BIOEDGE-First Course Content- August 2019-INSUGEN, BASALOG,

INSULINS
Topic- Trials & dosing
United Kingdom Prospective Diabetes Study-20 year study,5000 patients of Type 2 diabetes mellitus
(T2DM)It was done in 23 clinical centres based in England, Northern Ireland and Scotland.Study concluded
that benefits of intensive therapy to control glycaemia in reducing risks of retinopathy, nephropathy, and
neuropathy (overall micro-vascular complication rate was reduced by 25%)

Diabetes Control and Complications Trial (DCCT)

OBJECTIVE The Diabetes Control and Complications Trial (DCCT) was designed to test the glucose
hypothesis and determine whether the complications of type 1 diabetes (T1DM) could be prevented or delayed.

The DCCT (1982–1993) was a controlled clinical trial in 1,441 patients with T1DM comparing intensive therapy
(INT)

The DCCT followed >99% of the cohort for a mean of 6.5 years and demonstrated a 35–76% reduction in
the early stages of microvascular disease with INT, with a median HbA1c of 7%, compared with CONV,
with a median HbA1c of 9%.DCCT has demonstrated the effectiveness of INT in reducing the long-term
complications of T1DM and improving the prospects for a healthy life span.

Fix Fasting First -Controlling FPG will bring down the baseline glucose levels thereby bringing
down the level of hyperglycaemia reached with postprandial glucose spikes too. Therefore, “fixing
fasting plasma glucose levels first” is important in treatment of T2DM, which can be effectively
achieved with basal insulin

Glucotoxicity-

Untreated high blood sugar can lead to a condition called glucotoxicity (sometimes called glucose toxicity).
It’s caused by damaged beta cells. Glucotoxicity leads to structural and functional damage of beta cells.

Beta cells help your body create and release a hormone called insulin. Insulin pulls sugar (also called
glucose) out of your blood so your cells can use it for energy. This process also helps to regulate your blood
sugar levels.

Over time, high blood sugar (also called hyperglycemia) can damage your beta cells. Damaged beta cells
cause both a decrease in insulin production and an increase in your body’s resistance to insulin, leading to
glucotoxicity.

There is growing evidence that early, intensive treatment of new-onset diabetes mellitus aimed at tight
glucose control reduces the risk of micro- and macrovascular complications. Metabolic memory is a term
used to describe beneficial effects of immediate intensive treatment of hyperglycemia and the observation
that they are maintained for many years, regardless of glycemia in the later course of diabetes.
Insulin dose titration
Basal Insulin Initiation and Titration

Initial dose: 0.1-0.2 IU/kg body weight or 10 IU

Dose Titration of Basal Insulin:

Insulin glargine; adjust every 3 days

(Target FPG < 100 mg/dL)

FPG (mg/dL) Increase insulin dose (IU)

100–120 2

120–140 4

140–180 6

≥ 180 8

Decrease insulin dose (e.g., 2–4 units/day) if hypoglycaemia occurs

Initiation and Titration of Bolus Insulin

Methods Dosage

Initiation

Fixed initial dose 4 IU

Based on patients 0.05 U/kg

weight
Titration

Often 1 supplement unit of insulin is added for every

50 mg/dL that is above the glucose target, adjusting
for insulin sensitivity
Usual initiating dose is about 10 units of premix insulin either morning (AM) or night (PM)

Pre-meal Blood Glucose (mg/dL) Change in Insulin Dose (IU)

≤100 -2

100–110 0

110–140 +2

140–180 +4

≥180 +6

Priming-It ensures dose accuracy and shows that needle is not blocked. Turn the dose knob until you see
'2' in the dose window. With the needle pointing upwards, press the injection button until it stops and
dose window shows '0'. You should see 2–3 drops of insulin come out of the needle tip