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Cardio Diabetes Medicine 2017 427

els with pre-existing type 2 diabetes. to the fetus, a benefits of tight glycemic control on macrovascular
process termed “facilitated anabolism”. disease seem to become more evident with time, the
so-called “legacy effect” or “metabolic memory”.
It is advisable to select more stringent targets for
pregnant women with pre-existing type 2 diabetes
and gestational diabetes (FBG < 90 mg/dL, 1-h PP HYPERGLYCEMIA AND DIABETIC
< 130 mg/dL, and 2-h PP < 110 mg/dL) while more RETINOPATHY
relaxed glucose targets (FBG < 90 mg/dL, 1-h PP < The CURES Eye Study demonstrated a significant in-
140 mg/dL,and 2-h PP < 120 mg/dL) may be more crease in the prevalence of DR with increasing HbA1c
feasible in pregnant women with pre-existing type 1 levels. The multiple logistic regression analysis car-
diabetes. ried out using DR as a dependent variable showed a
significant trend of increasing retinopathy at different
HbA1c is lower in the first and second trimesters 2
of pregnancy compared to non-pregnant women. quartiles of HbA1c (trend χ = 51.6, p < 0.001).
At present, the ADA recommends HbA1c ≤ 6 % for Prevalence of retinopathy in quartiles of HbA1c levels
women with diabetes during pregnancy. Compara- in the CURES Eye study
tively, the Australian Diabetes Society recommends
glycemic targets based on type of diabetes during
pregnancy, i.e., HbA1c ≤ 7 % for pregnant women with <10.3 31.7
pre-existing type 1 diabetes and HbA1c ≤ 6 % for preg- 8.5-10.3 20.0
nant women with pre-existing type 2 DM. The risk for Quartiles of HbA1c (%) 6.9-8.4 13.3
fetal malformations was particularly high with HbA1c ≥
>6.9 8.1
9.3 % while some degree of risk (3 %) was also associ-
0 5 10 15 20 25 30 35
ated with a lower HbA1c in the range of 5.6–6.5 %.The Prevalence of DR (%)
corresponding blood glucose values below which the
risk of fetal malformations decreased were FBG < The long-term benefit of glycemic control on retinop-
104.4 mg/dL and PP < 163.8 mg/dL athy has been evaluated by two large studies: The
Diabetes Control and Complications Trial (DCCT) in
HYPERGLYCEMIA AND MACROVASCULAR type 1 diabetes, and the United Kingdom Prospec-
tive Diabetes Study (UKPDS) in type 2 diabetes. The
EVENTS DCCT and the UKPDS have demonstrated that inten-
An association between glucose and cardiovascular sive glycemic control (HbA1c ≤7%) reduced both the
disease exists at levels below those used to define development and progression of DR, with the bene-
diabetes. A recent meta-analysis of 20 studies in- ficial effects of intensive
cluding nearly 96,000 individuals without diabetes glycemic control persisting up to 10–20 years.The
showed that cardiovascular events increased by 1/3 overall inference from various trials is that good gly-
rd
as the fasting glucose levels increased from 4.2 to cemic control right from the time of diagnosis of dia-
6.1 mol/litre and by nearly 2/3rds when the 2-hour betes is beneficial in preventing the onset of DR and
glucose level was greater than 7.8mol/litre.
in delaying its progression. The long-term benefits
In patients with type 1 diabetes enrolled in the DCCT, of glycemic control outweigh the small risk of “early
cardiovascular event rates were similar in the two worsening” of DR. Targeting HbA1c level of<7% is rec-
groups at the end of the study period but six years ommended for slowing down the progression of DR.
later it had increased in both, with a significantly low-
er increase in those patients who had undertaken Plots of data from three epidemiological survey show-
intensified therapy. A meta-analysis on all appropri- ing prevalence of diabetic retinopathy against mea-
ate trial data in type1 diabetes confirms the bene- surements of glycemic control (Source Ref No: 8)
fits of glycemic control on macrovascular disease.
In type 2 diabetes, the UKPDS data suggests that
hyperglycemia has an independent effect on mac-
rovascular disease. A 14% reduction for MI was ob-
served for every 1% reduction in HbA1c which was
highly significant. In UKPDS cohorts there was also a
28% increased risk of peripheral vascular disease for
every 1% rise in HbA1c. However, no such association
was observed for stroke. Similar to the DCCT, the

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