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Differential effects of metformin on age related comorbidities in older men with type 2 diabetes.

ABSTRACT: To identify distinct temporal likelihoods of age-related comorbidity (ARC) diagnoses: cardiovascular diseases (CVD), cancer, depression, dementia, and frailty-related diseases (FRD) in older men with type 2 diabetes (T2D) but ARC naïve initially, and assess the heterogeneous effects of metformin on ARCs and mortality.We identified a clinical cohort of male veterans in the United States who were ?65years old with T2D and free from ARCs during 2002-2003. ARC diagnoses during 2004-2012 were analyzed using latent class modeling adjusted for confounders.The cohort consisted of 41,204 T2D men with age 74.6±5.8years, HbA1c 6.5±0.97%, and 8393 (20.4%) metformin users. Four ARC classes were identified. 'Healthy Class' (53.6%): metformin reduced likelihoods of all ARCs (from 0.14% in dementia to 6.1% in CVD). 'High Cancer Risk Class' (11.6%): metformin reduced likelihoods of CVD (13.3%), cancer (45.5%), depression (5.0%), and FRD (13.7%). 'High CVD Risk Class' (17.4%): metformin reduced likelihoods of CVD (48.6%), cancer (3.2%), depression (2.8%), and FRD (6.3%). 'High Frailty Risk Class' (17.2%): metformin reduced likelihoods of CVD (18.8%), cancer (3.9%), dementia (3.8%), depression (15.6%), and FRD (23.8%).Metformin slowed ARC development in old men with T2D, and these effects varied by ARC phenotype.

SUBMITTER: Wang CP

PROVIDER: S-EPMC5654524 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Differential effects of metformin on age related comorbidities in older men with type 2 diabetes.

Wang Chen-Pin CP Lorenzo Carlos C Habib Samy L SL Jo Booil B Espinoza Sara E SE

Journal of diabetes and its complications 20170128 4

<h4>Aims</h4>To identify distinct temporal likelihoods of age-related comorbidity (ARC) diagnoses: cardiovascular diseases (CVD), cancer, depression, dementia, and frailty-related diseases (FRD) in older men with type 2 diabetes (T2D) but ARC naïve initially, and assess the heterogeneous effects of metformin on ARCs and mortality.<h4>Methods</h4>We identified a clinical cohort of male veterans in the United States who were ≥65years old with T2D and free from ARCs during 2002-2003. ARC diagnoses ...[more]

PMID: 28190681

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Project description:BackgroundWhether metformin may reduce the risk of age-related macular degeneration (AMD) requires confirmation. This study compared the risk of AMD between ever users and never users of metformin matched on propensity score (PS) in Taiwanese patients with type 2 diabetes mellitus.MethodsWe enrolled study subjects from Taiwan's National Health Insurance. A total of 423,949 patients with new onset diabetes from 1999 to 2005 were identified. After excluding ineligible patients and enrolling only patients aged between 50 and 79 years, we created 13,303 pairs of ever users and never users of metformin matched on PS. The patients were followed from 1 January 2006 to 31 December 2011. We estimated hazard ratios by Cox regression.ResultsAMD was newly diagnosed in 506 ever users and 639 never users. The respective incidence rates (per 100,000 person-years) were 778.72 and 1016.62. The hazard ratio (HR) and 95% confidence interval (CI) for ever versus never users was 0.756 (0.673-0.850). While ever users were categorized by tertiles of cumulative duration (<31.8, 31.8-63.9 and >63.9 months) and cumulative dose (<947.1, 947.1-2193.5 and >2193.5 g) of metformin, a dose-response pattern was observed. For the respective tertiles of cumulative duration, the HRs (95% CIs) were 1.131 (0.961-1.330), 0.821 (0.697-0.967) and 0.464 (0.384-0.561), while compared to never users. For the respective tertiles of cumulative dose, the HRs (95% CIs) were 1.131 (0.962-1.329), 0.739 (0.624-0.876) and 0.525 (0.438-0.629). A risk reduction among ever users was observed for all tertiles of defined daily dose but was most remarkable for the third tertile with a defined daily dose of >0.64. Subgroup analyses suggested that the benefit of metformin could be similarly observed among men and women and for age subgroups of 50-64 and 65-79 years. However, patients with diabetic retinopathy would not be significantly benefited and metformin did not seem to be preventive for exudative AMD.ConclusionIn general, metformin significantly reduces the risk of AMD.

Project description:IntroductionThe global incidence of uterine cancer has increased substantially in recent decades. We evaluated if the trend of increasing prevalence of diabetes mellitus (DM) and obesity are attributed to the development of uterine cancer.MethodsUsing data derived from the National Health Insurance database and Taiwan Cancer Registry, multivariate Cox proportional hazards regression models were adapted to analyze the risk factors of uterine cancer with potential confounding variables.ResultsThere were a total of 5,104,242 women aged 30-70 years enrolled in the study and 147,772 of them were diagnosed with DM during 2005-2007. In a total of 11 years of follow-up, 14,398 subjects were diagnosed with uterine cancer. An elevated risk of uterine cancer was observed in women with DM of all ages (HR 1.66, 95% CI 1.53-1.81, p < 0.0001). The effect of DM was highest at age 30-39 years (RR 3.05, 95% CI 2.35-3.96, p < 0.0001). In the group of <50 years old, DM patients had at least a twofold higher risk of developing uterine cancer (HR 2.39, 95% CI 2.09-2.74, p < 0.0001). Subjects among all ages diagnosed with polycystic ovary syndrome (PCOS) (HR 2.91, 95% CI 2.47-3.42, p < 0.0001), obesity (HR 2.13, 95% CI 1.88-2.41, p < 0.0001), and those undergoing hormone replacement therapy (HRT) (HR 1.60, 95% CI 1.33-1.93, p < 0.0001) were also positively associated with uterine cancer. Positive associations of hyperlipidemia (HR 1.33, 95% CI 1.22-1.46, p < 0.0001) and statin use (HR 1.27, 95% CI 1.12-1.44, p = 0.0002) on uterine cancer were only observed in subjects <50 years. On the contrary, hyperlipidemia was negatively associated with uterine cancer in subjects ≥50 years (HR 0.91, 95% CI: 0.84-0.98, p = 0.0122).ConclusionsDM is in general the most important risk factor for uterine cancer, especially in premenopausal women. Obesity, PCOS, HPL, statin use, and HRT were also associated with uterine cancer in subjects younger than 50 years. Premenopausal women with DM and respective comorbidities should be aware of the development of uterine cancer.

Dataset Information

Differential effects of metformin on age related comorbidities in older men with type 2 diabetes.

Publications

Differential effects of metformin on age related comorbidities in older men with type 2 diabetes.

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