Prediabetes in Overweight Adult Men: Serum Testosterone Variations

International Journal of Biomedicine 15(4) (2025) 660-667 http://dx.doi.org/10.21103/Article15(4)_OA2 ORIGINAL ARTICLE INTERNATIONAL JOURNAL OF BIOMEDICINE Endocrinology Prediabetes in Overweight Adult Men: Serum Testosterone Variations Omar Babateen1, Zahir Hussain1* Department of Physiology, Faculty of Medicine, Umm Al-Qura University (UQU), Makkah 21955, Saudi Arabia 1 Abstract Background: Prediabetes (PD), an intermediate stage between normoglycemia and diabetes mellitus (DM), is characterized by elevated blood glucose levels, but not enough to be to be diagnosed as DM. Some studies show that men with hypogonadism are at an increased risk for insulin resistance (IR) and PD. This study aimed to evaluate the variation of testosterone levels in adult Saudi men with normal weight (NW) and PD (NW-PD) and men with overweight (OW) and PD (OW-PD). Methods and Results: This case-control study comprised 391 adult Saudi males (age range: 35-40 years). The subjects in the current study had a body mass index (BMI) of 18.5-29.9 kg/m². The adult subjects were categorized into four groups: 1) NW control (NW-C), 2) OW control (OW-C), 3) men with NW and PD (NW-PD), and 4) men with OW and PD (OW-PD). The serum testosterone level was determined using ELISA kits. Testosterone levels in the OW-PD group were significantly lower than those in the NW-PD group (P=0.03). BMI plotted against serum testosterone for the OW-PD group showed a significant negative linear correlation between BMI and testosterone (R²=0.05, P=0.03). Conclusion: The present study provides helpful information about the overweight status in association with decreased serum testosterone in men with prediabetes.(International Journal of Biomedicine. 2025;15(4):660-667.) Keywords: prediabetes • adult men • overweight • body mass index • testosterone For citation: Babateen O, Hussain Z. Prediabetes in Overweight Adult Men: Serum Testosterone Variations. International Journal of Biomedicine. 2025;15(4):660-667. doi:10.21103/Article15(4)_OA2 Abbreviations ADA, American Diabetes Association; BMI, body mass index; BW, body weight; DM, diabetes mellitus; FBG, fasting blood glucose; IFG, impaired fasting glucose; Hb, hemoglobin; IGT, impaired glucose tolerance; IR, insulin resistance; MetS, metabolic syndrome; NW, normal weight; OW, overweight; PD, prediabetes; SHBG, sex hormone-binding globulin; T2D, type 2 diabetes; TES, testosterone. Introduction Diabetes mellitus (DM)and prediabetes (PD) are global health challenges.1,2 Prediabetes (PD), an intermediate stage between normoglycemia and diabetes mellitus (DM), is characterized by elevated blood glucose levels, but not enough to be to be diagnosed as DM.3-5 The main factors that characterize PD are impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).6,7 Lifestyle modifications, particularly effective diet, exercise, and other weight management programs, are key factors in preventing PD and type 2 diabetes (T2D).8-13 According to recent studies, the rate of progression from PD to T2D is about 25% in 3–5 years, and it is estimated that 70% of individuals with PD will develop T2D in their lifetime.3,14-19 Prediabetes was initially recommended and defined by the ADA in 1997 as a fasting blood glucose (FBG) level of 110-125 mg/dL or IFG.20 The World Health Organization adopted this criterion. In 2003, the ADA lowered the FBG threshold to 100–125 mg/dL;21 however, the WHO did not adopt this lower cutoff and maintained its 110–125 mg/dL standard. The diagnosis of PD also includes IGT, which is based on a 2-hour oral glucose tolerance test (OGTT), with a 2-hour plasma glucose level of 140–199 mg/dL being the diagnostic range for IGT.22 661 O. Babateen & Z. Hussain / International Journal of Biomedicine 15(4) (2025) 660-667 Prediabetes is included in the International Classification of Diseases, Tenth Revision.23 Prediabetes is associated with insulin resistance (IR), obesity, fatty liver disease, metabolic syndrome (MetS), T2D, cardiovascular complications, and allcause mortality.24-29 Early intervention by dietary and lifestyle changes helps prevent it and its progression to other diseases, especially T2D.30 Among the main factors influencing the progression of PD to T2D, along with genetic factors, diet, lifestyle, obesity, and IR, one can also highlight the low level of testosterone in the blood serum in men.30-33 Various reports document decreased testosterone levels in men with obesity, PD, and T2D, and the effectiveness of testosterone intervention for preventing PD and T2D.34-43 A study by Souteiro et al.44 showed that IR, and not hyperglycemia and weight per se, seems to be the main determinant of low testosterone levels in obese males. Harrington et al.45 showed a 39% increase in HOMA-IR after one year of androgen deprivation therapy. Serum testosterone levels may vary across populations with different lifestyles/behaviors, and the role of testosterone in long-term outcomes and causation remains complex. In this study, we evaluated the variation of testosterone levels in adult Saudi men with normal weight (NW) and PD (NW-PD) and men with overweight (OW) and PD (OW-PD), and investigated the correlation between body mass index (BMI) and serum testosterone in men with PD. Materials and Methods This case-control study comprised 391 adult Saudi males (age range: 35-40 years) and was conducted at Umm Al-Qura University (UQU) and UQU-related hospitals in Makkah, Kingdom of Saudi Arabia (KSA), from January 20, 2024, to January 20, 2025. The adult subjects were categorized into four groups: 1) NW control (NW-C, n=99), 2) OW control (OW-C, n=98), 3) men with NW and PD (NW-PD, n=99), and 4) men with OW and PD (OW-PD, n=95) All groups of the subjects comprising NW-C, OW-C, NWPD, and OW-PD were age-matched. None of the patients had T2D, anemia, cardiovascular disorders, or other complicated conditions. Only the subjects with normal hemoglobin levels were included in the current study. The subjects in the present study included only non-smokers with no reproductive/ endocrine complications. It was confirmed by estimating sex hormone-binding globulin (SHBG) that they have no hypogonadism-related symptoms. The subjects in the current study had a BMI of 18.5-29.9 kg/m². Sample size was evaluated at the start of the study. The BMI ranges for the NW-C, OW-C, NW-PD, and OW-PD groups were 18.5-24.9 kg/m², 25.0-29.9 kg/m², 18.5-24.9 kg/m², and 25.0-29.9 kg/m², respectively. A questionnaire was prepared to measure general features and the history of the male subjects. Fasting was defined as ≥10 hours since the last meal. The PD was defined based on the FBG levels in the range of 110-125 mg/dL. Hemoglobin (Hb) levels were determined using the Sysmex XN-100i hematology analyzer (Sysmex Europe SE, Norderstedt, Germany). The serum SHBG and testosterone levels were determined using ELISA kits. Statistical analysis was performed using the statistical software package SPSS ver (...truncated)