Association of Glycemic Control Trajectory with Short-Term Mortality in Diabetes Patients with High Cardiovascular Risk: a Joint Latent Class Modeling Study.

BACKGROUND: The relationship between risk factor or biomarker trajectories and contemporaneous short-term clinical outcomes is poorly understood. In diabetes patients, it is unknown whether hemoglobin A1c (HbA1c) trajectories are associated with clinical outcomes and can inform care in scenarios in which a single HbA1c is uninformative, for example, after a diagnosis of coronary artery disease (CAD). OBJECTIVE: To compare associations of HbA1c trajectories and single HbA1c values with short-term mortality in diabetes patients evaluated for CAD DESIGN: Retrospective observational cohort study PARTICIPANTS: Diabetes patients (n = 7780) with and without angiographically defined CAD MAIN MEASURES: We used joint latent class mixed models to simultaneously fit HbA1c trajectories and estimate association with 2-year mortality after cardiac catheterization, adjusting for clinical and demographic covariates. KEY RESULTS: Three HBA1c trajectory classes were identified: individuals with stable glycemia (class A; n = 6934 [89%]; mean baseline HbA1c 6.9%), with declining HbA1c (class B; n = 364 [4.7%]; mean baseline HbA1c 11.6%), and with increasing HbA1c (class C; n = 482 [6.2%]; mean baseline HbA1c 8.5%). HbA1c trajectory class was associated with adjusted 2-year mortality (3.0% [95% CI 2.8, 3.2] for class A, 3.1% [2.1, 4.2] for class B, and 4.2% [3.4, 4.9] for class C; global P = 0.047, P = 0.03 comparing classes A and C, P > 0.05 for other pairwise comparisons). Baseline HbA1c was not associated with 2-year mortality (P = 0.85; hazard ratios 1.01 [0.96, 1.06] and 1.02 [0.95, 1.10] for HbA1c 7-9% and ≥ 9%, respectively, relative to HbA1c < 7%). The association between HbA1c trajectories and mortality did not differ between those with and without CAD (interaction P = 0.1). CONCLUSIONS: In clinical settings where single HbA1c measurements provide limited information, HbA1c trajectories may help stratify risk of complications in diabetes patients. Joint latent class modeling provides a generalizable approach to examining relationships between biomarker trajectories and clinical outcomes in the era of near-universal adoption of electronic health records.

Trends in Timing of and Glycemia at Initiation of Second-line Type 2 Diabetes Treatment in U.S. Adults.

OBJECTIVE: Therapeutic inertia threatens the potential long-term benefits of achieving early glycemic control after type 2 diabetes diagnosis. We evaluated temporal trends in second-line diabetes medication initiation among individuals initially treated with metformin. RESEARCH DESIGN AND METHODS: We included data from 199,042 adults with type 2 diabetes in the U.S. Department of Veterans Affairs health care system initially treated with metformin monotherapy from 2005 to 2013. We used multivariable Cox proportional hazards and linear regression to estimate associations of year of metformin monotherapy initiation with time to second-line diabetes treatment over 5 years of follow-up (primary outcome) and with hemoglobin A1c (HbA1c) at the time of second-line diabetes treatment initiation (secondary outcome). RESULTS: The cumulative 5-year incidence of second-line medication initiation declined from 47% among metformin initiators in 2005 to 36% in 2013 counterparts (P < 0.0001) despite a gradual increase in mean HbA1c at the end of follow-up (from 6.94 ± 1.28% to 7.09 ± 1.42%, Ptrend < 0.0001). In comparisons with metformin monotherapy initiators in 2005, adjusted hazard ratios for 5-year initiation of second-line diabetes treatment ranged from 0.90 (95% CI 0.87, 0.92) for 2006 metformin initiators to 0.68 (0.66, 0.70) for 2013 counterparts. Among those receiving second-line treatment within 5 years of metformin initiation, HbA1c at second-line medication initiation increased from 7.74 ± 1.66% in 2005 metformin initiators to 8.55 ± 1.92% in 2013 counterparts (Ptrend < 0.0001). CONCLUSIONS: We observed progressive delays in diabetes treatment intensification consistent with therapeutic inertia. Process-of-care interventions early in the diabetes disease course may be needed to reverse adverse temporal trends in diabetes care.

Oral diabetes medication monotherapy and short-term mortality in individuals with type 2 diabetes and coronary artery disease.

OBJECTIVE: To determine whether sulfonylurea use, compared with non-sulfonylurea oral diabetes medication use, was associated with 2-year mortality in individuals with well-controlled diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: We studied 5352 US veterans with type 2 diabetes, obstructive CAD on coronary angiography, hemoglobin A1c ≤7.5% at the time of catheterization, and taking zero or one oral diabetes medication (categorized as no medications, non-sulfonylurea medication, or sulfonylurea). We estimated the association between medication category and 2-year mortality using inverse probability of treatment-weighted (IPW) standardized mortality differences and IPW multivariable Cox proportional hazards regression. RESULTS: 49%, 35%, and 16% of the participants were on no diabetes medications, non-sulfonylurea medications, and sulfonylureas, respectively. In individuals on no medications, non-sulfonylurea medications, and sulfonylureas, the unadjusted mortality rates were 6.6%, 5.2%, and 11.9%, respectively, and the IPW-standardized mortality rates were 5.9%, 6.5%, and 9.7%, respectively. The standardized absolute 2-year mortality difference between non-sulfonylurea and sulfonylurea groups was 3.2% (95% CI 0.7 to 5.7) (p=0.01). In Cox proportional hazards models, the point estimate suggested that sulfonylurea use might be associated with greater hazard of mortality than non-sulfonylurea medication use, but this finding was not statistically significant (HR 1.38 (95% CI 1.00 to 1.93), p=0.05). We did not observe significant mortality differences between individuals on no diabetes medications and non-sulfonylurea users. CONCLUSIONS: Sulfonylurea use was common (nearly one-third of those taking medications) and was associated with increased 2-year mortality in individuals with obstructive CAD. The significance of the association between sulfonylurea use and mortality was attenuated in fully adjusted survival models. Caution with sulfonylurea use may be warranted for patients with well-controlled diabetes and CAD, and metformin or newer diabetes medications with cardiovascular safety data could be considered as alternatives when individualizing therapy.

Coronary artery disease severity modifies associations between glycemic control and both mortality and myocardial infarction.

AIMS: This study examined whether the association between hemoglobin A1c (HbA1c) and short-term clinical outcomes is moderated by CAD severity. METHODS: We studied 17,394 US Veterans with type 2 diabetes who underwent elective cardiac catheterization between 2005 and 2013. CAD severity was categorized as obstructive, non-obstructive, or no CAD. Using multivariable Cox proportional hazards regression, we assessed associations between time-varying HbA1c and two-year all-cause mortality and non-fatal MI, with an interaction term between HbA1c and CAD severity. RESULTS: 61%, 22%, and 17% of participants had obstructive, non-obstructive, and no CAD, respectively. CAD severity modified the relationship between HbA1c and each outcome (interaction p-value 0.0005 for mortality and <0.0001 for MI). Low HbA1c (<42 mmol/mol) was associated with increased mortality, relative to HbA1c of 48-52 mmol/mol, in individuals with obstructive CAD (HR 1.52 [1.17, 1.97]) and non-obstructive CAD (HR 2.61 [1.61, 4.23]), but not in those with no CAD (HR 0.91 [0.46, 1.79]). In contrast, higher HbA1c levels (≥53 mmol/mol) were associated with increased MI risk only in individuals with obstructive CAD. CONCLUSIONS: The associations between HbA1c and mortality and MI were moderated by CAD severity. Measures of cardiovascular disease severity may inform optimal individualized diabetes management.

African Americans Are Less Likely to Receive Care by a Cardiologist During an Intensive Care Unit Admission for Heart Failure.

OBJECTIVES: This study sought to determine whether the likelihood of receiving primary intensive care unit (ICU) care by a cardiologist versus a noncardiologist was greater for Caucasians than for African Americans admitted to an ICU for heart failure (HF). The authors further evaluated whether primary ICU care by a cardiologist is associated with higher in-hospital survival, irrespective of race. BACKGROUND: Increasing data demonstrate an association between better HF outcomes and care by a cardiologist. It is unclear if previously noted racial differences in cardiology care persist in an ICU setting. METHODS: Using the Premier database, adult patients admitted to an ICU with a primary discharge diagnosis of HF from 2010 to 2014 were included. Hierarchical logistic regression models were used to determine the association between race and primary ICU care by a cardiologist, adjusting for patient and hospital variables. Cox regression with inverse probability weighting was used to assess the association between cardiology care and in-hospital mortality. RESULTS: Among 104,835 patients (80.3% Caucasians, 19.7% African Americans), Caucasians had higher odds of care by a cardiologist than African Americans (adjusted odds ratio: 1.42; 95% confidence interval: 1.34 to 1.51). Compared with a noncardiologist, primary ICU care by a cardiologist was associated with higher in-hospital survival (adjusted hazard ratio: 1.20, 95% confidence interval: 1.11 to 1.28). The higher likelihood of survival did not differ by patient race (interaction p = 0.32). CONCLUSIONS: Among patients admitted to an ICU for HF, African Americans were less likely than Caucasians to receive primary care by a cardiologist. Primary care by a cardiologist was associated with higher survival for both Caucasians and African Americans.