Risk of Diabetic Retinopathy According to Subtype of Type 2 Diabetes.

Type 2 diabetes is a heterogeneous disease that can be subdivided on the basis of ß-cell function and insulin sensitivity. We investigated the presence, incidence, and progression of diabetic retinopathy (DR) according to subtypes of type 2 diabetes. In a national cohort, we identified three subtypes of type 2 diabetes: classical, hyperinsulinemic, and insulinopenic type 2 diabetes, based on HOMA2 measurements. From the Danish Registry of Diabetic Retinopathy we extracted information on level of DR. We used several national health registries to link information on comorbidity, medications, and laboratory tests. We found individuals with hyperinsulinemic type 2 diabetes were less likely to have DR at entry date compared with those with classical type 2 diabetes, whereas individuals with insulinopenic type 2 diabetes were more likely to have DR. In multivariable Cox regression analysis, individuals with hyperinsulinemic type 2 diabetes had a decreased risk of both incidence and progression of DR compared to those with classical type 2 diabetes. We did not find any clear difference in risk of incident or progression of DR in individuals with insulinopenic compared to classical type 2 diabetes. These findings indicate that subcategorization of type 2 diabetes is important in evaluating the risk of DR.

Longitudinal bidirectional associations between diabetic retinopathy and diagnosed depression: Results from a Danish nationwide registry-based cohort study.

OBJECTIVE: Diabetic retinopathy (DR) is a feared complication and a leading course of visual impairment, but the connection between DR and depression including the direction has never been studied in a nationwide cohort. We aimed to assess, whether the associations between DR and diagnosed depression are bidirectional. METHODS: We performed a national register-based cohort study of individuals with type 2 diabetes, who attended diabetic eye screening between January 2013 and June 2022. Level of DR was extracted from the Danish Registry of Diabetic Retinopathy. The severity of DR was assessed according to the International Clinical Diabetic Retinopathy severity scale. Diagnosed depression was ascertained by physician diagnostic codes of unipolar depression (F32), recurrent depression (F33) or dysthymia (F34.1) from the Danish National Patient Register. We estimated presence of diagnosed depression according to DR level at index date and risk of diagnosed depression during follow-up using multivariable logistic and Cox regression, respectively. Secondly, we assessed whether diagnosed depression at index date could predict incident DR. RESULTS: We included 240,893 individuals with type 2 diabetes with baseline rates of diagnosed depression ranging from 5.2 to 6.0 % for DR level 1-4. At index date, individuals with type 2 diabetes and DR were less likely to have a history of diagnosed depression (multivariable adjusted OR, 0.77 [95 % CI 0.73-0.82]). In 226,523 individuals with type 2 diabetes followed for 1,159,755 person-years, 1.7 % developed at least one episode of diagnosed depression. In a model adjusted for age and sex, individuals with DR at index date had an increased risk of incident diagnosed depression compared to those without DR (HR 1.25 [95 % CI 1.16-1.36]). Adjusting for marital status, use of glucose-, lipid- and blood pressure lowering medication, HbA1c, diabetic neuropathy and Charlson comorbidity index waived the above risk (multivariable adjusted HR 1.02 [95 % CI 0.93-1.12]). Furthermore a previous history of diagnosed depression was not associated with increased risk of incident DR (multivariable adjusted HR 0.89 [95 % CI 0.77-1.03]). CONCLUSION: In this nationwide cohort study, individuals with DR at first screening were 23 % less likely to have a history of depression, but our data did not support a bidirectional association between DR and depression. Selection bias may have occurred as diagnosed depression is a known barrier for attending DR-screening.

Structural and Metabolic Retinal Changes Associated With Mild Cognitive Impairment in Type 2 Diabetes.

Type 2 diabetes is associated with cognitive impairment and a twofold increased risk of dementia compared with age-matched individuals without diabetes. Given that the eye and the brain share similar embryologic origin and anatomical features, the retina offers a unique window to the brain. In this study, we wanted to determine whether there was a difference in retinal imaging-based neuronal and vascular markers in individuals with type 2 diabetes with or without mild cognitive impairment (MCI). We included 134 persons with type 2 diabetes. Based on neuropsychological tests, the prevalence of MCI was 28%. We performed seven-field color fundus photos, optical coherence tomography (OCT), OCT-angiography (OCT-A), and retinal oximetry to analyze retinal markers. In a multivariable cluster analysis, persons with MCI had a significantly thinner macular retinal nerve fiber layer and macular ganglion cell layer, and less venular oxygen saturation in the nasal quadrant compared with those without MCI. There were no differences in retinal vessel density, fractal dimension, width, tortuosity, or OCT-A markers. People with type 2 diabetes and MCI demonstrate alterations in retinal structure and metabolism, suggesting noninvasive retinal markers may be useful to detect people with type 2 diabetes at risk for cognitive dysfunction. ARTICLE HIGHLIGHTS: Type 2 diabetes is associated with mild cognitive impairment (MCI). Therefore, retinal and cerebral neurodegeneration may run in parallel. To assess whether there was a difference in retinal structure, vessel, and metabolic parameters in individuals with MCI. We found those with MCI had a thinner macular retinal nerve fiber layer, macular ganglion cell layer, and less venular oxygen saturation. We suggest noninvasive retinal markers may be useful to detect those at risk of cognitive dysfunction.

Bariatric surgery in individuals with type 2 diabetes is not associated with short or long-term risk of diabetic retinopathy progression: results from a nationwide cohort study.

AIMS: Bariatric surgery is used to induce weight loss and glycemic stability in type 2 diabetes (T2D). It has been a concern that this may lead to early worsening of diabetic retinopathy (DR) due to a rapid decline in HbA1c. In this study, we evaluated the risk of short and long-term DR development and need for ocular intervention in an entire nation of individuals with T2D undergoing bariatric surgery. METHODS: The study comprised a national, register-based cohort of individuals with T2D screened for DR. Cases were matched by age, sex and DR level at the date of surgery (index date) with non-bariatric controls. We extracted information on DR levels, in- and outpatient treatments, pharmaceutical prescriptions and laboratory values. We evaluated worsening of DR (incident and progressive DR) at follow-up (6 and 36 months). RESULTS: Amongst 238,967 individuals with T2D, who attended diabetic eye screening, we identified 553 that underwent bariatric surgery (0.2%) and 2677 non-bariatric controls. Median age was 49 years, and 63% were female. Cases had more comorbidities, lower HbA1c as well as more frequent use of glucose-lowering and antihypertensive medication than controls at index date. In a fully adjusted logistic regression model, the risk of DR worsening for cases was not significantly different compared to controls, neither short-term (OR 0.41 [CI 95% 0.13; 1.33], p = 0.14) nor long-term (OR 0.64 [CI 95% 0.33; 1.24], p = 0.18). CONCLUSIONS: In this nationwide study, bariatric surgery did not associate with increased risk of short- or long-term DR worsening.

Retinal microvascular markers in type 2 diabetes subphenotypes and latent autoimmune diabetes of adults.

PURPOSE: To estimate if newly diagnosed patients with different subphenotypes of type 2 diabetes (T2DM) or latent autoimmune diabetes of adults (LADA) differ with respect to subclinical retinal microvascular structure or diabetic retinopathy (DR). METHODS: This population-based, cross-sectional study of 340 patients (675 eyes) classified patients with recently diagnosed T2DM in different subphenotypes according to beta cell function and insulin sensitivity in to; classical (n = 218), hyperinsulinaemic (n = 86), insulinopenic (n = 20), or LADA (n = 16). Retinal 6-field images were graded according to the International Clinical DR Severity Scale by a retinal expert. Retinal microvascular structures were analysed in eyes by a semiautomatic software. RESULTS: Median age and duration of diabetes were 58.1 (49.9; 65.5) and 0.9 (0.5; 2.4) years, respectively, and 56.8% were male. In a multivariate linear mixed model regression analysis of eyes without DR (n = 570), there was no statistically significant difference in retinal venular or arteriolar width between subtypes and patients with classical T2DM. In addition, eyes from different subphenotypes did not differ according to vessel density, tortuosity or fractal dimension. In a multivariate logistic regression model adjusted for age, sex, HbA1c, diabetes duration, body mass index, mean arterial blood pressure and history of cardiovascular disease, there was a tendency towards persons with hyperinsulinaemic T2DM to be more likely to have DR (OR 1.97, 95% CI 0.95; 4.09) compared to classical T2DM. CONCLUSION: We found no difference in retinal microvascular structure in patients with newly diagnosed subtypes of T2DM. However, DR may be more prevalent in newly diagnosed patients with hyperinsulinaemic T2DM compared to individuals with classical T2DM.

Relationship between Diabetic Retinopathy and Systemic Neurodegenerative Diseases: A Systematic Review and Meta-analysis.

TOPIC: To examine the potential role of systemic neurodegeneration, this study aimed to provide an overview of the available evidence on the relationship between diabetic retinopathy (DR) and systemic neurodegeneration. CLINICAL RELEVANCE: The association between DR and systemic neurodegeneration is inconsistent in the literature. A summary estimate on the measures of association is important to establish whether DR may be used as a risk marker of systemic neurodegeneration. METHODS: We searched the literature databases PubMed/MEDLINE, EMBASE, and Cochrane Library on October 3, 2020, for all observational studies on humans evaluating the association between DR and systemic neurodegenerative diseases. Two authors conducted the literature search, study selection, and data extraction in an independent fashion. Studies were reviewed qualitatively in text and quantitatively in meta-analyses. Heterogeneity was evaluated with Cochran's Q and I2, and Funnel plot was used to investigate for skewed results and possible publication bias. RESULTS: We identified 27 eligible studies with a total of 1 398 041 patients with diabetes. Diagnosis of DR was made using fundus photography or examination (n = 20), health registries (n = 4), was self-reported (n = 1), or was not disclosed in the remaining studies. Neurodegenerative conditions studied were cognitive impairment (n = 23), Alzheimer's disease (n = 3), and Parkinson's disease (n = 1). In cross-sectional and longitudinal studies, respectively, presence of any DR was associated with present (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.02-2.43, P = 0.043) and incident (OR, 2.36; 95% CI, 1.50-3.71, P = 0.00021) systemic neurodegeneration, but severity of DR was not associated with differences in systemic neurodegeneration (OR, 0.98; 95% CI, 0.45-2.15, P = 0.96). CONCLUSIONS: In this systematic review, DR appears to be a marker of systemic neurodegeneration. Further studies are warranted to better elucidate the clinical practical implications of this relationship.

Diabetic retinopathy as a potential marker of Parkinson's disease: a register-based cohort study.

Neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, and an association between diabetic retinopathy and Parkinson's disease has been proposed. In this nationwide register-based cohort study, we investigated the prevalence and incidence of Parkinson's disease among patients screened for diabetic retinopathy in a Danish population-based cohort. Cases (n = 173 568) above 50 years of age with diabetes included in the Danish Registry of Diabetic Retinopathy between 2013 and 2018 were matched 1:5 by gender and birth year with a control population without diabetes (n = 843 781). At index date, the prevalence of Parkinson's disease was compared between cases and controls. To assess the longitudinal relationship between diabetic retinopathy and Parkinson's disease, a multivariable Cox proportional hazard model was estimated. The prevalence of Parkinson's disease was 0.28% and 0.44% among cases and controls, respectively. While diabetic retinopathy was not associated with present (adjusted odds ratio 0.93, 95% confidence interval 0.72-1.21) or incident Parkinson's disease (adjusted hazard ratio 0.77, 95% confidence interval 0.56-1.05), cases with diabetes were in general less likely to have or to develop Parkinson's disease compared to controls without diabetes (adjusted odds ratio 0.79, 95% confidence interval 0.71-0.87 and adjusted hazard ratio 0.88, 95% confidence interval 0.78-1.00). In a national cohort of more than 1 million persons, patients with diabetes were 21% and 12% were less likely to have prevalent and develop incident Parkinson's disease, respectively, compared to an age- and gender-matched control population without diabetes. We found no indication for diabetic retinopathy as an independent risk factor for incident Parkinson's disease.