Diabetologia

, Volume 36, Issue 12, pp 1275–1281

Hyperinsulinaemia, dyslipidaemia and exaggerated adrenal androgen response to adrenocorticotropin in male smokers

  • A. Hautanen
  • H. Adlercreutz
Originals

Summary

Insulin resistance and dyslipidaemia associated with smoking may result from increased secretion of anti-insulin hormones. We compared the pituitary-adrenocortical function using oral glucose tolerance, dexamethasone suppression and ACTH stimulation tests in smoking (n = 22) and non-smoking (n = 22) healthy males matched for age, body mass index, and waist-to-hip ratio. Smokers had lower HDL-cholesterol (p <0.02), and higher triglyceride (p <0.001), basal cortisol (p <0.05), insulin (p <0.05), and C-peptide (p <0.02) levels, and a higher response of insulin and C-peptide to oral glucose (p <0.005) than non-smokers, while the ACTH, cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone, and androstenedione responses to oral glucose were similar in both groups. No differences were found in the response of cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone, and androstenedione to dexamethasone. In contrast, the response of 17-hydroxyprogesterone (p = 0.04), dehydroepiandrosterone (p = 0.007), and androstenedione (p = 0.001) to ACTH was higher in smokers than non-smokers, while the increase in cortisol was of marginal significance (p = 0.07). In multiple regression analyses the dehydroepiandrosterone response to ACTH was a significant determinant of insulin, C-peptide, and triglyceride levels independent of physical activity, waist-to-hip ratio and HDL-cholesterol. Thus, smoking inhibits the adrenal 21-hydroxylase resulting in an increase in the production of adrenal androgens, which might contribute to the insulin resistance and dyslipidaemia in smokers.

Key words

Insulin resistance C-peptide lipoproteins obesity dehydroepiandrosterone androstenedione 17-hydroxyprogesterone cortisol 

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References

  1. 1.
    Friedman GD, Dales LG, Ury HK (1979) Mortality in middle aged smokers and non-smokers. N Engl J Med 300: 213–216Google Scholar
  2. 2.
    Facchini FS, Hollenbeck CB, Jeppesen J, Chen Y-DI, Reaven GM (1992) Insulin resistance and cigarette smoking. Lancet 339: 1128–1130Google Scholar
  3. 3.
    Craig WY, Palomaki GE, Haddow JE (1989) Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. BMJ 298: 784–788Google Scholar
  4. 4.
    Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1595–1607Google Scholar
  5. 5.
    Yeh J, Barbieri RL (1989) Effects of smoking on steroid production, metabolism, and estrogen-related disease. Semin Repr Endocrinol 7: 326–334Google Scholar
  6. 6.
    Barrett-Connor E, Khaw K-T, Yen SSC (1986) A prospective study of dehydroepiandrosterone sulphate, mortality, and cardiovascular disease. N Engl J Med 315: 1519–1524Google Scholar
  7. 7.
    Dai WS, Gutai JP, Kuller LH, Cauley JA for the MRFIT Research Group (1989) Cigarette smoking and serum sex hormones in men. Am J Epidemiol 128: 796–805Google Scholar
  8. 8.
    Salvini S, Stampfer MJ, Barbieri RL, Hennekens CH (1992) Effects of age, smoking and vitamins on plasma DHEAS levels: a cross-sectional study in men. J Clin Endocr Metab 74: 139–143Google Scholar
  9. 9.
    Hautanen A, Mänttäri M, Koskinen P, Manninen V, Adlercreutz H, Frick MH (1990) Dehydroepiandrosterone sulphate as a coronary risk factor in the Helsinki Heart Study. Circulation 82: III-S468 (Abstract)Google Scholar
  10. 10.
    Hill P, Wynder EL (1974) Smoking and cardiovascular disease. Effect of nicotine on the serum epinephrine and corticoids. Am Heart J 87: 491–496Google Scholar
  11. 11.
    Winternitz WW, Quillen D (1977) Acute hormonal response to cigarette smoking. J Clin Pharmacol 17: 389–397Google Scholar
  12. 12.
    Cryer PE, Haymond MW, Santiago JV, Shah SD (1976) Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events. N Engl J Med 295: 573–577Google Scholar
  13. 13.
    Wilkins JN, Carlson HE, Van Vunakis H, Hill MA, Gritz E, Jarvik ME (1982) Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chonic smokers. Psychopharmacology-Berl 78: 305–308Google Scholar
  14. 14.
    Rizza RA, Mandarino LJ, Gerich JE (1982) Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action. J Clin Endocrinol Metab 54: 131–138Google Scholar
  15. 15.
    Bratusch-Marrain PR, Smith D, DeFronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973–978Google Scholar
  16. 16.
    Shamoon H, Hendler R, Sherwin RS (1981) Synergistic interactions among anti-insulin hormones in the pathogenesis of stress hyperglycemia in humans. J Clin Endocrinol Metab 52: 1235–1241Google Scholar
  17. 17.
    Björntorp P (1992) Abdominal fat distribution and disease: an overview of epidemiological data. Ann Med 24: 15–18Google Scholar
  18. 18.
    Hypertension Detection and Follow-up Program Cooperative Group (1979) Five-year findings of the hypertension detection and follow-up program. JAMA 242: 2562–2570Google Scholar
  19. 19.
    Siedel J, Hägele OE, Ziegenhorn J, Wahlefeld AW (1983) Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency. Clin Chem 29: 1075–1080Google Scholar
  20. 20.
    Hautanen A, Sarna S, Pelkonen R, Adlercreutz H (1993) Serum sex-hormone binding globulin, cardiovascular risk factors and adrenal cortisol responses to dexamethasone and adrenocorticotropin. Metabolism 42Google Scholar
  21. 21.
    Finley PR, Schifman RB, Williams RJ, Lichti DA (1972) Cholesterol in high-density lipoprotein: use of Mg (2+)/dextran sulphate in its enzymic measurement. Clin Chem 18: 499–502Google Scholar
  22. 22.
    Kuoppasalmi K, Näveri H, Rehunen S, Härkönen M, Adlercreutz H (1976) Effect of strenuous anaerobic running exercise on plasma growth hormone, cortisol, luteinizing hormone, testosterone, androstendione, estrone and estradiol. J Steroid Biochem 7: 823–829Google Scholar
  23. 23.
    Hautanen A, Mänttäri M, Manninen V, Frick MH, Adlercreutz H (1992) Effects of gemfibrozil treatment on serum levels of androstanediol glucuronide and adrenal androgens. J Steroid Biochem Molec Biol 42: 433–434Google Scholar
  24. 24.
    Janzon L, Berntorp K, Hanson M, Lindell S-E, Trell E (1983) Glucose tolerance and smoking: a population study of oral and intravenous glucose tolerance test in middle-aged men. Diabetologia 25: 86–88Google Scholar
  25. 25.
    New MI, White PC, Pang S, Dupont B, Speiser PW (1989) The adrenal hyperplasias. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited diseases, Vol 2. McGraw-Hill, New York, pp 1881–1917Google Scholar
  26. 26.
    Barbieri RL, Friedman AJ, Osathanondh R (1989) Cotinine and nicotine inhibit human fetal adrenal 11β-hydroxylase. J Clin Endocr Metab 69: 1221–1224Google Scholar
  27. 27.
    De Simone G, Tommaselli AP, Rossi R et al. (1985) Partial deficiency of adrenal 11-hydroxylase. A possible cause of primary hypertension. Hypertension 7: 204–210Google Scholar
  28. 28.
    Buffington CF, Givens JR, Kitabchi AE (1991) Opposing actions of dehydroepiandrosterone and testosterone on insulin sensitivity. In vivo and in vitro studies of hyperandrogenic females. Diabetes 40: 693–700Google Scholar
  29. 29.
    Nestler JE, Barlascini CO, Clore JN, Blackard WG (1988) Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab 66: 57–61Google Scholar
  30. 30.
    Mortola JF, Yen SSC (1990) The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. I Clin Endocrinol Metab 71: 696–704Google Scholar
  31. 31.
    Nestler JE, McClanahan MA, Clore JN, Blackard WG (1992) Insulin inhibits adrenal 17,20-lyase activity in man. J Clin Endocrinol Metab 74: 362–367Google Scholar
  32. 32.
    Farah MJ, Givens JR, Kitabchi AE (1990) Bimodal correlation between the circulating insulin level and the production rate of dehydroepiandrosterone: positive correlation in controls and negative correlation in the polycystic ovary syndrome with acanthosis nigricans. J Clin Endocrinol Metab 70: 1075–1081Google Scholar
  33. 33.
    Muscat JE, Harris RE, Haley NJ, Wynder EL (1991) Cigarette smoking and plasma cholesterol. Am Heart J 121: 141–147Google Scholar
  34. 34.
    Hautanen A, Mänttäri M, Kupari M et al. (1993) Cigarette smoking is associated with elevated adrenal androgen response to adrenocorticotropin. J Steroid Biochem Molec Biol (in press)Google Scholar
  35. 35.
    Tikkanen MJ, Nikkilä E (1987) Regulation of hepatic lipase and serum lipoproteins by sex steroids. Am Heart J 113: 562–567Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • A. Hautanen
    • 1
  • H. Adlercreutz
    • 1
  1. 1.Department of Clinical ChemistryUniversity of HelsinkiHelsinkiFinland

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