Holley Allen

Diagnosis, screening and management of cystic fibrosis related diabetes mellitus: A consensus conference report

Cystic fibrosis (CF) is the most common lifethreatening autosomal recessive disease of Caucasians in the USA, affecting 1/3000 live births [1]. Gene defects on the long arm of chromosome 7 lead to defective production of a protein called the cystic fibrosis transmembrane regulator (CFTR). CFTR is a cAMP-dependent chloride channel which influences the water and electrolyte composition of secretions from sweat glands, airways, pancreatic ducts, hepatobiliary ducts and intestinal glands. The common pathological finding in these organs is accumulation of thick, viscous secretions associated with progressive obstruction, scarring and destruction; 84% of CF patients die from respiratory disease [2]. Improvements in pulmonary and nutritional care over the last few decades have led to dramatic improvements in the mortality rate, and now many patients with CF live into their third, fourth or fifth decades. The median life expectancy for CF patients at present is 31.3 years [2]. As CF patients Abbre6iations: ADA, American Diabetes Association; CF, cystic fibrosis; CFRD, cystic fibrosis related diabetes mellitus; CFTR, cystic fibrosis transmembrane regulator; DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose; GDM, gestational diabetes mellitus; 2-h PG, 2-h plasma glucose during oral glucose tolerance test; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; SMBG ,self-monitoring of blood glucose. * Corresponding author. Present address: Pediatric Department Box 404, University of Minnesota, 516 Delaware St. SE, Minneapolis, Minnesota 55455, USA. Tel.: +1-612-624-5409; fax: +1-612-624-2682. E-mail address: moran001@tc.umn.edu (A. Moran)

High Flow Nasal Cannulae Therapy in Infants with Bronchiolitis

OBJECTIVES To determine whether the introduction of heated humidified high-flow nasal cannulae (HFNC) therapy was associated with decreased rates of intubation for infants <24 months old with bronchiolitis admitted to a pediatric intensive care unit (PICU). STUDY DESIGN A retrospective chart review of infants with bronchiolitis admitted before and in the season after introduction of HFNC. RESULTS In the season after the introduction of HFNC, only 9% of infants admitted to the PICU with bronchiolitis required intubation, compared with 23% in the prior season (P=.043). This 68% decrease in need for intubation persisted in a logistic regression model controlling for age, weight, and RSV status. HFNC therapy resulted in a greater decrease in respiratory rate compared with other forms of respiratory support, and those infants with the greatest decrease in respiratory rate were least likely to be intubated. In addition, median PICU length of stay for children with bronchiolitis decreased from 6 to 4 days after the introduction of HFNC. DISCUSSION We hypothesize that HFNC decreases rates of intubation in infants with bronchiolitis by decreasing the respiratory rate and work of breathing by providing a comfortable and well-tolerated means of noninvasive ventilatory support.

Insulin Therapy to Improve BMI in Cystic Fibrosis–Related Diabetes Without Fasting Hyperglycemia: Results of the Cystic Fibrosis Related Diabetes Therapy Trial

OBJECTIVE Cystic fibrosis–related diabetes (CFRD) without fasting hyperglycemia (CFRD FH−) is not associated with microvascular or macrovascular complications, leading to controversy about the need for treatment. The Cystic Fibrosis Related Diabetes Therapy (CFRDT) Trial sought to determine whether diabetes therapy improves BMI in these patients. RESEARCH DESIGN AND METHODS A three-arm multicenter randomized trial compared 1 year of therapy with premeal insulin aspart, repaglinide, or oral placebo in subjects with cystic fibrosis who had abnormal glucose tolerance. RESULTS One hundred adult patients were enrolled. Eighty-one completed the study, including 61 with CFRD FH− and 20 with severly impaired glucose tolerance (IGT). During the year before therapy, BMI declined in all groups. Among the group with CFRD FH−, insulin-treated patients lost 0.30 ± 0.21 BMI units the year before therapy. After 1 year of insulin therapy, this pattern reversed, and they gained 0.39 ± 21 BMI units (P = 0.02). No significant change in the rate of BMI decline was seen in placebo-treated patients (P = 0.45). Repaglinide-treated patients had an initial significant BMI gain (0.53 ± 0.19 BMI units, P = 0.01), but this effect was not sustained. After 6 months of therapy they lost weight so that by 12 months there was no difference in the rate of BMI change during the study year compared with the year before (P = 0.33). Among patients with IGT, neither insulin nor repaglinide affected the rate of BMI decline. No significant differences were seen in the rate of lung function decline or the number of hospitalizations in any group. CONCLUSIONS Insulin therapy safely reversed chronic weight loss in patients with CFRD FH−.

Insulin Therapy to Improve BMI in Cystic Fibrosis Related Diabetes Without Fasting Hyperglycemia: Results of the CFRDT Trial

OBJECTIVE Cystic fibrosis–related diabetes (CFRD) without fasting hyperglycemia (CFRD FH−) is not associated with microvascular or macrovascular complications, leading to controversy about the need for treatment. The Cystic Fibrosis Related Diabetes Therapy (CFRDT) Trial sought to determine whether diabetes therapy improves BMI in these patients. RESEARCH DESIGN AND METHODS A three-arm multicenter randomized trial compared 1 year of therapy with premeal insulin aspart, repaglinide, or oral placebo in subjects with cystic fibrosis who had abnormal glucose tolerance. RESULTS One hundred adult patients were enrolled. Eighty-one completed the study, including 61 with CFRD FH− and 20 with severly impaired glucose tolerance (IGT). During the year before therapy, BMI declined in all groups. Among the group with CFRD FH−, insulin-treated patients lost 0.30 ± 0.21 BMI units the year before therapy. After 1 year of insulin therapy, this pattern reversed, and they gained 0.39 ± 21 BMI units (P = 0.02). No significant change in the rate of BMI decline was seen in placebo-treated patients (P = 0.45). Repaglinide-treated patients had an initial significant BMI gain (0.53 ± 0.19 BMI units, P = 0.01), but this effect was not sustained. After 6 months of therapy they lost weight so that by 12 months there was no difference in the rate of BMI change during the study year compared with the year before (P = 0.33). Among patients with IGT, neither insulin nor repaglinide affected the rate of BMI decline. No significant differences were seen in the rate of lung function decline or the number of hospitalizations in any group. CONCLUSIONS Insulin therapy safely reversed chronic weight loss in patients with CFRD FH−.

Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome.

OBJECTIVE We evaluated the hypothesis that metformin would improve signs and symptoms of polycystic ovary syndrome (PCOS) in adolescents as compared to oral contraceptive pills (OCP) and have a favorable effect on obesity. STUDY DESIGN Thirty-five obese, post-menarchal, non-sexually active adolescents aged 12-21 years with PCOS and hyperinsulinism were randomly assigned to receive either OCP or metformin for 6 months. RESULTS There was a significant decrease in BMI in the two groups over time, from 40.1 to 38.6 in the OCP group, and 37.3 to 36.3 in the metformin group, p = 0.0026, but no significant difference in the degree of change between the two groups. Both groups had decreased free testosterone (OCP: 1.8 pg/ml to 0.96 pg/ml; metformin: 2.1 pg/ml to 1.6 pg/ml), p < 0.0001, and improvements in insulin resistance as evidenced by increased glucose/insulin (G/I) ratio (p < 0.005) and increased QUICK1 scores (p < 0.0005). No significant differences in response to treatment were found between the metformin and OCP groups in outcome variables. CONCLUSION Adolescents with PCOS treated with metformin or OCP experienced similar beneficial outcomes including reduction in androgen levels, weight loss, and increased insulin sensitivity. The choice of a treatment agent for long-term use will depend on safety profiles, therapeutic goals and patient adherence.

Evidence of human immunodeficiency virus-associated lipodystrophy syndrome in children treated with protease inhibitors.

We conducted a prospective evaluation for evidence of the HIV-associated lipodystrophy syndrome of 26 children infected with HIV-1. Six children had evidence of body fat redistribution. Nine children showed laboratory evidence of insulin resistance. All children with body fat distribution or insulin resistance had been treated with protease inhibitors. Children treated with protease inhibitors had higher total cholesterol, higher low density lipoprotein-cholesterol and higher triglycerides than untreated children.

Site of initial diabetes education does not affect metabolic outcomes in children with T1DM

To determine the difference in metabolic outcomes at 1 and 2 yr post type 1 diabetes mellitus (T1DM) diagnosis in children depending on the site of initial diabetes education: inpatient, vs. outpatient, vs. mixed locations.

Continuous glucose monitoring in children with type 1 diabetes: before and after insulin pump therapy.

Abstract:  Objective:   The aim of continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM) is to mimic as closely as possible the normal physiologic pattern seen in individuals without diabetes. This study was undertaken to determine the specific areas of improved glycemic control in subjects after initiation of insulin pump therapy and times where further improvement is needed.

First-phase insulin release in normal children

Normal values for the first-phase insulin release during an intravenous glucose tolerance test are not yet well defined for children and adolescents. In this study, 69 normal subjects (aged 7 to 22 years) who had no family history of type I diabetes, a normal glycohemoglobin value, and a negative islet cell antibody test result underwent a standard intravenous glucose tolerance test. The mean (+/- SEM) first-phase insulin release increased with age and pubertal status: 7 to 10 years, 93 +/- 10.1 mIU/L; 11 to 15 years, 172.7 +/- 22.3 mIU/L; and 16 to 22 years, 163 +/- 28.5 mIU/L. The mean intraindividual variability in 11 subjects who underwent a second test was 23.6%. Acute stress, as estimated by observer assessment or by blood catecholamine levels, did not significantly correlate with first-phase insulin release. We conclude that first-phase insulin release is markedly lower in prepubertal children than in adolescents and young adults.

The Design of Trials for Prevention of IDDM

Several large clinical trials for the prevention of IDDM in islet cell antibody positive first-degree relatives are planned or underway. The design of these trials rests in part on assumptions about the natural history of autoimmunity during the prediabetic period and on the likely effectiveness of the intervention being tested. At this time, most of the factors that influence the required sample size can only be roughly estimated.