Frontiers in Endocrinology

Glucose effectiveness, defined as the ability of glucose itself to increase glucose utilization and inhibit hepatic glucose production, is an important mechanism maintaining normoglycemia. We conducted a minimal modeling analysis of glucose effectiveness at zero insulin (GEZI) using intravenous glucose tolerance test data from subjects with type 2 diabetes (T2D, n=154) and non-diabetic (ND) subjects (n=343). A hierarchical statistical analysis was performed, which provided a formal mechanism for pooling the data from all study subjects, to yield a single composite population model that quantifies the role of subject specific characteristics such as weight, height, age, sex, and glucose tolerance. Based on the resulting composite population model, GEZI was reduced from 0.021 min^–1 (standard error – 0.00078 min^–1) in the ND population to 0.011 min^–1 (standard error – 0.00045 min^–1) in T2D. The resulting model was also employed to calculate the proportion of the non–insulin-dependent net glucose uptake in each subject receiving an intravenous glucose load. Based on individual parameter estimates, the fraction of total glucose disposal independent of insulin was 72.8% ± 12.0% in the 238 ND subjects over the course of the experiment, indicating the major contribution to the whole-body glucose clearance under non-diabetic conditions. This fraction was significantly reduced to 48.8% ± 16.9% in the 30 T2D subjects, although still accounting for approximately half of the total in the T2D population based on our modeling analysis. Given the potential application of glucose effectiveness as a predictor of glucose intolerance and as a potential therapeutic target for treating diabetes, more investigations of glucose effectiveness in other disease conditions can be conducted using the hierarchical modeling framework reported herein.

Pituitary metastasis is an unusual situation in clinical practice, while the incidence is increasing with age. Breast cancer for women and lung cancer for men were the most frequent primary origins of pituitary metastasis. Diagnosing asymptomatic patients with unknown primary malignant origin is difficult, thus pituitary metastasis may be diagnosed as primary pituitary adenoma. Here, we report a case of a 65-year-old patient with visual changes and diabetes insipidus, showing an extensive mass in the sellar region which was initially thought to be a primary pituitary adenoma. Patient corticotropic deficits were corrected, and transnasal transsphenoidal surgery was adopted, leading to total tumor resection. Tumor texture during surgical procedure was similar to that of pituitary adenoma. However, the histopathological and immunohistochemistry results suggested it as a pituitary metastasis from lung neuroendocrine tumor. Postoperative chest CT scan confirmed a pulmonary mass consistent with primary neoplasm. Abdominal CT further detected multiple metastases in liver, pancreas, and colon. Despite intensive treatment, the patient continued to show decreased level of consciousness due to cachexia, resulting in death 1 week after surgery. This case highlights the importance of differential diagnosis of invasive lesions of the sellar region, especially in individuals over 60 years of age with diabetes insipidus.