Abnormal glucagon secretion contributes to a longitudinal decline in glucose tolerance.

Context: Defects in insulin secretion and action contribute to the progression of prediabetes to diabetes. However, the contribution of α-cell dysfunction to this process has been unclear.

Objective: Understand the relative contributions of α-cell and β-cell dysfunction to declining glucose tolerance.

Enhanced quantification of α-cell suppression by hyperglycemia using a high-sensitivity glucagon assay.

Accurate measurement of glucagon concentrations in a variety of conditions is necessary for subsequent estimation of glucagon secretion. Glucagon arises in the α-cell as a product of proglucagon processing. Modern two-site immunoassays have overcome prior problems with glucagon measurement caused by cross-reactivity with other proglucagon-derived fragments.

Inclusion of Rurality and Social Determinants of Health in Documents for the Primary Prevention of Type 2 Diabetes: A Systematic Review.

The type 2 diabetes (T2D) burden is disproportionately concentrated in low- and middle-income economies, particularly among rural populations. The purpose of the systematic review was to evaluate the inclusion of rurality and social determinants of health (SDOH) in documents for T2D primary prevention. This systematic review is reported following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.

Twin Pregnancy Complicated by Gestational Diabetes Mellitus: Maternal and Neonatal Outcomes.

Context: The risk of gestational diabetes mellitus (GDM) in twin pregnancies is more than double that of singleton pregnancies. Although twin pregnancies present unique challenges for fetal growth and prenatal management, the approach to GDM diagnosis and treatment is the same regardless of plurality. Data on pregnancy outcomes for individuals with GDM and a twin pregnancy are limited and conflicting.

County Rurality and Incidence and Prevalence of Diagnosed Diabetes in the United States.

Objective: To examine differences in the incidence and prevalence of diagnosed diabetes by county rurality.

Patients And Methods: This observational, cross-sectional study used US Centers for Disease Control and Prevention data from 2004 through 2019 for county estimates of incidence and prevalence of diagnosed diabetes. County rurality was based on 6 levels (large central metro counties [most urban] to noncore counties [most rural]).

Four weeks SGLT2 inhibition improves beta cell function and glucose tolerance without affecting muscle free fatty acid or glucose uptake in subjects with type 2 diabetes.

Aims: Sodium glucose co-transporter-2 (SGLT2) inhibition lowers glucose levels independently of insulin, leading to reduced insulin secretion and increased lipolysis, resulting in elevated circulating free fatty acids (FFAs). While SGLT2 inhibition improves tissue insulin sensitivity, the increase in circulating FFAs could reduce insulin sensitivity in skeletal muscle and the liver. We aimed to investigate the effects of SGLT2 inhibition on substrate utilization in skeletal muscle and the liver and to measure beta-cell function and glucose tolerance.

Characteristics of Normal Weight Insulin-Resistant Adults with Unfavorable Health Outcomes.

Insulin resistance can be present in otherwise healthy, normal weight adults. Whether there are phenotype/sex-differences between normal weight insulin-resistant (NWIR) and normal weight insulin-sensitive (NWIS) Caucasians and whether there are differences in adverse health outcomes are unknown. Our goal was to define phenotypes and intermediate-term health outcomes of NWIR versus NWIS Caucasian adults.

Ethanol Ablation for Benign Insulinoma: Intraoperative and Endoscopic Approaches.

Introduction: Ethanol ablation can be utilized to manage insulinoma. We aimed to analyze our outcomes of endoscopic ultrasound (EUS) and intraoperative ultrasound (IOUS) guided Ethanol ablation of insulinoma.

Methods: A single institution retrospective review of adults undergoing Ethanol ablation of benign pancreatic insulinoma (2007-2022) was performed.

Suppression of Endogenous Insulin Secretion by Euglycemic Hyperinsulinemia.

Context: The impact of insulin, particularly exogenous hyperinsulinemia, on insulin secretion in humans is debated.

Objective: We assessed the effects of exogenous hyperinsulinemia on insulin secretion and whether the response is altered in insulin resistance associated with obesity.

Methods: Insulin secretion rates (ISRs) during euglycemic hyperinsulinemic clamp studies (52 volunteers) were calculated using a model that employs plasma C-peptide concentrations.

Glucagon-like peptide-1 receptor blockade impairs islet secretion and glucose metabolism in humans.

BACKGROUNDProglucagon can be processed to glucagon-like peptide1 (GLP-1) within the islet, but its contribution to islet function in humans remains unknown. We sought to understand whether pancreatic GLP-1 alters islet function in humans and whether this is affected by type 2 diabetes.METHODSWe therefore studied individuals with and without type 2 diabetes on two occasions in random order.

International Guidelines for the Diagnosis and Management of Hyperinsulinism.

Background: Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children. In the 65 years since HI in children was first described, there has been a dramatic advancement in the diagnostic tools available, including new genetic techniques and novel radiologic imaging for focal HI; however, there have been almost no new therapeutic modalities since the development of diazoxide.

Summary: Recent advances in neonatal research and genetics have improved our understanding of the pathophysiology of both transient and persistent forms of neonatal hyperinsulinism.

Guidelines, position statements, and advisories for the primary prevention of type 2 diabetes, hypertension, and cardiovascular disease in rural populations: A systematic review protocol.

Introduction: Globally, noncommunicable diseases (NCDs), which include type 2 diabetes (T2D), hypertension, and cardiovascular disease (CVD), are associated with a high burden of morbidity and mortality. Health disparities exacerbate the burden of NCDs. Notably, rural, compared with urban, populations face greater disparities in access to preventive care, management, and treatment of NCDs.

Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of β-cell function and glucose metabolism in subjects without diabetes.

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased β-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions.

Nonlinear Mixed Effects Modeling of Glucagon Kinetics in Healthy Subjects.

Objective: To date, the lack of a model of glucagon kinetics precluded the possibility of estimating and studying glucagon secretion in vivo, e.g., using deconvolution, as done for other hormones like insulin and C-peptide.

Interventional vs surgical procedures in localized/nonmetastatic insulinomas (ablation vs surgery).

Localized insulinoma is an uncommon entity that can result in substantial morbidity due to the associated hypoglycemia. Recent studies have suggested an increase in the incidence of insulinoma in recent decades that may possibly be secondary to increased awareness, incidental diagnoses, and better diagnostic methods. Diagnosing and localizing insulinoma within the pancreas can be challenging, but advances in nuclear imaging may improve diagnostic accuracy.

Predictors of Metformin Failure: Repurposing Electronic Health Record Data to Identify High-Risk Patients.

Context: Metformin is the first-line drug for treating diabetes but has a high failure rate.

Objective: To identify demographic and clinical factors available in the electronic health record (EHR) that predict metformin failure.

Methods: A cohort of patients with at least 1 abnormal diabetes screening test that initiated metformin was identified at 3 sites (Arizona, Mississippi, and Minnesota).

Pitfalls in Diagnosing Hypoglycemia Due to Exogenous Insulin: Validation and Utility of an Insulin Analog Assay.

Objective: To overcome the limitations of commercially available insulin immunoassays which have variable detection of analog insulin and can lead to clinically discordant results and misdiagnosis in the workup of factitious hypoglycemia.

Patients And Methods: We performed analytical validation of a liquid chromatography high resolution accurate mass (LC-HRAM) immunoassay to detect insulin analogs. We completed clinical assessment using a large cohort of human serum samples from 78 unique individuals, and subsequently used the assay in the evaluation of eight individuals with high diagnostic suspicion for factitious hypoglycemia.