Testosterone deficiency in non-obese type 2 diabetic male patients
Abstract
Background and aims: it is unclear whether male hypogonadism is ascribable to the diabetic state per se, or because of other factors, such as obesity or age. We aimed to investigate the prevalence and identify the predictors for testosterone deficiency among non-obese type 2 diabetic males.
Methods: This cross-sectional study was conducted on 95 nonobese type 2 diabetic males with BMI below 30. We evaluated the total testosterone (TT) levels to determine prevalence and risk factors of testosterone deficiency. Serum TT ≤ 300 ng/dl defined testosterone deficiency.
Results: The prevalence of testosterone deficiency was 29.1%. Testosterone deficient patients had statistically significantly higher visceral adiposity index (VAI), waist, and triglyceride in comparison with normal testosterone patients. TT level correlated with VAI, waist, BMI, LH, and age. VAI was the only significant predictor of TT levels even after adjustment for age and BMI in regression analysis. Furthermore, VAI was a statistically significant risk factor for testosterone deficiency in binary logistic analysis.
Conclusions: testosterone deficient non-obese type 2 diabetic male patients had elevated VAI, waist, and triglyceride. Moreover, elevated VAI was a risk factor for testosterone deficiency. VAI could be an easily applicable and reliable index for the evaluation and prediction in type 2 non-obese diabetic males.
Keywords
References
- Hassan M, Hatata EZ, Al-Arman M, Aboelnaga MM. Urinary cystatin C as a biomarker of early renal dysfunction in type 2 diabetic patients [published online ahead of print, 2021 May 25]. Diabetes Metab Syndr. 2021;15(4):102152. doi:10.1016/j.dsx.2021.05.025. DOI: https://doi.org/10.1016/j.dsx.2021.05.025
- Gianatti EJ, Grossmann M. Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment. Diabet Med. 2020;37(2):174-186. doi:10.1111/dme.13977
- Anupam B, Shivaprasad C, Vijaya S, Sridevi A, Aiswarya Y, Nikhil K. Prevalence of hypogonadism in patients with type 2 diabetes mellitus among the Indian population. Diabetes Metab Syndr. 2020;14(5):1299-1304. doi:10.1016/j.dsx.2020.07.006
- Gianatti EJ, Grossmann M. Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment. Diabet Med. 2020;37(2):174-186. doi:10.1111/dme.13977.
- Castellano-Castillo D, Royo JL, Martínez-Escribano A, et al. Effects of SHBG rs1799941 Polymorphism on Free Testosterone Levels and Hypogonadism Risk in Young Non-Diabetic Obese Males. J Clin Med. 2019;8(8):1136. Published 2019 Jul 31. doi:10.3390/jcm8081136. DOI: https://doi.org/10.3390/jcm8081136
- Gianatti EJ, Grossmann M. Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment. Diabet Med. 2020;37(2):174-186. doi:10.1111/dme.13977 DOI: https://doi.org/10.1111/dme.13977
- Grossmann M. Low testosterone in men with type 2 diabetes: significance and treatment. J Clin Endocrinol Metab. 2011;96(8):2341-2353. doi:10.1210/jc.2011-0118. DOI: https://doi.org/10.1210/jc.2011-0118
- Mozafar Saadati H, Sabour S, Mansournia MA, Mehrabi Y, Hashemi Nazari SS. Effect modification of general and central obesity by sex and age on cardiovascular outcomes: Targeted maximum likelihood estimation in the atherosclerosis risk in communities study. Diabetes Metab Syndr. 2021;15(2):479-485. doi:10.1016/j.dsx.2021.02.024 DOI: https://doi.org/10.1016/j.dsx.2021.02.024
- Fernandez CJ, Chacko EC, Pappachan JM. Male Obesity-related Secondary Hypogonadism - Pathophysiology, Clinical Implications and Management. Eur Endocrinol. 2019;15(2):83-90. doi:10.17925/EE.2019.15.2.83 DOI: https://doi.org/10.17925/EE.2019.15.2.83
- Lee DM, O'Neill TW, Pye SR, et al. The European Male Ageing Study (EMAS): design, methods and recruitment. Int J Androl. 2009;32(1):11-24. doi:10.1111/j.1365-2605.2008.00879.x DOI: https://doi.org/10.1111/j.1365-2605.2008.00879.x
- Ng Tang Fui M, Hoermann R, Cheung AS, Gianatti EJ, Zajac JD, Grossmann M. Obesity and age as dominant correlates of low testosterone in men irrespective of diabetes status. Andrology. 2013;1(6):906-912. doi:10.1111/j.2047-2927.2013.00124.x DOI: https://doi.org/10.1111/j.2047-2927.2013.00124.x
- Amato MC, Giordano C, Galia M, et al. Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care. 2010;33(4):920-922. doi:10.2337/dc09-1825 DOI: https://doi.org/10.2337/dc09-1825
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2848]. J Clin Endocrinol Metab. 2010;95(6):2536-2559. doi:10.1210/jc.2009-2354 DOI: https://doi.org/10.1210/jc.2009-2354
- Tajar A, Forti G, O'Neill TW, Lee DM, Silman AJ, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Vanderschueren D, Huhtaniemi IT, Wu FC; EMAS Group. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010 Apr;95(4):1810-8. doi: 10.1210/jc.2009-1796. Epub 2010 Feb 19. PMID: 20173018.00.
- Ganesh HK, Vijaya Sarathi HA, George J, et al. Prevalence of hypogonadism in patients with type 2 diabetes mellitus in an Asian Indian study group. Endocr Pract. 2009;15(6):513-520. doi:10.4158/EP09035.ORR DOI: https://doi.org/10.4158/EP09035.ORR
- Al-Goblan AS, Al-Alfi MA, Khan MZ. Mechanism linking diabetes mellitus and obesity. Diabetes Metab Syndr Obes. 2014;7:587-591. Published 2014 Dec 4. doi:10.2147/DMSO.S67400 DOI: https://doi.org/10.2147/DMSO.S67400
- Turan E, Öztekin Ü. Relationship between visceral adiposity index and male infertility. Andrologia. 2020;52(4):e13548. doi:10.1111/and.13548 DOI: https://doi.org/10.1111/and.13548
- Haymana C, Sonmez A, Aydogdu A, et al. Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism. Arch Endocrinol Metab. 2017;61(3):282-287. doi:10.1590/2359-3997000000236. DOI: https://doi.org/10.1590/2359-3997000000236
- Akdemir AO, Karabakan M, Aktas BK, et al. Visceral adiposity index is useful for evaluating obesity effect on erectile dysfunction. Andrologia. 2019;51(6):e13282. doi:10.1111/and.13282. DOI: https://doi.org/10.1111/and.13282
- Dursun M, Besiroglu H, Cakir SS, Otunctemur A, Ozbek E. Increased visceral adiposity index associated with sexual dysfunction in men. Aging Male. 2018;21(3):187-192. doi:10.1080/13685538.2017.1406468... DOI: https://doi.org/10.1080/13685538.2017.1406468
- Ghazi S, Zohdy W, Elkhiat Y, Shamloul R. Serum testosterone levels in diabetic men with and without erectile dysfunction. Andrologia. 2012;44(6):373-380. doi:10.1111/j.1439-0272.2012.01292.x. DOI: https://doi.org/10.1111/j.1439-0272.2012.01292.x
- Al Hayek AA, Khader YS, Jafal S, Khawaja N, Robert AA, Ajlouni K. Prevalence of low testosterone levels in men with type 2 diabetes mellitus: a cross-sectional study. J Family Community Med. 2013;20(3):179-186. doi:10.4103/2230-8229.122006. DOI: https://doi.org/10.4103/2230-8229.122006
- Fui MN, Dupuis P, Grossmann M. Lowered testosterone in male obesity: mechanisms, morbidity and management. Asian J Androl. 2014;16(2):223-231. doi:10.4103/1008-682X.122365 DOI: https://doi.org/10.4103/1008-682X.122365
- Anupam B, Shivaprasad C, Vijaya S, Sridevi A, Aiswarya Y, Nikhil K. Prevalence of hypogonadism in patients with type 2 diabetes mellitus among the Indian population. Diabetes Metab Syndr. 2020;14(5):1299-1304. doi:10.1016/j.dsx.2020.07.006. DOI: https://doi.org/10.1016/j.dsx.2020.07.006
- Tajar A, Forti G, O'Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810-1818. doi:10.1210/jc.2009-1796 . DOI: https://doi.org/10.1210/jc.2009-1796
- Zheng R, Cao L, Cao W, et al. Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes. J Diabetes Res. 2016;2016:5162167. doi:10.1155/2016/5162167
- Rendong Zheng, Lin Cao, Wen Cao, Xiaoqiu Chu, Yongxin Hu, Huifeng Zhang, Juan Xu, Hongping Sun, Weiping Bao, Kemian Liu, Chao Liu, "Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes", Journal of Diabetes Research, vol. 2016, Article ID 5162167, 8 pages, 2016. https://doi.org/10.1155/2016/5162167 DOI: https://doi.org/10.1155/2016/5162167
- Cai X, Tian Y, Wu T, Cao CX, Li H, Wang KJ. Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Asian J Androl. 2014;16(1):146-152. doi:10.4103/1008-682X.122346. DOI: https://doi.org/10.4103/1008-682X.122346
- Fukui M, Tanaka M, Hasegawa G, Yoshikawa T, Nakamura N. Association between serum bioavailable testosterone concentration and the ratio of glycated albumin to glycated hemoglobin in men with type 2 diabetes. Diabetes Care. 2008;31(3):397-401. doi:10.2337/dc07-1898 DOI: https://doi.org/10.2337/dc07-1898
- Šimonienė D, Platūkiene A, Prakapienė E, Radzevičienė L, Veličkiene D. Insulin Resistance in Type 1 Diabetes Mellitus and Its Association with Patient's Micro- and Macrovascular Complications, Sex Hormones, and Other Clinical Data. Diabetes Ther. 2020;11(1):161-174. doi:10.1007/s13300-019-00729-5 DOI: https://doi.org/10.1007/s13300-019-00729-5
- Blaya R, Blaya P, Rhoden L, Rhoden EL. Low Testosterone Levels and Metabolic Syndrome in Aging Male. Curr Pharm Des. 2017;23(30):4470-4474. doi:10.2174/1381612823666170503150955.
- Dandona P, Dhindsa S. Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab. 2011;96(9):2643-2651. doi:10.1210/jc.2010-2724. DOI: https://doi.org/10.1210/jc.2010-2724
- Watanobe H, Hayakawa Y. Hypothalamic interleukin-1 beta and tumor necrosis factor-alpha, but not interleukin-6, mediate the endotoxin-induced suppression of the reproductive axis in rats. Endocrinology. 2003;144(11):4868-4875. doi:10.1210/en.2003-0644. DOI: https://doi.org/10.1210/en.2003-0644
- Brüning JC, Gautam D, Burks DJ, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289(5487):2122-2125. doi:10.1126/science.289.5487.2122. DOI: https://doi.org/10.1126/science.289.5487.2122
- Elsaied MA, Masallat D, Abdel-Hamid IA. Correlation of Adiponectin With Testosterone in Patients With and Without Type 2 Diabetes and Erectile Dysfunction. Am J Mens Health. 019;13(1):1557988318807049. doi:10.1177/1557988318807049. DOI: https://doi.org/10.1177/1557988318807049
- C. Langer, B. Gansz, C. Goepfert et al., “Testosterone up-regulates scavenger receptor BI and stimulates cholesterol efflux from macrophages,” Biochemical and Biophysical Research Communications, vol. 296, no. 5, pp. 1051–1057, 2002. DOI: https://doi.org/10.1016/S0006-291X(02)02038-7
- Feingold KR, Grunfeld C. The Effect of Inflammation and Infection on Lipids and Lipoproteins. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. South Dartmouth (MA): MDText.com, Inc.; January 8, 2019.
- Ji B, Qu H, Wang H, Wei H, Deng H. Association Between the Visceral Adiposity Index and Homeostatic Model Assessment of Insulin Resistance in Participants With Normal Waist Circumference. Angiology. 2017;68(8):716-721. doi:10.1177/0003319716682120. DOI: https://doi.org/10.1177/0003319716682120
- Štěpánek L, Horáková D, Cibičková Ľ, et al. Can Visceral Adiposity Index Serve as a Simple Tool for Identifying Individuals with Insulin Resistance in Daily Clinical Practice?. Medicina (Kaunas). 2019;55(9):545. Published 2019 Aug 29. doi:10.3390/medicina55090545. DOI: https://doi.org/10.3390/medicina55090545
- Amato MC, Pizzolanti G, Torregrossa V, Misiano G, Milano S, Giordano C. Visceral adiposity index (VAI) is predictive of an altered adipokine profile in patients with type 2 diabetes. PLoS One. 2014;9(3):e91969. Published 2014 Mar 20. doi:10.1371/journal.pone.0091969 DOI: https://doi.org/10.1371/journal.pone.0091969
- Al-Daghri NM, Al-Attas OS, Alokail MS, et al. Visceral adiposity index is highly associated with adiponectin values and glycaemic disturbances. Eur J Clin Invest. 2013;43(2):183-189. doi:10.1111/eci.12030 DOI: https://doi.org/10.1111/eci.12030
- Wang, N., Zhai, H., Han, B. et al. Visceral fat dysfunction is positively associated with hypogonadism in Chinese men. Sci Rep 6, 19844 (2016). https://doi.org/10.1038/srep19844 DOI: https://doi.org/10.1038/srep19844
- 46. Blaya R, Blaya P, Rhoden L, Rhoden EL. Low Testosterone Levels and Metabolic Syndrome in Aging Male. Curr Pharm Des. 2017;23(30):4470-4474. doi:10.2174/1381612823666170503150955. DOI: https://doi.org/10.2174/1381612823666170503150955
- Grossmann M, Hamilton EJ, Gilfillan C, Bolton D, Joon DL, Zajac JD. Bone and metabolic health in patients with non-metastatic prostate cancer who are receiving androgen deprivation therapy. Med J Aust. 2011;194(6):301-306. doi:10.5694/j.1326-5377.2011.tb02979.x DOI: https://doi.org/10.5694/j.1326-5377.2011.tb02979.x
- Pekgor S, Duran C, Berberoglu U, Eryilmaz MA. The Role of Visceral Adiposity Index Levels in Predicting the Presence of Metabolic Syndrome and Insulin Resistance in Overweight and Obese Patients. Metab Syndr Relat Disord. 2019;17(5):296-302. doi:10.1089/met.2019.0005 DOI: https://doi.org/10.1089/met.2019.0005
- Aboelnaga EM, Aboelnaga MM, Elkalla HM. Metformin addition to androgen deprivation therapy effect on cancer prostate patients with type 2 diabetes [published online ahead of print, 2021 Aug 18]. Diabetes Metab Syndr. 2021;15(5):102251. doi:10.1016/j.dsx.2021.102251 DOI: https://doi.org/10.1016/j.dsx.2021.102251
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