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221 result(s) for "Dunger, David B."
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Gestational Diabetes Mellitus in Africa: A Systematic Review
Gestational diabetes mellitus (GDM) is any degree of impaired glucose tolerance first recognised during pregnancy. Most women with GDM revert to normal glucose metabolism after delivery of their babies; however, they are at risk of developing type 2 diabetes later in life as are their offspring. Determining a country's GDM prevalence can assist with policy guidelines regarding GDM screening and management, and can highlight areas requiring research. This systematic review assesses GDM prevalence in Africa. Three electronic databases were searched without language restrictions; PubMed, Scopus and the Cochrane Library. Thirty-one search terms were searched. Eligible articles defined GDM, stated what GDM screening approaches were employed and reported GDM prevalence. The reporting quality and risk of bias within each study was assessed. The PRISMA guidelines for systematic reviews were followed. The literature search identified 466 unique records. Sixty full text articles were reviewed of which 14 were included in the systematic review. One abstract, for which the full text article could not be obtained, was also included. Information regarding GDM classification, screening methods and prevalence was obtained for six African countries; Ethiopia (n = 1), Morocco (n = 1), Mozambique (n = 1), Nigeria (n = 6), South Africa (n= 4) and Tanzania (n = 1). Prevalence figures ranged from 0% (Tanzania) to 13.9% (Nigeria) with some studies focussing on women with GDM risk factors. Most studies utilised the two hour 75 g oral glucose tolerance test and applied the World Health Organization's diagnostic criteria. Six countries, equating to 11% of the African continent, were represented in this systematic review. This indicates how little is known about GDM in Africa and highlights the need for further research. Considering the increasing public health burden of obesity and type 2 diabetes, it is essential that the extent of GDM is understood in Africa to allow for effective intervention programmes.
Feasibility of automated insulin delivery guided by continuous glucose monitoring in preterm infants
ObjectiveClosed-loop systems have been used to optimise insulin delivery in children with diabetes, but they have not been tested in neonatal intensive care. Extremely preterm infants are prone to hyperglycaemia and hypoglycaemia; both of which have been associated with adverse outcomes. Insulin sensitivity is notoriously variable in these babies and glucose control is time-consuming, with management requiring frequent changes of dextrose-containing fluids and careful monitoring of insulin treatment. We aimed to evaluate the feasibility of closed-loop management of glucose control in these infants.Design and settingSingle-centre feasibility study with a randomised parallel design in a neonatal intensive care unit. Eligibility criteria included birth weight <1200 g and <48 hours of age. All infants had subcutaneous continuous glucose monitoring for the first week of life, with those in the intervention group receiving closed-loop insulin delivery in a prespecified window, between 48 and 72 hours of age during which time the primary outcome was percentage of time in target (sensor glucose 4–8 mmol/L).ResultsThe mean (SD) gestational age and birth weight of intervention and control study arms were 27.0 (2.4) weeks, 962 (164) g and 27.5 (2.8) weeks, 823 (282) g, respectively, and were not significantly different. The time in target was dramatically increased from median (IQR) 26% (6-64) with paper guidance to 91% (78-99) during closed loop (p<0.001). There were no serious adverse events and no difference in total insulin infused.ConclusionsClosed-loop glucose control based on subcutaneous glucose measurements appears feasible as a potential method of optimising glucose control in extremely preterm infants.
Biomarkers of rapid chronic kidney disease progression in type 2 diabetes
Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case–control design nested within a prospective cohort of patients with baseline eGFR 30–60 ml/min per 1.73 m2. Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.
Summary and Recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus
Monogenic forms of diabetes such as maturity-onset diabetes of the young (MODY; autosomal dominant inheritance) and mitochondrial diabetes (maternal inheritance, often with other clinical manifestations) appear to contribute in a relatively minor way (<5% of cases) to GDM.
Closed-loop insulin delivery for treatment of type 1 diabetes
Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence, and remains a serious chronic disorder with increased morbidity and mortality, and reduced quality of life. Technological innovations positively affect the management of type 1 diabetes. Closed-loop insulin delivery (artificial pancreas) is a recent medical innovation, aiming to reduce the risk of hypoglycemia while achieving tight control of glucose. Characterized by real-time glucose-responsive insulin administration, closed-loop systems combine glucose-sensing and insulin-delivery components. In the most viable and researched configuration, a disposable sensor measures interstitial glucose levels, which are fed into a control algorithm controlling delivery of a rapid-acting insulin analog into the subcutaneous tissue by an insulin pump. Research progress builds on an increasing use of insulin pumps and availability of glucose monitors. We review the current status of insulin delivery, focusing on clinical evaluations of closed-loop systems. Future goals are outlined, and benefits and limitations of closed-loop therapy contrasted. The clinical utility of these systems is constrained by inaccuracies in glucose sensing, inter- and intra-patient variability, and delays due to absorption of insulin from the subcutaneous tissue, all of which are being gradually addressed.
Examining the relationships between body image, eating attitudes, BMI, and physical activity in rural and urban South African young adult females using structural equation modeling
The persistence of food insecurity, malnutrition, increasing adiposity, and decreasing physical activity, heightens the need to understand relationships between body image satisfaction, eating attitudes, BMI and physical activity levels in South Africa. Females aged 18-23 years were recruited from rural (n = 509) and urban (n = 510) settings. Body image satisfaction was measured using Stunkard's silhouettes, and the 26-item Eating Attitudes questionnaire (EAT-26) was used to evaluate participants' risk of disordered eating. Minutes per week of moderate to vigorous physical activity (MVPA) was assessed using the Global Physical Activity Questionnaire (GPAQ). Significant linear correlates were included in a series of regressions run separately for urban and rural participants. Structural equation modeling (SEM) was used to test the relationships between variables. Urban females were more likely to be overweight and obese than rural females (p = 0.02), and had a greater desire to be thinner (p = 0.02). In both groups, being overweight or obese was positively associated with a desire to be thinner (p<0.01), and negatively associated with a desire to be fatter (p<0.01). Having a disordered eating attitude was associated with body image dissatisfaction in the urban group (β = 1.27, p<0.01, CI: 0.38; 2.16), but only with a desire to be fatter in the rural group (β = 0.63, p = 0.04, CI: 0.03; 1.23). In the SEM model, body image dissatisfaction was associated with disordered eating (β = 0.63), as well as higher MVPA participation (p<0.01). These factors were directly associated with a decreased risk of disordered eating attitude, and with a decreased desire to be thinner. Findings indicate a shift in both settings towards more Westernised ideals. Physical activity may provide a means to promote a healthy body image, while reducing the risk of disordered eating. Given the high prevalence of overweight and obesity in both rural and urban women, this study provides insights for future interventions aimed at decreasing adiposity in a healthy way.
Effect of serum sample storage temperature on metabolomic and proteomic biomarkers
Prospective biomarker studies can be used to identify biomarkers predictive of disease onset. However, if serum biomarkers are measured years after their collection, the storage conditions might affect analyte concentrations. Few data exists concerning which metabolites and proteins are affected by storage at − 20 °C vs − 80 °C. Our objectives were to document analytes affected by storage of serum samples at − 20 °C vs − 80 °C, and to identify those indicative of the storage temperature. We utilized liquid chromatography tandem mass spectrometry and Luminex to quantify 300 analytes from serum samples of 16 Finnish individuals with type 1 diabetes, with split-aliquot samples stored at − 80 °C and − 20 °C for a median of 4.2 years. Results were validated in 315 Finnish and 916 Scottish individuals with type 1 diabetes, stored at − 20 °C and at − 80 °C, respectively. After quality control, we analysed 193 metabolites and proteins of which 120 were apparently unaffected and 15 clearly susceptible to storage at − 20 °C vs − 80 °C. Further, we identified serum glutamate/glutamine ratio greater than 0.20 as a biomarker of storage at − 20 °C vs − 80 °C. The results provide a catalogue of analytes unaffected and affected by storage at − 20 °C vs − 80 °C and biomarkers indicative of sub-optimal storage.
Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial
Closed-loop systems link continuous glucose measurements to insulin delivery. We aimed to establish whether closed-loop insulin delivery could control overnight blood glucose in young people. We undertook three randomised crossover studies in 19 patients aged 5–18 years with type 1 diabetes of duration 6·4 years (SD 4·0). We compared standard continuous subcutaneous insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery and standard treatment after exercise (n=10; APCam03). Allocation was by computer-generated random code. Participants were masked to plasma and sensor glucose. In APCam01, investigators were masked to plasma glucose. During closed-loop nights, glucose measurements were fed every 15 min into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. During control nights, patients' standard pump settings were applied. Primary outcomes were time for which plasma glucose concentration was 3·91–8·00 mmol/L or 3·90 mmol/L or lower. Analysis was per protocol. This trial is registered, number ISRCTN18155883. 17 patients were studied for 33 closed-loop and 21 continuous infusion nights. Primary outcomes did not differ significantly between treatment groups in APCam01 (12 analysed; target range, median 52% [IQR 43–83] closed loop vs 39% [15–51] standard treatment, p=0·06; ≤3·90 mmol/L, 1% [0–7] vs 2% [0–41], p=0·13), APCam02 (six analysed; target range, rapidly 53% [48–57] vs slowly absorbed meal 55% [37–64], p=0·97; ≤3·90 mmol/L, 0% [0–4] vs 0% [0–0], p=0·16]), and APCam03 (nine analysed; target range 78% [60–92] closed loop vs 43% [25–65] control, p=0·0245, not significant at corrected level; ≤3·90 mmol/L, 10% [2–15] vs 6% [0–44], p=0·27). A secondary analysis of pooled data documented increased time in the target range (60% [51–88] vs 40% [18–61]; p=0·0022) and reduced time for which glucose concentrations were 3·90 mmol/L or lower (2·1% (0·0–10·0) vs 4·1% (0·0–42·0); p=0·0304). No events with plasma glucose concentration lower than 3·0 mmol/L were recorded during closed-loop delivery, compared with nine events during standard treatment. Closed-loop systems could reduce risk of nocturnal hypoglycaemia in children and adolescents with type 1 diabetes. Juvenile Diabetes Research Foundation; European Foundation for Study of Diabetes; Medical Research Council Centre for Obesity and Related Metabolic Diseases; National Institute for Health Research Cambridge Biomedical Research Centre.
Anogenital Distance from Birth to 2 Years: A Population Study
Background: Anogenital distance (AGD) is sexually dimorphic in rodents anil humans, being 2- to 2. 5-fold greater in males. It is a reliable marker of androgen and antiandrogen effects in rodent reproductive toxicologic studies. Data on AGD in humans are sparse, with no longitudinal data collected during infancy. Objective: This study was designed to determine AGD from birth to 2 years in males and females and relate this to other anthropometric measures. Materials and Methods: Infants were recruited from the Cambridge Baby Growth Study. AGD was measured from the center of the anus to the base of the scrotum in males and to the posterior fourchette in females. Measurements were performed at birth and at 3, 12, 18, and 24 months of age. Results: Data included 2,168 longitudinal AGD measurements from 463 male and 426 female full-term infants (median = 2 measurements per infant). Mean AGD (± SD) at birth was 19.8 ± 6.1 mm in males and 9.1 ± 2.8 mm in females (p < 0.0001). AGD increased up to 12 months in both sexes and in a sex- dimorphic pattern. AGD was positively correlated with penile length at birth (r = 0.18, p = 0.003) and the increase in AGD from birth to 3 months was correlated with penile growth (r = 0.20, p = 0.001). Conclusion: We report novel, longitudinal data for AGD during infancy in a large U.K. birth cohort. AGD was sex dimorphic at all ages studied. The availability of normative data provides a means of utilizing this biological marker of androgen action in population studies of the effects of environmental chemicals on genital development.
A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region
In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard ) on chromosome 2q24.3. We found the association in an interim analysis of a genome-wide nonsynonymous SNP (nsSNP) scan, and we validated it in a case-control collection and replicated it in an independent family collection. In 4,253 cases, 5,842 controls and 2,134 parent-child trio genotypes, the risk ratio for the minor allele of the nsSNP rs1990760 A → G (A946T) was 0.86 (95% confidence interval = 0.82–0.90) at P = 1.42 × 10 −10 .