Retinopathy in an obesity WHO III cohort: prevalence and risk factors

Mattern, Juri; Lammert, Alexander; Otto, Mirko; Hammes, Hans‐Peter

doi:10.1136/bjophthalmol-2016-309566

Cited by 4 publications

(2 citation statements)

References 25 publications

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“…In human patients, diabetic retinopathy pathologies occur only to a low degree in patients who only have hyperlipidemia and insulin resistance without hyperglycemia or diabetes. As a clinical correlate to our pre-clinical ZF rat findings, it has been recently described that severely obese patients with strong dys- and hyperlipidemia have only a low grade of retinopathy assessed as microaneurysms or dot hemorrhages, while diabetes increases the risk for retinopathy by 8.3 fold[ 18 ].…”

Section: Discussionsupporting

confidence: 53%

The role of insulin resistance in experimental diabetic retinopathy—Genetic and molecular aspects

et al. 2017

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BackgroundDiabetic retinopathy is characterized by defects in the retinal neurovascular unit. The underlying mechanisms of impairment–including reactive intermediates and growth-factor dependent signalling pathways and their possible interplay are incompletely understood. This study aims to assess the relative role of hyperglycemia and hyperinsulinemia alone or in combination on the gene expression patterning in the retina of animal models of diabetes.Material and methodsAs insulinopenic, hyperglycemic model reflecting type 1 diabetes, male STZ-Wistar rats (60mg/kg BW; i.p. injection at life age week 7) were used. Male obese ZDF rats (fa/fa) were used as type-2 diabetes model characterized by persisting hyperglycemia and transient hyperinsulinemia. Male obese ZF rats (fa/fa) were used reflecting euglycemia and severe insulin resistance. All groups were kept till an age of 20 weeks on respective conditions together with appropriate age-matched controls. Unbiased gene expression analysis was performed per group using Affymetrix gene arrays. Bioinformatics analysis included analysis for clustering and differential gene expression, and pathway and upstream activator analysis. Gene expression differences were confirmed by microfluidic card PCR technology.ResultsThe most complex genetic regulation in the retina was observed in ZDF rats with a strong overlap to STZ-Wistar rats. Surprisingly, systemic insulin resistance alone in ZF rats without concomitant hyperglycemia did not induce any significant change in retinal gene expression pattern. Pathway analysis indicate an overlap between ZDF rats and STZ-treated rats in pathways like complement system activation, acute phase response signalling, and oncostatin-M signalling. Major array gene expression changes could be confirmed by subsequent PCR. An analysis of upstream transcriptional regulators revealed interferon-γ, interleukin-6 and oncostatin-M in STZ and ZDF rats. CONCLUSIONS: Systemic hyperinsulinaemia without hyperglycemia does not result in significant gene expression changes in retina. In contrast, persistent systemic hyperglycemia boosts much stronger expression changes with a limited number of known and new key regulators.

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Section: Discussionsupporting

confidence: 53%

The role of insulin resistance in experimental diabetic retinopathy—Genetic and molecular aspects

et al. 2017

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“…Epidemiological studies show that obesity has become a major problem worldwide and is associated with an increased risk of macrovascular diseases (1,2). However, the relationship between obesity and microvascular diseases remains controversial, especially in patients with type 2 diabetes mellitus (T2DM) who are at an increased risk of developing microvascular complications (3)(4)(5)(6). Prior experimental studies have found that obesity may lead to endothelial dysfunction, while only a small number of epidemiological studies have investigated the association between obesity, evaluated by body mass index (BMI), and microvascular diseases, such as retinopathy, nephropathy, and neuropathy, in patients with T2DM (3,4,7,8).…”

Section: Introductionmentioning

confidence: 99%

Association Between Obesity and Microvascular Diseases in Patients With Type 2 Diabetes Mellitus

et al. 2021

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This study aimed to evaluate the association between obesity, evaluated by fat mass index (FMI) with the risk of microvascular diseases in patients with type 2 diabetes mellitus (T2DM) and compare the magnitude of associations of FMI, body mass index (BMI), and waist circumference (WC) with the risk of microvascular diseases. We performed a post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes study. The primary microvascular outcomes of the present study included chronic kidney disease (CKD) progression, retinopathy, and neuropathy. Cox proportional-hazards models were performed to evaluate the association of FMI with microvascular diseases. A discordant analysis was performed to compare the magnitude of associations of FMI, BMI, and WC with the risk of microvascular diseases. Our study included 10,251 T2DM participants with a median of 5 years (interquartile range, 4.2–5.7) of follow-up. A total of 6,184 participants developed CKD progression, 896 participants had retinopathy, and 3,213 participants developed neuropathy (Michigan Neuropathy Screening Instrument, >2.0). After the confounding factors were adjusted for, patients in the highest FMI quartile had a higher risk of CKD progression (HR: 1.26, 95%CI: 1.16–1.36) and neuropathy (HR: 1.93, 95% CI: 1.74–2.15), except for retinopathy (HR: 1.17, 95% CI: 0.96–1.43), than those in the lowest quartile. Discordant analyses found that FMI and WC are better in identifying individuals with obesity-related risk of neuropathy, compared with BMI; neither is better in identifying individuals with obesity-related risk of CKD progression and retinopathy. Obesity is associated with CKD progression and neuropathy in T2DM participants. Further randomized trials are needed to test whether obesity control can improve the outcomes of T2DM participants with CKD or neuropathy. FMI and WC are more useful in identifying obesity-related risk of neuropathy compared with BMI in T2DM patients.Clinical Trial Registrationhttp://www.clinicaltrials.gov, NCT00000620.

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Iron aggravates hepatic insulin resistance in the absence of inflammation in a novel db/db mouse model with iron overload

Altamura

Müdder

Schlotterer

et al. 2021

Molecular Metabolism

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Retinopathy in an obesity WHO III cohort: prevalence and risk factors

Abstract: NCT00770276, Results.

Cited by 4 publications

References 25 publications

The role of insulin resistance in experimental diabetic retinopathy—Genetic and molecular aspects

The role of insulin resistance in experimental diabetic retinopathy—Genetic and molecular aspects

Association Between Obesity and Microvascular Diseases in Patients With Type 2 Diabetes Mellitus

Iron aggravates hepatic insulin resistance in the absence of inflammation in a novel db/db mouse model with iron overload

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