Single-nucleotide polymorphism, rs1799941 in the Sex Hormone-Binding Globulin (SHBG) gene, related to both serum testosterone and SHBG levels and the risk of myocardial infarction, type 2 diabetes, cancer and mortality in men: the Tromsø Study.
Our findings support a SBP treatment target of 140 mmHg and suspect no risk reduction attenuation on CVD for lower SBP targets (<120 or <130 mmHg) for most patients with uncomplicated T2DM.
Interest in SHBG has escalated in recent years because of its inverse association with polycystic ovary syndrome (PCOS), obesity, insulin resistance, metabolic syndrome, and diabetes type II.
Further, many of the environmental endocrine disrupting chemicals may exert their potential adverse effects on cardiometabolic outcomes via either estrogenic or androgenic signaling pathways, highlighting the importance of using the sex steroids and SHBG as important biochemical markers in both clinical and population studies in studying sex-specific mechanisms in the pathogenesis of T2D and its complications, as well as the need to equitably allocate resources in studying both men and women.
Associations of serum sex hormone binding globulin with bone mineral densities and higher 10-year probability of fractures in postmenopausal women with type 2 diabetes mellitus.
In terms of the prospective studies, our results showed decreases in TT (WMD: -2.35, 95%CI: -3.24 to -1.46), FT (WMD: -25.96, 95%CI: -83.98 to 32.05), and SHBG (WMD: -10.06, 95%CI: -13.29 to -6.84) in patients with T2DM.
Low circulating levels of sex hormone-binding globulin (SHBG) have been shown to be a direct and strong risk factor for type 2 diabetes, cardiovascular diseases, and hormone-dependent cancers, although the relationship between various aspects of dietary carbohydrates and SHBG levels remains unexplored in population studies.
These latter two variants are associated with T2D (risk haplotype GG; odds ratio 2.67; 95% CI 2.32-3.08; P = 2.43 × 10<sup>-4</sup>) in genome-wide association data (N = 402), but are more strongly associated with quantitative traits (DBP, SBP, ACR, eGFR) for hypertension and renal function in non-diabetic than diabetic subgroups.
In the EMPA-REG BP trial, empagliflozin significantly reduced systolic and diastolic blood pressure (SBP and DBP) compared with placebo at week 12 in patients with type 2 diabetes mellitus (T2DM) and hypertension.
Further analysis with adjustment for age, BMI, SBP, DBP, CHO and TG demonstrated that this SNP was strongly associated with T2D (P = 0.013, OR = 2.287).
Associations of SHBG with some anthropometric and metabolic variables in FDR suggests that lower levels is a marker for risk of developing T2D through obesity dependent metabolic pathways but low FAI is a better marker of state of diabetes in males.
Mendelian randomization suggested only minor, if any, causal effects of SHBG on lipid and metabolite measures and insulin resistance(n = 10,895).Causal effect estimates on type 2 diabetes for 41,439 cases and 103,870 controls indicated a causative protective role of SHBG (OR = 0.83 per 1-SD, 95% CI: 0.76, 0.91); however, effects were considerably weaker than observed in meta-analysis of prospective studies [hazard ratio (HR) = 0.47 per 1-SD, 95% CI: 0.41, 0.53].
Therefore, low SHBG could be a useful tool for identifying presymptomatic individuals with diabetes mellitus type 2 including those with androgen disorders.
This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls).
Although SHBG SNPs associated with type 2 diabetes mellitus do not appear to be associated with PCOS status, rs1799941 and rs727428 genotypes are associated with SHBG levels independent of the effects of insulin resistance and obesity.
The HR value was higher on the LTM versus the ATM independent of group and treadmill stage (P=0.002) and SBP was higher in the T2D group versus no T2D independent of treadmill mode and stage (P=0.01).
However, the AA genotype of SNP rs1800624 (-374T/A) was consistently associated with lower SBP [-5.0 mmHg (95% confidence interval -10.4 to 0.3)] and DBP [-4.2 (-7.2 to -1.3)], pulse pressure [-0.8 (-5.0 to 3.4)] as well as with less arterial stiffness [-0.56 SD (-1.04 to -0.09)] in individuals with normal glucose metabolism, but with higher SBP [6.2 (0.9-11.5)], DBP [2.1 (-0.7 to 5.0)] and pulse pressure [4.1 (-0.2 to 8.4)] in individuals with impaired glucose metabolism or type 2 diabetes mellitus (P for interaction <or=0.05 in all analyses).
Possible mechanisms by which high circulating SHBG prevents the development of type 2 diabetes involve regulation of fasting glycemia but not alteration of insulin secretory function.