Islet autoantibody status in a multi-ethnic UK clinic cohort of children presenting with diabetes.

OBJECTIVE: We prospectively determined islet autoantibody status in children presenting with diabetes to a single UK region in relation to ethnicity. DESIGN: 316 (68.0% non-white) children presenting with diabetes between 2006 and 2013 were tested centrally for islet cell autoantibodies (ICA) and glutamic acid decarboxylase autoantibodies (GAD-65) at diagnosis, and if negative for both, tested for insulin autoantibodies (IAA). The assay used to measure GAD-65 autoantibodies changed from an in-house to a standardised ELISA method during the study. RESULTS: Even with use of the standardised ELISA method, 25.8% of children assigned a diagnosis of type 1 diabetes still tested negative for all three autoantibodies. 30% of children assigned a diagnosis of type 2 diabetes were autoantibody positive, and these had the highest glycated haemoglobin (HbA1c) levels at 12 months follow-up compared with other groups (p value for analysis of variance <0.001), although the sample size was small. Autoantibody positivity was similar between non-white and white children regardless of assay used (60.0% (n=129) vs 56.4% (n=57), χ2=0.9, p=0.35), as was mean GAD-65 autoantibody levels, but fewer non-white children had two or more autoantibodies detectable (13% (n=28) vs 27.7% (n=28), χ2=12.1, p=0.001). CONCLUSION: Islet autoantibody positivity was associated with a more severe phenotype, as demonstrated by poorer glycaemic control, regardless of assigned diabetes subtype. Positivity did not differ by ethnic group

Effects of interrupting prolonged sitting with physical activity breaks on blood glucose, insulin and triacylglycerol measures : a systematic review and meta-analysis

Abstract: Background: Physical activity (PA) breaks in sitting time might attenuate metabolic markers relevant to the prevention of type 2 diabetes. Objectives: The primary aim of this paper was to systematically review and meta-analyse trials that compared the effects of breaking up prolonged sitting with bouts of PA throughout the day (INT) versus continuous sitting (SIT) on glucose, insulin and triacylglycerol (TAG) measures. A second aim was to compare the effects of INT versus continuous exercise (EX) on glucose, insulin and TAG measures. Methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Eligibility criteria consisted of trials comparing INT vs. SIT or INT vs. one bout of EX before or after sitting, in participants aged 18 or above, who were classified as either metabolically healthy or impaired, but not with other major health conditions such as chronic obstructive pulmonary disease or peripheral arterial disease. Results: A total of 42 studies were included in the overall review, whereas a total of 37 studies were included in the meta-analysis. There was a standardised mean difference (SMD) of − 0.54 (95% CI − 0.70, − 0.37, p = 0.00001) in favour of INT compared to SIT for glucose. With respect to insulin, there was an SMD of − 0.56 (95% CI − 0.74, − 0.38, p = 0.00001) in favour of INT. For TAG, there was an SMD of − 0.26 (95% CI − 0.44, − 0.09, p = 0.002) in favour of INT. Body mass index (BMI) was associated with glucose responses (β = − 0.05, 95% CI − 0.09, − 0.01, p = 0.01), and insulin (β = − 0.05, 95% CI − 0.10, − 0.006, p = 0.03), but not TAG (β = 0.02, 95% CI − 0.02, 0.06, p = 0.37). When energy expenditure was matched, there was an SMD of − 0.26 (95% CI − 0.50, − 0.02, p = 0.03) in favour of INT for glucose, but no statistically significant SMDs for insulin, i.e. 0.35 (95% CI − 0.37, 1.07, p = 0.35), or TAG i.e. 0.08 (95% CI − 0.22, 0.37, p = 0.62). It is worth noting that there was possible publication bias for TAG outcomes when PA breaks were compared with sitting. Conclusion: The use of PA breaks during sitting moderately attenuated post-prandial glucose, insulin, and TAG, with greater glycaemic attenuation in people with higher BMI. There was a statistically significant small advantage for PA breaks over continuous exercise for attenuating glucose measures when exercise protocols were energy matched, but no statistically significant differences for insulin and TAG

Changes in insulin sensitivity in response to different modalities of exercise: a review of the evidence

Summary: Type 2 diabetes is an increasingly prevalent condition with complications including blindness and kidney failure. Evidence suggests that type 2 diabetes is associated with a sedentary lifestyle, with physical activity demonstrated to increase glucose uptake and improve glycaemic control. Proposed mechanisms for these effects include the maintenance and improvement of insulin sensitivity via increased glucose transporter type four production. The optimal mode, frequency, intensity and duration of exercise for the improvement of insulin sensitivity are however yet to be identified. We review the evidence from 34 published studies addressing the effects on glycaemic control and insulin sensitivity of aerobic exercise, resistance training and both combined. Effect sizes and confidence intervals are reported for each intervention and meta-analysis presented. The quality of the evidence is tentatively graded, and recommendations for best practice proposed

Current concepts in osteogenesis imperfecta:bone structure, biomechanics and medical management

The majority of patients with osteogenesis imperfecta (OI) have mutations in the COL1A1 or COL1A2 gene, which has consequences for the composition of the bone matrix and bone architecture. The mutations result in overmodified collagen molecules, thinner collagen fibres and hypermineralization of bone tissue at a bone matrix level. Trabecular bone in OI is characterized by a lower trabecular number and connectivity as well as a lower trabecular thickness and volumetric bone mass. Cortical bone shows a decreased cortical thickness with less mechanical anisotropy and an increased pore percentage as a result of increased osteocyte lacunae and vascular porosity. Most OI patients have mutations at different locations in the COL1 gene. Disease severity in OI is probably partly determined by the nature of the primary collagen defect and its location with respect to the C-terminus of the collagen protein. The overall bone biomechanics result in a relatively weak and brittle structure. Since this is a result of all of the above-mentioned factors as well as their interactions, there is - considerable variation between patients, and accurate prediction on bone strength in the individual patient with OI is difficult. Current treatment of OI focuses on adequate vitamin-D levels and interventions in the bone turnover cycle with bisphosphonates. Bisphosphonates increase bone mineral density, but the evidence on improvement of clinical status remains limited. Effects of newer drugs such as antibodies against RANKL and sclerostin are currently under investigation. This paper was written under the guidance of the Study Group Genetics and Metabolic Diseases of the European Paediatric Orthopaedic Society

Case report: A 10-year-old girl with primary hypoparathyroidism and systemic lupus erythematosus

Hypoparathyroidism is a rare disease in children that occurs as a result of autoimmune destruction of the parathyroid glands, a defect in parathyroid gland development or secondary to physical parathyroid gland disturbance. Typical symptoms of hypoparathyroidism present as hypocalcaemia and hyperphosphatemia due to decreased parathyroid hormone secretion and may lead to nerve and muscles disturbances resulting in clinical manifestation of tetany, arrhythmias and epilepsy. Currently, there is no conventional hormone replacement treatment for hypoparathyroidism and therapeutic approaches include normalising mineral levels using an oral calcium supplement and active forms of vitamin D. We present the case of a 10-year old girl with primary hypoparathyroidism who had no prior history of autoimmune disorders, but who subsequently developed systemic lupus erythematosus

Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the <it>GNAS</it>1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly.</p> <p>Case presentation</p> <p>Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted.</p> <p>Conclusion</p> <p>Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base.</p

Plasma free fatty acids metabolic profile with LC-MS and appetite-related hormones in South Asian and White European men in relation to adiposity, physical activity and cardiorespiratory fitness : a cross-sectional study

South Asians have a greater cardiovascular disease (CVD) and type 2 diabetes (T2D) risk than white Europeans, but the mechanisms are poorly understood. This study examined ethnic differences in free fatty acids (FFAs) metabolic profile (assessed using liquid chromatography-mass spectrometry), appetite-related hormones and traditional CVD and T2D risk markers in blood samples collected from 16 South Asian and 16 white European men and explored associations with body composition, objectively-measured physical activity and cardiorespiratory fitness. South Asians exhibited higher concentrations of five FFAs (laurate, myristate, palmitate, linolenic, linoleate; p ≤ 0.040), lower acylated ghrelin (ES = 1.00, p = 0.008) and higher leptin (ES = 1.11, p = 0.004) than white Europeans; total peptide YY was similar between groups (p = 0.381). South Asians exhibited elevated fasting insulin, C-reactive protein, interleukin-6, triacylglycerol and ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C) and lower fasting HDL-C (all ES ≥ 0.74, p ≤ 0.053). Controlling for body fat percentage (assessed using air displacement plethysmography) attenuated these differences. Despite similar habitual moderate-to-vigorous physical activity (ES = 0.18, p = 0.675), V ˙ O2max was lower in South Asians (ES = 1.36, p = 0.001). Circulating FFAs in South Asians were positively correlated with body fat percentage (r2 = 0.92), body mass (r2 = 0.86) and AUC glucose (r2 = 0.89) whereas in white Europeans FFAs were negatively correlated with total step counts (r2 = 0.96). In conclusion, South Asians exhibited a different FFA profile, lower ghrelin, higher leptin, impaired CVD and T2D risk markers and lower cardiorespiratory fitness than white Europeans