The real-world data revealed a U-shaped relationship between glycemic control and CV disease risk, according to the authors.
Carlos Alatorre, PhD
A study presented a collection of data from real-world clinical practice patients with newly diagnosed type 2 diabetes mellitus (T2D) and early glycemic control, finding that early and sustained hemoglobin A1C (HbA1c) control between 6.5 and <7.0% is a modifiable factor that helps reduce CV risk.
Carlos Alatorre, PhD, and colleagues from Eli Lilly and Company in Indianapolis, Indiana, aimed to identify factors associated with cardiovascular (CV) events, including stroke, myocardial infarction, ischemic heart disease, unstable angina, and all-cause mortality in patients.
“Some observations from recent studies suggest that interventions designed to reduce CV and mortality risk may be different in people more recently diagnosed with diabetes than those with a more established disease,” Alatorre told MD Magazine. “Although intensive glucose treatment is important in the management of microvascular complications of diabetes, a period of poor glycemic control earlier in the course of the disease can increase the burden of macrovascular complications even if glycemic control is subsequently improved.”
The patients in the study had no recent CV events, and they were able to reach and maintain HbA1c ≤8.0%. They were selected based on their first instance of these events within 5 years of reaching HbA1c ≤ 8.0% for the first time (index date) after they had been diagnosed with T2D.
“The uniqueness and value of our study consisted in investigating factors from real-world clinical practice contributing to increased or reduced CV risk and all-cause mortality in people newly diagnosed with T2D with no recent history of CV events and who rapidly achieved and maintained some level of glycemic control (HbA1c ≤8.0%),” Alatorre said. “The study afforded the opportunity to evaluate a large and heterogeneous cohort of real-world patients with over two decades worth of observational data and included a broad set of factors from longitudinal medical records.”
Alatorre and colleagues obtained their data using a nested case-control design with Cox proportional hazards analysis to review results found in the Clinical Practice Research Datalink, dated January 1990 to December 2012. The team used risk-set sampling to choose the study’s controls, matching them 4:1 to study patients based on age, gender, time of exposure, index date, and the patients’ HbA1c at their index date.
“The analyses are among the most extensive investigations utilizing observational data to inform CV disease risk, by specific CV event type, and all-cause mortality in people with newly-diagnosed T2DM who achieve early and sustained glycemic control under real-world clinical practice conditions,” Alatorre said. “A key finding was that mean HbA1c was significantly associated with various CV outcomes: first CV event, stroke, ischemic heart disease (IHD), and myocardial infarction.”
“The pattern of HbA1c related observations suggest a U-shaped relationship between glycemic control and CV risk, with an increased CV risk for mean HbA1c levels <6.0% and ≥7.0% when compared to levels between 6.5% and 7.0%. These real-world findings affirm and extend the observations from the few relevant clinical trials and observational studies,” he added.
In total, 11,426 patients with T2D met the inclusion criteria for cases as defined by the study. Of those, 5261 experienced a CV event, with 40% experiencing stroke, 29% experiencing coronary artery disease (IHD), 22% myocardial infarction (MI), and 9% unstable angina (UA).
Mean HbA1c ≥7.0% over the length of exposure (vs 6.5 to <7.0%) was found to be associated with an increased risk of stroke, MI, and IHD, while mean HbA1c < 6.0% was associated with increased risk of stroke (HR = 1.29 [CI = 1.02—1.63]) and IHD (HR = 1.65 [CI = 1.25–2.19]).
Those using antiplatelet medications at baseline were linked to an increased risk of stroke (HR = 1.82 [CI = 1.60—2.06]), MI (HR = 1.67 [CI = 1.38–2.03]), and IHD (HR = 1.85 [CI = 1.57–2.17]). Meanwhile, the use of nitrate medications at baseline was associated with increased risk of MI (HR = 2.83 [CI = 2.24–3.57]), IHD (HR = 4.32 [CI = 3.57–5.22]), and UA (HR = 10.38 [CI = 7.67–14.03]).
“Our results suggest that, in people from real-world clinical practice who are newly-diagnosed with T2DM, sustained glycemic intervention from early in the disease process that helps maintain HbA1c on average between 6.5% and 7.0% appears to be associated with significantly lower CV risk and long-term CV protection versus higher glycemia or overly aggressive glycemic control,” Alatorre said. “These findings seem to confirm the importance of early, adequate, and sustained glycemic intervention in routine clinical practice for people with early diabetes, and appear particularly valuable to help prevent CV risk and improve patient outcomes which, in turn, can help reduce the significant burden of illness and societal impact of diabetes.”
The study, “Factors associated with stroke, myocardial infarction, ischemic heart disease, unstable angina, or mortality in patients from real world clinical practice with newly-diagnosed type 2 diabetes and early glycemic control,” was published in Current Medical Research and Opinion.