Genome-wide association identifies novel ROP risk loci in a multiethnic cohort.

We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide significance level (p < 5×10-8) and 9 with significance of p < 5×10-6 for ROP ≥ stage 3. The most significant locus, rs2058019, reached genome-wide significance within the full multiethnic cohort (p = 4.96×10-9); Hispanic and European Ancestry infants driving the association. The lead single nucleotide polymorphism (SNP) falls in an intronic region within the Glioma-associated oncogene family zinc finger 3 (GLI3) gene. Relevance for GLI3 and other top-associated genes to human ocular disease was substantiated through in-silico extension analyses, genetic risk score analysis and expression profiling in human donor eye tissues. Thus, we identify a novel locus at GLI3 with relevance to retinal biology, supporting genetic susceptibilities for ROP risk with possible variability by race and ethnicity.

Genome-wide association identifies novel ROP risk loci in a multi-ethnic cohort.

We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 2 loci at genome-wide significance level (p<5×10-8) and 7 at suggestive significance (p<5×10-6) for ROP ≥ stage 3. The most significant locus, rs2058019, reached genome-wide significance within the full multiethnic cohort (p=4.96×10-9); Hispanic and Caucasian infants driving the association. The lead single nucleotide polymorphism (SNP) falls in an intronic region within the Glioma-associated oncogene family zinc finger 3 (GLI3) gene. Relevance for GLI3 and other top-associated genes to human ocular disease was substantiated through in-silico extension analyses, genetic risk score analysis and expression profiling in human donor eye tissues. Thus, we report the largest ROP GWAS to date, identifying a novel locus at GLI3 with relevance to retinal biology supporting genetic susceptibilities for ROP risk with possible variability by race and ethnicity.

OMEGA-3 FATTY ACIDS ARE ASSOCIATED WITH DECREASED PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY: A Combined Analysis of MESA and GOLDR Cohorts.

PURPOSE: Inflammation is associated with diabetic retinopathy development and progression, and previous studies have demonstrated that omega-3 polyunsaturated fatty acids have anti-inflammatory properties. Therefore, the goal of this study was to determine if omega-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are associated with decreased risk and severity of retinopathy in individuals with type 2 diabetes. METHODS: In a combined population of 1,356 individuals with type 2 diabetes from the Multi-Ethnic Study of Atherosclerosis and Genetics of Latino Diabetic Retinopathy cohorts, odds ratios using logistic regression were determined to assess the association between polyunsaturated fatty acids and retinopathy. RESULTS: In 1,356 participants with type 2 diabetes, individuals in the fourth quartile of DHA were 17% less likely to have retinopathy compared with the first quartile ( P = 0.009, CI: 0.72-0.95). Secondary analysis revealed 38% lower severity of retinopathy in individuals in the fourth quartile compared with the first quartile of DHA ( P = 0.006; CI: 0.44-0.87) and EPA + DHA ( P = 0.004; CI: 0.44-0.85). No significant associations were observed between EPA and retinopathy. CONCLUSION: DHA is inversely associated with the presence and severity of diabetic retinopathy. Increased intake of dietary sources of DHA may provide some protection against retinopathy in individuals with type 2 diabetes and warrants more research as a preventative option.

Barriers to Healthy Eating and Diabetes Diet Education: Divergent Perspectives of Patients and Their Providers.

Patients report that adhering to diet is the most challenging aspect of diabetes management. Provision of diet education is often delegated to health care providers, despite a lack of nutrition education and training and limited awareness of environmental and cultural challenges faced by patients. Aim. We examined perceived barriers to diet self-management among low-income minority patients with type 2 diabetes and their health care providers within a single ecosystem, to test whether providers understood patient barriers. Method. We surveyed 149 members of a safety-net clinic (99 patients, 50 providers), using barriers derived from the literature. Binomial logistic regression was applied to investigate relationships between barriers and patients' sociodemographic variables and Pearson's χ2 was used to compare differences in perceived barriers between patients and providers. Results. Providers expressed divergent perceptions of patients' barriers to healthy eating, including more total barriers and little agreement with patients on their relative importance. Largest differences in providers' perceptions of patient barriers included poor motivation, high use of fast food, inadequate family support, and lack of cooking skills-all suggesting patient inadequacy. In contrast, patients showed evidence of high motivation-in rate of blood glucose measurement and desire for diet education. Patients identified primary care providers as a main source of nutrition education, yet providers indicated lack of time for diet discussion and preferred other staff do the teaching. Conclusion. The findings from this study strongly suggest that health systems need to consider patient, provider, and system barriers when implementing nutrition education and management programs.

Automated Reminders Improve Retinal Screening Rates in Low Income, Minority Patients with Diabetes and Correct the African American Disparity.

Diabetic retinopathy (DR) is a major cause of blindness in the United States. Prevention relies on periodic DR screening, yet overall national screening rates are not optimal, especially in low-income, minority patients. We prospectively evaluated show rates for prescheduled teleretinal DR screening appointments in diabetic patients (n = 301) in a large safety-net clinic in South Central Los Angeles. Patients were predominately African American (n = 88) and Latino (n = 200). Patients received either usual care telephone reminders or automated reminder calls in addition to usual care. The overall mean (SEM) show rate for DR screening, irrespective of reminder method, was low: 54 + 1.03%. Show rates with usual care alone were 46.3 + 2.6%, and with automated reminders added, 59.9 + 1.47% (p = 0.036). Show rate with usual care amongst African Americans was 23.6 + 6.46% compared with 53.2 + 3.41% for Latinos (p = 0.025). When automated calling was added, the show rate doubled amongst African Americans, to 51.6 + 3.96% (p = 0.002) with a slightly higher, non-significant show rate in Latinos. In summary, show rates for pre-scheduled teleretinal DR screening appointments were low with usual care alone in a safety-net clinic, with evidence for a racial disparity amongst low-income, minority patients with diabetes. Addition of a pre-recorded automated reminder call improved show rates, and corrected much of the racial disparity observed. Greater focus on failed appointments as an explanation for low DR screening rates and racial disparities, and as a potentially remediable target with automated reminders, may improve DR screening rates and reduce blindness in low-income minority patients with diabetes.

The GLP-1 response to glucose does not mediate beta and alpha cell dysfunction in Hispanics with abnormal glucose metabolism.

AIMS: Glucagon-like peptide-1 (GLP-1) contributes to insulin secretion after meals. Though Hispanics have increased risk for type 2 diabetes mellitus, it is unknown if impaired GLP-1 secretion contributes to this risk. We therefore studied plasma GLP-1 secretion and action in Hispanic adults. METHODS: Hispanic (H; n = 31) and non-Hispanic (nH; n = 15) participants underwent an oral glucose tolerance test (OGTT). All participants were categorized by glucose tolerance into four groups: normal glucose tolerant non-Hispanic (NGT-nH; n = 15), normal glucose tolerant Hispanic (NGT-H; n = 12), impaired glucose tolerant Hispanic (IGT-H; n = 11), or newly diagnosed type 2 diabetes mellitus, Hispanic (T2D-H; n = 8). RESULTS: Glucose-induced increments in plasma GLP-1 (Δ-GLP-1) were not different in NGT-H and NGT-nH (p = .38), nor amongst Hispanic subgroups with varying degrees of glucose homeostasis (p = .6). In contrast, the insulinogenic index in T2D-H group was lower than the other groups (p = .016). Subjects with abnormal glucose homeostasis (AGH), i.e., T2D-H plus IGT-H, had a diminished glucagon suppression index compared to patients with normal glucose homeostasis (NGT-H plus NGT-nH) (p = .035). CONCLUSIONS: GLP-1 responses to glucose were similar in Hispanic and Non-Hispanic NGT. Despite similar glucose-induced Δ-GLP-1, insulin and glucagon responses were abnormal in T2D-H and AGH, respectively. Thus, impaired GLP-1 secretion is unlikely to play a role in islet dysfunction in T2D. Although GLP-1 therapeutics enhance insulin secretion and glucagon suppression, it is likely due to pharmacological amplification of the GLP-1 pathways rather than treatment of hormonal deficiency.

Divergent Perceptions of Barriers to Diabetic Retinopathy Screening Among Patients and Care Providers, Los Angeles, California, 2014-2015.

INTRODUCTION: Despite availability of screening for diabetic retinopathy, testing is underused by many low-income and racial/ethnic minority patients with diabetes. We examined perceived barriers to diabetic retinopathy screening among low-income patients and their health care providers and provider staffers. METHODS: We collected survey data from 101 patients with diabetes and 44 providers and staffers at a safety-net clinic where annual diabetic retinopathy screening rates were low. Barriers specified in the survey were derived from the literature. RESULTS: Patients surveyed (mean [standard deviation] age, 54.0 [7.7] y; 41% were male) were primarily Hispanics (70%) and African Americans (27%) of low socioeconomic status. Overall, 55% of patients received diabetic retinopathy screening in the previous year. Patients who could not explain why this screening is needed reported more barriers than patients who could (2.5 vs 1.4 barriers, P = .02). Fewer patients reported that they experienced barriers such as transportation (15%), language issues (15%), cultural beliefs or myths (4%), denial (8%), and fear (5%), which providers and staffers considered very or extremely important (all P < .001). Financial burdens (26%) and depression (22%) were most commonly reported by patients as barriers, yet providers and staffers did not rate these barriers as important, P < .001. CONCLUSION: Patients and health care providers had markedly divergent perceptions of barriers to diabetic retinopathy screening. Patients with poor understanding of the need for screening were more likely to report such barriers. These results suggest a need for active community engagement to find key elements for education programs and other interventions to increase rates of diabetic retinopathy screening, particularly among low-income, minority populations.

Adiponectin, Insulin Sensitivity and Diabetic Retinopathy in Latinos With Type 2 Diabetes.

CONTEXT AND OBJECTIVE: Insulin resistance and chronic inflammation are key elements in the pathogenesis of type 2 diabetes. We hypothesized that similar mechanisms could have a role in the development of diabetic retinopathy (DR), an important microvascular complication in Latinos with type 2 diabetes. DESIGN AND SETTING: A cross-sectional, family-based, observational cohort study. PATIENTS: Latino subjects with type 2 diabetes (n = 507), ascertained in families via a proband with known diabetes duration of 10 years or more and/or with DR, were included. MAIN OUTCOME MEASURES: Serum adiponectin was measured and insulin sensitivity was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). DR was assessed by seven-field digital fundus photography and graded using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Scale (range of severity levels, 10-85). RESULTS: Fasting adiponectin concentrations were elevated in patients with DR compared to those without (12.9 ± 0.5 vs 10.5 ± 0.5 µg/mL; P = .0004) and remained significant after adjusting for multiple covariates (age, gender, body mass index, glycosylated hemoglobin, diabetes duration, statin use, blood pressure, and renal function; P = .013 to .018). Adiponectin was also positively correlated with severity of DR in patients with nonproliferative DR (P < .0003), significant also after all covariate adjustments (P = .018). When the proliferative DR group was included, this relationship was attenuated by adjustments, possibly an influence of estimated glomerular filtration rate reduction in the proliferative DR group. HOMA-IR was not different in the DR and non-DR groups. Although elevated, adiponectin retained a typical inverse relationship with HOMA-IR in DR, similar to that seen in the non-DR group. CONCLUSIONS: Serum adiponectin is elevated in DR, is positively correlated with DR severity in Latinos with type 2 diabetes, and maintains a relationship to insulin sensitivity. Adiponectin, whether as a marker or biological mediator, may play an important role in DR, which appears to be independent of its relationship to insulin sensitivity.

Association of fasting insulin and C peptide with diabetic retinopathy in Latinos with type 2 diabetes.

OBJECTIVE: Residual insulin secretion provides important protection against the development of diabetic retinopathy in type 1 diabetes. The data to support this in type 2 diabetes are unclear. We therefore tested in type 2 diabetes whether markers of residual beta-cell function are associated with the development of diabetic retinopathy, an important microvascular complication of diabetes. DESIGN: Prospective, cross-sectional, family-based study. PARTICIPANTS: 585 Latino type 2 diabetic participants, ascertained in families via a proband either with known diabetes duration of greater than 10 years and/or with diabetic retinopathy. OUTCOME MEASURES: CIRCULATING LEVELS OF FASTING INSULIN AND C PEPTIDE MEASURED AND CORRELATED TO DEGREE OF DIABETIC RETINOPATHY, ASSESSED BY DIGITAL FUNDUS PHOTOGRAPHY AND GRADED USING THE MODIFIED AIRLIE HOUSE CLASSIFICATION AND THE EARLY TREATMENT DIABETIC RETINOPATHY STUDY SCALE (RANGE: levels 10-85). RESULTS: Fasting plasma insulin (ß=-0.29; 95% CI -0.38 to -0.20; p<0.0001) and C peptide (ß=-0.21; 95% CI -0.30 to -0.13; p<0.0001) concentrations in these diabetic participants were significantly correlated with retinopathy and its degree of severity. This relationship remained significant after adjusting for potential covariates including age, gender, glycosylated hemoglobin, duration of diabetes, blood pressure, and renal function. CONCLUSIONS: These data suggest that residual endogenous insulin secretion is associated with the presence of diabetic retinopathy and its severity in Latinos with familial type 2 diabetes. It remains to be proven whether beta-cell targeted therapies, to maintain beta-cell mass and/or function in addition to glycemic control, will further the goal of preventing diabetic microvascular disease.