Double Diabetes: The Search for a Treatment Paradigm in Children and Adolescents

Discusses double diabetes -- the coexistence of features of both type 1 and type 2 diabetes in the same individual -- with a comprehensive discussion of the various aspects of this disorder and a focus on the search for a treatment paradigm in children and adolescents

Double Diabetes: The Evolving Treatment Paradigm in Children and Adolescents

The global pandemic of obesity in children and adolescents has resulted in a new expression of diabetes mellitus designated as double diabetes. The entity encompasses the autoimmune load of Type 1 Diabetes and the metabolic load of Type 2 Diabetes. There is no consensus on the best therapeutic modality for this new expression of diabetes mellitus. Optimal therapeutic options must address the coexistence of both metabolic and autoimmune components of diabetes mellitus in the patient. There have also been calls to revise the current classification of diabetes mellitus to take into account the surging prevalence of double diabetes in children and adolescents

Partial Clinical Remission of Type 1 Diabetes Mellitus in Children: Clinical Applications and Challenges with its Definitions

The honeymoon phase, or partial clinical remission (PCR) phase, of Type 1 diabetes mellitus (T1DM) is a transitory period that is marked by endogenous insulin production by surviving β cells following a diabetes diagnosis and the introduction of insulin therapy. It is a critical window in the course of the disease that has short and long-term implications for the patient, such as a significant reduction in the risk of long-term complications of T1DM. To promote long-term cardiovascular health in children with newly diagnosed T1DM, three key steps are necessary: the generation of a predictive model for non-remission, the adoption of a user-friendly monitoring tool for remission and non-remission, and the establishment of the magnitude of the early-phase cardiovascular disease risk in these children in objective terms through changes in lipid profile. However, only about 50% of children diagnosed with T1DM experience the honeymoon phase. Accurate and prompt detection of the honeymoon phase has been hampered by the lack of an objective and easily applicable predictive model for its detection at the time of T1DM diagnosis, the complex formulas needed to confirm and monitor PCR, and the absence of a straightforward, user-friendly tool for monitoring PCR. This literature review discusses the most up-to-date information in this field by describing an objective predictive model for non-remission, an easy tool for monitoring remission or non-remission, and objective evidence for the cardiovascular protective effect of PCR in the early phase of the disease. The goal is to present non-remission as an independent clinical entity with significantly poorer long-term prognosis than partial remission

Pseudohypoparathyroidism in Children

Summary: Albright hereditary osteodystrophy (AHO) is a genetic syndrome characterized by a distinctive set of developmental and skeletal defects that may easily be misdiagnosed as exogenous obesity in children. There are very few publications detailing the comprehensive management of children and adolescents with this disorder. This chapter provides a comprehensive discussion of the various aspects of this disorder. At the end, the reader should be able to: (1) List the clinical features of Albright hereditary osteodystrophy, (2) Identify the genetic and molecular abnormalities of AHO, (3) List the clinical features of pseudohypoparathyroidism type 1a (PHP 1a), (4) Describe the management of children and adolescents with PHP 1a

Does Hepatic Dysfunction Worsen Glucose Homeostasis by Impairing Vitamin D Metabolism?

The Management of diabetes mellitus (DM) remains an enigma even though the symptoms of the disease had been described more than 3000 years ago. This is because the central therapeutic goal of DM therapy, euglycemia, is influenced by complex physiologic and pathologic processes, some of which are clearly understood, while others are less clear. Suboptimal glycemic control is a recognized risk factor for acute and chronic complications of diabetes including microvascular and macrovascular diseases. The central question for this editorial is whether mild hepatic dysfunction could impair vitamin D metabolism and secondarily lead to sub-optimal glycemic control

Serum 25-hydroxyvitamin D levels do not correlate with asthma severity in a case-controlled study of children and adolescents

Background: There is no consensus on the association between vitamin D and asthma. Objective: To determine the relationship between 25-hydroxyvitamin D [25(OH)D] levels and asthma symptom severity in children and adolescents. Methods: A retrospective, case-control study of 263 subjects of ages 2–19 years with asthma who were compared to 284 non-asthmatic controls of similar ages. Subjects were excluded if they had diseases of calcium or vitamin D metabolism or were receiving calcium or vitamin D supplementation. Serum 25(OH)D was measured in all subjects. Asthma symptom severity, usually stratified into 6 steps, was stratified into five steps [1–5] based on the number and dose of controller medications used as outlined by the National Heart, Lung, and Blood Institute’s guidelines. Mean 25(OH)D values were compared between the asthmatic patients and controls, as well as among the five steps of asthma symptom severity. Results were adjusted for age, sex, BMI, race and severity of asthma symptoms. Results:There was no difference in 25(OH)D between asthmatic patients and controls (28.64±10.09 vs. 28.42±11.47, p=1.0). However, there was a significant difference in 25(OH)D between obese and non-obese asthmatic patients (23.33±7.67 vs. 30.16±10.20, p Conclusions: There were no differences in mean 25(OH)D levels between asthmatic patients and controls. Mean 25(OH)D level was significantly lower in both the obese asthmatic patients and obese controls. Asthma severity had no relationship to mean 25(OH)D levels

Is vitamin D deficiency a feature of pediatric celiac disease?

Background: Celiac disease (CD) is an autoimmune enteropathy characterized by villus atrophy and malabsorption of essential nutrients. Vitamin D deficiency has been described in autoimmune diseases, but its status in prepubertal children with CD has not been adequately studied. Objective: To determine the vitamin D status of prepubertal children with CD. Study design: A retrospective study of prepubertal children aged 3–12 years with CD (n=24) who were compared to prepubertal, non-CD children of the same age (n=50). Children were included in the study if they had a diagnosis of CD by intestinal biopsy, and were not on a gluten-free diet (GFD). Patients were excluded if they had diseases of calcium or vitamin D metabolism, or were receiving calcium or vitamin D supplementation or had other autoimmune diseases. All subjects had their serum 25-hydroxyvitamin D [25(OH)D] level measured. Results: There was no difference in 25(OH)D level between the CD and non-CD children (27.58±9.91 vs. 26.20±10.45, p=0.59). However, when the patients were subdivided into obese and non-obese groups, the non-obese CD patients had a significantly higher 25(OH)D level than the obese normal children (28.39±10.26 vs. 21.58±5.67, p=0.009). In contrast, there was no difference in 25(OH)D level between non-obese CD patients and non-obese normal children (28.39±10.26 vs. 30.64±12.08, p=0.52). The season of 25(OH)D measurement was not a significant confounder (p=0.7). Conclusions: Our data showed no difference in 25(OH)D levels between normal children and those with CD when adjusted for body mass index

The relationship between subnormal peak-stimulated growth hormone levels and auxological characteristics in obese children

Context: The hypothesis that obese children are overdiagnosed with growth hormone deficiency (GHD) has not been adequately investigated in the context of adiposity-related differences in auxology. Aim: To investigate the differences in auxological parameters between short, prepubertal, obese children, and normal-weight peers who underwent growth hormone stimulation testing (GHST). Hypothesis: Over-weight/obese children with GHD [peak growth hormone (GH) \u3c 10 μg/L] will have higher values for growth velocity (GV) standard deviation score (SDS), bone age minus chronological age (BA − CA), and child height SDS minus mid-parental height (MPTH) SDS when compared to normal-weight GHD peers. Subjects and Methods: A retrospective review of anthropometric and provocative GHST data of 67 prepubertal, GH-naïve children of age 10.21 ± 2.56 years (male n = 45, age 10.8 ± 2.60 years; female n = 22, age 8.94 ± 2.10). Inclusion criteria: GHST using arginine and clonidine. Exclusion criteria: hypopituitarism, abnormal pituitary magnetic resonance imaging scan, syndromic obesity, or syndromic short stature. Data were expressed as mean ± SD. Results: The over-weight/obese children with peak GH of \u3c10 μg/L had significantly lower value for natural log (ln) peak GH (1.45 ± 0.09 vs. 1.83 ± 0.35, p = 0.022), but similar values for GV SDS, insulin-like growth factor-I, insulin-like growth factor binding protein-3, bone age, BA − CA, MPTH, and child height SDS minus MPTH SDS compared to normal-weight peers with GHD. After adjusting for covariates, the over-weight/obese children (BMI ≥ 85th percentile) were \u3e7 times more likely than normal-weight subjects (BMI \u3c 85th percentile) to have a peak GH of \u3c10 μg/L, and 23 times more likely to have a peak GH of \u3c7 μg/L (OR = 23.3, p = 0.021). There was a significant inverse relationships between BMI SDS and the ln of peak GH (β = −0.40, r2 = 0.26, p = 0.001), but not for BMI SDS vs. GV SDS, ln peak GH vs. BA, or ln peak GH vs. GV SDS. Conclusion: Subnormal peak GH levels in obese prepubertal children are not associated with unique pre-GHST auxological characteristics

Adiposity is associated with early reduction in bone mass in pediatric inflammatory bowel disease

Background: The effect of adiposity on bone mass in the early phases of inflammatory bowel disease (IBD) in children and adolescents is unclear. Aims: To determine the role of adiposity on bone mass in the first 3 years of diagnosis of IBD. Hypothesis: Increased adiposity will be associated with increased bone mass in both the controls and IBD subjects. Setting: University tertiary institution. Methods: Height-adjusted bone mineral density (BMD) z-scores of 25 subjects, age 13.97 ± 2.70y, diagnosed with IBD for \u3c 4 years were compared to 24 controls, age 13.65 ± 2.60y. Overweight was defined as BMI of ≥85th but \u3c95th percentile, and obesity as BMI ≥95thpercentile. Severity of IBD was determined by the Pediatric Crohn’s Disease Activity Index and Lichtiger Colitis Activity Index. Results: Prior to stratification by BMI criterion, height-adjusted BMD z-scores were non-significantly lower in IBD subjects vs. controls for both the femoral neck (-0.8 ± 1.1 vs. -0.06 ± 1.1, p=0.070) and lumbar vertebrae (-0.4 ± 1.2 vs. 0.2 ± 1.2, p=0.086). Following stratification, height-adjusted BMD z-scores were significantly lower in the overweight/obese IBD subjects vs. overweight/obese controls for femoral neck (-0.9 ± 0.9 vs. 0.3 ± 1.3, p=0.032); and non-significantly lower for the lumbar spine z-score (-0.4 ± 1.6 vs. 0.5 ± 1.3, p=0.197). BMD z-score had no relationship with the duration of disease, steroid therapy, and the severity of disease. Conclusion: Adiposity was associated with reduced bone mass in the early phases of IBD, but with increased bone mass in the controls

The relationship between adiposity and stature in prepubertal children with celiac disease

Background and Aim: The pathogenesis of short stature in celiac disease (CD) is unknown. Obese children are generally taller than their non-obese peers; however, the role of adiposity on stature in CD is unclear. Our aim was to determine the association between adiposity and stature in CD. Subjects and methods: We compared the anthropometric characteristics of prepubertal children of ages 3-12 years, with biopsy-proven CD (n=40) and who were not on gluten-free diet, to same aged, prepubertal non-CD children (n=50). Body mass index (BMI) was calculated using the formula weight/height2. Sex-adjusted midparental target height (MPTH) standard deviation score (SDS) was calculated using National Children Health Statistics data for 18-year-old adults. Data were expressed as mean±standard deviation. Results: CD subjects had significantly lower BMI SDS than controls (0.61±1.22 vs. 1.28±1.60, p=0.027) but were not significantly shorter than the controls (-0.05±1.21 vs. 0.21±1.71, p=0.41). When the patients were subdivided into the normal-weight and overweight/obese groups, the normal-weight CD patients were of similar height as the normal-weight controls (p=0.76) but were significantly shorter than both the overweight/obese controls (p=0.003). The MPTH SDS did not differ between the groups. Conclusions: Overweight/obese prepubertal children with CD were taller than both their normal-weight CD peers and the normal-weight controls, but were of similar height as the overweight/obese control subjects