Stress Hormone Cortisol Associated With Increased Blood Sugar in T2D Population

Throughout the country, rising cases of coronavirus disease 2019 (COVID-19) prove stressful for individuals most at risk of dying from the disease, including those with underlying conditions such as diabetes.

As of June 2020, patients with diabetes hospitalized for COVID-19 accounted for more than 20% of individuals admitted to intensive care units (ICUs), while patients with diabetes represent 25% to 34% of the population receiving care in ICU and non-ICU settings, respectively, for COVID-19.

In addition to health risks, financial hardships are taking a toll on this population. New data from dQ&A, The Diabetes Research Company, and the American Diabetes Association found 24% of people with diabetes have used savings, loans, or money from their stimulus check to pay for diabetes care within the past 3 months.

According to results from the 5000-person survey, a quarter of individuals with diabetes have turned to self-rationing supplies to cut costs of diabetes care, while in June the unemployment rate among people with diabetes was higher than the national rate at 18% vs 12%.

Compounding these issues, new results from a study published in Psychoneuroendocrinology show the stress hormone cortisol is associated with higher blood sugar levels in individuals with type 2 diabetes (T2D), suggesting cortisol plays a detrimental role in contributing to glycemia in this population.

“Most people with T2D know the importance of exercising regularly, eating a healthy diet, and getting plenty of rest,” said Joshua J. Joseph, MD, a lead author of the study. “But stress relief is a crucial and often forgotten component of diabetes management.”

The hypothalamic-pituitary-adrenal (HPA) axis is responsible for responding to imminent or perceived threats and stressors through a response that involves the release of glucocorticoids. Glucocorticoids are also important in that they regulate energy balance and glucose homeostasis.

However, “little is known about the longitudinal association between fasting glucose (FG) and the diurnal cortisol profile among those with normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetes,” authors write.

To better understand this knowledge gap, researchers examined the longitudinal association between FG and cortisol curve features over 6 years in participants with NFG, IFG, and diabetes.

Using prospective data from the Multi-Ethnic Study of Atherosclerosis (MESA) study and the MESA Stress Ancillary Study, researchers analyzed the association between change in FG with change in diurnal cortisol features over 6 years, prior average annual FG change with diurnal cortisol features, and baseline cortisol features with changes in FG over 6 years.

Between 2000 and 2002, 6814 participants without clinical cardiovascular disease were recruited to MESA, during which measurements of glycemic status and salivary cortisol were taken. Investigators defined NFG as FG of 5.5 mmol/L or less (≤100 mg/dL) and IFG as FG of 5.6 to 6.9 mmol/L (100-125 mg/dL).

Adjusted analyses of the data revealed:

• In individuals with T2D, each annual percent change increase in wake-up cortisol, total area under the curve (AUC), and overall decline slope was associated with a significant increase in FG over 6 years in all models (all P < .05).
• A 1% prior annual increase in FG was associated with a 2.8% lower (−2.8%; 95% CI, −5.3 % to −0.4 %) bedtime cortisol among participants with NFG at baseline.
• A 1% flatter overall decline slope was associated with a 0.19% increase in subsequent annual percent change in FG over 6 years among participants with T2D.
• Among participants with T2D there was a positive association of change in wake-up cortisol, total AUC, and overall decline slope with change in FG.
• Baseline overall decline slope was positively associated with change in FG among the baseline diabetes group.

“In healthy people, cortisol fluctuates naturally throughout the day, spiking in the morning and falling at night,” Joseph said. “But in participants with T2D, cortisol profiles that were flatter throughout the day had higher glucose levels.”

The relationships were also independent of body mass index, leading authors to hypothesize that glucocorticoids affect glucose metabolism directly through effects on insulin secretion and insulin signaling.

Because average participant age ranged from 63.7 to 66.6 years, researchers caution results may not be generalizable to younger populations.

Future studies involving detailed clinical and metabolic phenotyping may help determine the mechanisms by which changes in cortisol secretion disrupt glucose metabolism and aid in developing future novel targets for T2D treatments.

Reference

Dias JP, Joseph JJ, Kluwe B, et al. The longitudinal association of changes in diurnal cortisol features with fasting glucose: MESA. Psychoneuroendocrinology. Published online July 13, 2020. doi:10.1016/j.psyneuen.2020.104698