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Metformin Use Reverses the Increased Mortality Associated With Diabetes Mellitus During Tuberculosis Treatment.

ABSTRACT: Background:The global type 2 diabetes mellitus (DM) epidemic threatens progress made in reducing tuberculosis (TB)-related mortality worldwide. Previous clinical studies have not fully evaluated potential confounding variables in addressing the impact of DM on TB treatment outcomes. The antidiabetic agent metformin regulates autophagy and may play a role as a host-directed therapeutic adjuvant to antitubercular treatment. Methods:We conducted a retrospective cohort study comprising patients aged ?13 years undergoing treatment for culture-confirmed, drug-susceptible pulmonary TB. We assessed the effect of DM on mortality during TB treatment and 2-month TB sputum-culture conversion. We also evaluated the effect of metformin use on survival during TB treatment. Results:Among 2416 patients undergoing TB treatment, after adjusting for age, sex, chronic kidney disease, cancer, hepatitis C, tobacco use, cavitary disease, and treatment adherence, patients with DM had 1.91 times higher odds (95% confidence interval [CI], 1.51-2.40) of death during TB treatment than patients without DM, and 1.72 (95% CI, 1.25-2.38) times higher odds of remaining culture-positive at 2 months. Metformin use in patients with DM was significantly associated with decreased mortality during TB treatment (hazard ratio, 0.56 [95% CI, .39-.82]), and metformin users had similar mortality as patients without DM. Conclusions:This study suggests that despite multiple potential confounding variables, DM poses an increased risk of adverse TB treatment outcomes. There was a significant association between metformin use and decreased mortality during TB treatment, suggesting a potential role for this agent as adjunctive, host-directed therapy.

SUBMITTER: Degner NR

PROVIDER: S-EPMC5848303 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Metformin Use Reverses the Increased Mortality Associated With Diabetes Mellitus During Tuberculosis Treatment.

Degner Nicholas R NR Wang Jann-Yuan JY Golub Jonathan E JE Karakousis Petros C PC

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20180101 2

<h4>Background</h4>The global type 2 diabetes mellitus (DM) epidemic threatens progress made in reducing tuberculosis (TB)-related mortality worldwide. Previous clinical studies have not fully evaluated potential confounding variables in addressing the impact of DM on TB treatment outcomes. The antidiabetic agent metformin regulates autophagy and may play a role as a host-directed therapeutic adjuvant to antitubercular treatment.<h4>Methods</h4>We conducted a retrospective cohort study comprisin ...[more]

PMID: 29325084

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Project description:ContextDepression and diabetes mellitus have been associated with an increased risk of all-cause and cardiovascular disease (CVD) mortality. However, data evaluating the joint effects of these 2 conditions on mortality are sparse.ObjectivesTo evaluate the individual and joint effects of depression and diabetes on all-cause and CVD mortality rate.DesignProspective cohort study.SettingThe 11 states of the Nurses' Health Study.ParticipantsA total of 78 282 women who participated in the Nurses' Health Study aged 54 to 79 years at baseline in 2000 were followed up until 2006. Depression was defined as having self-reported diagnosed depression, treatment with antidepressant medications, or a score indicating severe depressive symptoms (ie, a 5-item Mental Health Index score ≤52). Self-reported type 2 diabetes was confirmed using a supplementary questionnaire.Main outcome measuresAll-cause and CVD-specific mortality rate.ResultsDuring 6 years of follow-up (433 066 person-years), 4654 deaths were documented, including 979 deaths from CVD. Compared with participants without either condition, the age-adjusted relative risks (RRs) (95% confidence interval) for all-cause mortality were 1.76 (1.64-1.89) for women with depression only, 1.71 (1.54-1.89) for individuals with diabetes only, and 3.11 (2.70-3.58) for women with both conditions. The corresponding age-adjusted RRs of CVD mortality were 1.81 (1.54-2.13), 2.67 (2.20-3.23), and 5.38 (4.19-6.91), respectively. These associations were attenuated after multivariate adjustment for other demographic variables, body mass index, smoking status, alcohol intake, physical activity, and major comorbidities (including hypertension, hypercholesterolemia, heart diseases, stroke, and cancer) but remained significant, with the highest RRs for all-cause and CVD mortality found in those with both conditions (2.07 [1.79-2.40] and 2.72 [2.09-3.54], respectively). Furthermore, the combination of depression with a long duration of diabetes mellitus (ie, >10 years) or insulin therapy was associated with a particularly higher risk of CVD mortality after multivariate adjustment (RRs, 3.22 and 4.90, respectively).ConclusionsDepression and diabetes are associated with a significantly increased risk of all-cause and CVD mortality rate. The coexistence of these conditions identifies women at particularly high risk.

Project description:INTRODUCTION: Metformin has anti-inflammatory and anti-thrombotic effects that may improve the outcome of critical illness, but clinical data are limited. We examined the impact of preadmission metformin use on mortality among intensive care unit (ICU) patients with type 2 diabetes. METHODS: We conducted this population-based cohort study among all persons admitted to the 17 ICUs in Northern Denmark (population approximately 1.8 million). We focused on all patients with type 2 diabetes who were admitted to the ICUs between January 2005 and December 2011. Through individual-level linkage of population-based medical databases, type 2 diabetes was identified using a previously validated algorithm including hospital diagnoses, filled prescriptions for anti-diabetic drugs, and elevated HbA1c levels. Metformin use was identified by filled prescriptions within 90 days before admission. Covariates included surgery, preadmission morbidity, diabetes duration, and concurrent drug use. We computed 30-day mortality and hazard ratios (HRs) of death using Cox regression adjusted for covariates, both overall and after propensity score matching. RESULTS: We included 7,404 adult type 2 diabetes patients, representing 14.0% of 52,964 adult patients admitted to the ICUs. Among type 2 diabetes patients, 1,073 (14.5%) filled a prescription for metformin as monotherapy within 90 days before admission and 1,335 (18.0%) received metformin in combination with other anti-diabetic drugs. Thirty-day mortality was 17.6% among metformin monotherapy users, 17.9% among metformin combination therapy users, and 25.0% among metformin non-users. The adjusted HRs were 0.80 (95% confidence interval (CI): 0.69, 0.94) for metformin monotherapy users and 0.83 (95% CI: 0.71, 0.95) for metformin combination therapy users, compared to non-users. Propensity-score-matched analyses yielded the same results. The association was evident across most subgroups of medical and surgical ICU patients, but most pronounced in elderly patients and in patients with well-controlled diabetes. Former metformin use was not associated with decreased mortality. CONCLUSIONS: Preadmission metformin use was associated with reduced 30-day mortality among medical and surgical intensive care patients with type 2 diabetes.

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Metformin Use Reverses the Increased Mortality Associated With Diabetes Mellitus During Tuberculosis Treatment.

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Metformin Use Reverses the Increased Mortality Associated With Diabetes Mellitus During Tuberculosis Treatment.

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