Metabolic Brain Disease

, Volume 32, Issue 3, pp 757–764 | Cite as

Fasting leptin and glucose in normal weight, over weight and obese men and women diabetes patients with and without clinical depression

  • Darakhshan Jabeen Haleem
  • Shehnaz Sheikh
  • Asher Fawad
  • Muhammad A. Haleem
Original Article


A large number of diabetes patients suffer from major depression and are at high risk of mortality. In view of a role of leptin in diabetes, depression and energy homeostasis, the present study concerns circulating levels of leptin in different BMI groups of un-depressed and depressed diabetes patients. Six hundred thirty male and female patients with a primary diagnosis of diabetes were grouped according to BMI and with or without clinical symptoms of depression. Age matched healthy, normal weight male and female volunteers without clinical symptoms of depression or diabetes were taken as controls. Blood samples were obtained after an overnight fast of 12 h. Serum was stored for the determination of leptin and glucose. We found that there were more female than male diabetes patients with comorbid depression. Fasting leptin was higher in normal weight non-diabetes women than men; but comparable in normal weight men and women diabetes patients. Fasting glucose levels were higher in diabetes than non diabetes groups; values were comparable in men and women. Depression was associated with a decrease and increase in leptin respectively in normal-overweight and obese men and women diabetes patients. Glucose levels were also higher in obese depressed than un-depressed diabetes patients. The results suggested that the female gender is at greater risk to comorbid diabetes with depression. Adipo-insular axis plays an important role in diabetes, associated depression and in the greater risk of the female gender to comorbid diabetes with depression.


Leptin Diabetes Depression Obesity Gender difference Adipo-insular axis 


Compliance with ethical standards

Conflicts of interest

There are no conflicts of interest.


  1. Ali S, Stone MA, Peters JL, Davies MJ, Khunti K (2006) The prevalence of co-morbid depression in adults with type 2 diabetes: a systematic review and meta-analysis. Diabet Med 23:1165–1173CrossRefPubMedGoogle Scholar
  2. Atmaca M, Kuloglu M, Tezcan E, Ustundag B, Bayik Y (2002) Serum leptin and cholesterol levels in patients with bipolar disorder. Neuropsychobiology 46:176–179CrossRefPubMedGoogle Scholar
  3. Bandaru P, Shankar A (2011) Association between plasma leptin levels and diabetes mellitus. Metab Syndr Relat Disord 9:19–23CrossRefPubMedPubMedCentralGoogle Scholar
  4. Borer KT (2014) Counterregulation of insulin by leptin as key component of autonomic regulation of body weight. World J Diabetes 5:606–629CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bot M, Pouwer F, Zuidersma M, van Melle JP, de Jonge P (2012) Association of coexisting diabetes and depression with mortality after myocardial infarction. Diabetes Care 35:503–509CrossRefPubMedPubMedCentralGoogle Scholar
  6. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295CrossRefPubMedGoogle Scholar
  7. Eckel RH, Kahn SE, Ferrannini E, Goldfine AB, Nathan DM, Schwartz MW, Smith RJ, Smith SR (2011) Obesity and type 2 diabetes: what can be unified and what needs to be individualized? Endocrine Society; American Diabetes Association; European Association for the Study of diabetes. Diabetes 34:1424–1430Google Scholar
  8. Esel E, Ozsoy S, Tutus A, Sofuoglu S, Kartalci S, Bayram F, Kokbudak Z, Kula M (2005) Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 29:565–570CrossRefGoogle Scholar
  9. Fehmann HC, Peiser C, Bode HP, Stamm M, Staats P, Hedetoft C, Lang RE, Göke B (1997) Leptin: a potent inhibitor of insulin secretion. Peptides 18:1267–1273CrossRefPubMedGoogle Scholar
  10. Fiore V, Marci M, Poggi A, Giagulli VA, Licchelli B, Iacoviello M, Guastamacchia E, De Pergola G, Triggiani V (2015) The association between diabetes and depression: a very disabling condition. Endocrine 48:14–24CrossRefPubMedGoogle Scholar
  11. Fischer S, Hanefeld M, Haffner SM, Fusch C, Schwanebeck U, Köhler C, Fücker K, Julius U (2002) Insulin-resistant patients with type 2 diabetes mellitus have higher serumleptin levels independently of body fat mass. Acta Diabetol 39:105–110CrossRefPubMedGoogle Scholar
  12. Fuente-Martín E, Argente-Arizón P, Ros P, Argente J, Chowen JA (2013) Sex differences in adipose tissue: it is not only a question of quantity and distribution. Adipocytes 2:128–134CrossRefGoogle Scholar
  13. Geer EB, Shen W (2009) Gender differences in insulin resistance, body composition, and energy balance. Gend Med 6(Suppl 1):60–75CrossRefPubMedPubMedCentralGoogle Scholar
  14. Gobinath AR, Mahmoud R, Galea LA (2015) Influence of sex and stress exposure across the lifespan on endophenotypes of depression: focus on behavior, glucocorticoids, and hippocampus. Front Neurosci 8:420CrossRefPubMedPubMedCentralGoogle Scholar
  15. Haffner SM, Stern MP, Miettinen H, Wei M, Gingerich RL (1996) Leptin concentrations in diabetic and nondiabetic Mexican-Americans. Diabetes 45:822–824CrossRefPubMedGoogle Scholar
  16. Haleem DJ (2011) Raphe-hippocampal serotonin neurotransmission in the sex related differences of adaptation to stress: focus on serotonin-1A receptor. Curr Neuropharmacol 9:512–521CrossRefGoogle Scholar
  17. Haleem DJ (2014) Investigations into the involvement of leptin in responses to stress. Behav Pharmacol 25:384–397PubMedGoogle Scholar
  18. Haleem DJ (2016) Drug targets for obesity and depression: from serotonin to leptin. Curr Drug Targets 17:1282–1291CrossRefPubMedGoogle Scholar
  19. Haleem DJ, Haque Z, Inam QU, Ikram H, Haleem MA (2015) Behavioral, hormonal and central serotonin modulating effects of injected leptin. Peptides 74:1–8CrossRefPubMedGoogle Scholar
  20. Haque Z, Akbar N, Yasmin F, Haleem MA, Haleem DJ (2013) Inhibition of immobilization stress-induced anorexia, behavioral deficits, and plasma corticosterone secretion by injected leptin in rats. Stress 16:353–362CrossRefPubMedGoogle Scholar
  21. Hickey MS, Israel RG, Gardiner SN, Considine RV, McCammon MR, Tyndall GL, Houmard JA, Marks RH, Caro JF (1996) Gender differences in serum leptin levels in humans. Biochem Mol Med 59:1–6CrossRefPubMedGoogle Scholar
  22. Hopkins M, Blundell JE (2016) Energy balance, body composition, sedentariness and appetite regulation: pathways to obesity. Clin Sci (Lond) 130:1615–1628CrossRefGoogle Scholar
  23. Ioffe E, Moon B, Connolly E, Friedman JM (1998) Abnormal regulation of the leptin gene in the pathogenesis of obesity. Proc Natl Acad Sci U S A 95:11852–11857CrossRefPubMedPubMedCentralGoogle Scholar
  24. Jow GM, Yang TT, Chen CL (2006) Leptin and cholesterol levels are low in major depressive disorder, but high in schizophrenia. J Affect Disord 90:21–27CrossRefPubMedGoogle Scholar
  25. Juutilainen A, Kortelainen S, Lehto S, Rönnemaa T, Pyörälä K, Laakso M (2004) Gender difference in the impact of type 2 diabetes on coronary heart disease risk. Diabetes Care 27:2898–2904CrossRefPubMedGoogle Scholar
  26. Katon W, Fan MY, Unützer J, Taylor J, Pincus H, Schoenbaum M (2008) Depression and diabetes: a potentially lethal combination. J Gen Intern Med 23:1571–1575CrossRefPubMedPubMedCentralGoogle Scholar
  27. Kieffer TJ, Habener JF (2000) The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J Physiol Endocrinol Metab 278:E1–E14PubMedGoogle Scholar
  28. Klok MD, Jakobsdottir S, Drent ML (2007) The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev 8:21–34CrossRefPubMedGoogle Scholar
  29. Könner AC, Brüning JC (2012) Selective insulin and leptin resistance in metabolic disorders. Cell Metab 16:144–152CrossRefPubMedGoogle Scholar
  30. Kraus T, Haack M, Schuld A, Hinze-Selch D, Pollmächer T (2001) Low leptin levels but normal body mass indices in patients with depression or schizophrenia. Neuroendocrinology 73:243–247CrossRefPubMedGoogle Scholar
  31. Laferrère B, Caixas A, Fried SK, Bashore C, Kim J, Pi-Sunyer FX (2002) A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects. Eur J Endocrinol 146:839–845CrossRefPubMedPubMedCentralGoogle Scholar
  32. Lin EH, Heckbert SR, Rutter CM, Katon WJ, Ciechanowski P, Ludman EJ, Oliver M, Young BA, McCulloch DK, Von Korff M (2009) Depression and increased mortality in diabetes: unexpected causes of death. Ann Fam Med 7:414–421CrossRefPubMedPubMedCentralGoogle Scholar
  33. Liu J, Garza JC, Bronner J, Kim CS, Zhang W, Lu XY (2010) Acute administration of leptin produces anxiolytic-like effects: a comparison with fluoxetine. Psychopharmacology 207:535–545CrossRefPubMedGoogle Scholar
  34. Lu XY, Kim CS, Frazer A, Zhang W (2006) Leptin: a potential novel antidepressant. Proc Natl Acad Sci U S A 103:1593–1598CrossRefPubMedPubMedCentralGoogle Scholar
  35. Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG (2010) Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 67:220–229CrossRefPubMedGoogle Scholar
  36. Lustman PJ, Clouse RE (2005) Depression in diabetes patients: the relationship between mood and glycemic control. J Diabetes Complicat 19:113–122PubMedGoogle Scholar
  37. McCollum M, Hansen LS, Lu L, Sullivan PW (2005) Gender differences in diabetes mellitus and effects on self-care activity. Gend Med 2:246–254CrossRefPubMedGoogle Scholar
  38. Montague CT, Prins JB, Sanders L, Digby JE, O'Rahilly S (1997) Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes 46:342–347CrossRefPubMedGoogle Scholar
  39. Monti V, Carlson JJ, Hunt SC, Adams TD (2006) Relationship of ghrelin and leptin hormones with body mass index and waist circumference in a random sample of adults. J Am Diet Assoc 106:822–828CrossRefPubMedGoogle Scholar
  40. Moreno-Aliaga MJ, Stanhope KL, Havel PJ (2001) Transcriptional regulation of the leptin promoter by insulin-stimulated glucose metabolism in 3 t3-l1 adipocytes. Biochem Biophys Res Commun 283:544–548CrossRefPubMedGoogle Scholar
  41. Myers MG Jr, Leibel RL, Seeley RJ, Schwartz MW (2010) Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab 21:643–651CrossRefPubMedPubMedCentralGoogle Scholar
  42. Sayeed MA, Azad Khan AK, Mahtab H, Ahsan KA, Banu A, Khanam PA, Ahrén B (2003) Leptin is reduced in lean subjects with type 2 diabetes in Bangladesh. Diabetes Care 26:547CrossRefPubMedGoogle Scholar
  43. Seufert J (2004) Leptin effects on pancreatic beta-cell gene expression and function. Diabetes 53(Suppl 1):S152–S158CrossRefPubMedGoogle Scholar
  44. Seufert J, Kieffer TJ, Leech CA, Holz GG, Moritz W, Ricordi C, Habener JF (1999) Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. J Clin Endocrinol Metab 84:670–676PubMedPubMedCentralGoogle Scholar
  45. Siddiqui S (2014) Depression in type 2 diabetes mellitus--a brief review. Diabetes Metab Syndr 8:62–65CrossRefPubMedGoogle Scholar
  46. Siddiqui MA, Khan MF, Carline TE (2013) Gender differences in living with diabetes mellitus. Mater Sociomed 25:140–142CrossRefPubMedPubMedCentralGoogle Scholar
  47. Smith U, Kahn BB (2016) Adipose tissue regulates insulin sensitivity: role of adipogenesis, de novo lipogenesis and novel lipids. J Intern Med 280:465–475CrossRefPubMedGoogle Scholar
  48. Sudi KM, Tafeit E, Möller R, Reiterer E, Gallistl S, Borkenstein MH (2000) Relationship between different subcutaneous adipose tissue layers, fat mass, and leptin in response to short-term energy restriction in obese girls. Am J Hum Biol 12:803–813CrossRefPubMedGoogle Scholar
  49. Ter Horst JP, Carobrez AP, van der Mark MH, de Kloet ER, Oitzl MS (2012) Sex differences in fear memory and extinction of mice with forebrain-specific disruption of the mineralocorticoid receptor. Eur J Neurosci 36:3096–3102CrossRefPubMedGoogle Scholar
  50. Van Harmelen V, Reynisdottir S, Eriksson P, Thörne A, Hoffstedt J, Lönnqvist F, Arner P (1998) Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 47:913–917CrossRefPubMedGoogle Scholar
  51. Westling S, Ahrén B, Träskman-Bendz L, Westrin A (2004) Low CSF leptin in female suicide attempters with major depression. J Affect Disord 81:41–48CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Darakhshan Jabeen Haleem
    • 1
  • Shehnaz Sheikh
    • 2
  • Asher Fawad
    • 3
  • Muhammad A. Haleem
    • 4
  1. 1.Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug ResearchUniversity of KarachiKarachiPakistan
  2. 2.Department of BiochemistryLiaquat National Hospital & Medical CollegeKarachiPakistan
  3. 3.Baqai Institute of Diabetology and EndocrinologyKarachiPakistan
  4. 4.Department of Biomedical EngineeringSir Syed University of Engineering and TechnologyKarachiPakistan

Personalised recommendations