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Background: Observational studies have shown that higher cereal fiber intake is associated with reduced type 2 diabetes risk. However, it remains uncertain whether this association is causal., Objective: This study evaluated the feasibility of an intervention to increase cereal fiber intake in children using breakfast cereals., Methods: The study was a 2-arm parallel group randomized controlled trial in 9-10-y-old children, who received free supplies of high-fiber breakfast cereals (>3.5 g/portion) or low-fiber breakfast cereals (<1.0 g/portion) to eat daily for 1 mo with behavioral support to promote adherence. Children provided baseline and 1-mo fasting blood samples, physical measurements, and 24-h dietary recalls. The primary outcome was the group difference in change in plasma total alkylresorcinol (AR) concentration; secondary outcomes were group differences in nutrient intakes and adiposity indices. Analyses (complete case and multiple imputation) were conducted by regressing the final AR concentration on baseline AR in models adjusted for sex, ethnicity, age, and school (random effect)., Results: Two-hundred seventy-two children were randomly assigned (137 receiving a low-fiber and 135 a high-fiber diet) and 193 (71%) provided fasting blood samples at baseline and follow-up. Among randomized participants, median (IQR) of baseline AR was 43.1 (24.6-85.5) nmol/L and of cereal fiber intake was 4.5 (2.7-6.4) g; 87% of participants reported consuming the cereal on most or all days. Compared with changes in the low-fiber group, the high-fiber group had greater increases in AR (40.7 nmol/L; 95% CI: 21.7, 59.8 nmol/L, P < 0.0001) and in reported cereal fiber intake (2.9g/d; 95% CI: 2.0, 3.7 g; P < 0.0001). There were no appreciable differences in other secondary outcomes., Conclusions: We have developed a simple and acceptable nutritional intervention that increases markers of daily cereal fiber intake in children. This intervention could be used to test whether increases in cereal fiber intake in children might reduce insulin resistance. This trial was registered at www.isrctn.com as ISRCTN33260236., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Purpose: To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women., Design: Retinal imaging examination as part of the European Prospective Investigation into Cancer-Norfolk Eye Study., Participants: Retinal imaging and clinical assessments were carried out in 7411 participants. Retinal images were analyzed using a fully automated validated computerized system that provides novel measures of vessel morphometry., Methods: Associations between cardiometabolic risk factors, chronic disease, and retinal markers were analyzed using multilevel linear regression, adjusted for age, gender, and within-person clustering, to provide percentage differences in tortuosity and absolute differences in width., Main Outcomes Measures: Retinal arteriolar and venular tortuosity and width., Results: In all, 279 802 arterioles and 285 791 venules from 5947 participants (mean age, 67.6 years; standard deviation [SD], 7.6 years; 57% female) were analyzed. Increased venular tortuosity was associated with higher body mass index (BMI; 2.5%; 95% confidence interval [CI], 1.7%-3.3% per 5 kg/m 2 ), hemoglobin A1c (HbA1c) level (2.2%; 95% CI, 1.0%-3.5% per 1%), and prevalent type 2 diabetes (6.5%; 95% CI, 2.8%-10.4%); wider venules were associated with older age (2.6 μm; 95% CI, 2.2-2.9 μm per decade), higher triglyceride levels (0.6 μm; 95% CI, 0.3-0.9 μm per 1 mmol/l), BMI (0.7 μm; 95% CI, 0.4-1.0 per 5 kg/m 2 ), HbA1c level (0.4 μm; 95% CI, -0.1 to 0.9 per 1%), and being a current smoker (3.0 μm; 95% CI, 1.7-4.3 μm); smoking also was associated with wider arterioles (2.1 μm; 95% CI, 1.3-2.9 μm). Thinner venules were associated with high-density lipoprotein (HDL) (1.4 μm; 95% CI, 0.7-2.2 per 1 mmol/l). Arteriolar tortuosity increased with age (5.4%; 95% CI, 3.8%-7.1% per decade), higher systolic blood pressure (1.2%; 95% CI, 0.5%-1.9% per 10 mmHg), in females (3.8%; 95% CI, 1.4%-6.4%), and in those with prevalent stroke (8.3%; 95% CI, -0.6% to 18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8 μm; 95% CI, 0.6-1.0 μm per decade), higher systolic blood pressure (0.5 μm; 95% CI, 0.4-0.6 μm per 10 mmHg), total cholesterol level (0.2 μm; 95% CI, 0.0-0.3 μm per 1 mmol/l), and HDL (1.2 μm; 95% CI, 0.7-1.6 μm per 1 mmol/l)., Conclusions: Metabolic risk factors showed a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlated more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These noninvasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

The Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) study provides a unique opportunity to examine differences in mental health and well-being amongst adults seeking social, intermediate (affordable rent), and market-rent housing in a purpose built neighbourhood (East Village, the former London 2012 Olympic Athletes' Village), specifically designed to encourage positive health behaviours. Multi-level logistic regression models examined baseline differences in levels of depression, anxiety and well-being across the housing groups. Compared with the intermediate group, those seeking social housing were more likely to be depressed, anxious and had poorer well-being after adjustment for demographic and health status variables. Further adjustments for neighbourhood perceptions suggest that compared with the intermediate group, perceived neighbourhood characteristics may be an important determinant of depression amongst those seeking social housing, and lower levels of happiness the previous day amongst those seeking market-rent housing. These findings add to the extensive literature on inequalities in health, and provide a strong basis for future longitudinal work that will examine change in depression, anxiety and well-being after moving into East Village, where those seeking social housing potentially have the most to gain., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Objective: With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders., Design: Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS., Participants: Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013., Methods: Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration., Main Outcome Measures: Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome., Results: Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%-95.2%) for any retinopathy, 93.8% (92.9%-94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%-99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %-74.0%) for any retinopathy, 85.0% (83.6%-86.2%) for referable retinopathy, 97.9% (94.9%-99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective., Conclusions: Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings., (Copyright © 2016 American Academy of Ophthalmology. All rights reserved.)

Objective: To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends., Design: Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases., Participants: Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD)., Methods: Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI)., Main Outcome Measures: Log odds and prevalence of AMD., Results: There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8-4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0-1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1-2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3-7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%-2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%-7.7%) at age 80 and 20% (95% CrI, 14%-27%) at age 90., Conclusions: Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Ischemic heart disease (IHD) rates are lower in UK black Africans and black Caribbeans and higher in South Asians when compared with white Europeans. Ethnic differences in lipid concentrations may play a part in these differences., Objective: The objective was to investigate blood lipid and dietary patterns in UK children from different ethnic groups., Design: This was a cross-sectional study in 2026 UK children (including 285 black Africans, 188 black Caribbeans, 534 South Asians, and 512 white Europeans) attending primary schools in London, Birmingham, and Leicester. We measured fasting blood lipid concentrations and collected 24-h dietary recalls., Results: In comparison with white Europeans, black African children had lower total cholesterol (-0.14 mmol/L; 95% CI: -0.25, -0.04 mmol/L), LDL-cholesterol (-0.10 mmol/L; 95% CI: -0.20, -0.01 mmol/L), and triglyceride concentrations (proportional difference: -0.11 mmol/L; 95% CI: -0.16, -0.06 mmol/L); HDL-cholesterol concentrations were similar. Lower saturated fat intakes (-1.4%; 95% CI: -1.9%, -0.9%) explained the differences between total and LDL cholesterol. Black Caribbean children had total, LDL-cholesterol, HDL-cholesterol, and triglyceride concentrations similar to those for white Europeans, with slightly lower saturated fat intakes. South Asian children had total and LDL-cholesterol concentrations similar to those for white Europeans, lower HDL-cholesterol concentrations (-0.7 mmol/L; 95% CI: -0.11, -0.03 mmol/L), and elevated triglyceride concentrations (proportional difference: 0.14 mmol/L; 95% CI: 0.09, 0.20 mmol/L); higher polyunsaturated and monounsaturated fat intakes did not explain these lipid differences., Conclusions: Only black African children had a blood lipid profile and associated dietary pattern likely to protect against future IHD. The loss of historically lower LDL-cholesterol concentrations among UK black Caribbeans and South Asians may have important adverse consequences for future IHD risk in these groups.

Background: Earlier studies have suggested that infant feeding may program long-term changes in cholesterol metabolism., Objective: We aimed to examine whether breastfeeding is associated with lower blood cholesterol concentrations in adulthood., Design: The study consisted of a systematic review of published observational studies relating initial infant feeding status to blood cholesterol concentrations in adulthood (ie, aged >16 y). Data were available from 17 studies (17 498 subjects; 12 890 breastfed, 4608 formula-fed). Mean differences in total cholesterol concentrations (breastfed minus formula-fed) were pooled by using fixed-effect models. Effects of adjustment (for age at outcome, socioeconomic position, body mass index, and smoking status) and exclusion (of nonexclusive breast feeders) were examined., Results: Mean total blood cholesterol was lower (P = 0.037) among those ever breastfed than among those fed formula milk (mean difference: -0.04 mmol/L; 95% CI: -0.08, 0.00 mmol/L). The difference in cholesterol between infant feeding groups was larger (P = 0.005) and more consistent in 7 studies that analyzed "exclusive" feeding patterns (-0.15 mmol/L; -0.23, -0.06 mmol/L) than in 10 studies that analyzed nonexclusive feeding patterns (-0.01 mmol/L; -0.06, 0.03 mmol/L). Adjustment for potential confounders including socioeconomic position, body mass index, and smoking status in adult life had minimal effect on these estimates., Conclusions: Initial breastfeeding (particularly when exclusive) may be associated with lower blood cholesterol concentrations in later life. Moves to reduce the cholesterol content of formula feeds below those of breast milk should be treated with caution.

Objectives: Diabetes is associated with loss of capillaries and macrovessel dilation in the conjunctiva, similar to well-known vessel changes in the retina. However, little is known about the effect of diabetes on the tortuosity of vessels of the conjunctiva. The authors examined the tortuosity of conjunctival vessels in participants with and without diabetes., Design: Case-control study., Participants and Controls: Fifty-three patients with diabetes (17 with type 1 diabetes, 36 with type 2 diabetes) and 60 controls (all aged 20-94 years)., Methods: Digital red-free images of conjunctivae were analyzed using an automated computer algorithm to identify vessel axes and to quantify vessel tortuosity. Differences in vessel tortuosity were adjusted for age, gender, blood pressure, and smoking status., Main Outcome Measures: Tortuosity was expressed in units of curve energy (the square of the radian angular change between subsequent locations identified by the algorithm, standardized by vessel length)., Results: A longer duration of diabetes was associated with a reduction in overall vessel tortuosity (-2.8%; 95% confidence interval [CI], -4.3% to -1.3% per decade). This inverse association was driven by changes in larger vessels (40 microm in width or more), whereas increased tortuosity was observed in capillary sized vessels (<25 microm, 4.0%; 95% CI, -0.2% to 8.2% per decade). Compared with controls, those with type 1 diabetes (median duration of disease, 26 years) showed a 17.9% increase (95% CI, 4.7% to -31.0%) in capillary tortuosity. Conversely, those with type 1 diabetes showed a 7% decrease (95% CI, -11.8% to -2.3%) in tortuosity among vessels 40 to 80 microm or less in size and a 26.8% decrease (95% CI, -66.2% to 12.7%) in the fewer number of vessels more than 80 microm in size compared with controls. Similar, but smaller differences were seen in those with type 2 diabetes with shorter duration of diabetes (median, 7 years)., Conclusions: Macrovessel dilation associated with diabetes may result in vessel engorgement and straightening, especially among those with longer durations of disease. Increased tortuosity associated with diabetes among conjunctival capillaries mirrors established vessel changes observed in the retina. Conjunctival angiopathy associated with diabetes may contribute to susceptibility to anterior eye disease among patients with diabetes.

Background: It has been suggested that early life factors, including breastfeeding and birth weight, program childhood myopia., Objective: We examined the relation of reduced unaided vision (indicative of myopia) in childhood and adolescence with infant feeding, parental education, maternal age at birth, birth weight, sex, birth order, and socioeconomic status., Design: Three British cohorts recruited infants born in 1946 (n = 5362), 1958 (n = 18,558), and 1970 (n = 16,567). Adjusted odds ratios (ORs) for unaided vision of 6/12 or worse at ages 10-11 and 15-16 y from each cohort were pooled by using fixed-effects meta-analyses., Results: The prevalence of reduced vision ranged from 4.4% to 6.5% at 10-11 y and from 9.4% to 11.4% at 16 y, with marginally higher levels in later cohorts. Breastfeeding declined across successive cohorts (65%, 43%, and 22% in those breastfed for >1 mo, respectively). Pooled ORs showed no associations between infant feeding and vision after adjustment at either age. Parental education (OR: 1.48, high versus low education; 95% CI: 1.23, 1.79), maternal age (OR: 1.10, per 5-y increase; 95% CI: 1.04, 1.17), birth weight (OR: 0.85, per 1-kg rise; 95% CI: 0.76, 0.95), number of older siblings (OR: 0.89, per older sibling; 95% CI: 0.83, 0.94), and sex (OR: 1.10, girls versus boys; 95% CI: 0.98, 1.23) were related to adverse visual outcome in childhood. Stronger associations were observed in adolescence, except that the association with birth weight was null., Conclusions: Infant feeding does not appear to influence visual development. Consistent associations of reduced vision with parental education, sex, maternal age, and birth order suggest that other environmental factors are important for visual development and myopia in early life.

Objective: Retinovascular changes associated with diabetes have been clearly documented; changes in vessels of the conjunctiva are less well described. We examined changes in conjunctival vessel morphologic features in participants with and without diabetes., Design: Case-control study., Participants and Controls: Fifty-three patients with diabetes (17 with type 1 diabetes, 36 with type 2 diabetes) and 60 controls (all aged 20-94 years)., Methods: Digital red-free conjunctival images were captured and an automated computer algorithm was used to derive indices that describe the morphologic features of vessels of the conjunctiva. Percentage differences in vessel indices were adjusted for age, gender, blood pressure, and smoking status., Main Outcome Measures: Mean vessel diameter (micrometers) and vessel density (square millimeters of vessel per square centimeter of bulbar conjunctiva)., Results: A strong positive association between the duration of diabetes and overall mean vessel width was observed (P<0.001), resulting from changes in larger vessels (>80 mum in width). Conversely, the duration of diabetes showed a strong inverse association with vessel area (P<0.001) that appeared to be driven by the trend observed in smaller vessels (<40 mum in width). A 25% reduction (95% confidence interval [CI], -35% to -13%; P<0.001) in vessel density in those with type 1 diabetes and a 14% reduction (95% CI, -24% to -3%; P = 0.016) in those with type 2 diabetes, compared with controls, was observed. Mean vessel widths were 11% (95% CI, 4%-17%; P = 0.001) wider in type 1 and 5% (95% CI, 0%-10%; P = 0.073) wider in those with type 2 diabetes compared with controls. The difference in magnitude of effect for type 1 and type 2 diabetes compared with controls was explained by duration of diabetes. Grade of diabetic retinopathy and elevated blood pressure showed similar but less strong associations with vessel indices., Conclusions: Loss of capillaries and macrovessel dilation in the conjunctiva associated with diabetes compares with well-known vessel changes in the retina. Associations between morphologic changes in the conjunctiva and elevated blood pressure were similar but less strong; this may show that diabetic angiopathy predominates in those with both diabetes and elevated blood pressure.