Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial.

Aims/hypothesis: Insulin resistance and compensatory hyperinsulinaemia are core features leading to beta cell failure in youth-onset type 2 diabetes. Insulin clearance (IC) is also a key regulator of insulin concentrations, but few data exist on IC in youth-onset type 2 diabetes. In a secondary analysis of our Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomised clinical trial, we investigated potential sex-, race-, ethnicity- and treatment-related differences in IC in youth-onset type 2 diabetes and aimed to identify metabolic phenotypes associated with IC at baseline and in response to metformin, metformin plus a lifestyle intervention, and metformin plus rosiglitazone.

Major adverse events in youth-onset type 1 and type 2 diabetes: The SEARCH and TODAY studies.

Aims: To determine contemporary incidence rates and risk factors for major adverse events in youth-onset T1D and T2D.

Methods: Participant interviews were conducted once during in-person visits from 2018 to 2019 in SEARCH (T1D: N = 564; T2D: N = 149) and semi-annually from 2014 to 2020 in TODAY (T2D: N = 495). Outcomes were adjudicated using harmonized, predetermined, standardized criteria.

Factors associated with pubertal growth outcomes in cystic fibrosis: Early Growth and Puberty in CF.

Background: Pubertal delays in children with cystic fibrosis (CF) have historically been common. It is unclear to what degree puberty is affected in the new era of CF care or the role of early nutritional status. We hypothesized that more favorable early growth trajectories are associated with improved pubertal growth outcomes.

Clinician perspectives and practices related to sexual and reproductive care provision for males with cystic fibrosis.

Background: Males with cystic fibrosis (MwCF) have unique sexual and reproductive health (SRH) concerns. This study investigates multidisciplinary CF clinician perspectives related to SRH for MwCF in the current era of CF care.

Methods: We surveyed multidisciplinary clinicians exploring attitudes, practices, and preferences toward male CF SRH care.

Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations.

Cystic fibrosis (CF) may cause a spectrum of hepatobiliary complications, including portal hypertension, multilobular cirrhosis, and liver failure. Current guidelines on the detection and monitoring of hepatobiliary complications in CF were published in 1999. The CF Foundation assembled a committee to evaluate research advances and formulate revised guidelines for CF-associated liver disease.

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.

Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study.

Background: Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease.

Men's sexual and reproductive health in cystic fibrosis in the era of highly effective modulator therapies-A qualitative study.

Background: As people with cystic fibrosis (CF) are living longer, men with CF increasingly face both general and disease-specific sexual and reproductive health (SRH) concerns. This study explored the SRH experiences and preferences of men with CF in health care in the era of widespread use of highly effective CF modulator therapies.

Methods: We recruited men with CF aged 18 years and older to participate in a qualitative descriptive study using semi-structured telephone interviews to explore experiences and preferences related to CF SRH care.

Cardiovascular risk factor progression in adolescents and young adults with youth-onset type 2 diabetes.

Aims: Youth-onset type 2 diabetes (T2D) confers a high risk of early adverse cardiovascular morbidity. We describe the cumulative incidence and prevalence of cardiovascular risk factors over time and examine relationships with diabetes progression in young adults with youth-onset T2D from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

Methods: Longitudinal data was used to evaluate the relationships between hypertension, LDL-C dyslipidemia, hypertriglyceridemia, and smoking with risk factors in 677 participants.

Cystic fibrosis related liver disease and endocrine considerations.

Cystic fibrosis-liver disease (CFLD) is one of the most common non-pulmonary complications in the CF population, is associated with significant morbidity and represents the third leading cause of mortality in those with CF. CFLD encompasses a broad spectrum of hepatobiliary manifestations ranging from mild transaminitis, biliary disease, hepatic steatosis, focal biliary cirrhosis and multilobular biliary cirrhosis. The diagnosis of CFLD and prediction of disease progression remains a clinical challenge.

Exploring provider attitudes and perspectives related to men's health in cystic fibrosis.

Background: New modulator therapies have markedly improved the health of people with cystic fibrosis (CF), allowing an increased focus on quality-of-life improvements for men with CF, including those related to sexual and reproductive health (SRH). This study explored CF providers' attitudes and experiences with addressing men's health in CF.

Methods: We interviewed geographically diverse adult and pediatric United States (U.

Gynecologic health care for females with cystic fibrosis.

As females with cystic fibrosis (CF) increasingly reach their reproductive years, gynecologic issues have become an important area of clinical care and research. First, females with CF may have disease-specific gynecologic problems, including cyclic pulmonary symptoms, vaginal yeast infections, and urinary incontinence. Next, contraceptive methods are thought to be overall safe and effective, however further research is needed to confirm this and to understand the lower rates of uptake among females with CF compared to the general population.

Longitudinal changes in vascular stiffness and heart rate variability among young adults with youth-onset type 2 diabetes: results from the follow-up observational treatment options for type 2 diabetes in adolescents and youth (TODAY) study.

Aims: (1) To describe changes in arterial stiffness and heart rate variability (HRV) over a 5-year interval, (2) examine changes by sex and race-ethnicity, and (3) evaluate the risk factors associated with the longitudinal changes in arterial stiffness and HRV.

Methods: Participants with youth-onset type 2 diabetes enrolled in the observational follow-up phase of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial had arterial stiffness [(pulse wave velocity, augmentation index, brachial distensibility] and six indices of HRV measured 5 years apart. Multivariable linear regression models assessed risk factors associated with changes in the outcomes over time.

Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome.

The nitrate-nitrite-NO pathway regulates NO synthase-independent vasodilation and NO signaling. Ingestion of inorganic nitrite has vasodilatory and blood pressure-lowering effects. Preclinical studies in rodent models suggest there may be a benefit of nitrite in lowering serum triglyceride levels and improving the metabolic syndrome.

Effects of exercise modality on body composition and cardiovascular disease risk factors in adolescents with obesity: a randomized clinical trial.

We compared the effects of aerobic exercise, resistance exercise, and combined aerobic and resistance exercise on total, regional subcutaneous adipose tissue (SAT) and visceral AT (VAT), skeletal muscle (SM), and biomarkers of cardiovascular disease in adolescents. Adolescents with overweight/obesity ( = 118; body mass index ≥ 85th percentile; age, 12-17 years) were randomized to 1 of the following groups for 6 months (3 days/week, 180 min/week): aerobic exercise ( = 38), resistance exercise ( = 40), or combined aerobic and resistance exercise ( = 40). After accounting for age, sex, and baseline value, there was a greater ( < 0.

Glycemic control and FEV recovery during pulmonary exacerbations in pediatric cystic fibrosis-related diabetes.

Rationale: Whether short-term glucose control in cystic fibrosis-related diabetes (CFRD) is associated with FEV recovery during acute pulmonary exacerbations is unclear.

Methods: Data from all patients with CFRD ages 6-21 years hospitalized in 2010-2016 for pulmonary exacerbations at our CF Center were analyzed, including CFRD status at each encounter, all FEV recorded during each exacerbation, and relevant clinical covariates. Glucose control was analyzed using meter blood glucose area under the curve (AUC) indices.

Effect of Surgical Versus Medical Therapy on Diabetic Kidney Disease Over 5 Years in Severely Obese Adolescents With Type 2 Diabetes.

Objective: To compare diabetic kidney disease (DKD) rates over 5 years of follow-up in two cohorts of severely obese adolescents with type 2 diabetes (T2D) undergoing medical or surgical treatment for T2D.

Research Design And Methods: A secondary analysis was performed of data collected from obese participants of similar age and racial distribution enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and the Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) studies. Teen-LABS participants underwent metabolic bariatric surgery (MBS).

Female reproductive health in cystic fibrosis.

Women with cystic fibrosis (CF) are living longer and healthier lives, and opportunities for childbearing are increasingly promising. However, this population can also face sexual and reproductive health concerns, including menstrual irregularities, unplanned pregnancies, infertility and pregnancy complications. Additionally, more women are entering menopause and are at risk for the consequences of estrogen deficiency.

Adrenal function in cystic fibrosis.

Cystic fibrosis (CF) is not known to directly affect the adrenal gland, but commonly used CF therapies do impact the function of the hypothalamic-pituitary-adrenal (HPA) axis. By binding to the glucocorticoid receptor, medications such as inhaled and oral corticosteroids can enhance the systemic effects of cortisol and result in iatrogenic Cushing syndrome. Prolonged use suppresses the body's ability to make cortisol, resulting in iatrogenic adrenal insufficiency upon medication discontinuation.

Vitamin D deficiency and its treatment in cystic fibrosis.

Vitamin D deficiency is a common finding in individuals with cystic fibrosis (CF), despite routine supplementation. Hypovitaminosis D is often the result of fat malabsorption, but other contributors include increased latitude, poor nutritional intake, decreased sun exposure, impaired hydroxylation of vitamin D, and non-adherence to the prescribed vitamin D regimen. Vitamin D is critical for calcium homeostasis and optimal skeletal health, and vitamin D deficiency in CF can lead to skeletal complications of osteopenia and osteoporosis.

Effects of Exercise Modality on Insulin Resistance and Ectopic Fat in Adolescents with Overweight and Obesity: A Randomized Clinical Trial.

Objective: To examine whether a combined aerobic exercise and resistance exercise is more effective than either aerobic exercise or resistance exercise alone in improving insulin sensitivity and reducing total adiposity and ectopic fat in adolescents.

Study Design: A total of 118 sedentary adolescents with overweight/obesity (body mass index >85th percentile, 12-17 years) were recruited from October 2013 through April 2017 at Children's Hospital of Pittsburgh. Participants were randomized to 1 of the following 6-month exercise groups (3 d/wk, 180 min/wk): aerobic exercise (n = 38), resistance exercise (n = 40), and combined aerobic exercise and resistance exercise (n = 40).

Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate.

Dietary NO (nitrate) and NO (nitrite) support ˙NO (nitric oxide) generation and downstream vascular signaling responses. These nitrogen oxides also generate secondary nitrosating and nitrating species that react with low molecular weight thiols, heme centers, proteins, and unsaturated fatty acids. To explore the kinetics of NOand NOmetabolism and the impact of dietary lipid on nitrogen oxide metabolism and cardiovascular responses, the stable isotopes NaNO and NaNO were orally administered in the presence or absence of conjugated linoleic acid (cLA).

The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test Heralds Biomarkers of Type 2 Diabetes Risk in Obese Youth.

Objective: The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against more sensitive clamp-measured biomarkers of type 2 diabetes risk, and to examine incretin/pancreatic hormones and free fatty acid associations in these curve phenotypes in obese adolescents without diabetes.

Research Design And Methods: A total of 277 obese adolescents without diabetes completed a 2-h OGTT and were categorized to either a monophasic or a biphasic group.

SIRT3-AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction.

Background: Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension.

Early Biomarkers of Subclinical Atherosclerosis in Obese Adolescent Girls with Polycystic Ovary Syndrome.

Objectives: Because in obese youth, pulse wave velocity (PWV), an early cardiovascular disease marker, is elevated, we tested if obese girls with polycystic ovary syndrome (OB-PCOS) have higher PWV and carotid intima-media thickness (cIMT) compared with obese girls without PCOS (OB-non-PCOS) and normal-weight girls without PCOS (NW-non-PCOS) and whether PWV and cIMT correlate with inflammatory and circulating endothelial function biomarkers.

Study Design: Cross-sectional study of PWV and cIMT in 91 OB-PCOS, 30 obese controls (OB-non-PCOS), and 19 normal-weight controls (NW-non-PCOS). Body composition, blood pressure, fasting glucose, insulin, lipid concentrations, and endothelial function biomarkers were measured.