Testosterone Level and Risk of Diabetes: Follow-Up Study
Main Article Content
Abstract
Background: Epidemiological studies have documented an inverse relationship between testosterone levels and risk of cardiovascular disease. The present study aimed to explore the association between testosterone levels and risk of developing diabetes mellitus from 108 middle-aged men with no history of medical diseases.
Methods: Data regarding the age of subjects, smoking, alcohol consumption, waist-to-hip ratio, and family history of cardiovascular disease were collected at the time of inclusion. Testosterone levels were also measured. 15 years later the medical history of the men was reviewed to record the development of medical incidents with references to diabetes mellitus. Two groups of men were identified based on testosterone levels: hypogonadal (testosterone ≤12 nmol/L) and eugonadal (testosterone >12 nmol/L).
Results: In total, 10 (9.0%) out of 108 men developed diabetes during the 15-year follow-up period, of whom 6 (16%) out of 37 and 4 (6%) out of 71 were men in the hypogonadal and eugonadal cohorts respectively (p=0.08). Using Cox proportional hazards regression analysis, the adjusted risk for diabetes was significantly lower in eugonadal men compared to hypogonadal men (adjusted hazard ratio=0.236; 95% CI=0.062–0.898; P=0.03).
Conclusion: Our results showed a significant increased risk of diabetes in men with low testosterone levels compared to men with normal testosterone.
Keywords:
Diabetes, Hypertension, Hypogonadism, Eugonadism, Testosterone
Article Details
How to Cite
REZANEZHAD, Babak; BORGQUIST, Rasmus; ELZANATY, Saad.
Testosterone Level and Risk of Diabetes: Follow-Up Study.
Medical Research Archives, [S.l.], v. 11, n. 9, sep. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4473>. Date accessed: 16 may 2024.
doi: https://doi.org/10.18103/mra.v11i9.4473.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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14. Vikan T, Schirmer H, Njølstad I, Svartberg J. Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. Eur J Endocrinol. 2010; 162(4):747-54.
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25. Bobjer J, Katrinaki M, Tsatsanis C, Giwercman YL, Giwercman A. Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study. PLoS One. 2013,18;8(4):e61466
26. Maggio M, Basaria S, Ceda GP, Ble A, Ling SM, et al. The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest. 2005;28(11 Suppl Proceedings):116-9.
27. Maggio M, Blackford A, Taub D, Carducci M, Ble A, Metter EJ, et al. Circulating inflammatory cytokine expression in men with prostate cancer undergoing androgen deprivation therapy. J Androl. 2006;27(6):725-728.
28. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004; 89(7):3313-3318
29. Su X & Peng D. New insight into sortilin in controlling lipid metabolism and the risk of atherogenesis. Biol Rev. 209;95(1):232-43.
30. Ruscica M, Ferri N, Macchi C, Corsini A, Sirtori CR. Lipid lowering drugs and inflammatory changes: an impact on cardiovascular outcomes? Ann Med. 2018;50(5):461-84.
31. Kupelian V, Chiu GR, Araujo AB, Williams R E, Clark R V, McKinlay JB. Association of sex hormones and C-reactive protein levels in men. Clin Endocrinol (Oxf). 2010;72(4):527-533.
32. Magnussen LV, Glintborg D, Hermann P, Hougaard DM, Højlund K, Andersen M. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy. Diabetes Obes Metab. 2016;18(10):980-9.
33. Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation? Hypertension. 2006;48(6):1012-1017
34. Nguyen TT, Wang JJ, Islam FM, Mitchell P, Tapp RJ, Zimmet PZ, et al. Retinal arteriolar narrowing predicts incidence of diabetes: The Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. Diabetes. 2008;57(3):536-9.
35. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004;291(16):1978-1986.
36. Rezanezhad B, Borgquist R, Elzanaty S. Association between Testosterone Levels and Clinical Markers of Atherosclerosis. Annals of Clinical and Medical Case Reports. 2020;4(6):1-5
37. Maneschi E, Morelli A, Filippi S, Cellai I, Comeglio P, Mazzanti B, et al. Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements. J Endocrinol. 2012;215(3):347-62.
38. Wittert G, Bracken K, Robledo KP, Grossmann M, Yeap BB, Handelsman DJ, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol. 2021;9(1):32-45.
39. Vierhapper H, Nowotny P, Waldha W. Reduced Production Rates of Testosterone and Dihydrotestosterone in Healthy Men Treated With Rosiglitazone. Metabolism. 2003;52(2):230-2
40. Kapoor D, Channer KS, Jones TH. Rosiglitazone increases bioactive testosterone and reduces waist circumference in hypogonadal men with type 2 diabetes. Diabetes Vasc Dis Res.2008;5(2):135-7.
41. Oh JY, Barrett-Connor E, Wedick NM, Wingard D L. Endogenous sex hormones and the development of type 2 diabetes in older men and women: The Rancho Bernardo study. Diabetes Care. 2002;25(1):55-60
42. Ding E L, Song Y, Manson J E, Buring JE, Liu S. Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study. Diabetologia. 2007;50(10):2076-2084.
2. Yeap BB. Androgens and cardiovascular disease. Curr Opin Endocrinol Diabetes Obes. 2010; 17(3):269-276.
3. Cowie CC, Rust KF, Ford ES, Eberhardt MS, Byrd-Holt DD, Li C, et al. Full accounting of diabetes and prediabetes in the U.S. population in 1988–1994 and 2005–2006. Diabetes Care. 2009; 32(2):28794.
4. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: Principles of pathogenesis and therapy. Lancet. 2005; 365(9467):1333-1346
5. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001; 414(6865):482-487.
6. Magliano DJ, Barr EL, Zimmet PZ, Cameron AJ, Dunstan DW, Colagiuri S, et al. Glucose indices, health behaviors, and incidence of diabetes in Australia: The Australian Diabetes, Obesity and Lifestyle Study. Diabetes Care. 2008; 31(2):267-72.
7. Atlantis E, Lange K, Wittert GA. Chronic disease trends due to excess body weight in Australia. Obes Rev. 2009;10(5):543-53
8. Dunstan DW, Zimmet PZ, Welborn TA, De Courten MP, Cameron AJ, Sicree RA, et al. The rising prevalence of diabetes and impaired glucose tolerance: The Australian Diabetes, Obesity and Lifestyle Study. Diabetes Care. 2002; 25(5):829-34.
9. Barr EL, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, et al. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: The Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation. 2007; 116(2):151-7.
10. Kapoor D, Aldred H, Clark S, Channer KS, Jones TH. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity. Diabetes Care. 2007; 30(4):911-7
11. Ogbera OA, Chinenye S, Olufemi F, Wale A. Hypogonadism, and subnormal total testosterone levels in men with type 2 diabetes mellitus. J Coll Physicians Surg Pak. 2011;21(9):517-521
12. Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care. 2000; 23(4):490-494.
13. Laaksonen DE, Niskanen L, Punnonen K, Nyyssönen K, Tuomainen TP, Valkonen VP, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care. 2004; 27(5):1036-1041.
14. Vikan T, Schirmer H, Njølstad I, Svartberg J. Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. Eur J Endocrinol. 2010; 162(4):747-54.
15. Yassin A, Haider A, Haider KS, Caliber M, Doros G, Saad F, et al. Testosterone therapy in men with hypogonadism prevents progression from prediabetes to type 2 diabetes: eight-year data from a registry study. Diabetes Care. 2019; 42(6):1104-11.
16. Rezanezhad B, Borgquist R, Willenheimer R, Elzanaty S. The Association between Serum Testosterone and Risk Factors for Atherosclerosis. Curr Urol. 2019; 13(2):101-106.
17. Bener A, Yousafzai MT, Darwish S, Al-Hamaq AOAA, Nasralla E A, et al. Obesity Index That Better Predict Metabolic Syndrome: Body Mass Index, Waist Circumference, Waist Hip Ratio, or Waist Height Ratio. J Obes. 2013;2013:1-9.
18. Hardy DS, Stallings DT, Garvin JT, Gachupin FC, Xu H, Racette SB. Anthropometric discriminators of type 2 diabetes among White and Black American adults. J Diabetes. 2017;9(3):296-307.
19. Arver S & Lehtihet M. Current guidelines for the diagnosis of testosterone deficiency. Frontiers of Hormone Research. 2009;37:5-20.
20. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2006;91(6):1995-2010.
21. Tirosh A, Shai I, Bitzur R, Kochba I, Tekes-Manova D, Israeli E, et al. Changes in triglyceride levels over time and risk of type 2 diabetes in young men. Diabetes Care. 2008;31(10): 2032-7.
22. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world-a growing challenge. N Engl J Med. 2007; 356(3):213-5.
23. Felber JP & Golay A. Pathways from obesity to diabetes. Int J Obes Relat Metab Disord. 2002;26 suppl 2:39-45.
24. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116(7):1793-1801.
25. Bobjer J, Katrinaki M, Tsatsanis C, Giwercman YL, Giwercman A. Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study. PLoS One. 2013,18;8(4):e61466
26. Maggio M, Basaria S, Ceda GP, Ble A, Ling SM, et al. The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest. 2005;28(11 Suppl Proceedings):116-9.
27. Maggio M, Blackford A, Taub D, Carducci M, Ble A, Metter EJ, et al. Circulating inflammatory cytokine expression in men with prostate cancer undergoing androgen deprivation therapy. J Androl. 2006;27(6):725-728.
28. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004; 89(7):3313-3318
29. Su X & Peng D. New insight into sortilin in controlling lipid metabolism and the risk of atherogenesis. Biol Rev. 209;95(1):232-43.
30. Ruscica M, Ferri N, Macchi C, Corsini A, Sirtori CR. Lipid lowering drugs and inflammatory changes: an impact on cardiovascular outcomes? Ann Med. 2018;50(5):461-84.
31. Kupelian V, Chiu GR, Araujo AB, Williams R E, Clark R V, McKinlay JB. Association of sex hormones and C-reactive protein levels in men. Clin Endocrinol (Oxf). 2010;72(4):527-533.
32. Magnussen LV, Glintborg D, Hermann P, Hougaard DM, Højlund K, Andersen M. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy. Diabetes Obes Metab. 2016;18(10):980-9.
33. Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation? Hypertension. 2006;48(6):1012-1017
34. Nguyen TT, Wang JJ, Islam FM, Mitchell P, Tapp RJ, Zimmet PZ, et al. Retinal arteriolar narrowing predicts incidence of diabetes: The Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. Diabetes. 2008;57(3):536-9.
35. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004;291(16):1978-1986.
36. Rezanezhad B, Borgquist R, Elzanaty S. Association between Testosterone Levels and Clinical Markers of Atherosclerosis. Annals of Clinical and Medical Case Reports. 2020;4(6):1-5
37. Maneschi E, Morelli A, Filippi S, Cellai I, Comeglio P, Mazzanti B, et al. Testosterone treatment improves metabolic syndrome-induced adipose tissue derangements. J Endocrinol. 2012;215(3):347-62.
38. Wittert G, Bracken K, Robledo KP, Grossmann M, Yeap BB, Handelsman DJ, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol. 2021;9(1):32-45.
39. Vierhapper H, Nowotny P, Waldha W. Reduced Production Rates of Testosterone and Dihydrotestosterone in Healthy Men Treated With Rosiglitazone. Metabolism. 2003;52(2):230-2
40. Kapoor D, Channer KS, Jones TH. Rosiglitazone increases bioactive testosterone and reduces waist circumference in hypogonadal men with type 2 diabetes. Diabetes Vasc Dis Res.2008;5(2):135-7.
41. Oh JY, Barrett-Connor E, Wedick NM, Wingard D L. Endogenous sex hormones and the development of type 2 diabetes in older men and women: The Rancho Bernardo study. Diabetes Care. 2002;25(1):55-60
42. Ding E L, Song Y, Manson J E, Buring JE, Liu S. Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study. Diabetologia. 2007;50(10):2076-2084.