Hospital Practices and Research

Ghrelin, Leptin, Insulin, Glucose, and Lipid Profile interactions in Type 2 Diabetic Patients: A Comparative Analysis

Document Type : Original Article

Authors

Mohammed M Laqqan 1
Fatma M Abu-Snayma 2
Maged M Yassin 3

1 Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine

2 Faculty of Science, Department of Medical Technology, Islamic University of Gaza, Gaza, Palestine

3 Faculty of Medicine, Department of Human Physiology, Islamic University of Gaza, Gaza, Palestine

10.30491/hpr.2025.540939.1503
Abstract
Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disease characterized by impaired glucose homeostasis, insulin resistance, and progressive β-cell dysfunction, leading to significant multisystem complications and high global prevalence.
Objectives: This study was conducted to (I) measure and compare concentrations of ghrelin, leptin, and insulin in individuals with T2DM and non-diabetic controls; (II) analyze differences in metabolic profiles between the two groups; and (III) explore potential associations among insulin levels, BMI, and other hormonal and metabolic parameters assessed in the study.
Methods: A case-control study was conducted, comprising 80 individuals diagnosed with T2DM (cases) and 80 non-diabetic controls matched for age, sex, and body mass index (BMI). Clinical data were collected via standardized interviews, and venous blood samples were obtained to assess serum concentrations of ghrelin, leptin, insulin, glucose, lipid profile components, urea, and creatinine.
Results: Compared with the control group, participants with T2DM exhibited significantly higher insulin levels (28.8 ± 23.9 vs. 18.8 ± 13.5 μIU/ml; P = 0.025) and slightly elevated leptin concentrations (7.1 ± 2.7 vs. 5.9 ± 2.2 ng/ml; P = 0.081). Conversely, ghrelin concentrations were significantly lower among cases compared with controls (1189 ± 580 vs. 1531 ± 822 pg/ml; P = 0.038). Glucose (187.4 ± 74.1 vs. 98.3 ± 17.0 mg/dl; P<0.001) and triglyceride levels (212.5 ± 78.9 vs. 143.2 ± 50.4 mg/dl; P<0.001) were also markedly elevated in the cases group. Significant positive correlations were observed between insulin and both glucose (P = 0.011) and triglycerides (P = 0.049), whereas a weak, non-significant inverse correlation was identified between ghrelin and insulin levels (r = -0.213, P = 0.057).
Conclusion: Individuals with T2DM display distinct metabolic and hormonal alterations compared to non-diabetic controls, reflecting a complex endocrine interplay. The presence of both positive and inverse associations among insulin, leptin, and ghrelin highlights the multifaceted regulatory mechanisms underlying the pathophysiology of T2DM.

Keywords

Ghrelin
Insulin
Leptin
Lipid Profile
T2DM
1.       Jermendy G, N das J, Szigethy E, Sz les G, Nagy A, Hídvégi T, et al. Prevalence rate of diabetes mellitus and impaired fasting glycemia in hungary: Crosssectional study on nationally representative sample of people aged 20-69 years. Croat Med J. 2010;51(2):151-6. doi:10.3325/cmj.2010.51.151
2.       Ganesan V, Murugan M, Sundaramurthy R, Soundaram GV. Melioidosis in a tertiary care center from South India: a 5-year experience. Indian J Crit Care Med. 2021;25(3):327. doi:10.5005/jp-journals-10071-23766
3.       Leahy JL. Pathogenesis of type 2 diabetes mellitus. Arch Med Res. 2005;36(3):197-209. doi:10.1016/ j.arcmed.2005.01.003
4.       Chutto MA, Qadri HR, Abro HA, Shaikh MA, Shaikh BA. Awareness of diabetes mellitus and its complications in diabetic patients. Med channel. 2009;15(4):153-6.
5.       Goyal R, Singhal M, Jialal I. Type 2 diabetes. StatPearls. 2023.
6.       Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives. Nat Rev Endocrinol. 2012;8(4): 228-36. doi:10.1038/nrendo.2011.183
7.       Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98. doi:10.1038/nrendo.2017.151
8.       Pozo L, Bello F, Suarez A, Ochoa-Martinez FE, Mendez Y, Chang CH, et al. Novel pharmacological therapy in type 2 diabetes mellitus with established cardiovascular disease: Current evidence. World J Diabetes. 2019;10(5):291-303. doi:10.4239/wjd.v10. i5.291
9.       Azevedo M, Alla S. Diabetes in sub-saharan Africa: kenya, mali, mozambique, Nigeria, South Africa and zambia. Int J Diabetes Dev Countries. 2008;28(4):101. doi:10.4103/0973-3930.45268
10.     McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med. 2010;363(24):2339-50. doi:10.1056/ NEJMra0906948
11.     Wang LK, Wang H, Wu XL, Shi L, Yang RM, Wang YC. Relationships among resistin, adiponectin, and leptin and microvascular complications in patients with type 2 diabetes mellitus. J Int Med Res. 2020;48(4):1-8. doi:10.1177/0300060519870407
12.     Lee SH, Park SY, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J. 2022;46(1):15-37. doi:10.4093/dmj.2021.0280
13.     Bandaru P, Shankar A. Association between plasma leptin levels and diabetes mellitus. Metab Syndr Relat Disord. 2011;9(1):19-23. doi:10.1089/met.2010.0037
14.     Mechanick JI, Zhao S, Garvey WT. Leptin, an adipokine with central importance in the global obesity problem. Glob Heart. 2018;13(2):113-27. doi:10.1016/j.gheart.2017.10.003
15.     Steinberger J, Steffen L, Jacobs Jr DR, Moran A, Hong CP, Sinaiko AR. Relation of leptin to insulin resistance syndrome in children. Obes Res. 2003;11(9):1124-30. doi:10.1038/oby.2003.153
16.     Li YY, Wang H, Yang XX, Wu JJ, Geng HY, Kim HJ, et al. LEPR gene Gln223Arg polymorphism and type 2 diabetes mellitus: a meta-analysis of 3,367 subjects. Oncotarget. 2017;8(37):61927-34. doi:10.18632/ oncotarget.18720
17.     Chandralekshy C, Fathima Beevi O. A comparative study of serum leptin levels among type 2 diabetes mellitus patients and non-diabetic individuals – hospital based cross- sectional study in Thiruvanthpuram, Kerala. Glob J Med Public Health. 2023;12:1.
18.     Devi BJ, Rao Naidu BC, Tutor CK. Association of Leptin with Insulin resistance in Type 2 Diabetes mellitus: a prospective Study. Eur J Cardiovasc Med. 2023;13(2):p1607.
19.     Morton GJ, Schwartz MW. Leptin and the central nervous system control of glucose metabolism. Physiol Rev. 2011;91(2):389-411. doi:10.1152/ physrev.00007.2010
20.     Yassin MM, Mustafa AM, Abujami SM, Jaber EA. Leptin status and biochemical parameters in type 2 diabetic males from Gaza strip. AMBS J. 2017;3:4-10.
21.     Tena-Sempere M, Barreiro ML, Gonzalez LC, Gaytan F, Zhang FP, Caminos JE, et al. Novel expression and functional role of ghrelin in rat testis. Endocrinology. 2002;143(2):717-25. doi:10.1210/endo.143.2.8646
22.     Sato T, Nakamura Y, Shiimura Y, Ohgusu H, Kangawa K, Kojima M. Structure, regulation and function of ghrelin. J Biochem. 2012;151(2):119-28. doi:10.10 93/jb/mvr134
23.     L pez M, Nogueiras R. Ghrelin. Curr Biol. 2023;33(21):R1133-5. doi:10.1016/j.cub.2023.09.009
24.     Jawed M, Saeed MS, Shahid A, Jawed S. Ghrelin level in type 2 diabetes mellitus and obesity. Ann King Edw Med Univ. 2017;23(3). doi:10.21649/akemu.v23i3. 2014
25.     Vijayashankar U, Ramashetty R, Rajeshekara M, Vishwanath N, Yadav AK, Prashant A, et al. Leptin and ghrelin dynamics: unraveling their influence on food intake, energy balance, and the pathophysiology of type 2 diabetes mellitus. J Diabetes Metab Disord. 2024;23(1):427-40. doi:10.1007/s40200-024-01418-2
26.     Serra‐Prat M, Alfaro SR, Palomera E, Casamitjana R, Buquet X, Fern ndez‐Fern ndez C, et al. Relationship between ghrelin and the metabolic syndrome in the elderly: a longitudinal population‐based study. Clin Endocrinol. 2009;70(2):227-32. doi:10.1111/j.1365-2265.2008.03307.x
27.     Ozgen IT, Aydin M, Guven A, Aliyazıcıoglu Y. Characteristics of polycystic ovarian syndrome and relationship with ghrelin in adolescents. J Pediatr Adolesc. Gynecol. 2010;23(5):285-9. doi:10.1016/j. jpag.2010.02.011
28.     Ramachandran A, Snehalatha C, Raghavan A, Nanditha A. Classification and diagnosis of diabetes. Textbook of diabetes. 2024:22-7. doi:10.1002/978 1119697473.ch2
29.     Palestinian Ministry of Health. Diabetic questionnaire, Diabetic clinic records. Palestine: Gaza Strip; 2006.
30.     Yassin MM, Masoud AE, Yasin MM. Serum vitamin D status in type 2 diabetic patients from Gaza Strip. Diabetes Metab Syndr: Clin Res Rev. 2019;13(3): 1865-70. doi:10.1016/j.dsx.2019.04.015
31.     Backstrom C, Hursh-Cesar G. Survey research. Literary Licensing, LLC, Pennsylvania. 2012.
32.     Tang Q, Li X, Song P, Xu L. Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: developments in research and prospects for the future. Drug Discov Ther. 2015;9(6):380-5. doi:10.5582/ ddt.2015.01207
33.     Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. doi:10.1016/j.diabres.2021.109119
34.     Yassin MM, Altibi HI, El Shanti AE. Clinical and biochemical features of type 2 diabetic patients in Gaza Governorate, Gaza Strip. West Afr J Med. 2011;30(1):51-6. doi:10.4314/wajm.v30i1.69918
35.     Yassin MM, AbuMustafa AM, Yassin MM. Serum leptin in diabetic nephropathy male patients from Gaza Strip. Diabetes Metab Syndr: Clin Res Rev. 2019;13(2):1245-50. doi:10.1016/j.dsx.2019.02.004
36.     Umpierrez GE, Smiley D, Kitabchi AE. Narrative review: ketosis-prone type 2 diabetes mellitus. Ann Intern Med. 2006;144(5):350-7. doi:10.7326/0003-4819-144-5-200603070-00011
37.     Olimjonovna KO. Understanding the causes and risk factors of diabetes. biologiya va kimyo fanlari ilmiy jurnali. 2024;2(5):1-7.
38.     Tanenbaum ML, Kane NS, Kenowitz J, Gonzalez JS. Diabetes distress from the patient's perspective: qualitative themes and treatment regimen differences among adults with type 2 diabetes. J Diabetes Complications. 2016;30(6):1060-8. doi:10.1016/j. jdiacomp.2016.04.023
39.     Cheng AY. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. Introduction. Can J Diabetes. 2013;37:S1-3. doi:10.1016/j.jcjd.2013. 01.009
40.     Porksen S, Nielsen LB, Kaas A, Kocova M, Chiarelli F, rskov C, et al. Meal-stimulated glucagon release is associated with postprandial blood glucose level and does not interfere with glycemic control in children and adolescents with new-onset type 1 diabetes. J Clin Endocrinol Metab. 2007;92(8):2910-6. doi:10.12 10/jc.2007-0244
41.     Unachukwu CN, Young EE, Uchenna DI. Self blood glucose monitoring among diabetic patients in Port Harcourt, Nigeria. Afr J Diabetes Med. 2011;19:19-20.
42.     Roaeid RB, Kadiki OA. Prevalence of long-term complications among Type 2 diabetic patients in Benghazi, Libya. J Diabetol. 2011;2(3):3.
43.     Goldney J, Barker MM, Thomas M, Slater T, Mickute M, Sargeant JA, et al. Age at onset of type 2 diabetes and prevalence of vascular disease and heart failure: systematic review and dose-response meta-analysis. J Diabetes Complications. 2024;38(10):108849. doi:10.1016/j.jdiacomp.2024.108849
44.     Coimbra S, Brandão Proença J, Santos-Silva A, Neuparth MJ. Adiponectin, leptin, and chemerin in elderly patients with type 2 diabetes mellitus: a close linkage with obesity and length of the disease. Biomed Res Int. 2014;2014(1):701915. doi:10.1155/2014/ 701915
45.     Moonishaa TM, Nanda SK, Shamraj M, Sivaa R, Sivakumar P, Ravichandran K. Evaluation of leptin as a marker of insulin resistance in type 2 diabetes mellitus. Int J Appl Basic Med Res. 2017;7(3):176-80. doi:10.4103/ijabmr.IJABMR_278_16
46.     Sari A, Shaker Ahmed ZM. Study of serum ghrelin level in patients with diabetes mellitus type 2: in relation with insulin level. Phys Sci. 2023;18(1):1-6.
47.     Wu XY, Song HB, Wang JW. The association between leptin and diabetes: A meta‐analysis. J Obstet Gynaecol. 2024;50(7):1126-31. doi:10.1111/jog.15 942
48.     Al-Hakeim HK, Ali MM. Low ghrelin level is associated with poor control and bad prognosis parameters in obese diabetic patients. J Diabetol. 2012;3(1):5.
49.     Anderwald C, Brabant G, Bernroider E, Horn R, Brehm A, Waldhäusl W, et al. Insulin-dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabetic patients. Diabetes. 2003;52(7):1792-8. doi:10.2337/ diabetes.52.7.1792
50.     Sangiao-Alvarellos S, Cordido F. Effect of ghrelin on glucose‐insulin homeostasis: therapeutic implications. Int J Pept. 2010;2010(1):234709. doi:10.1155/ 2010/234709
51.     Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin-glucose axis. Front Neurosci. 2013;7:51. doi:10.3389/fnins.2013.00051
52.     Artha IM, Bhargah A, Dharmawan NK, Pande UW, Triyana KA, Mahariski PA, et al. High level of individual lipid profile and lipid ratio as a predictive marker of poor glycemic control in type-2 diabetes mellitus. Vasc Health Risk Manag. 2019:149-57. doi:10.2147/VHRM.S209830
53.     Shahwan MJ, Jairoun AA, Farajallah A, Shanabli S. Prevalence of dyslipidemia and factors affecting lipid profile in patients with type 2 diabetes. Diabetes Metab Syndr: Clin Res Rev. 2019;13(4):2387-92. doi:10.1016/j.dsx.2019.06.009
54.     Bjornstad P, Eckel RH. Pathogenesis of lipid disorders in insulin resistance: a brief review. Curr Diab Rep. 2018;18(12):127. doi:10.1007/s11892-018-1101-6
55.     Jaworski K, Sarkadi-Nagy E, Duncan RE, Ahmadian M, Sul HS. Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue. Am J Physiol Gastrointest Liver Physiol. 2007;293(1):G1-4. doi:10.1152/ajpgi.00554.2006
56.     Katsuki A, Sumida Y, Urakawa H, Gabazza EC, Murashima S, Maruyama N, et al. Increased visceral fat and serum levels of triglyceride are associated with insulin resistance in Japanese metabolically obese, normal weight subjects with normal glucose tolerance. Diabetes Care. 2003;26(8):2341-4. doi:10.2337/diacare.26.8.2341
57.  Hsu CC, Chang HY, Huang MC, Hwang SJ, Yang YC, Tai TY, et al. Association between insulin resistance and development of microalbuminuria in type 2 diabetes: a prospective cohort study. Diabetes Care. 2011;34(4):982-7. doi:10.2337/dc10-1718

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