Diabetes &CAD: Blood Sugar, How much low is safe.

Dr Ramachandra Barik,MD,DNB.

Assistant Professor,NIMS.

Define DM-II

Diabetes mellitus is a state of premature cardiovascular death associated with chronic hyperglycemia and may also be associated with blindness and renal failure. – Miles Fisher.

ADA-2012

95% of DM patients are Type 2

INDIAAsian Indian Phenotype” - 40-60% of global CVD burden within the next 10-15 years. India, Pakistan and Bangladesh- 3 of the top ten countries in world and together, the highest number of DM -related deaths. India - 50.8 million DM , the biggest. Delhi Diabetes Community (DEDICOM) and DiabCare Asia Sub-optimal Rx-50 % (HbA1c >8%) Aspirin-20% ,Lipid and BP targets- 50%, Severe late-stage complications -55%.

World DM II -21.9 % now and 26.3% by 2030 of total death

x2-4 ↑ risk of CVD.

AusDiab –

DM II-(HR 2.6,95%CI:1.4–4.7) IOGTT - (HR 2.5, 95% CI: 1.2–5.1).

CVD - 65-75% of deaths in DM II

DM Type II

The PathoPhysiology.Hyperglycemia and its 2ndary effect.

Worsening of atherogenic dyslipidaemia (small LDL, reduced HDL & ↑TG, SNS dysfunction,CKD. Endothelial dysfunction, vasoconstrictive, proinflammatoryand 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

DM II Update surrounding the relationship between glucose control and the risk of CVD.

Screen clipping taken: 28-Nov-12, 3:36 PM

Observational Studies1.Relation between glucose & CVD related death Linear ,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 & increasing HbA1c levels.

3. No association between HbA1c levels < 5.0% and fatal and non-fatal CHD.

4.↑ HbA1c levels were associated with an ↑ HR for CHD events of 1.38 (95% CI:1.22–1.56) when compared with a reference range HbA1c 5.0–5.5%.

5. United Kingdom Prospective Diabetes Study (UKPDS)- a study of subjects with newly DM II shows 1% ↓ HbA1c → 14%(95% CI: 8–21%) decrease in the relative risk 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 of approximately 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.

N=13867 newly DM II randomised to an intensive glucose control using of SU or 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 conventional Rx 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 with intensive glucose control.

metformin (N=343) Vs conventional Rx (n = 411) , no significant gap in HbA1c between 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 effect on microvascular complications metformin ↓ CV events that are to some extent independent of glucose control.

The United Kingdom Prospective Diabetes Study (UKPDS) Glucose Interventional Study-10Yrs F/u.

As most patients without DM II have an HbA1c level < 6.5%, the question remained after the completion of the UKPDS in 1997 as to whether targeting HbA1c levels close to the non-diabetic range might still result in a significant reduction in CV events.

intensive glucose control could reduce the risk of CV outcomes in DM II three large interventional trials published in mid 2008 .

Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial , the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) and the Veterans Administration Diabetes Trial (VADT) .

Recent Intensive Glucose Control Trials

Metaanalysis :Intensive glucose level lowering.1.Only glycemic not enough.2.Significant ↓ in MI rates with no increase in CV or all-cause mortality despite increased rates of severe hypoglycaemia.

3.↓ microvascular outcomes and that in the setting of newly diagnosed type 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 can be safely reduced toHbA1c levels between 6.5% and 7.0%.

6. ACCORD warns detail scanning ,before intensive GLU control for 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 glycemic controls.8.Metformain has over other hyglycemic agents to ↓ CVD till today in young obese till incretin analogs and DPP-4 inhibitors takes over.

Define DM-II

Diabetes mellitus is a state of premature cardiovascular death associated with chronic hyperglycemia and may also be associated with blindness and renal failure. – Miles Fisher.

ADA-2012

HbA1c levels of <7.0% still remains gold standard 1.In general good GLU control.2.New Dx DM3.Young without significant co-morbidities to ↓ microvascular and macrovascular complications.

TOO TIGHT FOR AGED AND LONG STANDING DM II IS HARMFUL. Australian Diabetes Society published a position statement on individualisation of HbA1c targets for DM II as below.

ARROWING THE TARGET

Life’s Simple 7 Tips to CV Health.

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