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Glucose Control and Cardiovascular Disease – 15 Year Follow-up

Dec 16, 2019
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Andrew Daoud, PharmD Candidate, Florida A&M University

Glucose control and cardiovascular disease: does intensive glucose control show heart benefits in long-term followup?. 

Cardiovascular disease is a condition that involves narrowed blood vessels that can lead to heart failure conditions. A study trial was conducted in patients with both type 1 and 2 diabetes to observe this relation. An increase in blood glucose levels affected large and small veins and capillaries directly. Trials involving  VADT (Veterans Affairs Diabetes Trials), in type 2 diabetes patients, showed there was a significant lowering of cardiovascular diseases with control of blood glucose in a span of 10yrs. In 3-6 years, there was no significant observation in the reduction of cardiovascular events with maintenance and control of blood glucose levels. The study follows up on VADT for a longer time (15 years) to observe the relation between control of blood glucose levels and cardiovascular disease, deaths, and even beneficial effects on diabetes with control of glucose levels.  

 

The study involved 1791 military veterans with diabetes type 2 who received more intensive therapy of glucose level control than was normal: glycated hemoglobin that was lower by 1.5% than those who received standard glucose control (glycated hemoglobin of 8%-9%), for a period of 5.6 years, observed through national data registries(complete cohort. This was from participants that were alive and still participated in the trials. Surveys and charts (survey cohort) gave additional data. Also, quality of life was assessed on a scale of 0-100, and a higher number showed a healthy, better life.

The prespecified primary outcome that was done by the end of 13.6 years (due to delay of availability of registry data) was new or worsening congestive heart failure, nonfatal myocardial infarction, amputation for ischemic gangrene, among others. The prespecified secondary outcome included deaths from any cause and quality of life related to health. Data was considered unimportant when participants died or withdrew from the study and had a primary outcome event. The Cox proportional hazards models were used to observe treatment and to examine the effects of glycated hemoglobin levels on intensive and standard therapy; three variables: duration of diabetes, history of cardiovascular disease, and baseline cardiovascular risk, were prespecified.

In the results, the median of glycated hemoglobin level in the intensive glucose control therapy (892 participants) and standard glucose control therapy (899) was 6.9%. Median separation of both averaged at 1.5% points and gradually dropped to 0.2%-0.3 percentage after trial completion in three years. During active treatment, intensive glucose control was linked with increased weight, which is when all active participants were enrolled. By the end of 5.6 years, risks were not lower in intensive therapy than in standard therapy. Cardiovascular disease outcome was just lower by 9%, non-significant lower risks of major diabetes events (hazard ratio for primary outcome 0.90; 95%s confidence interval cl 0.78 to 1.04) and non-significant quality of life improvement that had a mean score of 63.8, and 62.2 respectively. In the three pre-specified factors, there was no evidence that treatment affected any factor. Rate of hospitalization was the same (160 events per 1000 person in the intensive therapy group and 165 events per 1000 person in the standard group; Hazard ratio, 0.98; 95%CL, 0.88 to 1.09). During separation of the glycated haemoglobin hazard ratio, 0.83;95% CL 0.70 to 0.99, the risk of cardiovascular disease outcome seemed to reduce but did not reduce further after equalization of glycated hemoglobin levels 1.26;95% CL0.90 to 1.75. in 5 years.

The results conclude that there was no major significant change in a lower risk of cardiovascular events in intensive therapy than in the standard therapy group as per the duration of  5.6 years. Neither was there evidence of mortality benefit nor decrease in hospitalization. However, a 10 year follow up of separation of glycated haemoglobin curve showed some reduction of nearly 17% in primary cardiovascular disease outcomes. Thus, it concludes that patients with diabetes type 2 in intensive glucose-lowering therapy have a lower risk of cardiovascular events (9%) in the end after a 1-point reduction in glycated haemoglobin. Maintaining lower glycated haemoglobin levels is important to maintain lower outcomes of cardiovascular events. However, after the equalization of glycated haemoglobin levels, there were not many benefits to cardiovascular events.

There were some setbacks in the research. The original study consisted largely of men, and post trials were done electronically, which differed from the active trials done at the beginning of the study, although the outcome of the results did not differ much. Also, observation was the method used to find that cardiovascular events risk reduced after separation of glycated haemoglobin levels and not after equalization, which does not carry the same strength of a true experiment.

Practice Pearls:

  • The study involved type 2 patients who received intensive or standard glucose control therapies.
  • With 5.6 to 15 years of study follow up there was no significant change in risk of cardiovascular events, mortality benefit nor decreased rate of hospitalization in intensive therapy than in standard therapy
  • There was a lower risk of major cardiovascular events in participants with diabetes type 2 who were on intensive glucose management.

Reaven Peter et al. Intensive glucose control in patients with type 2 diabetes 15 years follow up NJEM  group 2019 retrieved fromhttps://www.nejm.org/doi/full/10.1056/NEJMoa1806802 in NJEM [6/6/2019]

Andrew Daoud, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy