, Volume 30, Issue 12, pp 924–929 | Cite as

Counterregulation in Type 2 (non-insulin-dependent) diabetes mellitus. Normal endocrine and glycaemic responses, up to ten years after diagnosis

  • S. R. Heller
  • I. A. Macdonald
  • R. B. Tattersall


We have examined hormonal and metabolic responses to insulin-induced hypoglycaemia in 10 Type 2 (non-insulin-dependent) diabetic patients treated with tablets and 10 age, sex and weight matched control subjects. Diabetic patients were under 110% ideal body weight, had no autonomie neuropathy and were well controlled (HbA1, 7.1±0.2%). After the diabetic patients were kept euglycaemic by an overnight insulin infusion, hypoglycaemia was induced in both groups by intravenous insulin at 30 mU·m–2·min−1 for 60 min and counterregulatory responses measured for 150 min. There were no significant differences between diabetic patients and control subjects in the rate of fall (3.3±0.3 vs 4.0±0.3 mmol·1−1·h−1), nadir (2.4±0.2 vs 2.3±0.1 mmol/l) and rate of recovery (0.027±0.002 vs 0.030±0.003 mmol·1−1·min−1) of blood glucose. Increments of glucagon (60.5±5.7 vs 70±9.2 ng/l) and adrenaline (1.22±0.31 vs 1.45±0.31 nmol/l) were similar in both groups. When tested using this model, patients with Type 2 diabetes, without microvascular complications and taking oral hypoglycaemic agents show no impairment of the endocrine response and blood glucose recovery following hypoglycaemia.

Key words

Type 2 (non-insulin-dependent) diabetes mellitus counterregulation hypoglycaemia glucagon adrenaline pancreatic polypeptide 


  1. 1.
    Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH (1973) Lack of glucagon response to hypoglycaemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science 182: 171–173Google Scholar
  2. 2.
    Bolli G, De Feo P, Compagnucci P, Cartechini MG, Angeletti G, Santeusanio F, Brunetti P, Gerich JE (1983) Abnormal glucose counterregulation in insulin-dependent diabetes mellitus: interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion. Diabetes 32: 134–141Google Scholar
  3. 3.
    Popp DA, Shah SD, Cryer PE (1982) Role of epinephrine mediated beta adrenergic mechanisms in hypoglycemic glucose counterregulation and posthypoglycemic hyperglycemia in IDDM. J Clin Invest 69: 315–326Google Scholar
  4. 4.
    Boden G, Reichard GA, Hoeldtke RD, Rezvani I, Owen OE (1981) Severe insulin-induced hypoglycemia associated with deficiencies in the release of counterregulatory hormones. N Engl J Med 305: 1200–1205Google Scholar
  5. 5.
    White NH, Skor DA, Cryer PE, Levandoski LA, Bier DM, Santiago JV (1983) Identification of type 1 diabetic patients at increased risk for hypoglycemia during intensive therapy. N Engl J Med 308: 485–491Google Scholar
  6. 6.
    Multicentre Study (1983) UK prospective study of therapies of maturity onset diabetes. 1. Effect of diet, sulphonylurea, insulin or biguanide therapy on fasting plasma glucose and body weight. Diabetologia 24: 404–411Google Scholar
  7. 7.
    Boden G, Soriano M, Hoeldtke RD, Owen OE (1983) Counterregulatory hormone release and glucose recovery after hypoglycemia in non insulin-dependent diabetic patients. Diabetes 32: 1055–1059Google Scholar
  8. 8.
    Polonsky KS, Herold KC, Gilden JL, Bergenstal RM, Fang VS, Moosa AR, Jaspan JB (1984) Glucose counterregulation in patients after pancreatectomy: comparison with other clinical forms of diabetes. Diabetes 33: 1112–1119Google Scholar
  9. 9.
    Bolli GB, Tsalikian E, Haymond MW, Cryer PE, Gerich JE (1984) Defective glucose counterregulation after subcutaneous insulin in noninsulin-dependent diabetes mellitus. J Clin Invest 73: 1532–1541Google Scholar
  10. 10.
    Bennett T (1983) Physiological investigation of diabetic autonomie failure. In: Bannister R (ed) Autonomie failure. A textbook of clinical disorders of the autonomie nervous system. Oxford University Press, Oxford, pp 403–436Google Scholar
  11. 11.
    Bolli GB, DeFeo P, De Cosmo S, Perriello G, Ventura MM, Massa Benedetti M, Santeusanio F, Gerich JE, Brunetti P (1984) A reliable and reproducible test for adequate glucose counterregulation in type 1 diabetes mellitus. Diabetes 33: 732–737Google Scholar
  12. 12.
    Lloyd B, Burin J, Smythe P, Alberti KGMM (1978) Enzymic flourimetric continuous-flow assays for blood glucose, lactate, alanine, glycerol and 3-hydroxybutyrate. Clin Chem 24: 1724–1729Google Scholar
  13. 13.
    Stout RW, Henry RW, Buchanan KD (1976) Triglyceride metabolism in acute starvation: the role of secretin and glucagon. Eur J Clin Invest 6: 179–185Google Scholar
  14. 14.
    O'Hare MMT, Daly JG, Buchanan KD (1983) Radioimmunoassay for pancreatic polypeptide, and it's age-related changes in concentration. Clin Chem 29: 1923–1927Google Scholar
  15. 15.
    Hales CN, Randle PJ (1963) Immunoassay of insulin. Biochem J 88: 137–146Google Scholar
  16. 16.
    Macdonald IA, Lake DM (1985) An improved technique for extracting catecholamines from body fluids. J Neurosci Methods 13: 239–248Google Scholar
  17. 17.
    Heding LG (1975) Radioimmunological determinations of human C-peptide in serum. Diabetologia 11: 541–554Google Scholar
  18. 18.
    Ambler J, Walker G, Janik B (1983) Measurement of glycosylated haemoglobin on cellulose acetate membrane. Clin Chem 29: 240–243Google Scholar
  19. 19.
    Genstat (1980) A General Statistical Program. Rothamstead Experimental Station. Numerical Algorithms Group Ltd, OxfordGoogle Scholar
  20. 20.
    Reynolds C, Molnar GD, Horwitz DL, Rubenstein AH, Taylor WF, Jiang NS (1977) Abnormalities of endogenous glucagon and insulin in unstable diabetes. Diabetes 26: 36–45Google Scholar
  21. 21.
    Campbell LV, Kraegen EW, Meler H, Lazarus L (1979) Hormonal responses to insulin infusion in diabetes mellitus. Diabetologia 16: 359–364Google Scholar
  22. 22.
    Levitt NS, Vinik AI, Sive AA, Child P, Jackson WPU (1979) Studies on plasma glucagon concentration in maturity-onset diabetics with autonomic neuropathy. Diabetes 28: 1015–1021Google Scholar
  23. 23.
    Cryer PE, Gerich JE (1985) Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus. N Engl J Med 313: 232–241Google Scholar
  24. 24.
    Campbell LV, Kraegen EW, Lazarus L (1977) Defective blood glucose counter-regulation in diabetics is a selective form of autonomie neuropathy. Br Med J 2: 1527–1529Google Scholar
  25. 25.
    Maher TD, Tanenberg RJ, Greenberg BZ, Hoffman JE, Doe RP, Goetz FC (1977) Lack of glucagon response to hypoglycaemia in diabetic autonomie neuropathy. Diabetes 26: 196–200Google Scholar
  26. 26.
    Samols E, Weir G, Bonner-Weir S (1983) Intra-islet insulin-glucagon-somatostatin relationships. In: Lefebvre PJ (ed) Handbook of Pharmacology. Glucagon II, Springer, Berlin Heidelberg New York, pp 133–173Google Scholar
  27. 27.
    Unger RH (1983) Insulin-glucagon relationships in the defence against hypoglycaemia. Diabetes 32: 575–583Google Scholar
  28. 28.
    Bolli G, De Feo P, Perriello G, De Cosmo S, Compagnucci P, Santeusanio F, Brunetti P, Unger RH (1984) Mechanisms of glucagon secretion during insulin-induced hypoglycaemia in man. Role of the beta cell and arterial hyperinsulinemia. J Clin Invest 73: 917–922Google Scholar
  29. 29.
    Buchanan KD, Mawhinney WAA (1973) Glucagon release from isolated pancreas in streptozotocin treated rats. Diabetes 22: 797–800Google Scholar
  30. 30.
    Samols E, Harrison J (1976) Intraislet negative insulin/glucagon feedback. Metabolism 25 (Suppl 1): 1443–1447Google Scholar
  31. 31.
    Berk MA, Clutter WE, Skor D, Shah SD, Gingerich RP, Parvin CA, Cryer PE (1985) Enhanced glycemie responsiveness to epinephrine in insulin-dependent diabetes mellitus is the result of the inability to secrete insulin. J Clin Invest 75: 1842–1851Google Scholar
  32. 32.
    Levitt NS, Vinik AI, Sive AA, Van Tonder S, Lund A (1980) Impaired pancreatic polypeptide responses to insulin induced hypoglycaemia in diabetic autonomie neuropathy. J Clin Endocrinol Metab 50: 445–449Google Scholar
  33. 33.
    Gray DE, Lickley HLA, Vranic M (1980) Physiologic effects of epinephrine on glucose turnover and plasma free fatty acid concentrations mediated independently of glucagon. Diabetes 29: 600–608Google Scholar
  34. 34.
    Schwartz TW (1983) Pancreatic polypeptide: a hormone under vagal control. Gastroenterology 85: 1411–1425Google Scholar
  35. 35.
    Sive AA, Vinik AI, Levitt N, Van Tonder S (1980) Adrenergic modulation of human pancreatic polypeptide (hPP) release. Gastroenterology 79: 665–672Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • S. R. Heller
    • 1
  • I. A. Macdonald
    • 2
  • R. B. Tattersall
    • 1
  1. 1.Department of MedicineUniversity Hospital and Nottingham University Medical School, Queen's Medical CentreNottinghamUK
  2. 2.Department of Physiology and PharmacologyUniversity Hospital and Nottingham University Medical School, Queen's Medical CentreNottinghamUK

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