Jonathan Q. Purnell
Adults with type 1 diabetes who gained excessive weight during a 6-year, intensive glycemic management regimen experienced a cardiovascular event rate over 13 years similar to that of participants who gained minimal weight with intensive control. However, CV event rates for those who gained excessive weight began to rise at year 14, matching the CV event rate of those treated with conventional therapy by year 20, according to an analysis of the Diabetes Control and Complications Trial and its long-term follow-up.
“The good news is that intensive diabetes control of type 1 diabetes improves cardiovascular outcomes, including the most significant ones, for a substantial period of time, even when patients experience unwanted weight gain,” Jonathan Q. Purnell, MD, professor with the Knight Cardiovascular Institute and the division of endocrinology, diabetes and clinical nutrition at Oregon Health & Science University in Portland, told Endocrine Today. “But there appears to be a time limit to that benefit, beginning roughly 20 years after starting intensive management, where presumably long-term exposure to a summation of multiple obesity-related CVD risk factors contributes to a greater numbers of CVD events.”
Purnell and colleagues analyzed data from 1,213 participants in the Diabetes Control and Complications Trial (DCCT), stopped after a mean follow-up of 6.5 years, and the ongoing follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, which began enrollment in 1994. Researchers stratified patients by quartiles of weight gain within the two treatment groups (intensive therapy vs. usual care), defined as the change in BMI from DCCT baseline to DCCT closeout. In each treatment group, the fourth quartile of weight gain was used to define “excessive” weight gain, compared with “minimal” weight gain defined by the first three quartiles. The separation in quartiles was maintained during the EDIC follow-up. Primary outcome was time to first CVD event. Researchers assessed the effect of excessive weight gain on CVD risk factors over 20 years of follow-up in the EDIC.
Compared with patients in the conventional treatment groups and those assigned to intensive therapy in the first through third quartiles of weight gain, those in the excessive weight gain intensive therapy group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m²), increases in CVD risk factors, and a greater need for hypertension and lipid-lowering medications, according to researchers.
During a mean 26 years of follow-up, there were no between-group differences for the number of major and total CVD events across BMI quartiles across the conventional and intensive therapy groups. However, at year 14, the incident CVD event curve became significantly higher in the quartile four intensive treatment group vs. the minimal weight gain intensive treatment group (P = .024) and was similar to that for the conventional treatment group, according to researchers.
In an exploratory analysis to test the difference between intensive and conventional treatment groups at year 14, researchers used Cox proportional hazard models to evaluate the interaction between weight-gain groups (excessive vs. minimal) and an indicator variable for study year. After year 14 in EDIC, incident CVD events in the excessive weight-gain group were higher vs. the minimal weight-gain intensive therapy group (unadjusted HR = 1.99; 95% CI, 1.12-3.63) and were comparable to incident CVD in the conventional therapy group. However, after adjustment for weight-related CVD risk factors, the HR failed to reach significance, according to researchers. “The protective benefit of intensive management on macrovascular outcomes appears to wane over time in this group,” Purnell said. “Both HbA1c and nonglucose modifiable CVD risk factors (eg, lipids, blood pressure) should be carefully monitored and treatment adjusted to optimize levels according to the most recent guidelines for type 1 diabetes, especially in patients with obesity.”
Excessive weight gain with intensive diabetes control worsened obesity-related CVD risk factors, the researchers noted; however, the rates of total CVD events and major adverse cardiac events during the first 13 years of observational follow-up in the intensive control group did not differ from the rates among those who experienced only minimal weight gain.
“However, this might have been due to CVD risk mitigation though (sic) the greater use of lipid-lowering and blood pressure medications by the excessive weight gain group,” the researchers wrote. “A significant divergence of CVD event rate curves after 14 years of follow-up in the EDIC study suggests that more revascularization procedures eventually are needed to delay or prevent [major adverse CV events]. Further follow-up of this well-characterized population with type 1 diabetes will determine whether excessive weight gain with [intensive control] eventually results in increased (‘breakthrough’) [major adverse CV events].” – by Regina Schaffer
Disclosure: Purnell reports he serves on an advisory board for Novo Nordisk.