Skip to main content
Log in

Effects of 3-month nifedipine treatment on endocrine-metabolic parameters in patients with abdominal obesity and mild hypertension

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

It is widely accepted that abdominal obesity presents with exaggerated insulin secretion, insulin resistance and a trend toward glucose intolerance. Hypertension is frequently associated to abdominal obesity, and hyperinsulinism could play a role in its pathogenesis. Some studies reported that Ca-antagonists positively influence insulin sensitivity and glucose tolerance in obese patients with normal or elevated blood pressure. However, other studies reported worsening of metabolic balance during treatment with Ca-antagonists in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients and in normal subjects. We studied 19 patients with abdominal obesity, mild hypertension and insulin resistance on balanced, mild hypocaloric diet (1400 Kcal), to verify the effects of the Ca-antagonist nifedipine on both basal and oral glucose tolerance test (OGTT)-induced glucose and insulin levels as well as on IGF-I basal and DHEA-S levels and fat mass (FM). To achieve this goal, 10 hypertensive obese subjects (HOB-NIFE, 3 males, 7 females, mean age±SD 44.6±1.7 yr; body mass index (BMI) 37.1±2.5 Kg/m2, WHR 0.95±0.02) received 3-month treatment with nifedipine (Adalat Crono 30 Bayer, 1 tab daily) while other 9 hypertensive obese (HOB, 3 males, 6 females, 42±2.4 yr, BMI 35.8±1.8 Kg/m2, WHR 0.91±0.03) were studied during diet only. The same parameters were studied also in 8 normotensive obese patients (OB: 3 males, 5 females, 48.1±2.1 yr, BMI 35.8±2.4 Kg/m2, WHR 0.90±0.03) on the same balanced hypocaloric diet. Basal systolic (SBP) and diastolic (DBP) blood pressure levels in HOB-NIFE and HOB were similar. At baseline, all groups had similar basal and OGTT-induced glucose, insulin and glucose insulin ratio (GIR) levels as well as IGF-I and DHEA-S levels. After 3 months BMI fell to the same extent in all groups (p<0.05 vs baseline) while WHR and FFM/FM ratio did not change. SBP and DBP decreased HOB-NIFE (p<0.02) but also during diet alone in both HOB and OB, though to a lesser extent (p<0.05). Both basal and OGTT-stimulated glucose and insulin levels as well as IGF-I and DHEA-S levels were not modified in HOB-NIFE as well as in HOB and OB. In conclusion, our data indicate that nifedipine treatment does not modify glucose tolerance as well as insulin secretion and sensitivity, IGF-I and DHEA-S levels in hypertensive abdominal obese patients. Thus, nifedipine treatment has no detrimental effects on endocrine-metabolic balance in hypertensive obese patients.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Karam J.H., Grodsky G.M., Forsham P.H. Excessive insulin response to glucose in obese subjects measured by immunochemical assay. Diabetes 12: 197, 1963.

    PubMed  CAS  Google Scholar 

  2. Polosky K.S., Given B.D., Van Cauter E. 24-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J. Clin. Invest. 82: 442, 1988.

    Article  Google Scholar 

  3. Koman O.G., Insel J., Saekow M., Olefky J.M. Mechanism of insulin resistance in human obesity. Evidence for receptor and post-receptor defects. J. Clin. Invest. 65: 1273, 1980.

    Google Scholar 

  4. Reaven G.M. Role of insulin resistance in human disease. Diabetes 37: 1595, 1988.

    Article  PubMed  CAS  Google Scholar 

  5. Stamler R., Stamler J., Riedlinger W.F., Algera G., Roberts R.H. Findings in hypertension screening of 1 million Americans. JAMA 240: 1607, 1978.

    Article  PubMed  CAS  Google Scholar 

  6. Landsberg L. Hyperinsulinemia: possible role in obesity-induced hypertension. Hypertension 19(suppl I): I–61, 1992.

    Google Scholar 

  7. DeFronzo R.A., Ferranini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: 3, 1991.

    Article  Google Scholar 

  8. Landsberg L., Krieger D.L. Obesity, metabolism and the sympathetic nervous system. Am. J. Hypertens. 2: 1255, 1989.

    Google Scholar 

  9. Ferranini E. Insulin and blood pressure: possible role of haemodynamics. Clin. Exp. Hypertens. A14: 271, 1992.

    Article  Google Scholar 

  10. Ganrot P.O. Insulin resistance syndrome: possible key role of blood flow in resting muscle. Diabetologia 36: 876, 1993.

    Article  PubMed  CAS  Google Scholar 

  11. Beer N.A., Jakubowicz D.J., Beer R.M., Arocha I.R., Nestler J.E. Effects of nitrendipine on glucose tolerance and serum insulin and dehydroepiandrosterone sulfate levels in insulin resistant obese and hypertensive men. J. Clin. Endocrinol. Metab. 76: 178, 1993.

    PubMed  CAS  Google Scholar 

  12. Tuck M.L., Bravo E.L., Krakof L.R., Friedman C.P., and the Modern Approach to the Treatment of Hypertension Study Group. Endocrine and renal effects of nifedipine gastrointestinal therapeutic system in patients with essential hypertension. Results of a multicentre trial. Am. J. Hypertens. 3: 333s, 1990.

    PubMed  CAS  Google Scholar 

  13. Valensi P., Uzzan B., Attali J.R., Perret G. Effects of nifedipine and nitrendipine in insulin secretion in obese patients. J. Cardiovasc. Pharmacol. 18(suppl 1): s91, 1991.

    Article  PubMed  Google Scholar 

  14. Charles S., Ketekslegers J., Lambert A. Hyperglycemic effect of nifedipine. Br. Med. J. 283: 19, 1981.

    Article  CAS  Google Scholar 

  15. Giuliano D., Torella R., Cacciapuoti F., Gentile S., Verza M., Varricchio M. Impairment of insulin secretion by nifedipine. Eur. J. Clin. Pharmacol. 18: 395, 1980.

    Article  Google Scholar 

  16. Stein P.P., Black H.R. Drug treatment of hypertension in patient with diabetes mellitus. Diabetes Care 14: 425, 1991.

    Article  PubMed  CAS  Google Scholar 

  17. Marin P., Kvist H., Lindstedt G., Sjostrom L., Biontorp P. Low concentration of insulin-like growth factor-I in abdominal obesity. Int. J. Obes. 17: 83, 1993.

    CAS  Google Scholar 

  18. Jakubowicz D.J., Beer N.A., Beer R.M., Nestler J.E. Disparate effects of weight reduction by diet on serum dehydroepiandrosterone-sulfate levels in obese men and women. J. Clin. Endocrinol. Metab. 80: 3373, 1995.

    PubMed  CAS  Google Scholar 

  19. Rasmussen M.H., Hvidberg A., Juul A., Main K.M., Gotfredsen A., Shakkebae N.E., Hilsted J. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J. Clin. Endocrinol. Metab. 80: 1407, 1995.

    PubMed  CAS  Google Scholar 

  20. Thissen J.P., Ketelslegers J.M., Underwood L.E. Nutritional regulation of the insulin-like growth factors. Endocr. Rev. 15: 80, 1994.

    PubMed  CAS  Google Scholar 

  21. Nestler J.E., Clore J.N., Strauss J.F., Blackard W.G. The effect of hyperinsulinemia on serum testosterone, progesterone, dehydroepiandrosterone sulfate, and cortisol levels in normal women and in a woman with hyperandrogenism, insulin resistance, and acanthosis nigricans. J. Clin. Endocrinol. Metab. 64: 180, 1987.

    Article  PubMed  CAS  Google Scholar 

  22. Houston B., O’Neil I.E. Insulin and growth hormone act synergistically to stimulate insulin-like growth factor-I production by cultured chicken hepatocytes. J. Endocrinol. 128: 389, 1991.

    Article  PubMed  CAS  Google Scholar 

  23. Jones J.I., Clemmons D.R. Insulin-like growth factors and their binding proteins: biological actions. Endocr. Rev. 16: 1, 1995.

    Article  Google Scholar 

  24. Fifth Report on the Joint National Committee on Detection, evaluation, and treatment of high blood pressure (JNC V). Arch. Intern. Med. 153: 154, 1993.

    Google Scholar 

  25. Caro J.F. Insulin resistance in obese and nonobese man. J. Clin. Endocrinol. Metab. 73: 691, 1991.

    Article  PubMed  CAS  Google Scholar 

  26. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039, 1979.

    Article  Google Scholar 

  27. Devis G., Somers, Van Obberghen E., Malaisse W.J. Calcium antagonists and islet function. Inhibition by verapamil. Diabetes 24: 547, 1975.

    Article  CAS  Google Scholar 

  28. Dominic J., Miller R.E., Anderson J., McAllister R. Pharmacology of verapamil. Impairment of glucose tolerance by verapamil in the conscious dog. Pharmacology 20: 196, 1980.

    Article  PubMed  CAS  Google Scholar 

  29. Westfall M.V., Sayeed M.M. Effect of diltiazem on skeletal muscle 3-O-methylglucose transport in bacteriemic rats. Am. J. Physiol. 256: R716, 1989.

    PubMed  CAS  Google Scholar 

  30. Bursztyn M., Raz I., Mekler J., Ben-Ishay D. Nitrendipine improves glucose tolerance and deoxyglucose uptake in hypertensive rats. Hypertension 23: 1051, 1994.

    Article  PubMed  CAS  Google Scholar 

  31. Andronico G., Piazza G., Mangano M.T., Mula G., Cerasola G. Nifedipine vs enalapril in treatment of hypertensive patients with glucose intolerance. J. Cardiovasc. Pharmacol. 18(Suppl. 1): 552, 1991.

    Google Scholar 

  32. Giugliano D., Saccomanno F., Paolisso G., et al. Nicardipine does not cause deterioration of glucose homeostasis in man: a placebo controlled study in elderly hypertensive with and without diabetes mellitus. Eur. J. Clin. Pharmacol. 43: 39, 1992.

    Article  PubMed  CAS  Google Scholar 

  33. Morris A.D., Donnelly R., Connel J.M.C., Reid J.L. Metabolic effects of lacidipine: a placebo-controlled study using the euglycemic hyperinsulinemic clamp. Br. J. Clin. Pharmacol. 35: 40, 1993.

    PubMed Central  PubMed  CAS  Google Scholar 

  34. Shen W.H.H., Swislockii A.L.M., Hoffman B., Chen Y.-D.Z., Reaven G.M. Comparison of the effects of atenolol and nitrendipine on glucose, insulin and lipid metabolism in patients with hypertension. Am. J. Hypertens. 4: 199, 1991.

    Article  CAS  Google Scholar 

  35. Byyny R.L., Lo Verde M., Lloyd S., et al. Cytosolic calcium and insulin resistance in elderly patients with essential hypertension. Am. J. Hypertens. 5: 459, 1992.

    PubMed  CAS  Google Scholar 

  36. Draznin B., Susman K.E., Echel R.H., Kao M., Yost T., Sherman N.A. Possible role of cytosolic free calcium concentrations in mediating insulin resistance of obesity and hyperinsulinemia. J. Clin. Invest 82: 1848, 1988.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. Fagerberg B., Andersson O.K., Isaksson B., Bjontorp P. Blood pressure control during weight reduction in obese hypertensive men: separate effects of sodium and energy restriction. Br. Med. J. 288: 7, 11, 1984.

    Article  CAS  Google Scholar 

  38. Schriock E.D., Buffington C.K., Hubert G.D., et al Divergent correlation of circulatory dehydroepiandrosterone sulfate and testosterone with insulin levels and insulin receptors binding. J. Clin. Endocrinol. Metab. 66: 1329, 1988.

    Article  PubMed  CAS  Google Scholar 

  39. Hafner S.M., Valdez R.A., Mykkanen L., Stern M.P., Kats M.S. Decreased testosterone and dehydroepiandrosterone sulfate concentrations are associated with increased insulin and glucose concentration in non diabetic men. Metabolism 43: 599, 1994.

    Article  Google Scholar 

  40. Pasquali R., Cantobelli S., Vicennati V., Casimirri F., Spinucci G., De lasio R., Mesini P., Boschi S., Nestler J.E. Nitrendipine treatment in women with polycystic ovarian syndrome: evidence for a lack of effects of calcium channel blockers on insulin, androgens and sex hormone-binding globulin. J. Clin. Endocrinol. Metab. 80: 3346, 1995.

    PubMed  CAS  Google Scholar 

  41. Clemmons D.R., Van Wyk J.J. Factors controlling blood concentrations of somatomedin C. J. Clin. Endocr. Metab. 13: 113, 1984.

    Article  CAS  Google Scholar 

  42. Villafuerte B.C., Koop B.L., Pao C.I., Phillips L.S. Glucocorticoid regulation of insulin-like growth factor-binding protein-3. Endocrinology 136: 1928, 1995.

    PubMed  CAS  Google Scholar 

  43. Veldhuis J.D., Iranmanesh A., Ho K.K.Y., et al. Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J. Clin. Endocrinol. Metab. 72: 51, 1991.

    Article  PubMed  CAS  Google Scholar 

  44. Williams T., Berelowitz M., Joffe S.N., et al. Impaired growth hormone responses to growth hormone-releasing factor in obesity. N. Engl. J. Med. 311: 1403, 1984.

    Article  PubMed  CAS  Google Scholar 

  45. Poulos J.E., Legget-Frazier N., Khazanie P., Long S., Sportsman R., MacDonald K., Caro J.F. Circulating insulin-like growth factor I concentrations in clinically severe obese patients with and without NIDDM in response to weight loss. Horm. Metab. Res. 26: 478, 1994.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maccario, M., Oleandri, S.E., Avogadri, E. et al. Effects of 3-month nifedipine treatment on endocrine-metabolic parameters in patients with abdominal obesity and mild hypertension. J Endocrinol Invest 21, 56–63 (1998). https://doi.org/10.1007/BF03347287

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347287

Key-words

Navigation