Androgen Receptor CAG Repeat Polymorphism Modulates Change in Triglycerides, Diastolic Blood Pressure and PSA during Testosterone Replacement Therapy in Men with Metabolic Syndrome or Type 2 Diabetes – The TIMES2 Study

2011 ◽  
pp. P1-330-P1-330
Author(s):  
Roger D Stanworth ◽  
Samia Akhtar ◽  
Kevin S Channer ◽  
Julian D Howell ◽  
T Hugh Jones
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Androgen Receptor ◽  
Replacement Therapy ◽  
Diastolic Blood Pressure ◽  
Cag Repeat ◽  
Testosterone Replacement Therapy ◽  
Repeat Polymorphism

scholarly journals Androgen receptor CAG repeat polymorphism is associated with serum testosterone levels, obesity and serum leptin in men with type 2 diabetes

2008 ◽  
Vol 159 (6) ◽  
pp. 739-746 ◽  
Author(s):  
R D Stanworth ◽  
D Kapoor ◽  
K S Channer ◽  
T H Jones
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Androgen Receptor ◽  
Glycaemic Control ◽  
Sex Hormones ◽  
Cag Repeat ◽  
Repeat Polymorphism ◽  
Serum Leptin ◽  
Testosterone Levels

ObjectiveTo determine the relationships between androgen receptor CAG repeat polymorphism length (AR CAG), sex hormones and clinical variables in men with type 2 diabetes (DM2). Men with DM2 are known to have a high prevalence of low testosterone levels. Studies suggest that testosterone replacement therapy may improve insulin sensitivity and glycaemic control in men with DM2 and reduces central obesity and serum leptin. AR CAG is known to correlate negatively with AR sensitivity and positively with body fat, insulin levels, and leptin in healthy men.DesignCross-sectional study set in a district general hospital diabetes centre.MethodsSex hormones, AR CAG and symptoms of hypogonadism were assessed in 233 men with DM2. Associations were sought between these variables and others such as obesity, leptin, glycaemic control, and blood pressure.ResultsTestosterone was negatively associated and AR CAG positively associated with obesity and leptin. The associations of AR CAG with leptin and obesity were independent of testosterone, estradiol, gonadotropins, and age. AR CAG was also independently associated with total, bioavailable and free testosterone, LH, waist circumference, body mass index, leptin, and systolic blood pressure. There was no association of AR CAG with sex hormone binding globulin, estradiol, HbA1C or the symptoms of hypogonadism.ConclusionsThe association of longer AR CAG with obesity and leptin suggests that shorter AR CAG may have an influence in maintaining healthy anthropomorphics and metabolism in men with DM2. Testosterone and LH levels are higher in men with longer AR CAG, probably reflecting reduced negative feedback through a less sensitive receptor.

scholarly journals The role of androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and type 2 diabetes: TIMES2 sub-study

2014 ◽  
Vol 170 (2) ◽  
pp. 193-200 ◽  
Author(s):  
R D Stanworth ◽  
S Akhtar ◽  
K S Channer ◽  
T H Jones
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Androgen Receptor ◽  
Clinical Response ◽  
Cag Repeat ◽  
Testosterone Replacement ◽  
Outcome Variable ◽  
Repeat Polymorphism

ContextThe TIMES2 (testosterone replacement in hypogonadal men with either metabolic syndrome or type 2 diabetes) study reported beneficial effects of testosterone replacement therapy (TRT) on insulin resistance and other variables in men with diabetes or metabolic syndrome. The androgen receptor CAG repeat polymorphism (AR CAG) is known to affect stimulated AR activity and has been linked to various clinically relevant variables.ObjectiveTo assess the role of AR CAG in the alteration of clinical response to TRT in the TIMES2 study.DesignSubgroup analysis from a multicentre, randomised, double-blind, placebo-controlled and parallel group study.SettingOutpatient study recruiting from secondary and primary care.PatientsA total of 139 men with hypogonadism and type 2 diabetes or metabolic syndrome, of which 73 received testosterone during the TIMES2 study.InterventionTestosterone 2% transdermal gel vs placebo.Main outcome measureRegression coefficient of AR CAG from linear regression models for each variable.ResultsAR CAG was independently positively associated with change in fasting insulin, triglycerides and diastolic blood pressure during TRT with a trend to association with HOMA-IR – the primary outcome variable. There was a trend to negative association between AR CAG and change in PSA. There was no association of AR CAG with change in other glycaemic variables, other lipid variables or obesity.ConclusionAR CAG affected the response of some variables to TRT in the TIMES2 study, although the association with HOMA-IR did not reach significance. Various factors may have limited the power of our study to detect the significant associations between AR CAG, testosterone levels and change in variables with testosterone treatment. Analysis of similar data sets from other clinical trials is warranted.

scholarly journals Androgen Receptor Gene CAG Repeat Polymorphism Regulates the Metabolic Effects of Testosterone Replacement Therapy in Male Postsurgical Hypogonadotropic Hypogonadism

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Giacomo Tirabassi ◽  
Nicola delli Muti ◽  
Giovanni Corona ◽  
Mario Maggi ◽  
Giancarlo Balercia
Keyword(s):  
Androgen Receptor ◽  
Replacement Therapy ◽  
Receptor Gene ◽  
Hypogonadotropic Hypogonadism ◽  
Cag Repeat ◽  
Pituitary Function ◽  
Metabolic Effects ◽  
Testosterone Replacement ◽  
Testosterone Replacement Therapy ◽  
Repeat Polymorphism

Aim. To evaluate the independent role of androgen receptor (AR) gene CAG repeat polymorphism on metabolic effects of testosterone replacement therapy (TRT) in male postsurgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the TRT-related metabolic effects are combined with those deriving from concomitant administration of metabolically active pituitary-function replacement therapies.Methods. 15 men affected by postsurgical hypogonadotropic hypogonadism were evaluated before and after TRT. Cardiovascular risk factors (CVRFs), pituitary-dependent hormones, and AR gene CAG repeat polymorphism were considered.Results. Testosterone, insulin-like growth factor 1 (IGF-1), and estradiol were the only hormones, which varied significantly between the two phases. All CVRFs significantly improved after TRT. The number of CAG triplets was positively and significantly correlated with all the variations (Δ-) of CVRFs (except for a significant negative correlation with Δ-high-density lipoprotein); the opposite occurred between the latter and Δ-testosterone. No correlation between Δ-IGF-1 or estradiol and Δ-CVRFs was found. At multiple linear regression, after correction for Δ-testosterone, nearly all the associations between the number of CAG triplets and Δ-CVRFs were confirmed.Conclusions. In male postsurgical hypogonadotropic hypogonadism, shorter AR gene CAG tract length seems to yield greater metabolic improvement after TRT, independently of the effects of concomitant pituitary-function replacement therapies.

scholarly journals Association of Metabolic Syndrome with Albuminuria in Diabetes Mellitus Type 2

2019 ◽  
Vol 2 (2) ◽  
pp. 82
Author(s):  
Husin Thamrin ◽  
Ari Sutjahjo ◽  
Agung Pranoto ◽  
Soebagijo Adi Soelistijo
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
The Metabolic Syndrome ◽  
Low Hdl

Background : Metabolic syndrome is a risk factor for cardiovascular disease as well as the occurrence of chronic kidney disease. According to the IDF, the metabolic syndrome is diagnosed when central obesity obtained with 2 or more metabolic abnormalities that include impaired glucose metabolism, increased blood pressure, hypertriglyceridemia, and low HDL-C. Several previous studies reported an  significant association found between the metabolic syndrome with albuminuria. In Indonesia, the association of metabolic syndrome with albuminuria in type 2 diabetes have not been.reported.Objectives : To investigate the association of metabolic syndrome with albuminuria in type 2 diabetes patients.Methods : This is an analytic observational study, cross-sectional design in type 2 diabetes mellitus patients and we studied 131 subjects. Criteria metabolic syndrome according to IDF consensus and albuminuria assessed using the ACR method and the classification of albuminuria was based on consensus of Perkeni 2006. As for Statistical analysis using spearman correlation and Mann-whitney test. Significance level used was 0.05.Results : Of the 131 type 2 diabetes patients with metabolic syndrome were found  normoalbuminuria proportion 65.4%, microalbuminuria 27.1% and macroalbuminuria 7.5%. Obtained a significant association between systolic blood pressure with albuminuria, p = 0.000, r = 0.325. Fasting blood sugar with albuminuria, p = 0.01, r = 0.223. But not found significant association between diastolic blood pressure with albuminuria, p = 0.153, r = 0.125, waist circumference with albuminuria, p = 0.311, r = 0.089, low HDL with albuminuria p = 0.771, r = -0.025. Hypertriglyceridemia with albuminuria, p = 0.727 and r=0,031  Conclusion : The results of this study indicate a strong association between the components of metabolic syndrome, systolic blood pressure with albuminuria, and fasting blood sugar with albuminuria. Whereas diastolic blood pressure, waist circumference, low HDL, and hypertriglyceridemia were not found significant associations.

scholarly journals Type 2 diabetes is more predictable in women than men by multiple anthropometric and biochemical measures

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tangying Li ◽  
Huibiao Quan ◽  
Huachuan Zhang ◽  
Leweihua Lin ◽  
Lu Lin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Diastolic Blood Pressure ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Regression Coefficient ◽  
Regression Coefficients ◽  
Sexually Dimorphic ◽  
Fasting Insulin

AbstractMen and women are sexually dimorphic but whether common anthropometric and biochemical parameters predict type 2 diabetes (T2D) in different ways has not been well studied. Here we recruit 1579 participants in Hainan Province, China, and group them by sex. We compared the prediction power of common parameters of T2D in two sexes by association, regression, and Receiver Operating Characteristic (ROC) analysis. HbA1c is associated with FPG stronger in women than in men and the regression coefficient is higher, consistent with higher prediction power for T2D. Age, waist circumference, BMI, systolic and diastolic blood pressure, triglyceride levels, total cholesterol, LDL, HDL, fasting insulin, and proinsulin levels all predict T2D better in women. Except for diastolic blood pressure, all parameters associate or tend to associate with FPG stronger in women than in men. Except for diastolic blood pressure and fasting proinsulin, all parameters associate or tend to associate with HbA1c stronger in women than in men. Except for fasting proinsulin and HDL, the regression coefficients of all parameters with FPG and HbA1c were higher in women than in men. Together, by the above anthropometric and biochemical measures, T2D is more readily predicted in women than men, suggesting the importance of sex-based subgroup analysis in T2D research.

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