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.

Exogenous insulin does not reduce protein catabolism in pre-diabetic cystic fibrosis patients: A randomized clinical trial.

Background: Cystic Fibrosis (CF) patients historically suffered from undernutrition, infection and inflammation. Insulin insufficiency-related protein catabolism further compromised health. We aimed to determine whether insulin improves protein catabolism in CF youth with abnormal glucose tolerance (AGT).

Short- and Long-Term Effects on Glucose Control of Nonadherence to Insulin Therapy in People With Type 2 Diabetes An Study.

Background: Strict adherence to multiple daily insulin (MDI) therapy is a cornerstone for the achievement of good glucose control in people with advanced type 2 diabetes (T2D). Here, we aim to assess glucose control in T2D subjects with poor adherence to MDI therapy.

Methods: We tuned the Padova T2D Simulator, originally describing early-stage T2D physiology, around advanced T2D people.

Hyperglycemia Suppresses Lactate Clearance During Exercise in Type 1 Diabetes.

Context: Circulating lactate concentration is an important determinant of exercise tolerance.

Objective: This work aimed to determine the role of hyperglycemia on lactate metabolism during exercise in individuals with type 1 diabetes (T1D).

Methods: The protocol at the University of Virginia compared 7 T1D participants and 7 participants without diabetes (ND) at euglycemia (5.

Controlling and powering a fully implantable artificial pancreas refillable by ingestible pills.

Over the past decade, there has been a growing interest in the development of an artificial pancreas for intraperitoneal insulin delivery. Intraperitoneal implantable pumps guarantee more physiological glycemic control than subcutaneous wearable ones, for the treatment of type 1 diabetes. In this work, a fully implantable artificial pancreas refillable by ingestible pills is presented.

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.

Developing the UVA/Padova Type 1 Diabetes Simulator: Modeling, Validation, Refinements, and Utility.

Arguably, diabetes mellitus is one of the best quantified human conditions. In the past 50 years, the metabolic monitoring technologies progressed from occasional assessment of average glycemia via HbA, through episodic blood glucose readings, to continuous glucose monitoring (CGM) producing data points every few minutes. The high-temporal resolution of CGM data enabled increasingly intensive treatments, from decision support assisting insulin injection or oral medication, to automated closed-loop control, known as the "artificial pancreas.

Temporal optimization of exercise to lower fasting glucose levels.

Exercise stimulates glucose uptake and increases insulin sensitivity acutely. Temporally optimizing exercise timing may minimize the nocturnal rise in glucose levels. This study examined the effect of exercise timing on evening and overnight glucose concentrations in individuals who were non-obese with normal fasting glucose levels (Non-Ob; n = 18) and individuals with obesity (OB) with impaired fasting glucose levels (OB+IFG) and without (n = 16 and n = 18, respectively).

Aetiology of Type 2 diabetes in people with a 'normal' body mass index: testing the personal fat threshold hypothesis.

Weight loss in overweight or obese individuals with Type 2 diabetes (T2D) can normalize hepatic fat metabolism, decrease fatty acid oversupply to β cells and restore normoglycaemia. One in six people has BMI <27 kg/m2 at diagnosis, and their T2D is assumed to have different aetiology. The Personal Fat Threshold hypothesis postulated differing individual thresholds for lipid overspill and adverse effects on β-cell function.

A new oral model of free fatty acid kinetics to assess lipolysis in subjects with and without type 2 diabetes.

Assessing free fatty acids (FFAs) kinetics and the role of insulin and glucose on FFA lipolysis and disposal may improve our understanding of the pathogenesis of type 2 diabetes (T2D). Some models have been proposed to describe FFA kinetics during an intravenous glucose tolerance test and only one during an oral glucose tolerance test. Here, we propose a model of FFA kinetics during a meal tolerance test and use it to assess possible differences in postprandial lipolysis in individuals with type 2 diabetes (T2D) and individuals with obesity without type 2 diabetes (ND).

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.

design and validation of a time-varying PID controller for an artificial pancreas with intraperitoneal insulin delivery and glucose sensing.

Type 1 diabetes (T1D) is a chronic autoimmune disease featured by the loss of beta cell function and the need for lifetime insulin replacement. Over the recent decade, the use of automated insulin delivery systems (AID) has shifted the paradigm of treatment: the availability of continuous subcutaneous (SC) glucose sensors to guide SC insulin delivery through a control algorithm has allowed, for the first time, to reduce the daily burden of the disease as well as to abate the risk for hypoglycemia. AID use is still limited by individual acceptance, local availability, coverage, and expertise.

β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT.

Context: The oral minimal model is a widely accepted noninvasive tool to quantify both β-cell responsiveness and insulin sensitivity (SI) from glucose, C-peptide, and insulin concentrations during a 3-hour 9-point oral glucose tolerance test (OGTT).

Objective: Here, we aimed to validate a 2-hour 7-point protocol against the 3-hour OGTT and to test how variation in early sampling frequency impacts estimates of β-cell responsiveness and SI.

Methods: We conducted a secondary analysis on 15 lean youth with stage 1 type 1 diabetes (T1D; ≥ 2 islet autoantibodies with no dysglycemia) who underwent a 3-hour 9-point OGTT.

Impaired Diurnal Pattern of Meal Tolerance and Insulin Sensitivity in Type 2 Diabetes: Implications for Therapy.

To assess the diurnal patterns of postprandial glucose tolerance and insulin sensitivity, 19 subjects with type 2 diabetes (8 women; 60 ± 11 years; BMI 32 ± 5 kg/m2) and 19 anthropometrically matched subjects with no diabetes (ND; 11 women; 53 ± 12 years; BMI 29 ± 5 kg/m2) were studied during breakfast (B), lunch (L), and dinner (D) with identical mixed meals (75 g carbohydrates) on 3 consecutive days in a randomized Latin square design. Three stable isotopes of glucose were ustilized to estimate meal fluxes, and mathematical models were used in estimating indices of insulin action and β-cell function. Postmeal glucose excursions were higher at D versus B and at D versus L in type 2 diabetes (P < 0.

Differential contribution of alpha and beta cell dysfunction to impaired fasting glucose and impaired glucose tolerance.

Aims/hypothesis: People with isolated impaired fasting glucose (IFG) have normal beta cell function. We hypothesised that an increased glucose threshold for beta cell secretion explains IFG.

Methods: We used graded glucose infusion to examine the relationship of insulin secretion rate (ISR) and glucagon secretion rate (GSR) with rising glucose.

Consensus Recommendations for the Use of Automated Insulin Delivery Technologies in Clinical Practice.

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies.

The relationship between insulin and glucagon concentrations in non-diabetic humans.

Abnormal postprandial suppression of glucagon in Type 2 diabetes (T2DM) has been attributed to impaired insulin secretion. Prior work suggests that insulin and glucagon show an inverse coordinated relationship. However, dysregulation of α-cell function in prediabetes occurs early and independently of changes in β-cells, which suggests insulin having a less significant role on glucagon control.

A software interface for in silico testing of type 2 diabetes treatments.

Background And Objective: The increasing incidence of diabetes continuously stimulates the research on new antidiabetic drugs. Computer simulation can save time and costs, alleviating the need of animal trials and providing useful information for optimal experiment design and drug dosing. We recently presented a type 2 diabetes (T2D) simulator as tool for in silico testing of new molecules and guiding treatment optimization.

Diabetes Technology Meeting 2021.

Diabetes Technology Society hosted its annual Diabetes Technology Meeting on November 4 to November 6, 2021. This meeting brought together speakers to discuss various developments within the field of diabetes technology. Meeting topics included blood glucose monitoring, continuous glucose monitoring, novel sensors, direct-to-consumer telehealth, metrics for glycemia, software for diabetes, regulation of diabetes technology, diabetes data science, artificial pancreas, novel insulins, insulin delivery, skin trauma, metabesity, precision diabetes, diversity in diabetes technology, use of diabetes technology in pregnancy, and green diabetes.

The Effect of Diabetes-Associated Variation in on Postprandial Glucose Metabolism When Glucagon and Insulin Concentrations Are Matched.

The rs7903146 variant in the gene is associated with defects in postprandial insulin and glucagon secretion and increased risk of type 2 diabetes. However, it is unclear if this variant has effects on glucose metabolism that are independent of islet function. We studied 54 nondiabetic subjects on two occasions where endogenous hormone secretion was inhibited by somatostatin.

Closed-form expressions and nonparametric estimation of COVID-19 infection rate.

Quantitative assessment of the infection rate of a virus is key to monitor the evolution of an epidemic. However, such variable is not accessible to direct measurement and its estimation requires the solution of a difficult inverse problem. In particular, being the result not only of biological but also of social factors, the transmission dynamics can vary significantly in time.

Intraperitoneal Insulin Delivery: Evidence of a Physiological Route for Artificial Pancreas From Compartmental Modeling.

Background: Intraperitoneal insulin delivery has proven to safely overcome a major limit of subcutaneous delivery-meal announcement-and has been able to optimize glycemic control in adults under controlled experimental conditions. In addition, intraperitoneal delivery avoids peripheral hyperinsulinemia resulting from the subcutaneous route and restores a physiological liver gradient.

Methods: Relying on a unique data set of intraperitoneal closed-loop insulin delivery obtained with a Model Predictive Controller (MPC), we develop a compartmental model of intraperitoneal insulin kinetics, which, once included in the UVa/Padova T1D simulator, will facilitate the investigation of various control strategies, for example, the simpler Proportional Integral Derivative controller versus MPC.