Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes

ObjectiveMen with type 2 diabetes are known to have a high prevalence of testosterone deficiency. No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy (TRT). We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone.Research design and methodsA total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.8±1.3 s.d. years. Mortality rates were compared between total testosterone >10.4 nmol/l (300 ng/dl; n=343) and testosterone ≤10.4 nmol/l (n=238). The effect of TRT (as per normal clinical practise: 85.9% testosterone gel and 14.1% intramuscular testosterone undecanoate) was assessed retrospectively within the low testosterone group.ResultsMortality was increased in the low testosterone group (17.2%) compared with the normal testosterone group (9%; P=0.003) when controlled for covariates. In the Cox regression model, multivariate-adjusted hazard ratio (HR) for decreased survival was 2.02 (P=0.009, 95% CI 1.2–3.4). TRT (mean duration 41.6±20.7 months; n=64) was associated with a reduced mortality of 8.4% compared with 19.2% (P=0.002) in the untreated group (n=174). The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 (95% CI 1.3–3.9, P=0.004).ConclusionsLow testosterone levels predict an increase in all-cause mortality during long-term follow-up. Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes.

Download Full-text

Testosterone Deficiency, Cardiac Health, and Older Men

International Journal of Endocrinology ◽

10.1155/2014/143763 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

G. Hackett ◽

M. Kirby ◽

A. J. Sinclair

Keyword(s):

Type 2 Diabetes ◽

Replacement Therapy ◽

Risk Groups ◽

Testosterone Replacement ◽

Current Evidence ◽

Testosterone Replacement Therapy ◽

Testosterone Deficiency ◽

Low Testosterone ◽

Low Levels

Low levels of testosterone are manifested by erectile dysfunction, reduced sexual desire, and loss of morning erections with increasing numbers of men are being diagnosed and require treatment. The prevalence rates of testosterone deficiency vary according to different studies but may be as high as 40% in populations of patients with type 2 diabetes. There is increasing evidence that testosterone deficiency is associated with increased cardiovascular and all-cause mortality. Screening for low testosterone is recommended in a number of high risk groups including those with type 2 diabetes and metabolic syndrome. There are recent data to suggest that testosterone replacement therapy may reduce cardiovascular mortality as well as improving multiple surrogate markers for cardiovascular events. Specific clinical trials of testosterone replacement therapy are needed in selected populations but in the meantime we must treat patients based on the best current evidence.

Download Full-text

Low Testosterone Levels Are Common and Associated with Insulin Resistance in Men with Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2177 ◽

2008 ◽

Vol 93 (5) ◽

pp. 1834-1840 ◽

Cited By ~ 232

Author(s):

Mathis Grossmann ◽

Merlin C. Thomas ◽

Sianna Panagiotopoulos ◽

Ken Sharpe ◽

Richard J. MacIsaac ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Free Testosterone ◽

Total Testosterone ◽

Testosterone Deficiency ◽

Testosterone Levels ◽

Low Testosterone

Abstract Context: Low testosterone levels are common in men with type 2 diabetes and may be associated with insulin resistance. Objective: We investigated prevalence of testosterone deficiency and the relationship between testosterone and insulin resistance in a large cohort of men with type 2 and type 1 diabetes. Design: The study was a cross-sectional survey of 580 men with type 2 diabetes and 69 men with type 1 diabetes. A subgroup of 262 men with type 2 diabetes was then reassessed after a median of 6 months. Results: Forty-three percent of men with type 2 diabetes had a reduced total testosterone, and 57% had a reduced calculated free testosterone. Only 7% of men with type 1 diabetes had low total testosterone. By contrast, 20.3% of men with type 1 diabetes had low calculated free testosterone, similar to that observed in type 2 diabetes (age-body mass index adjusted odds ratio = 1.4; 95% confidence interval = 0.7–2.9). Low testosterone levels were independently associated with insulin resistance in men with type 1 diabetes as well as type 2 diabetes. Serial measurements also revealed an inverse relationship between changes in testosterone levels and insulin resistance. Conclusions: Testosterone deficiency is common in men with diabetes, regardless of the type. Testosterone levels are partly influenced by insulin resistance, which may represent an important avenue for intervention, whereas the utility of testosterone replacement remains to be established in prospective trials.

Download Full-text

Long‐Term Mortality Associated With Use of Carvedilol Versus Metoprolol in Heart Failure Patients With and Without Type 2 Diabetes: A Danish Nationwide Cohort Study

Journal of the American Heart Association ◽

10.1161/jaha.121.021310 ◽

2021 ◽

Vol 10 (18) ◽

Author(s):

Brian Schwartz ◽

Colin Pierce ◽

Christian Madelaire ◽

Morten Schou ◽

Søren Lund Kristensen ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Mortality Benefit ◽

Reduced Ejection Fraction ◽

All Cause Mortality ◽

Long Term Mortality ◽

New Onset

Background Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and Results Using Danish nationwide databases between 2010 and 2018, we followed patients with new‐onset HFrEF treated with either carvedilol or metoprolol for all‐cause mortality until the end of 2018. Follow‐up started 120 days after initial HFrEF diagnosis to allow initiation of guideline‐directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well‐balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow‐up. We observed no mortality differences between carvedilol and metoprolol, multivariable‐adjusted hazard ratio (HR) 0.97 (0.90–1.05) in patients with T2D versus 1.00 (0.95–1.05) for those without T2D, P for difference =0.99. Rates of new‐onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75–0.91), P <0.0001. Conclusions In a contemporary clinical cohort of HFrEF patients with and without T2D, carvedilol was not associated with a reduction in long‐term mortality compared with metoprolol. However, carvedilol was associated with lowered risk of new‐onset T2D supporting the assertion that carvedilol has a more favorable metabolic profile than metoprolol.

Download Full-text

5-Year Clinical Outcomes of Successful Recanalisation for Coronary Chronic Total Occlusions in Patients With or Without Type 2 Diabetes Mellitus

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.691641 ◽

2021 ◽

Vol 8 ◽

Author(s):

Peizhi Wang ◽

Deshan Yuan ◽

Sida Jia ◽

Pei Zhu ◽

Ce Zhang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Propensity Score ◽

Diabetic Patients ◽

Chronic Total Occlusions ◽

All Cause Mortality

Background: Despite substantial improvement in chronic total occlusions (CTO) revascularization technique, the long-term clinical outcomes in diabetic patients with revascularized CTO remain controversial. Our study aimed to investigate the 5-year cardiovascular survival for patients with or without type 2 diabetes mellitus (DM) who underwent successful percutaneous coronary intervention (PCI) for CTO.Methods: Data of the current analysis derived from a large single-center, prospective and observational cohort study, including 10,724 patients who underwent PCI in 2013 at Fuwai Hospital. Baseline, angiographic and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which consisted of death, recurrent myocardial infarction (MI), stroke and target vessel revascularization (TVR). The secondary endpoint was all-cause mortality. Cox regression analysis and propensity-score matching was performed to balance the baseline confounders.Results: A total of 719 consecutive patients with ≥1 successful CTO-PCI were stratified into diabetic (n = 316, 43.9%) and non-diabetic (n = 403, 56.1%) group. During a median follow-up of 5 years, the risk of MACCE (adjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.08–2.00, P = 0.013) was significantly higher in the diabetic group than in the non-diabetic group, whereas the adjusted risk of all-cause mortality (HR 2.37, 95% CI 0.94–5.98, P = 0.068) was similar. In the propensity score matched population, there were no significant differences in the risk of MACCE (HR 1.27, 95% CI 0.92–1.75, P = 0.155) and all-cause mortality (HR 2.56, 95% CI 0.91–7.24, P = 0.076) between groups. Subgroup analysis and stratification analysis revealed consistent effects on 5-year MACCE across various subgroups.Conclusions: In patients who received successful CTO-PCI, non-diabetic patients were related to better long-term survival benefit in terms of MACCE. The risk of 5-year MACCE appeared to be similar in less-controlled and controlled diabetic patients after successful recanalization of CTO. Further randomized studies are warranted to confirm these findings.

Download Full-text

Impact of Type 2 Diabetes on Five-year Clinical Outcomes Following Successful Percutaneous Coronary Intervention on Chronic Total Occlusions: a Propensity Matched Cohort Analysis

10.21203/rs.3.rs-378689/v1 ◽

2021 ◽

Author(s):

Peizhi Wang ◽

Deshan Yuan ◽

Sida Jia ◽

Pei Zhu ◽

Ce Zhang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Percutaneous Coronary Intervention ◽

Coronary Intervention ◽

Diabetic Patients ◽

Chronic Total Occlusions ◽

Percutaneous Coronary ◽

All Cause Mortality

Abstract Background: Despite substantial improvement in chronic total occlusions (CTO) revascularization technique, the long-term clinical outcomes in diabetic patients with revascularized CTO remain controversial. Our study aimed to investigate the five-year cardiovascular survival for patients with or without type 2 diabetes mellitus (DM) who underwent successful percutaneous coronary intervention (PCI) for CTO. Methods: Data of the current analysis derived from a large single-center, prospective and observational cohort study, including 10,724 patients who underwent PCI in 2013 at Fuwai Hospital. Baseline, angiographic and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which consisted of death, recurrent myocardial infarction (MI), stroke and target vessel revascularization (TVR). The secondary endpoint was all-cause mortality. Cox regression analysis and propensity-score matching was performed to balance the baseline confounders. Results: A total of 719 consecutive patients with ≥ 1 successful CTO-PCI were stratified into diabetic (n=316, 43.9%) and non-diabetic (n=403, 56.1%) group. During a median follow-up of 5 years, the risk of MACCE (adjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.08-2.00, P = 0.013) was significantly higher in the diabetic group than in the non-diabetic group, whereas the adjusted risk of all-cause mortality (HR 2.37, 95% CI 0.94-5.98, P = 0.068) was similar. In the propensity score matched population, there were no significant differences in the risk of MACCE (HR 1.27, 95% CI 0.92-1.75, P = 0.155) and all-cause mortality (HR 2.56, 95% CI 0.91-7.24, P = 0.076) between groups. Subgroup analysis revealed a consistent effect on five-year MACCE across various subgroups.Conclusions: In patients who received successful CTO-PCI, non-diabetic patients were related to better long-term survival benefit in terms of MACCE. Further randomized studies are warranted to confirm these findings.

Download Full-text

SAT-045 Free Testosterone and Cardiometabolic Parameters in Adult Men - Comparison of Algorithms for Calculation of Serum Free Testosterone

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1685 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Stine Agergaard Holmboe ◽

Ravi Jasuja ◽

Laerke Priskorn ◽

Niels Jørgensen ◽

Anders Juul ◽

...

Keyword(s):

Type 2 Diabetes ◽

Free Testosterone ◽

Total Testosterone ◽

Inverse Association ◽

Serum Free ◽

Relative Standard ◽

All Cause Mortality

Abstract Context. Determining the free or bioavailable testosterone level has gained increasing interest over the years and different indirect algorithms have been suggested. Objective. To compare commonly used algorithms of calculation of serum free testosterone, specifically free androgen index (FAI), free testosterone estimated using the Vermeulen algorithm (cFTV) and the Zakharov algorithm (cFTZ) as well as total testosterone in relation to baseline and long-term cardiometabolic conditions. Design. A prospective cohort study of men participating in four independent population-based surveys (MONICA I-III and Inter99) from 1982 to 2001 and followed until December 2012 with baseline and follow-up information on cardiometabolic parameters. Setting and Participants. 5350 randomly selected men from the general population aged 30, 40, 50, 60, or 70 years at baseline participated. Main Outcome Measures. Baseline cardiometabolic parameters and follow-up information on type 2 diabetes, ischemic heart disease, cardiovascular disease mortality, and all-cause mortality. Results. Free testosterone levels calculated according to the two algorithms differed systematically but however correlated well (cFTV vs. cFTZ: r=0.9, p<0.01) and the relative standard deviations ranged from 37% to 41%. In general, men having cardiometabolic conditions at baseline had lower absolute levels of FAI, cFTV and cFTZ. However, when age-standardizing the hormone levels, FAI levels were higher in this group of men whereas cFTV and cFTZ remained lower compared to men without these conditions. The associations seen for cFTV and cFTZ were in line with the association seen for total testosterone. Cox proportional hazard models revealed that men in the highest quartiles of cFTV or cFTZ had lower risk of developing type 2 diabetes (cFTV: HR=0.74 (0.49-1.10), cFTZ: HR=0.59 (0.39-0.91)) than men in the lowest quartile. In contrast, men with highest levels of FAI had a 74% increased risk of developing type 2 diabetes compared to men in the lowest quartile (HR=1.74, 95% CI:1.17-2.59). In relation to all-cause mortality, FAI showed the strongest inverse association followed by cFTV, whereas cFTZ and total testosterone did not show any association. Conclusion. Free testosterone estimated by the Vermeulen and Zakharov algorithms differed systematically. However, the computed values correlated well and showed similar associations to baseline and long-term cardiometabolic parameters; albeit with subtle differences. In contrast, an empiric ratio, FAI showed opposite associations to several of the examined parameters and may reflect limited clinical utility.

Download Full-text

453-P: Metabolic Syndrome Severity Score, All-Cause Mortality, and Incident Vascular Events in Type 2 Diabetes: A 13-Year, Single-Centre, Follow-Up Study

Diabetes ◽

10.2337/db19-453-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 453-P

Author(s):

MONIA GAROFOLO ◽

ELISA GUALDANI ◽

DANIELA LUCCHESI ◽

LAURA GIUSTI ◽

VERONICA SANCHO-BORNEZ ◽

...

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Severity Score ◽

Single Centre ◽

Vascular Events ◽

Follow Up Study ◽

All Cause Mortality

Download Full-text

How Family Physicians Practice the Principle of Remission Along the Glycemic Continuum

Journal of Primary Care & Community Health ◽

10.1177/2150132720977744 ◽

2020 ◽

Vol 11 ◽

pp. 215013272097774

Author(s):

Stephanie T. Fulleborn ◽

Paul F. Crawford ◽

Jeremy T. Jackson ◽

Christy J.W. Ledford

Keyword(s):

Type 2 Diabetes ◽

Medical Record ◽

The United States ◽

Case Scenario ◽

Cross Sectional ◽

Normal Glucose ◽

Normal Glucose Regulation

Introduction Recent evidence reveals that diabetes and prediabetes (preDM) can be reversed to normal glucose regulation (NGR) through significant weight loss, but how physicians clinically identify the principles of partial and complete remission of diabetes is largely unknown. Methods As part of the cross-sectional omnibus survey conducted in March 2019 at a professional annual meeting in the United States, physician participants answered case scenario questions about the diagnosis and documentation of patients with preDM and type 2 diabetes (T2DM). Results Of the registered conference attendees, 387 (72.7%) responded. When presented with the initial case of preDM, 201 physicians (70.8%) selected R73.03 Prediabetes. In a follow-up encounter with improved lab results, 118 physicians (58.7%) indicated that they would not chart any diabetes-related code and 62 (30.8%) would chart preDM again. When presented with the case of T2DM, 256 physicians (90.1%) indicated E11.0–E11.9 Type 2 Diabetes. In the follow-up encounter, only 38 (14.8%) coded a diagnosis reflecting remission from T2DM to prediabetes and 211 (82.4%) charted T2DM. Conclusion Physicians may be reluctant to document diabetes regression as there is little evidence for long-term outcomes and “downgrading” the diagnosis in the medical record may cause screenings to be missed. Documenting this regression in the medical record should communicate the accurate point on the continuum of glucose intolerance with both the patient and the care team.

Download Full-text