INTRODUCTION

Recent epidemiologic studies have shown a significant rise in the prevalence of type 2 diabetes worldwide, resulting in increased burdens on individuals and health care systems [1,2]. This disease creates huge social, economic, and health problems, caused mainly by diabetic macro- and microvascular complications [2,3]. The frequent coexistence of diabetic macro- and microangiopathy was described decades ago [4-6].

For macroangiopathy, several measures of subclinical atherosclerosis have been developed as surrogate measures of cardiovascular disease (CVD) [7-11]. Atherosclerosis consists of two distinct processes: a structural process (atherosis) and a functional process (sclerosis) [12]. Common carotid artery intima-media thickness (CCA-IMT), ankle-brachial index (ABI), and carotid plaque presence are considered parameters of structural changes in atherosclerosis whereas brachial-ankle pulse wave velocity (baPWV) is a convenient measure of functional changes in atherosclerosis [13]. Similar to subclinical atherosclerosis, diabetic microangiopathy is associated with CVD risk in type 2 diabetic patients [14-16].

Such evidence is supported by a "common mechanism" for the development of macro- and microangiopathy in type 2 diabetes [17-20]. Several studies have evaluated the association between macroangiopathy and diabetic retinopathy [20-24]. However, these associations have not been adequately explored, particularly in the Korean population.

In this study, we evaluated the association between CCA-IMT, baPWV, carotid plaque, and peripheral arterial disease (PAD) as indicators of macroangiopathy, and diabetic retinopathy as an indicator of microangiopathy in type 2 diabetic patients.

METHODS

I. Subjects

The study population consisted of 1275 type 2 diabetic patients registered at a public health center of Seo-gu, Gwangju, and Gokseong-gun, Jeollanamdo, Korea. The subjects were participants in the surveys of the Seo-gu study (conducted between November 2008 and December 2008), and the Gokseong-gun study (conducted between June 2009 and November 2009).

In total, 1275 eligible subjects (Seo-gu: 681, Gokseong-gun: 594) were invited by telephone to participate. Of these, 709 (Seo-gu: 327, Gokseong-gun: 382) underwent clinical examinations following interviews. The response rate for the study was 55% (Seo-gu: 48.0%, Gokseong-gun: 64.3%). Ten patients who did not provide blood samples and twenty-six who did not provide urine samples were excluded from the study. Sixty-eight patients had no HbA1c, CCA-IMT, carotid plaque, baPWV, history of diabetic duration, or fundoscopic outcome and were excluded from the analysis. After excluding these patients, a total of 605 patients (Seo-gu: 290, Gokseong-gun: 315) participated in the study.

The study protocol was approved by the Institutional Review Board of Chonnam National University Hospital, and informed consent was obtained from each subject.

II. Methods

A well-trained examiner interviewed the patients using a questionnaire that included items on smoking status, diabetic duration, anti-diabetic medication use, antihypertension medication use, and a history of past illnesses.

Anthropometric measurements, including weight, height, and waist measurements, were obtained using standard techniques. The body mass index (BMI) was calculated using the following formula: weight (kg)/height² (m²). Blood pressure was measured on the right upper arm using a mercury sphygmomanometer (Baumanometer; WA Baum Co., Inc., Copiague, NY, USA) with an appropriately sized cuff after subjects had rested at least 10 min in a sitting position. The first appearance (phase I) and disappearance (phase V) of Korotkoff sounds were used to define systolic and diastolic blood pressure, which was read to the nearest 2 mmHg. Two consecutive measurements of systolic and diastolic blood pressure were taken in 5 minutes intervals, and the average was used in the analysis.

All laboratory specimens were taken following overnight fasting. The serum was separated onsite and stored at -70℃ until further analysis. All serum samples were examined using an automatic analyzer (Hitachi-7600, Hitachi Ltd, Tokyo, Japan). HbA1c was measured by high-performance liquid chromatography (HPLC) using the Variant II (Bio-Rad, Hercules, CA, USA). Total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride concentrations were analyzed using enzymatic methods. Low-density lipoprotein (LDL) cholesterol was estimated as proposed by Friedewald et al. [25], except when triglyceride levels exceeded 400 mg/dL. In such instances, the data were treated as missing.

Kidney function was assessed using the estimated glomerular filtration rate (eGFR), which was calculated by the Modification of Diet in Renal Disease (MDRD) formula as follows [26]: 186.3 × (serum creatinine-1.154) × (age-0.203) × 0.742 (if female), with the serum creatinine concentration expressed in mg/dL.

Non-mydriatic digital images of the retina of each eye were taken using a retinal camera (TRC-NW200, Topcon Co., Japan). Retinopathy was considered present if any characteristic lesions as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale were present (microaneurysms, hemorrhages, cotton wool spots, intraretinal microvascular abnormalities, hard exudates, and new retinal vessels). If the ETDRS severity score was 10, the patient was defined as having diabetic retinopathy [27].

The CCA-IMT and the presence of carotid plaques were assessed by physicians using high-resolution mode B ultrasonographic scans of the carotid arteries (SonoAce 9900, Medison, Korea) with an electrical linear array transducer (7.5 MHz). The CCA-IMT was defined as the distance from the leading edge of the first echogenic line to the second echogenic line, which indicated the media-adventitia interface. Images of the thickest point within 10 mm from the carotid bulb to the CCA were saved as CCA-IMT, and then measured using SigmaScan Pro version 5.0.0 (Systat Software Inc., Chicago, IL, USA).

The examiners evaluated the CCA, carotid bulb, and internal carotid artery to determine the levels of carotid plaque. Protrusions into the lumen that were 100% thicker than the nearest area were defined as plaques. If the plaque was the thickest point, the distance to the nearest point without plaques was defined as the CCA-IMT. The presence of carotid plaques was recorded if at least one lesion was detected in six segments.

After a minimum 5 minutes rest period, the baPWV and ABI were calculated automatically in the supine position using the VP-1000 system (Colin Co., Komaki, Japan) with cuffs around both arms and ankles. If any of the ABIs were < 0.9, the patient was defined as having PAD.

III. Statistical Analyses

Data are provided as the mean ± standard deviation (SD) for continuous variables, the percentage for categorical variables, and the median (interquartile range) for triglyceride and baPWV. An independent sample t-test or Mann-Whitney U test was used to examine significant differences in the mean values between the two groups, and a chi-square test was used to examine differences in the frequency. The associations between CCA-IMT, baPWV, and clinical characteristics were examined using partial correlation, controlling for age and sex. To evaluate the association between the surrogate of macroangiopathy (CCA-IMT, baPWV, carotid plaque, and PAD) and diabetic retinopathy, different models were constructed using multiple logistic regression analyses by adjusting for confounding risk variables (age, sex, duration of diabetes, HbA1c, total cholesterol (TC), log-transformed triglycerides, HDL cholesterol, eGFR, BMI, and history of hypertension). These confounding risk variables were selected through a literature review [22-24]. Because there is no clear cut-point for categorization, CCA-IMT and baPWV were divided into tertiles: CCA-IMT, 0.39 to 0.65 mm, 0.66 to 0.78 mm, and 0.79 to 1.30 mm; baPWV, 9.9 to 15.8 m/s, 15.9 to 18.9 m/s, and 19.0 to 38.0 m/s.

Statistical analyses were performed with the SPSS version 19.0 (SPSS Inc, Chicago, IL, USA). A level of p < 0.05 was accepted as statistically significant.

RESULTS

Table 1 summarizes the general characteristics of the study groups with and without retinopathy. The presence of diabetic retinopathy was confirmed in 114 (18.8%) of the 605 patients who were eligible to take part in the study. The mean age of the subjects with diabetic retinopathy was significantly lower compared to subjects without diabetic retinopathy. In addition, the response rate of the Gokseong-gun study (64.3%) was higher than that of the Seo-gu study (48.0%), and a significant mean age difference existed between the two regions. However, the mean age of the subjects with diabetic retinopathy was significantly lower compared to subjects without diabetic retinopathy in each of the two regions. The stratified analysis also showed that there was no evidence of effect modification by region (data not shown). The mean values of HbA1c and the duration of diabetes were significantly higher among subjects with diabetic retinopathy compared to subjects without diabetic retinopathy. The baPWV was higher in subjects with diabetic retinopathy, but this was not statistically significant.

The associations between CCA-IMT, baPWV, and clinical characteristics are presented in Table 2. The CCA-IMT was not correlated with clinical characteristics, while baPWV was significantly correlated with BMI (r=-0.158, p<0.001) and triglycerides (r=0.131, p=0.001).

The odds ratios (ORs) for diabetic retinopathy according to the CCA-IMT levels are listed in Table 3. When adjusted for other covariates (i.e., sex, age, duration of diabetes, HbA1c, TC, log-transformed triglycerides (logTG), HDL, eGFR, BMI, and history of HTN), the CCA-IMT was not significantly associated with diabetic retinopathy.

The ORs for diabetic retinopathy according to baPWV levels are listed in Table 3. Compared to the first tertile, crude ORs (95% confidence interval [CI]) for retinopathy were 1.45 (0.85 to 2.47) for the second tertile and 1.93 (1.16 to 3.24) for the third tertile. Adjustment for age and sex increased ORs (95% CI) for retinopathy: 2.48 (1.37 to 4.49) for the second tertile and 4.44 (2.38 to 8.31) for the third tertile. Further adjustment for other covariates (Model 2) did not change the association.

The ORs for diabetic retinopathy according to carotid plaques and PAD are listed in Table 3. When adjusted for all covariates (Model 2), the carotid plaques and PAD were not significantly associated with diabetic retinopathy.

DISCUSSION

The purpose of this study was to determine the association between macroangiopathy (CCA-IMT, baPWV, carotid plaque, and PAD) and diabetic retinopathy. We found that baPWV is significantly associated with diabetic retinopathy, whereas CCA-IMT, carotid plaque, and PAD are not.

There was no significant association between CCA-IMT and diabetic retinopathy among type 2 diabetic patients after adjusting for cardiovascular risk factors. These results are consistent with the findings of the Cardiovascular Health Study (CHS) [21]. However, the Chennai Urban Rural Epidemiology Study (CURES-2) and the Atherosclerosis Risk In Communities (ARIC) study reported a positive relationship between CCA-IMT and diabetic retinopathy [22,28]. We did not observe an independent association between carotid plaque, PAD, and diabetic retinopathy, whereas a positive relationship has previously been observed [20,29]. However, carotid plaque and PAD have been shown not to be significantly associated with diabetic retinopathy in some studies [30-32]. Selective survival may provide a potential explanation for these discrepant results. Severe atherosclerosis and retinopathy in diabetic patients were both associated with an increased risk of death, which may have resulted in individuals with these conditions being less likely to be examined than patients without these conditions [33]. The other potential reasons for the discrepant results may include different sample sizes, population characteristics, the lower magnification of our images, and the age distribution of the study population.

Arterial stiffness is a major contributor to CVD [34], and baPWV is correlated with the degree of atherosclerotic vascular damage [13,35]. The present study showed that baPWV has a distinct association with diabetic retinopathy contrary to other surrogates. The exact mechanisms underlying the association between atherosclerosis and diabetic retinopathy are poorly understood. In previous studies, analyses were conducted separately according to each surrogate [20,22-24,29,30]. An integrated theory to explain these observed phenomena has not been established. One possible explanation is that atherosclerosis and diabetic retinopathy share common risk factors in the causal pathway [17,18,20,22]. Although the adjustment for cardiovascular risk factors in our study did not change the association between surrogates of macroangiopathy and diabetic retinopathy, the possibility of an effect of unmeasured variables remained. In the present study, functional markers such as baPWV were associated with diabetic retinopathy, but structural markers such as IMT, carotid plaque, and PAD were not. This suggests that the association between macroangiopathy and microangiopathy may be due to a functional rather than structural process within the vascular system.

Interestingly, in the present study, without adjustment, there was no significant difference in the baPWV between subjects with diabetic retinopathy and subjects without diabetic retinopathy (p value=0.072). However, after adjustment for age and sex, baPWV was significantly associated with diabetic retinopathy. Therefore, this phenomenon may result from the positive confounding effect of age and sex.

This study has several limitations. First, this was a cross-sectional study. The association between macroangiopathy and diabetic retinopathy cannot be taken as a causal relationship. Nonetheless, we believe that the results may help shed light on the pathophysiological connections between the development and progression of macro- and microangiopathy in diabetes. Second, the study targets type 2 diabetic patients who were registered at a public health center in a certain area and does not represent the general population across the nation. Third, the mean age of the subjects with diabetic retinopathy was significantly lower than that of subjects without diabetic retinopathy. This phenomenon may be explained by selection bias due to either selective survival or nonparticipation (restricted movement). However, we cannot conclude that this phenomenon resulted from selection bias, because we did not compare general characteristics of study participants and nonparticipants. Fourth, we conducted multiple comparisons among the four phenotypes of macroangiopathy. However, after post-hoc multiple comparisons using the Bonferroni correction, these associations did not change substantially. Fifth, we used non-mydriatic color digital images of the retina. The accuracy of this method is slightly lower than the use of mydriatic color images. Despite these limitations, this study provides a valuable contribution, in that we evaluated the association between multiple phenotypes of macroangiopathy, including CCA-IMT, carotid plaque, PAD, and baPWV, and diabetic retinopathy in a single population.

In summary, baPWV is associated with diabetic retinopathy in type 2 diabetic patients, but CCA-IMT, carotid plaque, and PAD are not. Additional studies are required to further evaluate the common pathogenic mechanisms underlying these associations in Korean type 2 diabetic patients.

Notes

The authors have no conflicts of interest with the material presented in this paper.

This article is available at http://jpmph.org/.

REFERENCES

• 1. Girach A, Vignati L. Diabetic microvascular complications--can the presence of one predict the development of another? J Diabetes Complications 2006;20(4):228-237. 16798474ArticlePubMed
• 2. Malecki MT, Osmenda G, Walus-Miarka M, Skupien J, Cyganek K, Mirkiewicz-Sieradzka B, et al. Retinopathy in type 2 diabetes mellitus is associated with increased intimamedia thickness and endothelial dysfunction. Eur J Clin Invest 2008;38(12):925-930. 19021717ArticlePubMed
• 3. Jönsson B. CODE-2 Advisory Board. Revealing the cost of Type II diabetes in Europe. Diabetologia 2002;45(7):S5-S12. 12136405Article
• 4. Hiller R, Sperduto RD, Podgor MJ, Ferris FL 3rd, Wilson PW. Diabetic retinopathy and cardiovascular disease in type II diabetics. The Framingham Heart Study and the Framingham Eye Study. Am J Epidemiol 1988;128(2):402-409. 3293436PubMed
• 5. Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000;321(7258):412-419. 10938049ArticlePubMedPMC
• 6. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321(7258):405-412. 10938048ArticlePubMedPMC
• 7. Wofford JL, Kahl FR, Howard GR, McKinney WM, Toole JF, Crouse JR 3rd. Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis. Arterioscler Thromb 1991;11(6):1786-1794. 1931880ArticlePubMed
• 8. Bernard S, Serusclat A, Targe F, Charriére S, Roth O, Beaune J, et al. Incremental predictive value of carotid ultrasonography in the assessment of coronary risk in a cohort of asymptomatic type 2 diabetic subjects. Diabetes Care 2005;28(5):1158-1162. 15855582ArticlePubMed
• 9. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 2007;115(4):459-467. 17242284ArticlePubMed
• 10. Prati P, Tosetto A, Vanuzzo D, Bader G, Casaroli M, Canciani L, et al. Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events. Stroke 2008;39(9):2470-2476. 18617662ArticlePubMed
• 11. Vigili de Kreutzenberg S, Tiengo A, Avogaro A. Cerebrovascular disease in diabetes mellitus: the role of carotid intima-media thickness. Nutr Metab Cardiovasc Dis 2009;19(9):667-673. 19500958ArticlePubMed
• 12. Blankenhorn DH, Kramsch DM. Reversal of atherosis and sclerosis. The two components of atherosclerosis. Circulation 1989;79(1):1-7. 2642753ArticlePubMed
• 13. Zureik M, Temmar M, Adamopoulos C, Bureau JM, Courbon D, Thomas F, et al. Carotid plaques, but not common carotid intima-media thickness, are independently associated with aortic stiffness. J Hypertens 2002;20(1):85-93. 11791030ArticlePubMed
• 14. Cheung N, Wang JJ, Klein R, Couper DJ, Sharrett AR, Wong TY. Diabetic retinopathy and the risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Diabetes Care 2007;30(7):1742-1746. 17389333ArticlePubMed
• 15. Juutilainen A, Lehto S, Ronnemaa T, Pyörälä K, Laakso M. Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women. Diabetes Care 2007;30(2):292-299. 17259497ArticlePubMed
• 16. Romundstad S, Holmen J, Kvenild K, Hallan H, Ellekjaer H. Microalbuminuria and all-cause mortality in 2,089 apparently healthy individuals: a 4.4-year follow-up study. The Nord-Trondelag Health Study (HUNT), Norway. Am J Kidney Dis 2003;42(3):466-473. 12955674ArticlePubMed
• 17. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006;114(6):597-605. 16894049ArticlePubMed
• 18. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54(6):1615-1625. 15919781ArticlePubMed
• 19. Stern MP. Diabetes and cardiovascular disease. The "common soil" hypothesis. Diabetes 1995;44(4):369-374. 7698502ArticlePubMed
• 20. de Kreutzenberg SV, Coracina A, Volpi A, Fadini GP, Frigo AC, Guarneri G, et al. Microangiopathy is independently associated with presence, severity and composition of carotid atherosclerosis in type 2 diabetes. Nutr Metab Cardiovasc Dis 2011;21(4):286-293. 20163939ArticlePubMed
• 21. Klein R, Marino EK, Kuller LH, Polak JF, Tracy RP, Gottdiener JS, et al. The relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study. Br J Ophthalmol 2002;86(1):84-90. 11801510ArticlePubMedPMC
• 22. Rema M, Mohan V, Deepa R, Ravikumar R. Chennal Urban Rural Epidemiology Study-2. Association of carotid intima-media thickness and arterial stiffness with diabetic retinopathy: the Chennai Urban Rural Epide-miology Study (CURES-2). Diabetes Care 2004;27(8):1962-1967. 15277424ArticlePubMed
• 23. Ogawa O, Hayashi C, Nakaniwa T, Tanaka Y, Kawamori R. Arterial stiffness is associated with diabetic retinopathy in type 2 diabetes. Diabetes Res Clin Pract 2005;68(2):162-166. 15860245ArticlePubMed
• 24. Ogawa O, Hiraoka K, Watanabe T, Kinoshita J, Kawasumi M, Yoshii H, et al. Diabetic retinopathy is associated with pulse wave velocity, not with the augmentation index of pulse waveform. Cardiovasc Diabetol 2008;7: 11. 18439284ArticlePubMedPMC
• 25. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18(6):499-502. 4337382ArticlePubMedPDF
• 26. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999;130(6):461-470. 10075613ArticlePubMed
• 27. Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 1991;98(5 Suppl):786-806. 2062513ArticlePubMed
• 28. Klein R, Sharrett AR, Klein BE, Moss SE, Folsom AR, Wong TY, et al. The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes : the atherosclerosis risk in communities study. Ophthalmology 2002;109(7):1225-1234. 12093643ArticlePubMed
• 29. Papanas N, Symeonidis G, Mavridis G, Georgiadis GS, Papas TT, Lazarides MK, et al. Ankle-brachial index: a surrogate marker of microvascular complications in type 2 diabetes mellitus? Int Angiol 2007;26(3):253-257. 17622207PubMed
• 30. Miyamoto M, Kotani K, Okada K, Fujii Y, Konno K, Ishibashi S, et al. The correlation of common carotid arterial diameter with atherosclerosis and diabetic retinopathy in patients with type 2 diabetes mellitus. Acta Diabetol DOI: 10.1007/s00592-011-0287-8Article
• 31. Ogawa Y, Uchigata Y, Iwamoto Y. Progression factors of carotid intima-media thickness and plaque in patients with long-term, early-onset type 1 diabetes mellitus in Japan: simultaneous comparison with diabetic retinopathy. J Atheroscler Thromb 2009;16(6):821-828. 19763015ArticlePubMed
• 32. Mostaza JM, Suarez C, Manzano L, Cairols M, López-Fernández F, Aguilar I, et al. Sub-clinical vascular disease in type 2 diabetic subjects: relationship with chronic complications of diabetes and the presence of cardiovascular disease risk factors. Eur J Intern Med 2008;19(4):255-260. 18471673ArticlePubMed
• 33. Klein R, Klein BE, Moss SE, Cruickshanks KJ. Association of ocular disease and mortality in a diabetic population. Arch Ophthalmol 1999;117(11):1487-1495. 10565517ArticlePubMed
• 34. Safar ME, London GM. The Clinical Committee of Arterial Structure and Function. Working Group on Vascular Structure and Function of the European Society of Hypertension. Therapeutic studies and arterial stiffness in hypertension: recommendations of the European Society of Hypertension. J Hypertens 2000;18(11):1527-1535. 11081763ArticlePubMed
• 35. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37(5):1236-1241. 11358934ArticlePubMed

Figure & Data

References

Citations

Citations to this article as recorded by  

• Role of Systemic Factors in Improving the Prognosis of Diabetic Retinal Disease and Predicting Response to Diabetic Retinopathy Treatment
  Joe Mellor, Anita Jeyam, Joline W.J. Beulens, Sanjeeb Bhandari, Geoffrey Broadhead, Emily Chew, Ward Fickweiler, Amber van der Heijden, Daniel Gordin, Rafael Simó, Janet Snell-Bergeon, Anniina Tynjälä, Helen Colhoun
  Ophthalmology Science.2024; 4(4): 100494.     CrossRef
• Association between carotid ultrasonographic parameters and microvascular and macrovascular complications in diabetes: A systematic review and meta-analysis
  Meimei Liao, Sen Chen, Ruiqiang Guo
  Journal of Diabetes and its Complications.2023; 37(8): 108554.     CrossRef
• Cardiac autonomic neuropathy predicts diabetic retinopathy progression in Asian population with type 2 diabetes mellitus
  Chu-Yu Yen, Chun-Sen Chen, Kuo-Meng Liao, I-Mo Fang
  Graefe's Archive for Clinical and Experimental Ophthalmology.2022; 260(8): 2491.     CrossRef
• The association between carotid disease, arterial stiffness and diabetic retinopathy in type 2 diabetes: the Fremantle Diabetes Study Phase II
  J. J. Drinkwater, F. K. Chen, A. M. Brooks, B. T. Davis, A. W. Turner, T. M. E. Davis, W. A. Davis
  Diabetic Medicine.2021;[Epub]     CrossRef
• Low 25-hydroxyvitamin D is associated with arterial stiffness in Chinese with Type 2 diabetes mellitus
  Bingwei Ma, Yao Chen, Chunjun Sheng, Peng Yang, Xingchun Wang, Shen Qu
  European Journal of Clinical Nutrition.2021; 75(11): 1645.     CrossRef
• Increased Arterial Stiffness as a Predictor for Onset and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus
  Yaxin An, Yuxian Yang, Bin Cao, Huan Dong, Aihua Li, Wenying Zhao, Jing Ke, Dong Zhao, Akira Sugawara
  Journal of Diabetes Research.2021; 2021: 1.     CrossRef
• Retinopathy predicts stroke but not myocardial infarction in type 2 diabetes: the Fremantle Diabetes Study Phase II
  Jocelyn J. Drinkwater, Timothy M. E. Davis, Valentina Hellbusch, Angus W. Turner, David G. Bruce, Wendy A. Davis
  Cardiovascular Diabetology.2020;[Epub]     CrossRef
• Troponin T Parallels Structural Nerve Damage in Type 2 Diabetes: A Cross-sectional Study Using Magnetic Resonance Neurography
  Johann M.E. Jende, Jan B. Groener, Zoltan Kender, Artur Hahn, Jakob Morgenstern, Sabine Heiland, Peter P. Nawroth, Martin Bendszus, Stefan Kopf, Felix T. Kurz
  Diabetes.2020; 69(4): 713.     CrossRef

• Association Between Atherosclerosis and Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes Mellitus

  
  Chenghui Zhang, Suyuan Wang, Mingxia Li, Yunhong Wu
  Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 1911.     CrossRef
• High Pulse Wave Velocity is Associated with the Severity of Diabetic Retinopathy in Patients with Type 2 Diabetes
  Sung-Chen Liu, Shih-Ming Chuang, Hong-Mou Shih, Chao-Hung Wang, Ming-Chieh Tsai, Chun-Chuan Lee
  Journal of Investigative Medicine.2020; 68(6): 1159.     CrossRef
• Association between interarm blood pressure differences and diabetic retinopathy in patients with type 2 diabetes
  Ji Hyun Lee, Ye An Kim, Young Lee, Woo-Dae Bang, Je Hyun Seo
  Diabetes and Vascular Disease Research.2020; 17(4): 147916412094591.     CrossRef
• Peripheral Arterial Stiffness Increases the Risk of Progression of Renal Disease in Type 2 Diabetic Patients
  Tae Hoon Lim, Seung Min Chung, Dong Sung Lee, Se Ra Choi, Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
  Frontiers in Medicine.2020;[Epub]     CrossRef
• Carotid Disease and Retinal Optical Coherence Tomography Angiography Parameters in Type 2 Diabetes: The Fremantle Diabetes Study Phase II
  Jocelyn J. Drinkwater, Fred K. Chen, Alison M. Brooks, Brad T. Davis, Angus W. Turner, Timothy M.E. Davis, Wendy A. Davis
  Diabetes Care.2020; 43(12): 3034.     CrossRef
• Does retinopathy predict stroke recurrence in type 2 diabetes patients: A retrospective study?
  Ola Hjelmgren, Ulf Strömberg, Karl Gellerman, Anders Thurin, Madeleine Zetterberg, Göran Bergström, Rayaz A. Malik
  PLOS ONE.2019; 14(1): e0210832.     CrossRef
• Association of central arterial stiffness with the presence and severity of diabetic retinopathy in Asians with type 2 diabetes
  Xiao Zhang, Su Chi Lim, Subramaniam Tavintharan, Lee Ying Yeoh, Chee Fang Sum, Keven Ang, Darren Yeo, Serena Low, Neelam Kumari
  Diabetes and Vascular Disease Research.2019; 16(6): 498.     CrossRef
• Retinal vessel reactivity is not attenuated in patients with type 2 diabetes compared with matched controls and is associated with peripheral endothelial function in controls
  Jonathan Mathias Baier, Kristian Løkke Funck, Line Petersen, Liv Vernstrøm, Søren T. Knudsen, Toke Bek, Per Løgstrup Poulsen, Esben Laugesen
  Journal of Diabetes and its Complications.2019; 33(9): 641.     CrossRef
• Cardio-ankle vascular index is associated with diabetic retinopathy in younger than 70 years patients with type 2 diabetes mellitus
  Olga Lamacchia, Maria Rosaria Sorrentino, Giuseppe Picca, Matteo Paradiso, Pasquale Maiellaro, Salvatore De Cosmo
  Diabetes Research and Clinical Practice.2019; 155: 107793.     CrossRef
• Relación entre los valores de glucemia y la rigidez arterial en adultos no diabéticos
  Iván Cavero-Redondo, Vicente Martínez-Vizcaíno, Celia Álvarez-Bueno, José Ignacio Recio-Rodríguez, Manuel Ángel Gómez-Marcos, Luis García-Ortiz
  Medicina Clínica.2018; 150(2): 56.     CrossRef
• Relationship between glycaemic levels and arterial stiffness in non-diabetic adults
  Iván Cavero-Redondo, Vicente Martínez-Vizcaíno, Celia Álvarez-Bueno, José Ignacio Recio-Rodríguez, Manuel Ángel Gómez-Marcos, Luis García-Ortiz
  Medicina Clínica (English Edition).2018; 150(2): 56.     CrossRef
• Abnormally Low or High Ankle-Brachial Index Is Associated With the Development of Diabetic Retinopathy in Type 2 Diabetes Mellitus
  Mei-Yueh Lee, Pi-Jung Hsiao, Jiun-Chi Huang, Wei-Hao Hsu, Szu-Chia Chen, Jer-Ming Chang, Shyi–Jang Shin
  Scientific Reports.2018;[Epub]     CrossRef
• The comorbidity of increased arterial stiffness and microalbuminuria in a survey of middle-aged adults in China
  Rujia Miao, Liuxin Wu, Ping Ni, Yue Zeng, Zhiheng Chen
  BMC Cardiovascular Disorders.2018;[Epub]     CrossRef
• Cardio-Ankle Vascular Index and Indices of Diabetic Polyneuropathy in Patients with Type 2 Diabetes
  Akihiko Ando, Michiaki Miyamoto, Kazuhiko Kotani, Kenta Okada, Shoichiro Nagasaka, Shun Ishibashi
  Journal of Diabetes Research.2017; 2017: 1.     CrossRef
• Retinopathy is a Strong Determinant of Atherosclerosis in Type 2 Diabetes: Correlation with Carotid Intima Media Thickness
  Aasem Saif, Sherif Karawya, Alaa Abdelhamid
  Endocrine Practice.2015; 21(3): 226.     CrossRef
• Arterial stiffness in diabetes mellitus
  Stuart B. Prenner, Julio A. Chirinos
  Atherosclerosis.2015; 238(2): 370.     CrossRef
• Abnormally Low or High Ankle-Brachial Index Is Associated with Proliferative Diabetic Retinopathy in Type 2 Diabetic Mellitus Patients
  Szu-Chia Chen, Pi-Jung Hsiao, Jiun-Chi Huang, Kun-Der Lin, Wei-Hao Hsu, Yu-Li Lee, Mei-Yueh Lee, Jer-Ming Chang, Shyi–Jang Shin, Xiao-Feng Yang
  PLOS ONE.2015; 10(7): e0134718.     CrossRef
• High Prevalence of Lower Extremity Peripheral Artery Disease in Type 2 Diabetes Patients with Proliferative Diabetic Retinopathy
  Yi-Wen Chen, Ying-Ying Wang, Dong Zhao, Cai-Guo Yu, Zhong Xin, Xi Cao, Jing Shi, Guang-Ran Yang, Ming-Xia Yuan, Jin-Kui Yang, Yvonne Böttcher
  PLOS ONE.2015; 10(3): e0122022.     CrossRef
• Arterial Stiffness and Carotid Intima-Media Thickness in Diabetic Peripheral Neuropathy
  Bulent Behlul Altunkeser
  Medical Science Monitor.2014; 20: 2074.     CrossRef
• Role of phospholipases A2 in diabetic retinopathy: In vitro and in vivo studies
  Gabriella Lupo, Carla Motta, Giovanni Giurdanella, Carmelina Daniela Anfuso, Mario Alberghina, Filippo Drago, Salvatore Salomone, Claudio Bucolo
  Biochemical Pharmacology.2013; 86(11): 1603.     CrossRef
• Relationship between Stage of Diabetic Retinopathy and Pulse Wave Velocity in Japanese Patients with Type 2 Diabetes
  Kumiko Tanaka, Toshihide Kawai, Yoshifumi Saisho, Shu Meguro, Kana Harada, Yuka Satoh, Kaori Kobayashi, Kei Mizushima, Takayuki Abe, Hiroshi Itoh
  Journal of Diabetes Research.2013; 2013: 1.     CrossRef
• Arterial Stiffness Is Associated With Cardiovascular, Renal, Retinal, and Autonomic Disease in Type 1 Diabetes
  Simone Theilade, Maria Lajer, Frederik Persson, Christel Joergensen, Peter Rossing
  Diabetes Care.2013; 36(3): 715.     CrossRef
• Author Response
  Young-Hoon Lee, Min-Ho Shin
  Journal of Preventive Medicine and Public Health.2012; 45(2): 123.     CrossRef
• Ankle-brachial Index, Peripheral Arterial Disease, and Diabetic Retinopathy
  Hasan Kutsi Kabul, Aydogan Aydogdu, Ilker Tasci
  Journal of Preventive Medicine and Public Health.2012; 45(2): 122.     CrossRef