Abstract
Introduction
Prader Willi Syndrome (PWS), while rare, is the most common genetic cause of obesity. It is caused by a functional loss of paternally expressed genes from chromosomal region ...15q11-13. PWS is characterized by short stature, neurodevelopmental delay, obsessive-compulsive behaviors, hypothalamic dysfunction, and hyperphagia, associated with an aberrant satiety response and elevated levels of ghrelin. Excessive daytime sleepiness (EDS) and sleep-disordered breathing (SDB), including obstructive sleep apnea (OSA) and central sleep apnea, are common.
Report of Cases: A 17-year-old male, with PWS, morbid obesity, autism, and diabetes mellitus (DM) type-2 was referred for evaluation of snoring and EDS (Epworth Sleepiness Score 16). He had recently been admitted with diabetic ketoacidosis associated with binge eating. He had no prior sleep testing. He denied sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy. He had a body mass index of 54 kg/m2 with short stature (1.6m). On exam, he had a Mallampati score of 4 and 1+ tonsils. A recent echocardiogram was normal. Polysomnography showed sleep latency of 10 mins, apnea-hypopnea index (AHI) of 148/hr, nadir oxygen saturation of 73%, with 45% of total sleep time < 90%. Hypoventilation was not present. He was prescribed auto-titrating positive airway pressure (PAP) therapy. His mother was instructed to start locking access to food again. He was treated with insulin and metformin, with a plan to start on a glucagon-like peptide-1 (GLP-1) agonist. He had been on growth hormone (GH) previously, but in the context of his other morbidities, it was not reinitiated.
Conclusion
It is critical to screen and monitor patients with PWS for OSA, as SDB occurs in almost 70%. While PAP therapy may improve OSA, there is often residual EDS (likely due to underlying hypothalamic dysfunction), and alerting agents may be needed. GH can be considered for short stature but is contraindicated in patients with morbid obesity, untreated severe OSA, and uncontrolled diabetes. Management of diabetes, obesity, and hyperphagia in patients with PWS is challenging. Supervision and strict limitation of food intake using physical barriers are important. While data are limited, GLP-1 agonists may provide potential benefits for weight, glycemic, and appetite control in patients with PWS.
Support (If Any)
Context: The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort represents the largest and best-characterized national sample of American youth with recent-onset type 2 ...diabetes.
Objective: The objective of the study was to describe the baseline characteristics of participants in the TODAY randomized clinical trial.
Design: Participants were recruited over 4 yr at 15 clinical centers in the United States (n = 704) and enrolled, randomized, treated, and followed up 2–6 yr.
Setting: The study was conducted at pediatric diabetes care clinics and practices.
Participants: Eligible participants were aged 10–17 yr inclusive, diagnosed with type 2 diabetes for less than 2 yr and had a body mass index at the 85th percentile or greater.
Interventions: After baseline data collection, participants were randomized to one of the folllowing groups: 1) metformin alone, 2) metformin plus rosiglitazone, or 3) metformin plus a lifestyle program of weight management.
Main Outcome Measures: Baseline data presented include demographics, clinical/medical history, biochemical measurements, and clinical and biochemical abnormalities.
Results: At baseline the cohort included the following: 64.9% were female; mean age was 14.0 yr; mean diabetes duration was 7.8 months; mean body mass index Z-score was 2.15; 89.4% had a family history of diabetes; 41.1% were Hispanic, 31.5% were non-Hispanic black; 38.8% were living with both biological parents; 41.5% had a household annual income of less than $25,000; 26.3% had a highest education level of parent/guardian less than a high school degree; 26.3% had a blood pressure at the 90th percentile or greater; 13.6% had a blood pressure at the 95th percentile or greater; 13.0% had microalbuminuria; 79.8% had a low high-density lipoprotein level; and 10.2% had high triglycerides.
Conclusions: The TODAY cohort is predominantly from racial/ethnic minority groups, with low socioeconomic status and a family history of diabetes. Clinical and biochemical abnormalities and comorbidities are prevalent within 2 yr of diagnosis. These findings contribute greatly to our understanding of American youth with type 2 diabetes.
The TODAY cohort, representing the largest and best-characterized national sample of American youth with type 2 diabetes, is described at baseline.
Hemoglobin A(1c) (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the ...relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking.
We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of ∼2 years in 218 subjects.
At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C <5.7%), 21% at risk for diabetes (A1C 5.7-6.4%), and 1% with diabetes (A1C >6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95% CI 0.70-0.92). The threshold for identifying type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time.
The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents.
OBJECTIVE: Hemoglobin A₁c (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the ...relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking. RESEARCH DESIGN AND METHODS: We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of ~2 years in 218 subjects. RESULTS: At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C <5.7%), 21% at risk for diabetes (A1C 5.7-6.4%), and 1% with diabetes (A1C >6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95% CI 0.70-0.92). The threshold for identifying type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time. CONCLUSIONS: The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents.
CONTEXT Pediatric obesity has escalated to epidemic proportions, leading to an array of comorbidities, including type 2 diabetes in youth. Since most overweight children become overweight adults, ...this chronic condition results in serious metabolic complications by early adulthood. To curtail this major health issue, effective pediatric interventions are essential. OBJECTIVE To compare effects of a weight management program, Bright Bodies, on adiposity and metabolic complications of overweight children with a control group. DESIGN One-year randomized controlled trial conducted May 2002-September 2005. SETTING Recruitment and follow-up conducted at Yale Pediatric Obesity Clinic in New Haven, Conn, and intervention at nearby school. PARTICIPANTS Random sample of 209 overweight children (body mass index BMI >95th percentile for age and sex), ages 8 to 16 years of mixed ethnic groups were recruited. A total of 135 participants (60%) completed 6 months of study, 119 (53%) completed 12 months. INTERVENTION Participants were randomly assigned to either a control or weight management group. The control group (n = 69) received traditional clinical weight management counseling every 6 months, and the weight management group (n = 105) received an intensive family-based program including exercise, nutrition, and behavior modification. Intervention occurred biweekly the first 6 months, bimonthly thereafter. The second randomization within the weight management group assigned participants (n = 35) to a structured meal plan approach (dieting), but this arm of the study was discontinued while enrollment was ongoing due to a high dropout rate. MAIN OUTCOME MEASURES Change in weight, BMI, body fat, and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 and 12 months. RESULTS Six-month improvements were sustained at 12 months in weight management vs control, including changes in the following (mean 95% confidence interval): weight (+0.3 kg −1.4 to 2.0 vs +7.7 kg 5.3 to 10.0); BMI (−1.7 −2.3 to −1.1 vs +1.6 0.8 to 2.3); body fat (−3.7 kg −5.4 to −2.1 vs +5.5 kg 3.2 to 7.8); and HOMA-IR (−1.52 −1.93 to −1.01 vs +0.90 −0.07 to 2.05). CONCLUSION The Bright Bodies weight management program had beneficial effects on body composition and insulin resistance in overweight children that were sustained up to 12 months. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00409422
Many youth with diabetes struggle to meet glycemic targets. The new ultralong duration of action of insulin degludec (iDeg) holds potential to ameliorate missed doses of basal insulin and improve ...glycemic control in youth with diabetes.
A retrospective chart review was undertaken of youth age 13 to <24 years in our practice with type 1 diabetes (T1D) or type 2 diabetes (T2D) who had been switched from glargine or detemir to iDeg to evaluate the impact of this transition on glycemic control.
Glycated hemoglobin A1c (HbA1c) in youth with T1D (n = 82) remained stable during 6 months of treatment with iDeg (10.1 ± 2.11% 87 ± 23 mmol/mol at start of iDeg compared to 10.1 ± 2.12% 87 ± 23 mmol/mol at 6 months of treatment), whereas in youth with T2D (n = 16), HbA1c significantly declined from 10.6 ± 2.3% (92 ± 25 mmol/mol) to 8.3 ± 2.2% (67 ± 24 mmol/mol) ( P = .0024).
In youth switched to iDeg, which in our practice is commonly due to ineffectiveness of the patient's current regimen, the outcome differences we saw may be due to preserved beta-cell function in youth with T2D. It remains to be seen whether there are benefits of transition to iDeg in youth with T1D beyond glycemic outcomes, such as reduction in ketosis and episodes of diabetic ketoacidosis.
DKA = diabetic ketoacidosis; DPV = Diabetes-Patienten-Verlaufsdokumentation (German/Austrian Prospective Diabetes Follow-Up Registry); HbA1c = glycated hemoglobin A1c; iDeg = insulin degludec; T1D = type 1 diabetes; T2D = type 2 diabetes.
Introduction: Treatment of type 2 diabetes (T2D) in children and adolescents is particularly challenging. Metformin monotherapy is the standard initial treatment for youth with T2D, once metabolic ...control is restored with insulin in patients who present with ketosis and/or marked hyperglycemia. Insulin, the only other drug approved for use in youth with T2D, is also used as add-on therapy when patients fail metformin mono-therapy.
Areas covered: In this paper, we will summarize the current use of both metformin and insulin in the treatment of pediatric type 2 diabetes, as well as comment on their limitations. Given the rapid progression of T2D in youth, there is also considerable interest in treating youth with new oral and injectable agents that have been approved for use in adults with T2D. The potential for improving clinical outcomes of each of the main classes of new drugs for the treatment of pediatric T2D will be summerized.
Expert commentary: We will conclude by reviewing why phase 3 randomized clinical trials examining the safety and efficacy of these medications in the pediatric population have been difficult to complete and discuss a potential pathway to overcome these obstacles to regulatory approval for these drugs for adolescents with T2D.
Hemoglobin A^sub 1c^ (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the ...relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking. We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of ~2 years in 218 subjects. At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C <5.7%), 21% at risk for diabetes (A1C 5.7-6.4%), and 1% with diabetes (A1C >6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95% CI 0.70-0.92). The threshold for identifying type 2 diabetes was 5.8% , with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time. The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents.
A study with an aim to help curtail the epidemic of pediatric obesity among children and adolescents is conducted. The results led an array of ailments including diabetes and the results concluded ...that Bright Bodies weight management programme had beneficial effects on obese children for up to a year.
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