Obesity Surgery

, Volume 19, Issue 5, pp 601–607 | Cite as

Alterations in Proinsulin and Insulin Dynamics, HDL Cholesterol and ALT After Gastric Bypass Surgery. A 42-Months Follow-up Study

  • Johansson Hans-ErikEmail author
  • Haenni Arvo
  • Öhrvall Margareta
  • Sundbom Magnus
  • Zethelius Björn
Research Article



Roux-en-Y gastric bypass (RYGBP) powerfully reduces type 2 diabetes (T2DM) incidence. Proinsulin predicts development of T2DM. Adjustable gastric banding is associated with lowered proinsulin but after RYGBP information is scant.


Twenty-one non-diabetic morbidly obese patients who underwent RYGBP surgery were evaluated before (baseline), at 12 months (first follow-up), and at 42 months, range 36–50 (second follow-up), after surgery and compared to a control group, matched at baseline regarding fasting glucose, insulin, proinsulin, alanine aminotransferase (ALT), high-density lipoprotein (HDL) cholesterol, and body mass index (BMI).


In the RYGBP group, fasting serum proinsulin concentrations were markedly lowered from 13.5 to 3.5 pmol/l at first follow-up and to 4.9 pmol/l at second follow-up (p < 0.001, respectively). Fasting insulin concentrations were reduced from 83.4 to 24.6 pmol/l at first follow-up (p < 0.001) and to 36.4 pmol/l at second follow-up (p < 0.01). ALT was lowered from 0.62 to 0.34 μkatal/l at first follow-up and continued to lower to 0.24 μkatal/l at second follow-up (p < 0.001, respectively). The further decrease between first and second follow-up was also significant (p = 0.002). HDL cholesterol increased from 1.16 to 1.45 mmol/l at the first follow-up and continued to increase at second follow-up to 1.58 mmol/l (p < 0.001, respectively). The further increase between first and second follow-up was also significant (p = 0.006). The differences between groups at first follow-up were significant for BMI, proinsulin, insulin, ALT, and HDL cholesterol (p = 0.04–0.001).


RYGBP surgery in morbidly obese patients is not only characterized by markedly and sustained lowered BMI but also lowered concentrations of proinsulin, insulin, and ALT and increased HDL cholesterol.


Morbid obesity Gastric bypass surgery Proinsulin ALT HDL cholesterol 



This study is funded by research grants from: The Family Ernfors Fund for Diabetes Research, the Swedish Diabetes Association, the Erik, Karin, and Gösta Selander fund, Uppsala University, the Thureus fund, the Thuring family foundation, Uppsala County Research Development, Capio Research Fund, and finally the Research and Development Department, Primary Care, Uppsala County.


  1. 1.
    World Health Organization. Obesity and overweight: fact sheet no. 3011. Geneva: WHO; 2006.Google Scholar
  2. 2.
    Gumbs AA, Modlin IM, Ballantyne GH. Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss. Obes Surg 2005;15(4):462–73.CrossRefGoogle Scholar
  3. 3.
    Wickremesekera K, Miller G, Naotunne TD, et al. Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course study. Obes Surg 2005;15(4):474–81.CrossRefGoogle Scholar
  4. 4.
    Gleysteen JJ. Results of surgery: long-term effects on hyperlipidemia. Am J Clin Nutr 1992;55(2 Suppl):591S–3S.CrossRefGoogle Scholar
  5. 5.
    Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357(8):741–52.CrossRefGoogle Scholar
  6. 6.
    Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med 2007;357(8):753–61.CrossRefGoogle Scholar
  7. 7.
    Bonadonna RC, Groop L, Kraemer N, et al. Obesity and insulin resistance in humans: a dose–response study. Metabolism 1990;39:452–9.CrossRefGoogle Scholar
  8. 8.
    Johansson HE, Ohrvall M, Haenni A, et al. Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion. Diabet Med 2007;24(11):1213–20.CrossRefGoogle Scholar
  9. 9.
    Drake AJ, Greenhalgh L, Newbury-Ecob R, et al. Pancreatic dysfunction in severe obesity. Arch Dis Child 1990;84:261–2.CrossRefGoogle Scholar
  10. 10.
    Haffner SM, Stern MP, Hazuda HP, et al. Hyperinsulinemia in a population at high risk for non-insulin-dependent diabetes mellitus. N Engl J Med 1986;315:220–4.CrossRefGoogle Scholar
  11. 11.
    Zethelius B, Byberg L, Hales CN, et al. Proinsulin and acute insulin response independently predict type 2 diabetes mellitus in men—report from 27 years of follow-up study. Diabetologia 2003;46:20–6.CrossRefGoogle Scholar
  12. 12.
    Schulze MB, Solomon CG, Rifai N, et al. Hyperproinsulinaemia and risk of type 2 diabetes mellitus in women. Diabet Med 2005;22:1178–84.CrossRefGoogle Scholar
  13. 13.
    Wareham NJ, Byrne CD, Williams R, et al. Fasting proinsulin concentrations predict the development of type 2 diabetes. Diabetes Care 1999;22(2):262–70.CrossRefGoogle Scholar
  14. 14.
    Kahn SE, Leonetti DL, Prigeon RL, et al. Proinsulin levels predict the development of non-insulin-dependent diabetes mellitus (NIDDM) in Japanese–American men. Diabet Med 1996;13:S63–66.PubMedGoogle Scholar
  15. 15.
    Zethelius B, Byberg L, Hales CN, et al. Proinsulin is an independent predictor of coronary heart disease: report from a 27-year follow-up study. Circulation 2002;105:2153–8.CrossRefGoogle Scholar
  16. 16.
    Yudkin JS, May M, Elwood P, et al. Concentrations of proinsulin like molecules predict coronary heart disease risk independently of insulin: prospective data from the Caerphilly Study. Diabetologia 2002;45:327–36.CrossRefGoogle Scholar
  17. 17.
    Eckel RH. Mechanisms of the components of the metabolic syndrome that predispose to diabetes and atherosclerotic CVD. Proc Nutr Soc 2007;66(1):82–95.CrossRefGoogle Scholar
  18. 18.
    Castelli WP, Garrison RJ, Wilson PW, et al. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986;256(20):2835–8.CrossRefGoogle Scholar
  19. 19.
    Corti MC, Guralnik JM, Salive ME, et al. HDL cholesterol predicts coronary heart disease mortality in older persons. JAMA 1995;274(7):539–44.CrossRefGoogle Scholar
  20. 20.
    Yki-Jarvinen H. Fat in the liver and insulin resistance. Ann Med 2005;37:347–56.CrossRefGoogle Scholar
  21. 21.
    Kotronen A, Westerbacka J, Bergholm R, et al. Liver fat in the metabolic syndrome. J Clin Endocrinol Metab 2007;92(9):3490–7.CrossRefGoogle Scholar
  22. 22.
    Song HR, Yun KE, Park HS. Relation between alanine aminotransferase concentrations and visceral fat accumulation among nondiabetic overweight Korean women. Am J Clin Nutr 2008;88(1):16–21.CrossRefGoogle Scholar
  23. 23.
    Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351:2683–93.CrossRefGoogle Scholar
  24. 24.
    Ram E, Vishne T, Maayan R, et al. The relationship between BMI, plasma leptin, insulin and proinsulin before and after laparoscopic adjustable gastric banding. Obes Surg 2005;15:1456–62.CrossRefGoogle Scholar
  25. 25.
    Sundbom M, Gustavsson S. Bariatric surgery. Clin Dermatol 2004;22:325–31.CrossRefGoogle Scholar
  26. 26.
    Muscelli E, Mingrone G, Camastra S, et al. Differential effect of weight loss on insulin resistance in surgically treated obese patients. Am J Med 2005;118:51–7.CrossRefGoogle Scholar
  27. 27.
    Pereira JA, Lazarin MA, Pareja JC, et al. Insulin resistance in nondiabetic morbidly obese patients: effect of bariatric surgery. Obes Res 2003;11:1495–501.CrossRefGoogle Scholar
  28. 28.
    Kellum JM, Kuemmerle JF, O'Dorisio TM, et al. Gastrointestinal hormone responses to meals before and after gastric bypass and vertical banded gastroplasty. Ann Surg 1990;211:763–70. discussion 770–761.CrossRefGoogle Scholar
  29. 29.
    DeMaria EJ. Bariatric surgery for morbid obesity. N Engl J Med 2007;356(21):2176–83.CrossRefGoogle Scholar
  30. 30.
    Laferrère B, Teixeira J, McGinty J, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab 2008;93(7):2479–85.CrossRefGoogle Scholar
  31. 31.
    le Roux CW. Gut hormone profiles following bariatric surgery favor an anoretic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 2006;243:108–14.CrossRefGoogle Scholar
  32. 32.
    Machado M, Cortez-Pinto H. Non-alcoholic fatty liver disease and insulin resistance. Eur J Gastroenterol Hepatol 2005;17(8):823–6.CrossRefGoogle Scholar
  33. 33.
    Marchesini G, Babini M. Nonalcoholic fatty liver disease and the metabolic syndrome. Minerva Cardioangiol 2006;54(2):229–39.PubMedGoogle Scholar
  34. 34.
    Sattar N, McConnachie A, Ford I, et al. Serial metabolic measurements and conversion to type 2 diabetes in the west of Scotland coronary prevention study: specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor. Diabetes 2007;56(4):984–91.CrossRefGoogle Scholar
  35. 35.
    Ioannou GN, Weiss NS, Boyko EJ, et al. Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. Hepatology 2006;43(5):1145–51.CrossRefGoogle Scholar
  36. 36.
    Boden G. Obesity and free fatty acids. Endocrinol Metab Clin North Am 2008;37(3):635–46.CrossRefGoogle Scholar
  37. 37.
    Cowan GS Jr, Buffington CK. Significant changes in blood pressure, glucose, and lipids with gastric bypass surgery. World J Surg 1998;22(9):987–92.CrossRefGoogle Scholar
  38. 38.
    Stefan N, Kantartzis K, Häring H-U. Causes and metabolic consequences of fatty liver. Endocr Rev 2008;29:939–60.CrossRefGoogle Scholar
  39. 39.
    Pettersson J, Hindorf U, Persson P, et al. Muscular exercise can cause highly pathological liver function tests in healthy men. Br J Clin Pharmacol 2008;65(2):253–9.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Johansson Hans-Erik
    • 1
    Email author
  • Haenni Arvo
    • 1
  • Öhrvall Margareta
    • 1
  • Sundbom Magnus
    • 2
  • Zethelius Björn
    • 1
  1. 1.Department of Public Health and Caring Sciences/GeriatricsUppsala University HospitalUppsalaSweden
  2. 2.Department of Surgical SciencesUppsala University HospitalUppsalaSweden

Personalised recommendations