Association between serum insulin levels and heart failure-related parameters in patients with type 2 diabetes and heart failure treated with canagliflozin: a post-hoc analysis of the randomized CANDLE trial

被引:1
|
作者
Tanaka, Atsushi [1 ]
Imai, Takumi [2 ]
Shimabukuro, Michio [3 ]
Taguchi, Isao [4 ]
Sezai, Akira [5 ]
Toyoda, Shigeru [6 ]
Watada, Hirotaka [7 ]
Ako, Junya [8 ]
Node, Koichi [1 ]
机构
[1] Saga Univ, Dept Cardiovasc Med, 5-1-1 Nabeshima, Saga 8498501, Japan
[2] Osaka Metropolitan Univ, Grad Sch Med, Dept Med Stat, Osaka, Japan
[3] Fukushima Med Univ, Dept Diabet Endocrinol & Metab, Fukushima, Japan
[4] Dokkyo Med Univ, Dept Cardiol, Saitama Med Ctr, Koshigaya, Japan
[5] Nihon Univ, Dept Cardiovasc Surg, Sch Med, Tokyo, Japan
[6] Dokkyo Med Univ, Dept Cardiovasc Med, Sch Med, Mibu, Tochigi, Japan
[7] Juntendo Univ, Dept Metab & Endocrinol, Grad Sch Med, Tokyo, Japan
[8] Kitasato Univ, Dept Cardiovasc Med, Sch Med, Sagamihara, Kanagawa, Japan
关键词
Type; 2; diabetes; Chronic heart failure; Canagliflozin; Glimepiride; Insulin; COTRANSPORTER; 2; INHIBITORS; PRESERVED EJECTION FRACTION; SODIUM-HYDROGEN EXCHANGER; ADIPOSE-TISSUE; CARDIOVASCULAR-DISEASE; SGLT2; DOUBLE-BLIND; RESISTANCE; EMPAGLIFLOZIN; RISK;
D O I
10.1186/s12933-022-01589-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Insulin resistance and hyperinsulinemia in patients with type 2 diabetes (T2D) are adversely associated with the development and worsening of heart failure (HF). Herein, we sought to investigate the effect of canagliflozin on insulin concentrations and the associations of changes in insulin concentrations with HF-related clinical parameters in patients with T2D and HF. Methods This was a post-hoc analysis of the investigator-initiated, multicenter, open-label, randomized, controlled CANDLE trial for patients with T2D and chronic HF (UMIN000017669). The endpoints were the effects of 24 weeks of canagliflozin treatment, relative to glimepiride treatment, on insulin concentrations and the relationship between changes in insulin concentrations and clinical parameters of interest, including New York Heart Association (NYHA) classification. The effects of canagliflozin on those parameters were also analyzed by baseline insulin level. Results Among the participants in the CANDLE trial, a total of 129 patients (canagliflozin, n = 64; glimepiride, n = 65) who were non-insulin users with available serum insulin data both at baseline and week 24 were included in this analysis. Overall, the mean age was 69.0 +/- 9.4 years; 75% were male; the mean HbA1c was 6.8 +/- 0.7%; and the mean left ventricular ejection fraction was 59.0 +/- 14.1%, with parameters roughly balanced between treatment groups. Canagliflozin treatment significantly reduced insulin concentrations at week 24 (p < 0.001), and the between-group difference (canagliflozin minus glimepiride) in those changes was - 3.52 mU/L (95% confidence interval, - 4.85 to - 2.19; p < 0.001). Decreases in insulin concentrations, irrespective of baseline insulin level, were significantly associated with improvement in NYHA class in patients treated with canagliflozin. Conclusion Our findings suggest that canagliflozin treatment in patients with T2D and HF ameliorated excess insulin overload, contributing to the improvement of clinical HF status. Trial registration: University Medical Information Network Clinical Trial Registry, number 000017669, Registered on May 25, 2015.
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页数:11
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