Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes.

BACKGROUND: Incidence of type 2 diabetes (T2D) in children and adolescents is increasing, but treatment options are limited. METHODS: This was a 26-week, phase 3 trial with a 26-week extension among patients (10 to 17 years of age) with uncontrolled T2D (A1C 6.5 to 10.

Longitudinal Effects of Glucose-Lowering Medications on β-Cell Responses and Insulin Sensitivity in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

Objective: To compare the long-term effects of glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, and sitagliptin) when added to metformin on insulin sensitivity and β-cell function.

Research Design And Methods: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) cohort with type 2 diabetes (n = 4,801), HOMA2 was used to estimate insulin sensitivity (HOMA2-%S) and fasting β-cell function (HOMA2-%B) at baseline and 1, 3, and 5 years on treatment. Oral glucose tolerance test β-cell responses (C-peptide index [CPI] and total C-peptide response [incremental C-peptide/incremental glucose over 120 min]) were evaluated at the same time points.

Unmet Needs in the Treatment of Childhood Type 2 Diabetes: A Narrative Review.

Type 2 diabetes (T2D) in youth is a global health concern characterized by an increasing incidence and prevalence, especially among disadvantaged socioeconomic subgroups. Moreover, youth-onset T2D is more aggressive and causes earlier, more severe long-term cardio-renal complications compared with T2D in adults. The therapeutic options available are limited and often inadequate, partially due to the numerous challenges in implementing clinical trials for this vulnerable patient population.

Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

Importance: Type 2 diabetes (T2D) is the leading cause of kidney disease in the US. It is not known whether glucose-lowering medications differentially affect kidney function.

Objective: To evaluate kidney outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) trial comparing 4 classes of glucose-lowering medications added to metformin for glycemic management in individuals with T2D.

Impact of school-supervised ultra-long-acting basal insulin injections on ketosis in youth with T1D and elevated haemoglobin A1c: A pilot study.

Background: In youth with type 1 diabetes (T1D), high haemoglobin A1c (HbA1c) levels are associated with an increased risk for diabetic ketoacidosis (DKA).

Aims: This study examined whether daily school-supervised basal insulin injections were feasible and if they reduced the risk of morning ketosis in children and adolescents with high HbA1c levels. We hypothesized that supervised glargine and degludec would reduce the risk of ketosis and that the prolonged action of degludec would protect from ketosis after consecutive days of unsupervised injections.

Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial.

Background: The incidence of type 2 diabetes in young people is increasing, but treatments remain limited. We aimed to assess the efficacy and safety of an empagliflozin dosing regimen versus placebo and linagliptin versus placebo on glycaemic control in young people with type 2 diabetes.

Methods: In this double-blind, placebo-controlled trial done in 108 centres in 15 countries, participants with type 2 diabetes (aged 10-17 years; HbA 6·5-10·5% [48-91 mmol/mol]) who had been previously treated with metformin or insulin were randomly assigned (1:1:1) to oral empagliflozin 10 mg, oral linagliptin 5 mg, or placebo.

Retinopathy During the First 5 Years of Type 1 Diabetes and Subsequent Risk of Advanced Retinopathy.

Objective: To determine whether individuals with type 1 diabetes (T1D) who develop any retinopathy at any time prior to 5 years of diabetes duration have an increased subsequent risk for further progression of retinopathy or onset of proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), diabetes-related retinal photocoagulation, or anti-vascular endothelial growth factor injections. Additionally, to determine the influence of HbA1c and other risk factors in these individuals.

Research Design And Methods: Diabetic retinopathy (DR) was assessed longitudinally using standardized stereoscopic seven-field fundus photography at time intervals of 6 months to 4 years.

The obesity paradox: Retinopathy, obesity, and circulating risk markers in youth with type 2 diabetes in the TODAY Study.

Aim: To understand the relationship of obesity and 27 circulating inflammatory biomarkers to the prevalence of non-proliferative diabetic retinopathy (NPDR) in youth with type 2 diabetes.

Methods: Youth with type 2 diabetes who participated in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study were followed for 2-6.5 years.

DKA Prevention and Insulin Pumps: Lessons Learned From a Large Pediatric Pump Practice.

Purpose: This purpose of the study was to describe recent diabetic ketoacidosis (DKA) incidence data in youth with type 1 diabetes using insulin pumps and the impact of continuous glucose monitors (CGMs) on DKA rates.

Methods: DKA data were obtained through a retrospective chart review of insulin pump users (ages <26 years) between December 2019 and June 2021 in an academic pediatric endocrinology practice where 68% of patients were pump users.

Results: Among 591 pump patients, 28 events occurred (3.

Commentary on CDC data showing an increased risk for pediatric diabetes with COVID-19 infection.

We question certain aspects of the recent Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report (January 2022) showing a significant increase in the incidence of diabetes in children after COVID‐19 infection. We are concerned at the source of data being limited to commercial health insurances and lack of factoring race, ethnicity, social determinants of health, body mass index, type of diabetes, and viral variants in the interpretation of these data.

A Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes.

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system.

American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.

Objective: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers.

Methods: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development.

Once-Weekly Exenatide in Youth With Type 2 Diabetes.

Objective: Approved treatments for type 2 diabetes in pediatric patients include metformin, liraglutide, and insulin. However, approximately one-half of the youth fail metformin monotherapy within 1 year, insulin therapy is associated with challenges, and liraglutide requires daily injections. Consequently, the efficacy and safety of once-weekly injections of exenatide for the treatment of youth with type 2 diabetes was evaluated.

SGLT2i Improves Glycemic Control in Patients With Congenital Severe Insulin Resistance.

Insulin-resistant diabetes in Rabson-Mendenhall syndrome (RMS) is relatively unresponsive to first-line antidiabetic treatments, including metformin and insulin. We report 2 patients with RMS treated with 2 different sodium-glucose cotransporter inhibitors 2: empagliflozin in an 11-year-old boy and dapagliflozin in a 12-year-old girl. In the first patient, we began empagliflozin at 2.

Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study.

Background: Since there are few treatment options for young people with type 2 diabetes, we aimed to assess the efficacy and safety of dapagliflozin as add-on therapy in children, adolescents, and young adults with type 2 diabetes receiving metformin, insulin, or both.

Methods: This multicentre, placebo-controlled, double-blind, randomised phase 3 study was undertaken at 30 centres in five countries (Hungary, Israel, Mexico, Russia, and the USA). Participants aged 10-24 years with type 2 diabetes and HbA1c concentration of 6·5-11% (48-97 mmol/mol) were randomly assigned 1:1 to oral dapagliflozin 10 mg or placebo during a 24 week double-blind period, which was then followed by a 28 week open-label safety extension in which all participants received dapagliflozin.

Long-term Continuous Glucose Monitor Use in Very Young Children With Type 1 Diabetes: One-Year Results From the SENCE Study.

Objectives: Achieving optimal glycemic outcomes in young children with type 1 diabetes (T1D) is challenging. This study examined the durability of continuous glucose monitoring (CGM) coupled with a family behavioral intervention (FBI) to improve glycemia.

Study Design: This one-year study included an initial 26-week randomized controlled trial of CGM with FBI () and CGM alone () compared with blood glucose monitoring (BGM), followed by a 26-week extension phase wherein the BGM Group received the CGM+FBI () and both original CGM groups continued this technology.

Youth with type 2 diabetes have a high rate of treatment failure after discontinuation of insulin: A Pediatric Diabetes Consortium study.

Insulin is commonly used to reverse gluco-toxicity in youth with newly diagnosed type 2 diabetes (T2D), but many are subsequently weaned off insulin. We analyzed Pediatric Diabetes Consortium (PDC) data to determine how long glycemic control is maintained after termination of initial insulin treatment. Youth with T2D who had previously been on insulin but were on either an intensive lifestyle intervention alone or metformin alone upon enrollment in the PDC T2D Registry were studied (N = 183).

Continuous Glucose Monitoring in Adults With Type 1 Diabetes With 35 Years Duration From the DCCT/EDIC Study.

Objective: We evaluated blinded continuous glucose monitoring (CGM) profiles in a subset of adults with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study to characterize the frequency of glycemic excursions and contributing factors.

Research Design And Methods: CGM-derived metrics were compared for daytime and nighttime periods using blinded CGM for a minimum of 6.5 days (average 11.

Tobacco use patterns and clinical outcomes in the T1D exchange.

Aims: This study examined associations between tobacco use and diabetes outcomes using the T1D Exchange Registry.

Methods: Adult participants (N = 933) completed standardized questionnaires including self-reported outcomes: past year serious hypoglycemic and diabetic ketoacidosis episodes, diabetes self-care, diabetes distress, and self-monitoring of blood glucose. Chart-extracted outcomes included HbA1c, nephrology and neuropathy diagnoses, and BMI.

Late Endocrine Effects after Stem Cell Transplant in a Young Girl with Griscelli Syndrome.

. Griscelli syndrome (GS) is a rare disorder characterized by partial albinism and silver hair with alteration in genes necessary for melanin transport. Type 2 GS is fatal due to severe immunodeficiency without curative stem cell transplant (SCT).

Racial and Ethnic Disparities in Comorbidities in Youth With Type 2 Diabetes in the Pediatric Diabetes Consortium (PDC).

Background: Type 2 diabetes in the U.S. is more prevalent in youth of minority racial-ethnic background, but disparities in health outcomes have not been examined in this population.

A Pilot Study of Youth With Type 1 Diabetes Initiating Use of a Hybrid Closed-Loop System While Receiving a Behavioral Economics Intervention.

Objective: Many youth do not use the hybrid closed-loop system for type 1 diabetes effectively. This study evaluated the impact of financial incentives for diabetes-related tasks on use of the 670G hybrid closed-loop system and on glycemia.

Methods: At auto mode initiation and for 16 weeks thereafter, participants received a flat rate for wearing and calibrating the sensor ($1/day), administering at least 3 mealtime insulin boluses per day ($1/day), and uploading ($5/week).

Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes.

Objective: We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study followed for >35 years.

Research Design And Methods: Standardized longitudinal data collection included: ) stereoscopic seven-field retinal fundus photography centrally graded for retinopathy stage and clinically significant macular edema; ) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); ) cardiovascular autonomic neuropathy (CAN) reflex testing; and ) adjudicated CVD events, including death from CVD, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on electrocardiogram, confirmed angina, or coronary artery revascularization. Cox proportional hazards models assessed the association of microvascular complications with subsequent risk of CVD.

Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study.

Objective: To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia.

Research Design And Methods: One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean ± SD age at baseline 7.0 ± 1.