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OP20 CORRELATION OF BETATROPHIN WITH AGE AND CREATININE CLEARANCE IN JAPANESE PATIENTS WITH TYPE 2 DIABETES
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Oral presentation abstracts / Diabetes Research and Clinical Practice 106S1 (2014) S1–S41
interaction. Lee WJ, Huey-Herng Sheu W, Liu SH, Yi YC, Chen WC, Lin SY, Liang KW, Shen CC, Yeh HY, Lin LY, Tsai YC, Tien HR, Lee MR, Yang TJ, Sheu ML. Free Radic Biol Med. 2014 Jul 8; 74C: 294–306. [2] Advanced glycation end product Ne-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1regulated VEGFR-2 dephosphorylation. Liu SH, Sheu WH, Lee MR, Lee WJ, Yi YC, Yang TJ, Jen JF, Pan HC, Shen CC, Chen WB, Tien HR, Sheu ML. J Pathol. 2013 Jun; 230(2): 215–27. [3] The advanced glycation end product Nepsilon-(carboxymethyl)lysine is increased in serum from children and adolescents with type 1 diabetes. Berg TJ, Clausen JT, Torjesen PA, Dahl-Jørgensen K, Bangstad HJ, Hanssen KF. Diabetes Care. 1998 Nov; 21(11): 1997–2002.
OP19 CIRCULATING ADIPOCYTE FATTY ACID BINDING PROTEIN LEVELS PREDICT THE PROGRESSION OF NEPHROPATHY IN TYPE 2 DIABETES MELLITUS C.H. Lee1 , E. Hui1,2 , Y.C. Woo1 , C.Y. Yeung1 , W.S. Chow1 , M. Yuen1 , C. Fong1 , A.M. Xu2,3 , K. Lam1,2,3 . 1 Department of Medicine, Queen Mary Hospital, 2 Research Centre of Heart, Brain, Hormone and Healthy Aging, 3 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong Background: Adipocyte fatty acid binding protein (AFABP) is one of the most abundant proteins expressed in mature adipocytes. It has been demonstrated, from cross-sectional studies, to be associated with macrovascular complications in patients with diabetes and its levels predict incident diabetes as well as cardiovascular disease outcomes. Our previous work has shown that circulating levels of AFABP were higher in patients with advancing stages of diabetic nephropathy. We investigated whether serum AFABP could predict the progression of diabetic nephropathy. Method: Baseline serum AFABP levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. Chronic kidney disease (CKD) progression was defined as a drop in estimated glomerular filtration rate (eGFR) category accompanied by a 25% or greater drop in eGFR from baseline. The role of AFABP in predicting CKD progression over a median follow-up of 4 years was analyzed using Cox regression analysis. Result: At baseline, serum AFABP levels increased progressively with CKD staging (p for trend < 0.001). Amongst 1071 subjects with baseline CKD stage 3 or less, 171 subjects (16.0%) had CKD progression after a median follow up of 4 years. Subjects with CKD progression were older (p < 0.001), with longer duration of diabetes (p = 0.001) and higher baseline HbA1c levels (p = 0.008), more of them being hypertensive (p < 0.001) and on anti-hypertensive medications including ACEI or ARB (p < 0.001), lower baseline eGFR (p < 0.001), higher C-reactive protein (p < 0.001) and higher serum triglyceride levels (p < 0.001) than those without CKD progression. Serum AFABP levels were significantly higher in those with CKD progression during follow-up than those without progression (p < 0.001). Baseline sex-adjusted serum AFABP levels were higher in subjects with CKD progression (10.9 mg/L [IQR 6.76– 17.2] vs 7.00 mg/L [IQR 4.41–11.6] in male and 17.2 mg/L [IQR 11.1–28.0] vs 12.4 mg/L [IQR 7.94–21.9] in female; p < 0.001]). On multivariable Cox regression analysis including also other biologically relevant variables, baseline serum AFABP level was independently associated with CKD progression (Hazard ratio 1.52; 95% CI = 1.18–1.96; p < 0.001), together with sex, age, body mass index, smoking status, duration of diabetes, HbA1c, systolic blood pressure, the use of ACEI/ARB and C-reactive protein level at baseline. Conclusion: Elevated baseline serum AFABP level appears to be a useful biomarker for predicting kidney disease progression in diabetic nephropathy.
OP20 CORRELATION OF BETATROPHIN WITH AGE AND CREATININE CLEARANCE IN JAPANESE PATIENTS WITH TYPE 2 DIABETES S. Tokumoto1 , Y. Hamamoto1 , K. Fujimoto1 , E. Yamaguchi1 , Y. Shibayama1 , E. Okamura1 , Y. Wada1 , H. Ikeda1 , S. Honjo1 , A. Hamasaki1 . 1 Center for Diabetes & Endocrinology, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, osaka, Japan Background: Betatrophin(BTH) was recently found to be a potent promoter of beta-cell proliferation and insulin secretion in mice. Through the regulation of angiopoietinlike protein 3 (ANGPTL3), BTH is also involved in triglyceride metabolism. Since the pathophysiological role of BTH in patients with type 2 diabetes remains to be unknown, we measured plasma BTH levels in Japanese patients with type 2 diabetes(T2DM) and investigated the correlations of plasma BTH levels with other clinical parameters. Method: Blood samples were collected overnight fasting in P800 tubes (Becton Dickinson) from 41 patients with T2DM (mean age 59.4±10.6 years). Plasma BTH levels were determined with an ELISA (Wuhan Eiaab science, Wuhan, China; Catalogue No. E11644h). The subjects were characterized for age, BMI, glycosylated hemoglobin, fasting plasma glucose, total cholesterol, triacylglycerol, and creatinine clearance (CrCl) calculated by 24-hour urine collection. Correlations were evaluated by univariate linear regression using Pearson product moment. All data are presented as mean ±SD. P values < 0.05 were considered statistically significant. Result: Mean BTH concentration was 1203.07±585.38 pg/ml. A strong positive correlation between plasma BTH levels and age (r2 = 0.43, correlation coefficient 0.66, p < 0.001) and a negative correlation between BTH concentration and CrCl (r2 = 0.10, correlation coefficient 0.32, p = 0.037) were observed. There was no correlations between plasma BTH levels and BMI (r2 = 0.04, p = 0.09), total cholesterol (r2 = 0.04, p = 0.16), triacylglycerol concentration (r2 = 0.03, p = 0.25), HbA1c (r2 = 0.03, p = 0.23), and fasting plasma glucose (r2 = 0.00, p = 0.81). Conclusion: Circulating levels of BTH were significantly correlated positively with age and negatively with CrCl, but not with other clinical parameters of glucose homeostasis and lipid metabolism. From our results, BTH might be excreted in the urine and unlikely to affect glucose homeostasis. Reference(s) Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic b cell proliferation. Cell 2013; 153: 747–758.
Microvascular complications OP21 ASSOCIATION OF TYPE 2 DIABETES SUSCEPTIBILITY LOCI WITH PERIPHERAL NERVE FUCNTION IN A CHINESE POPULATION WITH DIABETES: RESULTS FROM NERVE CONDUCTION STUDIES J.Y. Lu1 , Y. Luo1 , C. Hu1 , R. Zhang1 , C.R. Wang1 , W.P. Jia1 . 1 Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai Key Laboratory of Diabetes Mellitus,Shanghai Clinical Center for Diabetes, Shanghai, China Background: Diabetic polyneuropathy (DPN) is the most common form of diabetic neuropathy with an estimated prevalence of 50%. Activation of the polyol pathway, excessive oxidative stress, advanced glycation end-products were widely thought to be involved in the development of DPN. In addition, there is emerging evidence that genetic predisposition may contribute to the development of DPN. To
Oral presentation abstracts / Diabetes Research and Clinical Practice 106S1 (2014) S1–S41
interaction. Lee WJ, Huey-Herng Sheu W, Liu SH, Yi YC, Chen WC, Lin SY, Liang KW, Shen CC, Yeh HY, Lin LY, Tsai YC, Tien HR, Lee MR, Yang TJ, Sheu ML. Free Radic Biol Med. 2014 Jul 8; 74C: 294–306. [2] Advanced glycation end product Ne-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1regulated VEGFR-2 dephosphorylation. Liu SH, Sheu WH, Lee MR, Lee WJ, Yi YC, Yang TJ, Jen JF, Pan HC, Shen CC, Chen WB, Tien HR, Sheu ML. J Pathol. 2013 Jun; 230(2): 215–27. [3] The advanced glycation end product Nepsilon-(carboxymethyl)lysine is increased in serum from children and adolescents with type 1 diabetes. Berg TJ, Clausen JT, Torjesen PA, Dahl-Jørgensen K, Bangstad HJ, Hanssen KF. Diabetes Care. 1998 Nov; 21(11): 1997–2002.
OP19 CIRCULATING ADIPOCYTE FATTY ACID BINDING PROTEIN LEVELS PREDICT THE PROGRESSION OF NEPHROPATHY IN TYPE 2 DIABETES MELLITUS C.H. Lee1 , E. Hui1,2 , Y.C. Woo1 , C.Y. Yeung1 , W.S. Chow1 , M. Yuen1 , C. Fong1 , A.M. Xu2,3 , K. Lam1,2,3 . 1 Department of Medicine, Queen Mary Hospital, 2 Research Centre of Heart, Brain, Hormone and Healthy Aging, 3 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong Background: Adipocyte fatty acid binding protein (AFABP) is one of the most abundant proteins expressed in mature adipocytes. It has been demonstrated, from cross-sectional studies, to be associated with macrovascular complications in patients with diabetes and its levels predict incident diabetes as well as cardiovascular disease outcomes. Our previous work has shown that circulating levels of AFABP were higher in patients with advancing stages of diabetic nephropathy. We investigated whether serum AFABP could predict the progression of diabetic nephropathy. Method: Baseline serum AFABP levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. Chronic kidney disease (CKD) progression was defined as a drop in estimated glomerular filtration rate (eGFR) category accompanied by a 25% or greater drop in eGFR from baseline. The role of AFABP in predicting CKD progression over a median follow-up of 4 years was analyzed using Cox regression analysis. Result: At baseline, serum AFABP levels increased progressively with CKD staging (p for trend < 0.001). Amongst 1071 subjects with baseline CKD stage 3 or less, 171 subjects (16.0%) had CKD progression after a median follow up of 4 years. Subjects with CKD progression were older (p < 0.001), with longer duration of diabetes (p = 0.001) and higher baseline HbA1c levels (p = 0.008), more of them being hypertensive (p < 0.001) and on anti-hypertensive medications including ACEI or ARB (p < 0.001), lower baseline eGFR (p < 0.001), higher C-reactive protein (p < 0.001) and higher serum triglyceride levels (p < 0.001) than those without CKD progression. Serum AFABP levels were significantly higher in those with CKD progression during follow-up than those without progression (p < 0.001). Baseline sex-adjusted serum AFABP levels were higher in subjects with CKD progression (10.9 mg/L [IQR 6.76– 17.2] vs 7.00 mg/L [IQR 4.41–11.6] in male and 17.2 mg/L [IQR 11.1–28.0] vs 12.4 mg/L [IQR 7.94–21.9] in female; p < 0.001]). On multivariable Cox regression analysis including also other biologically relevant variables, baseline serum AFABP level was independently associated with CKD progression (Hazard ratio 1.52; 95% CI = 1.18–1.96; p < 0.001), together with sex, age, body mass index, smoking status, duration of diabetes, HbA1c, systolic blood pressure, the use of ACEI/ARB and C-reactive protein level at baseline. Conclusion: Elevated baseline serum AFABP level appears to be a useful biomarker for predicting kidney disease progression in diabetic nephropathy.
OP20 CORRELATION OF BETATROPHIN WITH AGE AND CREATININE CLEARANCE IN JAPANESE PATIENTS WITH TYPE 2 DIABETES S. Tokumoto1 , Y. Hamamoto1 , K. Fujimoto1 , E. Yamaguchi1 , Y. Shibayama1 , E. Okamura1 , Y. Wada1 , H. Ikeda1 , S. Honjo1 , A. Hamasaki1 . 1 Center for Diabetes & Endocrinology, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, osaka, Japan Background: Betatrophin(BTH) was recently found to be a potent promoter of beta-cell proliferation and insulin secretion in mice. Through the regulation of angiopoietinlike protein 3 (ANGPTL3), BTH is also involved in triglyceride metabolism. Since the pathophysiological role of BTH in patients with type 2 diabetes remains to be unknown, we measured plasma BTH levels in Japanese patients with type 2 diabetes(T2DM) and investigated the correlations of plasma BTH levels with other clinical parameters. Method: Blood samples were collected overnight fasting in P800 tubes (Becton Dickinson) from 41 patients with T2DM (mean age 59.4±10.6 years). Plasma BTH levels were determined with an ELISA (Wuhan Eiaab science, Wuhan, China; Catalogue No. E11644h). The subjects were characterized for age, BMI, glycosylated hemoglobin, fasting plasma glucose, total cholesterol, triacylglycerol, and creatinine clearance (CrCl) calculated by 24-hour urine collection. Correlations were evaluated by univariate linear regression using Pearson product moment. All data are presented as mean ±SD. P values < 0.05 were considered statistically significant. Result: Mean BTH concentration was 1203.07±585.38 pg/ml. A strong positive correlation between plasma BTH levels and age (r2 = 0.43, correlation coefficient 0.66, p < 0.001) and a negative correlation between BTH concentration and CrCl (r2 = 0.10, correlation coefficient 0.32, p = 0.037) were observed. There was no correlations between plasma BTH levels and BMI (r2 = 0.04, p = 0.09), total cholesterol (r2 = 0.04, p = 0.16), triacylglycerol concentration (r2 = 0.03, p = 0.25), HbA1c (r2 = 0.03, p = 0.23), and fasting plasma glucose (r2 = 0.00, p = 0.81). Conclusion: Circulating levels of BTH were significantly correlated positively with age and negatively with CrCl, but not with other clinical parameters of glucose homeostasis and lipid metabolism. From our results, BTH might be excreted in the urine and unlikely to affect glucose homeostasis. Reference(s) Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic b cell proliferation. Cell 2013; 153: 747–758.
Microvascular complications OP21 ASSOCIATION OF TYPE 2 DIABETES SUSCEPTIBILITY LOCI WITH PERIPHERAL NERVE FUCNTION IN A CHINESE POPULATION WITH DIABETES: RESULTS FROM NERVE CONDUCTION STUDIES J.Y. Lu1 , Y. Luo1 , C. Hu1 , R. Zhang1 , C.R. Wang1 , W.P. Jia1 . 1 Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai Key Laboratory of Diabetes Mellitus,Shanghai Clinical Center for Diabetes, Shanghai, China Background: Diabetic polyneuropathy (DPN) is the most common form of diabetic neuropathy with an estimated prevalence of 50%. Activation of the polyol pathway, excessive oxidative stress, advanced glycation end-products were widely thought to be involved in the development of DPN. In addition, there is emerging evidence that genetic predisposition may contribute to the development of DPN. To