No causal association between serum vitamin D levels and diabetes retinopathy: A Mendelian randomization analysis.

BACKGROUND AND AIM: Diabetes retinopathy (DR) is a common microvascular complication of diabetes, and it is the main cause of global vision loss. The current observational research results show that the causal relationship between Vitamin D and DR is still controversial. Therefore, we conducted a Mendelian randomization study to determine the potential causal relationship between serum 25-hydroxyvitamin D 25(OH)D and DR. METHODS AND RESULTS: In this study, we selected aggregated data on serum 25(OH)D levels (GWAS ID: ebi-a-GCST90000615) and DR (GWAS ID: finn-b-DM_RETINOPATHY) from a large-scale GWAS database. Then use MR analysis to evaluate the possible causal relationship between them. We mainly use inverse variance weighted (IVW), supplemented by MR Egger and weighted median methods. Sensitivity analysis is also used to ensure the stability of the results, such as Cochran's Q-test, MR-PRESSO, MR-Egger interception test, and retention method. The MR analysis results showed that there was no significant causal relationship between 25(OH)D and DR (OR = 1.0128, 95%CI=(0.9593,1.0693), P = 0.6447); Similarly, there was no significant causal relationship between DR and serum 25 (OH) D levels (OR = 0.9900, 95% CI=(0.9758,1.0045), P = 0.1771). CONCLUSION: Our study found no significant causal relationship between serum 25(OH)D levels and DR, and vice versa. A larger sample size randomized controlled trial is needed to further reveal its potential causal relationship.

Diabetic Retinopathy Leading to Blindness- A Review.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes that damages the retina, leading to blindness. People with type 1 diabetes are at greater risk of developing DR than people with type 2 diabetes. Diabetic retinopathy may be divided into two primary categories: Proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR). There are multiple risk factors for the onset and progression of diabetic retinopathy, such as hypertension, obesity, smoking, duration of diabetes, and genetics. Numerous investigations have evaluated the levels of a wide range of inflammatory chemokines within DR patients' serum, vitreous, and aqueous fluids. In diabetic retinopathy, the vitreous fluid exhibited rises in angiogenic factors like platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF) or declines in antiangiogenic factors like pigment epithelium-derived factor (PEDF). For prevention of diabetic retinopathy, more physical activity as well as less sedentary behavior were linked to a reduced likelihood of DR. Supplementing with nutraceuticals containing vitamins (B1, B2, B6, B12, C, D, E, and l-methyl folate) and mineral (zinc) can help decrease or avoid an outbreak of DR. Only laser photocoagulation and Anti-vascular endothelial growth factor (Anti-VEGF) injections are advised as favorable therapies in severe retinopathy. When it comes to treating DR's VEGF levels, inflammation, oxidative stress, apoptosis, and angiogenesis, Traditional Chinese medicine (TCM) has an excellent future.

Association Between Atrial Fibrillation and Diabetes-Related Complications: A Nationwide Cohort Study.

OBJECTIVE: This study aimed to investigate the associations between concurrent atrial fibrillation and diabetes-related complications among patients with diabetes. RESEARCH DESIGN AND METHODS: This nationwide observational cohort study used the health checkup database from the Korean National Health Insurance Service. Patients diagnosed with diabetes who underwent health checkups between 2009 and 2012 were investigated. The patients with atrial fibrillation were matched in a 1:5 ratio with those without atrial fibrillation using propensity scores. Study outcomes included macrovascular, microvascular (diabetic retinopathy and diabetic nephropathy), and diabetic foot complications. The risks of clinical outcomes were measured using hazard ratios (HRs) with 95% CIs. RESULTS: A total of 65,760 patients with diabetes were analyzed (54,800 without atrial fibrillation and 10,960 with atrial fibrillation). After well-balanced propensity score matching, atrial fibrillation was associated with significantly higher risks of macrovascular complications (HR 1.12, 95% CI 1.09-1.16), diabetic nephropathy (HR 1.23, 95% CI 1.16-1.30), and diabetic foot complications (HR 1.13, 95% CI 1.09-1.17) compared with no atrial fibrillation, while the risk of diabetic retinopathy was comparable (HR 0.99, 95% CI 0.96-1.03). Patients with atrial fibrillation had a significantly higher risk of diabetic foot amputation (HR 4.12, 95% CI 1.98-8.56). CONCLUSIONS: Among patients with diabetes, concurrent atrial fibrillation was associated with increased risks for diabetes-related macrovascular complications, diabetic nephropathy, and diabetic foot. Such patients require holistic management to reduce the risk of adverse outcomes.

Patients views on a new surveillance pathway involving allied non-medical staff for people with treated diabetic macular oedema and proliferative diabetic retinopathy.

BACKGROUND/OBJECTIVE: To explore acceptability by patients and health care professionals of a new surveillance pathway for people with previously treated and stable diabetic macular oedema (DMO) and/or proliferative diabetic retinopathy (PDR). SUBJECT/METHODS: Structured discussions in 10 focus groups with patients; two with ophthalmic photographers/graders, and one with ophthalmologists, held across the UK as part of a large diagnostic accuracy study (EMERALD). RESULTS: The most prominent issues raised by patients concerned (i) expertise of the various professionals within clinic, (ii) quality of interactions with clinic professionals, especially the flow of information from professionals to patients, and (iii) wish to be treated holistically. Ophthalmologists suggested such issues could be best dealt with via a programme of patient education and tended to overlook deeper implications of patient concerns for the organisation of services. CONCLUSION: For patients, the clinical service should not only include the identification and treatment of disease but also exchange of information, reassurance, and mitigation of anxiety. Alterations in the standard care pathway need to take account of such concerns and their implications, in addition to any assessments of 'efficiency' that may flow from changes in diagnostic technology, or the division of professional labour.

Persistent diabetic macular edema: Definition, incidence, biomarkers, and treatment methods.

Intravitreal antivascular endothelial growth factor (anti-VEGF) treatment has drastically improved the visual and anatomical outcomes in patients with diabetic macular edema (DME); however, success is not always guaranteed, and a proportion of these eyes demonstrate persistent DME (pDME) despite intensive treatment. While standardized criteria to define these treatment-resistant eyes have not yet been established, many studies refer to eyes with no clinical response or an unsatisfactory partial response as having pDME. A patient is considered to have pDME if the retinal thickness improves less than 10-25% after 6 months of treatment. A range of treatment options have been recommended for eyes with pDME, including switching anti-VEGF agents, using corticosteroids and/or antioxidant drugs in adjunct with anti-VEGF therapy, and vitrectomy. In addition, multimodal imaging of DME eyes may be advantageous in predicting the responsiveness to treatment; this is beneficial when initiating alternative therapies. We explore the literature on persistent DME regarding its defining criteria, incidence, the baseline biological markers that may be useful in anticipating the response to treatment, and the available treatment options.

Magnesium Depletion Score Predicts Diabetic Retinopathy Risk among Diabetes: Findings from NHANES 2005-2018.

Magnesium is essential for material and energy metabolism. The magnesium depletion score (MDS) is recognized as a more valuable and reliable predictor of body magnesium status than any other clinical used markers such as serum and urine magnesium. However, research on the relationship between MDS and diabetic retinopathy (DR) is limited. As a result, the current study sought to assess this issue in diabetic samples from a large population-based database in the United States. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. MDS was calculated, and multivariate logistic regression analysis was applied to evaluate the presence of association between variables and DR risk. A total of 4308 participants was comprised in this study. Samples with DR consumed less magnesium (259.1 ± 113.6 vs 269.8 ± 113.2 mg, P < 0.001), and their MDS levels differed significantly from non-DR participants (P < 0.001). Increased dietary magnesium was linked to a lower incidence of DR (all P for trend < 0.05), and patients with a high level of MDS were more prone to DR (P = 0.001). Furthermore, subgroup analysis revealed that high (Q3) amount magnesium supplements was associated with lower DR risk when MDS was none to low or middle level (both P = 0.02). Our results indicated that MDS levels are associated with DR risk and that magnesium supplementation is benefit to DR prevention.

Do Nutrients and Nutraceuticals Play a Role in Diabetic Retinopathy? A Systematic Review.

Diabetic retinopathy (DR) is a multifactorial neuro-microvascular disease, whose prevalence ranges from 25% to 60% of subjects affected by diabetes mellitus, representing the main cause of legal blindness in adults of industrialized countries. The treatment of advanced stage of DR is based on invasive and expensive therapies, while few strategies are available for the early stage or prevention. The mechanisms underlying DR involve a complex interplay between the detrimental effects of hyperglycemia, dyslipidemia, hypoxia, and oxidative stress, providing several pathways potentially targeted by nutrients and nutraceuticals. In this study, we conducted a systematic review of observational and interventional studies, evaluating the effect of nutrients and/or nutraceuticals on the risk of DR and their potential use for the treatment of patients with DR. The analysis of the 41 included studies (27 observational and 14 interventional studies) suggests a promising preventive role of some nutrients, in particular for vitamins B (i.e., B1 and B12), D, and E. However, further investigations are necessary to clarify the potential clinical application of nutraceuticals in the prevention and treatment of DR.

Burden and Risk Factors of Diabetic Retinopathy Among Diabetic Patients Attending a Multispecialty Tertiary Eye Hospital in Nepal.

INTRODUCTION: As the number of people with diabetes mellitus is increasing because of urbanization and change in dietary habits and sedentary lifestyle, the number of diabetic retinopathy is also expected to increase in future. [1] [sa2] We aimed to find out the prevalence of diabetic retinopathy and associated risk factors among diabetic patients in the tertiary eye hospital. MATERIALS AND METHODS: This is the observational cross-sectional study enrolling 420 diabetic patients visiting the multispecialty tertiary eye hospital between March 2020 and February 2021. Anthropometry measurement, laboratory risk profiles and blood pressure were recorded Results: The prevalence of any diabetic retinopathy, proliferative diabetic retinopathy, and diabetic macular edema were 30.96 %, 6.19 %, and 5.95 % respectively. The duration of DM (p=0.001), hypertension (p=0.04), high SBP (p=0.023), abdominal obesity (p=0.015), high LDL(p=0.011) cholesterol, low HDL cholesterol(p=0.012), and creatinine (p=0.001) were associated with DR in our study. CONCLUSION: A holistic approach should target to control the modifiable risk factors like blood sugar, blood pressure, lipid profile, kidney function, and obesity to prevent DR. Anthropometric assessment of waist to height and waist circumference should be included in the holistic health promotion strategy in Nepal as BMI may not be risk factors for DR in Nepalese people.

Diabetic retinopathy screening and treatment through the Brazilian National Health Insurance.

The current study aimed to investigate diabetic retinopathy (DR) screening and treatment coverages among diabetic patients evaluated through the Brazilian National Health Insurance from 2014 to 2019. The Brazilian Public Health System Information Database was used as the primary data source. DR screening coverage was calculated as the rate of procedures of clinical dilated fundus exam and color fundus photograph over the number of diabetic patients. DR treatment coverage was calculated as the rate of procedures of intravitreal injection, photocoagulation, and panretinal photocoagulation over the number of diabetic patients presumably in need of DR treatment. The overall screening coverage increased from 12.1% in 2014 to 21.2% in 2019 (p < 0.001) with substantial regional discrepancies so that North region was the only one with no changes along the period. The overall treatment coverage increased from 27.7% in 2014 to 44.1% in 2019, with Southeast and Midwest absorbing the demand for service from the North, Northeast and South. Despite an improvement along the past years, both screening and treatment coverages for DR in diabetes patients are ineffective in Brazil. Public health policies should address resources disparities throughout the country aiming to offer same healthcare conditions to patients regardless their geographic location.

The Association of Homocysteine and Diabetic Retinopathy in Homocysteine Cycle in Chinese Patients With Type 2 Diabetes.

Objective: This study aimed to explore the relationship between homocysteine (Hcy) and diabetic retinopathy (DR) and the impacts of the Hcy pathway on this relationship against this background. Methods: This study retrieved 1979 patients with type 2 diabetes (T2D) from the First Affiliated Hospital of Liaoning Medical University in Jinzhou, Liaoning Province, China. Multiple logistic regression was used to analyze the effects of Hcy cycle on the relationship between Hcy and DR. Spearman's rank correlation analysis was used to analyze the correlation between risk factors related to DR progression and Hcy. Finally, the results of logistic regression were supplemented by mediation analysis. Results: We found there was a negative correlation between low concentration of Hcy and DR (OR : 0.83, 95%CI: 0.69-1). After stratifying all patients by cysteine (Cys) or Methionine (Met), this relationship remained significant only in low concentration of Cys (OR: 0.75, 95%CI: 0.61-0.94). Through the RCS curve, we found that the effect of Hcy on DR presents a U-shaped curve relationship. Mediating effect in Met and Hcy cycles was also significant [Total effect c (OR: 0.968, 95%CI: 0.938-0.998), Direct effect path c' (OR: 0.969, 95%CI: 0.940-0.999), Path a (OR: 1.047, 95%CI: 1.004-1.091), Path b (OR: 0.964, 95%CI: 0.932-0.998)]. Conclusions: The relationship between Hcy and DR presents a U-shaped curve and the homocysteine cycle pathway has an impact on it. And too low concentration of Hcy indicates a lack of other substances, such as vitamins. It is suggested that the progression of DR is the result of a combination of many risk factors. Further prospective studies are needed to determine the role of Hcy in the pathogenesis of DR.

Visual Acuity Outcomes in Diseases Associated with Reduced Visual Acuity: An Analysis of the National Health Insurance Service Database in Korea.

Visual acuity declines with age, and disease-related visual acuity changes vary. We evaluated factors affecting visual acuity and age-related visual acuity in diseases associated with reduced visual acuity such as hypertension, diabetes mellitus (DM), glaucoma, and diabetic retinopathy (DR). The Korean National Health Insurance Service 2015-2016 data were analyzed for age-related visual acuity changes and prevalence of diseases associated with reduced visual acuity. Among 993,062 participants, the prevalence rates of hypertension, DM, glaucoma, and DR were 27.0%, 15.1%, 13.8%, and 2.7%, respectively. Despite having the lowest prevalence, DR alone or DR with hypertension and glaucoma resulted in low visual acuity. Correlation analysis between disease frequency and mean age-related visual acuity revealed higher positive correlations in DR and hypertension than in DM and glaucoma, indicating lower visual acuity. Odds ratios for low visual acuity in cases including one disease such as hypertension, DM, glaucoma, and DR were 1.73, 1.23, 1.04, and 1.52, respectively. The prevalence and number of diseases associated with reduced visual acuity increased with age, and visual acuity decreased. The leading causes of vision loss were DR as a single disease and hypertension as a concomitant disease. Therefore, age-related vision management, through periodic eye examination and correction with age, should be performed along with management of diabetes and hypertension.

Coffee consumption and diabetic retinopathy in adults with diabetes mellitus.

We aimed to evaluate the association between the prevalence of diabetic retinopathy (DR) and coffee consumption in a Korean population. This cross-sectional study was based on data from the 2008-2011 Korean National Health and Nutrition Survey. Among 37,753 survey participants, the data of 1350 subjects with type 2 diabetes who underwent DR examination were analyzed. DR was graded using the modified Airlie House classification system. Coffee consumption data were obtained through food frequency questionnaires and categorized into four groups: almost none, < 1 cup/day, 1 cup/day, and ≥ 2 cups/day. The relationship between DR and coffee consumption was evaluated using multivariable logistic regression models adjusted for age, sex, education, occupation, income, smoking, alcohol intake, body mass index, physical activity, hypertension, dyslipidemia, diabetes duration, and glycated hemoglobin. The prevalence of DR was 20.0%. Non-proliferative DR was observed in 87.8% of all DR patients, and proliferative DR in 12.2%. The prevalence of DR and vision-threatening DR showed a significantly decreasing tendency according to daily coffee consumption (P for trend 0.025 and 0.005, respectively) after adjustment for possible confounders. This tendency was more prominent in those aged < 65 years (P for trend 0.005 and 0.003, respectively). Our findings suggest coffee consumption might be associated with DR reduction especially in Koreans with diabetes mellitus aged < 65 years.

Vitamin D Deficiency in Patients with Diabetes in French Guiana: Epidemiology and Relation with Microvascular and Macrovascular Complications.

Vitamin D (VD) insufficiency is common among patients with diabetes in French Guiana. The study aimed to evaluate the prevalence of VD deficiency in the different type of diabetes encountered and to analyze the relationship between VD deficiency and diabetes complications. METHODS: An observational study was conducted between May 2019 and May 2020 in French Guiana, based on data from the CODIAM study (Diabetes Cohort in French Amazonia), describing the characteristics of patients with diabetes mellitus. Among 600 patients enrolled with diabetes, 361 had an available VD assay. RESULTS: The mean 25(OH)VD (hydroxycalciferol) level was 27.9 ng/mL. The level of VD was inversely proportional to the HbA1c (glycated hemoglobin) level. Patients with angina pectoris had a greater proportion of deficiencies VD < 20 ng/mL than those without angina. By contrast, patients with retinopathy had higher vitamin D concentrations than those without retinopathy. There was no association between vitamin D and arteriopathy, stroke, nephropathy and polyneuropathy. VD deficiency was more frequent in women, and in patients with a high school education. CONCLUSION: The prevalence of VD deficiency was high in patients with diabetes in French Guiana, emphasizing the importance of VD supplementation.

Perceived barriers and enablers to the provision of diabetic retinopathy screening for young adults: a cross-sectional survey of healthcare professionals working in the UK National Diabetic Eye Screening Programme.

INTRODUCTION: Diabetic retinopathy screening (DRS) attendance in young adults is consistently below recommended levels. The aim of this study was to conduct a survey of screening providers in the UK Diabetic Eye Screening Programme (DESP) to identify perceived barriers and enablers to DRS attendance in young adults and elicit views on the effectiveness of strategies to improve screening uptake in this population. RESEARCH DESIGN AND METHODS: Members of the British Association of Retinal Screening (n=580) were invited to complete an anonymous online survey in July 2020 assessing agreement with 37 belief statements, informed by the Theoretical Domains Framework (TDF) of behavior change, describing potential barrier/enablers to delivering DRS for young adults and further survey items exploring effectiveness of strategies to improve uptake of DRS. RESULTS: In total, 140 (24%) responses were received mostly from screener/graders (67.1%). There was a high level of agreement that the DESP had a role in improving attendance in young adults (96.4%) and that more could be done to improve attendance (90.0%). The most commonly reported barriers related to TDF domains Social influences and Environmental context and resources including lack of integration of DRS with other processes of diabetes care, which limited the ability to discuss diabetes self-management. Other barriers included access to screening services and difficulties with scheduling appointments. Less than half (46.4%) of respondents reported having a dedicated strategy to improve screening uptake in young adults. Strategies perceived to be effective included: screening within the community; prompts/reminders and integrating eye screening with other diabetes services. CONCLUSIONS: Screening providers were concerned about screening uptake in young adults, although many programs lacked a dedicated strategy to improve attendance. Problems associated with a lack of integration between DRS with other diabetes care processes were identified as a major barrier to providing holistic care to young adults and supporting diabetes self-management.

Real-world artificial intelligence-based opportunistic screening for diabetic retinopathy in endocrinology and indigenous healthcare settings in Australia.

This study investigated the diagnostic performance, feasibility, and end-user experiences of an artificial intelligence (AI)-assisted diabetic retinopathy (DR) screening model in real-world Australian healthcare settings. The study consisted of two components: (1) DR screening of patients using an AI-assisted system and (2) in-depth interviews with health professionals involved in implementing screening. Participants with type 1 or type 2 diabetes mellitus attending two endocrinology outpatient and three Aboriginal Medical Services clinics between March 2018 and May 2019 were invited to a prospective observational study. A single 45-degree (macula centred), non-stereoscopic, colour retinal image was taken of each eye from participants and were instantly screened for referable DR using a custom offline automated AI system. A total of 236 participants, including 174 from endocrinology and 62 from Aboriginal Medical Services clinics, provided informed consent and 203 (86.0%) were included in the analysis. A total of 33 consenting participants (14%) were excluded from the primary analysis due to ungradable or missing images from small pupils (n = 21, 63.6%), cataract (n = 7, 21.2%), poor fixation (n = 2, 6.1%), technical issues (n = 2, 6.1%), and corneal scarring (n = 1, 3%). The area under the curve, sensitivity, and specificity of the AI system for referable DR were 0.92, 96.9% and 87.7%, respectively. There were 51 disagreements between the reference standard and index test diagnoses, including 29 which were manually graded as ungradable, 21 false positives, and one false negative. A total of 28 participants (11.9%) were referred for follow-up based on new ocular findings, among whom, 15 (53.6%) were able to be contacted and 9 (60%) adhered to referral. Of 207 participants who completed a satisfaction questionnaire, 93.7% specified they were either satisfied or extremely satisfied, and 93.2% specified they would be likely or extremely likely to use this service again. Clinical staff involved in screening most frequently noted that the AI system was easy to use, and the real-time diagnostic report was useful. Our study indicates that AI-assisted DR screening model is accurate and well-accepted by patients and clinicians in endocrinology and indigenous healthcare settings. Future deployments of AI-assisted screening models would require consideration of downstream referral pathways.

Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy.

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.

Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy.

Oxidative stress has been postulated as an underlying pathophysiologic mechanism of diabetic retinopathy (DR), the main cause of avoidable blindness in working-aged people. This review addressed the current daily clinical practice of DR and the role of antioxidants in this practice. A systematic review of the studies on antioxidant supplementation in DR patients was presented. Fifteen studies accomplished the inclusion criteria. The analysis of these studies concluded that antioxidant supplementation has a IIB level of recommendation in adult Type 1 and Type 2 diabetes mellitus subjects without retinopathy or mild-to-moderate nonproliferative DR without diabetic macular oedema as a complementary therapy together with standard medical care.

Religiousness, Anxiety and Depression in Patients with Glaucoma, Age-Related Macular Degeneration and Diabetic Retinopathy.

BACKGROUND: Many chronic medical conditions such as glaucoma, senile macular degeneration and diabetic retinopathy are further complicated by emotional and psychological disorders. Religiousness represents a part of a social culture and has a significant role in the prevention of mental difficulties of the patients, especially those belonging to older population. The aim of this study was to investigate the connection between religiousness, anxiety, and depression in patients with glaucoma, age-related macular degeneration and diabetic retinopathy and to test their connection related to different diagnosis. SUBJECTS AND METHODS: This cross-sectional study included 163 patients divided into three groups (glaucoma group, senile macular degeneration group and diabetic retinopathy group). Respondents voluntarily agreed to participate in the study and with assistance they fully completed the Scale of Religiousness, Hospital Anxiety and Depression Scale, General Health Questionnaire and demographic information (age, gender, education, employment and marital status). RESULTS: The results showed noticeable religiosity of the respondents (M=18.31, SD=5.28), but also the presence of anxiety (M=7.55, SD=3.73), especially in patients with glaucoma, as well as impaired mental health in AMD patients (M=19.56, SD=4.14). No differences were found in the severity of anxiety, depression, general health and religiosity between groups, but the presence of depression in subjects with age-related macular degeneration significantly affects the level of religiosity (p=0.032). CONCLUSION: These results unequivocally point to the need for further research and raising awareness of all health professionals about the importance of a holistic approach to the patient regardless of his diagnosis in order to identify the possible effective ways to deal with chronic disease considering all levels of patient's needs.

Sleep variability, 6-sulfatoxymelatonin, and diabetic retinopathy.

PURPOSE: Recent evidence suggests that diabetic retinopathy (DR) is associated with abnormal melatonin regulation, possibly related to dysfunction of the melanopsin-expressing intrinsically photosensitive retinal ganglion cells. This study explored melatonin regulation in type 2 diabetes (T2D) patients with DR and its relation to sleep and circadian functioning. METHODS: Thirty-five participants (10 non-diabetic controls, 10 T2D without DR, and 15 T2D with DR) were recruited. Overnight urine 6-sulfatoxymelatonin (aMT6s) and objective sleep and wrist activity (7-day actigraphy) were obtained. RESULTS: After adjusting for covariates, having T2D with DR was significantly associated with lower urinary aMT6s (ß = - 1.369, p = 0.004) compared with controls, while having T2D without DR was not (p = 0.418). T2D patients with DR reported poorer sleep quality (p = 0.014) and had greater variability of sleep duration (p = 0.017) than others, while no differences were found in sleep duration, efficiency, and rest-activity rhythm. After adjusting for covariates, lower nocturnal aMT6s was significantly associated with greater sleep variability. CONCLUSION: T2D patients with DR exhibited low overnight production of aMT6s which likely contributed to sleep irregularities possibly due to weak circadian signaling. Whether or not melatonin supplementation could improve health in T2D patients with DR remains to be explored.

Synergy between the pay-for-performance scheme and better physician-patient relationship might reduce the risk of retinopathy in patients with type 2 diabetes.

AIMS/INTRODUCTION: This study investigated whether participation by patients with type 2 diabetes in Taiwan's pay-for-performance (P4P) program and maintaining good continuity of care (COC) with their healthcare provider reduced the likelihood of future complications, such as retinopathy. MATERIALS AND METHODS: The analysis used longitudinal panel data for newly diagnosed type 2 diabetes from the National Health Insurance claims database in Taiwan. COC was measured annually from 2003 to 2013, and was used to allocate the patients to low, medium and high groups. Cox regression analysis was used with time-dependent (time-varying) covariates in a reduced model (with only P4P or COC), and the full model was adjusted with other covariates. RESULTS: Despite the same significant effects of treatment at primary care, the Diabetes Complications Severity Index scores were significantly associated with the development of retinopathy. After adjusting for these, the hazard ratios for developing retinopathy among P4P participants in the low, medium and high COC groups were 0.594 (95% confidence interval [CI] 0.398-0.898, P = 0.012), 0.676 (95% CI 0.520-0.867, P = 0.0026) and 0.802 (95% CI 0.603-1.030, P = 0.1062), respectively. Thus, patients with low or median COC who participated in the P4P program had a significantly lower risk of retinopathy than those who did not. CONCLUSIONS: Diabetes care requires a long-term relationship between patients and their care providers. Besides encouraging patients to participate in P4P programs, health authorities should provide more incentives for providers or patients to regularly survey patients' lipid profiles and glucose levels, and reward the better interpersonal relationship to prevent retinopathy.