Glucose Control: Does it lower CV risk?

Transcription

1 Glucose Control: Does it lower CV risk?

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

3

4

5

6

7

8 Incidence per 1000 Person Years (%) Incidence Rates of MI and Microvascular Endpoints by Mean Hemoglobin A 1c : UKPDS Myocardial Infarction 20 0 Microvascular Endpoints Updated Mean Hemoglobin A 1c Concentration (%) Adjusted for age, sex, and ethnic group Stratton IM et al. BMJ 2000;321: Slide Source: ukpds Lipids Online

9 2008

10 Cumulative incidence of non-fatal MI, stroke or death from CVD HbA 1C (%) DCCT/EDIC: glycaemic control reduces the risk of non-fatal MI, stroke or death from CVD in type 1 diabetes 9 Conventional treatment 8 Intensive treatment DCCT (intervention period EDIC (observational follow-up) Years % risk reduction in non-fatal MI, stroke or CVD death* (P = 0.02; 95% CI: 12 79%) Intensive treatment Conventional treatment 0.00 *Intensive vs conventional treatment DCCT (intervention period) EDIC (observational follow-up) Years Adapted from DCCT. N Engl J Med 1993; 329: DCCT/EDIC. JAMA 2002; 287: DCCT/EDIC. N Engl J Med 2005; 353:

11 3 major studies that are referred to, ADVANCE, ACCORD, VADT to provide answers All studies of Intensive glucose control vs looser glucose control All were in very high risk patients who had their diabetes for 8-11 years Either had documented vascular disease or Very high risk based on risk factors

12 Mean A1c 7.5% Mean A1c 6.4%

13 Non-fatal MI, non-fatal CVA, death from CV causes ACCORD: Mean A1c 7.5% Mean A1c 6.4%

14

15 Mean A1c s 9.4% to 8.4% 9.4% to 6.9% VADT

16 And 6.9% 8.4% hazard ratio in the intensive-therapy group of 0.88 (95% confidence interval [CI], 0.74 to 1.05). VADT

17 VADT

18 P =.o3 VADT

19 NEJM Vol 358, No 24, June12, 2008: ACCORD heterogeneity

20 Benefits of early vs late glycaemic intervention HbA 1c (%) Metabolic Memory = Glycaemic legacy 10 9 Estimated HbA 1c timecourse based on UKPDS data Enters VADT intensive treatment arm 8 7 Bad glycaemic legacy drives risk of complications HbA 1c time course in VADT 6 Ideal time-course of glycaemic control Time since diagnosis (years) UKPDS: United Kingdom Prospective Diabetes Study VADT: Veterans Affairs Diabetes Trial Adapted from Del Prato S. Diabetologia 2009;52:

21 Proportion of patients with events overweight patients Myocardial Infarction Conventional (411) Intensive (951) Metformin (342) M v C p=0.010 M v I p= Years from randomisation RRR 31% ukpds

22

23 Delay in Treatment Intensification Increases the Risks of Cardiovascular Events in Patients with Type 2 Diabetes Compared to patients with HbA1c <7%, in patients with HbA1c 7%, a 12 month delay in receiving treatment intensification was associated with significantly increased risk: MI 67% STROKE 51% HF 64% CVE 62% HR 1.67 (CI: 1.39, 2.01)* HR 1.51 (CI: 1.25, 1.83)* HR 1.64 (CI: 1.40, 1.91)* HR 1.62 (CI: 1.46, 1.80)* MI= myocardial infarction, HF=Heart Failure, CVE= composite MI, Stroke & HF Retrospective cohort study (N = 105,477) from the United Kingdom Clinical Practice Research Datalink Not Proof of Cause and Effect * P <0.01 Adapted from Paul SK et al. Cardiovasc Diabetol Aug 7;14:100.

24 NEJM Vol 358, No 24, June12, 2008 HR 1.22, p =.04

25 What does ACCORD really tell us? Tight glycemic control shows CV benefit after 5 years People who died had higher A1c s People who died were people in whom it was not possible to lower their A1c s People who died had a high Hemoglobin Glycation Index People who died tended not to be on beta blockers

26

27 When you look at who actually died.

28

29 Hemoglobin Glycation Index (HGI) Someone has a high HGI, (i.e., rapid glycator) if their glucoses are good but their A1c is high Someone has a low HGI, (i.e., slow glycator) if their glucoses are high but their A1c is low

30 Low HGI High HGI

31

32

33

34 High HGI Low HGI

35

36

37 People on beta blockers had more events (not as surprise they had more disease) but being on intensive therapy lowered the event rate People not on beta blockers didn t have as many events (less disease) but intensive therapy did not lower the event rate

38 People on beta blockers had more events (not as surprise they had more disease) but being on intensive therapy did not increase the event rate People not on beta blockers didn t have as many events (less disease) but intensive therapy increased the event rate

39 Summary and Conclusions (1): Good glycemic control lowers risk of microvascular disease Aggressive glucose control prior to the development of a large atherosclerotic burden seems to be best strategy Aggressive glucose control early in the course of diabetes seems to be the best strategy This does not mean that if an individual has had their diabetes for a long period or has had a CV event that they won t benefit will take more time

40 Summary and Conclusions (2): A1c does not always tell the whole story. Look at the glucoses Look at the Pt s glucose meter!!! If A1c is high but glucoses are good, this patient is a rapid glycator with a high HGI. This is a higher risk patient There seems no gain in pushing his glucoses down further to lower his A1c It won t happen It would increase risk of hypoglycemia Concentrate on other risk factors

41 Summary and Conclusions (3): In people with vascular disease, beta blockers appear to be synergistic with tightening glucose control to lessen CV complications Protection for adrenergic stimulation from either Hypoglycemia? Further hyperinsulinemia????

42 Individualizing A1C Targets 2013 Consider % if: which must be balanced against the risk of hypoglycemia guidelines.diabetes.ca BANTING ( ) diabetes.ca Copyright 2013 Canadian Diabetes Association

43

44 Hardin s suggestion for A1c target: Keep the above targets in mind, but Try to achieve the lowest A1c possible with the best balance of minimal highs and minimal lows The determination of best balance of minimal lows depends on risk of hypoglycemia and other general factors To do this, you must look at the meter and the logbook