. .

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() 2015 . 4,094 (2,8% ) [1]. () 7% (7,9 ) [2]. 12% ( 64 22%) [3]. , - 2- [4].

, , 70- : 4574 , , 2 5 [5]. , 2,5 , [6]. , 4- (. 1).

: HbA_1c, , , (), , , , , [3, 6]. , [3] . , [2]. , , 25% 9% . ( 40%) , (-) [6]. , . : , , 12 [2, 3].

. () . , 2- 37,6% , 8,3% [1]. - , (. 2).

, , , , (). 40 , () (-) [7]. , , ( 2- ), : (), , , (), - [8]. , , , /- , /- [9, 10], , [11] (. 1).

, ó , 1- , 2- [11].

, : , , , , , , , , , , (, α), (. 3) [6].

, ( II, ) [2]. , , , [12]. - . , , , - , [13].

2- , 150 [14]. , 2000- , , I, , - () , [14]. , , -, , , . , ( ) , - up- ( , ), , - , , [14].

UKPDS, 32% - , . (20052010 .) : (), , , [15]. , . , , , , , [16]. , 9 (34 504 ), 6 624 (19%), . , 20% ; (< 30%) ; ( ); , ; [16]. , , , , [17]. ( () , , , , ) ( ) 2- IIIII < 45% [18]. 2006 . , 2010 . . (Canadian Diabetes Association, American Diabetes Association), (European Society of Cardiology, ESC), [1921]. - [2]. - 2- : 2- III , , IIIIV , [22]. , , - , .

2- , - . , 2010 . 2- , , 2010 ., 2013 . . - . (, ) , , , , - [23]. , - - (), [23]. , 3, , 38 [24]. , , PPARγ ( , - , I, III , ), (rosiglitazone-induced myocardial hypertrophy) [24, 25]. ( ), ( 13 ), . , PPARγ- , [3]. 7 () (RR 1,72 (1,22,42)) - [26], 2 [27]. , , - [25, 29, 30]. PROactiv, 5238 - - , ( , , HbA_1c) (- , , ) [28]. , , , , [3, 30]. [22].

- ( ), : - , - , , ( , mitochondrial permeability transition pores, MPTP) [23]. MPTP, , , , MPTP (- , , ) [31].

- 2- , . - . UKPDS 33 [32]. , , [33]. 127 555 2- , 18 , , , , , -4, [34]. , SAFEGUARD (http://www.safeguard-diabetes.org/). 44 - 12 ( 967 . ), : 5 ; 3 ; 2 ; 5 . , 20% , , 40% , ( ); 20% , [30]. , , ( , ), - . , , 2- [2023].

1 (1)

, , (, , ) [3537], [38, 39]. 2- - ( ≤ 35%, IIIIV ) , [40]. 12 (IIIIV ) 5- 1 9 , , ( ) ( 6- , ) [41]. - 1 ELIXA (NCT01147250; 6068 ; * n = 3034; n = 3034; 60 , 2- 9,3 ) [42]. - 2- (83% , 13% ) 2013 . 22,3% 22,5% . (- , , ) (13,4% 13,2% ; HR 1,02; CI: 0,891,17). , (HR 0,96; CI: 0,751,23). , -c 2- 1: LEADER (/, n = 8754, 2018 .); SUSTAIN 6 (*/; n = 6000; 2016 .); EXSEL ( LR/; n = 9500; 2018 .); REWIND (/; n = 9600; 2018 .) [43].

- 4- (4)

- - SAVOR-TIMI, 16 492 2- ( n = 8280; n = 8212), - . 82% , 12,8% . (MACE: - , , ) (MACE+), / /. 27% (3,5% 2,8% , = 0,007; RR 1,27; 95% CI: 1,071,51) . , < 60 /² /. , NT- . C- , [44]. , 4 , , [45]. , , (6,2% 5,7% ), , , [46].

2- ( , 72 738 , 52 , 11% ) [47]. , 2- , . 2- 2014 . , ( ) 7620 ( 54 , 58% ), , , , , (12,5%; aOR: 1,84, 95% CI: 1,162,92) [48]. , , , . , , TECOS - - 14 671 2- - ( (18%)) - . ( - , , , ) . . TECOS ( ) - [49].

- (EXAMINE, n = 2701; n = 2679) ( 28% ) - - post hoc . SAVOR-TIMI [50]. (40 ) (19 ) 4 [51]. 2018 . - 2- : CAROLINA (NCT01243424; n = 6 000, ) CARMELINA (NCT01897532; n = 8300, -) [43].

, , 4 , [5255]. , 4 , , [22].

- . , , - 2- , . 2012 . - 2- (SGLT2) 2- . 2014 . . SGLT2, in vitro SGLT2 > 2500 SGLT1 ( , , , , , , [56]) > 3500 SGLT4 ( , , , , , , , ) [57]. , , , , , [58]. - III EMPA-REG Outcome (NCT01131676). 42 , 590 . : 2- ≥ 18 , ≤ 45 /², HbA_1c 710% ( HbA_1c 8,1%), ≥ 30 //1,73 ² (MDRD), - ( , , , ). - ( 63,1 , 2- 10 ) : (n = 2333), 10 / (10) (n = 2345) 25 / (25) (n = 2342). 81% (/), 65% β-, 43% , 6% (). 691 , (, - , ) 2,6 , 3,1 . - ( ). , - ( ), , , , , ( ). , , / .

, 2- (), - [59]. , (. 2).

. : (HR 0,63, 95% CI: 0,540,73; < 0,001); - (HR 0,64, 95% CI: 0,5673; < 0,001). , , , [60], , , , . . . , 10,1% ( 10,5%; 9,9%). - (. 3) 26 , .

/ , - , ͻ, - , . , , , , < 60 //1,73 ², , , , β-, /, . ( ) ó (), , . , , .

, EMPA-REG OUTCOME - 34% ( - 35 3 ). .

, , , [2]. - 2- . 2- ( ) .

, , , 2- - .

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