The association between sex hormone-binding globulin and type 2 diabetes in Nigerian men

Background: Epidemiological studies have shown that sex hormone-binding globulin (SHBG) has a role in glucose homeostasis in both men and women. However, a prospective study on Japanese-American subjects concluded that SHBG was not a significant risk factor in either men or women, suggesting ethnic differences. We were not aware of any evaluation of SHBG in subjects of African ancestry.Objectives: We investigated the association between SHBG and insulin resistance in type 2 diabetic diabetic men in a hospital in Nigeria.Method: Forty-eight male subjects with type 2 diabetes and 20 non-diabetic male subjects were recruited in this cross-sectional hospital-based study by the convenient sampling method.Height and circumferences around the waist and hip were measured to the nearest 0.5 cm and the waist–hip ratio was calculated from this measurement. Weight was measured and body mass index was calculated. Fasting plasma glucose concentration was measured by the glucose oxidase method with a between-run coefficient of variation of 3%. Insulin and SHBG were measured by means of enzyme-linked immunosorbent assay (ELISA).Results: There was a statistically-significant difference between test results for the diabetic and non-diabetic patients. The mean SHBG concentration was higher in the non-diabetic group (42.2 nmol/L) than the diabetic group (30.5 nmol/L). A significant inverse association between insulin resistance and SHBG was observed (r = 0.353, p < 0.015).Conclusion: This study supported earlier observations that a significant inverse correlation exists between SHBG and insulin resistance and provides evidence that the relationship may extend to type 2 diabetic men of African ancestry in Nigeria.

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The Biological Variation of Sex Hormone-Binding Globulin in Type 2 Diabetes: Implications for sex hormone-binding globulin as a surrogate marker of insulin resistance

Diabetes Care ◽

10.2337/diacare.27.1.278 ◽

2003 ◽

Vol 27 (1) ◽

pp. 278-280 ◽

Cited By ~ 18

Author(s):

V. Jayagopal ◽

E. S. Kilpatrick ◽

P. E. Jennings ◽

S. Holding ◽

D. A. Hepburn ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Surrogate Marker ◽

Biological Variation ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

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Sex Hormone Binding Globulin Is a Marker of Hepatic Insulin Sensitivity and Lipogenesis, but Is Not Independently Associated with Type 2 Diabetes Mellitus in Men

10.1210/endo-meetings.2011.part1.p15.p1-339 ◽

2011 ◽

pp. P1-339-P1-339

Author(s):

Gary Wittert ◽

Sean Martin ◽

David Wilson ◽

Alicia Jenkins ◽

Andre Araujo ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Sensitivity ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding ◽

Hepatic Insulin Sensitivity

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Level of sex hormone-binding globulin is positively correlated with insulin sensitivity in men with type 2 diabetes.

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.76.2.8432768 ◽

1993 ◽

Vol 76 (2) ◽

pp. 275-278 ◽

Cited By ~ 3

Author(s):

K I Birkeland ◽

K F Hanssen ◽

P A Torjesen ◽

S Vaaler

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

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The association of sex hormone-binding globulin with mortality is mediated by age and testosterone in men with type 2 diabetes

Andrology ◽

10.1111/andr.12520 ◽

2018 ◽

Vol 6 (6) ◽

pp. 846-853 ◽

Cited By ~ 5

Author(s):

S. Ramachandran ◽

R. C. Strange ◽

A. A. Fryer ◽

F. Saad ◽

G. I. Hackett

Keyword(s):

Type 2 Diabetes ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

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Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men

Acta Endocrinologica ◽

10.1530/eje-09-0943 ◽

2010 ◽

Vol 162 (4) ◽

pp. 747-754 ◽

Cited By ~ 85

Author(s):

Torkel Vikan ◽

Henrik Schirmer ◽

Inger Njølstad ◽

Johan Svartberg

Keyword(s):

Type 2 Diabetes ◽

Waist Circumference ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Total Testosterone ◽

Hormone Binding ◽

Adjusted Risk ◽

The Third ◽

Increased Risk

ObjectiveTo study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes.DesignPopulation-based prospective cohort study.MethodsFor the analyses, 1454 men who participated in the fourth Tromsø study (1994–1995) were used. Cases of diabetes were retrieved and validated until 31.12.05 following a detailed protocol. The prospective association between sex hormones and diabetes was examined using Cox proportional hazard regression analysis, allowing for multivariate adjustments.ResultsThere was a significantly lowered multi-adjusted risk for later diabetes with higher normal total testosterone levels, both linearly per s.d. increase (hazard ratio (HR) 0.71, confidence interval (CI) 0.54–0.92) and in the higher quartiles of total testosterone than in the lowest quartiles (HR 0.53, CI 0.33–0.84). A reduced multi-adjusted risk for incident diabetes was also found for men with higher sex hormone-binding globulin (SHBG) levels, both linearly per s.d. increase (HR 0.55, CI 0.39–0.79) and when comparing the third (HR 0.38, CI 0.18–0.81) and the fourth quartile (HR 0.37, CI 0.17–0.82) to the lowest quartile. The associations with total testosterone and SHBG were no longer significant after inclusion of waist circumference to the multivariate models. Estradiol (E2) was positively associated with incident diabetes after multivariate adjustments including waist circumference when comparing the second (HR 0.49, CI 0.26–0.93) and the third (HR 0.51, CI 0.27–0.96) quartile to the highest quartile.ConclusionMen with higher E2 levels had an increased risk of later diabetes independent of obesity, while men with lower total testosterone and SHBG had an increased risk of diabetes that appeared to be dependent on obesity.

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Sex hormone-binding globulin associations with circulating lipids and metabolites and the risk for type 2 diabetes: observational and causal effect estimates

International Journal of Epidemiology ◽

10.1093/ije/dyv093 ◽

2015 ◽

Vol 44 (2) ◽

pp. 623-637 ◽

Cited By ~ 53

Author(s):

Q. Wang ◽

A. J. Kangas ◽

P. Soininen ◽

M. Tiainen ◽

T. Tynkkynen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Causal Effect ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

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Association of sex hormone-binding globulin and free testosterone with mortality in men with type 2 diabetes mellitus

Acta Endocrinologica ◽

10.1530/eje-15-0672 ◽

2016 ◽

Vol 174 (1) ◽

pp. 59-68 ◽

Cited By ~ 20

Author(s):

Aye N Tint ◽

Rudolf Hoermann ◽

Henry Wong ◽

Elif I Ekinci ◽

Richard J MacIsaac ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Free Testosterone ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Inverse Association ◽

Hormone Binding ◽

All Cause Mortality

ObjectiveLow circulating testosterone levels have been associated with increased mortality in men. We hypothesized that the prognostic role of testosterone in men with type 2 diabetes mellitus (T2DM) is influenced by its carrier protein sex hormone-binding globulin (SHBG).DesignWe conducted a prospective cohort study at a tertiary referral centre.MethodsIn total, 531 men with T2DM presenting to a diabetes clinic in 2004–2005 were followed prospectively until death, or July 31, 2014, and a survival analysis was performed. The main outcome measure was all cause mortality.ResultsOver a mean (s.d.) follow up of 7.6 years (2.6) 175 men (33%) died. In Cox proportional hazard models both higher SHBG (Hazard Ratio (HR) 1.012 (95% CI 1.002–1.022), P=0.02) and lower calculated free testosterone (cFT) (HR 0.995 (95% CI 0.993–0.998), P=0.001) were risk factors for all cause mortality independently of age, BMI, presence of macro- and microvascular disease, duration of T2DM, hemoglobin, renal function, insulin use, C-reactive protein and homeostatic model of insulin resistance. By contrast, the inverse association of total testosterone (TT) with mortality weakened after these adjustments (P=0.11). SHBG remained associated with mortality (P<0.001) both if substituted for or added to TT in the multivariable model. In the fully adjusted model, an increase of SHBG by 17.3 nmol/l (1 s.d.) increased mortality by 22% and a decrease in cFT by 81 pmol/l (1 s.d.) increased mortality by 45%.ConclusionsThe association of SHBG with mortality in men with T2DM is novel. Whether SHBG acts via regulation of testosterone, has intrinsic biological roles, or is a marker of poor health requires further study.

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Serum Sex Hormone Binding Globulin (SHBG) Relation with Different Components of Metabolic Syndrome in Men with Type 2 Diabetes

Hormone and Metabolic Research ◽

10.1055/s-0043-123348 ◽

2017 ◽

Vol 50 (02) ◽

pp. 138-144 ◽

Cited By ~ 2

Author(s):

Khalid Siddiqui ◽

Khalid Al-Rubeaan ◽

Shaik Nawaz ◽

Khaled Aburisheh ◽

Anas Alaabdin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Fasting Blood Glucose ◽

International Diabetes Federation ◽

Free Testosterone ◽

Gonadal Hormones ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

AbstractSex hormone binding globulin (SHBG) is demonstrated to be decreased in subjects with metabolic syndrome (MetS). The aim of the present study was to investigate the association of SHBG in relation to MetS components among men with type 2 diabetes (T2D). This cross-sectional study was carried out among 429 Saudi T2D male patients aged >30 years. Metabolic syndrome was defined using International Diabetes Federation (IDF) criteria. Fasting blood glucose (FBG), HbA1c, albumin, and lipid parameter were measured. Gonadal hormones, namely total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG were determined using ELISA. The SHBG levels of the MetS group was significantly lower than non-MetS group 47.25±31.03 nmol/l vs. 56.55±37.84 nmol/l; p=0.013. As the MetS score increases, SHBG and HDL levels decrease while weight, BMI, waist circumference, SBP, DBP, FBG, HbA1c, TC, and TG levels increase. SHBG correlated with age, BMI, TG, HDL, TT, free testosterone, and bio-available testosterone. This is the first study that provides detailed analyses of SHBG with MetS components in male diabetic subjects. The mean serum SHBG levels gradually declined with the addition of MetS components in T2D men. TT, free testosterone, and bio-available testosterone remained independently associated with SHBG by multivariable regression analysis.

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