Summary Context Morphological characteristics of the glucose curve during an OGTT (time to peak and shape) may reflect different phenotypes of insulin secretion and action, but their ability to predict diabetes risk is uncertain. Objective To compare the ability of time to glucose peak and curve shape to detect prediabetes and β-cell function. Design and participants In a cross-sectional evaluation using an OGTT, 145 adults without diabetes (age 42±9y (mean±SD), range 24–62y, BMI 29.2±5.3 kg/m2, range 19.9–45.2 kg/m2) were characterized by peak (30 mins vs. >30 mins) and shape (biphasic vs. monophasic). Main Outcome Measures Prediabetes and disposition index (DI) – a marker of β-cell function. Results Prediabetes was diagnosed in 36% (52/145) of participants. Peak >30 mins, not monophasic curve, was associated with increased odds of prediabetes (OR: 4.0 vs. 1.1; P<0.001). Both monophasic curve and peak >30 mins were associated with lower DI (P≤0.01). Time to glucose peak and glucose AUC were independent predictors of DI (adjR2=0.45, P<0.001) Conclusion Glucose peak >30 mins was a stronger independent indicator of prediabetes and β-cell function than the monophasic curve. Time to glucose peak may be an important tool that could enhance prediabetes risk stratification.

Black women, compared with White women, have high rates of whole-body insulin resistance but a lower prevalence of fasting hyperglycemia and hepatic steatosis. This dissociation of whole-body insulin resistance from fasting hyperglycemia may be explained by racial differences in gluconeogenesis, hepatic fat, or tissue-specific insulin sensitivity. Two groups of premenopausal federally employed women, without diabetes were studied. Using stable isotope tracers, [2H2O] and [6,62-H2]glucose, basal glucose production was partitioned into its components (gluconeogenesis and glycogenolysis) and basal whole-body lipolysis ([2H5]glycerol) was measured. Indices of insulin sensitivity, whole-body (SI), hepatic (HISIGPR), and adipose tissue, were calculated. Hepatic fat was measured by proton magnetic resonance spectroscopy. Black women had less hepatic fat and lower fractional and absolute gluconeogenesis. Whole-body SI, HISIGPR, and adipose tissue sensitivity were similar by race, but at any given level of whole-body SI, Black women had higher HISIGPR. Therefore, fasting hyperglycemia may be a less common early pathological feature of prediabetes in Black women compared with White women, because gluconeogenesis remains lower despite similar whole-body SI.

Context Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. Case Description We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Conclusions Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.