Insulin Resistance, Elevated Blood Sugar Common in Cushing’s: Study

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Elevated blood sugar levels and a failure to respond properly to insulin – the hormone that helps regulate blood sugar – are common features in people with Cushing’s syndrome, according to a Chinese report.

Its authors suggest that measures of insulin sensitivity and a response from beta-cells – the cells that produce insulin in the pancreas – could be used to evaluate the risk for diabetes in these patients.

The study, “β-cell function and insulin sensitivity contributions on incident diabetes in patients with endogenous Cushing’s syndrome,” was published in Diabetes Research and Clinical Practice.

Cushing’s syndrome is caused by a chronic overproduction of cortisol, which can result in complications such as obesity, cardiovascular diseases, and metabolic disorders such as diabetes.

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With excess glucocorticoids such as cortisol, the body tends to accumulate higher glucose levels in the blood, mostly because patients become less sensitive to the action of insulin – known as insulin resistance.

And while there are mechanisms to counteract that resistance, namely by having beta cells produce more insulin, these cells seem to be dysfunctional in people with Cushing’s.

Researchers at the Nanjing Medical University, China, investigated the incidence of glucose intolerance — which ranges from high blood glucose levels in fasting conditions to prediabetes or overt diabetes — in people with Cushing’s. They also set out to determine how impaired beta-cell function and insulin sensitivity contribute to glucose intolerance.

The team retrospectively assessed data from 60 Cushing’s patients diagnosed at the First Affiliated Hospital of Nanjing Medical University between 2010 and 2021, who had an oral glucose tolerance test.

Participants included 54 women and six men (mean age, 37.5 years). Half had Cushing’s disease, meaning their Cushing’s was caused by a tumor in the pituitary gland, 43.3% had a tumor in the adrenal gland, and 6.7% had Cushing’s due to a mass elsewhere in the body.

Fifty healthy people without a history of diabetes were also included as controls.

Results from the oral glucose tolerance test, which assesses how well the body processes blood sugar, determined that 35% of patients were prediabetic and 48.3% had diabetes. The remaining 16.7% had normal test values.

“We demonstrated that more than four-fifths of patients with CS [Cushing’s syndrome] have abnormal glucose metabolism,” the researchers wrote.

The occurrence of either prediabetes or diabetes was independent of the underlying cause of Cushing’s, the research team noted.

The scientists then evaluated insulin resistance and beta-cell function in each of these groups and compared them with those in controls.

Insulin resistance was measured with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score test and was significantly higher in both Cushing’s syndrome patients with a normal glucose tolerance test and with prediabetes than in controls.

The team used another test to measure insulin resistance, the ISI-Matsuda index, which has been proposed to be superior to the HOMA-IR. In agreement with the previous test, the results showed all Cushing’s syndrome groups had higher insulin resistance than controls.

The activity of beta-cells was measured with another tool called HOMA-beta. It showed scores were significantly higher in the Cushing’s groups without diabetes than in healthy controls. Also, patients with normal glucose tolerance had significantly greater beta-cell function than prediabetic patients and also had greater function than diabetic patients.

This doesn’t imply better beta-cell function, but rather that these cells produced more insulin, likely as a way to respond to the lack of proper response to insulin, according to the researchers.

“The abnormal β-cell functions found in CS [Cushing’s syndrome] include increased insulin secretion to overcome decreased insulin sensitivity in the CS patients without diabetes and decreased insulin secretion in the CS patients with diabetes,” the team wrote.

Notably, the impaired beta-cell function was the greater predictor of diabetes development in Cushing’s patients, having a more profound effect that decreased insulin sensitivity.

These findings support the usefulness of the glucose tolerance test to evaluate abnormal blood glucose levels and beta-cell dysfunction in Cushing’s syndrome, the study concluded.