Original Data

Increased Levels of Total P-Cresylsulphate and Indoxyl Sulphate are Associated with Coronary Artery Disease in Patients with Diabetic Nephropathy

Cheng-An Chiu¹, Li-Fen Lu², Teng-Hung Yu¹, Wei-Chin Hung¹, Fu-Mei Chung¹, I-Ting Tsai³, Chih-Ying Yang³, Chia-Chang Hsu⁴, Yung-Chuan Lu⁵, Chao-Ping Wang^6,7, Yau-Jiunn Lee⁸

Abstract

BACKGROUND: Indoxyl sulphate (IS) and p-cresylsulphate (PCS) are uremic toxins with similar protein-binding, dialytic clearance, and proinflammatory features. Few studies have evaluated the possible associations between these solutes and coronary artery disease (CAD) in type 2 diabetes (T2D) patients. METHODS: A hospital-based case control study was performed. A total of 209 T2D patients were divided into two groups based on the presence/absence of significant CAD (≥50% luminal reduction). Serum total PCS and IS levels were measured using the Ultra Performance LC System. The relationship between total PCS and IS levels were investigated. Coronary calcium scores and the modified Gensini score were analyzed. RESULTS: Serum total PCS and IS levels were significantly higher in patients with both T2D and significant CAD, than in non-diabetic control subjects and T2D patients without CAD (all p < 0.05). Logistic regression analysis revealed independent and significant associations between the two solutes and CAD status. Serum total PCS, IS, and numbers of diseased vessels were elevated in groups with estimated glomerular filtration rate (eGFR) of 60-89 ml/min/1.73 m² and below. Also, serum total PCS and IS levels were significantly associated with eGFR, coronary calcium scores, Gensini score, adipocytokines (adiponectin, visfatin, and leptin), and total white blood cell count. CONCLUSIONS: Serum total PCS and IS levels were elevated in patients with T2D and CAD. These increases were associated with renal function deterioration, inflammation, and coronary atherosclerosis.

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A WFS1 Haplotype Consisting of the Minor Alleles of rs752854, rs10010131, and rs734312 Shows a Protective Role Against Type 2 Diabetes in Russian Patients

Dimitry A Chistiakov¹, Dmitry S. Khodyrev¹, Svetlana A. Smetanina², Larisa N. Bel'chikova², Lyudmila A. Suplotova², Valery V. Nosikov¹

Abstract

BACKGROUND: Rare variants of the WFS1 gene encoding wolframin cause Wolfram syndrome, a monogenic disease associated with diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. In contrast, common variants of WFS1 showed association with type 2 diabetes (T2D) in numerous Caucasian populations. AIM: In this study, we tested whether the markers rs752854, rs10010131, and rs734312, located in the WFS1 gene, are related to the development of T2D in a Russian population. METHODS: The polymorphic markers were genotyped in Russian diabetic (n = 1,112) and non-diabetic (n = 1,097) patients using a Taqman allele discrimination assay. The correlation between the carriage of disease-associated WFS1 variants and the patients' clinical and metabolic characteristics was studied using ANOVA and ANCOVA. Adjustment for confounding variables such as gender, age, body mass index, obesity, HbA1c, and hypertension was made. RESULTS: Haplotype GAG, consisting of the minor alleles of rs752854, rs10010131, and rs734312, respectively, showed association with decreased risk of T2D (OR = 0.44, 95% CI = 0.32-0.61, p = 4.3 x 10^-7). Compared to other WFS1 variants, non-diabetic individuals homozygous for GAG/CAG had significantly increased fasting insulin (p_adjusted = 0.047) and homeostasis model assessment of β-cell function (HOMA-β) index (p_adjusted = 0.006). Diabetic patients homozygous for GAG/GAG showed significantly elevated levels of 2-h insulin (p_adjusted = 0.029) and HOMA-β = 0.011. CONCLUSIONS: Disease-associated variants of WFS1 contribute to the pathogenesis of T2D through impaired insulin response to glucose stimulation and altered β-cell function.

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Prevalence of Undiagnosed Diabetes and Quality of Care in Diabetic Patients Followed at Primary and Tertiary Clinics in Abu Dhabi, United Arab Emirates

Hussein Saadi¹, Jumaa Al-Kaabi¹, Mahmoud Benbarka², Ali Khalili³, Wael Almahmeed², Nicolaas Nagelkerke⁴, Alessandro Salustri², Laila Abdel-Wareth⁵, Awad Al Essa¹, Javed Yasin¹, Bayan Al-Dabbagh¹, Elsadig Kazam¹

Abstract

AIMS: To investigate the prevalence of undiagnosed type 2 diabetes (T2D) at primary health care (PHC) clinics, and to assess the quality of care of diabetic patients followed at a tertiary hospital diabetes center in Abu Dhabi, United Arab Emirates (UAE). METHODS: Between May 2009 and October 2010, adult patients attending two PHC clinics, and adult diabetic patients attending the diabetes center, were invited to participate in the study. After overnight fast, participants returned for interview and laboratory tests. Undiagnosed T2D was defined by FPG ≥ 7.0 mmol/l or HbA1c ≥ 6.5%. Quality of care was assessed by reported care practices and achievement of internationally recognized targets. RESULTS: Out of 239 patients at PHC clinics without history of T2D, 14.6% had undiagnosed T2D, and 31% had increased risk of diabetes (FPG 5.6-7.0 mmol/l or HbA1c 5.7-6.5%). The independent predictors of undiagnosed T2D were age (adjusted OR per year 1.07, 95% CI 1.04-1.11, p < 0.001) and BMI ≥ 25 (adjusted OR 4.2, 95% CI 0.91-19.7, p = 0.033). Amongst all 275 diagnosed T2D patients, including those attending PHC clinics and those followed at the diabetes center, it was found that 40.1% followed dietary recommendations, 12% reported visiting a diabetes educator, 28.2% walked for exercise, and 13.5% attained recognized targets of HbA1c < 7%, blood pressure < 130/80 mmHg, and LDL cholesterol < 2.6 mmol/l. CONCLUSIONS: Almost half of the adult patients attending PHC clinics had undiagnosed T2D, or increased diabetes risk. Care practices, and achievement of treatment targets, were suboptimal.

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