Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus

Liang, Ching-Chao; Lin, Pi-Chen; Lee, Mei‐Yueh; Chen, Szu-Chia; Shin, Shyi–Jang; Hsiao, Pi‐Jung; Lin, Kun‐Der; Hsu, Wei-Hao

doi:10.3390/ijms17081248

Cited by 47 publications

(32 citation statements)

References 22 publications

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“…In this study, SUA was shown to be a risk factor for DR in T2D patients. In addition, this notion was supported by a recent study that the more severe DR, the more elevated level of SUA [6]. These findings are consistent with the previous studies by Lee et al 2014 andFukui et al 2008 [7,8].…”

Section: Discussionsupporting

confidence: 91%

Association of Serum Uric Acid and Lipid Profile in Type 2 Diabetic Patients With and Without Diabetic Retinopathy

Ramesh

Kumar

Kaliaperumal

et al. 2017

Asian J Pharm Clin Res

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Objectives: Diabetic retinopathy (DR) is one of the microvascular complications in type 2 diabetes (T2D). Elevated serum uric acid (SUA) has been shown to play a significant role in diabetic neuropathy and nephropathy but there is little information on retinopathy. Therefore, the present study was aimed to investigate the SUA and lipid profile in T2D patients with and without DR and the association between SUA and severity of DR.Methods: The study was conducted in the ophthalmology OPD at Sri Lakshmi Narayana Institute of Medical Sciences. The presence of T2D was confirmed by investigating fasting blood glucose level (normal limit < 110 mg/dl) in all the individuals. DR was examined by detailed dilated fundoscopic examination. Based on the fundus examination, patients were divided in to diabetes with signs of DR and those without signs of DR. Age and sex matched healthy were taken as controls. Fasting blood sugar, SUA and lipid profile were investigated for these groups. Results: The study found elevated SUA and abnormal lipid profile in DR group when compared to non-DR and control groups. We also found the significant association between SUA and severity of DR particularly in males.Conclusion: We found a significant association between SUA and severity of DR in T2D patients. Further studies with large sample size are needed to establish the role of elevated SUA and the mechanism involved in the pathogenesis of retinopathy in diabetic patients. Regular measurements of SUA level could be advised to the diabetic patients for the early management.

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Section: Discussionsupporting

confidence: 91%

Association of Serum Uric Acid and Lipid Profile in Type 2 Diabetic Patients With and Without Diabetic Retinopathy

Ramesh

Kumar

Kaliaperumal

et al. 2017

Asian J Pharm Clin Res

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“…HG group, cells incubated in DMEM/HG medium; HG+UA group, cells incubated in UA (10mg/dl) added to DMEM/HG medium; HG+ HUA+EMP group, cells incubated in DMEM/HG medium with UA (10mg/dl) and treated with 50 μM empagliflozin; HG+UA+ Compound C group, cells incubated in DMEM/HG medium with UA (10mg/dl) , AMPK inhibitor Compound C (10μM) and empagliflozin (50 μM) for 48 hours. HUA carries a significant risk for developing various diseases in T2DM [4][5][6][7][8], therefore, exploring the metabolism of UA and associated diseases has attracted researchers' much attention. However, it is a challenge to create hyperuricemic models in mice, because in rodents, uricase oxidizes UA to allantoin which is highly soluble in water and excreted unchanged in the urine, but not in humans [24].…”

Section: Discussionmentioning

confidence: 99%

“…Various studies have indicated that incidence of HUA in patients with T2DM was respectively 24.1% [2] and 33.8% [3]. Moreover, HUA has proven to be an independent risk factor for kidney disease progression [4,5], and significantly correlated with the severity of retinopathy in patients with T2DM [6]. Accumulating data has indicated that HUA was closely associated with risks of increased prevalence of cardiovascular disease [2,4], carotid intima-media thickness [7], hypertension [8] and metabolic syndrome [8] in individuals with T2DM.…”

Section: Introductionmentioning

confidence: 99%

Empagliflozin Attenuates Hyperuricemia by Upregulation of ABCG2 via AMPK/AKT/CREB Signaling Pathway in Type 2 Diabetic Mice

Lu¹,

Chang²,

Li³

et al. 2020

Int. J. Biol. Sci.

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Hyperuricemia (HUA) is a metabolic disease characterized by elevated serum uric acid (SUA). Empagliflozin, a kind of sodium-glucose cotransporter 2 inhibitors, has recently emerged as a new antidiabetic agent by facilitating glucose excretion in urine. Moreover, there was evidence of SUA reduction following treatment with empagliflozin in addition to glycaemic control, while the molecular mechanisms remain unknown. To investigate the potential mechanisms, the model of type 2 diabetes (T2DM) with HUA was established by combination of peritoneal injection of potassium oxonate and intragastric administration of hypoxanthine in KK-Ay mice. A series of method such as RT-PCR, western blot, immunochemistry, immunofluorescence were conducted to explore the mechanism. Our results showed that empagliflozin significantly ameliorated the levels of SUA and blood glucose in T2DM mice with HUA. Furthermore, in both kidney and ileum, empagliflozin obviously promoted protein expression of uric acid (UA) transporter ABCG2, p-AMPK, p-AKT and p-CREB. The same trend was observed in human tubular epithelial (HK-2) cells. Additionally, through application of an AMPK inhibitor (Compound C), it was further confirmed empagliflozin exerted its anti-hyperuricemic effects in an AMPK dependent manner. Meanwhile, with the help of ChIP assay and luciferase reporter gene assay, we found that CREB further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Taken together, our study demonstrated that empagliflozin treatment played an essential role in attenuating HUA by upregulation of ABCG2 via AMPK/AKT/CREB signaling pathway.

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“…17 A study conducted by Ching-Chao Liang et al, concluded that there were increased serum uric acid levels which correlated with the severity of diabetic Retinopathy in patients with type 2 DM. 18 Vitreous UA and glucose concentrations were higher in proliferative than in non-proliferative DR. Focal UA production in the vitreous is thought to be involved in the pathogenesis and progression of DR. 19 UA is lowered in Diabetes mellitus (DM) due to hyperfiltration 20 , but decreased UA excretion during renal dysfunction raises SUA levels. Nazir Shah et al 21 conducted a study in 2013 in 163 patients of diabetes mellitus (type 2) and proposed that elevation in the levels of uric acid was more in the diabetic patients with nephropathy (50%).…”

Section: Discussionmentioning

confidence: 86%

Is Serum Uric Acid an Added Risk Factor for Micro-Vascular Complications of Diabetes Mellitus? – A Prospective Study

Manickam¹,

Arun²,

Petchiappan³

et al. 2019

IJCMR

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Introduction: Diabetes is the leading cause of adult blindness due to retinopathy, end stage renal disease due to nephropathy and foot ulcers and lower limb amputation due to neuropathy. Serum uric acid levels independently predict the development of micro vascular complications. In this study, we analyse the association of serum uric acid with the micro vascular complications of diabetes. Material and methods: In this hospital based observational study, hundred diabetic patients were included; of which fifty had micro vascular complications, the remaining fifty had no complications. Blood investigations including fasting(FBS) and post prandial blood sugars(PPBS), glycosylated haemoglobin (HbA1C), and serum creatinine and serum uric acid were done in all patients. All the parameters were compared between the two groups. Results: Females presented with significantly higher complications as compared to males. The mean age of the patients presented with and without complications was 56.4 ± 9.3 and 59.9 ± 10.3 respectively. HbA1C had a positive correlation with the serum uric acid (SUA) (r=0.327, P = 0.001). Mean uric acid levels were higher among patients with complications (5.96 ± 2.16) compared to patients without complications (4.95 ± 2.04) which was statistically significant (P value =0.021). Patients with nephropathy and neuropathy had significant elevation in serum uric acid levels than those without; however this significance was not noted in those with retinopathy. Conclusion: Patients with micro vascular complications had higher levels of serum uric acid compared to those without complications. Also there was positive correlation between HbA1C and serum uric acid levels.

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Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus

Cited by 47 publications

References 22 publications

Association of Serum Uric Acid and Lipid Profile in Type 2 Diabetic Patients With and Without Diabetic Retinopathy

Association of Serum Uric Acid and Lipid Profile in Type 2 Diabetic Patients With and Without Diabetic Retinopathy

Empagliflozin Attenuates Hyperuricemia by Upregulation of ABCG2 via AMPK/AKT/CREB Signaling Pathway in Type 2 Diabetic Mice

Is Serum Uric Acid an Added Risk Factor for Micro-Vascular Complications of Diabetes Mellitus? – A Prospective Study

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