Relations Between Body Fat Mass and Insulin Resistance in Non-Obese Patients with Idiopathic Hypogonadotropic Hypogonadism and Normal Glucose Tolerance

Abstract

The purpose of this study was to investigate the relationship between body fat mass and insulin resistance in non-obese patients with idiopathic hypogonadotropic hypogonadism (IHH) and normal glucose tolerance. A total of 42 patients with IHH and normal glucose tolerance, and BMI lower than 28 kg/m² were recruited. Patients were required to have a normal glucose tolerance test for inclusion in the study. Ten Healthy subjects were recruited as control group. Laboratory studies included fasting insulin, testosterone, and lipids. Waist circumference (WC), weight, and body fat mass were measured, and waist-to-hip ratio (WHR), body mass index (BMI), HOMA-IR, and logHOMA-B were calculated. Data were compared between groups, and linear regression was used to determine relations. Blood pressure, fasting glucose, BMI, WHR, and lipids were similar between the groups. Fasting insulin levels (15.61±7.66 mIU/l vs. 7.60±3.84 mIU/l), logHOMA-B (2.39±0.29 vs. 2.03±0.21), HOMA-IR (3.38±1.71 vs. 1.64±0.91), and body fat mass (30.49±9.46% vs. 21.11±4.31%) were significantly greater in the IHH group compared with those in control group (all p<0.05). Multivariable linear regression showed that in IHH patients body fat mass was an independent predictor of fasting insulin level (β=0.71, p<0.01), logHOMA-B (β=0.02, p<0.05), and HOMA-IR (β=0.14, p<0.05). Body fat mass is an independent predictor of insulin resistance in non-obese IHH patients with normal glucose tolerance.

Key words

idiopathic hypogonadotropic hypogonadism - insulin resistance  - body fat mass - HOMA-IR - HOMA-B

^* These authors contributed equally to this work

Publication History

Received: 30 January 2022

Accepted after revision: 22 August 2022

Article published online:
07 October 2022

• References

• 1 Fraietta R, Zylberstejn DS, Esteves SC.. Hypogonadotropic hypogonadism revisited. Clinics (Sao Paulo) 2013; 68 (Suppl 1) 81-88
• 2 Bianco SD, Kaiser UB.. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol 2009; 5: 569-576
• 3 Layman LC.. Hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am 2007; 36: 283-296
• 4 Topaloğlu AK.. Update on the genetics of idiopathic hypogonadotropic hypogonadism. J Clin Res Pediatr Endocrinol 2017; 9 (Suppl 2) 113-122
• 5 King TF, Hayes FJ.. Long-term outcome of idiopathic hypogonadotropic hypogonadism. Curr Opin Endocrinol Diabetes Obes 2012; 19: 204-210
• 6 Howard SR, Dunkel L.. Management of hypogonadism from birth to adolescence. Best Pract Res Clin Endocrinol Metab 2018; 32: 355-372
• 7 Emanuele V.. Metabolic syndrome, obesity paradox and testosterone level. Endocrinol Metab Synd 2015; 04: 2
• 8 Zhang MN, Su B, Qian CH. et al. An idiopathic hypogonadotropic hypogonadism patient with metabolic disorder and diabetes: case report. Asian J Androl 2015; 17: 341-342
• 9 Bayram F, Elbuken G, Korkmaz C. et al. The effects of gonadotropin replacement therapy on metabolic parameters and body composition in men with idiopathic hypogonadotropic hypogonadism. Horm Metab Res 2016; 48: 112-117
• 10 Pitteloud N, Hardin M, Dwyer AA. et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab 2005; 90: 2636-2641
• 11 Muller M, Grobbee DE, den Tonkelaar I. et al. Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 2005; 90: 2618-2623
• 12 Caldas AD, Porto AL, Motta LD. et al. Relationship between insulin and hypogonadism in men with metabolic syndrome. Arq Bras Endocrinol Metabol 2009; 53: 1005-1011
• 13 Patel P, Abate N.. Body fat distribution and insulin resistance. Nutrients 2013; 5: 2019-2027
• 14 Pivonello R, Menafra D, Riccio E. et al. Metabolic disorders and male hypogonadotropic hypogonadism. Front Endocrinol (Lausanne) 2019; 10: 345
• 15 Kim JY, Han SH, Yang BM.. Implication of high-body-fat percentage on cardiometabolic risk in middle-aged, healthy, normal-weight adults. Obesity 2013; 21: 1571-1577
• 16 Stefan N.. Causes, consequences, and treatment of metabolically unhealthy fat distribution. Lancet Diabetes Endocrinol 2020; 8: 616-627
• 17 Kupelian V, Page ST, Araujo AB. et al. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab 2006; 91: 843-850
• 18 Zhu B, Lin S, Yang X. et al. Idiopathic hypogonadotropic hypogonadism combined with severe insulin resistance: one case report and literature review.
• 19 Petak SM, Nankin HR, Spark RF. et al. American association of clinical endocrinologists. American association of clinical endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients-2002 update. Endocr Pract 2002; 8: 440-456
• 20 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
• 21 Pitteloud N, Hardin M, Dwyer AA. et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab 2005; 90: 2636-2641
• 22 Volpi E, Lieberman SA, Ferrer DM. et al. The relationships between testosterone, body composition, and insulin resistance: a lesson from a case of extreme hyperandrogenism. Diabetes Care 2005; 28: 429-432
• 23 Pessin JE, Saltiel AR.. Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest 2000; 106: 165-169
• 24 Juan Ye, Ziting Yao, Aihua Tan. et al. Low Serum Sex Hormone-Binding Globulin Associated with Insulin Resistance in Men with Nonalcoholic Fatty Liver Disease. Horm Metab Res 2017; 49: 359-364
• 25 Peter A, Kantartzis K, Machann J. et al. Relationships of circulating sex hormone-binding globulin with metabolic traits in humans. Diabetes 2010; 59: 3167-3173
• 26 Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004; 114: 147–152
• 27 Suttontyrrell K, Wildman RP, Matthews KA. et al. Sex hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the study of women across the nation (SWAN). Circulation 2005; 111: 1242-1249
• 28 Ebrahimi F, Christ-Crain M.. Metabolic syndrome and hypogonadism--two peas in a pod. Swiss Med Wkly 2016; 146: w14283
• 29 Gevi F, Fanelli G, Zolla L.. Metabolic patterns in insulin-resistant male hypogonadism. Cell Death Dis 2018; 9: 671
• 30 Shetty GK, Mantzoros CS.. Insulin Resistance, Obesity, Body Fat Distribution, and Risk of Cardiovascular Disease. 2006
• 31 Salazar MR, Carbajal HA, Espeche WG. et al. Relationships among insulin resistance, obesity, diagnosis of the metabolic syndrome and cardio-metabolic risk [J]. Diabetes Vasc Disease Res 2011; 8: 109-116
• 32 Sandeep S, Gokulakrishnan K, Velmurugan K. et al. Visceral & subcutaneous abdominal fat in relation to insulin resistance & metabolic syndrome in non-diabetic south Indians. Indian J Med Res 2010; 131: 629-635
• 33 Simon D, Charles MA, Nahoul K. et al. Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: The Telecom Study. J Clin Endocrinol Metab 1997; 82: 682-685
• 34 Tchernof A, Després JP, Dupont A. et al. Relation of steroid hormones to glucose tolerance and plasma insulin levels in men. Importance of visceral adipose tissue. Diabetes Care 1995; 18: 292-299
• 35 Larsen MN, Krustrup P, Póvoas SCA. et al. Accuracy and reliability of the InBody 270 multi-frequency body composition analyser in 10-12-year-old children. PLoS One 2021; 16: e0247362