Is diabetes in Cushing's syndrome only a consequence of hypercortisolism?

Abstract

Objective: Diabetes mellitus (DM) is one of the most frequent complications of Cushing's syndrome (CS). The aim of this study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients. Design: Cross-sectional study on 140 patients with CS. Methods: A total of 113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7G15.7 years) and 27 men (19 with pituitary disease and eight with adrenal disease, aged 38.1G20.01 years) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes), and diabetes (CS/DM) groups. Results: Seventy-one patients had CS/NGT (49.3%), 26 (18.5%) had CS/prediabetes and 43 (30.8%) had CS/DM. Significant increasing trends in the prevalence of family history of diabetes (P!0.001), metabolic syndrome (P!0.001), age (P!0.001) and waist circumference (PZ0.043) and decreasing trends in HOMA-b (P!0.001) and oral disposition index (DIo) (P!0.002) were observed among the groups. No significant trends in fasting insulin levels, area under the curve for insulin (AUC INS ), Matsuda index of insulin sensitivity (ISI-Matsuda) and visceral adiposity index were detected. Conclusions: Impairment of glucose tolerance is characterized by the inability of b-cells to adequately compensate for insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with the duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in patients with a natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of those at a high risk of metabolic complications.

The degree of urinary hypercortisolism is not correlated with the severity of cushing’s syndrome

“…Unfortunately, concordance with LNSC has not been performed. However, previous studies have reported a significant correlation between UFC and LNSC [39][40][41], showing even a better performance of LNSC compared to UFC in the diagnosis of Cushing's syndrome.…”

Metabolic comorbidities in Cushing's syndrome

“…No significant gender differences have been reported (6). Diabetic CS patients have been found to be older than normoglycaemic or prediabetic CS patients (7). Nevertheless, reported prevalence could be underestimated because available data were largely based on the measurement of fasting blood glucose.…”

Incompatibility between fasting and postprandial plasma glucose in patients with Cushing’s syndrome

“…Diabetes mellitus in Cushing's syndrome is characterized by the inability of β-cells to compensate for insulin resistance [6]. Since diabetes mellitus causes various health problems such as cardiovascular disease, renal disease and neuropathies, the screening for diabetes in patients with Cushing's syndrome is important to improve their prognosis.…”