Anna Noczyńska

Advanced oxidation protein products (AOPPs) in juvenile overweight and obesity prior to and following weight reduction

OBJECTIVES To evaluate the formation of advanced oxidation protein products (AOPPs) in juvenile overweight/obesity and obesity-related disorders and to investigate the effect of weight reduction on AOPPs. DESIGN AND METHODS AOPPs were determined in 114 overweight/obese children and adolescents without/with insulin resistance and metabolic syndrome and compared with 53 lean controls. Measurements were repeated following weight reduction program (diet/exercise, bran-enriched diet/exercise, and diet/exercise plus metformin). RESULTS Overweight/obese subjects had higher AOPPs than lean controls, more elevated in patients with co-occurring metabolic syndrome. AOPPs positively correlated with central obesity, triglycerides, lipid peroxidation and insulin, and negatively with glucose to insulin ratio. AOPPs decreased following obesity intervention and DeltaAOPPs correlated with DeltaBMI%. AOPPs reduction was more pronounced in subjects on bran-enriched diet. Baseline AOPPs were a better predictor of clinically significant weight reduction than BMI%. CONCLUSIONS Juvenile overweight/obesity was associated with AOPPs accumulation, more pronounced in metabolic syndrome. Body mass reduction decreased oxidative stress, with bran-enriched diet being more effective than diet/exercise alone.

Efficacy and Safety of Sulfonylurea Use in Permanent Neonatal Diabetes Due to KCNJ11 Gene Mutations: 34-Month Median Follow-Up

BACKGROUND Recently, many patients with Kir6.2-related permanent neonatal diabetes mellitus (PNDM) have been successfully transferred from insulin therapy to sulfonylurea (SU) treatment. The long-term efficacy and safety of SU treatment in PNDM patients, however, have not yet been determined. METHODS We monitored glycemic control and the occurrence of potential side effects in 14 Kir6.2-related PNDM patients from Poland (median age, 12.0 years; range, 5-50 years) who were transferred to SU therapy at least 2 years ago. Three of the 14 patients were lost to follow-up, whereas for the remaining 11 individuals the median follow-up was 34 months (range, 27-51 months). RESULTS The initial reduction of glycated hemoglobin (HbA1c) after the switch to SU (approximately 3-6 months post-transfer) was 1.68% (range, 0.3-3.7%), and good metabolic control was maintained over the entire period of observation with an average HbA1c level of 6.0% (range, 5.3-6.7%) at the last visit. This was accompanied by a substantial drop in SU dose by 0.24 mg/kg, which constituted a 38.0% decrease. A rapid progression of retinal changes was observed in one patient, a 34-year-old woman at the beginning of the observation, with preexisting proliferative diabetic retinopathy. No causal relationship between these changes and SU treatment could be proven. Neither serious side effects nor progression of diabetes complications was observed in any other patients. No detrimental effect on growth in the observed minors was recorded. CONCLUSIONS In summary, the switch from insulin therapy to SU treatment in PNDM related to KCNJ11 mutations was found to be an efficient and safe therapeutic method over a period of 34-month median follow-up. Although no serious side effects were associated with SU treatment, their use in Kir6.2 PNDM requires further attention, particularly in children, adolescents, and patients with advanced chronic diabetes complications.

Mutations in the ABCC8 (SUR1 subunit of the KATP channel) gene are associated with a variable clinical phenotype

Objective  Mutations in the ABCC8 gene encoding the SUR1 subunits of the β‐cell K‐ATP channel cause neonatal diabetes (ND) mellitus. We aimed to determine the contribution of ABCC8 gene to ND in Poland, to describe the clinical phenotype associated with its mutations and to examine potential modifying factors.

The effect of a one-year weight reduction program on serum uric acid in overweight/obese children and adolescents.

Abstract Background: Hyperuricemia may underlie obesity and related disorders, but the impact of weight reduction and metformin on serum uric acid (sUA) in Caucasian children/adolescents is unknown. Methods: One hundred and thirteen children/adolescents were enrolled (83 completed) into 1-year weight reduction program (diet+exercise) without or with metformin. Anthropometric and biochemical measurements were conducted at baseline and at the end of follow-up (13±3 months). Results: sUA decreased in 86% females and 67% males. Significantly more patients substantially (≥10%) reduced their sUA than body mass index (BMI)%. In females, sUA decreased regardless of type of intervention, but more markedly in the metformin group, and ΔsUA correlated positively with ΔBMI%, ΔWHtR (waist-to-height ratio), Δinsulin, ΔHOMA (homeostasis model of assessment), and Δtriglycerides/high density lipoprotein (HDL), but correlated negatively with baseline sUA, HOMA, insulin, and triglycerides/HDL. Of these, metformin treatment, baseline sUA, and ΔBMI% were independent predictors of sUA reduction, explaining 77% of data variability. In males, sUA reduction was significant in the metformin group only, and negatively correlated with ΔWHR (waist-to-hip ratio), ΔWHtR, Δleptin, baseline sUA, and waist circumference. Of these, baseline sUA and ΔBMI% were independent predictors of sUA reduction, explaining 69% of data variability. Except for sUA, females reduced their BMI%, waist circumference, triglycerides, triglycerides/HDL and increased HDL, while males reduced total cholesterol. Conclusions: A longitudinal weight reduction program encompassing diet/exercise with or without metformin was more efficient in reducing sUA than weight and its effect on sUA and other metabolic parameters differed between genders. Weight loss did not condition sUA reduction, which was strongly dependent on baseline levels. The sUA reducing effects of metformin may contribute to its effects on blood pressure-lowering and endothelial function-improving properties in females.

Visfatin in juvenile obesity – the effect of obesity intervention and sex

Eur J Clin Invest 2011; 41 (12): 1284–1291

Gender-specific association of serum uric acid with metabolic syndrome and its components in juvenile obesity.

Abstract Background: Hyperuricemia has been implicated in the pathogenesis of obesity and related metabolic abnormalities. Studies on the association between serum uric acid (sUA) and metabolic syndrome (MetS) in juvenile obesity are scant. The effect of gender has not been evaluated. Methods: sUA (uricase method), anthropometric and biochemical indices were measured in gender-stratified children/adolescents consisting of 113 overweight/obese and 71 lean individuals. Results: In males, sUA was significantly elevated in overweight as well as obese patients. sUA was strongly associated with obesity indices and reflected sexual development, decreases in high density lipoprotein-cholesterol, and moderately, the number of MetS components. Waist circumference (WC) and Tanner stage explained 40% of sUA variability. Controlling for body mass index (BMI) and other MetS components, sUA was associated with abdominal obesity, explaining 30% of variability in WC. In females, sUA was significantly increased in obesity, high blood pressure (BP), and MetS and corresponded with the number of MetS components, indices of glucose metabolism, triglycerides (TG), and the atherogenecity index. Insulin-resistance (IR) (homeostasis model assessment; HOMA) and high BP explained 29% of sUA variability, whereas sUA, while controlling for BMI, age, and other MetS components, was associated with hypertriglyceridemia, hyperglycemia, high BP, and abdominal obesity. IR mediated the associations with high TG and glucose. Conclusions: The association between sUA and MetS components in juvenile obesity is gender-specific, with females being related more closely and to more metabolic abnormalities. It may explain why, despite its lower concentrations, sUA is an independent predictor of mortality from all causes and from vascular diseases exclusively in females. Our findings may help in identifying metabolic abnormalities which may possibly be targeted by reducing sUA in males and females.

Circulating adipocyte fatty acid-binding protein, juvenile obesity, and metabolic syndrome.

Abstract Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters associated with A-FABP elevation in children and adolescents and to evaluate the effect of obesity intervention and A-FABP diagnostic utility. A-FABP and anthropometric, metabolic, and inflammatory indices were measured in 31 lean and 114 overweight/obese children and adolescents and reassessed after obesity intervention (1 year; diet and enhanced physical activity, with or without metformin). A-FABP was significantly higher in overweight/obese than lean individuals, where it correlated with insulin, waist circumference (WC), and 2-h glucose independent of body mass index (BMI), age, gender, and developmental stage. The pattern of A-FABP associations differed between sexes. As a MetS indicator, A-FABP had 68% accuracy. The weight reduction program was effective in reducing A-FABP, BMI%, WC, triglycerides, and cholesterol. In conclusion, elevation in A-FABP is associated with MetS components independent of BMI status and can be reduced by diet and enhanced physical activity. A-FABP as a single MetS biomarker has a moderate accuracy.

Polymorphism of the FTO Gene Influences Body Weight in Children with Type 1 Diabetes without Severe Obesity

The objective was to compare the impact of clinical and genetic factors on body mass index (BMI) in children with type 1 diabetes (T1DM) without severe obesity. A total of 1,119 children with T1DM (aged 4–18 years) were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in children with T1DM included female gender (P = 0.0003), poor metabolic control (P = 0.0001), and carriage of the A allele of the FTO rs9939609 gene (P = 0.02). Conclusion. Our research indicates, when assessing, the risk of overweight and obesity carriage of the A allele in the rs9939609 site of the FTO gene adds to that of female gender and poor metabolic control. This trial is registered with ClinicalTrials.gov (NCT01279161).

The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype.

Published data on eye disorders in patients with Turner syndrome (TS) are limited. We aimed to evaluate the prevalence of eye disorders in patients with TS and assess the association with patient karyotype.

LPL gene mutation as the cause of severe hypertriglyceridemia in the course of ketoacidosis in a patient with newly diagnosed type 1 diabetes mellitus.

INTRODUCTION Severe hypertriglyceridemia is a condition associated with extremely high triglycerides (TG) plasma concentrations exceeding 1000mg/dl. This condition may result in mutations in genes encoding lipoprotein lipase (LPL), apolipoprotein C2 (APOC2) and apolipoprotein A5 (APOA5) characterized by an autosomal recessive inheritance pattern. AIM A case report of a patient in which clinical picture of type 1 diabetes mellitus (T1DM) was accompanied by diabetic ketoacidosis (DKA) and severe hypertriglyceridemia. CASE REPORT A 2.5-year-old boy was admitted to the hospital with ketoacidosis (pH - 7.0, BE - 20mmol/l, HCO3 10mmol/l), glucose level of 850mg%, hyponatremia (Na 100mmol/l) and hyperlipidemia (TG 13493 mg/dl, TC 734 mg/dl). The administered treatment resulted in nearly normal glycemic values and lipid disturbances normalization. This child was diagnosed with a heterozygous mutation of the LPL gene. Currently with an intensive insulin therapy and correct metabolic control of type 1 diabetes mellitus (T1DM), this patient maintains a normal lipid profile. CONCLUSION In patient with T1DM the diagnosis of severe hypertriglyceridemia in the course of ketoacidosis should be based on careful interpretation of laboratory tests results. Moreover genetic tests of the patient and his/her immediate relatives blood samples should be performed.