Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1993 Jan;35(1):40–45.

Metabolic effects of lacidipine: a placebo-controlled study using the euglycaemic hyperinsulinaemic clamp.

A D Morris 1, R Donnelly 1, J M Connell 1, J L Reid 1
PMCID: PMC1381488  PMID: 8448066

Abstract

1. Twelve healthy male volunteers received lacidipine 4 mg and matching placebo, each for 2 weeks, in a randomised, double-blind crossover study, and attended on 4 study days to evaluate the effects of single and multiple dosing using the euglycaemic hyperinsulinaemic 'clamp'. 2. On each study day, a primed constant-rate infusion of soluble insulin (1.5 mu kg-1 min-1) was administered for 180 min with a variable-rate infusion of 20% dextrose to maintain euglycaemia (5.2 mmol l-1). Whole-body insulin sensitivity was calculated during the past 40 min of the 'clamp'. At frequent intervals, measurements of BP and HR were recorded and venous blood samples collected for serum insulin, C-peptide, potassium, triglyceride (TG) and plasma noradrenaline concentrations. 3. Lacidipine was generally well tolerated and there were no adverse biochemical events. Mean values for insulin sensitivity +/- s.d. were 8.9 +/- 1.6 and 9.1 +/- 2.0 mg kg-1 min-1 after single doses of lacidipine and placebo respectively (95% CI, -1.0, 1.3), and correspondingly 9.6 +/- 2.1 and 9.7 +/- 1.5 mg kg-1 min-1 after 2 weeks (95% CI, -1.0, 1.3). 4. There was a significant reduction in fasting serum TG concentrations after 2 weeks of lacidipine: 0.7 +/- 0.3 mmol l-1 vs 0.9 +/- 0.6 (P < 0.001). However, changes in serum TG and potassium concentrations during the 'clamp' were not significantly different between the 4 study days. 5. Thus, in 'insulin sensitive' volunteers, lacidipine reduces fasting serum TG concentrations but has no effect on insulin-stimulated uptake of glucose, potassium and TG under euglycaemic hyperinsulinaemic conditions.

Full text

PDF
40

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amery A., Berthaux P., Bulpitt C., Deruyttere M., de Schaepdryver A., Dollery C., Fagard R., Forette F., Hellemans J., Lund-Johansen P. Glucose intolerance during diuretic therapy. Results of trial by the European Working Party on Hypertension in the Elderly. Lancet. 1978 Apr 1;1(8066):681–683. doi: 10.1016/s0140-6736(78)90797-3. [DOI] [PubMed] [Google Scholar]
  2. Baron A. D., Laakso M., Brechtel G., Edelman S. V. Mechanism of insulin resistance in insulin-dependent diabetes mellitus: a major role for reduced skeletal muscle blood flow. J Clin Endocrinol Metab. 1991 Sep;73(3):637–643. doi: 10.1210/jcem-73-3-637. [DOI] [PubMed] [Google Scholar]
  3. Bhatnagar S. K., Amin M. M., Al-Yusuf A. R. Diabetogenic effects of nifedipine. Br Med J (Clin Res Ed) 1984 Jul 7;289(6436):19–19. doi: 10.1136/bmj.289.6436.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Charles S., Ketelslegers J. M., Buysschaert M., Lambert A. E. Hyperglycaemic effect of nifedipine. Br Med J (Clin Res Ed) 1981 Jul 4;283(6283):19–20. doi: 10.1136/bmj.283.6283.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chellingsworth M. C., Kendall M. J., Wright A. D., Singh B. M., Pasi J. The effects of verapamil, diltiazem, nifedipine and propranolol on metabolic control in hypertensives with non-insulin dependent diabetes mellitus. J Hum Hypertens. 1989 Feb;3(1):35–39. [PubMed] [Google Scholar]
  6. Da Prada M., Zürcher Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci. 1976 Oct 15;19(8):1161–1174. doi: 10.1016/0024-3205(76)90251-4. [DOI] [PubMed] [Google Scholar]
  7. DeFronzo R. A., Tobin J. D., Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. doi: 10.1152/ajpendo.1979.237.3.E214. [DOI] [PubMed] [Google Scholar]
  8. Derkx F. H., Tan-Tjiong H. L., Man in 't Veld A. J., Schalekamp M. P., Schalekamp M. A. Activation of inactive plasma renin by plasma and tissue kallikreins. Clin Sci (Lond) 1979 Oct;57(4):351–357. doi: 10.1042/cs0570351. [DOI] [PubMed] [Google Scholar]
  9. Ferrannini E., Buzzigoli G., Bonadonna R., Giorico M. A., Oleggini M., Graziadei L., Pedrinelli R., Brandi L., Bevilacqua S. Insulin resistance in essential hypertension. N Engl J Med. 1987 Aug 6;317(6):350–357. doi: 10.1056/NEJM198708063170605. [DOI] [PubMed] [Google Scholar]
  10. Ferrari P., Weidmann P. Insulin, insulin sensitivity and hypertension. J Hypertens. 1990 Jun;8(6):491–500. doi: 10.1097/00004872-199006000-00001. [DOI] [PubMed] [Google Scholar]
  11. Gill J. S., Al-Hussary N., Zezulka A. V., Pasi K. J., Atkins T. W., Beevers D. G. Effect of nifedipine on glucose tolerance, serum insulin, and serum fructosamine in diabetic and nondiabetic patients. Clin Ther. 1987;9(3):304–310. [PubMed] [Google Scholar]
  12. Giugliano D., Torella R., Cacciapuoti F., Gentile S., Verza M., Varricchio M. Impairment of insulin secretion in man by nifedipine. Eur J Clin Pharmacol. 1980 Nov;18(5):395–398. doi: 10.1007/BF00636791. [DOI] [PubMed] [Google Scholar]
  13. Jauch K. W., Hartl W., Guenther B., Wicklmayr M., Rett K., Dietze G. Captopril enhances insulin responsiveness of forearm muscle tissue in non-insulin-dependent diabetes mellitus. Eur J Clin Invest. 1987 Oct;17(5):448–454. doi: 10.1111/j.1365-2362.1987.tb01141.x. [DOI] [PubMed] [Google Scholar]
  14. Klauser R., Prager R., Gaube S., Gisinger C., Schnack C., Küenburg E., Schernthaner G. Metabolic effects of isradipine versus hydrochlorothiazide in diabetes mellitus. Hypertension. 1991 Jan;17(1):15–21. doi: 10.1161/01.hyp.17.1.15. [DOI] [PubMed] [Google Scholar]
  15. Liu D., Moberg E., Kollind M., Lins P. E., Adamson U., Macdonald I. A. Arterial, arterialized venous, venous and capillary blood glucose measurements in normal man during hyperinsulinaemic euglycaemia and hypoglycaemia. Diabetologia. 1992 Mar;35(3):287–290. doi: 10.1007/BF00400932. [DOI] [PubMed] [Google Scholar]
  16. Marotta T., Ferrara L. A., Pasanisi F., Rubba P., Iovine C., Mancini M. Enhancement of exogenous triglyceride removal following calcium channel blockade. Artery. 1989;16(6):312–326. [PubMed] [Google Scholar]
  17. McKenzie J. K., Clements J. A. Simplified radioimmunoassay for serum aldosterone utilizing increased antibody specificity. J Clin Endocrinol Metab. 1974 Apr;38(4):622–627. doi: 10.1210/jcem-38-4-622. [DOI] [PubMed] [Google Scholar]
  18. Natali A., Santoro D., Palombo C., Cerri M., Ghione S., Ferrannini E. Impaired insulin action on skeletal muscle metabolism in essential hypertension. Hypertension. 1991 Feb;17(2):170–178. doi: 10.1161/01.hyp.17.2.170. [DOI] [PubMed] [Google Scholar]
  19. Pasanisi F., Marotta T., Ferrara L. A., Gnasso A., Cortese C., Mancini M. Acute and chronic effects of dihydropyridines on triglycerides in humans. J Cardiovasc Pharmacol. 1988;12 (Suppl 4):S140–S141. doi: 10.1097/00005344-198806124-00031. [DOI] [PubMed] [Google Scholar]
  20. Pollare T., Lithell H., Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med. 1989 Sep 28;321(13):868–873. doi: 10.1056/NEJM198909283211305. [DOI] [PubMed] [Google Scholar]
  21. Pollare T., Lithell H., Selinus I., Berne C. Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension. Diabetologia. 1988 Jul;31(7):415–420. doi: 10.1007/BF00271585. [DOI] [PubMed] [Google Scholar]
  22. Stout R. W. Insulin and atheroma. 20-yr perspective. Diabetes Care. 1990 Jun;13(6):631–654. doi: 10.2337/diacare.13.6.631. [DOI] [PubMed] [Google Scholar]
  23. Tentorio A., Ghilardi G., Pedroncelli A., Benco R., Stroppa S., Adib S., Gianola D., Pagani G. Insulin secretion and glucose tolerance in non-insulin dependent diabetic patients after chronic nifedipine treatment. Eur J Clin Pharmacol. 1989;36(3):311–313. doi: 10.1007/BF00558165. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES