–835.

    Article  PubMed  CAS  Google Scholar 

  48. DeFronzo RA, Andres R, Bedsoe TA, Boden G, Faloona GA, Tobin JD. A test of the hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses in man. Diabetes. 1972; 26: 445–452.

    Article  Google Scholar 

  49. Santiago JV, Clarke WL, Shah SD, Cryer PE. Epinephrine, norepinephrine, glucagon, and growth hormone release in association with physiological decrements in plasma glucose concentration in normal and diabetic man. J Clin Endocrinol Metab. 1980; 51: 877–883.

    Article  PubMed  CAS  Google Scholar 

  50. Field JB. Hypoglycemia. Endocrinol Clin North Am. 1989; 18: 27–43.

    CAS  Google Scholar 

  51. Liu D, Moberg E, Kollind M, Lin PE, Adamson U, Macdonald IA. Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinemic euglycemia and hypoglycemia. Diabetologia 1992; 35: 287–290.

    Article  PubMed  CAS  Google Scholar 

  52. Frizzell RT, Jones EM, Davis SN, et al. Counterregulation during hypoglycemia is directed by widespread brain regions. Diabetes 1993; 42: 1253–1261.

    Article  PubMed  CAS  Google Scholar 

  53. Lingenfelser T, Overkamp D, Renn W, Buettner U, Kimmerle K, Schmalfuss A, Jakober B. Insulin-associated modulation of neuroendocrine counterregulation, hypoglycemia perception, and cerebral function in insulin-dependent diabetes mellitus: evidence for an intrinsic effect of insulin on the central nervous system. J Clin Endocrinol Metab 1996; 81: 1197–1205.

    Article  PubMed  CAS  Google Scholar 

  54. Pardridge WM, Eisenberg J, Yang J. Human blood-brain barrier insulin receptor. J Neurochem 1985; 44: 1771–1778.

    Article  PubMed  CAS  Google Scholar 

  55. Baura GD, Foster DM, Porte D, et al. Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. J Clin Invest 1993; 92: 1824–1830.

    Article  PubMed  CAS  Google Scholar 

  56. Grundstein JS, James DE, Storlien LH, Smythe GA, Kraegen EW. Hyperinsulinemia suppresses glucose utilization in specific brain regions: in vivo studies using the euglycaemic clamp in the rat. Endocrinology 1985; 116: 604–610.

    Article  Google Scholar 

  57. Marfaing P, Penicaud L, Broer Y, Mraovitch S, Calando Y, Picon L. Effects of hyperinsulinemia on local cerebral insulin binding and glucose utilization in normoglycemic awake rats. Neurosci Lett 1985; 115: 1675–1679.

    Google Scholar 

  58. Fischer KF, Lees JA, Newman JH. Hypoglycemia in hospitalized patients. Causes and outcomes. N Engl J Med 1986; 315: 1245–1250.

    Article  PubMed  CAS  Google Scholar 

  59. Service H. Factitial hypoglycemia. The Endocrinologist 1992; 2: 173–176.

    Article  Google Scholar 

  60. Grunberger G, Weiner JL, Silverman R, et al. Factitious hypoglycemia due to surreptitious administration of insulin. Ann Intern Med 1988; 108: 252–257.

    PubMed  CAS  Google Scholar 

  61. Goldman J, Baldwin D, Rubenstein AH, et al. Characterization of circulating insulin and proinsulinbinding antibodies in autoimmune hypoglycemia. J Clin Invest 1979; 63: 1050–1059.

    Article  PubMed  CAS  Google Scholar 

  62. Hirata Y. Methimazole and insulin autoimmune syndrome with hypoglycaemia. Lancet 1983; 2: 1037–1038.

    Article  PubMed  CAS  Google Scholar 

  63. Moller DE, Ratner RE, Borenstein DH, Taylor SI. Autoantibodies to the insulin receptor as a cause of autoimmune hypoglycemia in systemic lupus erythematosus. Am J Med 1988; 84: 334–338.

    Article  PubMed  CAS  Google Scholar 

  64. Phillips LS, Robertson DG. Insulin-like growth factors and non-islet cell tumor hypoglycemia. Metabolism 1993; 42: 1093–1101.

    Article  PubMed  CAS  Google Scholar 

  65. Chung J, Henry RR. Mechanisms of tumor-induced hypoglycemia with intraabdominal hemangiopericytoma. J Clin Endocrinol Metab 1996; 81: 919–925.

    Article  PubMed  CAS  Google Scholar 

  66. Katz LEL, Liu F, Baker B, Agus MSD, Nunn SE, Hintz RL, Cohen P. The effect of growth hormone treatment on the insulin-like growth factor axis in a child with nonislet cell tumor hypoglycemia. J Clin Endocrinol Metab 1996; 81: 1141–1146.

    Article  PubMed  CAS  Google Scholar 

  67. Daughaday WH, Kapadia M. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet cell tumors. Proc Natl Acad Sci USA 1989; 86: 6778–6782.

    Article  PubMed  CAS  Google Scholar 

  68. Wing JR, Panz VR, Joffe BI, et al. Hypoglycemia in hepatocellular carcinoma: failure of short-term growth hormone administration to reduce enhanced glucose requirements. Metabolism 1991; 40: 508–515.

    Article  PubMed  CAS  Google Scholar 

  69. Frizzell M, Larsen PR, Field JB. Spontaneous hypoglycemia associated with chronic renal failure. Diabetes 1973; 22: 493–498.

    PubMed  CAS  Google Scholar 

  70. Gorden AJ, Bier DM, Cryer PE, et al. Hypoglycemia in compensated chronic renal insufficiency: substrate limitation of gluconeogenesis. Diabetes 1974; 23: 982–986.

    Google Scholar 

  71. Peitzman SJ, Agarwal BN. Spontaneous hypoglycemia in end-stage renal failure. Nephron 1977; 19: 131–139.

    Article  PubMed  CAS  Google Scholar 

  72. Bansal VK, Brooks MH, York JC, Hano JE. Intractable hypoglycemia in a patient with renal failure. Arch Intern Med 1979; 139: 100–102.

    Article  Google Scholar 

  73. Toth EL, Lee DW. “Spontaneous”/uremic hypoglycemia is not a distinct entity: substantiation from a literature review. Nephron 1991; 58: 325–329.

    Article  PubMed  CAS  Google Scholar 

  74. Benzing G, Schubert W, Huq G, et al. Simultaneous hypoglycemia and acute congestive heart failure. Circulation 1969; 40: 209–216.

    Article  PubMed  Google Scholar 

  75. Haymond MW, Pagliara AS. Ketotic hypoglycaemia. Clin Endocrinol Metab 1983; 12: 447–462.

    Article  PubMed  CAS  Google Scholar 

  76. Phillips RE. Hypoglycemia is an important complication of falciparum malaria. Q J Med 1989; 71: 477–483.

    PubMed  CAS  Google Scholar 

  77. Shalev O, Tsur A, Rahav G. Falciparum malaria-induced hypoglycaemia in a diabetic patient. Postgrad Med J 1992; 68: 281–282.

    Article  PubMed  CAS  Google Scholar 

  78. Miller AI, Wallace RJ, Musher DM, et al. Hypoglycemia as a manifestation of sepsis. Am J Med 1980; 68: 649–654.

    Article  PubMed  CAS  Google Scholar 

  79. Nouel O, Bernuau J, Rueff B, Benhamou J-P. Hypoglycemia. A common complication of septicemia in cirrhosis. Arch Intern Med 1981; 141: 1477–1478.

    Article  PubMed  CAS  Google Scholar 

  80. Bennish ML, Azad AK, Rahman O, Phillips RE. Hypoglycemia during diarrhea in childhood. Prevalence, pathophysiology, and outcome. N Engl J Med 1990; 322: 1357–1363.

    Article  PubMed  CAS  Google Scholar 

  81. Seltzer HS. Drug-induced hypoglycemia. Endocrinol Metab Clin North Am 1989; 18: 163–131.

    PubMed  CAS  Google Scholar 

  82. Jennings AM, Wilson RM, Ward JD. Symptomatic hypoglycemia in NIDDM patients treated with oral hypoglycemic agents. Diabetes Care 1989; 12: 203–208.

    Article  PubMed  CAS  Google Scholar 

  83. Atkin SH, Dasmahapatra A, Jaker MA, Chorost MI, Reddy S. Fingerstick glucose determination in shock. Ann Intern Med 1991; 114: 1020–1024.

    PubMed  CAS  Google Scholar 

  84. Rasaiah B. Self-monitoring of the blood glucose level: potential sources of inaccuracy. Can Med Assoc J 1985; 132: 1357–1361.

    PubMed  CAS  Google Scholar 

  85. Brodows RG, Williams C, Amatruda JM. Treatment of insulin reactions in diabetics. JAMA 1984; 252: 3378–3381.

    CAS  Google Scholar 

  86. Collier A, Steedman DJ, Patrick AW, et al. Comparison of intravenous glucagon and dextrose in treatment of severe hypoglycemia in an accident and emergency department. Diabetes Care 1987; 10: 712–715.

    Article  PubMed  CAS  Google Scholar 

  87. Karam JH, Young CW. Hypoglycemic disorders. In: Greenspan FS, Baxter JD, eds. Basic and Clinical Endocrinology. Appleton & Lange, East Norwalk, CT, pp. 635–648.

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ober, K.P. (1997). Alterations in Fuel Metabolism in Critical Illness. In: Ober, K.P. (eds) Endocrinology of Critical Disease. Contemporary Endocrinology, vol 4. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2584-1_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-2584-1_11

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-032-8

  • Online ISBN: 978-1-4757-2584-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics