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Table 2 Evidence of links between SHBG and sex hormones and insulin resistance/type 2 diabetes from non-genetic studies

From: Recent progress in the use of genetics to understand links between type 2 diabetes and related metabolic traits

Study Primary perturbation Effect on insulin secretion/resistance Reference(s)
Evidence that SHBG is upstream of type 2 diabetes
Prospective studies Altered levels of sex hormones Increased risk of type 2 diabetes [34]
PCOS in women Elevation in levels of androgens Increased risk of non-insulin-dependent diabetes mellitus [45]
Randomized controlled trial Androgen supplementation in men with low testosterone levels Increased insulin sensitivity [46]
Animal model (male mouse) Lack of androgen receptor Insulin resistance [47]
Animal model (female rat) Treatment with testosterone after oophorectomy Insulin resistance [48]
Evidence that SHBG is downstream of type 2 diabetes
In vitro study Incubation of hepatoblastoma cell line with IGF-I Decreased SHBG levels [49]
Animal model (mouse) and in vitro study Increased fasting glucose Downregulation of SHBG expression [50]
Intervention study Insulin lowering interventions in non-diabetic men and women (without PCOS) Increased SHBG levels [51, 52]
Study of obese women with PCOS Increase insulin levels Reduced serum SHBG levels [53]
  1. IGF-1, insulin-like growth factor I; PCOS, polycystic ovarian syndrome; SHBG, sex hormone binding globulin.