Clinical study

The effect of a low fat diet on the serum lipids in diabetes and its significance in diabetic retinopathy☆

Lipid metabolic abnormalities have emerged as potential risk factors for the development and progression of diabetic complications, including diabetic retinopathy (DR). This review article provides an overview of the results of clinical trials evaluating the potential benefits of lipid-lowering drugs, such as fibrates, omega-3 fatty acids, and statins, for the prevention and treatment of DR. Although several clinical trials demonstrated that treatment with fibrates leads to improvement of DR, there is a dissociation between the protective effects of fibrates in the retina, and the intended blood lipid classes, including plasma triglycerides, total cholesterol, or HDL:LDL cholesterol ratio. Guided by these findings, plasma lipid and lipoprotein-independent mechanisms are addressed based on clinical, cell culture, and animal model studies. Potential retinal-specific effects of fatty acid oxidation products, cholesterol, and ceramide, as well as lipid-independent effects of PPAR alpha activation, are summarized based on the current literature. Overall, this review highlights promising potential of lipid-based treatment strategies further enhanced by the new knowledge of intraretinal lipids and lipoproteins in DR.

Elevated lipid levels increase complications of diabetic retinopathy (DR). Uncontrolled diabetes increases these complications and causes unintentional weight loss, indicating an apparently normal body mass index (BMI). Thus, it is easy to assume that patients with DR and a normal BMI have optimal lipid status. Apolipoprotein (Apo) A-I and Apo B levels differentially indicate serum lipid status in DR. Subjective Global Assessment (SGA) scores are associated with DR status. If SGA scores and serum Apo A-I and B levels are found to be interrelated, their relationship can reflect lipid defects in patients with DR despite apparently normal BMI. The aim of the present study was to investigate the possible relationship between serum Apo A-I and B levels and SGA scores of patients with DR.

This was a case–control study conducted from November 2011 to April 2014. Serum Apo A-I and B levels and SGA scores were calculated for 40 healthy controls, 48 individuals without DR, 49 nonproliferative DR cases, and 48 proliferative DR cases. Pearson's correlation analysis was applied between Apo A-I, Apo B, Apo B/Apo A-I ratio, and SGA scores.

Negative correlation was observed between serum Apo A-I level (r = −0.567, P < 0.001) and positive correlation between serum Apo B level (r = 0.451, P < 0.001) and Apo B/Apo A-I ratio (r = 0.597, P < 0.001) with escalating SGA scores.

To our knowledge, this is the first study to report a novel correlation between serum Apo A-I, Apo B and Apo B/Apo A-I ratio and SGA scores. SGA scores can help predict lipid abnormalities in patients with DR even when they have an apparently normal BMI.

Background: Statins have mechanisms of action that expand their effects beyond cholesterol lowering and atherosclerotic medical conditions.

Objective: This review summarizes clinical evidence for the association of dyslipidemia and the effects of statin use on aortic stenosis, Alzheimer's dementia (AD), osteoporosis, prevention of diabetes mellitus (DM), diabetic retinopathy, age-related macular degeneration, and diabetic/nondiabetic nephropathy.

Methods: An English-language literature search was conducted using MEDLINE (1966-June 2003). Bibliographies of retrieved articles were reviewed. Search terms included statin, HMG-CoA reductase inhibitors, aortic stenosis, Alzheimer's dementia, osteoporosis, prevention of diabetis, diabetic retinopathy, age-related macular degeneration, diabetic nephropathy, and nondiabetic nephropathy.

Results: Three retrospective cohort trials have shown an association between statin use and the progression of aortic stenosis; one of these trials observed a 45% decrease in aortic valve area in 1 year. In AD, one cross-sectional analysis found 60% to 73% lower AD rates in lovastatin or pravastatin recipients (P < 0.001). Of the multiple observational studies on the effect of statins on fracture risk, some have shown a decreased risk, with an odds ratio as low as 0.50 (95% CI, 0.33–0.76); others have demonstrated no association. A post hoc analysis of the West of Scotland Coronary Prevention Study found a 30% reduction in the development of DM (P = 0.042), but this was not duplicated in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm. A small clinical trial of 6 patients (11 eyes) demonstrated improved retinal hard exudates with pravastatin treatment in patients with diabetic retinopathy. In a cross-sectional analysis, age-related macular degeneration was found to be less common among statin users than nonusers (4% [$\text{1}\text{27}$] vs 22% [$\text{76}\text{352}$]; P = 0.02. Multiple small clinical trials of 19 to 56 patients with diabetic and nondiabetic nephropathy at various stages generated inconsistent results for an association between statin use and decreased albumin excretion rate and decreased rate of decline in glomerular filtration.

Conclusion: Data of variable quantity and quality support the use of statins as adjuncts in the treatment of nonmacrovascular diseases.

Retinal microvascular dysfunction in diabetes is a major component of diabetic retinopathy. This review highlights recent observations regarding the cellular anatomy that contributes to the blood–retinal barrier and its breakdown, the alterations of macroglial, neuronal, and microglial cells in diabetes, and how these changes lead to loss of vision. In addition, the effects of systemic pathophysiologic influences, including metabolic control, blood pressure, and fluid volume on the formation of diabetic macular edema are discussed. Finally, an overview of inflammatory mechanisms and responses in the retina in diabetes is provided. Together, these new observations provide a broader clinical and research perspective on diabetic retinal vascular dysfunction than previously considered, and provide new avenues for improved treatments to prevent loss of vision.

There would seem to be little doubt that a diet high in fiber-rich carbohydrate can improve diabetic control and reduce levels of LDL cholesterol when compared with the more traditional low carbohydrate-high fat diabetic diet. The abnormalities of platelet function in diabetes and their association with certain essential fatty acids suggest that attention to the nature of the fat composition of the diet may be equally relevant in attempts to reduce the frequency of both micro- and macrovascular complications of diabetes. Only a very limited number of inter ventions studies have been carried out. More information is urgently required concerning the effects of modifying the fatty acid composition of the diabetic diet.