Higher Risk Of Diabetic Retinopathy Research Articles

Association Between Triglyceride-Glucose Index and Diabetic Retinopathy: A Meta-Analysis.

The objective of this study was to assess the relationship between the triglyceride-glucose (TyG) index, a recently proposed marker of insulin resistance, and the occurrence of diabetic retinopathy (DR), a complication associated with cardiovascular risk. This systematic review and meta-analysis aimed to evaluate the association between the TyG index and DR. To achieve the objective of the meta-analysis, an extensive search was conducted on databases such as PubMed, Embase, and Web of Science to identify observational studies with longitudinal follow-up. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. Twelve observational studies from 11 reports were included in the meta-analysis, which involved 16 259 patients with type 2 diabetes (T2D). Among them, 4302 (26.5%) were diagnosed as DR. Pooled results showed that a higher TyG index was associated with a higher risk of DR [odds ratio (OR) for the fourth versus the first quartile of TyG index: 1.91, 95% confidence interval (CI): 1.44 to 2.53, p<0.001; I2=72%]. Meta-analysis of TyG index analyzed in continuous variable showed consistent results (OR for per 1 unit increment of TyG index: 1.41, 95% CI: 1.08 to 1.86, p=0.01; I2=82%). Subgroup analysis showed that adjustment of HbA1c or the duration of diabetes did not significantly affect the results (p for subgroup difference all>0.05). In conclusion, a high TyG index was associated with the risk of DR in T2D patients.

Risk of diabetic retinopathy and diabetic macular oedema with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database.

A protective role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development of diabetic retinopathy and diabetic macular oedema has been described in some recent studies, which may extend beyond glycaemic control. We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin. This is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n=176,409; GLP1-ra + insulin, n=207,034) were compared against a control cohort (insulin with no SGLT2i/GLP1-ra, n=1,922,312). Kaplan-Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA1c, BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed. SGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208). Our study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated retinal imaging are required to determine the causal relationship with these therapies.

The Difference Between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate and Risk of Diabetic Microvascular Complications Among Adults With Diabetes: A Population-Based Cohort Study.

The impact of the difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) on diabetic microvascular complications (DMCs) remains unknown. We investigated the associations of eGFRdiff with overall DMCs and subtypes, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). This prospective cohort study included 25,825 participants with diabetes free of DMCs at baseline (2006 to 2010) from the UK Biobank. eGFRdiff was calculated using both absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based calculations. Incidence of DMCs was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with overall DMCs and subtypes. During a median follow-up of 13.6 years, DMCs developed in 5,753 participants, including 2,752 cases of DR, 3,203 of DKD, and 1,149 of DN. Each SD decrease of eGFRabdiff was associated with a 28% higher risk of overall DMCs, 14% higher risk of DR, 56% higher risk of DKD, and 29% higher risk of DN. For each 10% decrease in eGFRrediff, the corresponding hazard ratios (95% CIs) were 1.16 (1.14, 1.18) for overall DMCs, 1.08 (1.05, 1.11) for DR, 1.29 (1.26, 1.33) for DKD, and 1.17 (1.12, 1.22) for DN. The magnitude of associations was not materially altered in any of the sensitivity analyses. Large eGFRdiff was independently associated with risk of DMCs and its subtypes. Our findings suggested monitoring eGFRdiff in the diabetes population has potential benefit for identification of high-risk patients.

Associations of antidiabetic drugs with diabetic retinopathy in people with type 2 diabetes: an umbrella review and meta-analysis.

Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes. A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052). With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99). Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.

SR1375: Phase 1 results of a novel, orally administered lipoprotein‐associated phospholipase A2 inhibitor targeting diabetic macular oedema

Aims/Purpose: Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity have been linked to a higher risk of diabetic retinopathy and inhibiting Lp‐PLA2 activity showed improvement in vision and macular oedema for patients with diabetic macular oedema (DME). SR1375 is an orally available, selective inhibitor of Lp‐PLA2 that shows significant retinal vascular leakage reduction in preclinical studies, and is being developed for DME. A phase 1, randomized, double‐blind, placebo‐controlled study is conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SR1375 in healthy subjects.Methods: A total of 72 healthy subjects were enrolled, with 54 had received SR1375. 48 subjects were in the single ascending dose arms (1, 3, 10, 30, 100 and 200 mg) while 24 subjects were in the multiple ascending dose arms (5, 15 and 50 mg once daily for 14 days).Results: SR1375 was safe and well tolerated across all doses. It had excellent oral absorption with the exposure level increasing in an approximately dose proportional manner after single and multiple doses. The elimination of SR1375 was slow with a long t1/2 ranging from 28.8 to 90.0 h. The accumulation of SR1375 was not significant after multiple administrations. The plasma inhibition on Lp‐PLA2 activity by SR1375 was strong (up to 95%) and enduring, which was correlated with the concentration of SR1375 (IC50 as 1.41 ng/mL) and almost returned to basal level when the concentration of SR1375 was low enough.Conclusions: SR1375 was safe and effective in inhibiting plasma Lp‐PLA2. The safety and PK/PD profile supports the once daily therapy. A Phase 2 study for DME patients is planned later this year. It would be a 12‐week randomized, double‐blind and placebo‐controlled trial. The primary objective is to assess the effect of SR1375 on vision and oedema.

Ten-year clinical characteristics of patients with early-onset type 2 diabetes: A single-center experience in China.

The incidence of type 2 diabetes in China has exhibited an increasing trend, including younger individuals, over the past years. Early-onset type 2 diabetes (EOT2D) refers to diabetes diagnosed before 40 years of age. These patients have poor metabolic control and are highly susceptible to diabetic complications, which poses challenges for treatment. However, few studies have reported on the treatment of EOT2D. We determined clinical features and trends in drug use in patients with type 2 diabetes mellitus (T2DM). This retrospective study was performed at the Endocrinology Ward, Peking Union Medical College Hospital (PUMCH). "Diabetes" was used when searching PUMCH's Electronic Medical Record Analytical Database to obtain clinical data of patients between January 2013 and May 2022. The analysis included 1590 patients with T2DM. Among them, 609 (38.3%) had EOT2D. Compared with late-onset type 2 diabetes (LOT2D) patients, EOT2D patients exhibited worse glycemic control and higher body weight and lipid levels despite significant age differences. EOT2D patients also had a higher risk of diabetic retinopathy and nephropathy. Under the general trend of increasing use of dipeptidylpeptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 agonists, patients with EOT2D were more likely to use organ-protective drugs. Compared with LOT2D patients, EOT2D patients have a longer course of diabetes, worse metabolic control, and a higher rate of developingmicrovascular complications. The administration of combined therapy, including new agents, may require consideration when selecting hypoglycemic agents for treating EOT2D.

Prevalence and Determinants of Diabetic Retinopathy Among Type 2 Diabetic Patients in Saudi Arabia: A Systematic Review.

Diabetic retinopathy (DR) is a preventable complication of diabetes; however, it is a serious one if not early recognized and properly managed as it can lead to visual impairment. This review aimed to summarize the prevalence and determinants of DR among type 2 diabetic patients in Saudi Arabia. Eligible articles for this systematic review were quantitative observational studies that were English-published between 2015 and 2021, peer-reviewed, and conducted on patients with type 2 diabetes mellitus (DM). The studies were obtained by searching PubMed/Medline, ScienceDirect, Cochrane Library Database, and Google Scholar. The risk of bias was assessed using the National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. Out of 16 preliminary studies, 12 were eligible for inclusion in this systematic review. One study was a chart review, one was a prospective study, and the remaining were cross-sectional studies. Regarding the study tool, retinopathy was diagnosed by an ophthalmologist using fundus photography and/or slit-lamp examination in most of the studies (n=7). However, some studies reported obtaining data from patient interviews and medical files (n=4). Concerning the outcome, an overall high prevalence of DR (ranging between 6.25% and 88.1%) and some significant associated risk factors were determined, including longer duration of diabetes, older age, poor blood pressure control, poor glycemic control, and physical inactivity. Most studies showed moderate overall quality. In conclusion, DR is a common complication of type 2 diabetes in Saudi Arabia. Some avoidable risk factors are identified, through which the doctors can identify patients at high risk of DR through early screening and can, thus, initiate prompt treatment to reduce the risk of vision deterioration.

The Frequency of Undiagnosed Celiac Disease in Youth with Type 1 Diabetes and Its Association with Diabetic Retinopathy: The SEARCH for Diabetes in Youth Study

Aims. Celiac disease (CD) in adults with type 1 diabetes has been associated with increased cardiovascular risk and the earlier occurrence of diabetes-associated complications. In the Search for Diabetes in Youth study, we aimed to assess the frequency of CD and the potential for undiagnosed CD among youth with childhood onset type 1 diabetes. In addition, we assessed the burden of cardiovascular risk factors and diabetes-associated complications in youth with type 1 diabetes by CD status and IgA tissue transglutaminase autoantibody (tTGA) levels. Methods. 2,444 youths with type 1 diabetes completed a CD questionnaire and underwent tTGA testing. Integrating the celiac disease questionnaire and tTGA results for this cross-sectional analysis, participants were categorized as follows: (1) reported CD; (2) seropositive for CD (no reported CD and seropositive tTGA); and (3) type 1 diabetes only (comparison group: no reported CD and seronegative tTGA). Subanalyses were performed on those with no reported CD and tTGA ≥10x ULN, designated potentially undiagnosed CD. Cardiovascular risk factors and diabetes-associated complications were evaluated by CD status and tTGA levels utilizing a Poisson model to estimate relative risk. Results. Reported CD in youths with type 1 diabetes was 7%. Seropositivity for tTGA with no reported CD was present in 4%, and 1.2% had potentially undiagnosed CD. Youths with potentially undiagnosed CD had a 2.69x higher risk of diabetic retinopathy than comparison group. In addition, CD with tTGA &lt;0.05 (controlled CD) was associated with lower HbA1c. Conclusions. Undiagnosed CD is likely present in youths with type 1 diabetes and potentially undiagnosed CD is associated with a higher risk of diabetic retinopathy. These findings indicate the importance of routine screening for CD in type 1 diabetes in youths.

Qualitative analysis of nailfold capillaries in diabetes and diabetic retinopathy using dermatoscope in patients with coloured skin.

Introduction Diabetes mellitus (DM) is associated with significant morbidity and mortality due to vascular complications. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes. Videocapillaroscope has been the predominant tool for nailfold capillary analysis. We aimed at using the commonly available handheld dermatoscope and observe changes in the nailfold capillaries as a part of evaluating diabetic microvascular involvement. Materials and methods A cross-sectional observational study involving 262 patients of diabetes mellitus and 150 controls was conducted for nailfold capillaroscopic changes using a hand-held dermatoscope over a period of 1 year. Results All the capillaroscopic variables like tortuosity, increased capillary density, neoangiogenesis, microhaemorrhages, avascular areas, crossing and meandering capillaries and receding capillaries were significantly more among diabetic than healthy controls. Patients with diabetic retinopathy had significant nailfold capillaroscopic features as compared to patients without DR (P value < 0.001). Neoangiogenesis, receding capillaries and avascular area were significantly higher in proliferative DR as against nonproliferative DR (P < 0.001). A positive association was found between the duration of DM and HbA1c values and NFC features. A decrease in the visualisation of NFC features was noted with increasing skin tone. The difference was significantly more between Fitzpatrick skin phototypes 4 and 5. Limitations The study was limited by its qualitative nature of accessing parameters as precise quantitative assessment of various findings cannot be done by a hand-held dermatoscope. Conclusion Nailfold capillaroscopy is a quick, cost-effective screening tool for identifying patients at high risk of DR in patients with skin of colour. NFC findings may mirror DR changes. The qualitative findings of NFC using a hand-held dermatoscope were comparable to other modes of nailfold capillaroscopy.

Diabetic retinopathy prediction using Progressive Ablation Feature Selection: A comprehensive classifier evaluation

Diabetic Retinopathy (DR) is the leading cause of blindness among adults in the U.S. Since DR is asymptomatic at the early stages, diabetic patients do not feel the uncomfortable ophthalmic exams necessary. However, existing DR diagnosis approaches mainly rely on fundus images that require access to ophthalmologists and special equipment, which are typically unavailable in rural areas. Machine-learning-based predictive models could help primary care physicians identify patients with a high risk of DR and confidently recommend ophthalmic exams. However, existing DR prediction models require a large number of independent variables, making them challenging to utilize in a clinical setting. In this study, we designed a novel “Progressive Ablation Feature Selection method with XGBoost” which successfully reduced the number of predictors from 25 to 9 to create a more user-friendly DR prediction model without sacrificing accuracy with an Area Under Curve of 96.61%. This study suggests that diabetic retinopathy is closely associated with creatinine, followed by neuropathy, hematocrit, BUN, nephropathy, albumin, race, calcium, and sodium. We provide an insight into each selected feature and its medical associations with DR. The result of this work will help physicians use a small set of available variables to identify high-risk diabetic patients prone to develop DR. Medical doctors thus can intervene at the proper time to prevent vision loss. • More than 2.3 million diabetics across over 10 million visits analyzed. • A novel progressive ablation feature selection method. • Comes with medical analysis of selected features. • Diabetic retinopathy is closely associated with creatinine, followed by neuropathy, hematocrit, BUN, nephropathy, albumin, race, calcium, sodium, and anion gap blood.

Parapapillary Choroidal Microvasculature Predicts Diabetic Retinopathy Progression and Diabetic Macular Edema Development: A Three-Year Prospective Study

To determine the predictive value of the microcirculation of the optic nerve head by swept-source optical coherence tomography angiography for identifying individuals with high risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. Prospective observational cohort study. A total of 946 patients (1879 eyes) with type 2 diabetes mellitus were recruited who had no DR or mild nonproliferative DR at baseline, and no DME. All subjects underwent 3×3 mm swept-source optical coherence tomography angiography centered on the optic nerve head to generate angiograms in 4 layers: radial peripapillary plexus, superficial retinal capillary plexus (SCP), deep retinal capillary plexus, and choriocapillaris (CC). The CC flow deficit percentage (CC FD%), vessel density (VD), and perfusion density (PD) were quantified. During the 3 consecutive years of follow-up, 312 eyes (16.60%) experienced DR progression and 115 eyes (6.12%) developed DME. The DR progression was related to a lower VD of the SCP (relative risk per standard deviation decrease, 95% confidence interval): 1.30, 1.14-1.48; P < .001), a lower PD of the SCP (1.41, 1.24-1.60; P < .001), a lower VD of the radial peripapillary plexus (1.23, 1.08-1.40; P=.002), and an elevated CC FD% (1.62, 1.40-1.88; P < .001). The DME occurrence was associated with a lower VD of SCP (1.35, 1.09-1.66; P=.005), a lower PD of SCP (1.29, 1.05-1.59; P=.016), and a higher CC FD% (1.29, 1.03-1.61; P < .001). The CC FD% significantly improved the predictive power, with the increase of the C-statistic for DR progression and DME occurrence by 3.83% (P=.002) and 5.24% (P < .001), respectively. This study provides the first longitudinal evidence suggesting that peripapillary CC FD% can improve the prediction of DR progression and DME development beyond traditional risk factors.

Association Between Serum Albumin Level and Microvascular Complications of Type 2 Diabetes Mellitus.

ObjectiveTo analyze the associations between serum albumin (sALB) level and diabetic microvascular complications, including diabetic retinopathy (DR) and diabetic kidney disease (DKD), in patients with type 2 diabetes mellitus (T2DM).MethodsThis retrospective study included 951 hospitalized patients with T2DM who had completed screening for DR and DKD during hospitalization. Patients were divided into three groups according to sALB tertiles. Multivariate logistic regression analysis was used to assess the association of sALB with microvascular complications.ResultsThe prevalence of DR, DKD and macroalbuminuria increased with decreasing sALB levels. Multivariate logistic regression analysis showed that lower levels of sALB (Q1) were associated with higher risk of DR (odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.12–2.26), DKD (OR: 3.00, 95% CI: 2.04–4.41) and macroalbuminuria (OR: 9.76, 95% CI: 4.62–20.63) compared with higher levels of sALB (Q3) after adjustment for other risk factors. After stratification by sex and age, the effect of lower levels of sALB (Q1) on DR incidence was more obvious in patients with male (OR: 1.60, 95% CI: 1.00–2.56), and aged<65 years (OR: 1.74, 95% CI: 1.14–2.65) (P < 0.05 for all); the effect of lower levels of sALB (Q1) on the incidence of DKD was significant in both males (OR: 3.78, 95% CI: 2.26–6.32) and females (OR: 2.35, 95% CI: 1.26–4.35) (P < 0.05 for all), while only the age <65 years (OR: 3.46, 95% CI: 2.16–5.53) was significant in the age subgroup (P < 0.001).ConclusionDecreased sALB levels may be an independent risk indicator of DR and DKD in patients with T2DM, and significantly associated with DKD progression. For DR screening, special attention should be paid to men aged <65 years, while screening for DKD should pay attention to people <65 years old.

1144-P: Risk of Diabetic Retinopathy in Early-Onset Type 2 Diabetes in Mexico

Early onset type 2 diabetes (EOD) seems to have an aggressive disease progression with a higher risk for diabetes complications at an early age. Screening for Diabetic Retinopathy (DR) is poorly executed in primary care of low-and-middle income countries. Thus, we aimed to analyze the characteristics of EOD in comparison with later-onset group. Data were obtained from the largest cohort of patients evaluated for DR within the primary care in Mexico (DIABEMPIC program) . Early and later-onset groups were defined as age of diagnosis &amp;lt;40 and ≥40 years, respectively. DR assessment by an ophthalmologist included fundoscopy with a mydriatic camera. Proliferative DR and severe non-proliferative DR were considered as severe DR. A total of 3063 patients with T2D were included of which 9had EOD. Prevalence of DR and severe DR was significantly higher in the EOD group than in the later-onset group (p&amp;lt;0.0001) ; however, an increase in the prevalence of DR and severe DR was observed after years of diagnosis (p&amp;lt;0.0001) . Burden of DR at different diabetes durations are shown in Table 1. EOD was associated with increased risk of DR compared with late onset T2D (OR 2.18, 95%CI 1.85-2.57) . In conclusion, EOD patients with regular primary care presented a higher risk of DR and of severe DR not only explained for longer disease duration. Our study enhances the need for the management of DR risk factors and proper screening of DR in patients with T2D, especially in EOD. Disclosure R.Silva-tinoco: n/a. E.León-garcía: None. J.Ochoa-moreno: n/a. O.Lopez-arellano: None. T.Cuatecontzi-xochitiotzi: None. D.Cabrera-gerardo: n/a. V.Delatorre-saldaña: None. L.Castillo-martinez: None. F.Bernal-ceballos: None. E.B.Guzman: None. S.Bouchan-delino: None. A.Ramirez: None.

Novel clusters of newly-diagnosed type 2 diabetes and their association with diabetic retinopathy: a 3-year follow-up study.

Cluster analysis may assist in stratifying heterogeneous clinical presentations of type 2 diabetes (T2D). However, the association of cluster-based subgroups with diabetes-related outcomes such as diabetic retinopathy remains unclear. This study was aimed to address this issue with novel clusters of T2D derived from four simple parameters. We developed a k-means clustering model in participants with newly diagnosed T2D (N = 1910) from the SENSIBLE and SENSIBLE-Addition studies, based on body mass index (BMI), waist circumference (WC), mean arterial pressure (MAP), and hemoglobin A1c (HbA1c). Diabetic retinopathy was ascertained with the protocol from the Early Treatment of Diabetic Retinopathy Study. Participants (N = 515) without diabetic retinopathy at baseline were followed-up for 3years. Logistic regression analyses were performed to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Three clusters were identified, with cluster 0, 1 and 2 accounting for 48.2, 8.9 and 42.9%, respectively. Participants with T2D were featured by the lowest BMI, WC, MAP, and HbA1c in cluster 0, poor glycemic condition in cluster 1, and the highest BMI, WC, and MAP in cluster 2. Compared with cluster 0, cluster 1 was associated with increased odds of diabetic retinopathy in both the cross-sectional study (OR 6.25, 95% CI: 3.19-12.23) and the cohort study (OR 9.16, 95% CI: 2.08-40.34), while cluster 2 was not. Moreover, most participants remained their clusters unchanged during follow-up. Our cluster-based analysis showed that participants with poor glycemic condition rather than high blood pressure and obesity had higher risk of diabetic retinopathy.

Vitamin D Deficiency Is Significantly Associated with Retinopathy in Type 2 Diabetes Mellitus: A Case-Control Study

Aim: Results from meta-analyses point to an association between vitamin D deficiency and the onset of diabetic retinopathy (DR). The objectives of the present study were to evaluate the association of vitamin D for the development of DR and to determine the levels of vitamin D associated with a greater risk of DR. Methods: Between November 2013 and February 2015, we performed a case-control study based on a sample of patients with diabetes in Spain. The study population comprised all patients who had at least one evaluable electroretinogram and recorded levels of 25(OH)D. We collected a series of analytical data: 25(OH)D, 1,25(OH)2D, iPTH, calcium, albumin, and HbA1c. Glycemic control was evaluated on the basis of the mean HbA1c values for the period 2009–2014. A logistic regression analysis was performed to identify the variables associated with DR. Results: The final study sample comprised 385 patients, of which 30 (7.8%) had DR. Significant differences were found between patients with and without DR for age (69.54 vs. 73.43), HbA1c (6.68% vs. 7.29%), years since diagnosis of diabetes (10.9 vs. 14.17), level of 25(OH)D (20.80 vs. 15.50 ng/mL), level of 1,25(OH)2D (35.0 vs. 24.5 pg/mL), treatment with insulin (14.9% vs. 56.7%), hypertension (77.7% vs. 100%), cardiovascular events (33.2% vs. 53.3%), and kidney failure (22.0% vs. 43.3%). In the multivariate analysis, the factors identified as independent risk factors for DR were treatment of diabetes (p = 0.001) and 25(OH)D (p = 0.025). The high risk of DR in patients receiving insulin (OR 17.01) was also noteworthy. Conclusions: Levels of 25(OH)D and treatment of diabetes were significantly associated with DR after adjusting for other risk factors. Combined levels of 25(OH)D < 16 ng/mL and levels of 1,25(OH)2D < 29 pg/mL are the variables that best predict the risk of having DR with respect to vitamin D deficiency. The risk factor with the strongest association was the treatment of type 2 diabetes mellitus. This was particularly true for patients receiving insulin, who had a greater risk of DR than those receiving insulin analogues. However, further studies are necessary before a causal relationship can be established.

Screening for diabetic retinopathy with different levels of financial incentive in a randomized controlled trial.

Aims/IntroductionTo examine the impact of different levels of financial incentive in terms of fee subsidization on diabetic retinopathy screening in the private primary care setting in Hong Kong.Materials and MethodsAll general practitioners working in the private sector and registered in two electronic public databases were invited to participate. Consecutive patients with diabetes mellitus were then recruited by the participating practitioners. The recruited participants were randomly allocated to one of three screening groups with different fee levels (HK$0, HK$150 [US$19], HK$300 [US$39]) in a randomized controlled trial. Screening uptake and severity of diabetic retinopathy detected were compared.ResultsOut of 1,688 eligible practitioners, 105 participated and invited 402 patients, with 239 initially agreeing to participate (59.5%). After randomization, 78, 75 and 76 participants in the HK$0, HK$150 and HK$300 fee groups, respectively, reconfirmed their participation and were offered screening at the relevant fee. The uptake of screening was 79.5% (62/78), 81.3% (61/75) and 63.2% (48/76), in the HK$0, HK$150 and HK$300 groups, respectively (P < 0.018). Being in the HK$150 fee group was associated with higher uptake of screening than being in the HK$300 fee group (odds ratio 2.31, P = 0.039). No significant difference was found in the prevalence of any diabetic retinopathy (33.9%, 27.9% and 37.5%, P = 0.378) or sight‐threatening diabetic retinopathy (4.8%, 8.2% and 16.7%; P = 0.092) among the groups.ConclusionA screening fee of HK$150, representing approximately a half subsidy, appears to be as effective in maximizing uptake as a full subsidy (HK$0) and without deterring those at high risk of diabetic retinopathy from screening.

Identification of two novel subgroups in patients with diabetes mellitus and their association with clinical outcomes: A two‐step cluster analysis

Aims/IntroductionThe aim of this study was to determine whether distinct subphenotypes of patients with type 2 diabetes in the European classification exist in Chinese populations, and to further establish novel subphenotypes more suitable for Chinese populations.Material and MethodsThe research retrospectively analyzed 5414 patients with type 2 diabetes from the National Clinical Research Center for Metabolic Diseases Diabetes Center in China, and a two‐step cluster analysis was carried out. First, we confirmed the European classification in Chinese populations by six parameters, including age at disease onset, body mass index, glycosylated hemoglobin, homeostatic model assessment 2 to estimate β‐cell function and insulin resistance, and glutamate decarboxylase antibodies. Furthermore, triglycerides and uric acid were added to refine the cluster analysis, and Cox regression was used to evaluate the risk of diabetic complications.ResultsJust three clusters were replicated in our cohort according to Emma Ahlqvist's European classification. When other variables were added to the cluster analysis, seven subgroups were identified, including five clusters of the European classification and two novel subgroups, namely, uric acid‐related diabetes and inheritance‐related diabetes. Compared with patients with inheritance‐related diabetes, patients with severe insulin‐resistant diabetes showed a higher risk of diabetic peripheral neuropathy, hypertension and chronic kidney disease, and the uric acid‐related diabetes subgroup showed a higher risk of coronary heart disease, cerebral vascular disease and end‐stage renal disease. Patients with severe insulin‐deficient diabetes showed a higher risk of diabetic retinopathy and diabetic foot than those with inheritance‐related diabetes. Furthermore, there were sex‐specific associations between subgroups and clinical outcomes. No significant difference was observed in the prevalence of cancer in each subgroup.ConclusionsSeven subgroups of type 2 diabetes were identified in Chinese populations, with distinct characteristics and disparate clinical outcomes. This etiology‐based stratification might contribute to the diagnosis and management of type 2 diabetes.

Birth Weight and Diabetic Retinopathy: Results From the Population-Based Gutenberg Health Study (GHS)

ABSTRACT Purpose This study investigates the relationship between diabetic retinopathy (DR) and birth weight (BW) in diabetic subjects sampled from the general population. Methods The Gutenberg Health Study (GHS) is a population-based, observational cohort study in participants aged from 35 to 74 years. Criteria for diabetes diagnosis were HbA1c ≥6.5% at study entry, a doctor-diagnosis of diabetes, or diabetes medication. The presence of DR was determined by evaluating fundus photographs. BW was assessed by self-reports. GHS participants were divided into three different BW groups (low: <2500 g; normal: 2500–4000 g; high:>4000 g). Logistic regression analysis was conducted as uni- and multivariable analysis with adjustment for age and sex. Effect mediators were separately investigated. Results A total of 1,124 GHS participants (7.5% of the cohort) had diabetes at study entry. Of these, 402 subjects (35.8%) had gradable fundus photographs, reported BW data and were included into this study. Overall, 91/402 subjects (23%) had DR. With regard to BW groups, DR was descriptively more frequent in subjects with low (28.1% [95%-CI: 14.4–47.0%; n = 32]) and high BW (30.8% [95%-CI: 19.1–45.3%; n = 52]) compared to normal BW (20.8% [95%-CI: 16.5–25.7%; n = 318]). Both high and low BW were associated with DR in multivariable analysis (high: OR = 1.68, p = .037; low: OR = 1.81, p = .05). The BW effect was mediated by duration of diabetes in both BW groups and by arterial hypertension in the low BW group. Conclusion Low and high BW in persons with diabetes is related to higher risk of diabetic retinopathy. Longer duration of diabetes and higher prevalence of arterial hypertension are factors in these subjects explaining the elevated risk.

Aldose reductase (AC)n gene polymorphism in Iranian patients with type 2 diabetic microangiopathy; a case-control study.

(AC)n promoter region of the aldose reductase (ALR) genes polymorphism has been associated with diabetic microvascular complications (MVCs). The aim of this study was to find the relationship between dinucleotide repeat (AC)n polymorphisms of the ALR gene and the occurrence of MVCs, such as diabetic retinopathy, neuropathy, and nephropathy in Iranian type 2 diabetic (T2D) patients. This prospective case-control study was performed on T2D patients who were categorized into two groups based on the presence or absence of diabetic microangiopathy. All patients were provided informed consent. After extracting genomic DNA, the (AC)n of the ALR gene was determined using Polymerase chain reaction (PCR). Thirteen alleles of the (AC)n gene polymorphism were detected including Z + 16, Z + 14, Z + 8, Z + 6, Z + 4, Z + 2, Z, Z-2, Z-4, Z-6, Z-8, Z-10, and Z-12. The frequency of the Z-4 allele was significantly higher in patients with retinopathy, nephropathy, and autonomic neuropathy compared with those with long-term uncomplicated diabetes (P < 0.001, P < 0.001, P = 0.031, respectively). After controlling for baseline risk factors, we found that the carrier of the Z-4 allele of ALR (AC)n polymorphism had a higher risk of diabetic retinopathy and diabetic nephropathy (P < 0.001). The homozygosity for the Z-4 allele was found to be associated with diabetic microangiopathy. Our results showed that ALR (AC)n gene polymorphism in Iranian patients with type 2 diabetes independently, predispose retinal, renal and neural microvascular to diabetic complications.

Prevalence of diabetic retinopathy in children and adolescents at an urban tertiary eye care center.

Diabetic retinopathy (DR) is a serious complication that can progress to sight-threatening disease. The prevalence of DR in youth with diabetes has been reported to be 3.8% to 20%. We aimed to evaluate the prevalence of DR among youth with diabetes at a large ophthalmologic referral center. Secondary goals were to determine the risk factors for DR and severity of disease. Retrospective chart review of 343 patients with diabetes, <21 years of age, seen at a tertiary referral eye care center from 2013 to 2018. The study included 343 patients, of which 293 had type 1 diabetes (T1D) and 50 had type 2 diabetes (T2D). Thirteen of 343 patients had DR, with an overall incidence of 3.8% (3.4% in T1D and 6% T2D). DR severity included nine with mild non-proliferative, three moderate non-proliferative, and one with proliferative DR. Patients with hemoglobin A1c (HbA1c) > 8% had a higher risk of DR (P = .049). In this cohort, none of the patients with an HbA1c <8% had DR. In the multivariate analysis, a higher systolic blood pressure was marginally associated with risk for DR (P = .07). We found lower prevalence of DR in youth with diabetes than previously reported. The incidence of DR was higher among patients with T2D and occurred with a shorter duration of disease, as compared with T1D. While the incidence of DR in youth with T1D is low, with the increasing incidence of T2D in adolescents and early risk for DR, early screening must be emphasized.