Blood sugar- how much low is safe in coronary artery disease- copy


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  • intensive glucose control is associated with a reduced risk of MI, without a clear benefit on other CV diseases such as stroke, intensive glucose control is associated with increased rates of severe hypoglycaemia but not increased rates of CV or all-cause mortality. Aiming for HbA1c levels of <7.0% still remains the general target for good glucose control. Under certain circumstances, aiming for lowerHbA1c levels may be appropriate in setting of newly Dx DM in relatively young without significant co-morbidities and in patients treated with agents that minimise the risk of severe hypoglycaemia such as metformin. Whether this also applies to newer glucose lowering agents that target the incretin system will depend on CV outcomes of long-term studies which are in progress.
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  • Blood sugar- how much low is safe in coronary artery disease- copy

    1. 1. Diabetes &CAD: Blood Sugar, How much low is safe. Dr Ramachandra Barik,MD,DNB. Assistant Professor,NIMS.
    2. 2. ADA-2012 Define DM-IIDiabetes mellitus is a state of premature cardiovascular death associated withchronic hyperglycemia and may also be associated with blindness and renalfailure. – Miles Fisher.
    3. 3. 95% of DM patients are Type 2
    4. 4. World DM II -21.9 % now and 26.3% by 2030 of total deathINDIAAsian Indian Phenotype” - 40-60% ofglobal CVD burden within the next 10-15years. India, Pakistan and Bangladesh- 3 ofthe top ten countries in world andtogether, the highest number of DM DM Type II-related deaths. India - 50.8 million DM , the biggest. x2-4 ↑ risk of CVD. Delhi Diabetes Community(DEDICOM) and DiabCare Asia AusDiab – Sub-optimal Rx-50 % (HbA1c >8%)Aspirin-20% , DM II-(HR 2.6,95%CI:1.4–4.7)Lipid and BP targets- 50%,Severe late-stage complications -55%. IOGTT - (HR 2.5, 95% CI: 1.2–5.1). CVD - 65-75% of deaths in DM II
    5. 5. The PathoPhysiology. Hyperglycemia and its 2ndary effect. Worsening of atherogenic dyslipidaemia (small LDL, reduced HDL & ↑TG, SNS dysfunction,CKD. Endothelial dysfunction, vasoconstrictive, proinflammatory and prothrombotic processes that contribute to plaque development and rupture.  protein kinase C, and the formation of polyols,hexosamine and advanced glycation endproducts.  NKF-B & ↑ reactive O2 species- pivotal accelerated CVD . HTN
    6. 6. DM II Update surrounding the relationship between glucose controland the risk of CVD.
    7. 7. Screen clipping taken: 28-Nov-12, 3:36 PM
    8. 8. Observational Studies1.Relation between glucose & CVD related deathLinear ,continuous,“J-shaped” or U shape.2. In AusDiab Study N=10,000 without DM ,reported a continuous ↑ risk for CV mortality with↑ 2hrs glucose levels after OGTT & increasingHbA1c levels.3. No association between HbA1c levels < 5.0%and fatal and non-fatal CHD.4.↑ HbA1c levels were associated with an ↑ HR forCHD events of 1.38 (95% CI:1.22–1.56) whencompared with a reference range HbA1c 5.0–5.5%.
    9. 9. 5. United Kingdom Prospective Diabetes Study (UKPDS)- a study of subjects withnewly DM II shows 1% ↓ HbA1c → 14%(95% CI: 8–21%) decrease in the relativerisk MI .6. UK General Practice Research Database (elderly- 28,000) - “U-shaped”association between HbA1c levels and CV events and lowest at an HbA1c level ofapproximately 7.5% . These theoretical relationships between glycaemia and CV outcomes have been recently tested in interventional trials of intensive glucose control that have been published over the last two years.
    10. 10. The United Kingdom Prospective Diabetes Study(UKPDS) Glucose Interventional Study-10Yrs F/u.N=13867 newly DM II randomised to an intensive glucose control using of SUor insulin and a conventional lifestyle management.Intensively Rx - mean HbA1c of 7.0% compared with conventionally Rx - 7.9%.1% ↓ HbA1c and a 16% (RR 0.84, 95% CI: 0.71–1.0) ↓ MI compared to conventionalRx which just failed (p = 0.052).No effects of intensive glucose control on any other CVD outcomes.Intensive glucose control reduced the risk of microvascular complications by 25%(95% CI: 7–14, p = 0.01).Non-significant (6%) relative reduction in all-cause mortality associated withintensive glucose control. metformin (N=343) Vs conventional Rx (n = 411) , no significant gap in HbA1cbetween metformin or placebo , metformins associated with a 39% relative ↓ MI(p = 0.01) and a 36% relative ↓ in all-cause mortality (p = 0.01) without any effecton microvascular complications metformin ↓ CV events that are to someextent independent of glucose control.
    11. 11. Recent Intensive Glucose Control TrialsAs most patients without DM II have an HbA1c level < 6.5%, the questionremained after the completion of the UKPDS in 1997 as to whethertargeting HbA1c levels close to the non-diabetic range might still result ina significant reduction in CV events.intensive glucose control could reduce the risk of CV outcomes in DM IIthree large interventional trials published in mid 2008 .Action to Control Cardiovascular Risk in Diabetes (ACCORD)trial , the Action in Diabetes and Vascular Disease: Preteraxand Diamicron Modified Release Controlled Evaluation(ADVANCE) and the Veterans Administration Diabetes Trial(VADT) .
    12. 12. Metaanalysis :Intensive glucose level lowering.1.Only glycemic not enough.2.Significant ↓ in MI rates with no increase in CV or all-cause mortalitydespite increased rates of severe hypoglycaemia.3.↓ microvascular outcomes and that in the setting of newly diagnosedtype 2 diabetes→ benefit on CV outcomes.4.Early strict glycaemic control protects in long run.5. ADVANCE and VADT :if the correct strategy is used, glucose levels canbe safely reduced toHbA1c levels between 6.5% and 7.0%.6. ACCORD warns detail scanning ,before intensive GLU controlfor established DM II and at high CV risk, using a combination of multiple-insulin injections and oral agents to rapidly target an HbA1c of <6.5%should be avoided.7.Younger age and early onset of DM II do tolerate agressive glycemiccontrols.8.Metformain has over other hyglycemic agents to ↓ CVD till today inyoung obese till incretin analogs and DPP-4 inhibitors takes over.
    13. 13. ADA-2012 Define DM-IIDiabetes mellitus is a state of premature cardiovascular death associated withchronic hyperglycemia and may also be associated with blindness and renalfailure. – Miles Fisher.
    14. 14. ARROWING THE TARGET HbA1c levels of <7.0% still remains gold standard1.In general good GLU control.2.New Dx DM3.Young without significant co-morbidities to ↓ microvascular and macrovascularcomplications. TOO TIGHT FOR AGED AND LONG STANDING DM II IS HARMFUL. Australian Diabetes Society published a position statement on individualisationof HbA1c targets for DM II as below.
    15. 15. Life’s Simple 7 Tips to CV Health.