SGLT-2 Inhibitor Effects on Cardiac and Hepatic Metabolic Profiles for the Diabetes Patients Combined With Obesity

SGLT-2 Inhibitor Effects on Cardiac and Hepatic Metabolic Profiles for the Diabetes Patients Combined With Obesity

Mechanism of the Effect by Sodium-glucose Cotransporter-2 Inhibitor on Obesity Associated Cardiomyopathy

Obesity is closely associated with an increased risk of cardiomyopathy because of the high metabolic activity of excessive fat while effective treatment of obesity-related cardiomyopathy is currently unsolved. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) are a class of diabetic medications. Besides improving glucose control, SGLT2-i has been shown to be able to reduce the bodyweight as well as the mortality and hospitalization rates for heart failure and cardiovascular disease in the type 2 diabetes patients. It has been proposed that the heart protection by SGLT2-i might be caused by modulating the production of adipokine and cytokine. The investigators will enrolled 40 patients (diabetes mellitus with BMI>27 Kg/m2) from obesity weight-reduction clinics: 1) 20 patients treated with SGLT2-i (CANA) and regular weight-reduction plan; 2) 20 patients with regular weight reduction plan, without CANA, for 4 weeks. The investigators will compare the variation of Fibroblast growth factor-21 (FGF21) related proteins and RNA between these 2 groups of subjects. The investigators will arrange cardiac ultrasound, hepatic MRI and fibroscan, body composition dual energy x-ray absorptiometry to evaluate the possible mechanisms underlying the liver and heart modification process, as a scientific basis for precision medicine in the future. Conclusions: SGLT2-i treatment may increase the concentration of FGF21, either in the liver or heart, thus to protect the high-fat diet induced obesity associated heart dysfunction by activating FGF21 downstream protein expression.

The investigators will enrolled 40 diabetes mellitus with BMI>27 Kg/m2 patients from obesity weight-reduction clinics and will compare the variation of FGF21 related proteins between these 2 groups of subjects. Serial examinations will evaluate the possible mechanisms underlying the protective mechanism. This investigation expect that SGLT2-inhibitor can increase the concentration of FGF21 in the heart by increasing FGF21 in the liver, thereby modifying associated protein expressions and ultimately improving cardiac function and patient outcomes.

The fibrotic score and severity by MRI of the liver will be performed before and after the treatment. The measurement of fatty liver requires both in-phase (IP) and out-of-phase (OOP) imaging to be adequately assessed. Fatty liver appears: T1: hyperintense, T2: mildly hyperintense, IP/OOP imaging: signal drop out on OOP imaging On IP/OOP imaging, signal loss is demonstrated when there is 10-15% fat fraction with maximum signal loss occurring when there is 50% fatty infiltration of the liver. In situations in which there is >50% fatty infiltration, the out-of-phase sequence paradoxically becomes less hypointense than at 50%.

compare BMI before and after treatment; BMI is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and height in metres.

Inclusion Criteria: Age> 20 years of age With diagnosis of diabetic mellitus (HbA1C≧6.5%) by medical record or physicians BMI ≧ 27 kg/m2, which is the current definition of obesity from Health Promotion Administration, Ministry of Health and Welfare. Exclusion Criteria: Unwilling to participating current clinical trial Cannot tolerate SGLT2-i therapy Not willing to join the study History of failure treatment experience from SGLT2-i or other weight reduction plan Received pharmaceutical or clinical trials within past 1 year