title: Diastolic dysfunction in spontaneous type 2 diabetes rhesus monkeys: a study using echocardiography and magnetic resonance imaging.
abstract: BACKGROUND
  Diastolic heart failure is a common and deadly complication of diabetes mellitus, with the development of diabetic cardiomyopathy as one of the key determinants of the disease's complex pathology. The cause of the association is unknown and has no approved therapy strategies as of yet. However significant advances in this area may come from studies on suitable animal models.
  
  
  METHODS
  A total of 25 male rhesus monkeys (12-16 years, 9-13 kg) were enrolled. Fifteen of them were diagnosed as spontaneous type 2 diabetes mellitus (T2DM, FPG ≥ 104 mg/dl, HbA1c: 4.7-5.5 %, diabetes duration: 1-4 years). The other 10 monkeys were non-diabetic (ND, FPG < 90 mg/dl). Echocardiography and cardiac magnetic resonance were used for evaluating the cardiac structure and function. One T2DM monkey with impaired diastolic function and another ND monkey were both sacrificed to gain the necessary pathology and protein expression studies displayed here.
  
  
  RESULTS
  Six out of 15 T2DM rhesus monkeys were diagnosed with diastolic dysfunction (DD) by echocardiography. Additionally, no abnormalities were found in the group which we determined as the ND monkeys. The six DD monkeys all showed low e' velocity and decreased e'/a' ratio, among which three of them showing decreased E/A ratio and the other 3 having elevated E/A ratio, this appears to be similar to the impaired relaxation pattern and pseudonormal pattern found in human patients respectively. The EF and FS of monkeys with pseudonormal pattern decreased significantly compared with ND subjects. A CMR study showed that LVID at end systole of 5 DD monkeys is significantly longer than that of 3 ND monkeys. Of great interest, myocardium lesions and mitochondria impairments and increased expression of AGEs and caspase-3 were found in a sacrificed DD subject.
  
  
  CONCLUSIONS
  The changes in the imaging and physiological markers of spontaneous T2DM rhesus monkeys are similar to those key markers found in human type 2 diabetes and diastolic dysfunction. This monkey model could help the medical community and us to understand the pathology of this debilitating disease and serve as a beginning to explore important measures to prevent and treat diabetic cardiomyopathy.
authors.affiliation: Sichuan Industrial Institute of Antibiotics, Chengdu, China. qiancan8838@qq.com.|Sichuan PriMed Shines Bio-Tech Co., Ltd, Chengdu, China. qiancan8838@qq.com.
authors.forename: Can
authors.initials: C
authors.lastname: Qian
authors.affiliation: Sichuan PriMed Shines Bio-Tech Co., Ltd, Chengdu, China. gonglitony@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.affiliation: Sichuan PriMed Shines Bio-Tech Co., Ltd, Chengdu, China. yangzy@scprimed.com.
authors.forename: Zunyuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Radiology, West China Hospital, Sichuan University, Chengdu, China. chenwin2008@139.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Radiology, West China Hospital, Sichuan University, Chengdu, China. cys2013rui@163.com.
authors.forename: Yushu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Radiology, West China Hospital, Sichuan University, Chengdu, China. zqxu3872@163.com.
authors.forename: Ziqian
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Radiology, West China Hospital, Sichuan University, Chengdu, China. bingwu69@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Radiology, Yaan People's Hospital, Yaan, China. chungui313@126.com.
authors.forename: Chungui
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Radiology, West China Hospital, Sichuan University, Chengdu, China. gaofabao@yahoo.com.
authors.forename: Fabao
authors.initials: F
authors.lastname: Gao
authors.affiliation: Sichuan Industrial Institute of Antibiotics, Chengdu, China. zengwen10@vip.163.com.|Sichuan PriMed Shines Bio-Tech Co., Ltd, Chengdu, China. zengwen10@vip.163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D018619:Echocardiography, Doppler, Pulsed / Q000379:methods; D054144:Heart Failure, Diastolic / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D006801:Humans; D008253:Macaca mulatta; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods; D008297:Male; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology