PMID- 37900148
OWN - NLM
STAT- MEDLINE
DCOM- 20231031
LR  - 20231101
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 14
DP  - 2023
TI  - New evidence for the effect of type 2 diabetes and glycemic traits on 
      testosterone levels: a two-sample Mendelian randomization study.
PG  - 1238090
LID - 10.3389/fendo.2023.1238090 [doi]
LID - 1238090
AB  - OBJECTIVE: Type 2 diabetes mellitus (T2DM) is an endocrine-related disease with 
      an increasing incidence worldwide. Male sexual dysfunction is common in diabetic 
      patients. Therefore, we designed a Mendelian randomization (MR) study to 
      investigate the association of type 2 diabetes and 3 glycemic traits with 
      testosterone levels. METHODS: Uncorrelated single nucleotide polymorphisms (SNPs) 
      associated with T2DM (N = 228), fasting insulin (N = 38), fasting glucose (N = 
      71), and HbA1c (N = 75) at the genome-wide significance were selected as 
      instrument variables. Genetic associations with testosterone levels (total 
      testosterone, TT, bioavailable testosterone, BT, and sex hormone-binding 
      globulin, SHBG) were obtained from the UK Biobank studies and other large 
      consortia. Two-sample MR analysis was used to minimize the bias caused by 
      confounding factors and response causality. Multivariable MR analysis was 
      performed using Body mass index (BMI), Triglycerides (TG), LDL cholesterol (LDL), 
      and adiponectin to adjust for the effects of potential confounders. RESULTS: Type 
      2 diabetes mellitus was associated with the decrease of total testosterone (beta: 
      -0.021,95%CI: -0.032, -0.010, p<0.001) and sex hormone binding globulin (beta: 
      -0.048,95%CI: -0.065, -0.031, p<0.001). In males, total testosterone (beta: 0.058, 
      95% CI: 0.088, 0.028, p < 0.001) decreased. In females, it was associated with an 
      increase in bioavailable testosterone (beta: 0.077,95%CI: 0.058,0.096, p<0.001). 
      Each unit (pmol/L) increase in fasting insulin was associated with 0.283nmol/L 
      decrease in sex hormone-binding globulin (95%CI: -0.464, -0.102, p=0.002) and 
      0.260nmol/L increase in bioavailable testosterone (95%CI: -0.464, -0.102, p= 
      0.002). In males, sex hormone binding globulin decreased by 0.507nmol/L (95%CI: 
      -0.960, -0.054, p= 0.028) and bioavailable testosterone increased by 0.216nmol/L 
      (95%CI: 0.087,0.344, p= 0.001). In females, sex hormone binding globulin 
      decreased by 0.714 nmol/L (95%CI: -1.093, -0.335, p<0.001) and bioavailable 
      testosterone increased by 0.467nmol/L (95%CI: 0.286,0.648, p<0.001). Each unit 
      (%) increase in HbA1c was associated with 0.060nmol/L decrease in sex 
      hormone-binding globulin (95%CI: -0.113, -0.007, p= 0.026). In males, total 
      testosterone decreased by 0.171nmol/L (95%CI: -0.288, -0.053, p=0.005) and sex 
      hormone binding globulin decreased by 0.206nmol/L (95%CI: -0.340, -0.072, 
      p=0.003). Total testosterone increased by 0.122nmol/L (95%CI: 0.012,0.233, 
      p=0.029) and bioavailable testosterone increased by 0.163nmol/L (95%CI: 
      0.042,0.285, p=0.008) in females. CONCLUSIONS: Using MR Analysis, we found 
      independent effects of type 2 diabetes, fasting insulin, and HbA1c on total 
      testosterone and sex hormone-binding globulin after maximum exclusion of the 
      effects of obesity, BMI, TG, LDL and Adiponectin.
CI  - Copyright (c) 2023 Jiang, Wang, Yang and Yang.
FAU - Jiang, Chengyang
AU  - Jiang C
AD  - Department of Pediatric Surgery, Maternal and Child Hospital of Hubei Province, 
      Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 
      Hubei, China.
FAU - Wang, Yuwei
AU  - Wang Y
AD  - School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, 
      China.
FAU - Yang, Wenqiang
AU  - Yang W
AD  - School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, 
      China.
FAU - Yang, Xinghai
AU  - Yang X
AD  - Department of Pediatric Surgery, Maternal and Child Hospital of Hubei Province, 
      Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 
      Hubei, China.
LA  - eng
PT  - Journal Article
DEP - 20231011
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Sex Hormone-Binding Globulin)
RN  - 0 (Glycated Hemoglobin)
RN  - 0 (Adiponectin)
RN  - 3XMK78S47O (Testosterone)
RN  - 0 (Insulin)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Female
MH  - Humans
MH  - Male
MH  - *Diabetes Mellitus, Type 2/genetics/epidemiology
MH  - Sex Hormone-Binding Globulin/metabolism
MH  - Glycated Hemoglobin
MH  - Adiponectin/metabolism
MH  - Mendelian Randomization Analysis
MH  - Testosterone
MH  - Insulin/metabolism
MH  - Triglycerides
PMC - PMC10600375
OTO - NOTNLM
OT  - Mendelian randomization
OT  - diabetes
OT  - glycemic traits
OT  - sexual dysfunction
OT  - testosterone
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/10/30 06:47
MHDA- 2023/10/31 06:42
PMCR- 2023/01/01
CRDT- 2023/10/30 04:30
PHST- 2023/06/10 00:00 [received]
PHST- 2023/09/25 00:00 [accepted]
PHST- 2023/10/31 06:42 [medline]
PHST- 2023/10/30 06:47 [pubmed]
PHST- 2023/10/30 04:30 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2023.1238090 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2023 Oct 11;14:1238090. doi: 
      10.3389/fendo.2023.1238090. eCollection 2023.