Dataset Information

Evaluation of Frailty as an Unmeasured Confounder in Observational Studies of Antidiabetic Medications.

ABSTRACT:

Background

It is unknown whether observational studies evaluating the association between antidiabetic medications and mortality adequately account for frailty. Our objectives were to evaluate if frailty was a potential confounder in the relationship between antidiabetic medication regimen and mortality and how well administrative and clinical electronic health record (EHR) data account for frailty.

Methods

We conducted a retrospective cohort study in a single Veterans Health Administration (VHA) healthcare system of 500 hospitalizations-the majority due to heart failure-of Veterans who received regular VHA care and initiated type 2 diabetes treatment from 2001 to 2008. We measured frailty using a modified frailty index (FI, >0.21 frail). We obtained antidiabetic medication regimen and time-to-death from administrative sources. We compared FI among patients on different antidiabetic regimens. Stepwise Cox proportional hazards regression estimated time-to-death by demographic, administrative, clinical EHR, and FI data.

Results

Median FI was 0.22 (interquartile range 0.18, 0.27). Frailty differed across antidiabetic regimens (p < .001). An FI increase of 0.05 was associated with an increased risk of death (hazard ratio 1.45, 95% confidence interval 1.32, 1.60). Cox proportional hazards model for time-to-death including demographic, administrative, and clinical EHR data had a c-statistic of 0.70; adding FI showed marginal improvement (c-statistic 0.72).

Conclusions

Frailty was associated with antidiabetic regimen and death, and may confound that relationship. Demographic, administrative, and clinical EHR data, commonly used to balance differences among exposure groups, performed moderately well in assessing risk of death, with minimal gain from adding frailty. Study design and analytic techniques can help minimize potential confounding by frailty in observational studies.

SUBMITTER: Presley CA

PROVIDER: S-EPMC6625595 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Evaluation of Frailty as an Unmeasured Confounder in Observational Studies of Antidiabetic Medications.

Presley Caroline A CA Chipman Jonathan J Min Jea Young JY Grijalva Carlos G CG Greevy Robert A RA Griffin Marie R MR Roumie Christianne L CL

The journals of gerontology. Series A, Biological sciences and medical sciences 20190701 8

<h4>Background</h4>It is unknown whether observational studies evaluating the association between antidiabetic medications and mortality adequately account for frailty. Our objectives were to evaluate if frailty was a potential confounder in the relationship between antidiabetic medication regimen and mortality and how well administrative and clinical electronic health record (EHR) data account for frailty.<h4>Methods</h4>We conducted a retrospective cohort study in a single Veterans Health Admi ...[more]

PMID: 30256914

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Project description:ImportanceDiabetic men appear to have a lower risk of prostate cancer. Whether antidiabetic medications are protective or potentially mask prostate cancer by lowering prostate-specific antigen (PSA) levels is unclear.ObjectiveTo examine the associations of antidiabetic medication use with (1) PSA levels, (2) frequency of PSA testing, (3) receipt of biopsy following elevated PSA results, and (4) prostate cancer detection at biopsy.Design, setting, and participantsPopulation-based cohort study using data from the Stockholm PSA and Biopsy Register. Participants were all prostate cancer-free men aged 40 to 79 years residing in Stockholm County, Sweden, between January 1, 2006, and December 31, 2015. Data were analyzed from November 2018 to March 2019.ExposuresOne or more prescription for metformin, sulfonylurea, or insulin, as recorded in Sweden's National Prescribed Drug Register.Main outcomes and measuresLevels of PSA following first exposure to antidiabetic medications were assessed using multivariable linear regression. Frequency of PSA testing was assessed via multivariable Poisson regression. Biopsy following elevated PSA (≥3.0 ng/mL) and prostate cancer detection at biopsy were assessed via multivariable logistic regression.ResultsThe cohort of 564 666 men (median [range] age, 65 [40-79] years) consisted of 4583 men initially exposed to metformin, 1104 exposed to sulfonylurea, and 978 exposed to insulin who were age matched with unexposed men (1:5). Exposed men had lower median (interquartile range) PSA levels before starting antidiabetic medications compared with unexposed men (1.2 [0.7-2.5] vs 1.6 [0.8-3.2] ng/mL). After accounting for baseline differences, PSA levels did not vary from those of unexposed men following exposure to antidiabetic medications. Frequency of PSA testing was higher for those receiving metformin (rate ratio, 1.07; 95% CI, 1.06-1.09) and sulfonylurea (rate ratio, 1.06; 95% CI, 1.03-1.08) but was lower for those receiving insulin (rate ratio, 0.79; 95% CI, 0.77- 0.81). Likelihood of biopsy after elevated PSA was lower among men receiving metformin (odds ratio, 0.87; 95% CI, 0.80-0.96) and insulin (odds ratio, 0.83; 95% CI, 0.74-0.93). There were no differences in prostate cancer detection at biopsy, regardless of PSA levels that triggered the biopsy.Conclusions and relevanceThis study's findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer. They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes.

Dataset Information

Evaluation of Frailty as an Unmeasured Confounder in Observational Studies of Antidiabetic Medications.

Background

Methods

Results

Conclusions

Publications

Evaluation of Frailty as an Unmeasured Confounder in Observational Studies of Antidiabetic Medications.

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