BACKGROUND: Myocardial insulin resistance (IR) could be a predictive factor of cardiovascular events. This study aimed to introduce a new method using 123I-6-deoxy-6-iodo-D-glucose (6DIG), a pure tracer of glucose transport, for the assessment of IR using cardiac dynamic nuclear imaging. METHODS: The protocol evaluated first in rat-models consisted in two 6DIG injections and one of insulin associated with planar imaging and blood sampling. Compartmental modeling was used to analyze 6DIG kinetics in basal and insulin conditions and to obtain an index of IR. As a part of a translational approach, a clinical study was then performed in 5 healthy and 6 diabetic volunteers. RESULTS: In rodent models, the method revealed reproducible when performed twice at 7 days apart in the same animal. Rosiglitazone, an insulin-sensitizing drug, induced a significant increase of myocardial IR index in obese Zucker rats from 0.96 ± 0.18 to 2.26 ± 0.44 (P<.05) after 7 days of an oral treatment, and 6DIG IR indexes correlated with the gold standard IR index obtained through the hyperinsulinemic-euglycemic clamp (r=.68, P<.02). In human, a factorial analysis was applied on images to obtain vascular and myocardial kinetics before compartmental modeling. 1.5-fold to 2.2-fold decreases in mean cardiac IR indexes from healthy to diabetic volunteers were observed without reaching statistical significance. CONCLUSIONS: These preclinical results demonstrate the reproducibility and sensibility of this novel imaging methodology. Although this first in-human study showed that this new method could be rapidly performed, larger studies need to be planned in order to confirm its performance.
BACKGROUND: Myocardial insulin resistance (IR) could be a predictive factor of cardiovascular events. This study aimed to introduce a new method using 123I-6-deoxy-6-iodo-D-glucose (6DIG), a pure tracer of glucose transport, for the assessment of IR using cardiac dynamic nuclear imaging. METHODS: The protocol evaluated first in rat-models consisted in two 6DIG injections and one of insulin associated with planar imaging and blood sampling. Compartmental modeling was used to analyze 6DIG kinetics in basal and insulin conditions and to obtain an index of IR. As a part of a translational approach, a clinical study was then performed in 5 healthy and 6 diabetic volunteers. RESULTS: In rodent models, the method revealed reproducible when performed twice at 7 days apart in the same animal. Rosiglitazone, an insulin-sensitizing drug, induced a significant increase of myocardial IR index in obese Zucker rats from 0.96 ± 0.18 to 2.26 ± 0.44 (P<.05) after 7 days of an oral treatment, and 6DIG IR indexes correlated with the gold standard IR index obtained through the hyperinsulinemic-euglycemic clamp (r=.68, P<.02). In human, a factorial analysis was applied on images to obtain vascular and myocardial kinetics before compartmental modeling. 1.5-fold to 2.2-fold decreases in mean cardiac IR indexes from healthy to diabetic volunteers were observed without reaching statistical significance. CONCLUSIONS: These preclinical results demonstrate the reproducibility and sensibility of this novel imaging methodology. Although this first in-human study showed that this new method could be rapidly performed, larger studies need to be planned in order to confirm its performance.
Authors: Marie Ng; Tom Fleming; Margaret Robinson; Blake Thomson; Nicholas Graetz; Christopher Margono; Erin C Mullany; Stan Biryukov; Cristiana Abbafati; Semaw Ferede Abera; Jerry P Abraham; Niveen M E Abu-Rmeileh; Tom Achoki; Fadia S AlBuhairan; Zewdie A Alemu; Rafael Alfonso; Mohammed K Ali; Raghib Ali; Nelson Alvis Guzman; Walid Ammar; Palwasha Anwari; Amitava Banerjee; Simon Barquera; Sanjay Basu; Derrick A Bennett; Zulfiqar Bhutta; Jed Blore; Norberto Cabral; Ismael Campos Nonato; Jung-Chen Chang; Rajiv Chowdhury; Karen J Courville; Michael H Criqui; David K Cundiff; Kaustubh C Dabhadkar; Lalit Dandona; Adrian Davis; Anand Dayama; Samath D Dharmaratne; Eric L Ding; Adnan M Durrani; Alireza Esteghamati; Farshad Farzadfar; Derek F J Fay; Valery L Feigin; Abraham Flaxman; Mohammad H Forouzanfar; Atsushi Goto; Mark A Green; Rajeev Gupta; Nima Hafezi-Nejad; Graeme J Hankey; Heather C Harewood; Rasmus Havmoeller; Simon Hay; Lucia Hernandez; Abdullatif Husseini; Bulat T Idrisov; Nayu Ikeda; Farhad Islami; Eiman Jahangir; Simerjot K Jassal; Sun Ha Jee; Mona Jeffreys; Jost B Jonas; Edmond K Kabagambe; Shams Eldin Ali Hassan Khalifa; Andre Pascal Kengne; Yousef Saleh Khader; Young-Ho Khang; Daniel Kim; Ruth W Kimokoti; Jonas M Kinge; Yoshihiro Kokubo; Soewarta Kosen; Gene Kwan; Taavi Lai; Mall Leinsalu; Yichong Li; Xiaofeng Liang; Shiwei Liu; Giancarlo Logroscino; Paulo A Lotufo; Yuan Lu; Jixiang Ma; Nana Kwaku Mainoo; George A Mensah; Tony R Merriman; Ali H Mokdad; Joanna Moschandreas; Mohsen Naghavi; Aliya Naheed; Devina Nand; K M Venkat Narayan; Erica Leigh Nelson; Marian L Neuhouser; Muhammad Imran Nisar; Takayoshi Ohkubo; Samuel O Oti; Andrea Pedroza; Dorairaj Prabhakaran; Nobhojit Roy; Uchechukwu Sampson; Hyeyoung Seo; Sadaf G Sepanlou; Kenji Shibuya; Rahman Shiri; Ivy Shiue; Gitanjali M Singh; Jasvinder A Singh; Vegard Skirbekk; Nicolas J C Stapelberg; Lela Sturua; Bryan L Sykes; Martin Tobias; Bach X Tran; Leonardo Trasande; Hideaki Toyoshima; Steven van de Vijver; Tommi J Vasankari; J Lennert Veerman; Gustavo Velasquez-Melendez; Vasiliy Victorovich Vlassov; Stein Emil Vollset; Theo Vos; Claire Wang; XiaoRong Wang; Elisabete Weiderpass; Andrea Werdecker; Jonathan L Wright; Y Claire Yang; Hiroshi Yatsuya; Jihyun Yoon; Seok-Jun Yoon; Yong Zhao; Maigeng Zhou; Shankuan Zhu; Alan D Lopez; Christopher J L Murray; Emmanuela Gakidou Journal: Lancet Date: 2014-05-29 Impact factor: 79.321