A MODERN DAY PLAGUE?
Mike Cawthorne, director of the Clore Laboratory for Translational
Metabolic Research at the University of Buckingham, on the need for
better and more cost effective treatments for diabetes and obesity
he Clore Laboratory was developed as a diabetes and
obesity research centre and has been involved in the
discovery and development of every promising drug class
in diabetes and obesity. It undertakes both basic and applied
preclinical research with other universities worldwide and with
major pharmaceutical and biotech companies.
The International Diabetes Federation estimated in 2012 that
more than 371 million people had diabetes, with half of them
undiagnosed. Expenditure on healthcare of diabetes is more than
$471bn (~€357bn), which is more than 10% of the total
healthcare costs of adults aged 20-79 years.
In Europe, there are approximately 55 million people with
diabetes, of which 38% are unaware that they have the disease.
However, 80% of sufferers live in low or middle income countries,
with half the number of people (4.8 million in 2012) who die from
diabetes being under 60.
Types of diabetes
There are three main types of diabetes:
Type 1 diabetes is an autoimmune disorder which requires
insulin injections to treat;
Type 2 diabetes affects more than 90% of all people with the
disease. It usually occurs in adults, although with the high
prevalence of childhood obesity it is becoming more common in
children. There are two separate lesions in Type 2 diabetes –
insulin resistance, which is a failure of tissues to respond
adequately to the subject’s own insulin, and defective insulin
secretion. These two lesions interact. Patients can be controlled
with oral therapy, but over time they are likely to require
exogenous insulin following pancreatic islet failure; and
The third form of diabetes is gestational diabetes. Failure to
control blood glucose during pregnancy predisposes the mother
to develop diabetes in later life. It also programs the offspring to
have a higher risk of becoming obese and diabetic and, in
particular, be prone to gestational diabetes. Therefore, the
condition is a multi-generational programming mechanism.
Treatment of Type 2 diabetes
People with diabetes have an increased risk of diseases affecting
the heart and blood vessels, kidneys, eyes, nerves, teeth and skin.
The main oral drug used for treating Type 2 diabetes is metformin.
Generally an algorithmic approach is used with drugs being added
as patients fail to maintain control. There is a growing realisation
that this staging methodology is inadequate and if one attempts to
both control glucose (and lipids) and prevent (or at least delay)
pancreatic islet cell failure, then multiple treatments are needed
that fully address the pathophysiology of the disease. Potentially,
this requires drugs to improve insulin sensitivity in liver and skeletal
muscle, slow the absorption of nutrients from the gut and provide
islet cell protection.
The Clore Laboratory staff have a wealth of background
knowledge and experience in undertaking preclinical studies that
allow positioning of drugs into the therapeutic regimes of today
Prevention of Type 2 diabetes
There is a growing recognition of the need to prevent the
development of Type 2 diabetes. A major factor is obesity, which
results in insulin resistance and compensatory hyperinsulinaemia,
leading ultimately to islet cell exhaustion. All anti-obesity drugs to
date have either been centrally acting agents to reduce food
More than 500 peer-reviewed publications by Clore
Laboratory staff in the area of diabetes and obesity;
Clore Laboratory staff have made major contributions to the
development of insulin sensitiser drugs;
Clore Laboratory staff pioneered brown adipose tissue
research and the development of thermogenic drugs; and
More than 100 man-years of pharmaceutical industry research.
The Buckingham Institute of Translational Medicine
The University of Buckingham