HOW MUCH BLOOD SUGAR LEVEL IS SAFE.

1. Diabetes &CAD: Blood Sugar,
How much low is safe.
Dr Ramachandra Barik,MD,DNB.
Assistant Professor,NIMS.

2. ADA-2012
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.

3. 95% of DM patients are Type 2

4. World
DM II -21.9 % now and 26.3% by
2030 of total death
INDIA
Asian 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 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

6. 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

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

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

15. Observational Studies
1.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%.

16. 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.

17. 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 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.

19. Recent Intensive Glucose Control Trials
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) .

27. 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.

28. ADA-2012
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.

29. ARROWING THE TARGET
HbA1c levels of <7.0% still remains gold standard
1.In general good GLU control.
2.New Dx DM
3.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.

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