In healthy individuals, cortisol levels exhibit a circadian pattern, peaking in the morning and decreasing the rest of the day. Studies are inconclusive as to the relationship between high total cortisol levels and obesity, prediabetes, and type 2 diabetes. Since cortisol levels are circadian, many naturopathic physicians use a salivary test performed at four time points during the day to measure the overall pattern of secretion, rather than relying upon a blood draw from a single time point. Some physicians hypothesize that a dysregulated pattern of cortisol is more indicative of diabetes risk than a high mean cortisol level. A retrospective chart review was performed on obese, prediabetic, and type 2 diabetes patients in order to test this theory. The goals of this study were to determine whether people with, or at risk for, type 2 diabetes have abnormal circadian cortisol patterns and dehydroepiandrosterone (DHEA) levels. The chart review demonstrated four patterns of cortisol secretion, one of which is circadian, in this population.

Type 2 diabetes is a multi-factorial disease characterized by mild to severe glucose dysregulation with associations to increased mortality, and the development of polyneuropathy, nephropathy, and heart disease. Diagnoses of obesity and/or prediabetes increases the risk of developing type 2 diabetes.(1,2) In healthy individuals, blood glucose concentrations are maintained between 80 and 100 mg/ dL. Ingestion of carbohydrates causes an increase in blood glucose concentration and subsequent release of insulin by beta-islet cells within the pancreas. Insulin lowers blood glucose both by decreasing hepatic and adipose glucose production, and by accelerating the uptake of glucose into peripheral tissues. One of the probable first steps in the development of type 2 diabetes is insulin resistance, defined by impaired sensitivity to a normal concentration of insulin. Insulin resistance is a common factor of obesity, prediabetes, and type 2 diabetes.

In human studies, high cortisol has been shown to contribute to insulin resistance and is likely involved in the development of type 2 diabetes, as well as the persistence of high glucose levels. Cortisol is a glucocorticoid hormone produced by the adrenal cortex that is involved in the regulation of mineralocorticoids, blood pressure, immune function and metabolism. Conditions that involve excess cortisol are hypertension, hypercholesterolemia, central obesity, and glucose intolerance. In fact, one of the likely methods by which cortisol contributes to these diseases is by inducing a state of insulin resistance. As the primary glucocorticoid released during stress, cortisol has a variety of actions: 1) impairs insulin-dependent glucose uptake in the periphery, 2) enhances gluconeogenesis in the liver, and 3) inhibits insulin secretion from pancreatic b-islet cells. All of these actions contribute to elevated glucose levels. Dysregulated cortisol levels have been shown in persons with insulin resistance, prediabetes, and type 2 diabetes. Prediabetes is characterized by a fasting plasma glucose between 100-126 mg/dL. This is also known as Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT). Beyond 126 mg/dL is diagnostic of type 2 diabetes. Cortisol normally follows a circadian pattern of secretion, peaking 30 minutes after waking followed by a gradual decrease throughout the rest of the day. Cortisol should be lowest in the evening, allowing sleep at night. Due to the circadian nature of cortisol secretion, identification of cortisol dysregulation may not appear if measuring only total cortisol levels in blood at a single time point.

Cortisol and dehydroepiandrosterone (DHEA) are produced in closely related metabolic pathways. DHEA is an additional factor to consider in the development of type 2 diabetes. The production of both DHEA and cortisol is regulated by the release of adrenocorticotropic hormone (ACTH) from the adrenal cortex. DHEA and DHEA-sulfate (S) are metabolic intermediates in the formation of the active sex steroids testosterone, dihydrotestosterone, and estrogen. In human studies, exogenously administered glucocorticoids reduce basal and ACTH-stimulated blood levels of DHEA and DHEA-S.14 Several studies have suggested that DHEA and DHEA-S are related to glucose and insulin regulation. A decrease of DHEA and DHEA-S is observed when humans are rendered hyperinsulinemic. In addition, a reduction in serum insulin is associated with an increase in serum DHEA and DHEA-S.17 Cortisol and DHEA can also be measured in saliva, and salivary levels have been found to correlate with plasma levels. In clinical practice, some physicians order salivary cortisol and DHEA tests for patients who have or are at risk for diabetes, or to diagnose and monitor adrenal function.