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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.