editorial complications of diabetes 2016downloads.hindawi.com/journals/jdr/2016/6989453.pdf ·...

EditorialComplications of Diabetes 2016

Konstantinos Papatheodorou,1 Nikolaos Papanas,1 Maciej Banach,2

Dimitrios Papazoglou,1 and Michael Edmonds3

1Diabetes Clinic, Second Department of Internal Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece2Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland3Diabetic Foot Clinic, King’s College Hospital, London, UK

Correspondence should be addressed to Konstantinos Papatheodorou; [email protected]

Received 22 September 2016; Accepted 22 September 2016

Copyright © 2016 Konstantinos Papatheodorou et al. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

The prevalence of diabetes (DM) is constantly increasingworldwide at an alarming rate. According to the InternationalDiabetes Federation in 2015, an estimated 415 million peopleglobally were suffering from this condition [1]. Complica-tions of DM account for increased morbidity, disability, andmortality and represent a threat for the economies of allcountries, especially the developing ones [2]. The presentspecial issue has been devoted to the recent progress inour understanding of diabetic complications, including theunderlying molecular mechanisms, new diagnostic tools thatfacilitate early diagnosis, and novel treatment options. It con-sists of 20 articles covering 5 thematic areas: (a) epidemiologyand pathogenesis of diabetic complications, (b) microvas-cular complications, (c) macrovascular complications, (d)miscellaneous complications, and (e) treatment options.

(a) Epidemiology and Pathogenesis of Diabetic Complications.There is growing evidence that the underlying mechanismsin the pathogenesis of diabetic complications include certaingenetic and epigenetic modifications, nutritional factors,and sedentary lifestyle [3]. In a paper of this special issueentitled “Epigenetic Studies Point toDNAReplication/RepairGenes as a Basis for the Heritable Nature of Long TermComplications in Diabetes,” A. A. Leontovich et al., using azebrafish diabetic model, have explored the role of epigeneticmechanisms on the persistence of diabetic complicationseven after euglycemic control is achieved, a condition knownas metabolic memory. They found that DNA-methylation,in or near genes belonging to the DNA replication/DNAmetabolism process group, might play a key role in thisprocess. Regarding basic risk factors for macro- and

microvascular complications, the Irish Longitudinal Studyon Ageing (TILDA), as M. L. Tracey et al. describe in theirarticle “Risk Factors for Macro- and Microvascular Compli-cations amongOlder Adults withDiagnosed Type 2Diabetes:Findings from The Irish Longitudinal Study on Ageing,”has recognized ageing, male gender, smoking, low level ofphysical activity, and high cholesterol as independent predic-tors of macrovascular complications. Conversely, smoking,hypertension, and duration of DM over 10 years proved to bepredictive factors for microvascular complications.

(b) Microvascular Complications.Diabetic nephropathy, neu-ropathy, and retinopathy are the main microvascular compli-cations induced by chronic hyperglycemia via several mech-anisms such as the production of advanced glycation endproducts (AGEs), the creation of a proinflammatory mi-croenvironment, and the induction of oxidative stress [4, 5].

Four articles in this special issue focus on diabetic neph-ropathy (DN). The first, by K. Sawada et al. entitled “Up-regulation of 𝛼3𝛽1-Integrin in Podocytes in Early-StageDiabetic Nephropathy” shed light on the mechanism ofpodocyte detachment from the glomerular basement mem-brane, which is considered to be a key factor in the devel-opment of DN. The authors conclude that the early stagesof this procedure are mediated by an upregulation of 𝛼3𝛽1-integrin in podocytes. In the second article about DNentitled “Oxidative Stress inDiabetic Nephropathywith EarlyChronic Kidney Disease,” A. G. Miranda-Dıaz et al. havereviewed the effects of hyperglycemia-induced productionof reactive oxygen species (ROS) on the renin-angiotensinsystem and the signaling pathway of the transforming growth

Hindawi Publishing CorporationJournal of Diabetes ResearchVolume 2016, Article ID 6989453, 3 pageshttp://dx.doi.org/10.1155/2016/6989453

2 Journal of Diabetes Research

factor-beta (TGF-𝛽). They have concluded that oxidativestress leads to the production of chronic inflammation andthe glomerular and tubular hypertrophy, which characterizethe early stages of DN. Turning their attention to the diag-nosis of early diabetic nephropathy, C. Gluhovschi et al., inanother paper of this issue titled “Urinary Biomarkers in theAssessment of Early Diabetic Nephropathy,” have attemptedto review novel biomarkers indicating renal injury such astransferrin, ceruloplasmin, podocalyxin, and VEGF. Thesemarkers can detect renal injury even before the presenceof microalbuminuria, which still remains the most validbiomarker for DN in clinical practice. The last paper on thesame topic, by X. Li et al., entitled “Histone Acetylation andits Modifiers in the Pathogenesis of Diabetic Nephropathy,”provides an overview of the potential involvement of epi-genetic mechanisms, such as histone acetylation and othercellular processes in the development and progression of DN.It may be hoped that these mechanisms can help towardsdefining new therapeutic approaches for this microvascularcomplication of DM.

Three more articles have been included in the presentspecial issue referring to diabetic retinopathy and neuropa-thy. The article entitled “Diabetic Retinopathy Is StronglyPredictive of Cardiovascular Autonomic Neuropathy in Type2 Diabetes” has evaluated risk factors for cardiovascularautonomic neuropathy (CAN) in patients with T2DM. Inthis article, C.-C. Huang et al., using the deep breathingtest, the Valsalva maneuver method, and the CompositeAutonomic Scoring Scale to estimate the severity of auto-nomic neuropathy, found that diabetic retinopathy is themost significant predictive factor for CAN. In a further work,L. Forga et al. have conducted an observational, retrospectivestudy in order to identify risk factors for the developmentof diabetic retinopathy (DR) in patients with type 1 DM. Intheir study entitled “Influence of Age at Diagnosis and Time-Dependent Risk Factors on the Development of DiabeticRetinopathy in Patients with Type 1 Diabetes,” they maintainthat age at onset of type 1 DM, indexes of glycemic control,HDL-cholesterol levels, and diastolic blood pressure are allparameters predicting DR. In this regard, the study “HeartRate Variability as Early Biomarker for the Evaluation ofDiabetes Mellitus Progress” by R. E. Arroyo-Carmona et al.has used heart rate variability (HRV) as a tool to identify earlydiabetic complications and progress ofDM in streptozotocin-induced diabetic mice.

(c) Macrovascular Complications. Atherosclerosis is morecommon in peoplewithDM than in thosewithout. For exam-ple, DM increases the risk for stroke in people aged 20 to 65yearsmore than 5 times [6].The present special issue includesarticles on macrovascular complications of DM as well. J.Zhang et al. in the article entitled “Coronary Plaque Char-acteristics Assessed by 256-Slice Coronary CT Angiographyand Association with High-Sensitivity C-Reactive Protein inSymptomatic Patients with Type 2 Diabetes” have performeda coronary Computed Tomography Angiography to evaluatecoronary plaque subtypes and luminal narrowing in patientswith and without type 2 DM. They report that patients withDM are more prone to have significant stenosis with calcified

plaques and such findings are accompanied by higher hs-CRP levels. Moreover, in a review article entitled “TheRole of AGE/RAGE Signaling in Diabetes-Mediated VascularCalcification,” A. M. Kay et al. emphasize the key role ofAGE/RAGE signaling on the promotion of DM-mediatedvascular calcification. In this process, many intracellularsignaling pathways contribute to increased oxidative stress,which in turn leads to deposition of hydroxyapatite mineralsinto the extracellular matrix and vascular calcification. Fur-thermore,M. Samos et al. in their work “The Impact of Type 2Diabetes on the Efficacy ofADPReceptor Blockers in Patientswith Acute ST Elevation Myocardial Infarction: A PilotProspective Study” have presented data from a prospectivestudy that aimed to investigate platelet reactivity in patientswith acute ST elevation myocardial infarction (STEMI) withor without T2DM, who have been treated with adenosinediphosphate (ADP) receptor blockers. Of note, this studyhas shown no difference between the two groups regardingplatelet reactivity and the number of nonresponders to ADPreceptor blockers. The last article of this thematic area isa retrospective quantitative study conducted in Australia.As B. T. Rodrigues et al. describe in their manuscriptentitled “Prevalence and Risk Factors for Diabetic LowerLimb Amputation: A Clinic-Based Case Control Study,”ethnicity has been recognized as an independent risk factorfor lower limb amputation in patients with diabetic foot,among whom indigenous Australians were most commonlyaffected.

(d) Miscellaneous Complications. Diabetic cardiomyopathyis a specific complication that develops independently ofcoronary artery disease or hypertension and it is possible tolead to increased morbidity and mortality [7]. The aim of thestudy “Assessment of LeftVentricular Structural Remodellingin Patients with Diabetic Cardiomyopathy by CardiovascularMagnetic Resonance” by Y. Shang et al. was to evaluate thestructural remodeling of left ventricular (LV)mass in patientswith diabetic cardiomyopathy (DCM) using cardiovascularmagnetic resonance (CMR). The authors contend that CMRcan be a valid tool to estimate LV remodeling and its severityin patients with DCM. Y. Yu et al. in their article entitled“The Protective Effect of Low Dose Ethanol on MyocardialFibrosis throughDownregulating the JNK Signaling PathwayinDiabetic Rats” have explored the protective role of lowdoseethanol on myocardial fibrosis in diabetic rats. In this study,low dose ethanol consumption was associated with lowermean arterial pressure, lower heart rate, high hydroxyprolinecontent, and collagen volume fraction in myocardial tissue,together with decreased expression of ALDH2 and down-regulation of the JNK pathway. Finally, in the review paper“Molecular and Electrophysiological Mechanisms Underly-ing Cardiac Arrhythmogenesis in Diabetes Mellitus,” G. Tseet al. discuss in detail the role of several cardiac factors (e.g.,abnormalities in conduction or repolarization, electrophys-iological, and structural remodeling) on arrhythmogenesisin patients with DM. They suggest that deeper investigationof these mechanisms can help towards defining new targetmolecules for potential future antiarrhythmic therapy forpatients with DM.

Journal of Diabetes Research 3

(e) Treatment Options. The last thematic area covered by thepresent special issue relates to novel therapeutic options andit comprises four articles. In the first entitled “The Yin andYang of the Opioid Growth Regulatory System: Focus onDiabetes: The Lorenz E. Zimmerman Tribute Lecture,” J. W.Sassani et al. provide an extensive overview of the role ofthe Opioid Growth Regulatory System on the developmentof diabetic complications. The authors have summarizedall recent evidence indicating that certain pharmaceuticalmodifications in the function of this system can have prof-itable effects on diabetic animals. Clearly, there is a lot tolearn about these intricate issues in the future. The secondmanuscript, “Implementation of a Diabetes Educator-CareModel to Reduce Paediatric Admission for Diabetic Ketoaci-dosis” byA.Deeb et al., has evaluated a diabetes educator-caremodel aiming to reduce the frequency of hospital admissionof children and adolescents due to Diabetic Ketoacidosis(DKA). The authors have demonstrated that this modelwas an effective and sustainable measure for DM treatmentachieving a significant reduction in the admission rate forDKA. L. Voroneanu et al. in their article entitled “Silymarinin Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials” have conducteda comprehensive review and meta-analysis to evaluate theefficacy and safety of silymarin administration in patientswith T2DM.They have found that this extract of milk thistleis an efficient and safe antidiabetic agent that might alsohave beneficial effects on renal function. However, significantheterogeneity and low quality of the available evidence werenoted and lead to the need for further investigation of thisissue. The final study pertains to the treatment of diabeticfoot ulcers. M. Janka-Zires et al. in their article titled “TopicalAdministration of Pirfenidone Increases Healing of ChronicDiabetic Foot Ulcers: A Randomized Crossover Study” haveconducted a randomized crossover study to assess the effectof topical administration of pirfenidone on noninfectedchronic diabetic foot ulcers. Their findings confirm thatthe healing of these ulcers improves significantly by topicaladdition of pirfenidone.

Acknowledgments

The guest editors express their thanks to all the authors whosubmitted their work for consideration and the reviewerswho helped with the evaluation of the papers. Without theirinvaluable contribution, the present issue would not havebeen completed and published.

Konstantinos PapatheodorouNikolaos Papanas

Maciej BanachDimitrios Papazoglou

Michael Edmonds

References

[1] International Diabetes Federation, IDF Diabetes Atlas, Interna-tional Diabetes Federation, Brussels, Belgium, 7th edition, 2015,http://www.diabetesatlas.org.

[2] A. Naslafkih and F. Sestier, “Diabetesmellitus relatedmorbidity,risk of hospitalization and disability,” Journal of InsuranceMedicine, vol. 35, no. 2, pp. 102–113, 2003.

[3] A. Kautzky-Willer, J. Harreiter, and G. Pacini, “Sex and genderdifferences in risk, pathophysiology and complications of type 2diabetes mellitus,” Endocrine Reviews, vol. 37, no. 3, pp. 278–316,2016.

[4] N. C. Chilelli, S. Burlina, and A. Lapolla, “AGEs, rather thanhyperglycemia, are responsible formicrovascular complicationsin diabetes: a ‘glycoxidation-centric’ point of view,” Nutrition,Metabolism andCardiovascular Diseases, vol. 23, no. 10, pp. 913–919, 2013.

[5] D. V. Nguyen, L. C. Shaw, and M. B. Grant, “Inflammation inthe pathogenesis of microvascular complications in diabetes,”Frontiers in Endocrinology, vol. 3, article 170, 2012.

[6] J. C. Khoury, D. Kleindorfer, K. Alwell et al., “Diabetes mellitus:a risk factor for ischemic stroke in a large biracial population,”Stroke, vol. 44, no. 6, pp. 1500–1504, 2013.

[7] G. Jia, V. G. DeMarco, and J. R. Sowers, “Insulin resistance andhyperinsulinaemia in diabetic cardiomyopathy,”Nature ReviewsEndocrinology, vol. 12, no. 3, pp. 144–153, 2016.

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