The role of adipokines in causing inflammation and insulin resistance in normal weight and obese patients is generally well studied. However, there are often conflicting results regarding their levels in type 1 diabetes mellitus (T1DM) patients and their relationship to micro- and macrovascular disease. We therefore investigated which serum adipokine levels are independently associated with markers of early atherosclerosis and microvascular complications in patients with T1DM.
A cross-sectional study was performed in the Diabetes Outpatient Clinic of Hippokrateion General Hospital, Thessaloniki, Greece. Sixty T1DM patients (30 females, mean age 38.8 ± 10.6 years, mean diabetes duration 17.4 ± 9.9 years) were included. Plasma adiponectin, leptin, and resistin, carotid artery intima media thickness (cIMT), and arterial stiffness (pulse wave velocity, PWV/SpygmoCor CP System and Mobil-O-Graph 24 h PWA) were assessed.
Leptin and resistin levels were significantly higher in overweight and obese patients (p = 0.002 and p = 0.039, respectively). Adiponectin was the only adipokine negatively correlated with BMI (rs = − 0.41, p = 0.001). We report a bivariate association between serum adiponectin levels and retinopathy (p = 0.007). Resistin was the only adipokine that showed significant correlation with systolic (rs = 0.42, p = 0.001) and diastolic (rs = 0.29, p = 0.024) hypertension and PWV (p = 0.035).
Serum adipokine levels demonstrate similar bivariate associations with anthropometric variables in patients with T1DM to those in normal weight subjects. Although microvascular complications are associated with serum adipokine levels by bivariate analysis, only resistin, an inflammatory marker, is independently associated with arterial stiffness in patients with T1DM.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
The datasets generated during the current study are available from the corresponding author on request.
Body mass index
Central blood pressure
Common carotid artery
Carotid artery intima media thickness
Maximum carotid artery intima media thickness
Michigan Neuropathy Screening Instrument
Chronic kidney disease
Diastolic blood pressure
Estimated glomerular filtration rate
Pulse wave velocity
Systolic blood pressure
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Urine albumin to creatinine ratio
Tuomi T, Santoro N, Caprio S, Cai M, Weng J, Groop L (2014) The many faces of diabetes: a disease with increasing heterogeneity. Lancet 383:1084–1094. https://doi.org/10.1016/S0140-6736(13)62219-9
Minges KE, Whittemore R, Grey M (2013) Overweight and obesity in youth with type 1 diabetes. Annu Rev Nurs Res 31:47–69. https://doi.org/10.1891/0739-6686.31.47
Xu P, Cuthbertson D, Greenbaum C, Palmer JP, Krischer JP, Diabetes Prevention Trial-Type 1 Study Group (2007) Role of insulin resistance in predicting progression to type 1 diabetes. Diabetes Care 30:2314–2320. https://doi.org/10.2337/dc06-2389
Fourlanos S, Narendran P, Byrnes GB, Colman PG, Harrison LC (2004) Insulin resistance is a risk factor for progression to type 1 diabetes. Diabetologia 47:1661–1667. https://doi.org/10.1007/s00125-004-1507-3
Athyros V, Tziomalos K, Karagiannis A, Anagnostis P, Mikhailidis D, Fiorino G, Rovida S, Correale C, Malesci A, Danese S (2009) Should adipokines be considered in the choice of the treatment of obesity-related health problems? Curr Drug Targets 11:122–135. https://doi.org/10.2174/138945010790030992
Yoo HJ (2014) Adipokines as a novel link between obesity and atherosclerosis. World J Diabetes 5:357. https://doi.org/10.4239/wjd.v5.i3.357
(2015) Standards of medical care in diabetes-2015. https://doi.org/10.2337/dc15-S001
Association AD (2021) 11. Microvascular complications and foot care: standards of medical care in diabetes—2021. Diabetes Care 44:S151–S167. https://doi.org/10.2337/DC21-S011
Berukstis A, Jarasunas J, Daskeviciute A, Ryliskyte L, Baranauskas A, Steponeniene R, Laucevicius A (2019) How to interpret 24-h arterial stiffness markers: comparison of 24-h ambulatory Mobil-O-Graph with SphygmoCor office values. Blood Press Monit 24:93–98. https://doi.org/10.1097/MBP.0000000000000369
Kumar R, Mal K, Razaq MK, Magsi M, Memon MK, Memon S, Afroz MN, Siddiqui HF, Rizwan A (2020) Association of leptin with obesity and insulin resistance. Cureus 12.https://doi.org/10.7759/cureus.12178
Park H-KK, Ahima RS (2015) Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism 64:24–34. https://doi.org/10.1016/j.metabol.2014.08.004
Mantzoros CS, Magkos F, Brinkoetter M, Sienkiewicz E, Dardeno TA, Kim S-Y, Hamnvik O-PR, Koniaris A (2011) Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab 301:E567–E584. https://doi.org/10.1152/ajpendo.00315.2011
S. Popovic D, Sekerus V (2016) Levels of different adipocytokines in chronic complications of type 1 diabetes mellitus. Integr Obes Diabetes 2: . https://doi.org/10.15761/IOD.1000156
Verrotti A, Basciani F, De Simone M, Morgese G, Chiarelli F (2000) Leptin concentration in non-obese and obese children with type 1 diabetes mellitus. Biomed Pharmacother 54:69–73. https://doi.org/10.1016/S0753-3322(00)88854-X
Majewska KA, Majewski D, Skowrońska B, Stankiewicz W, Fichna P (2015) Serum leptin and adiponectin levels in children with type 1 diabetes mellitus - relation to body fat mass and disease course. Adv Med Sci 61:117–122. https://doi.org/10.1016/j.advms.2015.10.002
Kiess W, Anil M, Blum WF, Englaro P, Juul A, Attanasio A, Dötsch J, Rascher W (1998) Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index. Eur J Endocrinol 138:501–509
Greco AV, Mingrone G, Giancaterini A, Manco M, Morroni M, Cinti S, Granzotto M, Vettor R, Camastra S, Ferrannini E (2002) Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes 51:144–151. https://doi.org/10.2337/diabetes.51.1.144
Gil-Campos M, Cañete R, Gil A (2004) Hormones regulating lipid metabolism and plasma lipids in childhood obesity. Int J Obes 28:S75–S80. https://doi.org/10.1038/sj.ijo.0802806
Cui J, Panse S, Falkner B (2011) The role of adiponectin in metabolic and vascular disease: a review. Clin Nephrol 75:26–33
Galler A, Gelbrich G, Kratzsch J, Noack N, Kapellen T, Kiess W (2007) Elevated serum levels of adiponectin in children, adolescents and young adults with type 1 diabetes and the impact of age, gender, body mass index and metabolic control: a longitudinal study. Eur J Endocrinol 157:481–489. https://doi.org/10.1530/EJE-07-0250
Blaslov K, Bulum T, Zibar K, Duvnjak L (2013) Relationship between adiponectin level, insulin sensitivity, and metabolic syndrome in type 1 diabetic patients. Int J Endocrinol 2013:535906. https://doi.org/10.1155/2013/535906
Kishida K, Kim KK, Funahashi T, Matsuzawa Y, Kang H-C, Shimomura I (2011) Relationships between circulating adiponectin levels and fat distribution in obese subjects. J Atheroscler Thromb 18:592–595. https://doi.org/10.5551/jat.7625
Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, Retzlaff BM, Knopp RH, Brunzell JD, Kahn SE (2003) Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 46:459–469. https://doi.org/10.1007/s00125-003-1074-z
Mantzoros CS, Li T, Manson JE, Meigs JB, Hu FB (2005) Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes. J Clin Endocrinol Metab 90:4542–4548. https://doi.org/10.1210/jc.2005-0372
Sabbatini AR, Fontana V, Laurent S, Moreno H (2015) An update on the role of adipokines in arterial stiffness and hypertension. J Hypertens 33:435–444. https://doi.org/10.1097/HJH.0000000000000444
Van de Voorde J, Pauwels B, Boydens C, Decaluwé K (2013) Adipocytokines in relation to cardiovascular disease. Metabolism 62:1513–1521. https://doi.org/10.1016/j.metabol.2013.06.004
Kim DH, Kim C, Ding EL, Townsend MK, Lipsitz LA (2013) Adiponectin levels and the risk of hypertension. Hypertension 62:27–32. https://doi.org/10.1161/HYPERTENSIONAHA.113.01453
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935. https://doi.org/10.1210/jcem.86.5.7463
Chandran M, Phillips SA, Ciaraldi T, Henry RR (2003) Adiponectin: more than just another fat cell hormone? Diabetes Care 26:2442–2450
Fu Z, Gong Y, Löfqvist C, Hellström A, Smith LEH (2016) Review: adiponectin in retinopathy. Biochim Biophys Acta - Mol Basis Dis 1862:1392–1400
Hadjadj S, Aubert R, Fumeron F, Pean F, Tichet J, Roussel R, Marre M (2005) Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects. Diabetologia 48:1088–1092. https://doi.org/10.1007/s00125-005-1747-x
Ferreira-Hermosillo A, Molina-Ayala M, Ramírez-Rentería C, Vargas G, Gonzalez B, Isibasi A, Archundia-Riveros I, Mendoza V (2015) Inflammatory cytokine profile associated with metabolic syndrome in adult patients with type 1 diabetes. J Diabetes Res 2015:972073. https://doi.org/10.1155/2015/972073
Redondo MJ, Rodriguez LM, Haymond MW, Hampe CS, Smith EO, Balasubramanyam A, Devaraj S (2014) Serum adiposity-induced biomarkers in obese and lean children with recently diagnosed autoimmune type 1 diabetes. Pediatr Diabetes 15:543–549. https://doi.org/10.1111/pedi.12159
Schäffler A, Büchler C, Müller-Ladner U, Herfarth H, Ehling A, Paul G, Schölmerich J, Zietz B (2004) Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus. Horm Metab Res 36:702–707. https://doi.org/10.1055/s-2004-826015
Fehmann H-C, Heyn J (2002) Plasma resistin levels in patients with type 1 and type 2 diabetes mellitus and in healthy controls. Horm Metab Res 34:671–673. https://doi.org/10.1055/s-2002-38241
Takata Y, Osawa H, Kurata M, Kurokawa M, Yamauchi J, Ochi M, Nishida W, Okura T, Higaki J, Makino H (2008) Hyperresistinemia is associated with coexistence of hypertension and type 2 diabetes. Hypertension 51:534–539. https://doi.org/10.1161/HYPERTENSIONAHA.107.103077
Thomopoulos C, Daskalaki M, Papazachou O, Rodolakis N, Bratsas A, Papadopoulos DP, Papavasileiou MV, Perrea D, Makris T (2011) Association of resistin and adiponectin with different clinical blood pressure phenotypes. J Hum Hypertens 25:38–46. https://doi.org/10.1038/jhh.2010.22
Zhang Y, Li Y, Yu L, Zhou L (2017) Association between serum resistin concentration and hypertension: a systematic review and meta-analysis. Oncotarget 8:41529–41537. https://doi.org/10.18632/oncotarget.17561
Papadopoulos DP, Makris TK, Perrea D, Papazachou O, Daskalaki M, Sanidas E, Votteas V (2008) Adiponectin – insulin and resistin plasma levels in young healthy offspring of patients with essential hypertension. Blood Press 17:50–54. https://doi.org/10.1080/08037050701876307
Zhang L, Curhan GC, Forman JP (2010) Plasma resistin levels associate with risk for hypertension among nondiabetic women. J Am Soc Nephrol 21:1185–1191. https://doi.org/10.1681/ASN.2009101053
Kawamura R, Doi Y, Osawa H, Ninomiya T, Hata J, Yonemoto K, Tanizaki Y, Iida M, Makino H, Kiyohara Y (2010) Circulating resistin is increased with decreasing renal function in a general Japanese population: the Hisayama study. Nephrol Dial Transplant 25:3236–3240. https://doi.org/10.1093/ndt/gfq155
Tsioufis C, Dimitriadis K, Selima M, Miliou A, Toutouzas K, Roussos D, Stefanadi E, Tousoulis D, Kallikazaros I, Stefanadis C (2010) Association of resistin with urinary albumin excretion in nondiabetic patients with essential hypertension. Am J Hypertens 23:681–686. https://doi.org/10.1038/ajh.2010.34
Cebeci E, Cakan C, Gursu M, Uzun S, Karadag S, Koldas M, Calhan T, Helvaci S, Ozturk S (2019) The main determinants of serum resistin level in type 2 diabetic patients are renal function and inflammation not presence of microvascular complication, obesity and insulin resistance. Exp Clin Endocrinol Diabetes 127:189–194. https://doi.org/10.1055/s-0043-121262
Bulum T, Vučić Lovrenčić M, Tomić M, Vučković-Rebrina S, Roso V, Kolarić B, Vuksan V, Duvnjak L (2019) Serum adipocytokines are associated with microalbuminuria in patients with type 1 diabetes and incipient chronic complications. Diabetes Metab Syndr Clin Res Rev 13:496–499. https://doi.org/10.1016/j.dsx.2018.11.001
Menzaghi C, Salvemini L, Fini G, Thompson R, Mangiacotti D, Di Paola R, Morini E, Giorelli M, De Bonis C, De Cosmo S, Doria A, Trischitta V (2012) Serum resistin and kidney function: a family-based study in non-diabetic, untreated individuals. PLoS ONE 7:e38414. https://doi.org/10.1371/journal.pone.0038414
Tziomalos K, Athyros V, Karagiannis A (2014) Treating arterial stiffness in young and elderly patients with the metabolic syndrome. Curr Pharm Des 20:6106–6113. https://doi.org/10.2174/1381612820666140417101523
Csongrádi É, Káplár M, Nagy B, Koch CA, Juhász A, Bajnok L, Varga Z, Seres I, Karányi Z, Magyar MT, Oláh L, Facskó A, Kappelmayer J, Paragh G (2017) Adipokines as atherothrombotic risk factors in obese subjects: associations with haemostatic markers and common carotid wall thickness. Nutr Metab Cardiovasc Dis 27:571–580. https://doi.org/10.1016/j.numecd.2017.02.007
Ntaios G, Gatselis NK, Makaritsis K, Dalekos GN (2013) Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis 227:216–221. https://doi.org/10.1016/j.atherosclerosis.2012.12.029
Atabek ME, Kurtoglu S, Demir F, Baykara M (2004) Relation of serum leptin and insulin-like growth factor-1 levels to intima-media thickness and functions of common carotid artery in children and adolescents with type 1 diabetes. Acta Paediatr 93:1052–1057
Yazıcı D, Yavuz D, Öğünç AV, Şirikçi Ö, Toprak A, Deyneli O, Akalın S (2012) Serum adipokine levels in type 1 diabetic patients: association with carotid intima media thickness. Metab Syndr Relat Disord 10:26–31. https://doi.org/10.1089/met.2011.0052
Shah AS, Dolan LM, Lauer A, Davis C, Dabelea D, Daniels SR, Hamman RF, Marcovina S, Wadwa RP, Urbina EM (2012) Adiponectin and arterial stiffness in youth with type 1 diabetes: the SEARCH for diabetes in youth study. J Pediatr Endocrinol Metab 25:717–721. https://doi.org/10.1515/jpem-2012-0070
Alman AC, Talton JW, Wadwa RP, Urbina EM, Dolan LM, Hamman RF, D’Agostino RB, Marcovina SM, Dabelea DM (2018) Inflammation, adiposity, and progression of arterial stiffness in adolescents with type 1 diabetes: the SEARCH CVD study. J Diabetes Complications 32:995–999. https://doi.org/10.1016/j.jdiacomp.2018.08.004
Ruscica M, Baragetti A, Catapano AL, Norata GD (2017) Translating the biology of adipokines in atherosclerosis and cardiovascular diseases: gaps and open questions. Nutr Metab Cardiovasc Dis 27:379–395. https://doi.org/10.1016/j.numecd.2016.12.005
We wish to thank all volunteers who participated in this trial.
This work was supported by the Northern Greece Diabetes Association.
The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics in Research Committee of the School of Public Health of the Aristotle University of Thessaloniki.
Consent to participate
All participants provided written informed consent.
Consent for publication
All authors read and approved the final manuscript before submission.
Conflict of interest
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Below is the link to the electronic supplementary material.
About this article
Cite this article
Kollari, E., Zografou, I., Sampanis, C. et al. Serum adipokine levels in patients with type 1 diabetes are associated with degree of obesity but only resistin is independently associated with atherosclerosis markers. Hormones (2021). https://doi.org/10.1007/s42000-021-00328-9