Endocrinol Metab.  2017 Jun;32(2):230-240. 10.3803/EnM.2017.32.2.230.

Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects

Affiliations
  • 1Department of Internal Medicine and Clinical Biochemistry Laboratory, King Abdulaziz Hospital, National Guard Health Affairs, Al-Ahsa, Saudi Arabia.
  • 2Clinical Biochemistry Laboratory, Salmaniya Medical Complex, Manama, Bahrain.
  • 3Primary Health Centre, National Guard Health Affairs, Al-Ahsa, Saudi Arabia.
  • 4Department of Medical Biochemistry, Arabian Gulf University College of Medicine and Medical Sciences, Manama, Bahrain. gehaha2002@yahoo.com

Abstract

BACKGROUND
Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM.
METHODS
Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique.
RESULTS
Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM.
CONCLUSION
The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM.

Keyword

Diabetes mellitus; Insulin resistance; Ghrelin; Saudi Arabia

MeSH Terms

Body Weight
Diabetes Mellitus
Diabetes Mellitus, Type 2*
Fasting
Ghrelin*
Healthy Volunteers
Homeostasis
Humans
Insulin Resistance*
Insulin*
Plasma*
Prevalence
Radioimmunoassay
Saudi Arabia
Ghrelin
Insulin

Figure

  • Fig. 1 Fasting plasma levels of ghrelin (pmol/L) in subjects with type 2 diabetes mellitus (T2DM) and healthy non-diabetic controls from Saudi Arabia. Comparison between (A) all subjects with T2DM versus all control subjects, and (B) age- and sex-matched subjects with T2DM versus healthy subjects. Ghrelin levels were consistently significantly lower in patients with T2DM. The horizontal line within each box represents the median, while the lower and upper ends of the box are the 25th and 75th percentiles, the cap of the vertical line is the 95th percentile, and the closed circles are outliers.

  • Fig. 2 Fasting plasma levels of ghrelin (pmol/L); comparison between (A) all study subjects (type 2 diabetes mellitus [T2DM] subjects and controls) with or without insulin resistance (IR) (homeostatic model assessment of insulin resistance [HOMA-IR] ≥3 and <3, respectively), (B) T2DM subjects with or without IR, and (C) T2DM subjects with moderate IR (HOMA-IR 3 to 5) and severe IR (HOMA-IR >5). Ghrelin levels were significantly lower in subjects with IR in (A) and (B) (P<0.001 and P=0.049, respectively). The horizontal line within each box represents the median, while the lower and upper ends of the box are the 25th and 75th percentiles, the cap of the vertical line is the 95th percentile, and the closed circles are outliers.


Cited by  1 articles

Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population
Faris Elbahi Joatar, Ali Ahmed Al Qarni, Muhalab E. Ali, Abdulaziz Al Masaud, Abdirashid M. Shire, Nagalla Das, Khalid Gumaa, Hayder A. Giha
Endocrinol Metab. 2017;32(3):360-369.    doi: 10.3803/EnM.2017.32.3.360.


Reference

1. Joslin EP, Kahn CR, Weir GC. Joslin's diabetes mellitus. 13th ed. Philadelphia: Lea & Febiger;1994. p. 240–264. Chapter 16, Pathogenesis of non-insulin dependent (type II) diabetes mellitus.
2. Report of a WHO Study Group. Diabetes mellitus. World Health Organ Tech Rep Ser. 1985; 727:1–113. PMID: 3934850.
3. Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest. 2006; 116:1802–1812. PMID: 16823478.
4. Grundy SM. Atherogenic dyslipidemia associated with metabolic syndrome and insulin resistance. Clin Cornerstone. 2006; 8(Suppl 1):S21–S27. PMID: 16903166.
Article
5. Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol. 2006; 47:1093–1100. PMID: 16545636.
Article
6. Hunter SJ, Garvey WT. Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system. Am J Med. 1998; 105:331–345. PMID: 9809695.
7. Ma ZA, Zhao Z, Turk J. Mitochondrial dysfunction and beta-cell failure in type 2 diabetes mellitus. Exp Diabetes Res. 2012; 2012:703538. PMID: 22110477.
8. McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes. 2002; 51:7–18. PMID: 11756317.
9. Stannard SR, Johnson NA. Insulin resistance and elevated triglyceride in muscle: more important for survival than “thrifty” genes? J Physiol. 2004; 554:595–607. PMID: 14608009.
Article
10. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001; 7:941–946. PMID: 11479627.
Article
11. Kwon H, Pessin JE. Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne). 2013; 4:71. PMID: 23781214.
Article
12. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013; 2013:139239. PMID: 24455420.
Article
13. Sanchez D, Miguel M, Aleixandre A. Dietary fiber, gut peptides, and adipocytokines. J Med Food. 2012; 15:223–230. PMID: 22181071.
14. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402:656–660. PMID: 10604470.
Article
15. Dezaki K, Sone H, Yada T. Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis. Pharmacol Ther. 2008; 118:239–249. PMID: 18433874.
Article
16. Yada T, Dezaki K, Sone H, Koizumi M, Damdindorj B, Nakata M, et al. Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential. Curr Diabetes Rev. 2008; 4:18–23. PMID: 18220691.
Article
17. Pacifico L, Poggiogalle E, Costantino F, Anania C, Ferraro F, Chiarelli F, et al. Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome. Eur J Endocrinol. 2009; 161:861–870. PMID: 19773372.
Article
18. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature. 2000; 407:908–913. PMID: 11057670.
Article
19. Lopez M, Lage R, Saha AK, Perez-Tilve D, Vazquez MJ, Varela L, et al. Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab. 2008; 7:389–399. PMID: 18460330.
20. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004; 27:1487–1495. PMID: 15161807.
Article
21. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979; 237:E214–E223. PMID: 382871.
Article
22. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008; 294:E15–E26. PMID: 17957034.
Article
23. Laakso M. How good a marker is insulin level for insulin resistance? Am J Epidemiol. 1993; 137:959–965. PMID: 8317453.
Article
24. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28:412–419. PMID: 3899825.
25. Prudom C, Liu J, Patrie J, Gaylinn BD, Foster-Schubert KE, Cummings DE, et al. Comparison of competitive radioimmunoassays and two-site sandwich assays for the measurement and interpretation of plasma ghrelin levels. J Clin Endocrinol Metab. 2010; 95:2351–2358. PMID: 20194708.
Article
26. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002; 346:1623–1630. PMID: 12023994.
Article
27. Poykko SM, Kellokoski E, Horkko S, Kauma H, Kesaniemi YA, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. Diabetes. 2003; 52:2546–2553. PMID: 14514639.
28. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999; 104:787–794. PMID: 10491414.
Article
29. Katsuki A, Urakawa H, Gabazza EC, Murashima S, Nakatani K, Togashi K, et al. Circulating levels of active ghrelin is associated with abdominal adiposity, hyperinsulinemia and insulin resistance in patients with type 2 diabetes mellitus. Eur J Endocrinol. 2004; 151:573–577. PMID: 15538935.
Article
30. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001; 50:707–709. PMID: 11289032.
31. Goldfine ID. The insulin receptor: molecular biology and transmembrane signaling. Endocr Rev. 1987; 8:235–255. PMID: 3308443.
Article
32. Ukkola O, Poykko S, Paivansalo M, Kesaniemi YA. Interactions between ghrelin, leptin and IGF-I affect metabolic syndrome and early atherosclerosis. Ann Med. 2008; 40:465–473. PMID: 19160571.
Article
33. Annuzzi G, De Natale C, Iovine C, Patti L, Di Marino L, Coppola S, et al. Insulin resistance is independently associated with postprandial alterations of triglyceride-rich lipoproteins in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2004; 24:2397–2402. PMID: 15458975.
Article
34. Rocha NP, Siqueira-Catania A, Barros CR, Pires MM, Folchetti LD, Ferreira SR. Analysis of several anthropometric measurements for the identification of metabolic syndrome, with or without disturbance of glucose metabolism. Arq Bras Endocrinol Metabol. 2010; 54:636–643. PMID: 21085769.
35. Dezaki K, Yada T. Islet beta-cell ghrelin signaling for inhibition of insulin secretion. Methods Enzymol. 2012; 514:317–331. PMID: 22975062.
36. Mayfield J. Diagnosis and classification of diabetes mellitus: new criteria. Am Fam Physician. 1998; 58:1355–1362. 1369–1370. PMID: 9803200.
37. Natali A, Muscelli E, Mari A, Balkau B, Walker M, Tura A, et al. Insulin sensitivity and beta-cell function in the offspring of type 2 diabetic patients: impact of line of inheritance. J Clin Endocrinol Metab. 2010; 95:4703–4711. PMID: 20660046.
38. Gayoso-Diz P, Otero-Gonzalez A, Rodriguez-Alvarez MX, Gude F, Garcia F, De Francisco A, et al. Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study. BMC Endocr Disord. 2013; 13:47. PMID: 24131857.
Article
39. UK Prospective Diabetes Study Group. UK Prospective Diabetes Study. XII: Differences between Asian, Afro-Carib-bean and white Caucasian type 2 diabetic patients at diagnosis of diabetes. Diabet Med. 1994; 11:670–677. PMID: 7955993.
40. Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet. 1992; 340:925–929. PMID: 1357346.
Article
41. Horwitz DL, Starr JI, Mako ME, Blackard WG, Rubenstein AH. Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. J Clin Invest. 1975; 55:1278–1283. PMID: 1133173.
Article
Full Text Links
  • ENM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr