Inhaled Corticosteroids and Diabetes Onset

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1 Inhaled Corticosteroids and the Risks of Diabetes Onset and Progression Journal Club October 13, 2010 By Anya Litvak, Kik Keiko Greenberg, and Jonathan Chrispin

2 Background Inhaled corticosteroids are commonly used for the treatment of asthma and COPD Systemic corticosteroids are known to increase diabetes risk, ikbut the effects of high dose inhaled corticosteroids are unknown

3 Hypothesis Inhaled corticosteroids increase the risk of diabetes onset and progression in a dose dependent fashion

4 Participants All patients on a computerized database of the Régie de l'assurance maladie du Québec, the agency responsible for administering the universal health insurance program of the province of Québec, Canada, for all its 7 million residents

5 Data Collection Database included information on demographics, medical services rendered, and diagnostic code of the service (7 million patients) The prescription drug database included outpatientprescription prescription medicationsdispensedto dispensed to all people aged 65 years or older, all social welfare recipients, and all residents who choose to join the provincial drug plan (3 million patients)

6 Study Design

7 Main Outcome Diabetic: defined as a patient who started an antidiabetic medication after being prescribed 3 or more respiratory medications Diabetes progression: defined as a patient who developed diabetes after being prescribed 3 or more respiratory medications and then progressing to insulin

8 Analytical Method Conditional logistic regression was used to estimate the adjusted rate ratios of diabetes onset and progression associated with current use and dose of inhaled corticosteroid Adjusted for age, sex, severity of respiratory disease, and co morbidity (including cardiac, CNS diseases) Sensitivity analyses were performed to assess for possible confounding by concurrent oral corticosteroid use and the underlying respiratory diagnosis (asthma vs COPD)

9 Results 388,584 non diabetic patients treated for asthma or COPD made up the cohort 30,167 started on antidiabetic medication Mean duration of follow up = 5.5 years Incidence of new diabetes onset = 14.2 per 1000 per year 2,099 started on oral agents later started on insulin Incidence of diabetes progression = 19.8 per 1000 per year

10 Characteristics of Cases/Controls

11 Diabetes Onset

12 Dose Response Curve

13 Diabetes Progression

14 Sensitivity Analysis Exclusion of subjects who used oral corticosteroids within a year of diabetes onset showed comparable rate ratio of diabetes onset (RR 1.28; 95% CI, ) Rate ratio was similar in patients with probable asthma (RR 1.39; 95% CI ) or probable COPD (RR 1.28; 95% CI ) )

15 Conclusion/Implications High doses of inhaled aedcorticosteroids coste o commonly o used in patients with COPD are associated with an increased risk of diabetes and progression of disease Patients instituting therapy with high doses of inhaled corticosteroids t id should ldbe assessed for possible hyperglycemia treatment with high doses of inhaled corticosteroids should be limited to situations where the benefit is clear

16 Strengths A large population based cohort of approximately 400,000 patients observed over 18 years were studied The study shows temporality The study shows a dosage response

17 Weaknesses The definition of diabetes was the start of The definition of diabetes was the start of antihyperglycemics and the definition of progression of diabetes was insulin initiation Multiple residual confounders (ex. BMI, race, lifestyle choices, eating habits, family history, history of gestational diabetes, degree of hypertension, hypercholestolemia, etc) Lack of documentation of patients treated outside of the universal health system

18 Discussion Points Will this study influence you to change the way you prescribe high dose inhaled corticosteroids in patients withasthma or COPD

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