Tuesday, 29 January 2008

UpDates in Diabetes Care with Potential Application To Japanese Medical Practise

The 2008 Guidelines for the Standards of Medical Care in Diabetes have been released by the American Diabetes Association.

I have endeavoured to summarize the important elements of the current ADA guidelines in addition to adding my opinion on their application to clinical practise in Japan plus any other recent evidence in support or contradicting these current guidelines to try and give an overall view of things.

Interestingly, the guidance refers to several interesting areas in particular which include:

1) HbA1c: aiming to get the HbA1c (DCCT-aligned value) as near to 7% is the goal with the aim to avoid hypoglycaemia. However, there is now the goal to get the HbA1c into the normal range if possible. The thought behind this is likely to maximise the advantage of avoiding the microscopic and macroscopic changes associated with diabetes. The HbA1c value that the ADA are advocating is to reduce it to less than 6%, if possible ,with the avoidance of hypoglycaemia.

This may of course be possible in proportionately more type 2 patients than type 1 patients as the severity of disease may be different and the former have relative insulin resistance rather than deficiency. The problem with attaining an HbA1c of <7%>

The downside to the application of such guidelines in Japan is the inability for type 2 patients taking oral hypoglycaemic agents to check their daily blood glucose levels because such monitoring therapy is not currently covered by the medical insurance system and therefore, patients are unable to know if their blood glucose levels are being well maintained on therapy or not. HbA1c measurement every 3 months is insufficient to really know if the patient is having good control. I say this because patients can have a seemingly good HbA1c result but still have frequent hypoglycaemic episodes and hyperglycaemic episodes alike.

Diabetes control can be imagined to be something like the climate and daily weather. The climate is the gradual change in temperature that beig like the HbA1c whereas the daily weather is the blood glucose level. We all know that one day there can be sun and the next there can be rain. The climate does not tell us what has happened on a day to day basis. Hence, measuring the HbA1c only tells us of an average of the glucose control over the last 2-3 months and particularly the last 1 month prior to testing.
Therefore, in Japan, the clinic doctors need to ask particularly about hypoglycaemic episodes and encourage at least urine testing for glucose. However, if patients can afford to buy their own glucose monitoring kits and to manage their diabetes through empowerment and better understanding, then in my opinion, they should be encouraged to do so.

2) Carbohydrate monitoring:
There is advice on carbohydrate counting and glycemic index which is of course part of the famous DAFNE thinking (Diabetes Adjustment for Normal Eating), which allows patients to adjust their insulin doses according to the amount of carbohydrate they consume. This is opposed to the traditional way of doing things where the person eats similar amounts of food every day and fixes their insulin doses. The latter can certainly work in those individuals who have a strict daily regimen, but is inflexible for young patients with hectic lives and who eat infrequently. I have seen such treatment used in the UK to good effect.

The usual regimen of insulin is the fast acting novorapid/humalog isulin for every time food is consumed and a long acting insulin at night to prevent hyperglycaemia e.g. detemir / glargine. However, such a carbohydrate monitoring regimen may not be possible in Japan because Lantus (glargine) was discontuned due to a problem of administration and as far as I am currently aware, detemir has yet to reach these shores. Hence, older regimens of longer acting insulins might be required instead e.g. insulatard, which have a shorter period of activity and can result in severe nocturnal hypoglycaemia.

Currently, some institutions are using mixed combinations of insulins e.g. novomix, three times a day with interesting results in HbA1c, in view of the lack of longer acting insulin availability, but this in my opinion, still does not provide the flexibility in insulin-food control that the DAFNE style of therapy can do. Moreover, I have yet to see any patient thus far being treated with combination of oral hypoglycaemic agent with insulin in Japan, which is standard practise in the USA and UK, with good results in HbA1c levels and reduced weight gain and lower amounts of insulin being required e.g. metformin with insulin.

3) Immunisation: The ADA guidelines suggests that all DM patients should be vaccinated for influenza on an annual basis of more than 6 months of age. Patients should also receive pneumococcal vaccination if more than 65 years of age. The pneumococcal vaccine is available in Japan and should be used in such high risk patients. I am aware though that stocks of the vaccine were previously low and hence, again, it may or may not be possible to administer such therapy depending on your local resources.

4) Lipid Management: Statin therapy should be added to lifestyle therapy (dieting and weight loss) REGARDLESS OF BASELINE LIPID LEVELS for diabetic patients:
i) with overt cardiovascular disease (CVD)

ii) without CVD who are over the age of 40 and have ONE or more CVD risk factors (e.g. hypertension, family history)

The above guidance is also in line with the International Diabetes Federation guidance (IDF) of 2005.

Statin therapy should be considered in patients with low risk if the LDL cholesterol remains > 100mg/dl or in those with multiple CVD risk factors.
Aim for LDL cholesterol in those patients with low risk is less than 100mg/dl.
In patients with overt CVD, a lower LDL cholesterol level of less than 70mg/dl, using high dose statin, is an option.
In the event that LDL-cholesterol levels do not reach these targets, a reduction of LDL-cholesterol of about 40% from baseline is an alternative therapeutic goal.

5) Antiplatelet Agents:Aspirin should be used in patients with a history of CVD as secondary prevention. Aspirin should also be used as Primary prevention in type 1 or type 2 patients at increased cardiovascular risk including all patients over 40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria).

Aspirin is not recommended under 30 years of age due to lack of evidence of benefit in this age group and certainly not to those aged less than 21 years because of the risk of Reye's Syndrome.

Combination with other anti-platelet agents e.g. clopidogrel (Plavix) should be used in patients with severe and progressive CVD.

6) Glucose Goals: There are also guidelines for use of tight control in patients with severe illness. There have been previous trials of use of insulin in critical care patients and the overall outcome has been a benefit in survival. However, a recent German study using insulin in such patients saw a detriment in using tight insulin control.
However, when one reads the methods of the study, they measured blood glucose levels every 1-4 hours. This is a major downfall with the study leaving a potential cause for the increased mortality. In fact, when tight control is required in such patients, hourly blood sugars should be done, and a four hour delay is dangerous, in my opinion. This study was published in a famous journal and the monitoring delay, which I see as a flaw in the study design, was not addressed in the conclusions by the Authors, which is disappointing. I would not advocate a change to the current advice of tight control in critically ill patients unless there are future studies with more rigorous designs showing similar adverse outcomes

There are many other areas of advice in the current ADA guidelines but are too much for today's blog. If you want to read more please go to Diabetes Care, Volume 31, Supplement 1, Jan 2008.

Monday, 28 January 2008

Probe Your Patients For History

Dear Bloggers

I have written about history and its importance many times on this blog and here is yet another example of why it is so important.

This case has been anonymised as usual to maintain patient confidentiality.

An elderly male was admitted into another hospital following a two-day history of chills, lower abdominal discomfort and frequency.

He had attended a local hospital in the vicinity and a UTI was diagnosed for which intravenous antibiotics were prescribed to be continued as an outpatient.

However, the chills continued and urinary incontinence occurred as a new problem prompting admission to another hospital.

At the current hospital it was elucidated that he had a long history of Benign Prostatic Hypertrophy. He had no recent sexual contacts and no change in bowel habit and no weight loss.

He otherwise had a history of ischaemic heart disease with an AMI several years before for which he had a Coronary Artery Bypass Graft (CABG), hyperlipidemia and hypertension. He had no known history of diabetes mellitus.

Medications included
  • Aspirin
  • Atorvastatin
  • Amlodipine
  • Medication for BPH (name unknown)
He was an ex-smoker and drank no alcohol. He was other wise normally fit and well.

When he was examined by the admitting resident, he was apyrexial and had normal vital sign. His cardiovascular, respiratory and abdominal examinations were within normal limits apart from evidence of a previous sternotomy scar for his CABG operation and a loud aortic systolic murmur. Rectal examination revealed a large smooth prostate which was non-tender.

Clinically the patient was admitted with a simple UTI secondary to obstruction to urinary outflow.

A catheter was inserted to drain the excess urine (residual volume unknown) and antibiotics were continued.

Up to this point, things seemed relatively straight forwards.

However, a Senior doctor reviewed the history, physical and lab data as things seemed not quite right.

There was no history about the severity of the urinary outflow symptoms. Moreover, the lab data revealed evidence of a raised CK of about 350 (normal CK-MB) and some mild renal impairment BUN 25, Creat 1.4. Previous blood tests several years ago also revealed a mildly raised HbA1c of 6.4% and a follow-up was normal.

The ECG had T wave inversion from V3-V6 inclusive and it had been initially considered to be old except when it was compared to a recent ECG within the last few weeks, and the current tracing showed NEW T wave inversion in V3 and V4 inclusive.

There was a high suspicion of an Acute MI. However, the resident clearly stated that the patient had not complained of any other problems.

The Senior doctor nevertheless went back to the bedside and asked the questions again. On this occasion, the patient had said that he had become breathless, with central heavy chest and leg pains, with him almost having lost consciousness. The pain was described in severity as 10/10 and lasted for up to 1 hour. There was no radiation to the neck, jaw, arms, back, or abdomen and no sweating or vomiting.

Asking about the urinary symptoms, the patient mentioned that he only passed very small amounts of urine, had frequency and felt he never had completely voided his urine in some time despite treatment for BPH.

Hence, from the history, it would appear that the patient was experiencing an Acute Coronary Syndrome several days prior to admission which might account for the new ischaemic ECG changes and raised CK.

Most people will now think, hey, the CK-MB was normal, so not an acute coronary syndrome! No! The serum levels of CK drop rapidly within 24-48 hours of an MI with other markers such as LDH and Troponin T remaining raised for much longer periods, the latter for up to 10 days post-infarct. Hence, it is of no surprise that the CK-MB fraction might be normal at the time of presentation to hospital.

In view of the previously raised HbA1c, it is also plausible that the patient had undiagnosed diabetes. In fact, the American Diabetes Association states that HbA1c should not be used to diagnose diabetes as a significant number of people even with normal HbA1c can still have diabetes-- it is not a fool proof test for diagnosing diabetes.

Also, having DM might also put the patient at increased risk for development of a UTI on a background of urinary outflow obstruction.

On examination the patient indeed had a loud Aortic Ejection systolic murmur with radiation to the carotid arteries in addition to left renal angle tenderness on bimanual palpation.


1) Outflow obstruction from BPH
2) UTI due to 1 above with complication of pyelonephritis
3) Likely Acute Coronary Syndrome ? Aortic Stenosis
4) Possible undiagnosed Type 2 DM


The senior doctor suggested the following;

  • Obtain Troponin-T level
  • Add Clopidogrel ( this is advocated for use in NSTEMI and was proven to be more effective when combined with aspirin than just aspirin alone in the CURE trial; a newer analogue is being trialled at present in the USA with even better anti-platelet effects when combined with aspirin)
  • Increase the Statin dose (a recent meta-analysis of 14 Statin trials in Lancet 2008 has suggested that benefit from statin therapy occurs in diabetic and non-diabetic patients to the same level with the most benefit derived from patients with high LDL-cholesterol levels; however, all patients benefit with cholesterol lowering therapy independent of starting level of cholesterol. The meta-analysis suggests that for every reduction of 1mmol/L LDL-cholesterol there is a 20% reduction in cardiovascular events. Moreover, there is no lower level of cholesterol which to attain. The ADA guidelines of 2008 suggest that statin dose should be used to the maximum tolerated dose to reduce cholsterol as low a possible e.g. below 70mg/dl in patients with known cardiovascular disease.
  • In Japan, I have often heard doctors stating that the cholesterol has reached normal levels or is normal to start with, and that they do not need to start or increase the statin dose despite the patient having had a new coronary event with them being at high risk. The international medical data and current guidelines suggests that a normal cholesterol can still be a risk, and hence, statins should be commenced or increased in 'at risk' patients. Moreover, use of statins is an acute treatment in AMI and not only helps to stabilise atherosclerotic plaques, there is also some data that it can increase the success rate of delayed PCI therapy.
  • Consider switching the calcium-channel blocker (amlodipine) to a beta-blocker. The thought behind this was, firstly, the blood pressure systolic value was about 100mmHg and further anti-hypertensive therapy on top of the calcium blocker might result in hypotension and cause worsening angina. Moreover, the pulse rate was about 80 per minute. This is not ideal in patients with ischaemic heart disease. Use of beta-blockers reduced heart rate (improving blood flow time) and vasodilates the coronary arteries. They also have the effect of reducing ventricular rupture and can treat dysrrhythmias unlike a peripherally acting calcium blocker that has little chronotropic effect. A beta-blocker with both alpha and beta effects might also be useful in that it might help with the prostatic hypertrophy too.
  • Obtain an echocardiogram
  • Discuss with the cardiologists about a coronary angiogram
  • Discuss with the urologists about a long term catheter or an operation (TURP); but to remember that an immediate operation would be contra-indicated in light of a possible ACS.
  • Screen patient for diabetes with fasting blood sugar and perform an oral glucose tolerance test (the Gold Standard test for diagnosing DM).
Additional Results

The Troponin was positive at 0.72 thereby confirming an Acute Coronary Syndrome in this patient and this therefore was a contra-indication to any planned urological interventional surgery that might have been considered.

Indeed, the echocardiogram confirmed a good systolic wall motion. However, it also revealed an Aortic Valve gradient of 0.6cm2, and a maximum ejection pressure of 78mmHg with an average of 49mmHg consistent with Severe Aortic Stenosis.

It is usual for testing of DM to be performed several weeks after an AMI, unless the hyperglycaemia is obviously present and with DM then easy to diagnose, because of the phenomenon of stress hyperglycaemia. As AMI is a strong stressor, hyperglycaemia can occur but when patients recover, a significant number return to normoglycaemia in the post-infarct period.


In this case, the patient had symptoms of an obstructive uropathy with infection. The admitting medical doctors had failed to obtain a thorough history of ischaemic heart disease despite a previous history of the problem and with the patient having had a CABG. Moreover, the ECG and raised CK had not been fully appreciated.
With a thorough history retaken at the bedside with focused questions to rule in or rule out ischaemic chest pain, it was possible to elicit salient information from the patient to thereby determine that there was a likely ACS.
Indeed, with a positive Troponin T and with severe aortic stenosis being found, it is likely that the stress from the infection resulted in coronary ischaemia by means of cardiac outflow obstruction and atherosclerosis as the demand for increased blood flow could not be met.

In patients >70 years of age, the usual cause of AS is due to atherosclerotic-like changes of the tri-leaflet valve itself. Many features affecting the valve are similar to atherosclerosis but use of statin therapy does not reverse the changes, which can otherwise occur with atherosclerotic plaques in main blood vessels. Moreover, analysis of excised valves can also show bone and cartilage formation too !!
In the younger age group <70>40mmHg is consistent with severe AS (please see UpToDate 15.3).

Patients with severe aortic stenosis tend to suffer with the following problems:

  1. Ischaemic chest pain e.g. angina, AMI
  2. Syncope / Dizziness e.g. fall in cardiac output under stress
  3. Heart Failure, as an end-stage complication
This patient had already suffered the first two symptoms in addition to echocardiographic proof of severe AS. In view that the patient was otherwise in good health, he was referred to the cardiothoracic surgeons for workup of an aortic valve replacement.

In view of the patient's advanced age and the antecedent risks of anticoagulation with mechanical valves, it was felt that a bioprosthetic valve would best suit this patient and he underwent successful valve replacement.

Moral Of The Story

The moral of this story is, don't ignore ECG changes and always compare ECGs to old ones for new changes when possible.
Never accept a raised Creatinine Kinase (CK) as trivial and always try to elicit a cardiac history in such circumstances especially when there is a previous history of such problems. Even if there is no obvious history but the suspicion of an acute coronary syndrome is high, a Troponin T should be always measured (at a minimum of 6-12 hours after the onset of any cardiac sounding chest pain).
I am afraid that using CK-MB to rule out MI is simply too unreliable and if you just use this, you WILL MISS Acute Coronary Syndromes. Troponin-T is cardiac specific but moreover, it is more sensitive a test than CK-MB and remains elevated for longer than CK.

In the presence of an aortic systolic murmur, dizziness, ischaemic chest pain, and new ECG changes consistent with an ACS, severe aortic stenosis should be considered, as it was in this case.

Hence, an apparent simple UTI turned out to be a blessing in disguise for this patient because a life-threatening cardiac condition was identified, investigated and effectively treated.

Lastly, do not expect your patients to simply tell you every aspect of their history and health. Many patients forget things and do not think unrelated events are important. It is up to you as doctors to ask the questions. The questions can be asked as part of a Body Systems Review which I have discussed at length on this blog already. For information on the Body Systems Review, please search under this topic at the top of this blog page. I would also recommend the book 'The Patient History- Evidence Based Approach' by Professor Lawrence Tierney, Lange Publishers.

Please consider....

Sunday, 27 January 2008

A Benkyokai Bonanza

Dear Bloggers

Yesterday afternoon saw two acclaimed speakers attend our institution to teach the residents their wisdom.

Firstly, Professor Alan Lefor, Professor of Surgery, Jichi University presented talks on Trauma followed by Surgical Site Infections.

Professor Lefor's strident and direct approach were refreshing and it was interesting to see evidence based practise at work.

There was the presentation of several cases from the United States which showed trauma surgery at work.

There was emphasis on ATLS, including the elements of ABC, reassessment, D, E an so on.

The residents were very receptive to this different approach to teaching.

The talk on Surgical Site Infections presented the current evidence for use of antibiotics, warming the patient, not shaving patients, etc...

The two-hour set of talks were very interesting and Professor Lefor's talks are certainly well worth it!

Next was Dr Kitahara of Keio University who is also American trained with specialist interests in Infection and Haematology.

He was presented several difficult and unusual cases by the Department of General Internal Medicine and it was interesting to hear his view on the cases.

All in all, the two speakers provided an excellent opportunity for the residents of our institution to get up-to-date training on both surgery and medicine alike.

It was a really good day of teaching and it was enjoyed by the residents and myself alike.