Diabetic nephropathy 'faculty'

Attended an industry-sponsored faculty meeting to talk about diabetic nephropathy at the Vale of Glamorgan hotel. The aim was to come up with some form of consensus on blood pressure targets, and the role of various antihypertensives but it drifted into a lot of other aspects including glycaemic control in nephropathy, the forthcoming Renal NSF and so on.

Choice of Angiotensin Receptor Blockers (ARB) for the treatment and prevention of diabetic nephropathy in Type 2 diabetes was discussed. (ACE inhibitors have more evidence in Type 1 Diabetes and, perhaps, should be favoured in Type 2 Diabetes where there is coronary heart disease or LVF). The ARB candidates for Type 2 Diabetes are losartan (RENAAL study), irbesartan (IDNT, IRMA-2 studies) and valsartan (MARVAL study) but only losartan and irbesartan have licenses for this indication. All seem to have benefits over and above absolute blood pressure control but the studies are difficult to directly compare. (ARB trials summary table).

It looks like the MDRD formula for calculating GFR will be adopted in Wales. The pathology labs will report it routinely with every serum creatinine measurement. When the reporting starts there may be an increased referral from primary care for patients with normal(ish) serum creatinine but who now have renal impairment on calculated GFR. This leads to some tricky questions.

• What level of GFR should be referred to secondary care?
• Which is more important, the absolute level or change in GFR?
• At what level of GFR would we advise against the use of metformin?

The rational for combining ACE inhibitors with Angiotensin Receptor Blockers (ARBs) was covered. Angiotensin II can be produced by pathways other than ACE (such as chymase) and Angiotensin II levels can return to normal with chronic ACE inhibition despite continued blood pressure control. Angiotensin II receptors also upregulate with ACE inhibition. The combination of Candersartan and Lisinopril in hypertensive Type 2 diabetics (CALM study - BMJ. 2000 Dec 9;321(7274):1440-4) showed that combination therapy is well tolerated and more effective at reducing blood pressure. Other studies have also shown a reduction in microalbuminuria (Review article - Ann Pharmacother. 2004 Jul-Aug;38(7-8):1278-82). However the case is not fully proven since it can be argued that combination therapy has not been tested against full doses of individual agents and complete blockade of the renin-angiotensin system puts the kidneys at greater risk during episodes of dehydration.

RD Lawrence medal

Had the Glamorgan Gazette around for a photo opportunity today because one of our patients was receiving the RD Lawrence medal from Diabetes UK for being dependent on insulin for 60 years.

The medal is dedicated to Dr RD Lawrence, who, together with the author HG Wells, founded the British Diabetic Association, now Diabetes UK, in 1934. Robin Lawrence, a house surgeon at King's College Hospital was diagnosed as having Type 1 Diabetes at the age 28 in 1920, 2 years before the discovery of insulin in 1922. Since Diabetes had such a poor prognosis (3 - 4 years on the Allen starvation diet) at that time he moved to Florence to practice and to enjoy some Italian culture for what little life he had left. He was alerted to the discovery of insulin by telegram from Dr GA Harrison, the biochemist at King's College Hospital London which said "I've got some insulin. It works. Come back quick." He received his first dose on 31st May 1923.

Pioglitazone prevents macrovascular events

The PROactive study (PROspective Actos Clinical Trial In macroVascular Events) compared the addition of Pioglitazone or placebo to 5238 conventionally aggressively treated Type 2 Diabetics. It showed that treatment with Pioglitazone prevented macrovascular events and death and was safe

PROactive results at EASD 2005

The final results, reported at the EASD meeting in Athens in September 2005, show that the use of pioglitazone significantly reduces the incidence of Myocardial Infarction, strokes and 'all-cause' mortality in high-risk patients with Type 2 Diabetes. Metformin has been shown to reduce the risk of MI and death in the UKPDS but this was compared to 'conventional' treatment at the time not the currently advocated aggressive target-driven treatment.

Treatment with pioglitazone showed there was no liver toxicity and no increase in the death rate from heart failure. There was an increase in the rate of admission to hospital with CCF (5.7% vs 4.1%), an increase in peripheral oedema, non-serious hypoglycaemia and an average weight gain of 3.6 kg. Those with heart failure (NYHA II – IV) were excluded from the study.

The trial failed to show prove its primary combined endpoint (all cause mortality, non-fatal MI, stroke, leg amputation above the ankle, acute coronary syndrome, CABG or percutaneous coronary intervention and leg revascularisation). The rates for this endpoint were 21% in the treatment group vs. 23.5% in the placebo group but the difference is not statistically significant.

The secondary endpoint of all cause mortality, non-fatal MI or stroke was statistically significant 12.3% in the treatment group vs. 14.4% in the control group.

What does this mean?

- Treating 48 Type 2 Diabetics with pioglitazone over a 3 year period will prevent one first major cardiovascular event.

- Pioglitazone should be avoided in patients with established heart failure (NYHA II – IV) but is otherwise safe.

- Pioglitazone, if used, should be titrated to its full dose of 30 – 45 mg/day.

- As part of an aggressive treatment regime pioglitazone would be expected to reduce HbA1c by a further 0.5% and will defer the conversion to insulin.

Diabetes Update

Worked on an idea for a diabetes update newsletter for Bridgend. Put some bits together including the PROactive results.

Looks rather technical and dull but will get some ideas as to how it should look.

EASD conference

Attended the European Association for the Study of Diabetes (EASD) conference in the Peace and Friendship Stadium, Athens 10th - 15th September 2005. The picture shows the stadium.

About this blog

This blog is a collection of articles and news items that I have found interesting. It helps me keep abreast of new issues in medicine and by putting my efforts online I hope that others may also find it a useful shortcut.

Dr Dean Jenkins