Summary
Recent studies have reported reduced endocrine and symptomatic responses to hypoglycaemia 18–24 h after antecedent hypoglycaemia in both non-diabetic subjects and those with insulin-dependent diabetes mellitus. We examined these and peripheral physiological responses in eight nondiabetic subjects aged 23–35 years in the week following antecedent hypoglycaemia. Blood glucose levels were held at plateaus of 5 mmol/l and 2.5 mmol/l for 30 min during hyperinsulinaemic (60 mU · m−2 · min−1) morning clamps on days 1, 3 and 8 of two study periods separated by at least 4 weeks. Measurements were made at time 0, 15 and 30 min of each plateau on each day. On the afternoon of Day 1 we also induced either euglycaemia with a blood glucose level of 5 mmol/l (control week) or hypoglycaemia of 2.9 mmol/l (hypo week) for 2 h in random order. The adrenaline response to morning hypoglycaemia (p<0.01 on all days) was attenuated on Day 3 (p<0.05) and Day 8 (p<0.05) compared to Day 1 of hypo week only. Sweating was also attenuated on Day 3 (p<0.05) and Day 8 (p<0.02) of hypo week only. Noradrenaline levels and tremor increased during hypoglycaemia on each study day (p<0.05) but did not differ between days in either week. During hypo week only, the total symptom score response to hypoglycaemia was attenuated on Day 3 (p<0.03) but not Day 8 (p=0.10). Autonomic symptoms were similarly affected. In summary, the physiological responses to hypoglycaemia are affected differentially by antecedent hypoglycaemia with sweating and adrenaline responses remaining impaired for at least 5 days.
Article PDF
Similar content being viewed by others
Abbreviations
- RMS:
-
Root mean square
- RIA:
-
radioimmunoassay
- AUC:
-
area under curve
- IDDM:
-
insulin dependent diabetes mellitus
- hypo:
-
hypoglycaemia
References
The Diabetes Control and Complications Trial Research Group (1993) 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 329: 977–986
The Diabetes Control and Complications Trial Research Group (1991) Epidemiology of severe hypoglycemia in DCCT. Am J Med 90: 450–459
Bolli GB, De Feo P, Compagnucci P et al. (1983) Abnormal glucose counterregulation in IDDM. Interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion. Diabetes 32: 134–141
Cryer PE, Fisher JN, Shamoon H (1994) Hypoglycaemia. Diabetes Care 17: 734–755
Cryer PE (1993) Glucose counterregulation: the prevention and correction of hypoglycemia in humans. Am J Physiol 264: E149–E155
Heller SR, Macdonald IA (1991) Physiological disturbances in hypoglycaemia: effect on subjective awareness. Clin Sci 81: 1–9
Heller SR, Macdonald IA, Herbert M, Tattersall RB (1987) Influence of sympathetic nervous system on hypoglycaemic warning symptoms. Lancet II: 359–363
Hepburn DA, Patrick AW, Brash HM, Thomson I, Frier BM (1991) Hypoglycaemia unawareness in type 1 diabetes: a lower plasma glucose in required to stimulate sympathoadrenal activation. Diabet Med 8: 934–945
Gold AE, MacLeod KD, Frier BM (1994) Frequency of severe hypoglycaemia in insulin-dependent diabetic patients with altered awareness of hypoglycemia. Diabetes Care 17: 697–703
Pramming S, Thorsteinsson B, Bendtson I, Binder C (1991) Symptomatic hypoglycaemia in 411 type 1 diabetic patients. Diabet Med 8: 217–222
Amiel SA, Sherwin RS, Simonson DC, Tamborlane WV (1988) Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release. Diabetes 37: 901–907
Cryer PE (1992) Iatrogenic hypoglycemia as a cause of hypoglycaemia-associated autonomic failure in IDDM: a vicious cycle. Diabetes 41: 255–260
Heller SR, Cryer PE (1991) Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans. Diabetes 40: 223–226
Veneman T, Mitrakou A, Mokan M, Cryer PE, Gerich JE (1993) Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia. Diabetes 42: 1233–1237
Dagogo-Jack SE, Craft S, Cryer PE (1993) Hypoglycemia-associated autonomic failure in insulin-dependent diabetes mellitus. J Clin Invest 91: 819–828
Smallwood RH, Thomas SE (1985) An inexpensive portable monitor for measuring evaporative water loss. Clin Phys Physiol Meas 6: 2: 147–154
Birmingham AT, Wharrad HJ, Williams EJ, Wilson CG (1985) Accelerometric measurements of finger tremour: analysis of the analogue signal. J Physiol (Lond) 361: 12P(Abstract)
Hepburn DA, Deary IJ, Frier BM, Patrick AW, Quinn JD, Fisher BM (1991) Symptoms of acute hypoglycaemia in humans with and without IDDM (factor analysis approach). Diabetes Care 14: 949–957
Macdonald IA, Lake DM (1985) An improved technique for extracting catecholamines from body fluids. J Neuroscience Meth 13: 239–240
Soeldner JS, Slone D (1965) Critical variables in the RIA of serum insulin using the double antibody system. Diabetes 14: 771–779
Matthews JNS, Altman DG, Campbell MJ, Royston P (1990) Analysis of serial measurements in medical research. BMJ 300: 230–235
Davis M, Shamoon H (1991) Counterregulatory adaptation to recurrent hypoglycemia in normal humans. J Clin Endocr Metab 73: 995–1001
Widom B, Simonson DC (1992) Intermittent hypoglycemia impairs glucose counterregulation. Diabetes 41: 1597–1602
Lingenfelser T, Renn W, Sommerwerck U et al. (1993) Compromised hormonal counterregulation, symptom awareness, and neurophysiological function after recurrent short term episodes of insulin-induced hypoglycemia in IDDM patients. Diabetes 42: 610–618
Macdonald IA, Maggs DG (1993) Cutaneous blood flow, sweating, tremour and temperature regulation in hypoglycaemia. In: Frier BM, Fisher BM (eds) Hypoglycaemia and diabetes. Edward Arnold, London, pp 132–143
Mitrakou A, Ryan C, Veneman T et al. (1991) Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms and cerebral dysfunction. Am J Physiol 260: E67–E74
Cryer PE (1993) Glucose counterregulation: the physiological mechanisms that prevent or correct hypoglycemia. In: Frier BM (ed) Hypoglycaemia and diabetes. Edward Arnold, London, pp 34–55
Hoffman RP, Sinkey CA, Anderson EA (1994) Hypoglycemia increases muscle sympathetic nerve activity in IDDM and control subjects. Diabetes Care 17: 673–680
Dagogo-Jack SE, Rattarasarn C, Cryer PE (1994) Reversal of hypoglycemia unawareness, but not defective glucose counterregulation, in IDDM. Diabetes 43: 1426–1434
McCall AL, Fixman LB, Fleming N, Torneheim K, Chick W, Ruderman NB (1986) Chronic hypoglycemia increases brain glucose transport. Am J Physiol 251: E442–E447
McCall AL (1993) Effects of glucose deprivation on glucose metabolism in the central nervous system. In: Frier BM, Fisher BM (eds) Hypoglycaemia and diabetes. Edward Arnold, London, pp 56–71
Boyle PJ, Nagy RJ, O'Connor AM, Kempers SF, Yeo RA, Qualls C (1994) Adaptation in brain glucose uptake following recurrent hypoglycemia. Proc Natl Acad Sci USA 91: 9352–9356
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
George, E., Harris, N., Bedford, C. et al. Prolonged but partial impairment of the hypoglycaemic physiological response following short-term hypoglycaemia in normal subjects. Diabetologia 38, 1183–1190 (1995). https://doi.org/10.1007/BF00422367
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00422367