BMI is an important driver of beta-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children.

OBJECTIVE: Body weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. DESIGN: Multicentre longitudinal study carried out at diagnosis and up to 1-year follow-up. METHODS: Data on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (5 years 10 years 18 years, n=410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c. RESULTS: In individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed >18 years, we found no association between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (beta 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m(2) higher baseline BMI (P=0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (beta=0.026, 95% CI=0.0097, 0.042; P=0.002). CONCLUSIONS: These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10-18 years. This should be considered in studies of beta-cell function in type 1 diabetes

The utility of superficial abdominal reflex in the initial diagnosis of scoliosis: a retrospective review of clinical characteristics of scoliosis with syringomyelia

<p>Abstract</p> <p>Background</p> <p>With increasing use of magnetic resonance imaging (MRI), underlying syringomyelia is increasingly found in patients with presumed idiopathic scoliosis. To determine the indications for MRI in the differential diagnosis of scoliosis, several clinical characteristics of syringomyelia have been reported. Neurological signs, particularly abnormal superficial abdominal reflex (SAR), are important in establishing the initial diagnosis of scoliosis. However, the prevalence of abnormal SAR in patients with scoliosis and the sensitivity of this sign in predicting syringomyelia are not well known. We aimed to determine the diagnostic utility of SAR and other characteristics of syringomyelia in patients with scoliosis.</p> <p>Methods</p> <p>We reviewed the medical records of 93 patients with scoliosis, 90 of whom underwent corrective surgery. All patients underwent MRI to determine the presence of syringomyelia. Mean age at surgery was 12.5 years. Abnormal SAR was defined as unilateral or bilateral absence or hyporeflexia of SAR. We calculated indices of diagnostic utility of abnormal SAR for non-idiopathic scoliosis and for syringomyelia. Abnormal SAR, left thoracic curve pattern, gender, and curve flexibility were compared between scoliosis with syringomyelia and idiopathic scoliosis. Logistic regression analysis was performed with the existence of syringomyelia as the dependent variable and curve flexibility as the independent variable.</p> <p>Results</p> <p>Abnormal SAR was observed in 20 patients (prevalence 22%). All 6 patients with myopathic scoliosis displayed bilateral absence of SAR. The sensitivity of abnormal SAR for non-idiopathic scoliosis was 38%, with 96% specificity, 90% PPV (positive predictive value), and 60% NPV (negative predictive value). Syringomyelia was identified in 9 of the 93 patients (9.7%); 8 of these had abnormal SAR. The sensitivity of abnormal SAR for syringomyelia in presumed idiopathic scoliosis was 89%, with 95% specificity, 80% PPV, and 98% NPV. Gender, abnormal neurological findings, and curve flexibility differed significantly between patients with syringomyelia and those with idiopathic scoliosis (P < 0.05). In the logistic regression model, the area under the receiver operating characteristic (ROC) curve was 0.79 and the cut-off value of curve flexibility for syringomyelia was 50% (P = 0.08).</p> <p>Conclusion</p> <p>Abnormal SAR was a useful indicator not only for syringomyelia, but also for myogenic scoliosis.</p

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans