Trajectories of eGFR and risk of albuminuria in youth with type 2 diabetes: results from the TODAY cohort study.

Background: We conducted exploratory analyses to identify distinct trajectories of estimated glomerular filtration rate (eGFR) and their relationship with hyperfiltration, subsequent rapid eGFR decline, and albuminuria in participants with youth-onset type 2 diabetes enrolled in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

Methods: Annual serum creatinine, cystatin C, urine albumin, and creatinine measurements were obtained from 377 participants followed for ≥ 10 years. Albuminuria and eGFR were calculated.

Insights from rare variants into the genetic architecture and biology of youth-onset type 2 diabetes.

Youth-onset type 2 diabetes (T2D) is a growing public health concern. Its genetic basis and relationship to other forms of diabetes are largely unknown. To gain insight into the genetic architecture and biology of youth-onset T2D, we analyzed exome sequences of 3,005 youth-onset T2D cases and 9,777 ancestry matched adult controls.

The Metreleptin Effectiveness and Safety Registry (MEASuRE): concept, design and challenges.

Background: Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin deficiency in patients with lipodystrophy - a group of rare diseases characterized by a paucity of adipose tissue. MEASuRE (Metreleptin Effectiveness And Safety Registry) is a post-authorization, voluntary registry that gathers long-term safety and effectiveness data on metreleptin. Here, we present the aims and evolution of MEASuRE.

Initial Insights into the Genetic Variation Associated with Metformin Treatment Failure in Youth with Type 2 Diabetes.

Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold ( < 1 × 10), though none including published adult variants reached genome-wide significance.

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.

Genome-wide Association Study of Lipid Traits in Youth With Type 2 Diabetes.

Context: Dyslipidemia is highly prevalent in youth with type 2 diabetes (T2D), yet the pathogenic components of dyslipidemia in youth with T2D are poorly understood.

Objective: To evaluate the genetic determinants of lipid traits in youth with T2D through a genome-wide association study.

Design Participants And Main Outcome Measures: We genotyped 206 928 variants and imputed 17 642 824 variants in 1076 youth (mean age 15.

Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis.

Glycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the essential roles of glycans. Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.

Measuring Insulin Resistance in Humans.

Background: Insulin resistance is a pathophysiological condition associated with diabetes and cardiometabolic diseases that is characterized by a diminished tissue response to insulin action. Our understanding of this complex phenomenon and its role in the pathogenesis of cardiometabolic diseases is rooted in the discovery of insulin, its isolation and purification, and the challenges encountered with its therapeutic use.

Summary: In this historical perspective, we explore the evolution of the term "insulin resistance" and demonstrate how advances in insulin and glucose analytics contributed to the recognition and validation of this metabolic entity.

Maternal diet alters human milk oligosaccharide composition with implications for the milk metagenome.

Human milk is the optimal nutrition source for infants, and oligosaccharides represent the third most abundant component in milk after lactose and fat. Human milk oligosaccharides (HMO) are favorable macromolecules which are, interestingly, indigestible by the infant but serve as substrates for bacteria. Hypothesizing that the maternal diet itself might influence HMO composition, we sought to directly determine the effect maternal diet on HMO and the milk bacteria.

Metformin improves blood glucose by increasing incretins independent of changes in gluconeogenesis in youth with type 2 diabetes.

Aims/hypothesis: Metformin is the only approved oral agent for youth with type 2 diabetes but its mechanism of action remains controversial. Recent data in adults suggest a primary role for the enteroinsular pathway, but there are no data in youth, in whom metformin efficacy is only ~50%. Our objectives were to compare incretin concentrations and rates of glucose production and gluconeogenesis in youth with type 2 diabetes before and after short-term metformin therapy compared with peers with normal glucose tolerance (NGT).

Free fatty acid processing diverges in human pathologic insulin resistance conditions.

BACKGROUNDPostreceptor insulin resistance (IR) is associated with hyperglycemia and hepatic steatosis. However, receptor-level IR (e.g.

Beta cell function and insulin sensitivity in obese youth with maturity onset diabetes of youth mutations vs type 2 diabetes in TODAY: Longitudinal observations and glycemic failure.

Objective: In treatment options for type 2 diabetes in adolescents and youth (TODAY), 4.5% of obese youth clinically diagnosed with type 2 diabetes (T2D) had genetic variants consistent with maturity onset diabetes of youth (MODY) diagnosis. The course of IS and β-cell function in obese youth with MODY remains unknown.

Healthcare and associated costs related to type 2 diabetes in youth and adolescence: the TODAY clinical trial experience.

The economic issues related to medical treatments in youth with type 2 diabetes (T2D) are rarely reported and thus not fully understood. The Treatment Options for type 2 Diabetes in Adolescents and Youth clinical trial of youth recently diagnosed with T2D collected healthcare and related cost information from the largest cohort studied to date. Costs related to medical treatments and expenses faced by caregivers were identified over a 2-year period from 496 participants.

Use of Glucagon in Patients With Type 1 Diabetes.

Glucagon is an invaluable tool for patients with type 1 diabetes who experience severe hypoglycemia, but little is known about the actual use of rescue glucagon in this patient population. This survey study found that patients with type 1 diabetes were not adequately prescribed glucagon or educated about the use of glucagon, and patients reported various administration issues in using it. These results strongly suggest the need for standards of practice to increase the prescribing of glucagon and the provision of initial and ongoing education about its use and administration and the development of a glucagon rescue device or a glucagon product that would eliminate the complexity of its current formulation and packaging.

Self-Monitoring of Blood Glucose in Youth-Onset Type 2 Diabetes: Results From the TODAY Study.

Objective: To determine whether self-monitoring of blood glucose (SMBG) is associated with lower HbA in youth with type 2 diabetes taking oral medications only or after starting insulin for persistently elevated HbA.

Research Design And Methods: Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study participants ( = 699) taking oral medications were asked to perform SMBG twice daily. After reaching primary outcome (PO) (HbA ≥8% [64 mmol/mol]) over 6 months or an inability to wean from temporary insulin because of metabolic decompensation), insulin glargine was started.

Gluconeogenesis and risk for fasting hyperglycemia in Black and White women.

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.

Obesity-Related Metabolic Risk in Sedentary Hispanic Adolescent Girls with Normal BMI.

Hispanic adolescent girls with normal BMI frequently have high body fat %. Without knowledge of body fat content and distribution, their risk for metabolic complications is unknown. We measured metabolic risk indicators and abdominal fat distribution in post-pubertal Hispanic adolescent girls with Normal BMI (N-BMI: BMI < 85th percentile) and compared these indicators between girls with Normal BMI and High Fat content (N-BMI-HF: body fat ≥ 27%; = 15) and Normal BMI and Normal Fat content (N-BMI-NF: body fat < 27%; = 8).

Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial.

PurposeMonogenic diabetes accounts for 1-2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D).

Comparison of Surgical and Medical Therapy for Type 2 Diabetes in Severely Obese Adolescents.

Importance: Because of the substantial increase in the occurrence of type 2 diabetes in the pediatric population and the medical complications of this condition, therapies are urgently needed that will achieve better glycemic control than standard medical management.

Objective: To compare glycemic control in cohorts of severely obese adolescents with type 2 diabetes undergoing medical and surgical interventions.

Design, Setting, And Participants: A secondary analysis of data collected by the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) consortia was performed.

Racial and ethnic differences among children with new-onset autoimmune Type 1 diabetes.

Aim: To compare demographic and clinical characteristics among children from ethnic minorities and non-Hispanic white children with new-onset autoimmune Type 1 diabetes.

Methods: We analysed a single-centre series of 712 children with new-onset autoimmune Type 1 diabetes between January 2008 and March 2011. The median (range) age was 9.

Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes.

A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature.

Efficacy and Safety of Mini-Dose Glucagon for Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes.

Context: Standard treatment of hypoglycemia is oral carbohydrate, but it often results in hyperglycemia and entails extra caloric intake.

Objective: To evaluate low-dose glucagon to treat mild hypoglycemia in ambulatory adults with type 1 diabetes (T1D).

Design: Randomized crossover trial (two 3-week periods).