All India Institute of Medical sciences (AIIMS) New Delhi,
was established through an Act of Parliament with the mandate
to provide state of the art patients care and conduct research
on health problems of national relevance as well as suggest
remedial measures for them. We summarize here two recent
research publications from the AIIMS, which address the
problem of insulin requiring diabetics and their treatment
in the country. 1,2 These are contextual to the mandate
of the parliament and pressing needs of the youth with diabetes
in the country.
There is also a disturbing trend of rising prevalence of
diabetes among Indians during the last decade. World Health
Organization has recently acknowledged that the number of
diabetics in India would increase to 57 million by the year
2025. Eight decades have passed since Best and Banting,
in 1921, described bovine insulin and its use to save the
lives Of Youth with diabetes The long, experience with the
natural insulin (bovine and porcine insulin) has been extremely
satisfying both for the patients as well as their physicians
especially after the availability of highly purified and
mono-component natural insulin. Since 1980, synthetic insulin
manufactured adopting recombinant DNA technology and using
E.coli or yeast for expression is being used with mandatory
warning on hypoglycemic episodes expressed on the commercial
product.3,4 Early studies showed no difference with regard
to three-dimensional structure of the bovine, porcine and
synthetic insulin.
The binding affinity of insulin receptor at the three major
site of insulin action namely muscle, adipocyte and hepatocyte,
as well as the post receptor events in terms of autophosphorylation
of Insulin receptor substrate have been found to be similar
with bovine, porcine and recombinantly produced synthetic
insulins.6 Onset of action of synthetic insulin has been
found to be faster by about 15 min due to its rapid absorption.
This effect however, has been found to have no bearing on
the overall glycemic control achieved, though of late there
have been several reports of hypoglycemia unawareness following
the use of synthetic insulin.3,1 Even in pregnancy, no difference
has been observed in terms of neonatal macrosomia and ponderal
index between users of bovine and synthetically produced
insulin. A careful review of literature showed no relationship
between insulin antibodies produced and long term complications
of diabetes like retinopathy, nephropathy and neuropathy.
Synthetic insulin was introduced primarily with the promise
that cost of insulin therapy would come down remarkably
and insulin antibody formation may not occur with its use.
In reality however, after two decades of its use, it has
been observed that synthetic insulin also cause formation
of antibodies in substantial number of users (55%). The
major projected benefit of recombinant insulin viz. substantial
reduction in the cost has never been realized. I"Paradoxically,
despite 20 years of technology use for insulin production,
the cost of synthetically produced insulin continues to
mount, threatening to price out of existence those who depend
on it for treatment.
This is primarily because of the fact that unlike in the
West, treatment cost of most Indian patients is not met
by insurance, and patients have to fend for themselves.
Since the nature or cause of youth onset diabetes in India
remain unknown, and also since their insulin treatment is
becoming progressively jeopardized by escalating cost of
synthetic insulin and declining availability of affordable
natural insulin due to alleged immunogenicity we investigated
the nature and significance of antibody formation to purified
bovine insulin therapy which was the preferred insulin provided
in our clinic to the patients. The results of these two
studies published as two papers in a peer reviewed international
journal are being summarized and presented for information
to all professional concerned with diabetes and insulin
therapy in India for their critical review and appropriate
action.
Since the availability of synthetic recombinant insulin,
insulin-requiring diabetics in Western countries have switched
over to human insulin. However, majority of young diabetics
in India prefers bovine insulin therapy due to the prohibitive
cost of recombinant Human insulin.
In view of this it becomes important to know the functional
significance of the insulin antibody formed in response
to bovine insulin therapy. The present study provides such
data.
"The results show that all the patients treated with
bovine insulin showed high titers of insulin antibodies
with sd score ranging from 5.1 to 42.0. Antibodies developed
in response to bovine insulin have low affinity constant
(two order magnitude less than the native ligand i.e. Insulin
receptors) as well as have negligible insulin neutralizing
power. The results of our study also Showed that the antibodies
developed in response to bovine insulin therapy do not result
in insulin resistance with daily insulin dose requirement
with in physiological range of 20-30 units per day".
Diabetes Research and Clinical Practice 49 (2000) 7-15.
"In our experience the use of relatively low cost
purified bovine insulin is as effective as human insulin".
JAMA India The Physicians update Apr'01 V61.4 No.4
