Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families.

BACKGROUND: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children, and carries a considerable risk of neurological damage and developmental delays if diagnosis and treatment are delayed. Despite rapid advances in diagnosis and management, long-term developmental outcomes have not significantly improved in the past years. CHI remains a disease that is associated with significant morbidity, and psychosocial and financial burden for affected families, especially concerning the need for constant blood glucose monitoring throughout patients' lives. RESULTS: In this review, we discuss the key clinical challenges and unmet needs, and present insights on patients' and families' perspective on their daily life with CHI. Prevention of neurocognitive impairment and successful management of patients with CHI largely depend on early diagnosis and effective treatment by a multidisciplinary team of specialists with experience in the disease. CONCLUSIONS: To ensure the best outcomes for patients and their families, improvements in effective screening and treatment, and accelerated referral to specialized centers need to be implemented. There is a need to develop a wider range of centers of excellence and networks of specialized care to optimize the best outcomes both for patients and for clinicians. Awareness of the presentation and the risks of CHI has to be raised across all professions involved in the care of newborns and infants. For many patients, the limited treatment options currently available are insufficient to manage the disease effectively, and they are associated with a range of adverse events. New therapies would benefit all patients, even those that are relatively stable on current treatments, by reducing the need for constant blood glucose monitoring and facilitating a personalized approach to treatment.

Congenital hyperinsulinism (CHI) is a rare disease that causes newborn babies and children to have low blood sugar because of the abnormal release of insulin. Insulin is a hormone produced by the pancreas that promotes the transfer of sugar from the blood into the body's cells. In a healthy person, insulin is released only after a meal when the level of blood sugar is high, but infants and children with CHI make insulin even if the blood sugar is low. This can lead to dangerously low blood sugar levels, which can cause brain damage if left untreated. Unfortunately, diagnosis and treatment are often delayed, resulting in avoidable brain damage and developmental delays in these children. CHI is associated with substantial stress and anxiety for the families, especially due to the need for frequent feeding and the fear of low blood sugars added to the constant need to measure blood sugar levels. This article discusses the most important challenges and unmet needs in this rare disease, including the limited treatment options, the side effects of available treatment options and the heavy psychological, social and financial burden on affected families. Effective screening of newborns for CHI needs to be improved, and quick referral to specialized treatment centers is necessary to ensure the best outcomes for patients and families. In addition, awareness of CHI has to be raised in all medical professions caring for newborns and infants, and new medications are urgently needed to ensure the best possible treatment for all patients with CHI.

Prevalence and healthcare costs of obesity-related comorbidities: evidence from an electronic medical records system in the United States.

OBJECTIVE: This study estimated the economic burden of obesity-related comorbidities (ORCs) in the US, at both the person and population levels. METHODS: The Geisinger Health System provided electronic medical records and claims between January 2004 and May 2013 for a sample of 153,561 adults (50% males and 97% white). Adults with < 2 years of data, who were underweight (body mass index (BMI) < 18.5 kg/m(2)), or had diseases causing major weight change (e.g., malignancy) during the study period (i.e., continuous enrollment in health plans) were excluded. A total of 21 chronic conditions, with established association with obesity in the literature, were identified by diagnosis codes and/or lab test results. The total healthcare costs were measured in each year. The association between annual costs and ORCs was assessed by a regression, which jointly considered all the ORCs. The per-person incremental costs of a single comorbidity, without any of the other ORCs, were calculated. The population-level economic burden was the product of each ORC's incremental costs and the annual prevalence of the ORC among 100,000 individuals. The prevalence of ORCs was stratified by obesity status to estimate the economic burden among 100,000 individuals with obesity and among those without. RESULTS: This study identified 56,895 adults (mean age = 47 years; mean BMI = 29.6 kg/m(2)). The annual prevalence of ORCs ranged from 0.5% for pulmonary embolism (PE) to 41.8% for dyslipidemia. The per-person annual incremental costs of a single ORC ranged from $120 for angina to $1665 for PE. Hypertensive diseases (HTND), dyslipidemia, and osteoarthritis were the three most expensive ORCs at the population level; each responsible for ≥$18 million annually among 100,000 individuals. HTND and osteoarthritis were much more costly among individuals with obesity than those without obesity. LIMITATIONS: Data were from a small geographic region. CONCLUSIONS: ORCs are associated with substantial economic burden, especially for those requiring continuous treatments.

Variation in the risk of progression between glycemic stages across different levels of body mass index: evidence from a United States electronic health records system.

OBJECTIVE: The purpose of this study was to assess how the risks of glycemic stage transitions observed in clinical practice vary with body mass index (BMI). These transitions included progression from euglycemia ('normal') to prediabetes (PreD) and from PreD to type 2 diabetes (T2D), as well as from normal directly to T2D, and reversions from PreD to normal. METHODS: We examined the Geisinger Health System electronic health records and insurance claims data, segmenting a subject's medical history into normal, PreD, and/or T2D glycemic stages via diagnosis codes, glycosylated hemoglobin A1c (HbA1c) or fasting plasma glucose lab results, and use of anti-diabetic drugs. Weibull survival models, adjusted for age, gender, race, and smoking, were used to estimate the glycemic progression hazard ratios for BMI categories relative to normal BMI. RESULTS: The sample included 32,864 adults with normal glycemic levels at baseline and 4483 with PreD. The adjusted hazard ratios for normal to PreD progression ranged from 1.8 (25 ≤ BMI < 30 kg/m(2)) to 6.5 (BMI ≥ 40 kg/m(2)); for PreD to T2D, 1.3 to 2.9; for normal to T2D, 1.8 to 9.5; and for PreD to normal, ∼0.7 across all BMI. LIMITATIONS: The glycemic transitions may be recognized after the true onset since periodic glycemic testing was not required across the study population. CONCLUSIONS: A positive association between the risks of progression along the glycemic continuum and BMI levels was observed in a real-world United States practice setting.

A comparison of preferences for two GLP-1 products--liraglutide and exenatide--for the treatment of type 2 diabetes.

OBJECTIVE: To use time trade-off (TTO) to compare patient preferences for profiles of two glucagon-like peptide (GLP-1) products for the treatment of type 2 diabetes (liraglutide and exenatide) that vary on four key attributes - efficacy (as measured by hemoglobin A(1C)), incidence of nausea, incidence of hypoglycemia, and dosing frequency (QD vs. BID) - and measure the contribution of those attributes to preferences. METHODS: A total of 382 people with T2DM were recruited to participate in an internet-based survey consisting of a series of health-related questions, a conjoint exercise and a set of time trade-off items. In the conjoint exercise, respondents were presented with eight pairs of hypothetical GLP-1 profiles, and completed a time-tradeoff exercise for each pair. RESULTS: The product profile representing liraglutide was preferred by 96% of respondents and resulted in significantly higher health utilities (0.038) than the product profile representing exenatide (0.978 vs. 0.94, p < 0.05). Estimated preference scores from the conjoint analysis revealed that efficacy measured by hemoglobin A(1C) is the most important attribute, followed by nausea, hypoglycemia, and dosing schedule. LIMITATIONS: On-line participants may not represent 'typical' type 2 diabetes patients, and brief product profiles represented results from clinical trials, not clinical practice CONCLUSION: Based on the four attributes presented, patients prefer liraglutide over exenatide. Preference is based on superior efficacy and less nausea more than less hypoglycemia and once-daily dosing.

Results of a model analysis of the cost-effectiveness of liraglutide versus exenatide added to metformin, glimepiride, or both for the treatment of type 2 diabetes in the United States.

BACKGROUND: Nearly half of all US patients with type 2 diabetes mellitus (T2DM) are unable to maintain adequate glycosylated hemoglobin (HbA1(c)) control (ie, <7.0%). OBJECTIVE: The aim of this work was to determine the long-term cost-effectiveness of incretin-based therapy with once-daily liraglutide (vs twice-daily exenatide) combined with metformin, glimepiride, or both for the treatment of T2DM. METHODS: Patient data were obtained from the Liraglutide Effect and Action in Diabetes 6 (LEAD 6) trial. Baseline data included mean HbA1(c) (8.15%), age (56.7 years), disease duration (8 years), sex, body mass index, blood pressure, lipid levels, cardiovascular and renal risk factors, and other complications. The IMS Center for Outcomes Research Diabetes Model was used to project and compare lifetime (ie, 35-year) clinical and economic outcomes for once-daily liraglutide 1.8 mg compared with twice-daily exenatide 10 (ig, each used as add-on therapy with maximum-dose metformin and/or glimepiride. Treatment-effect assumptions were also derived from the LEAD 6 trial. Transition probabilities, utilities, and complication costs were obtained from published sources. All outcomes were discounted at 3% per annum, and the analysis was conducted from the perspective of a third-party payer in the United States. RESULTS: The base-case analysis indicated that, compared with exenatide, liraglutide add-on therapy was associated with a mean (SD) increase in life expectancy of 0.187 (0.250) years and an increase in qualityadjusted life-years of 0.322 (0.164) years. Compared with exenatide, total lifetime treatment costs for liraglutide were $12,956 higher, yielding an incremental costeffectiveness ratio (ICER) of $40,282. However, the costs of diabetes-related complications were lower with liraglutide than with exenatide ($49,784 vs $52,429, respectively). Sensitivity analysis indicated that setting patient HbA(1c) levels at the 95% upper limit reduced the ICER for liraglutide compared with exenatide to $33,086. CONCLUSION: In this model analysis using published clinical data and current medication acquisition price assumptions, liraglutide (in combination with metformin and/or glimepiride) appeared to be cost-effective in the US payer setting over a 35-year time horizon.