Design of Insulin Variants for Improved Treatment of Diabetes - Peptide and Protein Design for Biopharmaceutical Applications - page 252

blood glucose levels during treatment of high blood sugars. With regard
to weight, the new glucagon-like peptide-1 incretin drugs ( exenatide ,
alias Byetta , from Eli Lilly, and liraglutide , alias Victoza , from Novo
Nordisk) appear very promising for type 2 treatment, since they not only
help glucose control, but also affect weight loss [25].
As mentioned, tight glucose control is crucial for good diabetes treat-
ment. Home blood glucose monitors were not widely available until
around 1990, but blood glucose can now be measured with these handy
devices [26]. They do however require fresh blood, and a finger prick is
the most common source. The finger prick is in fact more painful than
insulin injections. However, with the modern blood glucose monitors,
only about 0.5 microlitres of blood is required, so the procedure is quite
gentle. Unfortunately, many diabetes patients rarely test their blood
sugar, despite this being the proven way to achieve good control. The
pain, the hassle and perhaps the unpleasant facing of many non-ideal
values are some of the reasons for neglect of blood glucose monitoring.
The average blood glucose level over the last two to three months can be
evaluated by measuring glycated haemoglobin (HbA1c) [27], a procedure
which is typically carried out at the diabetes clinic. In a healthy person,
HbA1c is in the range of 4-6% relative to total haemoglobin. Poorly con-
trolled diabetes can lead to HbA1c values above 10%. HbA1c values below
7 or 6.5% have been recommended as targets for diabetes management [28].
With such low values, the risk of long-term complications has been shown to
be significantly reduced in both type 1 and type 2 diabetes [2,3].
Accordingly, the main goal of diabetes management is to achieve blood
glucose values near normal, ideally near 4-6 mM in the fasted state, and
not much higher than 8-10 mM after a meal. However, too much insulin
at the wrong time will lead to low blood sugar (hypoglycaemia), which
can be acutely dangerous. Blood glucose in the range of 2-3 mM can
make the patient feel tired, hungry and/or confused, and levels below 1-2
mM can lead to coma or death. The brain neurons are highly dependent
on glucose and can die after short periods with too low glucose.
Insulin treatment is therefore a narrow balance between too high and
too low blood glucose (hyperglycaemia and hypoglycaemia) [29,30]. It is
very difficult to reach normal values without also nearing the dangerous
hypoglycaemic state at times. For this reason, patients and caretakers
dose insulin cautiously, which results in overall higher levels than ideal.
Some patients use the same timing and dosing of insulin shots every single
day, but motivated patients, who are more careful with home blood
glucose monitoring, can self-adjust their doses to the individual pattern
of any given day, and this will generally provide better results.