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.

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.

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.

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 (β=-0.29; 95% CI -0.38 to -0.20; p<0.0001) and C peptide (β=-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.

Retinopathy is a microvascular complication of diabetes mellitus (DM); however, it is also increasingly recognized in persons without DM. The microvascular diseases may play a prominent role in coronary heart disease (CHD) development in individuals with DM. We performed the study to evaluate the relation between non-DM retinopathy and CHD and also the association between baseline retinopathy and incidence and progression of CHD in individuals with and without DM. We included 5709 subjects with and without DM from the Multi-Ethnic Study of Atherosclerosis, who had retinal photos and coronary artery calcium score (CACS) available. We studied the association between baseline retinopathy and incidence and progression of coronary artery calcification (CAC) in subjects with and without DM. In DM group, the presence of retinopathy was significantly associated with an increased rate of CAC (RR 1.3 (95% CI [1.02, 1.66]) after adjusting for age, sex, race, follow-up time, and CHD risk factors. In non-DM group, the presence of retinopathy was not significantly associated with increased risk of CAC, however, the interaction between presence of retinopathy and DM status was not statistically significant. Within the DM group with CAC present at baseline, the presence of retinopathy was significantly associated with greater CAC progression (113 Agatson units (AU) greater, (95% CI [51-174]). In the non-DM group with present CAC at baseline; the presence of retinopathy was associated with 24 (95% CI [-0.69, 48.76]) AU higher CAC progression. All findings were adjusted for CHD risk factors. In conclusion, after adjustment for major CHD risk factors, retinopathy was associated with progression of CAC in both DM and non-DM individuals. However, the association was stronger in those with DM.

Prevention and management of coronary artery disease (CAD) is of great concern in patients with diabetes mellitus. Although the impact of coronary atherosclerosis is described well for subjects older than 40 years, the prevalence and types of coronary atherosclerosis in young patients are not well known. The aim of this study was to evaluate the prevalence, extent, severity, and volumes of coronary plaque in type 2 diabetes mellitus (T2DM) population younger than of 40 years. This prospective study enrolled 181 subjects (25-40 year old) undergoing coronary computed tomography angiography, with 86 T2DM and 95 nondiabetic age/gender-matched subjects. Coronary artery calcium (CAC), plaque assessment including total segment stenosis (sum of individual segmental stenosis), total plaque scores (sum of semiquantitative segmental plaque burden), segment involvement scores (number of segments with plaque) were evaluated. In addition, we quantitatively measured plaque volumes in total, fibrous, fibrous fatty, dense calcified, and low-attenuation plaque using novel plaque software. Compared with nondiabetic patients, the prevalence of CAD, calcified, and noncalcified plaques was higher in patients with T2DM (19% vs 58%; p <0.001). In patients with a zero CAC, T2DM had a higher prevalence (46%) of noncalcified plaque (p <0.0001). In multivariate linear regression models after adjusting for traditional cardiovascular risk factors, increased total segmental stenosis, total plaque scores, and segment involvement scores were associated with T2DM. Regarding quantitative plaque assessment, all volumes in noncalcified plaque type were approximately threefold higher in patients with T2DM. In conclusion, young patients with T2DM are susceptible to premature CAD with more calcified and noncalcified plaques. Early prevention program using computed tomography angiography might be helpful in identifying young diabetic patients with subclinical atherosclerosis.

Genetic variants contribute to normal variation of iron-related traits and may also cause clinical syndromes of iron deficiency or excess. Iron overload and deficiency can adversely affect human health. For example, elevated iron storage is associated with increased diabetes risk, although mechanisms are still being investigated. We conducted the first genome-wide association study of serum iron, total iron binding capacity (TIBC), transferrin saturation, and ferritin in a Hispanic/Latino cohort, the Hispanic Community Health Study/Study of Latinos (>12 000 participants) and also assessed the generalization of previously known loci to this population. We then evaluated whether iron-associated variants were associated with diabetes and glycemic traits. We found evidence for a novel association between TIBC and a variant near the gene for protein phosphatase 1, regulatory subunit 3B (PPP1R3B; rs4841132, β = -0.116, P = 7.44 × 10-8). The effect strengthened when iron deficient individuals were excluded (β = -0.121, P = 4.78 × 10-9). Ten of sixteen variants previously associated with iron traits generalized to HCHS/SOL, including variants at the transferrin (TF), hemochromatosis (HFE), fatty acid desaturase 2 (FADS2)/myelin regulatory factor (MYRF), transmembrane protease, serine 6 (TMPRSS6), transferrin receptor (TFR2), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ABO blood group (ABO), and GRB2 associated binding protein 3 (GAB3) loci. In examining iron variant associations with glucose homeostasis, an iron-raising variant of TMPRSS6 was associated with lower HbA1c levels (P = 8.66 × 10-10). This association was attenuated upon adjustment for iron measures. In contrast, the iron-raising allele of PPP1R3B was associated with higher levels of fasting glucose (P = 7.70 × 10-7) and fasting insulin (P = 4.79 × 10-6), but these associations were not attenuated upon adjustment for TIBC-so iron is not likely a mediator. These results provide new genetic information on iron traits and their connection with glucose homeostasis.

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.

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P < 1 × 10-6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (P < 0.05 and consistent direction of effect, and P < 5 × 10-8 after meta-analysis), including two for WHRadjBMI (rs13301996, rs79478137); one for WCadjBMI (rs3168072) and one for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI, 10 for WCadjBMI and 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity susceptibility that may be ancestry-specific.