July 14, 2020
In patients with type 2 diabetes, but not other people, levels of the stress hormone cortisol tended to remain high during the day, and this was associated with increasing fasting plasma glucose levels over the years, in a new study.
The results show that to maintain better glycemic control, patients with type 2 diabetes need to learn to manage stress, as well as pay attention to other lifestyle factors, say the authors, led by Jenny Pena Dias, PhD, MPH, a physiologist at Johns Hopkins University School of Medicine, Baltimore, Maryland.
The findings were published online July 13 in Psychoneuroendocrinology.
"These results suggest a detrimental role of cortisol contributing to glycemia among individuals with diabetes," Pena Dias and colleagues say.
"Most people with type 2 diabetes know the importance of exercising regularly, eating a healthy diet, and getting plenty of rest," said senior author Joshua J. Joseph, MD, an endocrinologist from Ohio State University Wexner Medical Center, Columbus.
"But stress relief is a crucial and often forgotten component of diabetes management," he remarked in a statement from his university.
"Whether it's a yoga class, taking a walk, or reading a book, finding ways to lower your stress levels is important to everyone's overall health, especially for those with type 2 diabetes," Joseph emphasized.
Circadian Pattern of Cortisol Levels
The researchers explain that healthy diurnal cortisol regulation follows a circadian pattern, with high levels upon awakening, which increase by 50% to 75% between 0 to 30 minutes post-awakening (cortisol awakening response). Cortisol levels decline during the remainder of the day, reaching a nadir in the late evening 16 to 18 hours after awakening.
However, the relationship between cortisol and fasting glucose over time in individuals with normal or impaired fasting glucose or diabetes was not clear.
To investigate this, researchers analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who had normal or impaired fasting plasma glucose or type 2 diabetes.
They had tests to determine salivary cortisol levels 6 to 8 times during 2 or 3 days as well as morning fasting plasma glucose levels each year for 6 years.
They examined baseline cortisol features (wake-up levels, cortisol awakening response, total area under the curve [total cortisol excreted], overall decline in slope of diurnal cortisol, and bedtime cortisol) and subsequent annual percentage change in fasting glucose in 1275 participants.
They also studied how annual percentage change in cortisol features was related to annual percentage change in fasting glucose over 6 years in 512 participants, and how baseline cortisol features were related to annual percentage change in fasting glucose in 700 participants.
About 62% of participants had normal fasting glucose, 20% had impaired fasting glucose, and 18% had type 2 diabetes.
After multivariable adjustment, among participants with diabetes, each annual percentage increase in wake-up cortisol, total area under the curve, and overall decline in slope was associated with a significant increase in fasting plasma glucose over the 6 years (P < .05).
In addition, among participants with diabetes, a 1% flatter slope in the decline of cortisol from wake-up to bedtime was associated with a 0.19% increase in subsequent annual percentage change in fasting glucose.
The relationship of cortisol with glucose levels was only observed in those with diabetes.
"These relationships were independent of body mass index, suggesting that glucocorticoids impact glucose metabolism directly through effects on insulin secretion and insulin signaling," something that has been previously demonstrated (Endocrinol Metab Clin North Am. 2014;43:75-102), according to Pena Diaz and colleagues.
"Future studies are needed to examine these relationships with detailed clinical and metabolic phenotyping to determine the mechanisms by which changes in cortisol secretion disrupt glucose metabolism, and to develop future novel targets for treatment of type 2 diabetes," they note.
The group is investigating the relationship between cortisol and the development of diabetes and cardiovascular disease.
They have also started a trial to examine if mindfulness practices can lower blood glucose in people with type 2 diabetes.
However, practicing mindfulness "isn't the only effective form of stress relief," said Joseph. "It's important to find something you enjoy and make it a part of your everyday routine."
The research was supported by the National Heart, Lung, and Blood Institute and the National Center for Research Resources. Joseph was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases and the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation. The authors have reported no relevant financial relationships.