Top

Journal of Endocrinological Investigation

Published in:

Open Access 13-10-2023 | Type 1 Diabetes | Original Article

Adiponectin rs1501299 and chemerin rs17173608 gene polymorphism in children with type 1 diabetes mellitus: relation with macroangiopathy and peripheral artery disease

Authors: N. Y. Salah, S. S. Madkour, K. S. Ahmed, D. A. Abdelhakam, F. A. Abdullah, R. A. E. H. Mahmoud

Published in: Journal of Endocrinological Investigation | Issue 4/2024

Abstract

Aim

Although macrovascular complications represent the leading cause of mortality in type 1 diabetes mellitus (T1DM), the prevalence of subtle macrovascular affection including peripheral artery disease (PAD) among children with T1DM and its genetic predictors remains to be unraveled. Increasing evidence suggests a link between adiponectin rs1501299 and chemerin rs17173608 gene polymorphism and atherogenesis, and insulin resistance. Hence, this study assess the prevalence of these variants among children with T1DM in comparison to healthy controls and their association with macrovascular complications, namely PAD and hyperlipidemia.

Methods

Fifty children with T1DM and 50 matched controls underwent a thorough assessment including adiponectin rs1501299 and chemerin rs17173608 gene polymorphisms, fasting lipids, glycated hemoglobin (HbA1c), and ankle–brachial index (ABI). Cochran–Armitage trend test was used to decide the risk allele and evaluate the association between the candidate variant and PAD using a case–control design.

Results

Children with T1DM were found to have significantly higher ABI (p = 0.011) than controls. Chemerin gene polymorphism was detected in 41 children with T1DM (82.0%), while adiponectin gene polymorphism was detected in 19 children (38.0%). Children with T1DM having GG chemerin variant and those having TT adiponectin variant had significantly higher cholesterol with significantly lower HDL-C and ABI than those having the other two variants (p < 0.005). Children with T1DM having abnormal ABI had significantly higher chemerin G (p = 0.017) and adiponectin T (p = 0.022) alleles than those with normal ABI. Cholesterol and ABI were independently associated with chemerin and adiponectin gene polymorphism by multivariable regression analysis.

Conclusion

Children with T1DM having chemerin and adiponectin gene polymorphisms have significantly higher cholesterol and ABI than those without these polymorphisms and controls.

Trial registration

The Research Ethics Committee of Ain Shams University, approval number R 31/2021.

Schofield J, Ho J, Soran H (2019) Cardiovascular risk in type 1 diabetes mellitus. Diabetes Ther 10(3):773–789. https://doi.org/10.1007/s13300-019-0612-8CrossRefPubMedPubMedCentral

Soedamah-Muthu S, Fuller J, Mulnier H, Raleigh V, Lawrenson R, Colhoun H (2006) High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.: a cohort study using the general practice research database. Diabetes Care 29(4):798–804. https://doi.org/10.2337/diacare.29.04.06. (dc05-1433)CrossRefPubMed

Bjornstad P, Donaghue KC, Maahs DM (2018) Macrovascular disease and risk factors in youth with type 1 diabetes: time to be more attentive to treatment? Lancet Diabetes Endocrinol 6(10):809–820. https://doi.org/10.1016/S2213-8587(18)30035-4. (Epub 2018 Feb 20. Erratum in: Lancet Diabetes Endocrinol. 2018 Apr 10;: PMID: 29475800; PMCID: PMC6102087)CrossRefPubMedPubMedCentral

de Ferranti SD, de Boer IH, Fonseca V, Fox CS, Golden SH, Lavie CJ, Magge SN, Marx N, McGuire DK, Orchard TJ, Zinman B, Eckel RH (2014) Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Diabetes Care 37(10):2843–2863. https://doi.org/10.2337/dc14-1720CrossRefPubMedPubMedCentral

Carter RE, Lackland DT, Cleary PA, Yim E, Lopes-Virella M, Gilbert G, Orchard T, The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group (2007) Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group Intensive treatment of diabetes is associated with a reduced rate of peripheral arterial calcification in the Diabetes Control and Complications Trial. Diabetes Care 30:2646–2648. https://doi.org/10.2337/dc07-0517CrossRefPubMed

Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Marie D, Lookstein R, Misra S, Mureebe L, Olin J, Patel R, Regensteiner J, Schanzer A, Shishehbor M, Stewart K, Treat-Jacobson D, Walsh M (2017) AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 135:e726–e779. https://doi.org/10.1161/CIR.0000000000000471CrossRefPubMed

Criqui M, Matsushita K, Aboyans V, Hess C, Hicks C, Kwan T, McDermott M, Misra S, Ujueta F, On behalf of the American Heart Association Council on Epidemiology and Prevention; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Lifestyle and Cardiometabolic Health; Council on Peripheral Vascular Disease; and Stroke Council (2021) Lower extremity peripheral artery disease: contemporary epidemiology, management gaps, and future directions: a scientific statement from the American Heart Association. Circulation 144:e171–e191. https://doi.org/10.1161/CIR.0000000000001005CrossRefPubMedPubMedCentral

Liang W, Ye D (2019) The potential of adipokines as biomarkers and therapeutic agents for vascular complications in type 2 diabetes mellitus. Cytokine Growth Factor Rev 48:32–39. https://doi.org/10.1016/j.cytogfr.2019.06.002CrossRefPubMed

Bevan S, Meidtner K, Lorenz M, Sitzer M, Grant P, Markus H (2011) Adiponectin level as a consequence of genetic variation, but not leptin level or leptin adiponectin ratio, is a risk factor for carotid intima-media thickness. Stroke 42:1510–1514. https://doi.org/10.1161/STROKEAHA.110.602375CrossRefPubMed

10.

Zylla S, Dörr M, Völzke H, Schminke U, Felix S, Nauck M, Friedrich N (2018) Association of circulating chemerin with subclinical parameters of atherosclerosis. Results of a population-based study. Arteriosclerosis Thrombosis Vascular Biol 38:1656–1664. https://doi.org/10.1161/ATVBAHA.118.311219CrossRef

11.

Welsh P, Murray HM, Buckley BM, de Craen AJ, Ford I, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Sattar N (2009) Leptin predicts diabetes but not cardiovascular disease: results from a large prospective study in an elderly population. Diabetes Care 32:308–310CrossRefPubMedPubMedCentral

12.

Heid IM, Wagner SA, Gohlke H, Iglseder B, Mueller JC, Cip P, Ladurner G, Reiter R, Stadlmayr A, Mackevics V, Illig T, Kronenberg F, Paulweber B (2006) Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1727 healthy Caucasians. Diabetes 55:375–384CrossRefPubMed

13.

Patel S, Flyvbjerg A, Kozakova M, Frystyk J, Ibrahim IM, Petrie JR, Avery PJ, Ferrannini E, Walker M, RISC Investigators (2008) Variation in the ADIPOQ gene promoter is associated with carotid artery intima media thickness independent of plasma adiponectin levels in healthy subjects. Eur Heart J 29:386–393CrossRefPubMed

14.

Er LK, Wu S, Hsu LA, Teng MS, Sun YC, Ko YL (2018) Pleiotropic associations of RARRES2 gene variants and circulating chemerin levels: potential roles of chemerin involved in the metabolic and inflammation-related diseases. Mediators Inflamm 2018:4670521. https://doi.org/10.1155/2018/4670521CrossRefPubMedPubMedCentral

15.

Neves KB, Dinh Cat AN, Lopes RA, Rios FJ, Anagnostopoulou A, Lobato NS, de Oliveira AM, Tostes RC, Montezano AC, Touyz RM (2015) Chemerin regulates crosstalk between adipocytes and vascular cells through Nox. Hypertension 66:657–666. https://doi.org/10.1161/HYPERTENSIONAHA.115.05616CrossRefPubMed

16.

Ji Q, Lin Y, Liang Z, Yu K, Liu Y, Fang Z, Liu L, Shi Y, Zeng Q, Chang C, Chai M, Zhou Y (2014) Chemerin is a novel biomarker of acute coronary syndrome but not of stable angina pectoris. Cardiovasc Diabetol 13:145. https://doi.org/10.1186/s12933-014-0145-4CrossRefPubMedPubMedCentral

17.

Yoo HJ, Choi HY, Yang SJ, Kim HY, Seo JA, Kim SG, Kim NH, Choi KM, Choi DS, Baik SH (2012) Circulating chemerin level is independently correlated with arterial stiffness. J Atheroscler Thromb 19:59–66 (discussion 67)CrossRefPubMed

18.

Aronis KN, Sahin-Efe A, Chamberland JP, Spiro A, Vokonas P, Mantzoros CS (2014) Chemerin levels as predictor of acute coronary events: a case-control study nested within the veterans’ affairs normative aging study. Metabolism 63:760–766. https://doi.org/10.1016/j.metabol.2014.02.013CrossRefPubMed

19.

Aydin K, Canpolat U, Akin S, Dural M, Karakaya J, Aytemir K, Ozer N, Gurlek A (2016) Chemerin is not associated with subclinical atherosclerosis markers in prediabetes and diabetes. Anatol J Cardiol 16:749–755PubMed

20.

Mayer-Davis E, Kahkoska A, Jefferies C, Dabelea D, Balde N, Gong C, Craig M (2018) ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 19:7–19CrossRefPubMedPubMedCentral

21.

Couch S, Urbina E, Crandell J, Liese A, Dabelea D, Kim G, Mayer-Davis E (2019) Body mass index z-score modifies the association between added sugar intake and arterial stiffness in youth with type 1 diabetes: the search nutrition ancillary study. Nutrients 11(8):1752CrossRefPubMedPubMedCentral

22.

Flynn J, Kaelber D, Baker-Smith C, Blowey D, Carroll A, Daniels S, de Ferranti S, Dionne J, Falkner B, Flinn S, Gidding S, Goodwin C, Leu M, Powers M, Rea C, Samuels J, Simasek M, Thaker V, Urbina E (2017) Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 140(3):e20171904. https://doi.org/10.1542/peds.2017-1904CrossRefPubMed

23.

Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29(1):308–311CrossRefPubMedPubMedCentral

24.

FMcGuigan F, Ralston S (2002) Single nucleotide polymorphism detection: allelic discrimination using TaqMan. Psychiatr Genet 12:133–136CrossRef

25.

Harley C, Gandhi S, Blasetto J, Heien H, Sasane R, Nelson SP (2008) Lipid levels and low-density lipoprotein cholesterol goal attainment in diabetic patients: rosuvastatin compared with other statins in usual care. Expert Opin Pharmacother 9:669–676CrossRefPubMed

26.

Goldstein D, Little R, Wie-dmeyer H, England J, McKenzie E (1986) Glycated hemoglobin: methodologies and clinical applications. Clin Chem 32(10):B64-70PubMed

27.

Aboyans V, Criqui MH, Abraham P, Allison M, Creager M, Diehm C, Fowkes F, Hiatt W, Jönsson B, Lacroix P, Marin B, McDermott M, Norgren L, Pande R, Preux P, Stoffers H, Treat-Jacobson D, American Heart Association Council on Peripheral Vascular Disease; Council on Epidemiology and Prevention; Council on Clinical Cardiology; Council on Cardiovascular Nursing; Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia (2012) Measurement and interpretation of the ankle–brachial index: a scientific statement from the American Heart Association. Circulation 126:2890–2909. https://doi.org/10.1161/CIR.0b013e318276fbcbCrossRefPubMed

28.

Zheng G, Gastwirth J (2006) On estimation of the variance in Cochran-Armitage trend tests for genetic association using case-control studies. Stat Med 25:3150–3159CrossRefPubMed

29.

Nattero-Chávez L, Redondo López S, Alonso Díaz S, Garnica Ureña M, Fernández-Durán E, Escobar-Morreale HF, Luque-Ramírez M (2019) The peripheral atherosclerotic profile in patients with type 1 diabetes warrants a thorough vascular assessment of asymptomatic patients. Diabetes Metab Res Rev 35(2):e3088CrossRefPubMed

30.

Ferreira-Divino LF, Suvitaival T, Rotbain Curovic V, Tofte N, Trošt K, Mattila IM, Theilade S, Winther SA, Hansen TW, Frimodt-Møller M, Legido-Quigley C, Rossing P (2022) Circulating metabolites and molecular lipid species are associated with future cardiovascular morbidity and mortality in type 1 diabetes. Cardiovasc Diabetol 21(1):135. https://doi.org/10.1186/s12933-022-01568-8CrossRefPubMedPubMedCentral

31.

Brewer L, Chai H, Bailey K, Kullo I (2007) Measures of arterial stiffness and wave reflection are associated with walking distance in patients with peripheral arterial disease. Atherosclerosis 191(2):384–390CrossRefPubMed

32.

Nattero-Chávez L, López S, Díaz S, Ureña M, Fernández-Durán E, Escobar-Morreale H, Luque-Ramírez M (2019) Association of cardiovascular autonomic dysfunction with peripheral arterial stiffness in patients with type 1 diabetes. J Clin Endocrinol Metab 104(7):2675–2684. https://doi.org/10.1210/jc.2018-02729CrossRefPubMed

33.

Li J, Luo Y, Xu Y, Yang J, Zheng L, Hasimu B, Yu J, Hu D (2007) Risk factors of peripheral arterial disease and relationship between low ABI and mortality from all-cause and cardiovascular disease in Chinese patients with type 2 diabetes. Circ J 71:377–381CrossRefPubMed

34.

Pastore I, Bolla A, Montefusco L, Lunati M, Rossi A, Assi E, Zuccotti G, Fiorina P (2020) The impact of diabetes mellitus on cardiovascular risk onset in children and adolescents. Int J Mol Sci 21:4928. https://doi.org/10.3390/ijms21144928CrossRefPubMedPubMedCentral

35.

Perumalsamy S, Ahmad W, Huri H (2021) Single nucleotide polymorphism rs17173608 in the chemerin encoding gene: is it a predictor of insulin resistance and severity of coronary artery disease in non-obese type 2 diabetes? Healthcare 9(6):623. https://doi.org/10.3390/healthcare9060623CrossRefPubMedPubMedCentral

36.

Abdelhamid A, Zaafan M (2019) Association of Chemerin rs17173608 and Vaspin rs2236242 polymorphisms with type two diabetes mellitus and its impact on their corresponding serum levels in Egyptian population. Biomed J Sci Tech Res 15(3):1–6

37.

Howlader M, Sultana M, Akter F, Hossain M (2021) Adiponectin gene polymorphisms associated with diabetes mellitus: a descriptive review. Heliyon 7(8):e07851. https://doi.org/10.1016/j.heliyon.2021.e07851CrossRefPubMedPubMedCentral

38.

Cui M, Gao Y, Zhao Y, Pang H, Chen L, Wang Z, Zhao L, Li M (2020) Association between Adiponectin gene polymorphism and environmental risk factors of Type 2 diabetes mellitus among the Chinese population in Hohhot. Biomed Res Int 2020:6383906. https://doi.org/10.1155/2020/6383906CrossRefPubMedPubMedCentral

39.

Dahpy M, Khairallah M, Azoz N, Ezzat G (2020) The associations among RARRES2 rs17173608 gene polymorphism, serum chemerin, and non-traditional lipid profile in patients with metabolic syndrome. Egypt J Med Hum Genet 21:21. https://doi.org/10.1186/s43042-020-00063-7CrossRef

40.

Shin HY, Lee DC, Chu SH, Jeon J, Lee M, Im J, Lee J (2012) Chemerin levels are positively correlated with abdominal visceral fat accumulation. Clin Endocrinol 77:47–50CrossRef

41.

Tsuzaki K, Kotani K, Sano Y, Fujiwara S, Gazi I, Elisaf M, Sakane N (2012) The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study. Metab Clin Exp 61(1):17–21CrossRefPubMed

42.

Kennedy AJ, Yang P, Read C, Kuc RE, Yang L, Taylor EJ, Taylor CW, Maguire JJ, Davenport AP (2016) Chemerin elicits potent constrictor actions via chemokine-like receptor 1 (CMKLR1), not G-protein-coupled receptor 1 (GPR1), in human and rat vasculature. J Am Heart Assoc 5(10):e004421. https://doi.org/10.1161/JAHA.116.004421CrossRefPubMedPubMedCentral

43.

Ding M, Carrão AC, Wagner RJ, Xie Y, Jin Y, Rzucidlo EM, Yu J, Li W, Tellides G, Hwa J, Aprahamian TR, Martin KA (2012) Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype. J Mol Cell Cardiol 52:474–484CrossRefPubMed

44.

Araki T, Emoto M, Teramura M, Yokoyama H, Mori K, Hatsuda S, Maeno T, Shinohara K, Koyama H, Shoji T, Inaba M, Nishizawa Y (2006) Effect of adiponectin on carotid arterial stiffness in type 2 diabetic patients treated with pioglitazone and metformin. Metabolism 55:996–1001CrossRefPubMed

45.

Matsuzawa Y, Funahashi T, Kihara S, Shimomura I (2004) Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 24:29–33CrossRefPubMed

Title: Adiponectin rs1501299 and chemerin rs17173608 gene polymorphism in children with type 1 diabetes mellitus: relation with macroangiopathy and peripheral artery disease
Authors: N. Y. Salah
S. S. Madkour
K. S. Ahmed
D. A. Abdelhakam
F. A. Abdullah
R. A. E. H. Mahmoud
Publication date: 13-10-2023
Publisher: Springer International Publishing
Keywords: Type 1 Diabetes
Peripheral Arterial Disease
Peripheral Arterial Disease
Arterial Diseases
Published in: Journal of Endocrinological Investigation / Issue 4/2024
Electronic ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-023-02215-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aim

Methods

Results

Conclusion

Trial registration

Please log in to get access to this content

Other articles of this Issue 4/2024

Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention

Nano Morgante: the most famous buffoon of Cosimo I de’Medici

Body mass index is a good predictor of metabolic abnormalities in polycystic ovary syndrome

Refracture following vertebral fragility fracture when bone fragility is not recognized: summarizing findings from comparator arms of randomized clinical trials

The triglycerides and glucose index is more strongly associated with metabolically healthy obesity phenotype than the lipid and obesity indices

A revisit of drugs and potential therapeutic targets against non-alcoholic fatty liver disease: learning from clinical trials

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage