Dataset Information

Diabetic Retinopathy and Dementia in Type 1 Diabetes.

ABSTRACT: OBJECTIVE:Retinopathy impacts over one-third of those with diabetes mellitus and is associated with impaired cognitive performance and cerebrovascular lesions in middle-aged adults with type 1 diabetes. However, the association between diabetic retinopathy (DR) and risk of dementia in type 1 diabetes is unknown. We investigated the association between DR and incident dementia in a large, elderly population with type 1 diabetes. METHODS:A cohort of 3742 patients with type 1 diabetes aged 50 years and above was followed from January 1, 1996 to September 30, 2015 for incident dementia. DR diagnoses were identified from electronic medical records. Age as timescale Cox proportional hazard models evaluated associations between time-updated DR and dementia risk. Models were adjusted for demographics, severe glycemic events, glycosylated hemoglobin, and vascular comorbidities. RESULTS:Among 3742 patients with type 1 diabetes (47% female, 21% nonwhite), 182 (5%) were diagnosed with dementia during a mean follow-up of 6.2 years. No significant association was found between DR and incident dementia in the main analyses [adjusted Hazard Ratio=1.12; 95% confidence interval, 0.82-1.54), nor among subgroup restricted to those aged 60 years and above or 70 years and above. CONCLUSIONS:DR was not associated with risk of dementia, suggesting that pathophysiological processes underlying dementia may be different in type 1 versus type 2 diabetes.

SUBMITTER: Rodill LG

PROVIDER: S-EPMC5963957 | biostudies-literature | 2018 Apr-Jun

REPOSITORIES: biostudies-literature

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Diabetic Retinopathy and Dementia in Type 1 Diabetes.

Rodill Liora G LG Exalto Lieza G LG Gilsanz Paola P Biessels Geert Jan GJ Quesenberry Charles P CP Whitmer Rachel A RA

Alzheimer disease and associated disorders 20180401 2

<h4>Objective</h4>Retinopathy impacts over one-third of those with diabetes mellitus and is associated with impaired cognitive performance and cerebrovascular lesions in middle-aged adults with type 1 diabetes. However, the association between diabetic retinopathy (DR) and risk of dementia in type 1 diabetes is unknown. We investigated the association between DR and incident dementia in a large, elderly population with type 1 diabetes.<h4>Methods</h4>A cohort of 3742 patients with type 1 diabete ...[more]

PMID: 29261519

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Project description:BackgroundWe examined components of systemic and intestinal renin-angiotensin system on gut barrier permeability, glucose homeostasis, systemic inflammation, and progression of diabetic retinopathy (DR) in human subjects and mice with type 1 diabetes (T1D).MethodsT1D individual with (n=18) and without (n=20) DR and controls (n=34) were examined for changes in gut-regulated components of the immune system, gut leakage markers (FABP2 [fatty acid binding protein 2] and peptidoglycan), and Ang II (angiotensin II); Akita mice were orally administered a Lactobacillus paracasei (LP) probiotic expressing humanized ACE2 (angiotensin-converting enzyme 2) protein (LP-ACE2) as either a prevention or an intervention. Akita mice with genetic overexpression of humanAce2 by small intestine epithelial cells (Vil-Cre.hAce2KI-Akita) were similarly examined. After 9 months of T1D, circulatory, enteral, and ocular end points were assessed.ResultsT1D subjects exhibit elevations in gut-derived circulating immune cells (ILC1 cells) and higher gut leakage markers, which were positively correlated with plasma Ang II and DR severity. The LP-ACE2 prevention cohort and genetic overexpression of intestinal ACE2 preserved barrier integrity, reduced inflammatory response, improved hyperglycemia, and delayed development of DR. Improvements in glucose homeostasis were due to intestinal MasR activation, resulting in a GSK-3β (glycogen synthase kinase-3 beta)/c-Myc (cellular myelocytomatosis oncogene)-mediated decrease in intestinal glucose transporter expression. In the LP-ACE2 intervention cohort, gut barrier integrity was improved and DR reversed, but no improvement in hyperglycemia was observed. These data support that the beneficial effects of LP-ACE2 on DR are due to the action of ACE2, not improved glucose homeostasis.ConclusionsDysregulated systemic and intestinal renin-angiotensin system was associated with worsening gut barrier permeability, gut-derived immune cell activation, systemic inflammation, and progression of DR in human subjects. In Akita mice, maintaining intestinal ACE2 expression prevented and reversed DR, emphasizing the multifaceted role of the intestinal renin-angiotensin system in diabetes and DR.

Project description:BackgroundThe proportion of patients with diabetic retinopathy (DR) has grown with increasing number of diabetes mellitus patients in the world. It is among the major causes of blindness worldwide. The main objective of this study was to identify contributing risk factors of DR among people with type II diabetes mellitus.MethodA sample of 191 people with type II diabetes mellitus was selected from the Black Lion Specialized Hospital diabetic unit from 1 March 2018 to 1 April 2018. A multivariate stochastic regression imputation technique was applied to impute the missing values. The response variable, DR is a categorical variable with two outcomes. Based on the relationship derived from the exploratory analysis, the odds of having DR were not necessarily linearly related to the continuous predictors for this sample of patients. Therefore, a semiparametric model was proposed to identify the risk factors of DR.ResultFrom the sample of 191 people with type II diabetes mellitus, 98 (51.3%) of them had DR. The results of semiparametric regression model revealed that being male, hypertension, insulin treatment, and frequency of clinical visits had a significant linear relationships with the odds of having DR. In addition, the log- odds of having DR has a significant nonlinear relation with the interaction of age by gender (for female patients), duration of diabetes, interaction of cholesterol level by gender (for female patients), haemoglobin A1c, and interaction of haemoglobin A1c by fasting blood glucose with degrees of freedom [Formula: see text], respectively. The interaction of age by gender and cholesterol level by gender appear non significant for male patients. The result from the interaction of haemoglobin A1c (HbA1c) by fasting blood glucose (FBG) showed that the risk of DR is high when the level of HbA1c and FBG were simultaneously high.ConclusionClinical variables related to people with type II diabetes mellitus were strong predictive factors of DR. Hence, health professionals should be cautious about the possible nonlinear effects of clinical variables, interaction of clinical variables, and interaction of clinical variables with sociodemographic variables on the log odds of having DR. Furthermore, to improve intervention strategies similar studies should be conducted across the country.

Dataset Information

Diabetic Retinopathy and Dementia in Type 1 Diabetes.

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Diabetic Retinopathy and Dementia in Type 1 Diabetes.

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