Diabetes & Metabolism Journal

Original Article

Complications
Association between Serum Cystatin C and Vascular Complications in Type 2 Diabetes Mellitus without Nephropathy: Hye Jeong Kim, Dong Won Byun, Kyoil Suh, Myung Hi Yoo, Hyeong Kyu Park; Diabetes Metab J. 2018;42(6):513-518. Published online October 15, 2018; DOI: https://doi.org/10.4093/dmj.2018.0006

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Background

Recent studies have correlated serum cystatin C (CysC) with vascular complications, but few studies have investigated this correlation in diabetes patients without nephropathy. This study aimed to evaluate if higher serum CysC levels increase the risk for vascular complications in type 2 diabetes mellitus patients with normal renal function or mild renal impairment.

Methods

A total of 806 consecutive patients with type 2 diabetes mellitus who were admitted to the diabetes center of Soonchunhyang University Hospital for blood glucose control were retrospectively reviewed. Patients with nephropathy were excluded. Subjects were categorized into quartiles of serum CysC levels (Q1, ≤0.65 mg/L; Q2, 0.66 to 0.79 mg/L; Q3, 0.80 to 0.94 mg/L; and Q4, ≥0.95 mg/L).

Results

The proportion of patients with diabetic retinopathy (DR) (P for trend <0.001), coronary heart disease (CHD) (P for trend <0.001), and stroke (P for trend <0.001) increased across the serum CysC quartiles. After adjustment for confounding factors, the highest serum CysC level remained a significant risk factor for DR (odds ratio [OR], 1.929; 95% confidence interval [CI], 1.007 to 4.144; P=0.040). Compared with Q1, a significant positive association was observed between serum CysC and CHD in Q2 (OR, 7.321; 95% CI, 1.114 to 48.114; P=0.012), Q3 (OR, 6.027; 95% CI, 0.952 to 38.161; P=0.020), and Q4 (OR, 8.122; 95% CI, 1.258 to 52.453; P=0.007). No associations were observed between CysC and stroke after additional adjustment for confounding variables.

Conclusion

Serum CysC levels are independently associated with DR and CHD, suggesting that CysC may be useful for identifying type 2 diabetes mellitus patients without nephropathy who are at high risk for vascular complications.

Citations

Citations to this article as recorded by

A systematic literature review of machine learning based risk prediction models for diabetic retinopathy progression
Tiwalade Modupe Usman, Yakub Kayode Saheed, Augustine Nsang, Abel Ajibesin, Sandip Rakshit
Artificial Intelligence in Medicine.2023; 143: 102617. CrossRef
Serum cystatin C for risk stratification of prediabetes and diabetes populations
Kun Xiong, Shiran Zhang, Pingting Zhong, Zhuoting Zhu, Yanping Chen, Wenyong Huang, Wei Wang
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(11): 102882. CrossRef
Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
Jing Wei, Jincheng Zhang, Yanan Shi, Huiqin Zhang, Yan Wu
Open Medicine.2023;[Epub] CrossRef
Diagnostic circulating biomarkers to detect vision‐threatening diabetic retinopathy: Potential screening tool of the future?
Karen Frudd, Sobha Sivaprasad, Rajiv Raman, Subramanian Krishnakumar, Yeddula Rebecca Revathy, Patric Turowski
Acta Ophthalmologica.2022;[Epub] CrossRef
Association between circulating cystatin C and hyperuricemia: a cross-sectional study
Yanjun Guo, Hangkai Huang, Yishu Chen, Chao Shen, Chengfu Xu
Clinical Rheumatology.2022; 41(7): 2143. CrossRef
Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy
Sarega Gurudas, Karen Frudd, Jayapal Jeya Maheshwari, Yeddula Rebecca Revathy, Sobha Sivaprasad, Shruthi Mahalakshmi Ramanathan, Vignesh Pooleeswaran, A. Toby Prevost, Eleni Karatsai, Sandra Halim, Shruti Chandra, Paul Nderitu, Dolores Conroy, Subramanian
JAMA Ophthalmology.2022; 140(6): 587. CrossRef
A Cross-Sectional Study of Serum and Urine Fluoride in Diabetes in Fluoride Exposed Population
Sai Deepika Ram Mohan, Shashidhar Kurpad Nagaraj, Raveesha Anjanappa, Muninarayana Chandrappa
Journal of Evolution of Medical and Dental Sciences.2021; 10(11): 798. CrossRef
Cystatin C predicts the risk of incident cerebrovascular disease in the elderly
Xin Zheng, Hong-da She, Qiao-xin Zhang, Tong Si, Ku-sheng Wu, Ying-xiu Xiao
Medicine.2021; 100(28): e26617. CrossRef
Proteinuria Is Associated with Carotid Artery Atherosclerosis in Non-Albuminuric Type 2 Diabetes: A Cross-Sectional Study
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Journal of Clinical Medicine.2020; 9(1): 136. CrossRef

Case Reports

A Case of Multifocal Pyomyositis in Diabetes Mellitus.: Eun Seo Park, Joo Hyun Kim, Bo Yong Jung, Jae Ho Park, Ji Hun Ahn, Jun Young Lee, Soon Ho Hwang, Kyung Wook Lee, Jong Kyu Han, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2006;30(2):140-144. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.140

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Abstract PDF: Pyomyositis is an acute bacterial infection of skeletal muscle, usually caused by Staphylococcus aureus. It is common in the tropics but rare in temperate climates. In temperature climate there are predisposing factors, such as diabetes, HIV infection, malignancy. The incidence of reported bacterial pyomyositis is increasing in recently, especially among immunocompromised persons such as HIV infection or diabetes mellitus. We experience multifocal pyomyositis in 49-year-old man with type 2 diabetes mellitus presented with drowsy mental state. Muscular USG and MRI finding shows multifocal abscess in thigh. Blood culture revealed Staphyloccus aureus. And patient received a intravenous broad-spectrum antibiotics, incision and drainage. He was successfully managed with drainage and antibiotics then discharge. Since diabetes or infection with HIV predisposes patients to bacterial infection, pyomyositis will occur more frequently. Increased awareness if the disease will improve management.

A Case of Acute Multifocal Bacterial Nephritis Associated with Diabetic Autonomic Neuropathy.: Eun Kyung Park, Jae Hak Lee, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2003;27(4):379-384. Published online August 1, 2003

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Abstract PDF: Acute multifocal bacterial nephritis is a severe form of acute renal infection in which a heavy leukocytic infiltrate occurs throughout the kidney. It is also an early phase of renal corticomedullary abscess. Clinically, patients have evidence of a severe urinary tract infection secondary to a gram-negative organism and there are frequently signs of sepsis. About half of the reported patients have been diabetics. Urinary tract infections are more common in diabetic women than in non-diabetic women. A variety of factors may contribute. The most important predisposing factor may be bladder dysfunction as a result of diabetic neuropathy and cystopathy. Diabetic cystopathy begins as decreased bladder sensation and decreased reflex detrusor activity caused by neuropathy affecting sympathetic and parasympathetic afferent fibers. Impaired bladder sensation results in bladder distention and increased residual urine volume. Long-term effects may eventually be vesicoureteral reflux and recurrent upper urinary tract infection. However, until now no diabetic patient with acute multifocal bacterial nephritis has been reported in Korea. Acute multifocal bacterial nephritis can be diagnosed by clinical manifestations and on radiologic grounds, including abdominal computed tomography showing multiple, wedge shaped, poorly defined areas of decreased contrast enhancement in multiple renal lobes. Therefore, we report the first Korean case of acute multifocal bacterial nephritis associated with diabetic autonomic neuropathy and review the literatures.

A Case of Invasive Aspergillosis of the Nasal Septum in a Patient with Diabetes Mellitus.: Tae Hoon Kim, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Jang Mook Kim, Yoon Jung Kim; Korean Diabetes J. 2003;27(4):373-378. Published online August 1, 2003

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Abstract PDF: Invasive aspergillosis of the nasal cavity and paranasal sinuses is characterized by invasion and destruction of the bony sinus walls, the orbit, and other soft tissues of the face. It occurs particularly in patients with severe immune deficits, and less frequently in patients with diabetes mellitus. The therapeutic outcome of invasive aspergillosis is unsatisfactory. Mortality rates range from 50 to 80%, depending primarily on the underlying disease. In general, the prognosis depends on making a prompt diagnosis of infection and providing early treatment. However the diagnosis of invasive aspergillosis is difficult because there is no specific symptom, nor any rapid diagnostic method for confirmation. We report a case of a 64-year old woman with diabetes mellitus and invasive aspergillosis of the nasal septum. She was diagnosed by biopsy of the nasal septum and treated with systemic antifungal agent and surgical debridement. (Ed- paragraphs combined here) In conjunction with this case we review the previous literatures and suggest that prompt antifungal therapy with glycemic control is an important element in the treatment of invasive aspergillosis in a diabetic patient.

A Case of Endogenous Endophthalmitis in a Patient with Diabetic Retinopathy.: Chang Hee Han, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Jun Sun Kim; Korean Diabetes J. 2003;27(4):367-372. Published online August 1, 2003

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Abstract PDF: Infectious endogenous endophthalmitis can occur by entrance of a pathogenic microorganism into the eye from various primary infection sites other than the eye. Although relatively rare, it results in visual loss frequently in spite of early diagnosis and treatment. It occurs in the process of systemic infection and its underlying conditions are diabetes, advanced liver disease, and immune suppressive state or drug abuse. We report a case of a 51-year old man with proliferative diabetic retinopathy and endogenous endophthalmitis caused by S. aureus from a skin infection. The ocular symptoms improved after systemic and intravitreal antibiotic therapy but visual loss could not be prevented. In conjunction with this case, we review the available literatures and stress the seriousness of this disease when concurrent in diabetic patients.

Original Articles

Polymorphism of the Uncoupling Protein 1 (UCP-1) Gene and Fatty Acid Binding Protein 2 (FABP2) Gene in Korean Type 2 Diabetic Patients.: Sun Gyu Kim, Chul Hee Kim, Seog Ki Yun, Yeo Il Yun, Yong Hyun Kim, Il Song Nam, Ju Young Lee, Ji O Mok, Hyeong Kyu Park, Young Sun Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2001;25(4):262-272. Published online August 1, 2001

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Abstract PDF: BACKGROUND
It is well known that genetic component plays an important role in developing obesity and type 2 diabetes mellitus. A number of candidate genes have been suggested, but the major gene determining the development of obesity and type 2 diabetes has not yet been uncovered. Previous studies suggest that polymorphisms of the intestinal fatty acid binding protein (FABP2) and uncoupling protein 1 (UCP-1) gene were related with obesity and/or insulin resistance in several populations. METHODS: We examined 76 type 2 diabetic patients (aged 44+/-6 years) and 96 healthy controls (aged 25+/-3 years). Ala54Thr polymorphism of the FABP2 gene and A to G polymorphism (-3826) of the UCP-1 gene were determined by polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: The Thr54 allele of the FABP2 gene was found with a frequency of 0.33 in nondiabetic controls and 0.36 in type 2 diabetic patients. The genotype frequency of the Ala54Thr polymorphism was similar in nondiabetic and diabetic subjects ( 2=0.87, P=0.64). The -3826 G allele of UCP-1 gene was found with a frequency of 0.51 in nondiabetic controls, and 0.46 in type 2 diabetic patients. The genotype frequency of the -3826 A to G polymorphism was also similar in nondiabetic and diabetic subjects ( 2=1.46, p=0.46). When the subjects of each groups were subdivided into nonobese and obese group by BMI of 25 kg/m2, there was no significant difference in genotype frequencies of the UCP-1 and FABP2 gene polymorphisms. CONCLUSION: These results suggest that either the Ala54Thr polymorphism of the FABP2 gene or the A to G polymorphism (-3826) of UCP-1 gene do not play a major role in developing type 2 diabetes mellitus or obesity in Korean.

Association Between Uncoupling Protein-1 and 3-adrenergic Receptor Gene Polymorphisms and Energy Metabolism in normal Korean Adults.: Jae Han Kim, Seog Ki Yun, Chul Hee Kim, Dong Won Byun, Young Sun Kim, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 1999;23(6):803-813. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The beta3-adrenergic receptor (beta3-AR) and uncoupling protein 1 (UCP-1), expressed mainly in brown adipose tissue, are involved in the regulation of thermogenesis and lipolysis. Recent studies have shown that polymorphisms of the 3-AR (Trp64Arg) and UCP-1 (-3826, A to G) genes are associated with low basal metabolic rate (BMR) and obesity. METHODS: We investigated the effects of the beta3- AR and UCP-1 gene polymorphisms on body fat and energy metabolism in 65 normal Korean men aged from 21 to 36 years. The Trp64Arg mutation of the beta3-AR gene and A to G polymorphism (-3826) of UCP-1 gene were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. RESULT: In normal Koreans, Arg64 allele frequency of the beta3-AR was 0.15 and the allele frequency of the A to G substitution of the UCP-1 gene was 0.48. No significant difference was found in BMR, body fat and abdominal fat amount in relation to beta3-AR or UCP-1 genotypes. However, when the polymorphisms of the two genes were combined, the subjects with the polymorphisms of both UCP-1 and g-AR genes were found to have higher body mass index, higher total fat and abdominal fat amount, lower BMR, and lower fat oxidation rate when compared with the subjects without these polymorphisms. CONCLUSION: These results suggest that the polymorphisms of either beta3-AR or UCP-1 gene alone did not significantly affect BMR, fat oxidation and body fat amounts, but both UCP-1 and beta3-AR genes polymorphisms have synergistic effects on decreased basal metabolic rate, fat oxidation rate, and increased body fat in normal Korean adults.

Association between FABP2 Gene Polymorphism and Energy Metabolism in Normal Korean.: Seog Ki Yun, Chul Hee Kim, Young Sun Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Guk Bae Kim; Korean Diabetes J. 1998;22(4):457-466. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The human intestinal fatty acid binding protein (FABP2) locus has been proprosed to be a major candidate gene in determining insulin resistance. It has been hypothesized that alanine to threonine substitution at codon 54 (Ala54Thr) of the FABP2 gene may result in enhanced intestinal uptake of fatty acids, and thereby an impairment of insulin action. FABP2 polymorphism was recently shown to be associated with insulin resistance in several populations including Mexican-Americans, Pima Indians, and Japanese, but not associated in the English, Wales, and Finn. METHODS: We investigated the association ot the FABP2 gene polymorphism and insulin resistance, fat absorption, and body fuel metabolism in 96 normal Korean men aged between 21 and 36 years. RESULTS: In normal Koreans, the alanine-encoding allele frequency was 0.66 and threonine encoding allele frequency was 0.34. Subjects with threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a higher insulin resistance index, and a higher basal fat oxidation rate compared with subjects who were homozygous for the alanine-encoding allele. CONCLUSION: These results show that the Ala54Thr substitution in the FABP2 gene is associated with increased fat oxidation and insulin resistance in normal Korean men.

Soluble P-selectin, E-selectin, and VCAM-1 as Markers of Vascular Endothelial Damage in Diabetic Patients with Microangiopathy.: Young Sun Kim, Dong Won Byun, Kyo Il Seo, Myung Hi Yoo, Guk Bae Kim, Seong Soo Koong; Korean Diabetes J. 1998;22(1):35-46. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Vascular complications of diabetic patients are common and are known as the major cause of death. Hyperglycemia has been supposed to be the leading cause of vascular complications by unknown mechanisms. In recent reports, hyperglycemia stimulated the expression of leukocyte-endothelial adhesion molecules in the endothelial cells, and increased plasma concentrations of their soluble forms. The aim of this study was to evaluate the role of plasma concentrations of soluble P-selectin(sP-selectin), soluble E-selectin(sE-selectin), and soluble VCAM-1(sVCAM-1) in diabetic patients with microvascular complications as markers of vascular endothelial damage. METHODS: In this study, plasma levels of sP-selection, sE-selectin and sVCAM-1 were determined by ELISA in 39 diabetic patients and 25 normal conirols. RESULTS: The concentrations of sP-selectin, sE-selectin, and sVCAM-1 in diabetic group were significantly higher than those in control group. The concentrations of sP-selectin and sE-selectin decreased sigruficantly after contol of hyperglycemia in diabetic group, but sVCAM-1 level was not altered by treatment. In diabetic group with microvascular complications, the concentrations of sP-selectin and sE-selectin significantly were elevated as compared with the diabetic group without microvascular complication, but the concentration of sVCAM-l was not different between the two groups. In diabetic group, the levels of sP-selectin, sE-selcctin, and sVCAM-1 were not correlated with the concentration of C-peptide, HbA1, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol. There was no difference between control group and diabetic group in terms of age and sex. There were not any differences of sP-selectin, sE-selectin, and sVCAM-1 concentration according to the duration of diabetes and the presence of hypertension. CONCLUSION: Hyperglycemia might stimulated the expression of P-selectin, E-selectin, and VCAM-1 in the endothelial cells and increased the plasma levels of their soluble forms. sP-selectin and sE-selectin could be used as indicators of ongoing vascular dysfunction in diabetes as well as a dynamic surrogate marker for the effectiveness of therapeutic interventions.

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