Clinical & Experimental Cardiology

Clinical & Experimental Cardiology
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Research Article - (2017) Volume 8, Issue 10

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Impact of Acarbose on the Serum YKL-40 Concentrations of Coronary Heart Disease Patients with Impaired Glucose Tolerance

Yihong Ni*
Department of Endocrinology, The Second Hospital of Shandong University, China
*Corresponding Author: Yihong Ni, Department of Endocrinology, The Second Hospital of Shandong University, BeiYuan Road 247#, JiNan, ShanDong, 250033, China, Tel: +86 531-85875772 Email:

Abstract

Background: YKL-40 is involved in inflammation and endothelial dysfunction, and associated with diabetes and atherosclerosis  disease. In the present study we investigated the effect of an alpha-glucosidase inhibitor, acarbose, on coronary heart disease patients with impaired glucose tolerance (IGT) and the impact of acarbose on the serum YKL-40 concentrations of these patients.
Methods: This was a 24 weeks study in patients with established coronary artery disease (CAD) (50% stenosis on quantitative coronary angiography) who were newly diagnosed with IGT. After undergoing coronary angiography, CAD patients with IGT were randomly allocated to receive either acarbose 100 mg/d (C group) or no treatment group (B group) for 24 weeks. 30 patients with CAD and normal glucose tolerance were enrolled in control group (A group). Anthropometrical evaluation, fast blood glucose (FBG), postprandial blood glucose (PBG), serum fast insulin (FINS), lipid profile including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), HbA1c and serum YKL-40 were measured at baseline and 24 weeks end point.
Results: There were no significant differences among tree groups in terms of age, gender distributions, SBP, DBP, TGTC, HDL-C, LDL-C, FBG. The levels of WHR, BMI, FINS, HOMA-IR, YKL-40 in the B group were significantly higher than A group. After 24-weeks treatment of acarbose (100 mg/d), the levels of WHR, TG, YKL-40 FINS, PBG, HbA1c and HOMA-IR were significantly reduced (p<0.05).
Conclusions: After the treatment of acarbose 100 mg/d, the coronary heart disease patients with IGT had a beneficial effect in the glucose and lipid metabolism, the insulin resistance and serum YKL-40 concentrations were decreased.

Keywords: Acarbose; Coronary heart disease; Impaired glucose tolerance (IGT); YKL-40

Abbreviations

CAD: Coronary Artery Disease; IGT: Impaired Glucose Tolerance; T2DM: Type 2 Diabetes Mellitus; WHO: World Health Organization; OGTT: Oral Glucose Tolerance Test; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; WHR: Waist Circumference/Hip Circumference; BMI: Body Mass Index; FBS: Fasting Blood Sugar (FBS);FINS: Fasting Insulin; TG: Triglycerides; TC: Total Cholesterol; HDL-C: High-density Lipoprotein Cholesterol; LDL-C: Low-density Lipoprotein Cholesterol; HOMA-IR: Homeostasis Model Assessment of Insulin Resistance

Background

Insulin resistance is an important factor that substantially increases the risk for atherosclerotic cardiovascular disease and diabetes [1,2]. Impaired glucose tolerance (IGT) is considered a pre stage of the onset of T2DM and this stage has the typical characteristics of insulin resistance. Several clinical studies had confirmed the increased risk of coronary artery disease (CAD) in patients with IGT [3,4]. Insulin resistance could explain the increased risk for CAD in patients with IGT because insulin resistance is associated with IGT and postprandial hyperglycemia [5]. To investigate the pathogenesis of IGT and CAD, seek the effective control measures to improve the insulin resistance is beneficial for the treatment of CAD patients. YKL-40 is a 40 kDa heparin-and chitin-binding glycoprotein. It is secreted in vitro by several cell-types with relation to the innate immune system, e.g. activated macrophages and vascular smooth muscle cells [6,7]. YKL-40 is a potent angiogenic factor and is thought to facilitate the formation of atherosclerotic plaques [8]. In addition, elevated YKL- 40 levels have been found in cardiovascular disease, diabetes (T2DM), and several types of cancer [9,10,11]. In this study we aimed to investigate the effect of an alpha-glucosidase inhibitor, acarbose, on coronary heart disease patients with impaired glucose tolerance (IGT) and the impact of acarbose on the serum YKL-40 concentrations of these patients.

Materials and Methods

Subjects and methods

Participants were recruited from the Department of Cardiology and Endocrinology at the Second Hospital of Shandong University (Jinan, China) for elective coronary angiography between January 2016 and August 2016. According to the coronary angiography outcome, patients should have 50% stenosis on quantitative coronary angiography and be diagnosed CAD. At the same time, all of the subjects exhibited a normal oral glucose tolerance test (75 g glucose) according to World Health Organization (WHO) 1999 criteria [12]. IGT was defined as a fasting plasma glucose concentration 70 years, history of unstable angina, myocardial infarction, heart failure, cerebrovascular accident or major surgery within the 6 months preceding the study. Patients with acute or chronic inflammatory disease, history of kidney, respiratory, hypertension, DM disease, tumor diseases, rheumatic immune diseases, and any disease that might affect absorption of medications were excluded. None of the patients had previously received acarbose therapy. All patients didn’t have the medication history of any non-steroidal anti-inflammatory drugs, -blockers, anticoagulants and antipsychotics drugs. Tea and coffee were forbid before 12 h of the test. A total of 52 subjects met with the enroll criteria and they were then randomly allocated to either the acarbose ( Bayer Healthcare Pharmaceuticals Inc ) 100-mg/d group for 24 weeks (C group, 26 cases) or the control group (no treatment B group, 26 cases). We chose another 30 subjects (A group, 30 cases) with simple CAD and normal glucose tolerance as control group. One patient in C group withdrew because of gastrointestinal side effects during the first month. This study was approved by the human research ethics committee of the hospital, and informed consent was obtained from each patient.

Clinical and biochemical measurements

All subjects underwent anthropometrical evaluation. Height, weight, waist circumference, and hip circumference were measured by a trained nurse. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were also measured. Biochemical parameters including fast blood glucose (FBG), postprandial blood glucose (PBG), serum fast insulin (FINS), lipid profile including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), HbA1c and serum YKL-40 were performed at baseline and at the end of the study. Venous blood was collected after overnight fasting, centrifuged, and the separated serum was frozen immediately at -80°C. FBG was measured by the glucose-oxidase method. Fasting insulin was assessed using a commercially available radioimmuno assay kit (Linco Research, St. Louis, MO, USA). Serum total cholesterol, HDL cholesterol, and triglycerides were measured using the Beckman DXC 800 analyzer (USA). LDL cholesterol was calculated from these results. YKL-40 (Quidel, San Diego, CA, USA) was measured by using commercially available enzyme-linked immunosorbent assays (ELISA) according to the manufacturer’s protocol. The intra-assay coefficients of variation were 9% and inter-assay coefficients of variation were 11%. Insulin resistance was estimated using the homeostasis model assessment equation (homeostasis model assessment of insulin resistance (HOMAIR)=fasting insulin (mU/ml) *fasting glucose (mmol/L)/22.5. BMI=body weight/ body height [2]. After 24 weeks, the 25 patients with severe CAD repeated the same clinical and biochemical measurements.

Statistics analysis

Data were expressed as mean ± standard deviation (M ± SD), median (interquartile range). Before analysis, data were tested for normality of distribution using the Shapiro-Wilk test. The t-test was applied to compare the differences of the measurement data between the groups. Pearson’s correlation coefficient univariate and stepwise multivariate linear regression analyses were performed for calculation of associations between serum YKL-40 and other variables. SPSS 19.0 software was used for statistical analysis. P

Results

The characteristics of the participants are shown in Table 1 and Table 2

The study enrolled 82 patients including 30 cases of CAD without IGT in A group and 26 untreated cases of CAD with IGT in B group and 26 treated cases of CAD with IGT in C group. One patient in C group withdrew because of gastrointestinal side effects during the first month. There was no cardiovascular event during 24 weeks. The baseline characteristics of the patients with complete follow-up data are summarized in Table 1. As can be seen, there were no significant differences among tree groups in terms of age, gender distributions, SBP, DBP, TGTC, HDL-C, LDL-C, FBG. The levels of WHR, BMI, FINS, HOMA-IR, YKL-40 in the B group were significantly higher than A group. After 24 weeks treatment of acarbose (100 mg/d), we got the same indexes of 25 patients with CAD and IGT. As showed in Table 2, the levels of WHR, TG, YKL-40, FINS, PBG, HbA1c and HOMA-IR in C group were significantly reduced comparing to B group (p<0.05).

  A group B group C group
Cases(n) 30 26 25
Male/female (M/F) 16/14 12/14 13/12
Age 58 ± 9 56 ± 7 59 ± 10
SBP (mmHg) 132 ± 14 135 ± 16 134 ± 13
DBP (mmHg) 80 ± 12 81 ± 14 84 ± 11
WHR (cm) 0.83 ± 0.18 0.92 ± 0.15* 0.89 ± 0.25*
BMI (Kg/m2) 23.12 ± 2.38 25.09 ± 1.52* 25.16 ± 1.23*
FBG (mmol/L) 4.68 ± 0.77 4.98 ± 0.51 5.10 ± 0.63
PBG (mmol/L,2) 6.43 ± 1.30 8.98 ± 1.10* 8.36 ± 0.84*
HbA1C (%) 5.0 ± 0.5 5.8 ± 0.6* 6.0 ± 0.38*
FINS (mU/L) 9.48 ± 1.71 12.20 ± 1.02* 12.94 ± 1.73*
TG (mmol/L) 1.75 ± 0.62 1.82 ± 0.63 1.79 ± 0.37
TC (mmol/L) 5.27 ± 1.38 5.43 ± 1.20 5.31 ± 0.84
HDL-C (mmol/L) 1.35 ± 0.31 1.30 ± 0.43 1.35 ± 0.21
LDL-C (mmol/L) 3.25 ± 0.83 3.31 ± 1.14 3.20 ± 0.72
HOMA-IR 1.97 ± 0.49 2.72 ± 0.37* 2.80 ± 0.35*
YKL-40 (ug/L) 85.93 ± 15.41 122.3 ± 20.35 * 125.2 ± 15.32*

Table 1: Baseline demographic and clinical characteristics of study patients, A group: Patients with simple CAD and normal glucose tolerances; B group: Patients with CAD and impaired glucose tolerance; C group: Patients with CAD and impaired glucose tolerance and 100-mg/d acarbose treatment.

  B group C group
SBP (mmHg) 130 ± 12 132 ± 15
DBP (mmHg) 84 ± 11 81 ± 17
WHR (cm) 0.91 ± 0.13 0.88 ± 0.12#
BMI (Kg/m2) 25.29 ± 1.56 23.35 ± 2.20#
FBG (mmol/L) 4.88 ± 0.66 4.70±0.63
PBG (mmol/L,) 9.12 ± 1.08 6.24 ± 0.96#
HbA1C (%) 5.9 ± 0.5 5.2 ± 0.66#
FINS (mU/L) 13.16 ± 1.37 10.35 ± 1.56#
TG (mmol/L) 1.90 ± 0.49 1.69 ± 0.49#
TC (mmol/L) 5.33 ± 1.38 5.20 ± 0.96
HDL-C (mmol/L) 1.32 ± 0.81 1.36 ± 0.29
LDL-C (mmol/L) 3.28 ± 1.21 3.22 ± 0.77
HOMA-IR 2.85 ± 0.37 2.16 ± 0.44#
YKL-40 (ug/L) 129.3 ± 15.76 101.8 ± 10.26#

Table 2: Metabolic index after 24 weeks in B group and C group. Note: Compared with B group #P

Metabolic parameters and their correlations with serum YKL-40 levels

Next, we evaluated the correlation between serum YKL-40 levels and various metabolic parameters (Table 2). Pearson’s correlation analysis indicated that serum YKL-40 was positively correlated with WHR (r=0.303, p=0.01), HOMA-IR (r=0.425, p=0.004), FINS (r=0.462, p=0.002), TG (r=0.337, p=0.009), HbA1C (r=0.382, p=0.006) significantly. There was a negative correlation between YKL-40 and HDL-C but not significantly (Table 3).

  YKL-40 (r) p values
WHR 0.303 0.01*
HOMA-IR 0.425 0.004*
PBG 0.485 0.001
FINS 0.462 0.002*
TG 0.337 0.009*
HbA1C 0.382 0.006*

Table 3: Correlation coefficients (r) between YKL-40 and selected variables. Note: *P<0.05.

Logistic regression analysis was performed using CAD as a dependent variable

YKL-40 was selected as an independent variable together with age, BMI, WHR TC, TG, HDL-C, LDL-C, and HOMA-IR in all subjects. Homeostasis model assessment for PBG (OR 1.392, 95% CI 1.072 to 1.451; P=0.012), HOMA-IR (OR 1.308, 95% CI 1.069 to 1.370; P=0.008) and YKL-40 (OR 1.208, 95% CI 1.034 to 1.217; P=0.005) were independent variables associated with CAD.

Discussion

Coronary artery disease (CAD) is the leading cause of mortality worldwide, accounting for 17.1 million deaths [13]. The Euro Heart Survey (Germany) found that more than one third of the patients with CAD who underwent an OGTT had an impaired glucose tolerance [14]. Prospective studies have shown that hyperglycemia itself is clearly involved in predicting CAD [15]. A graded relationship has been demonstrated in non-diabetic subjects between fasting and postprandial glucose levels and subsequent cardiovascular event risk, indicating that the relationship between blood glucose levels and increased cardiovascular risk starts below the diabetic threshold. The Honolulu Heart Study was the first epidemiological investigation to describe the association between the plasma glucose 1 h post-glucose load and incidence of CAD [16]. Blood glucose levels, even below the diabetic range, are a significant risk marker for future CAD. With respect to fasting plasma glucose (FPG), postprandial glucose is a more important risk factor to vascular damage and CAD. As data continue to emerge, highlighting the importance of postprandial hyperglycaemia (PPHG) in predicting CAD risk, several professional bodies including the IDF have issued guidelines on the management of PPHG in type 2 diabetes.

Insulin resistance, a key feature of type 2 diabetes, is an independent risk factor for developing cardiovascular diseases (CAD). Insulin resistance in the absence of overt diabetes has been associated with endothelial dysfunction, a surrogate marker of atherosclerosis [17,18]. Insulin resistance-associated postprandial hyper-glycemia may play a role in the development and progression of CAD in patients with recently diagnosed diabetes. Study showed that individuals with elevated HOMA-IR index have the twofold risk of cardiovascular disease [19]. Quebec cardiovascular study showed that high fasting insulin is the predictor of coronary heart disease and the level of insulin is an important independent risk factor of CAD. In our study the CAD patients with IGT had higher level of FINS, HOMA-IR than the patients with simple CAD. Logistic regression analysis also showed that HOMA-IR was independent risk factor of CAD that consistent with previous findings [20]. It indicates that improvement of hyperinsulinemia and insulin resistance is important to CAD treatment.

In IGT, sustained hyperglycemia causes increased intracellular concentrations of glucose metabolites in endothelial cells and increased secretion of proinflammatory cytokines such as IL-6, TNF-α. Moreover, postprandial hyperglycemia elicited oxidative stress generation induces platelet activation and thrombin generation and aggravated the progression of atherosclerosis [21,22]. YKL-40, also known as human cartilage glycoprotein-39 (HCgp-39) or chitinase-3- like protein 1 (CHI3L1), is a heparin and chitin-binding lectin without any enzymatic activity. It is secreted in vitro by several cell-types with relation to the innate immune system, e.g. activated macrophages and vascular smooth muscle cells [23]. YKL-40 is found to be a potent angiogenic factor [24] and is thought to facilitate the formation of atherosclerotic plaques [25]. Studies found that the serum YKL-40 levels were elevated in cardiovascular disease [26,27], Elevated circulating levels of YKL-40 has been considered as marker of atherosclerosis. Recent studies reported that in T2DM subjects the levels of YKL-40 were elevated significantly and the index is proportional with the HOMA-IR. High level of YKL-40 also appeared in adult subjects who did not report a medical history of T2D and CAD comorbidities [28,29], even at the childhood stage [30]. Stine B found that in a Danish sample of non-diabetic relatives to T2DM patients fasting serum level of YKL-40 was positively associated with waist-hip-ratio, and fasting plasma triglyceride levels. None of the insulin sensitivity indexes were significantly associated with YKL-40. They suggested a role of serum YKL-40 in obesity-related low grade inflammation, but do not indicate that YKL-40 is directly involved in the development of T2DM [31]. Our study showed that the level of fasting serum YKL-40 in CAD patients with IGT was significantly higher than CAD patients. Furthermore, YKL-40 was correlated positively with HOMA-IR. It indicates that the level of YKL-40 maybe elevates form the state of IGT. As a marker of inflammation, YKL-40 should play a role in the development of insulin resistance and T2DM.

Aimed at reducing overall cardiovascular risk, the management of blood glucose levels should be as important as cardiovascular treatment. Studies have proved that effective PPHG management in individuals with IGT could reduce the risk of CAD endpoints. Acarbose is an effective drug for controlling PPHG excursion and HbA1c as cardiovascular risk factors in patients with T2DM. Post-marketing surveillance of acarbose treatment in patients with type 2 diabetes and people with IGT in China HbA1c was reduced by 1.4% and 0.9% respectively [32]. This is in accordance with data from a large 5 year follow-up study in Germany [33]. The effect of acarbose on the glucose was reliable in our study. Moreover, treatment of 24 weeks of acarbose in the study improved the FINS and HOMA-IR in the patients of CAD with IGT. This may mainly be due to reduction of PPHG. Prevention of rapid rise of PPHG and fluctuations may also protect β-cells from glucotoxicity. The effect of acarbose treatment on CAD events was first shown in the STOP-NIDDM study [34]. The STOP-NIDDM Trial investigated the effects of acarbose on the incidence of type2 diabetes and the development of cardiovascular events. It demonstrated that early intervention with acarbose in individuals with IGT significantly reduces the occurrence of newly diagnosed diabetes. The STOP-NIDDM Trial also showed that treatment of acarbose is associated with a significant reduction in cardiovascular endpoints. Other vivo and vitro experiments provided proof for the conclusion. Administration of acarbose for 12 weeks in non-obese type 2 diabetic rats improved postprandial hyperglycemia, triglyceride, and fatty acid levels. Oral administration of acarbose decreased serum levels of MCP-1 and its expression in aorta in fructose-fed rats. Furthermore, acarbose efficiently reduced the number of monocytes adherent to aortic endothelial layer, improved acethychol independent vasodilation and reduced intimal thickening of the aorta. These findings suggested that acarbose could exert athero protective properties. In our study the PPHG, TG and LDL-C of the patients with CAD and IGT got significantly decrease after 24 weeks treatment of acarbose. The improvement of glucose and lipid metabolism will be beneficial to cardiovascular disease. At the same time, the reduction of FINS and HOMA-IR comparing to baseline indicated that the improvement of insulin resistance. The serum YKL-40 level of patients who received acarbose treatment was decreased significantly. In the light of closed relationship of YKL-40 with insulin resistance and atherosclerosis, the decrease of YKL-40 should reduce the inflammation and has a protective effect on artery plaque.

Conclusion

In conclusion the patients of CAD with IGT got the improvement of glucose, lipid metabolism and insulin resistance after 24 weeks acarbose treatment. Serum YKL-40 level was also decreased significantly. The 24 weeks of acarbose treatment had a beneficial effect on the patients of CAD with IGT. The major limitation of this study is the relatively small sample size. The present study population might not represent ordinal non-diabetic subjects and thus further studies in a large number of general subjects are required to confirm our results.

Funding

This work was funded by the seed fund of the Second Hospital of Shandong University (No. S2014010004), the Science and Chinese Society of Endocrinology (No. 13020230408), Independent Innovation Foundation of Shandong University, IIFSDU (No. 26010275611071), National Natural Science Foundation of China (81670753). Shandong Provincial Natural Science Foundation, China (No. ZR2015 PH 041), the Scientific and Technological Projects of Shandong Province 2014GSF118041.

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Second Hospital of Shandong University and national research committee and with the 1964 Helsinki declaration and its later amendments ethical standards. Informed consent was obtained from all individual participants included in the study.

Author's Contributions

Xianghua Zhuang, Dianhui Wang and Dongqing Jiang participated in the data acquisition. Yihong Ni participated in the design of the study. Xiaobo Li and Fufang Wang participated in the statistical analysis. All authors read and approved the final manuscript.

References

  1. Duffy JY, Hameed AB (2015) Cardiovascular disease screening. Semin Perinatol. 39: 264-267.
  2. Ginter E, Simko V (2015) Recent data on Mediterranean diet, cardiovascular disease, cancer, diabetes and life expectancy. Bratisl Lek Listy 116: 346-348.
  3. Lathief S, Inzucchi SE (2016) Approach to diabetes management in patients with CVD. Trends Cardiovasc Med 26: 165-179.
  4. Popp Switzer M, Elhanafi S, San Juan ZT (2015) Change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance. Curr Cardiol Rep 17: 562.
  5. Kanat M, DeFronzo RA, Abdul-Ghani MA (2015) Treatment of prediabetes. World J Diabetes 6: 1207-1222.
  6. Prakash M, Bodas M, Prakash D, Nawani N, Khetmalas M, et al. (2013) Diverse pathological implications of YKL-40: answers may lie in 'outside-in' signaling. Cell Signal 25: 1567-1573.
  7. Housley WJ, Pitt D, Hafler DA (2015) Biomarkers in multiple sclerosis. Clin Immunol 161: 51-58.
  8. Shao R (2013) YKL-40 acts as an angiogenic factor to promote tumor angiogenesis. Front Physiol 4: 122.
  9. Rathcke CN, Vestergaard H (2006) YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. Inflamm Res 55: 221-227.
  10. Rathcke CN, Vestergaard H (2009) YKL-40--an emerging biomarker in cardiovascular disease and diabetes. Cardiovasc Diabetol 8: 61.
  11. Yasar O, Akcay T, Obek C, Turegun FA (2016) Diagnostic potential of YKL-40 in bladder cancer. Urol Oncol 34: 257.e19-24.
  12. Grimaldi A, Heurtier A (1999) Diagnostic criteria for type 2 diabetes. Rev Prat 49: 16-21.
  13. Park JY, Lerman A, Herrmann J (2016) Use of fractional flow reserve in patients with coronary artery disease: The right choice for the right outcome. Trends Cardiovasc Med 27:106-120.
  14. Drechsler K, Fikenzer S, Sechtem U, Blank E, Breithardt G, et al. (2008) The Euro Heart Survey - Germany: diabetes mellitus remains unrecognized in patients with coronary artery disease. Clin Res Cardiol 97: 364-370.
  15. Uusitupa MI, Niskanen LK, Siitonen O, Voutilainen E, Pyorala K (1993) Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin- dependent) diabetic and non-diabetic subjects. Diabetologia 36: 1175-1184.
  16. Rodriguez BL, Lau N, Burchfiel CM, Abbott RD, Sharp DS, et al. (1999) Glucose intolerance and 23-year risk of coronary heart disease and total mortality: the Honolulu Heart Program. Diabetes Care 22:1262-1265.
  17. Yamagishi S, Nakamura K, Matsui T (2007) Potential utility of telmisartan, an angiotensin II type 1 receptor blocker with perox- isome proliferator-activated receptor-gamma (PPAR-gamma)- modulating activity for the treatment of cardiometabolic disorders. Curr Mol Med 7: 463-469.
  18. Hsueh WA, Quinones MJ (2003) Role of endothelial dysfunction in insulin resistance. Am J Cardiol 92: 10J-17J.
  19. Karastergiou K, Kaski JC (2008) Medical management of the diabetic patient with coronary artery disease. Curr Pharm Des 14: 2527-2536.
  20. Vintila VD, Roberts A, Vinereanu D, Fraser AG (2012) Progression of subclinical myocardial dysfunction in type 2 diabetes after 5 years despite improved glycemic control. Echocardiography 29: 1045-1053
  21. Ofstad AP (2016) Myocardial dysfunction and cardiovascular disease in type 2 diabetes. Scand J Clin Lab Invest 76: 271-281.
  22. Kayama Y, Raaz U, Jagger A, Adam M, Schellinger IN, et al. (2015) Diabetic Cardiovascular Disease Induced by Oxidative Stress. Int J Mol Sci 16: 25234-25263.
  23. Rathcke CN, Vestergaard H (2006) YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. Inflamm Res 55: 221-227.
  24. Shao R (2013) YKL-40 acts as an angiogenic factor to promote tumor angiogenesis. Front Physiol 4: 122.
  25. Michelsen AE, Rathcke CN, Skjelland M, Holm S, Ranheim T, et al. (2010) Increased YKL-40 expression in patients with carotid atherosclerosis. Atherosclerosis 211: 589-95.
  26. Wang Y, Ripa RS, Johansen JS, Gabrielsen A, Steinbruchel DA, et al. (2008) YKL-40 a new biomarker in patients with acute coronary syndrome or stable coronary artery disease. Scand.Cardiovasc J 42: 295–302.
  27. Kucur M, Isman FK, Karadag B, Vural VA, Tavsanoglu S (2007) Serum YKL-40 levels in patients with coronary artery disease. Coron. Artery Dis 18: 391-396.
  28. Rathcke CN, Johansen JS, Vestergaard H (2006) YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance. Inflamm Res 55: 53–59.
  29. Rathcke CN, Persson F, Tarnow L, Rossing P, Vestergaard H (2009) YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care 32: 323–328.
  30. Kyrgios I, Galli-Tsinopoulou A, Stylianou C, Papakonstantinou E, Arvanitidou M, et al. (2012) Elevated circulating levels of the serum acute-phase protein YKL-40 (chitinase 3-like protein 1) are a marker of obesity and insulin resistance in prepubertal children. Metabolism 61: 562–568.
  31. Thomsen SB, Gjesing AP, Rathcke CN, Ekstrom CT, Eiberg H, et al. (2015) Associations of the Inflammatory Marker YKL-40 with Measures of Obesity and Dyslipidaemia in Individuals at High Risk of Type 2 Diabetes. PLoS One 10: e0133672.
  32. Mertes G. (2001) Safety and efficacy of acarbose in the treatment of Type 2 Diabetes: data from 5-year surveillance study. Diabetes Res Clin Pract 2: 193–204.
  33. Chiasson JL, Josse RG, Hunt JA, Palmason C, Rodger NW, et al. (1994) The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial. Ann Intern Med 121: 928–935.
  34. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, et al. (2002) Acarbose for prevention of type 2 diabetes mellitus: the STOPNIDDM randomised trial. Lancet 359: 2072–2077.
Citation: Ni Y (2017) Impact of Acarbose on the Serum YKL-40 Concentrations of Coronary Heart Disease Patients with Impaired Glucose Tolerance. J Clin Exp Cardiolog 8: 549.

Copyright: © 2017 Ni Y. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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