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      Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

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          Abstract

          Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high morbidity rates and a heavy social and economic burden. Currently, available therapeutic options to counter the evolution of diabetic microvascular complications are clearly insufficient, which strongly recommends further research. Animal models are essential tools to dissect the molecular mechanisms underlying disease progression, to unravel new therapeutic targets, as well as to evaluate the efficacy of new drugs and/or novel therapeutic approaches. However, choosing the best animal model is challenging due to the large number of factors that need to be considered. This is particularly relevant for models induced by dietary modifications, which vary markedly in terms of macronutrient composition. In this article, we revisit the rodent models of diet-induced DPN, DR, and DN, critically comparing the main features of these microvascular complications in humans and the criteria for their diagnosis with the parameters that have been used in preclinical research using rodent models, considering the possible need for factors which can accelerate or aggravate these conditions.

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          Most cited references88

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          Pathologic classification of diabetic nephropathy.

          Although pathologic classifications exist for several renal diseases, including IgA nephropathy, focal segmental glomerulosclerosis, and lupus nephritis, a uniform classification for diabetic nephropathy is lacking. Our aim, commissioned by the Research Committee of the Renal Pathology Society, was to develop a consensus classification combining type1 and type 2 diabetic nephropathies. Such a classification should discriminate lesions by various degrees of severity that would be easy to use internationally in clinical practice. We divide diabetic nephropathy into four hierarchical glomerular lesions with a separate evaluation for degrees of interstitial and vascular involvement. Biopsies diagnosed as diabetic nephropathy are classified as follows: Class I, glomerular basement membrane thickening: isolated glomerular basement membrane thickening and only mild, nonspecific changes by light microscopy that do not meet the criteria of classes II through IV. Class II, mesangial expansion, mild (IIa) or severe (IIb): glomeruli classified as mild or severe mesangial expansion but without nodular sclerosis (Kimmelstiel-Wilson lesions) or global glomerulosclerosis in more than 50% of glomeruli. Class III, nodular sclerosis (Kimmelstiel-Wilson lesions): at least one glomerulus with nodular increase in mesangial matrix (Kimmelstiel-Wilson) without changes described in class IV. Class IV, advanced diabetic glomerulosclerosis: more than 50% global glomerulosclerosis with other clinical or pathologic evidence that sclerosis is attributable to diabetic nephropathy. A good interobserver reproducibility for the four classes of DN was shown (intraclass correlation coefficient = 0.84) in a test of this classification.
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            Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease.

            Currently, we are experiencing an epidemic of cardiorenal disease characterized by increasing rates of obesity, hypertension, the metabolic syndrome, type 2 diabetes, and kidney disease. Whereas excessive caloric intake and physical inactivity are likely important factors driving the obesity epidemic, it is important to consider additional mechanisms. We revisit an old hypothesis that sugar, particularly excessive fructose intake, has a critical role in the epidemic of cardiorenal disease. We also present evidence that the unique ability of fructose to induce an increase in uric acid may be a major mechanism by which fructose can cause cardiorenal disease. Finally, we suggest that high intakes of fructose in African Americans may explain their greater predisposition to develop cardiorenal disease, and we provide a list of testable predictions to evaluate this hypothesis.
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              Diabetic Neuropathies: A statement by the American Diabetes Association

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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                18 January 2020
                January 2020
                : 12
                : 1
                : 250
                Affiliations
                [1 ]Institute of Pharmacology & Experimental Therapeutics, & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; i.preguica@ 123456campus.fct.unl.pt (I.P.); alves.andrefb@ 123456gmail.com (A.A.); sara_nunes20@ 123456hotmail.com (S.N.); pgomes70@ 123456gmail.com (P.G.); rcfernandes@ 123456fmed.uc.pt (R.F.); sofia_viana@ 123456estescoimbra.pt (S.D.V.)
                [2 ]Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal
                [3 ]Department of Biomedicine, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
                [4 ]Center for Health Technology and Services Research (CINTESIS), University of Porto, 4200-450 Porto, Portugal
                [5 ]Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, 3046-854 Coimbra, Portugal
                Author notes
                [* ]Correspondence: freis@ 123456fmed.uc.pt ; Tel.: +351-239-480-053
                [†]

                Equally contributed.

                Author information
                https://orcid.org/0000-0002-8161-5239
                https://orcid.org/0000-0002-0240-9059
                https://orcid.org/0000-0003-1766-9133
                https://orcid.org/0000-0003-3401-9554
                Article
                nutrients-12-00250
                10.3390/nu12010250
                7019796
                31963709
                17ce81a4-233c-4af3-8ef4-c5a9384e5b68
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 December 2019
                : 13 January 2020
                Categories
                Review

                Nutrition & Dietetics
                type 2 diabetes mellitus,microvascular complications,diabetic peripheral neuropathy,diabetic retinopathy,diabetic nephropathy,rodent models,diet-induced

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