CHANGE OF GHRELIN CONCENTRATION IN TYPE 2 DIABETES MELLITUS ASSOCIATED WITH OBESITY IN THE EARLY AND DELAYED PERIOD AFTER LAPAROSCOPIC SLEEVE GASTRECTOMY
S.V. Kosiukhno1, O.Yu. Usenko2, I.M. Todurov1, О.І. Plehutsa1
- State Scientific Institution “Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine”, Kyiv, Ukraine
- Shalimov National Institute of Surgery and Transplantology, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz69.03.050
Abstract
Laparoscopic sleeve gastrectomy (LSG) is an effective
method of treating obesity complicated by type 2 diabetes
mellitus (T2DM). The performance of this metabolic surgical
intervention involves removal fundus of the stomach, which
in turn leads to an effect on the eating behavior of patients
in the form of a decrease in appetite and loss of excess body
weight with a parallel effect on the compensation of T2DM
in the postoperative period, regardless of the loss of body
weight. At present, mechanisms of T2DM compensation after
LSG have not yet been clearly defined. The aim of our study
was to study the effect of LSG on the dynamics of changes
in the blood plasma ghrelin levels in patients with T2DM
associated with obesity. The plasma ghrelin levels were
assessed in the fasted state, 15, 30, 60, and 90 min after a
standard breakfast carbohydrate preload, which included 125
ml of Nutricia Nutridrink, a balanced high-energy protein.
The examination was carried out before the operation, on the 4th postoperative day and 3 months after the operation. 7
patients were diagnosed with T2DM for the first time, 3 had
a history of diabetes for 2 years, one patient had a history of
3.5 years, and another had a history of 10 years. The average
content of glycated hemoglobin before the operation was 7.7 ±
1.6%, 3 months after LSG - 5.9 ± 0.4%. The fasting ghrelin
concentration before LSG performing was 6.8 ± 1.1 ng/ml, on
the 4th postoperative day – 4.6 ± 0.7 ng/ml, and 3 months after
the operation – 4.4 ± 0.6 ng/ml (P = 0.001 in comparison with
preoperative indicators). The peak insulin concentration was
noted 30 min after the carbohydrate preload 3 months after
the operation and was 175.1 ± 9.9 μU/ml, and its fasting levels
in the postoperative period reached a statistically significant
difference compared to the preoperative values (30 ± 11.3
μU/ml before surgery and 25.3 ± 10.9 μU/ml 3 months after
LSG). Thus, LSG leads to an early and significant suppression
of fasting ghrelin secretion in patients with obesity-associated
T2DM and likely to restore insulin secretion and/or reduce
insulin resistance. Rapid postoperative improvement of
carbohydrate metabolism components indicates the importance
of the early reduction of ghrelin secretion in combination
with the incretin effect of LSG in the implementation of the
mechanisms of early compensation of T2DM and explains the
metabolic activity of this operation and the significant role of
the stomach in the regulation of glucose metabolism.
Keywords:
type 2 diabetes mellitus associated with obesity; bariatric/metabolic surgery; laparoscopic sleeve gastrectomy; ghrelin.
References
- Danaei G, Finucane MM, Lu Y, et al. Global burden of metabolic risk factors of chronic diseases collaborating group (blood glucose). National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 countryyears and 2.7 million participants. Lancet. 2011;378 (9785):31-40.
CrossRef
PubMed
- Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and metanalysis. Am J Med 2009;122(3):248-56.
CrossRef
PubMed
- Thrasher J. Pharmacologic management of type 2 diabetes mellitus: Available therapies. Am J Med. 2017;130(6S):S4-S17.
CrossRef
PubMed
- Cho JM, Kim HJ Menzo El, Park S, Szomstein S, Rosenthal RJ. Effect of sleeve gastrectomy on type 2 diabetes as an alternative treatment modality to Roux-en-Y gastric bypass: systemic review and meta-analysis. Surg Obes Relat Dis. 2015 Mar 5. pii: S1550-7289(15)00056-8.
- Angrisani L, Santonicola A, Iovino P, et al. IFSO Worldwide Survey 2016: Primary, Endoluminal, and Revisional Procedures. Obes Surg. 2018;28(12):3783-94.
CrossRef
PubMed
- Blaire Anderson, Noah J. Switzer, Ahmad Almamar, Xinzhe Shi, Daniel W, Birch, Shahzeer Karmali. The impact of laparoscopic sleeve gastrectomy on plasma ghrelin levels: A systematic review. Obes Surg. 2013;23(9):14760-80.
CrossRef
PubMed
- Todurov IM, Kosiukhno SV, Perekhrestenko OV, Kalashnikov OO, Potapov OА, Plehutsa ОІ. Dynamics of glucagon-like peptide-1 after laparoscopic sleeve gastrectomy in patients with type 2 diabetes mellitus associations with obesity. Fiziol Zh. 2021; 67 (4):44-51.
CrossRef
- Hutch CR, Sandoval D. The role of GLP-1 in the metabolic success of bariatric surgery. Endocrinology. 2017;158(12):4139-51.
CrossRef
PubMed PubMedCentral
- Cummings DE, Rubino F. Metabolic surgery for the treatment of type 2 diabetes in obese individuals. Diabetologia. 2018;61(2):257-64.
CrossRef
PubMed PubMedCentral
- Benaiges D, Más-Lorenzo A, Goday A, et al. Laparoscopic sleeve gastrectomy: More than a restrictive bariatric surgery procedure? World J Gastroenterol. 2015;21(41):11804-14.
CrossRef
PubMed PubMedCentral
- Sanches E, Timmermans M, Topal B, et al. Cardiac remodeling in obesity and after bariatric and metabolic surgery; is there a role for gastro-intestinal hormones? Expert Rev Cardiovascul Ther. 2019;17(11):771-90.
CrossRef
PubMed
- Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346(21):1623-30.
CrossRef
PubMed
- Su DW, Wei WW, Yao RR, Yang CJ, Tian H. Research on sleeve gastrectomy for the treatment of rats with type 2 diabetes mellitus and the regulation of ghrelin and intestinal lesions. Eur Rev Med Pharmacol Sci. 2020;24(20):10653-62.
- Casajoana A, Guerrero-Pérez F, García Ruiz de Gordejuela A, et al. Role of gastrointestinal hormones as a predictive factor for long-term diabetes remission: Randomized trial comparing metabolic gastric bypass, sleeve gastrectomy, and greater curvature plication. Obes Surg. 2021;31(4):1733-44.
CrossRef
PubMed
- Andarini S, Kangsaputra FB, Handayani D. Pre- and postprandial acylated ghrelin in obese and normal weight men. Asia Pac J Clin Nutr. 2017;26(Suppl 1):S85-S91.
- Cohen R, Uzzan B, Bihan H, Khochtali I, Reach G, and Catheline JM. Ghrelin levels and sleeve gastrectomy in super-super-obesity. Obes Surg. 2005;15(10):1501-2.
CrossRef
PubMed
- Cottam D, Qureshi FG, Mattar SG, et al. Laparoscopic sleeve gastrectomy as an initial weight-loss procedure for high-risk patients with morbid obesity. Surg Endosc. 2006;20:859-63.
CrossRef
PubMed
- Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402(6762):656-60.
CrossRef
PubMed
- Dornonville de la Cour C, Björkqvist M, Sandvik AK, et al. A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control. Regul Pept. 2001;99(2- 3):141-50.
CrossRef
PubMed
- Popovic V, Miljic D, Pekic S, Pesko P, Djurovic M, Doknic M, et al. Low plasma ghrelin level in gastrectomized patients is accompanied by enhanced sensitivity to the ghrelin-induced growth hormone release. J Clin Endocrinol Metab. 2005;90 (4):2187-91.
CrossRef
PubMed
- Wierup N, Björkqvist M, Weström B, Pierzynowski S, Sundler F, Sjölund K. Ghrelin and motilin are cosecreted from a prominent endocrine cell population in the small intestine. J Clin Endocrinol Metab. 2007;92(9):3573-81.
CrossRef
PubMed
- Wierup N, Sundler F, Heller RS. The islet ghrelin cell. J Mol Endocrinol. 2013;52(1):R35-R49. Published 2013 Dec 19.
CrossRef
PubMed
- Gray SM, Page LC, Tong J. Ghrelin regulation of glucose metabolism. J Neuroendocrinol. 2019;31(7):e12705.
CrossRef
PubMed PubMedCentral
- Gómez-Díaz RA, Gómez-Medina MP, Ramírez-Soriano E, et al. Lower plasma ghrelin levels are found in women with diabetes-complicated pregnancies. J Clin Res Pediatr Endocrinol. 2016;8(4):425-31.
CrossRef
PubMed PubMedCentral
- Segerstolpe Å, Palasantza A, Eliasson P, et al. Singlecell transcriptome profiling of human pancreatic islets in health and type 2 diabetes. Cell Metab. 2016;24(4): 593-607.
CrossRef
PubMed PubMedCentral
- Yada T, Damdindorj B, Rita RS, et al. Ghrelin signalling in β-cells regulates insulin secretion and blood glucose. Diabet Obes Metab. 2014;16 Suppl 1:111-7.
CrossRef
PubMed
- Yanagi S, Sato T, Kangawa K, Nakazato M. The homeostatic force of ghrelin. Cell Metab. 2018;27(4): 786-804.
CrossRef
PubMed
- Gagnon J, Baggio LL, Drucker DJ, Brubaker PL. Ghrelin є novel regulator of GLP-1 secretion. Diabetes. 2015; 64 (5): 1513-21.
CrossRef
PubMed
- Andersen DB, Holst JJ. Peptides in the regulation of glucagon secretion. Peptides. 2022;148:170683.
CrossRef
PubMed
- Broglio F, Gottero C, Benso A, et al. Effects of ghrelin on the insulin and glycemic responses to glucose, arginine, or free fatty acids load in humans. J Clin Endocrinol Metab. 2003;88(9):4268-72.
CrossRef
PubMed
|