Relationship between asymmetric dimethylarginine, homocysteine and insulin resistance in adolescents with metabolic syndrome

WSTĘP. W ostatnich latach rozważa się znaczenie asymetrycznej dimetyloargininy (ADMA) jako nowego czynnika ryzyka miażdżycy, dysfunkcji śródbłonka oraz insulinooporności. W metabolizmie ADMA istotną rolę może odgrywać homocysteina (Hcy, homocysteine). Zwiększone stężenie ADMA wpływa na zmniejszenie biodostępności tlenku azotu (NO) przez hamowanie syntazy NO - eNOS. Celem pracy była próba poszukiwania zależności między ADMA, Hcy oraz NO u młodzieży z zespołem metabolicznym (MS, metabolic syndrome) . MATERIAŁ I METODY. Do badań zakwalifikowano 21 pacjentów z rozpoznanym MS, w wieku średnim 14,8 roku. Schorzenie rozpoznawano na podstawie kryteriów według Światowej Organizacji Zdrowia (WHO, World Health Organization) i Adult Treatment Panel III (III ATP). Grupę kontrolną stanowiło 26 zdrowych nastolatków w średnim wieku 14,6 roku. Stężenie ADMA, Hcy oraz NO (za pomocą pochodnych NOx) oznaczono metodami immunoenzymatycznymi ELISA. Ocenę stężenia wysokoczułego białka C-reaktywnego (hs-CRP, high sensitivity C-reactive protein) dokonano za pomocą metody immunoturbidymetrycznej, z użyciem odczynnika Tina-quant CRP (Latex) HS, firmy Roche. WYNIKI. U dzieci z MS stwierdzono istotnie wyższe stężenie ADMA (0,69 v. 0,46 &#956;mol/l; p < 0,001), Hcy (12,1 v. 9,4 &#956;mol/l; p = 0,003) oraz hs-CRP (0,22 v. 0,11 mg/dl; p = 0,01) w porównaniu z grupą kontrolną. Stężenie NOx było podobne w obu grupach (46,2 v. 44,8 &#956;mol/l, ns). W analizie wykazano korelację ADMA z hs-CRP (r = 0,42; p = 0,003), Hcy (r = 0,48; p = 0,01). Wskaźnik masy ciała (BMI, body mass index) (r = 0,44; p = 0,02), ciśnieniem skurczowym, rozkurczowym oraz wskaźnikiem insulinooporności HOMA (r = 0,31; p = 0,04). Dla NOx nie wykazano żadnych istotnych zależności. WNIOSKI. 1. Zespołowi metabolicznemu stwierdzanemu u nastolatków towarzyszy zwiększone stężenie ADMA, Hcy i hsCRP. 2. Stwierdzone korelacje między stężeniami ADMA, Hcy i hsCRP oraz wskaźnikiem HOMA sugerują obecność wspólnego patomechanizmu zwiększonego stężenia tych substancji i insulinooporności.INTRODUCTION. The latest research studies consider asymmetric dimethylarginine (ADMA) as a new atherosclerosis risk factor and factor for endothelial dysfunction and insulin resistance. Homocysteine (Hcy) may play significant role in ADMA metabolism Elevated ADMA results in impaired bioavailibility of nitric oxide (NO) via inhibition of nitric oxide synthase (eNOS). The aim of the study was to search the possible relationship between ADMA, Hcy and NO in teenagers with metabolic syndrome (MS). MATERIAL AND METHODS. We recruited 21 patients with MS, aged 14,8 years. Metabolic syndrome was recognized based on the WHO and ATP III criteria. Control group consisted of 26 healthy adolescents aged 14,6 years. ADMA, Hcy and NO (as NOx) concentrations were measured with immunoenzymatic (ELISA) methods. hsCRP was assessed with use of immunoturbidymetric method. RESULTS. In adolescents with MS we showed significantly elevated ADMA (0.69 v. 0.46 &#956;mol/l; p < 0.001), Hcy (12.1 v. 9.4 &#956;mol/l; p = 0.003) and hs-CRP (0.22 v. 0.11 mg/dl; p = 0.01) compared with control group. NOx concentration was similar to the control group (46.2 v. 44.8 &#956;mol/l, ns). We found significant correlations between ADMA and hs-CRP (r = 0.42; p = 0.003), Hcy (r = 0.48; p = 0.01), BMI (r = 0.44; p = 0.02), systolic blood pressure, diastolic blood pressure and insulin resistance (HOMA) (r = 0.31; p = 0.04). NOx did not correlate significantly with any of the study parameters. CONCLUSIONS. 1. In teenagers with MS we showed elevated levels of ADMA, Hcy and hs-CRP. 2. Correlations between ADMA, Hcy, hs-CRP and HOMA suggest existence of common pathomechanism of increased concentrations of these substances with insulin resistance

Excessive BMI is associated with higher C-peptide level at recognition but also with its greater loss in two years clinical observation in children with new onset type 1 diabetes

IntroductionThe prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual β-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation.MethodsWe assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and β-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS &gt;1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients’ levels of selected inflammatory cytokines at baseline.ResultsSubjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS &gt;1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS &gt;1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS &lt;1 and BMI-SDS &gt;1 groups and were significantly higher within BMI-SDS &gt;1 group.DiscussionHigher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual β-cell function. The process seems to be mediated by inflammatory cytokines

Polymorphism of the FTO

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)

Empowerment in the Treatment of Diabetes and Obesity

As the available therapies for diabetes and obesity are not effective enough, diabetologists and educators search for new methods to collaborate with patients in order to support their health behaviors. The aim of this review is to discuss perspectives for the development of new empowerment-type therapies in the treatment of diabetes/obesity. Empowerment is a process whereby patients gain the necessary knowledge to influence their own behavior to improve the quality of their lives. It is carried out in five stages: (1) identify the problem, (2) explain the feelings and meanings, (3) build a plan, (4) act, and (5) experience and assess the execution. Although many years have passed since the advent and popularization of the concept of empowerment, the area remains controversial, mainly with regard to the methodology of therapy. Some previous studies have confirmed the positive effect of empowerment on body weight, metabolic control, and quality of life of patients with type 2 diabetes; however, few studies have been conducted in patients with type 1 diabetes. There is still a need to confirm the effectiveness of empowerment in accordance with Evidence Based Medicine by performing long-term observational studies in a large group of patients. In future, empowerment may become part of the standard of care for patients with diabetes and/or obesity

Not Only Metabolic Complications of Childhood Obesity

The increasing incidence of obesity in the pediatric population requires attention to its serious complications. It turns out that in addition to typical, well-known metabolic complications, obesity as a systemic disease carries the risk of equally serious, although less obvious, non-metabolic complications, such as cardiovascular diseases, polycystic ovary syndrome, chronic kidney disease, asthma, thyroid dysfunction, immunologic and dermatologic conditions, and mental health problems. They can affect almost all systems of the young body and also leave their mark in adulthood. In addition, obesity also contributes to the exacerbation of existing childhood diseases. As a result, children suffering from obesity may have a reduced quality of life, both physically and mentally, and their life expectancy may be shortened. It also turns out that, in the case of obese pregnant girls, the complications of obesity may also affect their unborn children. Therefore, it is extremely important to take all necessary actions to prevent the growing epidemic of obesity in the pediatric population, as well as to treat existing complications of obesity and detect them at an early stage. In summary, physicians treating a child with a systemic disease such as obesity must adopt a holistic approach to treatment

Contemporary methods of self-control and their use in children and teenagers with type 1 diabetes

Sukcesem współczesnej diabetologii jest wypracowanie kompleksowego leczenia substytucyjnego i objawowego, które jest efektywne i umożliwia normalne życie chorych na cukrzycę, pod warunkiem sumiennego przestrzegania przez pacjenta określonych reguł i obowiązków. Jest to szczególnie istotne dla pacjentów młodych, gdyż skuteczna terapia przekłada się nie tylko na ich aktualną dobrą kondycję fizyczną, ale także na prawidłowy rozwój psychofizyczny, emocjonalny i społeczny, nie naznaczony piętnem przewlekłych powikłań cukrzycowych. Jednym z takich obowiązków, a zarazem fundamentem całego procesu terapeutycznego cukrzycy jest samokontrola, czyli wszystkie działania wykonywane przez pacjenta w celu oceny wyrównania metabolicznego i ryzyka rozwoju lub też postępu powikłań, a także w celu kontroli i wpływania na własny stan zdrowia. Stanowi ona podstawę do wprowadzania zmian w leczeniu insuliną. Do elementów samokontroli należą: oznaczanie stężenia glukozy we krwi za pomocą glukometrów i/lub systemów ciągłego monitorowania glikemii, oznaczanie stężenia glukozy i ciał ketonowych w moczu, prowadzenie dzienniczka samokontroli, oznaczanie ciśnienia tętniczego, pielęgnacja stóp, a także systematyczne badania kontrolne, wysiłek fizyczny, dieta i edukacja. Wśród wymienionych elementów samokontroli najistotniejsze jest oznaczanie glikemii, gdyż na wynikach samokontroli stężenia cukru we krwi opiera się ocena wyrównania metabolicznego oraz codzienne prowadzenie modyfikacji w leczeniu, które wobec nieregularnego trybu życia dzieci i młodzieży staje się dużym wyzwaniem dla pacjentów, ich rodziców i lekarzy diabetologów. W niniejszej pracy zostały przedstawione pojęcia, metodologia, elementy i znaczenie samokontroli, rola i znaczenie wysiłku fizycznego oraz diety, jako elementów samokontroli. Omówiono również najnowsze urządzenia stosowane w samokontroli i analizie danych, a także znaczenie aspektów psychoemocjonalnych w samokontroli u młodych pacjentów z cukrzycą.The success of contemporary diabetology is the development of a comprehensive supportive care that is effective and allows for normal life with diabetes as long as the patient diligently complies with certain rules and responsibilities. This is especially important in case of young patients, as effective therapy does not only affect their current physical condition, but also the proper psychological, emotional and social development not marked by chronic diabetic complications. One of these duties, which is also the foundation of the entire therapeutic process, is self-control, namely all the actions undertaken by the patient in order to evaluate their metabolic status and risk of complications or progress, as well as to control and influence their own health. This forms the basis for making changes in an insulin therapy. The elements of self-control are: determination of blood glucose with the use of glucose meters and/or systems of continuous glucose monitoring, evaluation of glucose and ketones in the urine, keeping diabetes logbook, determination of blood pressure, foot care and regular follow-up examinations, exercise, diet and education. This article presents the concept, methodology, elements and importance of self-control, the role and importance of physical activity and diet as part of self-control. It also discusses the newest devices used in self-control and data analysis, and the importance of psychoemocional aspects in self-control among young patients with diabetes