INTRODUCTION
Type 2 diabetes mellitus (DM) is a significant health problem affecting major populations worldwide. India is known as the “diabetes capital of the world.”[1] Hypogonadism is a complication of type 2 DM.[2] Hypogonadism is a clinical syndrome that consists of clinical symptoms, with or without signs, and is associated with biochemical evidence of testosterone deficiency.[3] A decrease in testosterone levels can lead to different degrees of pathophysiologic changes in bone, muscle, fat, and the cardiovascular system.[4]
Visceral obesity is a significant cause of insulin resistance, an essential feature of type 2 DM. Obesity is a pro-inflammatory state in which the visceral fat produces inflammatory cytokines, adipokines, and other pro-inflammatory factors. Obesity also leads to increased release of estrogen and free fatty acids. These factors can potentially contribute to suppressing the hypothalamus–pituitary–gonadal axis leading to androgen deficiency.[5]
It appears from the literature that hypogonadism is a common finding in men with type 2 DM, i.e., often missed. Low-testosterone levels appear to predict many adverse effects, which may be potentially reversible by testosterone therapy. However, the data regarding hypogonadism in type 2 DM in India are scarce, and it is very important to understand the present disease burden. It is still unclear, which correlates of diabetes are associated with hypogonadism. Therefore, it is, especially important to explore the risk factors for hypogonadism to facilitate prevention, diagnosis, and early treatment.
The present study was conducted to evaluate the prevalence of hypogonadism in men with type 2 DM and to observe the correlation between diabetes and risk factors for male hypogonadism and establish whether these risk factors for hypogonadism are independent of each other in male patients with type 2 DM.
METHODS
This cross-sectional study was conducted on 200 type 2 DM male patients (diagnosed as per the American Diabetes Association criteria) in the age group between 30 and 60 years, visiting Justice KS Hegde Charitable Hospital, Deralakatte, Mangaluru. Patients with known causes of hypogonadism, type 1 DM, chronic liver disease, advanced malignancy, debilitating diseases such as tuberculosis, malabsorption, inflammatory bowel disease, pyrexia of unknown origin, acquired immunodeficiency syndrome, and sickle cell disease, autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, any inflammatory disease or infection, and participants already receiving hormone replacement therapy were excluded from the study.
After obtaining the informed consent 4 ml of venous blood was collected from antecubital vein after 8–12 h of fasting under aseptic conditions. Samples were centrifuged at 3000 rpm for 10 min, and serum obtained was used for the analysis.
Method of biochemical analysis
Total testosterone was estimated by spectrophotometric, kinetic, and enzymatic methods. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and dehydroepiandrosterone sulfate (DHEA-S) were estimated by electrochemiluminescence immunoassay. Sex hormone-binding globulin (SHBG) was estimated by enzyme-linked immunosorbent assay. Total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-c), and LDL-c were estimated by enzymatic colorimetric assay. Insulin was estimated by electrochemiluminescence immunoassay.
Body weight was measured using a standard analog weighing scale to the nearest kilogram.
Body mass index (BMI) was calculated as weight (kg)/height2 (m).
Statistical analysis
The percentage was used to document the prevalence of hypogonadism in type 2 diabetics. Quantitative data were represented as mean ± standard deviation for data following normal distribution or median and interquartile range for skewed data.
The correlation of metabolic index parameters of type 2 diabetes with sex hormone levels was done using Pearson’s correlation test. P < 0.05 was considered statistically significant. Statistical analysis will be performed using SPSS for windows version 20.0(SPSS Inc.,Chicago IL,USA).
RESULTS
Mean weight of the study population was 67.08± 6.7 kg, Mean height of the study population was 1.63± 0.37 m, Mean BMI of the study population was 25.02±2.01 [Table 1].
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Table 1: Anthropometric parameters of the study population
The mean FBS in the study subjects was 191.51± 71.75. Mean fasting insulin level was 11.28± 11.37 The mean Total cholesterol level was 210.83± 56.83(mg/dL). The mean Triglyceride level was 180.9± 65.86(mg/dL). Mean HDL-c was 35.65± 9.52(mg/dL). Mean LDL-c was 143.8± 51.14(mg/dL). Mean VLDL was 36.5± 19.72 [Table 2].
Table 2: Biochemical parameters of the study population
Distribution of study subjects based on BMI showed 53.5% were normal, 17.5% were overweight and 29% were obese) [Table 3 and Figure 1].
Table 3: Distribution of the study population based on body mass index
Figure 1: BMI status of the study population. BMI: Body mass index
Hypogonadism was defined as testosterone values <3 ng/mL.[6] Secondary (hypogonadotropic hypogonadism (HH)) was defined as TT levels <3 ng/mL and LH values <10 IU/L. Primary hypogonadism was defined as TT levels <3 ng/mL and LH levels >10 IU/L.
The prevalence of hypogonadism in male type 2 diabetics was 26% [Table 4]. Primary hypogonadism was present in 48.1% and secondary hypogonadism was present in 51.9% of male type 2 diabetics [Table 5 and Figure 2]. The percentage of the study participants with hypogonadism increased with an increase in BMI [Figure 3].
Table 4: Prevalence of hypogonadism in the study population
Table 5: Prevalence of primary and secondary hypogonadism
Figure 2: Prevalence of hypogonadism among the study population
Figure 3: Distribution of hypogonadism in the study population based on BMI groups. BMI: Body mass index
Total testosterone showed a negative correlation with BMI, which was statistically significant (r = −0.246 and P < 005). Total testosterone showed a negative correlation with TC (r = −0.139, P = 0.130), triglyceride (r = −0.069, and P = 0.33), LDL-c (r = −0.107 and P = 0.130), very-low-density lipoprotein (VLDL) (r = −0.029 and P = 0.68), and a positive correlation with HDL-c (r = 0.070 and P = 0.326) which was not statistically significant.
Total testosterone showed a negative correlation with insulin levels (r = −0.074 and P = 0.300) and HOMA-IR (r = −0.079 and P = 0.268) which was not statistically significant.
Fasting Blood Sugar (FBS) and BMI correlated negatively with SHBG and were statistically significant (r = −0.196 and P < 0.01), (r = −0.175 and P < 0.05). A positive correlation was present between TG and BMI with DHEA-S (r = 0.139, P < 0.05, and r = 0.161, P < 0.05) [Table 6].
Table 6: Correlation of biochemical parameters among the study participants
DISCUSSION
The present study intended to study the prevalence of hypogonadism in male patients with type 2 DM and to determine its associated factors. The prevalence of hypogonadism observed in the present study was 26%. Primary hypogonadism is associated with low-testosterone levels, and high-normal to high levels of LH and FSH were present in 48.1% of the study population. Secondary hypogonadism (HH), which is associated with low testosterone levels and normal to low levels of LH and FSH, was present in 51.9% of the study population [Table 5 and Figure 3]. This finding is consistent with the study by Alhazek etal. who found that 36.4% of patients with type 2 DM had total testosterone levels <3 ng/mL, and HH was the predominant type of hypogonadism.[7]
Our study demonstrated that the percentage of the study participants with hypogonadism increased with an increase in BMI. Obesity increases the conversion of testosterone into estrogen by aromatase which results in decreased testosterone levels.[8]
Our study showed a negative correlation between total testosterone and TC (r = −0.139, P = 0.130, triglyceride (r = −0.069, and P = 0.33), LDL-c (r = −0.107 and P = 0.130) and VLDL (r = −0.029 and P = 0.68) and a positive correlation with HDL-c (r = 0.070 and P = 0.326), but it was not statistically significant [Table 6]. The relationship between testosterone and lipid profile is still unclear. A study by Abate etal. reported that testosterone increases the expression of hepatic lipase in HepG2 cells and regulates HDL cholesterol levels, promotes reverse cholesterol transport, and exerts an antiatherogenic effect.[9]
The present study showed a negative correlation between testosterone and insulin levels (r = −0.074 and P = 0.300) and HOMA-IR (r = −0.079 and P = 0.268), but it was not statistically significant [Table 6]. Zheng etal. in their study showed that total testosterone correlated negatively with insulin and HOMA-IR, which was statistically significant.[10]
Our study also demonstrated that FBS and BMI correlated negatively with SHBG and was statistically significant (r = −0.196 and P < 0.01), (r = −0.175 and P < 0.05), which was in accordance with the study by Mohammed etal., who showed that SHBG to be negatively affected by FBS.[11] Hyperinsulinemia and insulin resistance are associated with low-SHBG levels suggesting that insulin level and insulin resistance are suppressive to SHBG production.[12]
CONCLUSIONS
India is called the diabetes capital of the world. Given the large numbers of individuals with diabetes in India, diabetic patients with low-serum testosterone are profoundly high. This urgently calls for implementing early, universal screening programs, irrespective of the symptoms of androgen deficiency, to detect those who have low-serum total testosterone levels at an early stage and supplement testosterone accordingly.
Limitation of the study
Free testosterone levels can reflect the extent of testosterone’s biological activities, the free testosterone concentration should be used to assess hypogonadism, but the determination of free testosterone is difficult, so free testosterone is calculated frequently with formula.
Ethical statement
Ethical clearance was taken from the institutional ethical committee (INST.EC/EC/075/2018-19).
Financial support and sponsorship
The study was support by the Research Society for Study of Diabetes in India (RSSDI).
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
The authors would like to thank Nitte (Deemed to be University) for providing an opportunity to conduct this research.
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