Roux-en-Y gastric bypass (RYGBP) is the most commonly performed type of bariatric surgery, which is used in the treatment of obesity and type 2 diabetes. Recent case reports and case series have described a rare complication of RYGBP, status post-gastric-bypass hyperinsulinemic hypoglycemia, which was mainly managed successfully with pancreatectomy. In this letter, we describe the first successful management of status post-gastric-bypass hyperinsulinemic hypoglycemia with diazoxide.

Depression, type 2 diabetes (T2D), and metabolic syndrome (MetS) are often comorbid. Depression per se increases the risk for T2D by 60%. This risk is not accounted for by the use of antidepressant therapy. Stress causes hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis, by triggering the hypothalamic corticotropin-releasing hormone (CRH) secretion, which stimulates the anterior pituitary to release the adrenocorticotropin hormone (ACTH), which causes the adrenal secretion of cortisol. Depression is associated with an increased level of cortisol, and CRH and ACTH at inappropriately “normal” levels, that is too high compared to their expected lower levels due to cortisol negative feedback. T2D and MetS are also associated with hypercortisolism. High levels of cortisol can impair mood as well as cause hyperglycemia and insulin resistance and other traits typical of T2D and MetS. We hypothesize that HPA axis hyperactivation may be due to variants in the genes of the CRH receptors (CRHR1, CRHR2), corticotropin receptors (or melanocortin receptors, MC1R-MC5R), glucocorticoid receptor (NR3C1), mineralocorticoid receptor (NR3C2), and of the FK506 binding protein 51 (FKBP5), and that these variants may be partially responsible for the clinical association of depression, T2D and MetS. In this review, we will focus on the correlation of stress, HPA axis hyperactivation, and the possible genetic role of the CRHR1, CRHR2, MCR1–5, NR3C1, and NR3C2 receptors and FKBP5 in the susceptibility to the comorbidity of depression, T2D, and MetS. New studies are needed to confirm the hypothesized role of these genes in the clinical association of depression, T2D, and MetS.

The TCF7L2 protein is a key transcriptional effector of the Wnt/β‐catenin signaling pathway, regulating gene expression. It was initially identified in cancer research and embryologic developmental studies. Later, the TCF7L2 gene was linked to type 2 diabetes (T2D), implicating TCF7L2 and Wnt‐signaling in metabolic disorders and homeostasis. In fact, TCF7L2‐T2D variants confer the greatest relative risk for T2D, unquestionably predicting conversion to T2D in individuals with impaired glucose tolerance. We aim to describe the relevance of TCF7L2 in other human disorders. The TCF7L2‐single nucleotide polymorphisms (SNPs) and T2D‐risk association have been replicated in numerous follow‐up studies, and research has now been performed in several other diseases. In this article, we discuss common TCF7L2‐T2D variants within the framework of their association with human diseases. The TCF7L2 functional regions need to be further investigated because the molecular and cellular mechanisms through which TCF7L2 contributes to risk associations with different diseases are still not fully elucidated. In this review, we show the association of common TCF7L2‐T2D variants with many types of diseases. However, the role of rare genetic variations in the TCF7L2 gene in distinct diseases and ethnic groups has not been explored, and understanding their impact on specific phenotypes will be of clinical relevance. This offers an excellent opportunity to gain a clearer picture of the role that the TCF7L2 gene plays in the pathophysiology of human diseases. The potential pleiotropic role of TCF7L2 may underlie a possible pathway for comorbidity in human disorders.