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Restored insulin inhibition on insulin secretion in nondiabetic severely obese patients after weight loss induced by bariatric surgery

Abstract

OBJECTIVE: To examine the impact of important weight loss on insulin inhibition of its own secretion during experimentally induced hyperinsulinemia under euglycemic conditions.

DESIGN: Longitudinal, clinical intervention study—bariatric surgery (vertical banded gastroplasty—gastric bypass—Capella technique), re-evaluation after 4 and 14 months.

SUBJECTS: Nine obese patients class III (BMI=54.6±2.6 kg/m2) and nine lean subjects (BMI=22.7±0.7 kg/m2).

MEASUREMENTS: Euglycemic hyperinsulinemic clamp (insulin infusion: 40 mU/min m2), C-peptide plasma levels, electrical bioimpedance methodology, and oral glucose tolerance test (OGTT).

RESULTS: BMI was reduced in the follow-up: 44.5±2.2 and 33.9±1.5 kg/m2 at 4 and 14 months. Insulin-induced glucose uptake was markedly reduced in obese patients (19.5±1.9 μmol/min kg FFM) and improved with weight loss, but in the third study, it was still lower than that observed in controls (35.9±4.0 vs 52.9±2.2 μmol/min kg FFM). Insulin-induced inhibition of its own secretion was blunted in obese patients (19.9±5.7%, relative to fasting values), and completely reversed to values similar to that of lean ones in the second and third studies (−60.8±4.2 and −54.0±6.1%, respectively).

CONCLUSION: Weight loss in severe obesity improved insulin-induced glucose uptake, and completely normalized the insulin inhibition on its own secretion.

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References

  1. DeFronzo RA . Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev 1997; 5: 177–269.

    Google Scholar 

  2. Bonadonna RC, Groop L, Kraemer N, Ferrannini E, Del Prato S, DeFronzo RA . Obesity and insulin resistance in humans: a dose–response study. Metabolism 1990; 39: 452–459.

    Article  CAS  Google Scholar 

  3. Gerich JE . Insulin resistance is not necessarily an essential component of type 2 diabetes. J Clin Endocrinol Metab 2000; 85: 2113–2115.

    CAS  PubMed  Google Scholar 

  4. Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ . Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334: 952–957.

    Article  CAS  Google Scholar 

  5. Reaven GM . Banting lecture: role of insulin resistance in human disease. Diabetes 1988; 37: 595–607.

    Article  Google Scholar 

  6. Ferrannini E, Natali A, Bell P, Cavallo-Perin P, Lalic N, Mingrone G . Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J Clin Invest 1997; 100: 1166–1173.

    Article  CAS  Google Scholar 

  7. Muscelli E, Pereira JA, Lazarin MACT, Silva CA, Pareja JC, Saad MJA . Lack of insulin inhibition on insulin secretion in non-diabetic morbidly obese patients. Int J Obes Relat Metab Disord 2001; 25: 798–804.

    Article  CAS  Google Scholar 

  8. Polonsky KS, Given BD, Hirsch L, Shapiro ET, Tillil H, Beebe C, Galloway JA . Quantitative study of insulin secretion and clearance in normal and obese subjects. J Clin Invest 1988; 81: 435–441.

    Article  CAS  Google Scholar 

  9. Cavallo-Perin P, Bruno A, Scaglione L, Gruden G, Cassader M, Pagano G . Feedback inhibition of insulin and glucagon secretion by insulin is altered in abdominal obesity with normal or impaired glucose tolerance. Diabetologia 1993; 30: 154–158.

    Article  CAS  Google Scholar 

  10. Elahi D, Nagulesparan M, Hershcopf RJ, Muller DC, Tobin JD, Blix PM, Rubenstein AH, Unger RH, Andres R . Feedback inhibition of insulin secretion by insulin: relation to the hyperinsulinemia of obesity. N Engl J Med 1982; 306: 1196–1202.

    Article  CAS  Google Scholar 

  11. Robertson DA, Singh BM, Hale PJ, Nattrass M . Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion. Metabolism 1992; 41: 604–612.

    Article  CAS  Google Scholar 

  12. Pincelli AI, Brunani A, Caumo A, Scacchi M, Pasqualinotto L, Tibaldi A, Dubini S, Bonadonna S, Cavagnini F . Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men. Metabolism 2001; 50: 107–111.

    Article  CAS  Google Scholar 

  13. Obesity: preventing and managing the Global Epidemic. WHO Technical Report series 894. World Health Organization: Geneva; 2000: pp 6–15.

  14. Muscelli E, Camastra S, Catalano C, Quinones G, Ciociaro D, Baldi S, Ferrannini E . Metabolic and cardiovascular assessment in moderate obesity: effect of weight loss. J Clin Endocrinol Metab 1997; 82: 2937–2943.

    Article  CAS  Google Scholar 

  15. Long SD, O’Brien K, MacDonald KG, Leggett-Frazier N, Swanson MS, Pories WJ, Caro JF . Weight loss in severely obese subjects prevents the progression of impaired glucose tolerance to type II diabetes. A longitudinal interventional study. Diabetes Care 1994; 17: 372–375.

    Article  CAS  Google Scholar 

  16. Sjöstrom CD, Lissner L, Wedel H, Sjöstrom L . Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Interventional Study. Obes Res 1999; 7: 477–484.

    Article  Google Scholar 

  17. Jimenez J, Zuniga-Guajardo S, Zinman B, Angel A . Effects of weight loss in massive obesity on insulin and C-peptide dynamics: sequential changes in insulin production, clearance, and sensitivity. J Clin Endocrinol Metab 1987; 64: 661–668.

    Article  CAS  Google Scholar 

  18. National Institute of Health Conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med 1991; 115: 956–961.

  19. Capella JF, Capella RF . The weight reduction operation of choice: vertical banded gastroplasty or gastric bypass? Am J Surg 1996; 171: 74–79.

    Article  CAS  Google Scholar 

  20. Joint National Committee on detection, evaluation and treatment of high blood pressure. The fifth report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure (JNC V). Arch Intern Med 1993; 153: 154–183.

  21. American Diabetes Association: Report of Expert Committee on Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–1197.

  22. Fulcher GR, Farrer M, Walker M, Rodham D, Clayton B, Alberti KGM . A. Comparison of measurements of lean body mass derived by bioelectrical impedance, skinfold thickness and total body potassium. A study in obese and non-obese normal subjects. Scand J Lab Invest 1991; 51: 245–253.

    Article  CAS  Google Scholar 

  23. DeFronzo RA, Tobin JD, Andres R . Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214–E223.

    CAS  Google Scholar 

  24. McGuire EAH, Heldermann JH, Tobin JD, Andres R, Berman M . Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol 1976; 41: 1312–1318.

    Article  Google Scholar 

  25. Polonsky K, Jaspan J, Pugh W, Cohen D, Schmeider M, Schwartz T, Moossa AR, Tager H, Rubenstein AH . Metabolism of C-peptide in the dogs: in vivo demonstration of the absence of hepatic extraction. J Clin Invest 1983; 72: 1114–1124.

    Article  CAS  Google Scholar 

  26. Liljenquist JE, Horwitz DL, Jennings AS, Chiasson JL, Keller U, Rubenstein AH . Inhibition of insulin secretion by exogenous insulin in normal man as demonstrated by C-peptide assay. Diabetes 1978; 27: 563–570.

    Article  CAS  Google Scholar 

  27. Kulkarni RN, Wang Z, Wang R, Hurley JD, Smith DM, Ghatei MA, Withers DJ, Gardiner JV, Balley CJ, Bloom SR . Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in vivo, in mice. J Clin Invest 1997; 100: 2729–2736.

    Article  CAS  Google Scholar 

  28. Geloneze B, Tambascia MA, Pareja JC, Repetto EM, Magna LA, Pereira SG . Serum leptin levels after bariatric surgery across a range of glucose tolerance from normal to diabetes. Obes Surg 2001; 11: 693–698.

    Article  CAS  Google Scholar 

  29. Bratusch-Marrain PR, Waldhäusl W . Suppression of basal, but not glucose stimulated secretion by human insulin in healthy and obese hyperinsulinemic subjects. Metabolism 1985; 34: 188–193.

    Article  CAS  Google Scholar 

  30. Kraegen EW, Lazarus L, Campbell LV . Failure of insulin infusion during euglycemia to influence endogenous basal insulin secretion. Metabolism 1983; 32: 622–627.

    Article  CAS  Google Scholar 

  31. Peiris AN, Stagner JI, Vogel RL, Samols E, Nakagawa A . Lack of insulin feedback inhibition in non-obese and obese men. Metabolism 1993; 42: 371–375.

    Article  CAS  Google Scholar 

  32. Bonora E, Moghetti P, Zancarano C, Cigolini M, Querena M, Cacciatori V, Zenere M, Corgnati A, Muggeo M . Normal inhibition by somatostatin of glucose-stimulated B cell secretion in obese subjects. Horm Metabol Res 1990; 22: 584–588.

    Article  CAS  Google Scholar 

  33. Polonsky KS . Dynamics of insulin secretion in obesity and diabetes. Int J Obes Relat Metab Disord 2000; 24: S29–S31.

    Article  CAS  Google Scholar 

  34. Boden G, Chen X, Desantis R, Kolaczynski J, Morris M . Evidence that suppression of insulin secretion by insulin itself is neurally mediated. Metabolism 1993; 42: 786–789.

    Article  CAS  Google Scholar 

  35. Anderson EA, Hoffman RP, Balon TW, Sinkey CA, Mark AL . Hyperinsulinemia produces both sympathetic neural activation and vasodilatation in normal humans. J Clin Invest 1991; 87: 2246–2252.

    Article  CAS  Google Scholar 

  36. Muscelli E, Emdin M, Natali A, Pratali L, Camastra S, Gastaldelli A, Baldi S, Carpeggiani C, Ferrannini E . Autonomic and hemodynamic responses to insulin in lean and obese humans. J Clin Endocrinol Metab 1998; 83: 2084–2090.

    CAS  PubMed  Google Scholar 

  37. Scherrer U, Randin D, Tappy L, Vollenweider P, Jéquier E, Nicod P . Body fat and sympathetic nerve activity in healthy subjects. Circulation 1994; 89: 2634–2640.

    Article  CAS  Google Scholar 

  38. Emdin M, Gastaldelli A, Muscelli E, Macerata A, Natali A, Camastra S, Ferrannini E . Hyperinsulinemia and autonomic nervous system dysfunction in obesity: effects of weight loss. Circulation 2001; 103: 513–519.

    Article  CAS  Google Scholar 

  39. Velloso LA, Carneiro EM, Crepaldi SC, Boschero AC, Saad MJA . Glucose and insulin-induced phosphorylation of the insulin receptor and its primary substrates IRS-1 and IRS-2 in rat pancreatic islets. FEBS 1995; 377: 353–357.

    Article  CAS  Google Scholar 

  40. Rothenberg PL, Willison LD, Simon J, Wolf BA . Glucose induced receptor tyrosine phosphorylation in insulin-secretion beta cells. Diabetes 1995; 44: 802–809.

    Article  CAS  Google Scholar 

  41. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn R . Tissue-specific knockout of the insulin receptor in pancreatic β cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 1999; 96: 329–339.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Fundação de Apoio ao Ensino e Pesquisa (FAEP, UNICAMP) is acknowledged.

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Correspondence to E Muscelli.

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Pereira, J., Claro, B., Pareja, J. et al. Restored insulin inhibition on insulin secretion in nondiabetic severely obese patients after weight loss induced by bariatric surgery. Int J Obes 27, 463–468 (2003). https://doi.org/10.1038/sj.ijo.0802269

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