Longitudinal analyses of polysomnographic variables, serum androgens, and parameters of glucose metabolism in obese adolescents with polycystic ovarian syndrome.

PURPOSE: The prevalence of obstructive sleep apnea syndrome (OSAS) is clearly increased in adults with polycystic ovarian syndrome (PCOS), whereas OSAS does not seem to be frequent in adolescents with PCOS, pointing towards the fact that some patients with PCOS develop OSAS in the further course of the disease. We therefore aimed to analyze the changes of polysomnographic variables in obese adolescents with PCOS in a longitudinal analysis. METHODS: Fifteen adolescents with PCOS (age 15.3 years ± 1.2, BMI 32.9 kg/m(2) ± 6.4, SDS-BMI 2.5 ± 0.8) underwent overnight 12-channel polysomnography at baseline and after a mean duration of 28 ± 6 months (age 17.8 years ± 1.1, BMI 32.7 kg/m(2) ± 7.0, SDS-BMI 2.1 ± 0.9). After performing the initial polysomnography, we treated hyperandrogenemia and insulin resistance in the study group. We determined parameters of body weight/body composition, parameters of glucose metabolism, and serum androgens in all patients at baseline and follow-up. At follow-up, we compared the polysomnographic variables of the study group to those of healthy female adults. RESULTS: The polysomnographic variables, the parameters of body weight/body composition, and the parameters of glucose metabolism in the study group did not change significantly during the observation period. The serum levels of total testosterone and sex hormone binding globulin increased significantly, whereas free androgen index decreased significantly. At follow-up, the polysomnographic variables of the study group did not differ from those of healthy female adults. CONCLUSIONS: OSAS does not seem to develop in adolescents with PCOS being treated for hyperandrogenism and insulin resistance. The pathogenesis of OSAS in PCOS needs to be examined in larger controlled studies.

Leptin concentrations are a predictor of overweight reduction in a lifestyle intervention.

OBJECTIVE: Leptin resistance is discussed to be involved in the genesis of obesity. Therefore, we hypothesized that leptin levels were negatively associated with degree of weight loss in obese children participating in a lifestyle intervention. METHODS: We studied 248 obese children aged 8-14 years attending the "Obeldicks" lifestyle intervention (mean age 10.6+/-0.2 years, 53% female, 48% pubertal, mean body mass index (BMI) 27.8+/-0.3 kg/m2, and mean standard deviation score [SDS]-BMI 2.43+/-0.03). Baseline leptin concentrations were correlated with change of weight status, waist circumference, and percentage body fat, as calculated from skinfold measurements in the one-year intervention by Pearson correlation and multiple linear regression analyses. Furthermore, the relationship between leptin and cardiovascular risk factors (insulin, insulin resistance index HOMA, blood pressure, lipids, and glucose) were analyzed. RESULTS: A total of 212 children (85%) reduced their overweight, 9 children (4%) dropped out, and 27 children (11%) did not reduce their overweight in the lifestyle intervention "Obeldicks". The mean reduction of SDS-BMI was 0.34+/-0.02. The reduction of SDS-BMI (r=- 0.27), waist circumference (r=- 0.64), and percentage body fat (r=- 0.26) were significantly negatively associated with baseline leptin levels both in univariate analyses and in multiple regression analyses, adjusted to baseline age, BMI, gender and pubertal stage. Baseline leptin concentrations were significantly associated with BMI, pubertal stage, gender, waist circumference, and insulin, but not to any other cardiovascular risk factors in multiple regression analyses. CONCLUSIONS: The finding that baseline leptin concentrations were significantly negatively correlated with the degree of weight loss in a lifestyle intervention supports the hypothesis of leptin resistance in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

Plasma and thrombocyte levels of coenzyme Q10 in children with Smith-Lemli-Opitz syndrome (SLOS) and the influence of HMG-CoA reductase inhibitors.

INTRODUCTION: SLOS is caused by a defect of cholesterol synthesis. HMG-CoA reductase inhibitors have been shown to improve biochemical parameters in this condition, but they have also been associated with CoQ10 deficiency in patients with hypercholesterolemia. The aim of this study was to analyse plasma and intracellular CoQ10 levels in SLOS patients and to determine the influence of HMG-CoA reductase inhibitors. METHODS: Plasma concentrations of CoQ10 and vitamin E were measured in 14 patients, intracellular CoQ10 levels were determined in platelets of 10 patients with SLOS and compared to controls. RESULTS: Plasma CoQ10 and vitamin E levels were significantly lower in SLOS patients. This difference equalised after adjustment to cholesterol concentrations. Treatment with simvastatin did not influence CoQ10 levels and redox status. Platelet CoQ10 concentrations were similar between patients and controls but there were striking differences in the CoQ10 redox status with a decrease of oxidised CoQ10. CONCLUSION: Decreased concentrations of plasma CoQ10 and vitamin E in SLOS patients are due to a diminished carrier capacity. The higher percentage of reduced CoQ10 in platelets points to an up-regulation of mitochondrial protection mechanisms. Further studies are needed to evaluate a possible benefit of CoQ10 supplementation in SLOS patients.

Enrichment of coenzyme Q10 in plasma and blood cells: defense against oxidative damage.

Coenzyme Q10 (CoQ10) concentration in blood cells was analyzed by HPLC and compared to plasma concentration before, during, and after CoQ10 (3 mg/kg/day) supplementation to human probands. Lymphocyte DNA 8-hydroxydeoxy-guanosine (8-OHdG), a marker of oxidative stress, was analyzed by Comet assay. Subjects supplemented with CoQ10 showed a distinct response in plasma concentrations after 14 and 28 days. Plasma levels returned to baseline values 12 weeks after treatment stopped. The plasma concentration increase did not affect erythrocyte levels. However, after CoQ10 supplementation, the platelet level increased; after supplementation stopped, the platelet level showed a delayed decrease. A positive correlation was shown between the plasma CoQ10 level and platelet and white blood cell CoQ10 levels. During CoQ10 supplementation, delayed formation of 8-OHdG in lymphocyte DNA was observed; this effect was long-lasting and could be observed even 12 weeks after supplementation stopped. Intracellular enrichment may support anti-oxidative defense mechanisms.

Coenzyme Q10 in maternal plasma and milk throughout early lactation.

In contrast to other lipophilic antioxidants Coenzyme Q10 originates from food intake as well as from endogenous synthesis. The CoQ10 concentration and lipid content of maternal milk and maternal plasma was investigated during early lactation. Breast milk was obtained from 23 women: A: colostrums (24-48 hours postpartum), B: transitional milk (day 7 pp), C: mature milk (day 14 pp). At the same time capillary blood specimens were collected. Milk and plasma were stored at -84 degrees C until CoQ10 was analysed after hexane extraction by HPLC. The lipid content was determined by PAP-analysis of cholesterol. The plasma content of CoQ10 was the highest soon after delivery (A: 1.29, B:1.20, C:1.07 pmol/microl; Wilcoxon p < 0.05 A vs. C and B vs. C). This tendency was still evident after lipid-adjustment (A:209, B:180, C:175 micromol CoQ10/mol cholesterol; Wilcoxon p < 0.01 A vs. B and C). The level of CoQ10 in milk showed a gradual decline during early lactation (A:0.80, B:0.57, C:0.44 pmol/microl; Wilcoxon p < 0.02 A vs. B and C). After lipid-adjustment this tendency became even more evident (A: 137, B:86, C:67 micromol CoQ10/mol cholesterol; Wilcoxon p < 0.002 A vs. B and C, p < 0.05 B vs. C). The content of CoQ10 in plasma and milk showed a correlation with early milk (Spearman p < 0.005) but not with mature milk. Although lipid content is low the colostrums is a rich source for the lipophilic antioxidant CoQ10.

Simultaneous analysis of coenzyme Q10 in plasma, erythrocytes and platelets: comparison of the antioxidant level in blood cells and their environment in healthy children and after oral supplementation in adults.

BACKGROUND: Coenzyme Q10 (CoQ10) originates from food intake as well as from endogenous synthesis. While plasma concentrations may be influenced by dietary uptake, little is known whether concentrations in plasma reflect or influence intracellular concentrations. METHODS: For clinical routine investigation of intracellular CoQ10 contents, blood erythrocytes and platelets were isolated by Ficoll separating solution and CoQ10 analysed using HPLC. The intracellular concentrations were compared to environmental plasma concentrations of 50 clinically healthy infants and additionally after exogenous pharmaceutical supplementation of CoQ10 (3 mg/kg/day) to 12 adult probands for 14 days. RESULTS: In healthy children, no correlation between plasma concentration and content in blood cells was found. A negative correlation exists between the year of life of the infants and CoQ10 concentrations in plasma correlated to cholesterol content. Probands supplemented with CoQ10 showed a distinct response in plasma concentrations after 14 days. While excessive environmental supplementation was without influence on erythrocyte concentrations, a positive correlation exists between plasma content and concentrations in platelets as mitochondria containing cell lines. CONCLUSIONS: Under physiologically normal conditions, blood cells or organs may regulate their CoQ10 content independently from environmental supply. Effects may be expected in situations of deficiency or excessive supply. Erythrocyte concentration of CoQ10 keeps independent from environmental supply. Thus incorporation into outer cell membranes may be limited. However, an excessive environmental supply may influence inner compartments like mitochondrial membranes.

Coenzyme Q10 in plasma and erythrocytes: comparison of antioxidant levels in healthy probands after oral supplementation and in patients suffering from sickle cell anemia.

BACKGROUND: The membrane-associated antioxidant coenzyme Q10 (CoQ10) or ubiquinone-10 is frequently measured in serum or plasma. However, little is known about the total contents or redox status of CoQ10 in blood cells. METHODS: We have developed a method for determination of CoQ10 in erythrocytes. Total CoQ10 in erythrocytes was compared to the amounts of ubiquinone-10 and ubihydroquinone-10 in plasma using high-pressure liquid chromatography (HPLC) with electrochemical detection and internal standardisation (ubiquinone-9, ubihydroquinone-9). RESULTS: Investigations in 10 healthy probands showed that oral intake of CoQ10 (3 mg/kg/day) led to a short-term (after 5 h, 1.57+/-0.55 pmol/microl plasma) and long-term (after 14 days, 4.00+/-1.88 pmol/microl plasma, p<0.05 vs. -1 h, 1.11+/-0.24 pmol/microl plasma) increase in plasma concentrations while decreasing the redox status of CoQ10 (after 14 days, 5.37+/-1.31% in plasma, p<0.05 vs. -1 h, 6.74+/-0.86% in plasma). However, in these healthy probands, CoQ10 content in red blood cells remained unchanged despite excessive supplementation. In addition, plasma and erythrocyte concentrations of CoQ10 were measured in five patients suffering from sickle cell anemia, a genetic anemia characterised by an overall accelerated production of reactive oxygen species. While these patients showed normal or decreased plasma levels of CoQ10 with a shifting of the redox state in favour of the oxidised part (10.8-27.2% in plasma), the erythrocyte concentrations of CoQ10 were dramatically elevated (280-1,093 pmol/10(9) ERY vs. 22.20+/-6.17 pmol/10(9) ERY). CONCLUSIONS: We conclude that normal red blood cells may regulate their CoQ10 content independently from environmental supplementation, but dramatic changes may be expected under pathological conditions.