Disorganization of Retinal Inner Layers (DRIL) and Neuroretinal Dysfunction in Early Diabetic Retinopathy.

Purpose: To elucidate the relationship between disorganization of retinal inner layers (DRILs) and retinal function in diabetic patients without diabetic retinopathy (DR) and with nonproliferative DR, but without diabetic macular edema (DME). Methods: Fifty-seven participants with diabetes mellitus (DM) and 18 healthy controls underwent comprehensive ophthalmic examination, fundus photography, and spectral-domain optical coherence tomography. Scans of the fovea were evaluated for the presence of DRIL. Retinal function was evaluated using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, the quick contrast sensitivity function (qCSF) on the AST Sentio Platform, short-wavelength automated perimetry (SWAP), standard automated perimetry (SAP), and frequency doubling perimetry (FDP). ANOVA and Kruskal-Wallis were used to compare retinal function in subjects with and without DRIL. Tukey-Kramer test and Wilcoxon were used for post hoc analysis. Results: DRIL was identified in 9 of 57 diabetic subjects. DRIL subjects had higher body mass index and longer diabetes duration compared to diabetic subjects without DRIL (P = 0.03 and P = 0.009, respectively). Subjects with DRIL had reduced ETDRS visual acuity (P = 0.003), contrast sensitivity function (P = 0.0003), and SAP performance (PSD, P < 0.0001) compared to controls and diabetic subjects without DRIL. Structural analysis revealed inner retinal thinning, and some outer retinal thinning, associated with DRIL. Conclusions: Diabetic subjects with DRIL have reduced retinal function compared to those without DRIL, and defective retinal lamination may be an early cellular consequence of diabetes responsible for this in some patients. Following further longitudinal studies, DRIL may be a readily available and reliable structural biomarker for reduced retinal function in early diabetic neuroretinal disease.

Multidimensional Functional and Structural Evaluation Reveals Neuroretinal Impairment in Early Diabetic Retinopathy.

Purpose: To test whether quantitative functional tests and optical coherence tomography (OCT)-defined structure can serve as effective tools to diagnose and monitor early diabetic neuroretinal disease. Methods: Fifty-seven subjects with diabetes (23 without diabetic retinopathy [no DR], 19 with mild nonproliferative diabetic retinopathy [mild NPDR], 15 with moderate to severe [moderate NPDR]), and 18 controls underwent full ophthalmic examination, fundus photography, spectral-domain optical coherence tomography (SD-OCT), e-ETDRS (Early Treatment Diabetic Retinopathy Study) acuity, and the quick contrast sensitivity function (qCSF) method. Perimetry testing included short-wavelength automated perimetry (SWAP), standard automated perimetry (SAP), frequency doubling perimetry (FDP), and rarebit perimetry (RBP). Results: ETDRS acuity and RBP were not sensitive for functional differences among subjects with diabetes. AULCSF, a metric of qCSF, was reduced in diabetics with moderate compared to mild NPDR (P = 0.03), and in subjects with no DR compared to controls (P = 0.04). SWAP and SAP mean deviation (MD) and foveal threshold (FT) were reduced in moderate compared to mild NPDR (SWAP, MD P = 0.002, FT P = 0.0006; SAP, MD P = 0.02, FT P = 0.007). FDP 10-2 showed reduced MD in moderate compared to mild NPDR (P = 0.02), and FDP 24-2 revealed reduced pattern standard deviation (PSD) in mild NPDR compared to no DR (P = 0.02). Structural analysis revealed thinning of the ganglion cell layer and inner plexiform layer (GCL+IPL) of moderate NPDR subjects compared to controls. The thinner GCL+IPL correlated with impaired retinal function. Conclusions: This multimodal testing analysis reveals insights into disruption of the neuroretina in diabetes and may accelerate the testing of novel therapies.

Overuse of colonoscopy for colorectal cancer screening and surveillance.

BACKGROUND: Ongoing efforts to increase colorectal cancer (CRC) screening rates have raised concerns that these exams may be overused, thereby subjecting patients to unnecessary risks and wasting healthcare resources. OBJECTIVE: Our aim was to measure overuse of screening and surveillance colonoscopies among average-risk adults, and to identify correlates of overuse. DESIGN, SETTING, AND PARTICIPANTS: Our approach was a retrospective cohort study using electronic health record data for patients 50-65 years old with no personal history of CRC or colorectal adenomas with an incident CRC screening colonoscopy from 2001 to 2010 within a multispecialty physician group practice. MAIN OUTCOME MEASURES: We measured time to next screening or surveillance colonoscopy and predictors of overuse (exam performed more than one year earlier than guideline recommended intervals) of colonoscopies. KEY RESULTS: We identified 1,429 adults who had an incident colonoscopy between 2001 and 2010, and they underwent an additional 871 screening or surveillance colonoscopies during a median follow-up of 6 years. Most follow-up screening colonoscopies (88%) and many surveillance colonoscopies (49%) repeated during the study represented overuse. Time to next colonoscopy after incident screening varied by exam findings (no polyp: median 6.9 years, interquartile range [IQR]: 5.1-10.0; hyperplastic polyp: 5.7 years, IQR: 4.9-9.7; low-risk adenoma: 5.1 years, IQR: 3.3-6.3; high-risk adenoma: 2.9 years, IQR: 2.0-3.4, p < 0.001). In logistic regression models of colonoscopy overuse, an endoscopist recommendation for early follow-up was strongly associated with overuse of screening colonoscopy (OR 6.27, 95% CI: 3.15-12.50) and surveillance colonoscopy (OR 13.47, 95% CI 6.61-27.46). In a multilevel logistic regression model, variation in the overuse of screening colonoscopy was significantly associated with the endoscopist performing the previous exam. CONCLUSIONS: Overuse of screening and surveillance exams are common and should be monitored by healthcare systems. Variations in endoscopist recommendations represent targets for interventions to reduce overuse.

Assessing research interest and capacity in community health centers.

OBJECTIVE: Community health centers (CHCs) have great potential to participate in the development of evidence-based primary care but face obstacles to engagement in clinical translational research. METHODS: To understand factors associated with CHC interest in building research infrastructure, Harvard Catalyst and the Massachusetts League of Community Health Centers conducted an online survey of medical directors in all 50 Massachusetts CHC networks. RESULTS: Thirty-two (64%) medical directors completed the survey representing 126 clinical sites. Over 80% reported that their primary care providers (PCPs) were slightly to very interested in future clinical research and that they were interested in building research infrastructure at their CHC. Frequently cited barriers to participation in research included financial issues, lack of research skills, and lack of research infrastructure. In bivariate analyses, PCP interest in future clinical research and a belief that involvement in research contributed to PCP retention were significantly associated with interest in building research infrastructure. CONCLUSION: CHCs critical role in caring for vulnerable populations ideally positions them to raise relevant research questions and translate evidence into practice. Our findings suggest a high interest in engagement in research among CHC leadership. CTSAs have a unique opportunity to support local CHCs in this endeavor.

Effects of trans fatty acids on glucose homeostasis: a meta-analysis of randomized, placebo-controlled clinical trials.

BACKGROUND: Although evidence from cohort studies has suggested that trans fatty acid (TFA) consumption may be associated with insulin resistance and diabetes, randomized placebo-controlled trials (RCTs) have yielded conflicting results. OBJECTIVE: In a meta-analysis, we combined all available RCTs that examined the role of TFA intake on glucose homeostasis. DESIGN: A systematic review of PubMed was performed, and a total of 7 RCTs were included in the meta-analysis. Primary outcomes were glucose and insulin concentrations. Secondary outcomes were total, LDL-, and HDL-cholesterol and triglyceride concentrations. The pooled effect size (ES) was calculated through fixed- and random-effects meta-analyses. The potential existence of publication bias was evaluated by using funnel-plot analysis. Metaregression analysis was performed to evaluate for potential dose-response relations between the ES of outcomes and TFA intake. RESULTS: Increased TFA intake did not result in significant changes in glucose or insulin concentrations. Increased TFA intake led to a significant increase in total and LDL-cholesterol [ES (95% CI): 0.28 (0.04, 0.51) and 0.36 (0.13, 0.60), respectively] and a significant decrease in HDL-cholesterol concentrations [ES (95% CI): -0.25 (-0.48, -0.01)]. Our analysis also showed the absence of publication bias and any dose-response relations between the ES and TFA intake. CONCLUSIONS: Increased TFA intake does not result in changes in glucose, insulin, or triglyceride concentrations but leads to an increase in total and LDL-cholesterol and a decrease in HDL-cholesterol concentrations. There is no evidence to support a potential benefit of the reduction of dietary TFA intake on glucose homeostasis.

Leptin as a modulator of neuroendocrine function in humans.

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions.