Association of continuous subcutaneous insulin therapy and diabetic retinopathy in type 1 diabetes: A national cohort study.

AIM: This study aimed to investigate the short-and long-term effect on diabetic retinopathy (DR) in individuals with type 1 diabetes treated with continuous subcutaneous insulin injections (CSII) compared to those using multiple daily injections (MDI). METHODS: We conducted a register-based matched cohort study utilizing data from the Danish Registry of Diabetic Retinopathy as well as several other national Danish health registers. Our cohort consisted of all individuals with type 1 diabetes who attended the Danish screening program for DR from 2013 to 2022. We included individuals registered with CSII treatment, and compared them to individuals using MDI, matched by age, sex, and DR level. Cox regression analysis was performed to evaluate the outcomes. RESULTS: The study included 674 individuals treated with CSII and 2006 matched MDI users. In our cohort 53.4 % were female and median age was 36 (IQR 27-47). Average follow-up risk-time was 4.8 years. There was no difference in the risk of DR worsening between the CSII group and MDI group (HR 1.05 [95%CI 0.91; 1.22], p = 0.49). However, an increased risk of focal photocoagulation was observed in the CSII group (HR 2.40 [95%CI 1.11; 5.19], p = 0.03). CONCLUSIONS: Our findings indicate that CSII treatment does not confer a significant difference in the overall short- and long-term risk of DR worsening or ocular intervention compared to MDI treatment. These results provide insights into the DR outcomes of CSII treatment in individuals with type 1 diabetes.

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.

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.

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.

Inverse Cross-sectional and Longitudinal Relationships between Diabetic Retinopathy and Obstructive Sleep Apnea in Type 2 Diabetes: Results from a National Screening Program.

Purpose: In previous smaller studies, associations were demonstrated between diabetic retinopathy (DR) and obstructive sleep apnea (OSA), but longitudinal relationships have not been evaluated in larger cohorts. The aim of the present study was to assess the cross-sectional and prospective associations between DR and OSA in a national cohort of patients with type 2 diabetes. Design: Cross-sectional and 5-year longitudinal registry-based cohort study. Participants: For cases, we included 153 238 patients with type 2 diabetes who had attended diabetic eye screening and were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each of these were matched by 5 control participants without diabetes of the same age and gender (n = 746 148). Methods: Exposure and outcome data as well as systemic morbidity and use of medications were identified in national registers, including the DiaBase, the Danish National Patient Register, the Danish National Prescription Registry, and the Danish Civil Registration System. The index date was defined as the date of the first DR screening registered in DiaBase. Main Outcome Measures: Exposure was defined as present and level-specific DR, and main outcomes were crude, age- and gender-adjusted, and multivariable adjusted odds ratios (ORs) for prevalent OSA as well as hazard ratios (HR) for 5-year incident OSA and DR. Results: Patients with type 2 diabetes independently were more likely to have prevalent OSA (OR, 2.01; 95% confidence interval [CI], 1.95-2.08) and to develop OSA within 5 years (HR, 1.55; 95% CI, 1.46-1.64). Patients with type 2 diabetes and DR at baseline were less likely to have prevalent OSA (OR, 0.57; 95% CI, 0.52-0.62) or to demonstrate incident OSA (HR, 0.86; 95% CI, 0.74-0.99). Likewise, patients with OSA had a lower risk to develop DR (HR, 0.83; 95% CI, 0.74-0.92). Conclusions: In a registry-based national cohort study, patients with type 2 diabetes had a higher risk of OSA. However, a 43% decreased risk of prevalent OSA was demonstrated in patients with DR, and prospectively, OSA and DR both were related inversely with each other.

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.

Cystic fibrosis-related diabetes: the presence of microvascular diabetes complications.

OBJECTIVE: Cystic fibrosis (CF)-related diabetes has been regarded as a mild form of diabetes with a low risk of severe diabetes complications. The prevalence of CF-related diabetes increases with age, resulting in a 50% prevalence of diabetes at age 30 years. We sought to investigate whether microvascular complications in CF-related diabetes appear with a relevant frequency. RESEARCH DESIGN AND METHODS: Thirty-eight patients aged 30 (range 18-55) years with CF-related diabetes for 20 (0-31) years were screened for diabetes complications. Because of chronic pulmonary infections, the majority of patients were regularly treated with aminoglycoside and cyclosporine given frequently. RESULTS: Since the pharmacological treatment of lung transplant patients could influence metabolical regulation and renal function, the results are given separately for nontransplanted (n = 29) and transplanted (n = 9) CF patients. Nine patients (27%) had retinopathy, two of which had proliferative retinopathy and needed laser treatment. Lung transplantation did not affect the prevalence of retinopathy. In nontransplanted patients, nine had hypertension, three microalbuminuria, and one elevated creatinine. None had macroalbuminuria. In transplanted patients, eight of nine had hypertension, two had microalbuminuria, and none had macroalbuminuria. Seven of nine lung transplant patients had elevated plasma creatinine, and severely reduced glomerular filtration rate was significantly more frequent. CONCLUSIONS: A high frequency of diabetic retinopathy was found in patients with insulin-treated CF-related diabetes, stressing the need for a regular screening program as in type 1 diabetes. Severely impaired kidney function was common in lung transplant patients, probably secondary to cyclosporine treatment.

Thickening of inner retinal layers in the parafovea after bariatric surgery in patients with type 2 diabetes.

PURPOSE: Bariatric surgery dramatically improves the metabolic profile in patients with type 2 diabetes (T2D). We have previously reported a thickening of the retina after bariatric surgery and aimed to investigate these subclinical changes in retinal thickness and vessel calibres in more detail. METHODS: We examined 51 patients with T2D 2 weeks before and 1, 3, 6 and 12 months after bariatric surgery. Retinal thickness was measured with optical coherence tomography and automated segmentation in the fovea, parafovea and perifovea in each retinal layer. Retinal vessels were semiautomatically measured in a zone 0.5-1 disc diameters from the optic disc. RESULTS: The total macula thickened with a peak after 6 months in both univariate (2.7 ± 0.4 µm, p < 0.001) and multivariate analysis (2.2 ± 0.7 µm, p = 0.001). The thickening was most prominent in the parafoveal ring 1-3 mm from the centre and in the retinal nerve fibre layer and outer nuclear layer. A fall in HbA1c (p = 0.01) and longer duration of diabetes (p = 0.01) were associated with more thickening. The central retinal artery equivalent widened 22.1 µm (±8.9, p = 0.01) in the multivariate analysis 12 months postoperatively. A reduction in blood pressure was associated with less widening of the arterioles (p = 0.01). CONCLUSION: Patients with T2D had thickening of the retina after gastric bypass surgery with a peak 6 months postoperatively. The thickening was most pronounced in the retinal nerve fibre layer and the outer nuclear layer of the parafovea. In multivariate analysis, the central retinal artery equivalent increased at 12 months.

Pregnancy-induced increase in circulating IGF-I is associated with progression of diabetic retinopathy in women with type 1 diabetes.

OBJECTIVE: To evaluate the influence of Insulin-like Growth factor-I (IGF-I) and Placental Growth Hormone (GH) on progression of diabetic retinopathy during pregnancy in women with type 1 diabetes. DESIGN: Observational study of 88 consecutive pregnant women with type 1 diabetes for median 16.5 years (range 1-36) and HbA(1c) 6.6% (5.2-10.5) in early pregnancy. At 8, 14, 21, 27 and 33 weeks blood samples were drawn for measurement of IGF-I, placental GH and Hemoglobin A(1c) (HbA(1c)) and blood pressure was recorded. Fundus photography was performed at 8 and 27 weeks. Diabetic retinopathy was classified in five stages. Progression was defined as deterioration of at least one stage of diabetic retinopathy and/or development of macular edema on at least one eye. RESULTS: Placental GH and IGF-I levels increased throughout pregnancy and new onset or progression of diabetic retinopathy occurred in 22 (25%). A steeper increase in women with progression of diabetic retinopathy resulted in higher IGF-I levels at 27 weeks (p=0.01) and 16% higher IGF-I levels throughout pregnancy (p=0.02) compared with women without progression while similar levels of placental GH (p=0.58) and HbA(1c) (p=0.85) were observed throughout pregnancy. In a multivariate logistic regression analysis, progression of diabetic retinopathy was associated with higher IGF-I levels at 33 weeks (odds ratio 2.0 [95% confidence interval 1.1-3.6], p=0.02) and higher systolic blood pressure at 8 weeks (1.9 [1.1-3.2], p=0.02) independent of placental GH and HbA(1c) levels. CONCLUSIONS: Pregnancy-induced increase in IGF-I levels is associated with progression of diabetic retinopathy in women with type 1 diabetes.

[Diabetic retinopathy during pregnancy]. / Diabetisk retinopati under graviditet.

INTRODUCTION: The aim was to evaluate the prevalence and progression of diabetic retinopathy during pregnancy in women with type 1 or type 2 diabetes. MATERIAL AND METHODS: Dilated fundal photography was performed at approximately 10 and 28 gestational weeks in 58 and 18 women with type 1 and type 2 diabetes, respectively. Retinopathy was classified as five stages +/- macular oedema. Progression was defined as deterioration corresponding to at least one stage between the two examinations. Clinical parameters were obtained from the medical records. RESULTS: Diabetic retinopathy was found in 36 (62%) women with type 1 and three (17%) with type 2 diabetes at the first examination. In 26 (34%) retinopathy progressed; four women developed proliferations, three macular oedema and three reduction of visual acuity >/=0.2 on Snellen's chart in at least one eye. HbA1c in early pregnancy was the only significant predictor of progression (odds ratio = 1.75, 95% confidence interval = 1.09-2.82). Progression of retinopathy also tended to be associated with type 1 diabetes and long diabetes duration. CONCLUSION: The risk of progression of diabetic retinopathy during pregnancy was considerable, especially among women with high HbA1c values in early pregnancy. A few women developed proliferations, macular oedema and reduction of visual acuity. Development of sight-threatening alterations during pregnancy remains a clinical problem.