Martin Borkenstein

COXSACKIE B, MUMPS, RUBELLA, AND CYTOMEGALOVIRUS SPECIFIC IgM RESPONSES IN PATIENTS WITH JUVENILE-ONSET INSULIN-DEPENDENT DIABETES MELLITUS IN BRITAIN, AUSTRIA, AND AUSTRALIA

Patients from England, Austria, and Australia with recently diagnosed juvenile-onset insulin-dependent diabetes (type 1) mellitus (IDDM) and matched controls were tested for specific IgM responses to Coxsackie B1-5 viruses. 37 of 122 (30%) patients aged less than 15, but only 15 of 204 (6%) controls, were positive (p less than 0.005). Differences in Coxsackie B virus specific IgM responses between patients and controls were statistically significant for patients in England and Austria (p less than 0.005). Coxsackie B virus specific IgM responses were detected in only 3 of 31 patients aged greater than 16. Virus-specific IgM responses were directed against a single serotype, usually Coxsackie B4 or 5, in 23 of 37 (62.5%) children aged less than 15; 10 of 13 (77%) of children aged less than 7 had monotypic responses. Among families of Austrian patients with IDDM, 8 of 79 (10%) siblings had Coxsackie B virus specific IgM responses, 1 of whom subsequently had IDDM, but none of the 80 parents was positive. In contrast, there was no evidence of recent infection by mumps, rubella, or cytomegalovirus (CMV), since mumps-virus specific IgM was present in only 2 of 100 children with IDDM and 5 of 139 controls; no rubella or CMV specific IgM responses were detected in 60 sera from patients with IDDM.

Changes in serum interleukin-6 concentrations in obese children and adolescents during a weight reduction program.

OBJECTIVE: To investigate the effect of short term energy restriction combined with physical activity on serum concentrations of Interleukin-6 (IL-6) in obese children and adolescents.DESIGN: Longitudinal intervention study of 3.8–5 MJ daily with exercise.SUBJECTS: Forty-nine white obese children and adolescents (31 girls, age 11.9±1.8 y; 18 boys, age 11.6±1.7 y).MEASUREMENTS: Indexes of obesity, IL-6, leptin, estradiol, systolic and diastolic blood pressure, heart rate at baseline and after 3 weeks.RESULTS: All determined parameters decreased significiantly during the 3 week program (IL-6: 3.9±4.7 vs 2.0±2.2 pg/ml; P<0.05). Body mass index (BMI) fat mass, percentage fat mass (indexes of obesity), and leptin were not related to IL-6 before the program. In contrast, IL-6 concentrations correlated significantly with indexes of obesity and leptin after weight loss. IL-6 concentrations did not correlate with estradiol, systolic and diastolic blood pressure, and heart rate. Changes in IL-6 concentrations correlated significantly with changes in BMI (r=0.25, P<0.05).CONCLUSION: An improved body composition induced by restriction of energy intake and increase in physical activity is associated with more favorable serum concentrations of IL-6 in obese children and adolescents.

Effect of an individualised training programme during weight reduction on body composition: a randomised trial

OBJECTIVE To study the effect of a standardised training programme focusing on maintenance of fat free mass during weight reduction by energy reduction in obese children. DESIGN Randomised trial of physical training programme and dietary advice (group A) versus dietary advice alone (group B). SUBJECTS Thirty obese children and adolescents (14 group A, 16 group B) participated in the 12 week long programme; 20 children (10 group A, 10 group B) were also reassessed after one year. MEASUREMENTS Fat free mass was estimated from the resistance index, obtained by bioelectrical impedance analysis at baseline, after four, eight, and 12 weeks in all subjects, and after one year in 20 subjects. RESULTS The mean (SD) change in fat free mass was significantly different between the two groups after 12 weeks (group A, 2.68 (3.74) kg; group B, 0.43 (1.65) kg). The change in body weight after one year was inversely correlated with the change in fat free mass after 12 weeks (r = −0.44), as assessed in the 20 subjects. CONCLUSIONS A standardised training programme as used in this study can prevent reduction in fat free mass during weight loss in obese children. Reduction in fat free mass during weight reduction might be a risk factor for regain of weight.

COXSACKIE-B-VIRUS-SPECIFIC IgM RESPONSES, COMPLEMENT-FIXING ISLET-CELL ANTIBODIES, HLA DR ANTIGENS, AND C-PEPTIDE SECRETION IN INSULIN-DEPENDENT DIABETES MELLITUS

To evaluate the role of Coxsackie B viruses in the pathogenesis of insulin-dependent (juvenile-onset, type 1) diabetes mellitus (IDDM), attempts were made to correlate virus-specific IgM responses with HLA genes, autoimmune responses, and C-peptide secretion. HLA DR3, DR4, or both were present in 73 of 90 (81%) diabetic patients; 22 of 23 (96%) with Coxsackie-B-virus-specific IgM had at least one of these HLA types, compared with 51 of 67 (76%) without virus-specific IgM. There was no correlation between HLA A, B, or C types or immunoglobulin allotypes and virus-specific IgM responses. 16 of 22 (64%) patients with Coxsackie-B-virus-specific IgM compared with 26 of 72 (36%) without had complement-fixing islet-cell antibodies; no relation was found between virus-specific IgM and antibodies against thyroid or adrenal tissue or parietal cells. C-peptide secretion was significantly lower in patients with Coxsackie-B-virus-specific IgM.

The influence of weight loss on fibrinolytic and metabolic parameters in obese children and adolescents.

We studied i) whether short-term weight loss alters plasminogen activator inhibitor-1 antigen (PAI-1-Ag) and tissue-type plasminogen activator antigen (tPA-Ag) in obese children, and ii) whether changes in body composition and/or abdominal adiposity are responsible for changes in PAI-1 and tPA-Ag. 20 obese boys (mean age 11.9 yr) and 40 obese girls (mean age 12 yr) were studied before and after three weeks of low-caloric diet and physical activity. Body composition was assessed by means of bioelectrical impedance, and the waist-to-hip ratio (WHR) was measured. Blood samples were determined for insulin, glucose, triglycerides, PAI-1-Ag, tPA-Ag, and the fasting insulin resistance index (FIRI) was calculated. Boys had a greater WHR, higher levels of glucose, and a slightly greater FIRI than girls. Estimates of adiposity, insulin, and triglycerides were correlated with PAI-1 and tPA-Ag. WHR was significantly correlated with fibrinolytic parameters only in girls. Insulin and tPA-Ag contributed to PAI-1 (adj. R2 = 0.36, p <0.0001), whereas percentage fat mass and triglycerides contributed to tPA-Ag (adj. R2 = 0.469, p <0.0001). The weight loss program significantly reduced adiposity, abdominal adiposity, and lowered fibrinolytic and metabolic parameters. Initial levels of PAI-1 and changes in body mass contributed to the fall in PAI-1 (adj. R2 = 0.18, p = 0.0016) and initial levels of tPA-Ag contributed significantly to changes in tPA-Ag (adj. R2 = 0.57, p <0.0001). The results suggest that changes in fibrinolytic parameters are associated with the loss in body mass but can occur independently of a concomitant reduction in fatness. Although initial PAI-1 and tPA-Ag predict the changes of these fibrinolytic parameters, the results do not exclude the possibility that the improvement in metabolic state and changes in unmeasured parameters related to physical activity and low-caloric diet could have influenced our findings.

Effects of weight loss on leptin, sex hormones, and measures of adiposity in obese children.

Adipose tissue influences steroid conversion by paracrine and autocrine mechanisms. Leptin is secreted by adipocytes and influenced by sex hormones and adiposity. Short-term weight loss in the treatment of childhood obesity reduces leptin and adipose tissue. We therefore asked, Do alterations in sex hormones occur owing to weight loss? and can these alterations be explained by changes in fat mass or sc fat and are alterations in sex hormones directly related to the fall in leptin? Twenty obese boys and 40 obese girls were studied before and after 3 wk of low-calorie diet and physical activity. The weight loss program significantly lowered fat mass, abdominal fat distribution, sc fat (all p<0.0001), leptin, insulin, and estradiol (all p<0.0001) but not testosterone. Changes in leptin were related to changes in body mass and to changes in fat mass in boys. In girls, changes in leptin were related to changes in sc fatness and also to changes in insulin. In boys, the reduction in sc fat was positively correlated to changes in testosterone (r=0.54; p<0.01) and inversely related to the fall in estradiol (r=−0.41; p<0.05). In girls, changes in testosterone (r=0.33; p<0.05) and in estradiol (r=0.40; p<0.001) were related to changes in insulin. Stepwise regression showed that initial leptin was the best determinant for the fall in leptin (adjusted R2=0.87; p<0.0001). The results show that alterations in sex hormones are related to changes in certain fat depots in boys where as in girls changes in insulin might participate in changes in sex hormones. A greater fall in leptin owing to short-term weight loss is not associated with greater alterations in sex hormones and initial leptin is the best determinant to explain the variability in changes in leptin. The possibility of sex differences in changes in sex hormones secondary to the reduction in fatness warrants further study.

Effects of short-term energy restriction and physical training on haemostatic risk factors for coronary heart disease in obese children and adolescents

OBJECTIVE: To study the changes of haemostatic risk factors for coronary heart disease during a weight reduction programme in obese children and adolescents.DESIGN: A short-term longitudinal study.SUBJECTS: Thirty-seven obese white girls (age, 12±1.8 y; body mass index (BMI), 26.9±5.25) and 19 obese white boys (age, 11.9±1.7 y; BMI, 26.2±5.2).MEASUREMENTS: Fibrinogen, factor VII coagulant activity, von Willebrand factor antigen, and soluble P-selectin were determined before and after a 3 week programme including energy restriction and physical activities.RESULTS: All determined haemostatic risk factors decreased significantly during the programme. Changes in risk factors were correlated to changes in body composition. Children and adolescents with the highest initial concentrations showed the greatest decreases.CONCLUSION: Energy restriction combined with physical activity improves the haemostatic risk profile in obese children and adolescents.International Journal of Obesity (2001) 25, 529–532

Determinants of haemostatic risk factors for coronary heart disease in obese children and adolescents.

OBJECTIVE: To investigate the contribution of serum lipids, parameters of glucose metabolism, body composition and cardiovascular fitness to the variance of several haemostatic risk factors for coronary heart disease (CHD) in obese children and adolescents.SUBJECTS AND MEASUREMENTS: Forty-two healthy, obese children and adolescents (20 male, 22 female, age 12.6±3.2 y; body mass index (BMI), 30.4±5.3 kg/m2), were screened for haemostatic and metabolic risk factors for CHD. Thirty-five of the participants (18 male, age 13.5±2.9 y; BMI, 29.9±4.5 kg/m2; 17 female, age 12.8±2.1 y, BMI, 31.1±5.3 kg/m2) were assessed for cardiovascular fitness by means of incremental cycle ergometer exercise.RESULTS: After adjustment for age, fat mass correlated significantly with plasminogen activator inhibitor-1 antigen (PAI-1-Ag) in boys and girls and factor VIIc only in girls. Children with lower power output (≤ 2.77 W/kg) showed significantly higher values for factor VIIc, fibrinogen and tissue-type plasminogen activator antigen (tPA-Ag). Neither body composition nor cardiovascular fitness contributed independently to the variance of the determined haemostatic risk factors, except PAI-1-Ag, which has been shown to be determined by fat mass. In multiple linear regression analysis, triglycerides and PAI-1-Ag explained significant independent proportions of the variance of tPA-Ag. Factor VIIc was explained by C-peptide, insulin and fibrinogen. Von Willebrand factor antigen (vWF-Ag) was significantly related to glucose and insulin.CONCLUSION: The results suggest that in obese children and adolescents the haemostatic risk factors factor VIIc, vWF-Ag and tPA-Ag are mainly determinated by plasma insulin and triglyceride concentrations, but are primarily independent of body composition and cardiovascular fitness.

Elevated Factor VIII Activity and Factor Vlll-related Antigen in Diabetic Children Without Vascular Disease

Factor VIII coagulant activity (VIM C) and factor Vlllrelated antigen (VIII R:Ag) were studied in 86 insulindependent diabetic children. All children were without signs of vascular disease based on a negative funduscopy, negative fluorescein angiography, normal serum creatinine levels, and absence of proteinuria. Age ranged from 4 to 17 yr; duration of clinical diabetes ranged from 1 to 12 yr. The children were grouped according to their urinary sugar excretion, the HbA1 levels, and the duration of clinical diabetes. The group with high urinary sugar excretion and the group withhigh HbA1 levels had a significantly higher VIII C than the group with low urinary sugar excretion and the group with low HbA1 levels. VIII C levels did not differ significantly in the groups with a different duration of clinical diabetes, but VIII R:Ag was significantly higher in the group with the longest duration of diabetes as compared with the group with the shortest duration. VIII R:Ag levels did not differ significantly in the groups with different degrees of urinary sugar excretion or different HbA1 levels. The results show that in children without vascular disease, and even in children with a short duration of diabetes, alterations of the factor VIII complex can be demonstrated.

The relationship between different subcutaneous adipose tissue layers, fat mass and leptin in obese children and adolescents.

We studied the relationships of subcutaneous adipose tissue layers (SAT-layers), body fat mass (FM) and waist-to-hip ratio (WHR) with leptin in obese children and adolescents. Twenty-nine obese children and adolescents (12 boys: age: 11.3 +/- 3.7 yr; body mass index [BMI]: 28.5 +/- 4) and 17 girls (age: 12.2 +/- 2.2 yr; BMI: 29.8 +/- 4.7) (mean +/- SD) were studied. FM was estimated by bioelectrical impedance. SAT-layers were determined at 15 different body sites from 1-neck to 15-calf by the Lipometer optical device. Leptin and insulin were determined by RIA. Maturity was associated with a greater thickness of certain SAT-layers from the upper body and with a lower thickness of SAT-layers from the abdominal region and lower extremities. Significant correlations were found for all estimates of adiposity and leptin (all p<0.001). Waist and hip circumferences were not correlated to leptin after adjustment for FM. SAT-layers from the upper body were significantly and positively correlated to leptin. Multiple regression analysis revealed FM as a main contributor to the variation in leptin (R2=0.53, p<0.0001). FM together with SAT-layers 5-front chest and 13-rear thigh explained 72% of the variation in leptin (p<0.0001). In a body fat distribution model, hip circumference together with SAT-layers 4-upper back and 2-triceps explained 75% of the variation in leptin (p< 0.0001). The results suggest that SAT-layers and their topography are main determinants for leptin in obese children and adolescents. Maturity in obese children is associated with higher values of upper body SAT-layers and lower values of abdominal and lower extremities SAT-layers. Whether leptin is under the control of certain subcutaneous adipose tissue depots from the upper body remains to be elucidated by longitudinal studies.