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426 Glycemic Control- How Tight It Should Be?

ACCORD,the ADVANCE (Action in Diabetes and Vas- However, the selected HbA1c target may need to be
cular Disease: Preterax and Diamicron MR Controlled relaxed to a range of 6.5–7.5 % for those being man-
Evaluation), and the VADT (Veterans Affairs Diabetes aged with basal-bolus insulin therapy. As duration of
Trial) studies. First, these trials were all short (3.5 to 5 diabetes increases beyond 10 years, microvascular
years). Secondly, the patient populations in these 3 and macrovascular complications set in; hence, the
trials were older, had diabetes for longer (eg, an av- selected targets can then fall into the range of HbA1c
erage of 10 years in the ACCORD study), and were at ≤ 7.0–8.0 %, with the lower end being pursued only if
higher risk of cardiovascular events, compared with safely achievable.
the DCCT and UKPDS studies in which the patient
populations were younger or recently diagnosed. TARGETS IN TYPE 2 DIABETES

All 3 trials were able to achieve sustained reduc- Selection of targets for the management type 2
tions in HbA levels for the duration of the studies, diabetes requires more factors to be considered:
1c
something that was difficult to achieve in previous age, duration of diabetes, presence of microvascu-
trials, particularly the UKPDS. The ADVANCE study lar and/or macrovascular complications, complexity
showed a significant reduction in microvascular com- of therapeutic regimen, and risk for hypoglycemia.
plications (14%, 95% confidence interval 3% to 23%) Notably, the risk for hypoglycemia is strongly linked
and a non-significant reduction in the macrovascu- with the pharmacological therapies used. The risk is
lar events in the intervention group. By choosing an low with OHAs other than sulfonylureas, moderate
HbA target of 6.5%, there was a 21% reduction in with addition of basal insulin, and high with further
1c
new or worsening nephropathy. Neither the VADT nor addition of prandial insulin. A glycemic target in the
the ADVANCE studies showed increased mortality range of HbA1c 6.5–7.0 % can be selected for patients
or cardiovascular event rate; however, the ACCORD <65 years of age, disease duration<10 years without
study, which attempted the most aggressive established microvascular and/or macrovascular
lowering of HbA levels (targeting < 6% in 6 months), complications, and where treatment used does not
1c
showed a slight increase in deaths—1.7% versus 1.1% include prandial insulin. With advancing age (65–75
in the intensive control group as compared to the years), longer duration of diabetes >10 years, and
conventional control group. This was, however, the addition of prandial insulin to achieve glycemic
less than the predicted rate (4%), and overall the control, it is advisable to select a HbA1c target in the
cardiovascular event rates in the intensive and range of 7.0–7.5 %.In patients >75 years of age with
standard groups (6.9% and 10.6%, respectively) were pre-existing macrovascular complications, it is logical
much lower than expected. Moreover, a prespecified to select a glycemic target between 7.5 and 8.5 %
subanalysis in the ACCORD study showed that preferentially based on the potential risk for hypogly-
patients treated intensively who showed the greatest cemia. In all these situations, it is prudent to pursue
reduction in primary macrovascular end points were lower targets only if safely achievable.
at earlier stages of disease, with lower baseline Suggested glycemic targets for individuals with type 1 and
HbA values and no known baseline vascular type 2 diabetes mellitus
1c
diseases.Likewise in the VADT study, those with the
shortest duration of diabetes (< 15 years) benefited Type 2 Initial 2–5 years of disease <6.5 %
the most from intensive control. diabetes 5–10 years of disease <7.0 %
mellitus
>10 years of disease with or with- <7.5 %
TARGETS IN TYPE 1 DIABETES out cardiovascular, renal, retinal,
In type 1 diabetes, the key factors to take into consid- neurological complications
eration when selecting glycemic goals are duration Type 1 With intensified insulin therapy or <7.0 %
of diabetes, presence of microvascular complications diabetes insulin pump therapy
and/or macrovascular complications, and treatment mellitus With standard insulin therapy <7.5 %
modality. As insulin therapy is the cornerstone of With cardiovascular, renal, retinal, <8.0 %
management among these patients, risk for hypo- neurological complications
glycemia will remain moderate to high. A target range
of HbA1c 6.5–7.0 % can be used for those with dis- GLYCEMIC TARGETS IN PREGNANCY
ease duration <10 years with or without established
microvascular complications. The lower end of this Physiologically, profound metabolic changes occur
range (HbA1c ≤ 6.5 %), if safely achievable, can be tar- during pregnancy to favor optimal growth of the fe-
geted especially for those on insulin pump therapy. tus. Maternal insulin resistance develops normally as
an adaptation to ensure availability of appropriate fu-

GCDC 2017