Body composition helps to elucidate the different origins of low serum magnesium in children with obesity compared to children with type 1 diabetes.

Hypomagnesemia in patients with type 1 diabetes (T1D) as well as in obesity has been related to insulin resistance in adults, but not yet in pediatric patients. In this observational single-center study, we aimed to investigate the relation between the magnesium homeostasis, insulin resistance, and body composition in children with T1D and in children with obesity. Children with T1D (n = 148) and children with obesity and proven insulin resistance (n = 121) and healthy controls (n = 36) were included in this study. Serum and urine samples were collected to determine magnesium and creatinine. The total daily dose of insulin (for children with T1D), results from the oral glucose tolerance test (OGTT, for children with obesity), and biometric data were extracted from the electronic patient files. Furthermore, body composition was measured via bioimpedance spectroscopy. Serum magnesium levels were decreased in both children with obesity (0.87 ± 0.07 mmol/l) and children with T1D (0.86 ± 0.07 mmol/l) compared to healthy controls (0.91 ± 0.06; p = 0.005). A lower magnesium level was associated with more severe adiposity in children with obesity, while a worse glycemic control was associated with lower magnesium levels in children with T1D.   Conclusion: Children with T1D and children with obesity have decreased serum magnesium levels. An increased fat mass is associated with lower magnesium levels in childhood obesity, indicating that the adipose tissue is an important factor in magnesium homeostasis. In contrast, glycemic control was the main determining factor for serum magnesium levels in children with T1D. What is Known: • Hypomagnesaemia has been related to insulin resistance in both adults with T1D and adults with obesity. • There is an increasing prevalence of obesity and T1D in childhood, but little is known about the relationship between magnesium and insulin resistance in these children. What is New: • Both children with T1D and children with obesity have decreased serum magnesium levels. • In childhood obesity an increased fat mass is associated with lower magnesium levels, while glycaemic control is the main determining factor for serum magnesium in children with T1D.

Urinary epidermal growth factor reflects vascular health in boys with either obesity or type 1 diabetes. A role for renin, or beyond?

An increased blood pressure is a known comorbidity of both type 1 diabetes (T1DM) and obesity in children. Increasing evidence suggests a subtle interplay between epidermal growth factor (EGF) and renin along the juxtaglomerular system, regulating the impact of blood pressure on kidney health and the cardiovascular system. In this study, we investigated the relation between urinary EGF, serum renin and blood pressure in children with obesity or T1DM. 147 non-obese children with T1DM and 126 children with obesity, were included. Blood pressure was measured and mean arterial pressure (MAP) and the pulse pressure (PP) were calculated. Serum renin and urinary EGF levels were determined with a commercial ELISA kit. Partial Spearman rank correlation coefficients and multiple linear regression models were used to study the association between renin, the urinary EGF/urinary creatinine ratio and blood pressure parameters. The urinary EGF/urinary creatinine ratio is correlated with the SBP and the MAP in boys with obesity as well as in boys with T1DM. Multiple regression analysis showed that sex and pulse pressure in male subjects were found to be independently associated with renin. Sex, the presence of diabetes, age, the glomerular filtration rate and both pulse pressure and mean arterial pressure in male subjects were independently associated with urinary EGF/urinary creatinine. In conclusion, in boys with either obesity or diabetes, pulse pressure and mean arterial pressure are negatively associated with the functional integrity of the nephron, which is reflected by a decreased expression of urinary EGF.

Efficacy and safety of a 4-year combination therapy of growth hormone and gonadotropin-releasing hormone analogue in pubertal girls with short predicted adult height.

Objectives: To improve adult height in pubertal girls with a poor height prediction, treatment with growth hormone (GH) can be used in combination with a gonadotropin releasing hormone agonist (GnRHa), to delay closure of the growth plates. However, there are few studies to support this practice, and they show conflicting results. The objective of this trial is to assess the safety and efficacy of this combination treatment in early pubertal girls with a short predicted height, in comparison with matched controls. Design patients and methods: We designed an open-label, multicenter, interventional case-control study. Early pubertal girls with predicted adult height (PAH) below -2.5 SDS, were recruited in tertiary care centers in Belgium. They were treated for four years with GH and GnRHa. The girls were followed until adult height (AH) was reached. AH vs PAH, AH vs Height at start, and AH vs Target Height (TH) were evaluated, as well as safety parameters. Control data were assembled from historical patient files or from patients who preferred not to participate in the study. Results: Sixteen girls with mean age ( ± SD) at start of 11.0 years (± 1.3) completed the study protocol and follow-up. Their mean height ( ± SD) increased from 131.3 ± 4.1 cm (-2.3 ± 0.7 SDS) at start of treatment to 159.8 ± 4.7 cm (-1.1 ± 0.7 SDS) at AH. In matched controls, height increased from 132.3 ± 4.2 cm (-2.4 ± 0.5 SDS) to 153.2 ± 3.4 cm (-2.1 ± 0.6 SDS) (p<0.001). AH surpassed initial PAH by 12.0 ± 2.6 cm in treated girls; and by 4.2 ± 3.6 cm in the controls (p<0.001). Most treated girls reached normal adult height (>-2SD) (87.5%) and 68.7% reached or superseded the target height (TH), which was the case in only a minority of the controls (37.5% and 6.2%, respectively) (p= 0.003 and 0.001). A serious adverse event possibly related to the treatment, was a fracture of the metatarsals. Conclusion: A four-year GH/GnRHa treatment in early pubertal girls with a poor PAH seems safe and results in a clinically relevant and statistically significant increase in AH compared with matched historical controls. Clinical trial registration: ClinicalTrials.gov, identifier NCT00840944.

The next generation: Urinary epidermal growth factor is associated with an early decline in kidney function in children and adolescents with type 1 diabetes mellitus.

AIMS: Micro-albuminuria is considered an early clinical sign of diabetes nephropathy, however, early decrease of glomerular filtration can be present years before the presence of microalbuminuria. In this study, we explored whether urinary epidermal growth factor (uEGF) might serve as an early marker of diabetes nephropathy compared to microalbuminuria in children and adolescents. METHODS: Children with type 1 diabetes mellitus (n = 158) and healthy controls (n = 40) were included in this study. Serum and urine samples were collected three times with an interval of at least one month to determine creatinine (serum and urine), epidermal growth factor and albumin (urine). Demographic data and routine lab values were extracted out of the electronic patient files. RESULTS: uEGF was significantly lower in children with T1DM compared to healthy controls (p = 0.032). A relatively lower glomerular filtration rate (eGFR) was associated with a decreased uEGF (p < 0.001). uEGF was independently associated with eGFR in a multivariate analysis. CONCLUSION: This study provides evidence that uEGF can serve as an early marker of diabetes nephropathy in children and adolescents.

Prevalence and Prevention of Contact Dermatitis Caused by FreeStyle Libre: A Monocentric Experience.

OBJECTIVE: Cutaneous adverse events (CAE) from FreeStyle Libre include allergic contact dermatitis (ACD) caused by the allergen isobornyl acrylate (IBOA). We aim to report CAE from this glucose sensor, ACD to IBOA in particular, and the outcome of using barrier films as a prevention. RESEARCH DESIGN AND METHODS: A monocentric, retrospective review of medical files from adult and pediatric patients with diabetes using Freestyle Libre, in the period between December 2016 and April 2019, was performed with a focus on CAE. RESULTS: Fifty-seven of 1,036 patients with diabetes (5.5%) were referred to our dermatology department because of CAE from FreeStyle Libre. Thirty-nine of 1,036 (3.8%) had ACD due to IBOA. Only two patients, of whom one sensitized to IBOA, had a benefit from using barrier films. CONCLUSIONS: CAE occurred in 5.5% of FreeStyle Libre users, and 3.8% suffered from ACD due to IBOA. Barrier films had limited value in the prevention.

Lisinopril in paediatric medicine: a retrospective chart review of long-term treatment in children.

OBJECTIVE: To investigate the antihypertensive efficacy, dosing, tolerability and effects on growth of lisinopril (off label-use) in paediatric patients during long-term treatment. DESIGN: We conducted a retrospective analysis of data from 123 patients treated with lisinopril in a paediatric nephrology clinic over a 9.3-year period. Patients were categorised by age group and predominant clinical diagnosis: hypertension (n=59), renal parenchymal disease (n=27), diabetes mellitus (n=33) and miscellaneous (n=4). RESULTS: The vast majority were Caucasian (93%) and boys (66%). Mean duration of treatment was 2.0 years. Age at start of treatment ranged from two months to 17.7 years. Mean lisinopril starting and final doses were 0.105 mg/kg/day for hypertensive patients and 0.108 mg/kg/day for patients with renal disease, respectively. The most common adverse event was hypotension (8.6% of the patients). Haematology and serum biochemistry profiles were unaffected by lisinopril. Growth was not different from data recorded by Belgian population studies. In 29 of the 47 hypertensive patients who received lisinopril monotherapy, comparing blood pressure (BP) at baseline and after six months treatment, mean reductions in systolic/diastolic BP were 19/18 mmHg. CONCLUSIONS: Lisinopril was well tolerated in paediatric patients. Doses of 0.1 mg/kg/day produced clinically significant BP reduction in hypertensive patients.