Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus

International Journal of Obesity volume 24, pages 976–981 (2000)Cite this article

Abstract

OBJECTIVE: To determine the relation between plasma leptin concentrations and metabolic control in human diabetes mellitus.

DESIGN AND SUBJECTS: Cross sectional study consisting of 156 patients with diabetes mellitus type 1 (n=42), type 2 (n=114), and non-diabetic subjects (n=74).

RESULTS: Plasma leptin concentrations were lower (P<0.05) in type 1 (8.3±1.7 ng/ml) and type 2 diabetic (14.9±1.8 ng/ml) than in non-diabetic humans (18.3±1.9 ng/ml). Only female type 1 and type 2 diabetic subjects also had decreased leptin/BMI ratios (P<0.05 vs non-diabetic females). The log rank test identified age-adjusted correlation of plasma leptin concentration with sex (P<0.0004) and body mass index (P<0.0218), but not with glycosylated haemoglobin A1c (P>0.5) in all groups. Plasma leptin was correlated with age (P<0.0058) and serum triglycerides (P<0.0199) in type 1 diabetic patients, and with serum cholesterol (P<0.0059) and LDL (P<0.0013) in type 2 diabetic patients.

CONCLUSIONS: Defective leptin production and/or secretion might be present independently of metabolic control in female patients with type 1 or type 2 diabetes mellitus.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Pelleymounter M, Cullen M, Baker M, Hecht R, Winters D, Boone T, Collins F . Effects of the ob gene product on body weight regulation in ob/ob mice Science 1995 269: 540–543.

    Article  CAS  Google Scholar 

  2. Chen H, Charlat O, Tartaglia LA, Woolf EA, Wang X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Bretbart RE, Duyk GM, Tepper RI, Morgenstern JP . Evidence that the diabetic gene encodes the leptin receptor; identification of a mutation in the leptin receptor gene in db/db mice Cell 1996 84: 491–495.

    Article  CAS  Google Scholar 

  3. Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV . Leptin: the tale of an obesity gene Diabetes 1996 45: 1455–1462.

    Article  CAS  Google Scholar 

  4. Considine RV, Considine EL, William CJ, Nyce MR, Zhang P, Opentanova I, Ohannesian JP, Kolaczynski JW, Bauer TL, Moore JH, Caro JF . Mutation screening and identification of a sequence variation in the human ob gene coding Biochem Biophys Res Commun 1996 220: 735–739.

    Article  CAS  Google Scholar 

  5. Montague CT, Prins JB, Sanders L, Digby JE, O'Rahilly S . Depot and sex specific differences in human leptin mRNA expression: implications for the control of regional fat distribution Diabetes 1997 46: 342–347.

    Article  CAS  Google Scholar 

  6. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro J . Serum immunoreactive leptin concentrations in normal-weight and obese humans N Engl J Med 1996 334: 292–295.

    Article  CAS  Google Scholar 

  7. Kennedy A, Gettys TW, Watson P, Wallace P, Ganaway E, Pan Q, Garvey WT . The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity and energy expenditure J Clin Endocr Metab 1997 82: 1293–1300.

    CAS  PubMed  Google Scholar 

  8. Reaven GM . Role of insulin resistance in human disease, Banting lecture 1988 Diabetes 1988 37: 1595–1607.

    Article  CAS  Google Scholar 

  9. Kiefer TJ, Heller RS, Leech CA, Holz GG, Habener JF . Leptin suppression of insulin secretion by the activation of ATP-sensitive K channels in pancreatic beta cells Diabetes 1997 46: 1087–1093.

    Article  Google Scholar 

  10. Shimabukuro M, Koyama K, Chen G, Wang M-Y, Trieu F, Lee Y, Newgard CB, Unger RH . Direct antidiabetic effect of leptin through triglyceride depletion of tissues Proc Natl Acad Sci USA 1997 94: 4637–4641.

    Article  CAS  Google Scholar 

  11. Nemecz M, Preininger K, Englisch R, Fürnsinn C, Schneider B, Waldhäusl W, Roden M . Acute effect of leptin on hepatic glycogenolysis and gluconeogenesis in perfused liver Hepatology 1999 29: 166–172.

    Article  CAS  Google Scholar 

  12. Müller G, Ertl J, Gerl M, Preibisch G . Leptin impairs metabolic actions of insulin in isolated rat adipocytes J Biol Chem 1997 272: 10585–10593.

    Article  Google Scholar 

  13. Wabitsch M, Jensen PB, Blum WF, Chrostoffersen CT, Englaro P, Heinze E, Rascher W, Teller W, Tornqvist H, Hauner H . Insulin and cortisol promote leptin production in cultured human fat cells Diabetes 1996 45: 1435–1438.

    Article  CAS  Google Scholar 

  14. Segal KR, Landt M, Klein S . Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men Diabetes 1996 45: 988–991.

    Article  CAS  Google Scholar 

  15. Kautzky-Willer A, Ludwig C, Nowotny P, Roden A, Huemer C, Widhalm F, Vierhapper H, Waldhäusl W, Roden M . Elevation of plasma leptin concentrations in obese hyperinsulinemic hypothyroidism before and after treatment Eur J Clin Invest 1999 29: 395–403.

    Article  CAS  Google Scholar 

  16. Turpeinen AK, Haffner SM, Louheranta AM, Niskanen LK, Miettinen H, Uusitupa MIJ . Serum leptin in subjects with impaired glucose tolerance in relation to insulin sensitvity and first-phase insulin response Int J Obes Relat Metab Disord 1997 21: 284–287.

    Article  CAS  Google Scholar 

  17. Haffner S, Stern M, Miettinen H, Ming W, Gingerich R . Leptin concentrations in diabetic and nondiabetic Mexican-Americans Diabetes 1996 45: 822–824.

    Article  CAS  Google Scholar 

  18. Mantzoros CS, Dunaif A, Flier JS . Leptin concentrations in the polycystic ovary syndrome J Clin Endocr Metab 1997 82: 1687–1691.

    CAS  PubMed  Google Scholar 

  19. Laughlin GA, Yen SSC . Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea J Clin Endocr Metab 1997 82: 318–321.

    Article  CAS  Google Scholar 

  20. Dagogo-Jack S, Fanelli C, Paramore D, Brothers J, Landt M . Plasma leptin and insulin relationships in obese and nonobese humans Diabetes 1996 45: 695–698.

    Article  CAS  Google Scholar 

  21. Pratley RE, Nicolson M, Bogardus C, Ravussin E . Effects of acute hyperinsulinemia on plasma leptin concentrations in insulin-sensitive and insulin-resistant Pima Indians J Clin Endocr Metab 1996 81: 4418–4421.

    CAS  PubMed  Google Scholar 

  22. Ryan AS, Elahi D . The effects of acute hyperglycemia and hyperinsulinemia on plasma leptin levels: its relationships with body fat, visceral obesity, and age in women J Clin Endocr Metab 1996 81: 4433–4438.

    CAS  PubMed  Google Scholar 

  23. Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, Marco C, Caro JF . Nocturnal rise of leptin in lean, obese, and non-insulin dependent diabetes mellitus subjects J Clin Invest 1996 97: 1344–1347.

    Article  CAS  Google Scholar 

  24. Shimizu H, Kakizaki S, Tsuchiya T, Nagamine T, Takagi H, Takayama H, Kobayashi I, Mori M . An increase of circulating leptin in patients with liver cirrhosis Int J Obes Relat Metab Disord 1998 22: 1234–1238.

    Article  CAS  Google Scholar 

  25. Widjaja A, Stratton I, Horn R, Holman R, Turner R, Brabant G . UKPDS: plasma leptin, obesity and plasma insulin in type 2 diabetic subjects J Clin Endocr Metab 1997 82: 654–658.

    Article  CAS  Google Scholar 

  26. Kristensen K, Pedersen SB, Fisker S, Nørrelund H, Rosenfalck AM, Jørgensen JOL, Richelsen B . Serum leptin levels and leptin expression in growth hormone (GH)-deficient and healthy adults: influence of GH treatment, gender, and fasting Metabolism 1998 47: 1514–1519.

    Article  CAS  Google Scholar 

  27. Ostlund RE, Yang JW, Klein S, Gingerich R . Relation between plasma leptin concentration and body fat, gender, diet, age and metabolic covariates J Clin Endocr Metab 1996 81: 3909–3913.

    CAS  PubMed  Google Scholar 

  28. Moller N, O'Brien P, Nair KS . Disruption of the relationship between fat content and leptin levels with aging in humans J Clin Endocr Metab 1998 83: 931–934.

    CAS  PubMed  Google Scholar 

  29. Beck-Nielsen H. Groop LC . Metabolic and genetic characterization of prediabetic states. Sequence of events leading to non-insulin-dependent diabetes mellitus J Clin Invest 1994 94: 1714–1721.

    Article  Google Scholar 

  30. Larsson H, Elmstahl S, Ahren B . Plasma leptin levels correlate to islet function independently of body fat in postmenopausal women Diabetes 1996 45: 1580–1584.

    Article  CAS  Google Scholar 

  31. Clement K, Lahlou N, Ruiz J, Hager J, Bougneres P, Basdevant A, Guygrand B, Froguel P . Association of poorly controlled diabetes with low serum leptin in morbid obesity Int J Obes Relat Metab Disord 1997 21: 556–561.

    Article  CAS  Google Scholar 

  32. Malmstrom R, Taskinen M, Karonen S, Yki-Jarvinen H . Insulin increases plasma leptin concentrations in normal subjects and patients with NIDDM Diabetologia 1996 39: 993–996.

    Article  CAS  Google Scholar 

  33. Kolaczynski JW, Nyce MR, Considine RV, Boden G, Nolan JJ, Henry RR, Mudaliar SR, Olefsky J, Caro JF . Acute and chronic effect of insulin on leptin production in humans Diabetes 1996 40: 699–701.

    Article  Google Scholar 

  34. O'Meara NM, Sturis J, Van Cauter E, Polonsky KS . Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus J Clin Invest 1993 92: 262–271.

    Article  CAS  Google Scholar 

  35. Schmitz O, Fisker S, Ørskov L, Hove KY, Nyholm B, Moller N . Effects of hyperinsulinemia and hypoglycemia on circulating leptin levels in healthy lean males Diabetes Metab 1997 23: 80–83.

    CAS  PubMed  Google Scholar 

  36. Nolan JJ, Olefsky JM, Nyce MR, Considine RV, Caro JF . Effect of troglitazone on leptin production: studies in vitro and in human subjects Diabetes 1996 45: 1276–1278.

    Article  CAS  Google Scholar 

  37. Tritos NA, Mantzoros CS . Leptin: its role in obesity and beyond Diabetologia 1997 40: 1371–1379.

    Article  CAS  Google Scholar 

  38. Meyer C, Robson D, Rackovsky N, Nadkarni V, Gerich J . Role of kidney in human leptin metabolism Am J Physiol 1997 273: E903–E907.

    CAS  PubMed  Google Scholar 

  39. Rainwater DL, Comuzzie AG, VandeBerg JL, Mahaney MC, Blangero J . Serum leptin levels are independently correlated with two measures of HDL Atherosclerosis 1997 132: 237–243.

    Article  CAS  Google Scholar 

  40. Unger RH . Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications Diabetes 1995 44: 863–870.

    Article  CAS  Google Scholar 

  41. Roden M, Price TB, Perseghin G, Falk-Petersen K, Cline GW, Rothman DL, Shulman GI . Mechanism of free fatty acid induced insulin resistance in humans J Clin Invest 1996 97: 2859–2865.

    Article  CAS  Google Scholar 

  42. Peinò R, Fernández Alvarez J, Penãlva A, Considine RV, Rodriguez-Segade S, Rodriguez-Garcia J, Cordido F, Casanueva FF, Dieguez C . Acute changes in free-fatty acids (FFA) do not alter serum leptin levels J Endocr Invest 1998 21: 526–530.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Vienna, Austria

    M Roden, C Ludwig, P Nowotny, M Clodi, H Vierhapper, A Roden & W Waldhäusl

  2. Department of Medical Statistics, University of Vienna, Vienna, Austria

    B Schneider

Authors
  1. M Roden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Nowotny
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Clodi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Vierhapper
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Roden
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W Waldhäusl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Roden.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roden, M., Ludwig, C., Nowotny, P. et al. Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus. Int J Obes 24, 976–981 (2000). https://doi.org/10.1038/sj.ijo.0801266

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801266

Keywords

This article is cited by

Search

Advanced search

Quick links