What's new in diabetes?

What’s new in diabetes?

Dr. Neil Munro, Esher, United Kingdom

Diabetes is a growing epidemic and it is estimated that by 2050, 1 in 3 Americans will have the condition. However, hypoglycaemia is a major issue in both Type 1 and Type 2 diabetics. Indeed, type 1 diabetics suffer between 1.1-3.2 major hypoglycaemic episodes a year whilst in type 2 diabetics the rate is between 0.1-0.7 episodes a year. Hypoglycaemia results in a number of physiological effects including an increased sympatho-adrenal response, increased heart rate, inflammation and arterial stiffness. The ACCORD study showed that patients with Type 2 diabetes who experience hypoglycaemia are at risk of sudden death. Between 6-10% of Type 1 diabetics die of severe hypoglycaemia whilst nocturnal hypoglycaemia is thought to be particularly dangerous due to reduced awareness.
A recent meta-analysis showed that statins are associated with a 9% increased risk in new-onset diabetes. Meta-regression then showed that the risk of developing diabetes with statins was highest in older participants, though neither baseline body-mass index nor LDL-cholesterol concentrations accounted for the residual variation in risk.
Regarding insulins, the patents are due to expire on aspart in 2012, lispro in 2013 and glargine in 2014. The BNF (2007) advises that when using biological products such as these it is good practice to use brand names. Innovations in insulin technology include degludec, a 48 hour flat-profile insulin with equivalent glucose lowering to hlargine but with less potential for hypoglycaemia and the Insulin Patch Project, which heats the infusion site to 38.5C prior to administering a bolus of insulin in order to enable improved absorption.

Exenatide is a GLP1 agonist which promotes insulin secretion when food is present in the bowel. This can now be placed into a “duros” rod and implanted in the medial aspect of the arm in order to improve blood glucose control and offer improved convenience over the usual twice-daily administration. The trial results in this area are encouraging as a phase two 48 week extension study showed 1.5% reduction in HbA1c and a weight loss of 3.5kgs. However, there were issues with nausea, diarrhoea and injection site problems. Alternatively, exenatide can now be administered in a weekly preparation and this has been shown to be non-inferior to once-daily liraglutide. Phase 1 studies have also been completed for a monthly preparation of exenatide: this is achieved by attaching it to the long tail of a hydrophilic amino acid as this prolongs the half-life.
Non alcoholic fatty liver disease is very common in type 2 diabetics and 27% of those over 65 years have a co-morbid diagnosis of this condition. This results in increased mortality due to cirrhosis. Non alcoholic steato-hepatitis is also common in diabetics and has a more sinister prognosis, with 15% developing cirrhosis or hepatocellular cancer. Meanwhile, type 2 diabetes has also been shown to increase the risk of fractures in women (as demonstrated in the ADOPT and Pro-Active trials): this is due to the loss of trabecular bone and mainly affects post-menopausal women. In terms of therapy, GLP1 agonists are the only hypoglycaemic agents that do not increase the risk of fractures and this is due to a reduced rate of bone absorption.
The European Medicines Agency has recently recommended new contraindications and warnings for pioglitazone to reduce the small increased risk of bladder cancer. Prescribers are now advised not to use these medicines in those with a current or previous history of bladder cancer or in those with un-investigated microscopic haematuria. Risk factors for bladder cancer should be carefully assessed before initiating treatment with pioglitazone.
New methods of glucose monitoring are now emerging. The Scout DS device is currently being developed to measure glucose non-invasively by placing the arm within a machine. This works by the detection of multiple spectral signatures from fluorophores in the epidermis. Further work is also on-going with exhaled breath glucose monitoring. This uses breath acetone and volatile organic compounds in order to derive the glucose level.

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