Skip to main content
Top
Published in: Obesity Surgery 2/2020

Open Access 01-02-2020 | Bariatric Surgery | Original Contributions

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

Authors: G. Rega-Kaun, C. Kaun, G. Jaegersberger, M. Prager, M. Hackl, S. Demyanets, J. Wojta, P. J. Hohensinner

Published in: Obesity Surgery | Issue 2/2020

Login to get access

Abstract

Background

Obesity is closely linked to increased markers of metabolic syndrome and development of diabetes. Roux-en-Y bariatric surgery reduces hyperinsulinemia and improves insulin sensitivity and hence benefits morbidly obese patients.

Aim

To determine changes in markers of metabolic syndrome, pancreatic function, and hepatic insulin sensitivity in patients before and 1 year after undergoing Roux-en-Y gastric bypass surgery.

Methods

We enrolled 43 consecutive patients in a single center. Markers for metabolic syndrome included proinsulin, insulin, C-peptide, liver enzymes, and serum levels of selected microRNAs hsa-miR-122, hsa-miR-130, hsa-miR-132, and hsa-miR-375.

Results

After surgery, all patients showed a significant 37% drop of body mass index (p < 0.001). Furthermore, proinsulin (59% reduction, p < 0.001), insulin (76% reduction, p < 0.001), and C-peptide (56% reduction, p < 0.001) were all reduced 1 year after surgery. Using the hepatic insulin clearance score, we determined a significant increase in hepatic insulin clearance after surgery (76% increase, p < 0.001). Especially diabetic patients showed a marked 2.1-fold increase after surgery. Hepatic enzymes ALT (35% reduction, p = 0.002) and γGT (48% reduction, p < 0.001) were significantly reduced in all patients with similar improvement in diabetic and non-diabetic patients. miRNAs hsa-miR-122, hsa-miR-130, and hsa-miR-132 were all significantly reduced whereas hsa-miR-375 was increased after gastric bypass surgery (p < 0.001 for all miRNAs).

Conclusion

Both liver and pancreatic stress parameters were reduced significantly 1 year after Roux-en-Y gastric bypass surgery suggesting an overall amelioration of the metabolic syndrome in all patients regardless of previous health status.
Literature
1.
go back to reference Pivovarova O, Bernigau W, Bobbert T, et al. Hepatic insulin clearance is closely related to metabolic syndrome components. Diabetes Care. 2013;36(11):3779–85.PubMedPubMedCentral Pivovarova O, Bernigau W, Bobbert T, et al. Hepatic insulin clearance is closely related to metabolic syndrome components. Diabetes Care. 2013;36(11):3779–85.PubMedPubMedCentral
2.
go back to reference Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–607.PubMed Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–607.PubMed
3.
go back to reference Mokdad AH, Bowman BA, Ford ES, et al. The continuing epidemics of obesity and diabetes in the United States. Jama. 2001;286(10):1195–200.PubMed Mokdad AH, Bowman BA, Ford ES, et al. The continuing epidemics of obesity and diabetes in the United States. Jama. 2001;286(10):1195–200.PubMed
4.
go back to reference Kahn SE, Prigeon RL, McCulloch DK, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993;42(11):1663–72.PubMed Kahn SE, Prigeon RL, McCulloch DK, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993;42(11):1663–72.PubMed
5.
go back to reference Le Stunff C, Bougneres P. Early changes in postprandial insulin secretion, not in insulin sensitivity, characterize juvenile obesity. Diabetes. 1994;43(5):696–702.PubMed Le Stunff C, Bougneres P. Early changes in postprandial insulin secretion, not in insulin sensitivity, characterize juvenile obesity. Diabetes. 1994;43(5):696–702.PubMed
6.
go back to reference Bojsen-Moller KN, Lundsgaard AM, Madsbad S, et al. Hepatic insulin clearance in regulation of systemic insulin concentrations-role of carbohydrate and energy availability. Diabetes. 2018;67(11):2129–36.PubMed Bojsen-Moller KN, Lundsgaard AM, Madsbad S, et al. Hepatic insulin clearance in regulation of systemic insulin concentrations-role of carbohydrate and energy availability. Diabetes. 2018;67(11):2129–36.PubMed
7.
go back to reference 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.PubMed 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.PubMed
8.
go back to reference Johansson HE, Haenni A, Ohrvall M, et al. Alterations in proinsulin and insulin dynamics, HDL cholesterol and ALT after gastric bypass surgery. A 42-months follow-up study. Obes Surg. 2009;19(5):601–7.PubMed Johansson HE, Haenni A, Ohrvall M, et al. Alterations in proinsulin and insulin dynamics, HDL cholesterol and ALT after gastric bypass surgery. A 42-months follow-up study. Obes Surg. 2009;19(5):601–7.PubMed
9.
go back to reference 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.PubMed 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.PubMed
10.
go back to reference Johansson HE, Ohrvall M, Haenni A, et al. Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion. Diabet Med: a journal of the British Diabetic Association. 2007;24(11):1213–20. Johansson HE, Ohrvall M, Haenni A, et al. Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion. Diabet Med: a journal of the British Diabetic Association. 2007;24(11):1213–20.
11.
go back to reference Hohensinner PJ, Kaun C, Ebenbauer B, et al. Reduction of premature aging markers after gastric bypass surgery in morbidly obese patients. Obes Surg. 2018;28(9):2804–10.PubMedPubMedCentral Hohensinner PJ, Kaun C, Ebenbauer B, et al. Reduction of premature aging markers after gastric bypass surgery in morbidly obese patients. Obes Surg. 2018;28(9):2804–10.PubMedPubMedCentral
12.
go back to reference Rega-Kaun G, Kaun C, Ebenbauer B, et al. Bariatric surgery in morbidly obese individuals affects plasma levels of protein C and thrombomodulin. J Thromb Thrombolysis. 2019;47(1):51–6.PubMed Rega-Kaun G, Kaun C, Ebenbauer B, et al. Bariatric surgery in morbidly obese individuals affects plasma levels of protein C and thrombomodulin. J Thromb Thrombolysis. 2019;47(1):51–6.PubMed
13.
go back to reference Matsuda A, Makino N, Tozawa T, et al. Pancreatic fat accumulation, fibrosis, and acinar cell injury in the Zucker diabetic fatty rat fed a chronic high-fat diet. Pancreas. 2014;43(5):735–43.PubMedPubMedCentral Matsuda A, Makino N, Tozawa T, et al. Pancreatic fat accumulation, fibrosis, and acinar cell injury in the Zucker diabetic fatty rat fed a chronic high-fat diet. Pancreas. 2014;43(5):735–43.PubMedPubMedCentral
14.
go back to reference Lautenbach A, Wernecke M, Riedel N, et al. Adaptive changes in pancreas post Roux-en-Y gastric bypass induced weight loss. Diabetes Metab Res Rev. 2018;34(7):e3025.PubMed Lautenbach A, Wernecke M, Riedel N, et al. Adaptive changes in pancreas post Roux-en-Y gastric bypass induced weight loss. Diabetes Metab Res Rev. 2018;34(7):e3025.PubMed
15.
go back to reference Sullivan CA, Cacicedo JM, Rajendran I, et al. Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: a pilot study. PLoS One. 2018;13(11):e0207065.PubMedPubMedCentral Sullivan CA, Cacicedo JM, Rajendran I, et al. Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: a pilot study. PLoS One. 2018;13(11):e0207065.PubMedPubMedCentral
16.
go back to reference Uchizono Y, Alarcon C, Wicksteed BL, et al. The balance between proinsulin biosynthesis and insulin secretion: where can imbalance lead? Diabet Obes Metab. 2007;9(Suppl 2):56–66. Uchizono Y, Alarcon C, Wicksteed BL, et al. The balance between proinsulin biosynthesis and insulin secretion: where can imbalance lead? Diabet Obes Metab. 2007;9(Suppl 2):56–66.
17.
go back to reference Rhodes CJ. Type 2 diabetes-a matter of beta-cell life and death? Science. 2005;307(5708):380–4.PubMed Rhodes CJ. Type 2 diabetes-a matter of beta-cell life and death? Science. 2005;307(5708):380–4.PubMed
18.
go back to reference Kahn SE, Halban PA. Release of incompletely processed proinsulin is the cause of the disproportionate proinsulinemia of NIDDM. Diabetes. 1997;46(11):1725–32.PubMed Kahn SE, Halban PA. Release of incompletely processed proinsulin is the cause of the disproportionate proinsulinemia of NIDDM. Diabetes. 1997;46(11):1725–32.PubMed
19.
go back to reference Watkins RA, Evans-Molina C, Terrell JK, et al. Proinsulin and heat shock protein 90 as biomarkers of beta-cell stress in the early period after onset of type 1 diabetes. Transl Res. 2016;168:96–1060.PubMed Watkins RA, Evans-Molina C, Terrell JK, et al. Proinsulin and heat shock protein 90 as biomarkers of beta-cell stress in the early period after onset of type 1 diabetes. Transl Res. 2016;168:96–1060.PubMed
20.
go back to reference Kruschitz R, Luger M, Kienbacher C, et al. The effect of roux-en-Y vs. omega-loop gastric bypass on liver, metabolic parameters, and weight loss. Obes Surg. 2016;26(9):2204–12.PubMedPubMedCentral Kruschitz R, Luger M, Kienbacher C, et al. The effect of roux-en-Y vs. omega-loop gastric bypass on liver, metabolic parameters, and weight loss. Obes Surg. 2016;26(9):2204–12.PubMedPubMedCentral
21.
go back to reference Llave C, Xie Z, Kasschau KD, et al. Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science. 2002;297(5589):2053–6.PubMed Llave C, Xie Z, Kasschau KD, et al. Cleavage of Scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science. 2002;297(5589):2053–6.PubMed
22.
go back to reference Victoria B, Nunez Lopez YO, Masternak MM. MicroRNAs and the metabolic hallmarks of aging. Mol Cell Endocrinol. 2017;455:131–47.PubMedPubMedCentral Victoria B, Nunez Lopez YO, Masternak MM. MicroRNAs and the metabolic hallmarks of aging. Mol Cell Endocrinol. 2017;455:131–47.PubMedPubMedCentral
23.
go back to reference Runkel N, Colombo-Benkmann M, Hüttl TP, et al. Evidence-based German guidelines for surgery for obesity. Int J Color Dis. 2011;26(4):397–404. Runkel N, Colombo-Benkmann M, Hüttl TP, et al. Evidence-based German guidelines for surgery for obesity. Int J Color Dis. 2011;26(4):397–404.
24.
go back to reference Disse E, Pasquer A, Espalieu P, et al. Greater weight loss with the omega loop bypass compared to the Roux-en-Y gastric bypass: a comparative study. Obes Surg. 2014;24(6):841–6.PubMed Disse E, Pasquer A, Espalieu P, et al. Greater weight loss with the omega loop bypass compared to the Roux-en-Y gastric bypass: a comparative study. Obes Surg. 2014;24(6):841–6.PubMed
25.
go back to reference Blondal T, Jensby Nielsen S, Baker A, et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods. 2013;59(1):S1–6.PubMed Blondal T, Jensby Nielsen S, Baker A, et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods. 2013;59(1):S1–6.PubMed
26.
go back to reference Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.PubMed Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.PubMed
27.
go back to reference Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):2402–10.PubMed Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85(7):2402–10.PubMed
28.
go back to reference Bojsen-Moller KN, Dirksen C, Jorgensen NB, et al. Increased hepatic insulin clearance after Roux-en-Y gastric bypass. J Clin Endocrinol Metab. 2013;98(6):E1066–71.PubMed Bojsen-Moller KN, Dirksen C, Jorgensen NB, et al. Increased hepatic insulin clearance after Roux-en-Y gastric bypass. J Clin Endocrinol Metab. 2013;98(6):E1066–71.PubMed
29.
go back to reference Zhang L, Bai M, Tang H, et al. Role of hepatic neuregulin 4 in the regulation of gluconeogenesis in mice. Life Sci. 2019;217:185–92.PubMed Zhang L, Bai M, Tang H, et al. Role of hepatic neuregulin 4 in the regulation of gluconeogenesis in mice. Life Sci. 2019;217:185–92.PubMed
30.
go back to reference Ofori JK, Salunkhe VA, Bagge A, et al. Elevated miR-130a/miR130b/miR-152 expression reduces intracellular ATP levels in the pancreatic beta cell. Sci Rep. 2017;7:44986.PubMedPubMedCentral Ofori JK, Salunkhe VA, Bagge A, et al. Elevated miR-130a/miR130b/miR-152 expression reduces intracellular ATP levels in the pancreatic beta cell. Sci Rep. 2017;7:44986.PubMedPubMedCentral
31.
go back to reference Seyhan AA, Nunez Lopez YO, Xie H, et al. Pancreas-enriched miRNAs are altered in the circulation of subjects with diabetes: a pilot cross-sectional study. Sci Rep. 2016;6:31479.PubMedPubMedCentral Seyhan AA, Nunez Lopez YO, Xie H, et al. Pancreas-enriched miRNAs are altered in the circulation of subjects with diabetes: a pilot cross-sectional study. Sci Rep. 2016;6:31479.PubMedPubMedCentral
32.
go back to reference Eliasson L. The small RNA miR-375 - a pancreatic islet abundant miRNA with multiple roles in endocrine beta cell function. Mol Cell Endocrinol. 2017;456:95–101.PubMed Eliasson L. The small RNA miR-375 - a pancreatic islet abundant miRNA with multiple roles in endocrine beta cell function. Mol Cell Endocrinol. 2017;456:95–101.PubMed
34.
go back to reference Courcoulas AP, Christian NJ, Belle SH, et al. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. Jama. 2013;310(22):2416–25.PubMedPubMedCentral Courcoulas AP, Christian NJ, Belle SH, et al. Weight change and health outcomes at 3 years after bariatric surgery among individuals with severe obesity. Jama. 2013;310(22):2416–25.PubMedPubMedCentral
35.
go back to reference Barazzoni R, Palmisano S, Cappellari G, et al. Gastric bypass–induced weight loss alters obesity-associated patterns of plasma pentraxin-3 and systemic inflammatory markers. Surg Obes Relat Dis. 2016;12(1):23–32.PubMed Barazzoni R, Palmisano S, Cappellari G, et al. Gastric bypass–induced weight loss alters obesity-associated patterns of plasma pentraxin-3 and systemic inflammatory markers. Surg Obes Relat Dis. 2016;12(1):23–32.PubMed
36.
go back to reference Sims EK, Bahnson HT, Nyalwidhe J, et al. Proinsulin secretion is a persistent feature of type 1 diabetes. Diabetes Care. 2019;42(2):258–64.PubMed Sims EK, Bahnson HT, Nyalwidhe J, et al. Proinsulin secretion is a persistent feature of type 1 diabetes. Diabetes Care. 2019;42(2):258–64.PubMed
37.
go back to reference Poy MN, Hausser J, Trajkovski M, et al. miR-375 maintains normal pancreatic alpha- and beta-cell mass. Proc Natl Acad Sci U S A. 2009;106(14):5813–8.PubMedPubMedCentral Poy MN, Hausser J, Trajkovski M, et al. miR-375 maintains normal pancreatic alpha- and beta-cell mass. Proc Natl Acad Sci U S A. 2009;106(14):5813–8.PubMedPubMedCentral
38.
go back to reference Cai C, Lin M, Xu Y, et al. Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study. BMC Med. 2016;14(1):165.PubMedPubMedCentral Cai C, Lin M, Xu Y, et al. Association of circulating neuregulin 4 with metabolic syndrome in obese adults: a cross-sectional study. BMC Med. 2016;14(1):165.PubMedPubMedCentral
39.
go back to reference Chen LL, Peng MM, Zhang JY, et al. Elevated circulating Neuregulin4 level in patients with diabetes. Diabetes Metab Res Rev. 2017;33:4. Chen LL, Peng MM, Zhang JY, et al. Elevated circulating Neuregulin4 level in patients with diabetes. Diabetes Metab Res Rev. 2017;33:4.
40.
go back to reference Jorgensen NB, Dirksen C, Bojsen-Moller KN, et al. Exaggerated glucagon-like peptide 1 response is important for improved beta-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes. 2013;62(9):3044–52.PubMedPubMedCentral Jorgensen NB, Dirksen C, Bojsen-Moller KN, et al. Exaggerated glucagon-like peptide 1 response is important for improved beta-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes. 2013;62(9):3044–52.PubMedPubMedCentral
41.
go back to reference Martinussen C, Bojsen-Moller KN, Dirksen C, et al. Augmented GLP-1 secretion as seen after gastric bypass may be obtained by delaying carbohydrate digestion. J Clin Endocrinol Metab. 2019;104(8):3233–44.PubMed Martinussen C, Bojsen-Moller KN, Dirksen C, et al. Augmented GLP-1 secretion as seen after gastric bypass may be obtained by delaying carbohydrate digestion. J Clin Endocrinol Metab. 2019;104(8):3233–44.PubMed
42.
go back to reference Dirksen C, Jorgensen NB, Bojsen-Moller KN, et al. Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass. Diabetologia. 2012;55(7):1890–901.PubMed Dirksen C, Jorgensen NB, Bojsen-Moller KN, et al. Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass. Diabetologia. 2012;55(7):1890–901.PubMed
43.
go back to reference Kunutsor SK. Gamma-glutamyltransferase-friend or foe within? Liver Int: official journal of the International Association for the Study of the Liver. 2016;36(12):1723–34. Kunutsor SK. Gamma-glutamyltransferase-friend or foe within? Liver Int: official journal of the International Association for the Study of the Liver. 2016;36(12):1723–34.
44.
go back to reference Nilssen O, Forde OH. Seven-year longitudinal population study of change in gamma-glutamyltransferase: the Tromso Study. Am J Epidemiol. 1994;139(8):787–92.PubMed Nilssen O, Forde OH. Seven-year longitudinal population study of change in gamma-glutamyltransferase: the Tromso Study. Am J Epidemiol. 1994;139(8):787–92.PubMed
45.
go back to reference Nilssen O, Forde OH, Brenn T. The Tromso Study. Distribution and population determinants of gamma-glutamyltransferase. Am J Epidemiol. 1990;132(2):318–26.PubMed Nilssen O, Forde OH, Brenn T. The Tromso Study. Distribution and population determinants of gamma-glutamyltransferase. Am J Epidemiol. 1990;132(2):318–26.PubMed
46.
go back to reference Satishchandran A, Ambade A, Rao S, et al. MicroRNA 122, regulated by GRLH2, protects livers of mice and patients from ethanol-induced liver disease. Gastroenterology. 2018;154(1):238–52 e7.PubMed Satishchandran A, Ambade A, Rao S, et al. MicroRNA 122, regulated by GRLH2, protects livers of mice and patients from ethanol-induced liver disease. Gastroenterology. 2018;154(1):238–52 e7.PubMed
47.
go back to reference Zhang Y, Jia Y, Zheng R, et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem. 2010;56(12):1830–8.PubMed Zhang Y, Jia Y, Zheng R, et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem. 2010;56(12):1830–8.PubMed
48.
go back to reference Starlinger P, Hackl H, Pereyra D, et al. Predicting postoperative liver dysfunction based on blood derived microRNA signatures. Hepatology. 2019;69(6):2636–51.PubMedPubMedCentral Starlinger P, Hackl H, Pereyra D, et al. Predicting postoperative liver dysfunction based on blood derived microRNA signatures. Hepatology. 2019;69(6):2636–51.PubMedPubMedCentral
49.
go back to reference Jones A, Danielson KM, Benton MC, et al. miRNA signatures of insulin resistance in obesity. Obesity. 2017;25(10):1734–44.PubMed Jones A, Danielson KM, Benton MC, et al. miRNA signatures of insulin resistance in obesity. Obesity. 2017;25(10):1734–44.PubMed
Metadata
Title
Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients
Authors
G. Rega-Kaun
C. Kaun
G. Jaegersberger
M. Prager
M. Hackl
S. Demyanets
J. Wojta
P. J. Hohensinner
Publication date
01-02-2020
Publisher
Springer US
Published in
Obesity Surgery / Issue 2/2020
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-019-04190-y

Other articles of this Issue 2/2020

Obesity Surgery 2/2020 Go to the issue