April 4, 2024—(BRONX, NY)—Three papers co-authored by diabetes researchers at Albert Einstein College of Medicine are included in a special collection of reports in the April issue of Diabetes Care describing results of the multicenter Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). The Einstein papers focus on whether the emotional distress often associated with type 2 (T2D) diabetes affects adherence to treatment and success in controlling blood-sugar levels and whether particular diabetes therapies influence patients’ emotional distress levels.
![Jeffrey S. Gonzalez, Ph.D.]()
Jeffrey S. Gonzalez, Ph.D.
Faculty Profile
"It is imperative that we ask—and listen to—our patients about their experiences,” said Jeffrey Gonzalez, Ph.D., a senior or first author on the papers, and professor of medicine, of epidemiology & population health, and director of the New York Regional Center for Diabetes Translational Research at Einstein. “Our research clearly demonstrates that we must understand what they are going through if we want to provide them with high-quality care and the most effective treatment for type 2 diabetes." Dr. Gonzalez is also a psychologist at Montefiore Health System, and professor of psychology at Ferkauf Graduate School of Psychology at Yeshiva University.
Making the GRADE
Diabetes affects more than 1 in 10—or more than 38 million—Americans. People with diabetes who keep their blood sugar levels in the near-normal range generally have a much lower risk of developing diabetes complications such as heart, kidney, and eye diseases. The challenge is that most people with diabetes require more than one medication to control blood sugar levels over time.
![Jill P. Crandall, M.D.]()
Jill P. Crandall, M.D.
Faculty ProfileResearch ProfileExpert Profile for Media
The multicenter GRADE Study, which was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH), was conducted between 2013 and 2021 and enrolled 5,047 volunteer participants with T2D from diverse racial and ethnic groups. GRADE compared four common diabetes drugs used to treat T2D to find which performed better when combined with metformin, the drug most often used for managing T2D. The treatment goal was glycemic control, i.e., maintaining blood glucose levels in the recommended range.
“GRADE has been essential in improving our understanding about which combinations of medications are best at controlling blood sugar over time,” said Jill Crandall, M.D., principal investigator of GRADE at Montefiore Einstein, and chief of endocrinology, professor of medicine, and the Anita and Jack Saltz Chair in Diabetes Research at Montefiore Einstein. “The results of the new studies led by Dr. Gonzalez look more deeply at emotional aspects of quality of life and how this can impact health.”
The Emotional Toll of Diabetes
The Einstein-authored papers pertained to a sub-section of GRADE known as the Emotional Distress Substudy (EDS) involving 1,739 GRADE participants. EDS prospectively examined whether participants’ baseline emotional-distress levels influenced their subsequent adherence to treatment regimens and their clinical outcomes. The study also provided a unique opportunity to determine whether participants’ emotional distress, including depressive symptoms and diabetes-related distress (e.g., feeling overwhelmed by diabetes and feelings of failure related to self-care) were associated with particular glucose-lowering medications used in the GRADE study.
![Claire J. Hoogendoorn, Ph.D.]()
Claire J. Hoogendoorn, Ph.D.
Faculty Profile
“Emotional distress is a significant and common problem for people with type 2 diabetes,” said Claire Hoogendoorn, Ph.D., research assistant professor of medicine at Einstein, first author of one of the Diabetes Care papers and co-author on the two other papers. “Studies have shown that depression is up to twice as common among adults with diabetes compared with those without the disease, and 35% of patients experience moderate to severe levels of diabetes distress. It’s imperative that we identify ways to address this and determine how medication type can influence it.” Gladys Crespo-Ramos, Ph.D., research assistant professor of medicine at Einstein, was also a co-author on two of the studies.
Key Findings
Findings from the three Einstein-authored papers on GRADE EDS can be summarized as follows:
- For people who have had diabetes for a relatively short time, baseline levels of diabetes distress and depressive symptoms are not associated with whether or not they achieved glycemic control during the study, regardless of the assigned treatment. (All GRADE participants were enrolled within 10 years of their diabetes diagnosis.)
- Having elevated baseline levels of depressive symptoms and diabetes distress strongly predicted that patients with type 2 diabetes would not adhere to treatment. Patients’ adherence was also influenced by their concerns over the medications and their treatment satisfaction.
- GRADE EDS found no evidence that adding daily insulin injections to metformin therapy caused worsening of emotional distress. Treatment with insulin and the other injectable drug (liraglutide) actually lowered distress related to diabetes. These findings largely debunk the myth that insulin therapy, once started, diminishes patients’ quality of life.
Our research clearly demonstrates that we must understand what they are going through if we want to provide them with high-quality care and the most effective treatment for T2D.
Jeffrey Gonzalez, Ph.D.
The GRADE Study was supported by a grant from the NIDDK (U01DK098246). Additional support was provided by NIH’s National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, and National Center for Advancing Translational Sciences; the Centers for Disease Control and Prevention; and the American Diabetes Association. The Department of Veterans Affairs provided resources and facilities. Material support in the form of donated medications and supplies has been provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck & Co., Inc., Novo Nordisk, Roche Diagnostics, and Sanofi. ClinicalTrials.gov number: NCT01794143.