Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice.Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents ...around the world in all ethnicities,even if the prevalence of obesity is not increasing any more.The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American,Hispanic,Asian/Pacific Islanders and American Indians.Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood.Therefore,a screening seems meaningful especially in high risk groups such as children and adolescents with obesity,relatives with type 2 diabetes mellitus,and clinical features of insulin resistance(hypertension,dyslipidemia,polycystic ovarian syndrome,or acanthosis nigricans).Treatment of choice is lifestyle intervention followed by pharmacological treatment(e.g.,metformin).New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type2 diabetes mellitus.However,recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type2 diabetes mellitus requires some remodeling of current healthcare practices.
Chemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic ...Syndrome (MetS) in obese children before and after weight reduction.
We determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children.
Obese children demonstrated significantly (p < 0.001) higher chemerin concentrations compared to normal-weight children (96.2 ± 23.0 versus 63.1 ± 12.4 ng/ml). The chemerin concentrations were not related to age or gender. Prepubertal children had higher (p = 0.024) chemerin concentrations than pubertal children (71.0 ± 13.4 versus 58.0 ± 8.9 ng/ml). Weight loss was associated with a decrease of chemerin (-14.0 ± 22.0 ng/ml; p < 0.001) and an improvement of all parameters of the MetS. Chemerin was significantly related to BMI-SDS, WC, and bioLep in cross-sectional and longitudinal analyses. Chemerin and its changes were significantly related to insulin, HDL-cholesterol, triglycerides and their changes in multiple linear regression analyses adjusted to age, gender, pubertal stage, leptin and BMI.
Since chemerin was related to parameters of central fat mass and MetS both in cross-sectional and longitudinal analyses these findings suggest an impact of chemerin on factors of the MetS in obese children.
Zusammenfassung
Die Diagnose eines Syndroms polyzystischer Ovarien („polycystic ovary syndrome“ PCOS) im Jugendalter kann nur nach Ausschluss von Differenzialdiagnosen (beispielsweise ...hyperandrogenisierende Erkrankung wie Nebennierentumor oder Late-onset-Form eines adrenogenitalen Syndroms) bei Kombination von klinischer oder laborchemischer Hyperandrogenämie und Zyklusstörungen wie Oligomenorrhö frühestens 2 Jahre nach der Menarche gestellt werden. Das PCOS beruht auf einer Insulinresistenz, sodass weitere mit Insulinresistenz assoziierte Erkrankungen wie Diabetes mellitus Typ 2, metabolisches Syndrom und Fettleber gehäuft beim PCOS im Jugendalter auftreten. Die Therapie der Wahl besteht in einer Steigerung der körperlichen Aktivität und in einer Gewichtsreduktion bei adipösen Mädchen, was sich im Alltag häufig nicht realisieren lässt. Abhängig vom Leitsymptom und den begleitenden Risikofaktoren sollte dann eine Metformin- oder eine lokale Lasertherapie eingesetzt werden, während (antiandrogene) Kombinationspräparate aus Östrogenen und Gestagenen nicht als Medikamente der ersten Wahl empfohlen werden.
Context:
Knowing the changes of cardiovascular risk factors (CRFs) in relation to weight loss would be helpful to advise overweight children and their parents and to decide whether drugs should be ...prescribed in addition to lifestyle intervention.
Objective:
The objective of the study was to determine the body mass index (BMI)-SD score (SDS) reduction to improve CRFs in overweight children.
Design:
This was a prospective observation study.
Setting:
The study was conducted at a specialized outpatient obesity clinic.
Patients:
A total of 1388 overweight children (mean BMI 27.9 ± 0.1 kg/m2, mean age 11.4 ± 0.1 y, 43.8% male, 45.5% prepubertal) participated in the study.
Intervention:
The study included a 1-year lifestyle intervention.
Main Outcome Measures:
We studied changes of blood pressure (BP), fasting high-density lipoprotein- and low-density lipoprotein-cholesterol, triglycerides, glucose, and homeostasis model assessment (HOMA) of insulin resistance index. Change of weight status was determined by δBMI-SDS based on the recommended percentiles of the International Task Force of Obesity.
Results:
BMI-SDS change was associated with a significant improvement of all CRFs except fasting glucose and low-density lipoprotein-cholesterol after adjusting for multiple confounders such as baseline CRFs, age, gender, BMI, pubertal stage, and its changes. BMI-SDS reduction of 0.25–0.5 was related to a decrease of systolic blood pressure (BP) (−3.2 ± 1.4 mm Hg), diastolic BP (−2.2 ± 1.1 mm Hg), triglycerides (−6.9 ± 5.8 mg/dL), HOMA (−0.5 ± 0.3), and triglyceride/high-density lipoprotein)-cholesterol (−0.3 ± 0.2), whereas high-density lipoprotein (HDL)-cholesterol increased (+1.3 ± 1.2 mg/dL). A reduction of greater than 0.5 BMI-SDS led to more pronounced improvement (systolic BP −6.0± 1.3 mm Hg, diastolic BP −5.1 ± 1.3 mm Hg, triglycerides −16.4 ± 7.1 mg/dL, HDL-cholesterol +1.6 ± 1.5 mg/dL, HOMA −0.9 ± 0.3). Per 0.1 BMI-SDS reduction in systolic BP (−1.0 mm Hg), diastolic BP (−0.8 mm Hg), triglycerides (−2.3 mg/dL), HOMA (−0.2), and triglyceride/HDL-cholesterol (−0.5) decreased significantly, whereas HDL-cholesterol (0.2 mg/dL) increased significantly in linear regression analyses and accounted for multiple confounders.
Conclusions:
A BMI-SDS reduction of 0.25 or greater significantly improved hypertension, hypertriglyceridemia, and low HDL-cholesterol, whereas a BMI-SDS greater than 0.5 doubled the effect.
A BMI-SDS reduction of 0.25 which is approximately a stable BMI over a 1y period improves the cardiovascular risk profile in obese children.
Context: There are very limited data available concerning the relationships between fetuin-A, weight status, nonalcoholic fatty liver disease (NAFLD), and features of the metabolic syndrome (MetS) in ...obese humans, and especially in children.
Objective: Our objective was to study the longitudinal relationships between fetuin-A, NAFLD, and MetS in obese children.
Design: This was a 1-yr longitudinal follow-up study.
Setting: This study was performed in primary care.
Patients: A total of 36 obese and 14 lean children was included in the study.
Intervention: An outpatient 1-yr intervention program based on exercise, behavior, and nutrition therapy was performed.
Main Outcome Measures: Changes of weight status (sd score-body mass index), waist circumference, fetuin-A, blood pressure, lipids, transaminases, insulin resistance index homeostasis model assessment (HOMA), and prevalence of NAFLD (defined by liver ultrasound) were calculated.
Results: The 12 obese children with NAFLD had significantly higher fetuin-A levels (0.35 ± 0.07 g/liter) than the 24 obese children without NAFLD (0.29 ± 0.06 g/liter) and the 14 normal weight children (0.29 ± 0.05 g/liter). Fetuin-A levels were independent of age, pubertal stage, and gender. Fetuin-A correlated significantly to systolic (r = 0.50) and diastolic blood pressure (r = 0.41), insulin resistance index HOMA (r = 0.28), and high-density lipoprotein-cholesterol (r = −0.31). Changes of fetuin-A correlated significantly to changes of insulin resistance index HOMA (r = 0.34), systolic (r = 0.31) and diastolic blood pressure (r = 0.37), and waist circumferences (r = 0.36). Substantial weight loss in 21 children led to a significant decrease of fetuin-A and the prevalence of NAFLD in contrast to the 15 children without substantial weight loss.
Conclusions: Fetuin-A levels were higher in children with NAFLD, and were related to insulin resistance and to features of the MetS in both cross-sectional and longitudinal analyses. Therefore, fetuin-A might be a new promising link between obesity and its comorbidities.
Context:
The concept of metabolic healthy obese (MHO) status has been proposed also for children. However, it is unclear whether this is a stable status in childhood.
Objective:
The aim was to ...analyze the changes of MHO status over time.
Design and Setting:
This is 1-year longitudinal analysis of our obesity cohort.
Participants:
All obese children of our outpatient obesity clinic with 1-year follow-up were included.
Interventions:
Standard care intervention was used.
Main outcome measures:
We examined body mass index (BMI), waist circumference, pubertal stage, blood pressure, fasting lipids, glucose, and insulin resistance index homeostasis model assessment (HOMA). MHO status was defined by absence of cardiovascular risk factors.
Results:
A total of 2017 obese children (mean age, 11.6 ± 2.8 y; 45% male; BMI, 28.5 ± 5.3 kg/m2; BMI-z score, 2.4 ±0.5) were enrolled onto the study, and 49.3% of the children were MHO at baseline. After 1 year, the majority of the MHO remained MHO (68.0%). MHO children were significantly younger, more frequently prepubertal, and less overweight compared with metabolic unhealthy obese (MUO) children (all P < .05). In the longitudinal analyses, entering into puberty (OR, 1.9; 95% confidence interval, 1.3–2.8; P = .004) doubled the risk for switching from MHO to MUO, whereas changing from mid to late puberty nearly tripled the likelihood for switching from MUO to MHO (OR 3.1 2.1–4.5, P < .001) in multiple logistic regression analyses adjusted for age, sex, and changes of body mass index standard deviation score (BMI-SDS).
Conclusions:
MHO is a stable status in childhood obesity as long as pubertal status remains stable. Due to the strong association between puberty and MUO status, the concept of MHO is questionable, at least in pubertal children.
Context:
Irisin is a recently identified myokine affecting metabolic and glucose homeostasis. However, the role of irisin in obesity and its metabolic consequences are controversial, and data in ...children are scarce.
Objective:
To study the relationships between irisin, insulin resistance, and puberty before and after weight loss in obese children with and without impaired glucose tolerance.
Design:
One-year follow-up study in obese children participating in a lifestyle intervention.
Setting:
Primary care.
Patients:
Forty obese children and 20 normal-weight children of similar age, gender, and pubertal stage.
Intervention:
A 1-year outpatient intervention program based on exercise, behavior, and nutrition therapy.
Main Outcomes Measures:
Fasting serum irisin, weight status (body mass index BMI SD score), and the following parameters of the metabolic syndrome: insulin resistance index (homeostasis model of assessment), blood pressure, and lipids.
Results:
The irisin levels were the highest in obese children with impaired glucose tolerance, followed by obese children with normal glucose tolerance, and levels were lowest in normal-weight children (P < .001). In a multiple linear regression analysis, baseline irisin was significantly associated with pubertal stage, high-density lipoprotein-cholesterol, and homeostasis model of assessment, but not to age, gender, BMI, or any other parameter of the metabolic syndrome. The irisin concentrations were significantly (P = .010) lower in the prepubertal compared to the pubertal children. In longitudinal analyses, changes of irisin were significantly associated with entry into puberty, change of fasting glucose, and 2-hour glucose in an oral glucose tolerance test, but not with change of BMI or any other parameter.
Conclusions:
Irisin levels are related to pubertal stage and insulin resistance but not to weight status in childhood.
Obesity in adolescence will probably have major implications not only for the affected adolescents but also for society. Those who have obesity during adolescence usually have obesity into adulthood, ...which causes many medical and psychological issues that can result in premature death. Furthermore, obesity in adolescents is associated with a range of social problems, including difficulties securing an apprenticeship or a job or finding a partner. Adolescents with obesity are also at increased risk of having children with obesity later in life. All these consequences lead to high costs for the health-care system. Although efficient treatment options are available that have been proven in randomized controlled trials, such as lifestyle interventions for adolescents with obesity and bariatric surgery for adolescents with severe obesity, these interventions frequently fail in clinical practice as treatment adherence is low in adolescents and most adolescents with obesity do not seek medical care. Therefore, improving treatment adherence and identifying treatment barriers are necessary.
Context:
Fibroblast growth factor 21 (FGF-21), a potent activator of glucose uptake, has been proposed to be related to insulin resistance, metabolic syndrome (MetS), nonalcoholic fatty liver disease ...(NAFLD), and weight status.
Objective:
Our objective was to study the relationships between FGF-21, parameters of MetS, and NAFLD before and after weight loss in obese children.
Design and Setting:
This was a cross-sectional comparison between obese and normal-weight children and longitudinal 1-yr follow-up study in obese children participating in a lifestyle intervention in a primary care setting.
Patients:
Patients included 60 obese and 40 lean children of same age, gender, and pubertal stage.
Intervention:
The outpatient 1-yr intervention program was based on exercise, behavior, and nutrition therapy.
Main Outcomes Measures:
We evaluated fasting serum FGF-21, weight status body mass index (BMI) expressed as sd score (SDS), body fat, insulin resistance index (homeostasis model assessment), leptin, transaminases, free fatty acids (FFA), waist circumference, blood pressure, and lipids.
Results:
Compared with the normal-weight children, obese children demonstrated significantly (P < 0.001) increased FGF-21, leptin, and homeostasis model assessment levels. FGF-21 was significantly (P < 0.05) correlated to BMI, SDS-BMI, FFA, and leptin both in cross-sectional and longitudinal analyses but not to any additional analyzed parameter. Children with and without MetS or NAFLD did not differ significantly with respect to their FGF-21 concentrations. A decrease of SDS-BMI was associated with a significant (P = 0.038) decrease of FGF-21 levels (mean −34%).
Conclusions:
FGF-21 concentrations are reversibly increased in obese children and are related to leptin and FFA. However, our data do not support a significant relationship between FGF-21, insulin resistance, and features of MetS or NAFLD in children.
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