Ismail Dahashan¹, Hassan Shora²*, Nada Ahmed³ and Seham Ibrahim¹

¹Family Medicine Department, Faculty of Medicine, Suez Canal University, Egypt
²Biochemistry Department, Faculty of Medicine, Port-Said University, Egypt
³Clinical Pathology Department, Faculty of Medicine, Suez Canal University Hospital, Egypt

*Corresponding Author: Hassan A Shora, Senior Research Scientist, Head of Medicine and Diabetes Center, Port-Said University and Ismailia Medical Complex, Egypt.

Received: January 05, 2023; Published: January 20, 2023

Abstract

Background: Long-term research into adiponectin and other adipose tissue hormones as a biomarker for atherosclerotic changes in cardiometabolic and type 2 diabetes patients has shown mixed findings. This study aimed for evaluating urinary adiponectin (uAPN) as a potential biomarker for prediction of carotid atherosclerosis in metabolic syndrome patients with or without type 2 diabetes mellitus.

Subjects and Methods: This study recruited 220 participants from patients attending Endocrine and Diabetes outpatient centre in Ismailia Medical complex who were assigned into four groups, each had 55 participants: control, non-diabetic cardiometabolic, diabetic non-cardiometabolic, and diabetic cardiometabolic group. Urine and venous blood samples were collected to measure urinary and plasma adiponectin as well as other common blood assays according to the standard methods. Carotid Ultrasonography was performed to estimate carotid plaque score (CPS).

Results: Compared with control group, urinary adiponectin concentration was significantly higher in the three cardiometabolic and diabetic groups with values 7 ± 2.7, 6.6 ± 2.9, and 9.3 ± 3.9, respectively. Carotid plaque scores as median (IQR) showed a progressively higher value from group 1 to group 4 with statistically significant differences between the 4 groups. The results of the multivariate linear regression analysis for the prediction of CPS showed a highly statistically significant Beta of 39% for urinary adiponectin. ROC curve analysis for the performance of urinary adiponectin level as a diagnostic test for prediction of above median CPS showed a significant cut-off value of 6.42 ng/mg creatinine, with and a sensitivity of 85.8%, and specificity of 82.2%.

Conclusion: In the absence of additional controlled research, the measurement of urine adiponectin excretion is thought to be a credible urine biomarker for assessing higher risk of vascular events in people with type 2 diabetes and cardiometabolic disease.

Keywords: Urinary Adiponectin; Cardiometabolic Syndrome Carotid Plaque Score; Type 2 Diabetes

References

1. Maximus PS., et al. “Adipocytokines: Are they the Theory of Everything?” Cytokine 133 (2020): 155144.
2. Khoramipour K., et al. “Adiponectin: Structure, Physiological Functions, Role in Diseases, and Effects of Nutrition”. Nutrients4 (2021): 1180.
3. Achari AE and Jain SK. “Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction”. International Journal of Molecular Sciences 6 (2017): 1321.
4. Lihn AS., et al. “Adiponectin: action, regulation and association to insulin sensitivity”. Obesity Review1 (2005): 13-21.
5. Kumada M., et al. “Association of hypoadiponectinemia with coronary artery disease in men”. Arteriosclerosis, Thrombosis, and Vascular Biology 23 (2003): 85-89.
6. Hashimoto N., et al. “Association of hypoadiponectinemia in men with early onset of coronary heart disease and multiple coronary artery stenoses”. Metabolism: Clinical and Experimental 55 (2006): 1653-1657.
7. Mitsuhashi H., et al. “Adiponectin level and left ventricular hypertrophy in Japanese men”. Hypertension 49 (2007): 1448-1454.
8. Imatoh T., et al. “Adiponectin levels associated with the development of hypertension: A prospective study”. Hypertension Research 31 (2008): 229-233.
9. Kozakova M., et al. “Adiponectin and left ventricular structure and function in healthy adults”. The Journal of Clinical Endocrinology and Metabolism 93 (2008): 2811-2818.
10. Leon BM and Maddox TM. “Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research”. World Journal of Diabetes 6 (2015): 1246-1258.
11. Woodward L., et al. “Unravelling the adiponectin paradox: Novel roles of adiponectin in the regulation of cardiovascular disease”. British Journal of Pharmacology 174 (2017): 4007-4020.
12. Stern MP. “Diabetes and cardiovascular disease. The "common soil" hypothesis”. Diabetes 4 (1995): 369-374.
13. Jeon WS., et al. “Urinary adiponectin concentration is positively associated with micro- and macro-vascular complications”. Cardiovascular Diabetology 12 (2013): 137.
14. Maximilian von Eynatten., et al. “Urinary Adiponectin Excretion: A Novel Marker for Vascular Damage in Type 2Diabetes”. Diabetes9 (2009): 2093-2099.
15. Yamakado S., et al. “Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy”. BMJ Open Diabetes Research and Care 7 (2019): e000661.
16. Saif-Ali R., et al. “Relationship of metabolic syndrome defined by IDF or revised NCEP ATP III with glycemic control among Malaysians with Type 2 Diabetes”. Diabetology and Metabolic Syndrome1 (2020).
17. Mehta A., et al. “Association of Carotid Artery Plaque with Cardiovascular Events and Incident Coronary Artery Calcium in Individuals With Absent Coronary Calcification”. Circulation: Cardiovascular Imaging4 (2021).
18. Merel van Andel., et al. “Chapter Five - Adiponectin and Its Isoforms in Pathophysiology”. Editor (s): Gregory S. Makowski, Advances in Clinical Chemistry, Elsevier, 85 (2018): 115-147.
19. N Hales and D J P Barker. “The thrifty phenotype hypothesis”. British Medical Bulletin 60 (2001): 5-20.
20. T Kadowaki and T Yamauchi. “Adiponectin and adiponectin receptors”. Endocrine Reviews3 (2005): 439-451.
21. T Schraw., et al. “Plasma adiponectin complexes have distinct biochemical characteristics”. Endocrinology5 (2008): 2270-2282.
22. J Fruebis., et al. “Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice”. Proceedings of the National Academy of Sciences of the United States of America 4 (2001): 2005-2010.
23. K Kishida., et al. “Disturbed secretion of mutant adiponectin associated with the metabolic syndrome”. Biochemical and Biophysical Research Communications1 (2003): 286-292.
24. E K Calton., et al. “Factors determining the risk of the metabolic syndrome: is there a central role for adiponectin?” The European Journal of Clinical Nutrition5 (2013): 485-491.
25. A Daniele., et al. “Decreased concentration of adiponectin together with a selective reduction of its high molecular weight oligomers is involved in metabolic complications of myotonic dystrophy type 1”. European Journal of Endocrinology6 (2011): 969-975.
26. A de Rosa., et al. “Adiponectin oligomers as potential indicators of adipose tissue improvement in obese subjects”. European Journal of Endocrinology1 (2013): 37-43.
27. A Daniele., et al. “Analysis of adiponectin gene and comparison of its expression in two different pig breeds”. Obesity8 (2008): 1869-1874.
28. KA Simpson and M A F Singh. “Effects of exercise on adiponectin: a systematic review”. Obesity 16.2 (2008): 241-256.
29. M H Rokling-Andersen., et al. “Effects of long-term exercise and diet intervention on plasma adipokine concentrations”. The American Journal of Clinical Nutrition5 (2007): 1293-1301.
30. A Tsuchida., et al. “Peroxisome proliferator-activated receptor (PPAR)𝛼 activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPAR𝛼, PPAR𝛾, and their combination”. Diabetes12 (2005): 3358-3370.
31. S A Phillips., et al. “Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue”. The American Journal of Physiology: Endocrinology and Metabolism4 (2008): E842-E850.
32. A Sahebkar. “Head-to-head comparison of fibrates versus statins for elevation of circulating adiponectin concentrations: a systematic review and meta-analysis”. Metabolism12 (2013): 1876-1885.
33. G de Pergola and F Silvestris. “Obesity as a major risk factor for cancer”. Journal of Obesity (2013): 11.
34. CM Diaz-Melean., et al. “Mechanisms of adverse cardiometabolic consequences of obesity”. Current Atherosclerosis Reports11 (2013): 364.
35. Furman D., et al. “Chronic inflammation in the etiology of disease across the life span”. Nature Medicine 25 (2019): 1822-1832.
36. Zocchi M., et al. “A Potential Interplay between HDLs and Adiponectin in Promoting Endothelial Dysfunction in Obesity”. Biomedicines 10 (2022): 1344.
37. N Ouchi., et al. “Obesity, adiponectin and vascular inflammatory disease”. Current Opinion in Lipidology6 (2003): 561-566.
38. Y Iwashima., et al. “Hypoadiponectinemia is an independent risk factor for hypertension”. Hypertension6 (2004): 1318-1323.
39. G Rega-Kaun., et al. “More than a simple storage organ: adipose tissue as a source of adipokines involved in cardiovascular disease”. Thrombosis and Haemostasis4 (2013): 641-650.
40. S H Choi., et al. “Clinical implications of adipocytokines and newly emerging metabolic factors with relation to insulin resistance and cardiovascular health”. Frontiers in Endocrinology 4 (2013): 97.
41. M T Villarreal-Molina and B Antuna-Puente. “Adiponectin: anti-inflammatory and cardioprotective effects”. Biochimie 10 (2012): 2143-2149.
42. M Matsuda and I Shimomura. “Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases”. Reviews in Endocrine and Metabolic Disorders1 (2014): 1-10.
43. Cian-Huei Shih., et al. “Association of Low Serum Adiponectin Levels with Aortic Arterial Stiffness in Patients with Type 2 Diabetes”. Journal of Clinical Medicine 8 (2019): 887.
44. Cruickshank K., et al. “Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function?” Circulation 106 (2002): 2085-2090.
45. N Sattar., et al. “High molecular weight adiponectin is not associated with incident coronary heart disease in older women: a nested prospective case-control study”. The Journal of Clinical Endocrinology and Metabolism5 (2008): 1846-1849.
46. Ersilia Nigro., et al. “New Insight into Adiponectin Role in Obesity and Obesity-Related Diseases”. BioMed Research International (2014): 14.
47. Kopf S., et al. “Urinary excretion of high molecular weight adiponectin is an independent predictor of decline of renal function in type 2 diabetes”. Acta Diabetology 51 (2014): 479-489.
48. Panduru NM., et al. “Urinary adiponectin is an independent predictor of progression to end-stage renal disease in patients with type 1 diabetes and diabetic nephropathy”. Diabetes Care 38 (2015): 883-890.
49. Rovin BH., et al. “Plasma, urine, and renal expression of adiponectin in human systemic lupus erythematosus”. Kidney International 68 (2005): 1825-1833.
50. Koshimura J., et al. “Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy”. Biochemical and Biophysical Research Communications 316 (2004): 165-169.
51. Yamamoto M., et al. “A study of high, middle and low molecular weight adiponectin in urine as a surrogate marker for early diabetic nephropathy using ultra-sensitive ICT-EIA”. Annals of Clinical Biochemistry (2018): 4563217748681.

Citation

Citation: Ismail Dahashan, Hassan Shora, Nada Ahmed and Seham Ibrahim. “Urinary Adiponectin as a Predictor of Carotid Atherosclerosis in Metabolic Syndrome Patients with or without Type 2 Diabetes Mellitus”.Acta Scientific Medical Sciences 7.2 (2023): 118-134.

Copyright

Copyright: © 2022 Hassan Shora., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.