INTRODUCTION
CASE IN DETAIL
DP was admitted to hospital 1 day ago by her physician to optimise her blood sugar control. The blood sugar levels have varied between 16 and 28 mmol/L for about 6 months. She has also complained of polyuria, polydipsia, nocturia and lethargy associated with a weight gain of 7 kg in 3 months.
DP’s diabetes was diagnosed 22 years ago when she presented with polyuria, polydipsia and lethargy. Initially she was treated with oral hypoglycaemic agents, namely metformin and glibenclamide. She is currently on metformin 500 mg three times daily. Fourteen years ago glibenclamide was replaced by regular insulin.
Her insulin regimen includes subcutaneous rapid-acting insulin 30 units given before meals three times daily and long-acting insulin 50 units given before dinner. She self-injects these. She monitors her blood sugar levels only occasionally. She regularly experiences mild episodes of hypoglycaemia, which manifest as lethargy and intense hunger, but has never had seizures or loss of consciousness. She has multiple complications associated with diabetes mellitus:
1. She suffers from recurrent urinary tract infections, for which she has had multiple hospital admissions in the past at irregular intervals, and the last admission was 3 months ago. She is currently managed with prophylactic antibiotic therapy with nitrofurantoin 50 mg daily. She denies any urethral symptoms currently and any side effects associated with this therapy.
3. She was diagnosed with early diabetic nephropathy 3 years ago on detection of proteinuria by her diabetician. She is unaware of her current level of renal function. She suffers from early-morning headaches and bilateral ankle oedema, symptoms suggestive of possible renal failure. The ankle oedema is treated with indapamide hemihydrate 5 mg every morning with good effect. She denies nausea, pruritus or any other symptom of uraemia.
4. She suffers from postural dizziness and chronic diarrhoea, symptoms suggestive of diabetic autonomic neuropathy, but no formal diagnosis has yet been made. She has had watery diarrhoea 7–8 times a day for many years with occasional abdominal discomfort and bloating. Despite multiple investigations including colonoscopy, no diagnosis has been made. Her bloating is treated with cisapride 10 mg daily, with some relief.
5. She has paraesthesias in the feet bilaterally but denies any loss of sensation or chronic superficial pain. She has never had nerve conduction studies performed.
6. She suffers from ischaemic heart disease and experiences frequent unstable angina, almost daily. She also suffers from dyspnoea on minimal exertion, orthopnoea and paroxysmal nocturnal dyspnoea. She has been investigated with exercise stress testing and nuclear imaging within the past 3 months, but surprisingly she is not on any anti-ischaemia therapy.
She denies ever having had a stroke or leg claudication.
She was diagnosed with hypercholesterolaemia 6 months ago, and is treated with simvastatin 40 mg daily. Her latest blood cholesterol level was 4 mmol/L. She denies any side effects associated with this treatment.
She was diagnosed with hypertension 3 years ago and is currently managed with verapamil one tablet daily. She denies any side effects associated with this therapy. Her GP monitors her blood pressure every 2 weeks, and lately the readings have been around 160/90 mmHg.
Her risk factor profile for coronary artery disease, in addition to diabetes mellitus, hypertension and hypercholesterolaemia, includes physical inactivity, obesity and a positive family history. Her mother had an acute myocardial infarction at age 55 and she has a brother aged 63 who suffers from ischaemic heart disease.
She has hypothyroidism, diagnosed many years ago when she presented with lethargy and cold intolerance. She is currently treated with thyroxine 100 µg daily. She does not know the causative pathology behind her hypothyroidism and denies any symptoms suggestive of ongoing thyroid disease.
She has had osteoarthritis involving the distal and proximal interphalangeal joints bilaterally, the lower cervical spine and the lumbar spine, for many years. She experiences frequent pain and impairment of mobility due to stiffness, particularly at night. However, she is not on any treatment.
She has had asthma for almost 20 years. She is currently managed with salbutamol via a metered dose inhaler as needed. Currently she uses it on average four times a week. She has previously been treated with inhaled steroids but the treatment was stopped due to the side effect of persistent cough. She has never been treated with systemic steroids. Five years ago she had an admission to hospital with exacerbation of asthma. She has not had any other hospital admissions for asthma. She has recurrent nocturnal cough. She does not monitor her peak flow. The only trigger factor for exacerbations she has identified is exercise, and she has not noticed any seasonal variation of her asthma symptoms.
She has glaucoma in both eyes, diagnosed 12 years ago. She has previously been treated with laser iridotomy bilaterally and is currently on topical pilocarpine therapy twice daily and topical acetazolamide twice daily.
She was diagnosed with reflux oesophagitis 10 years ago when she presented with burning epigastric pain. She was investigated with upper gastrointestinal endoscopy. She is being treated with omeprazole 10 mg twice daily but still suffers from dyspeptic symptoms.
She was diagnosed with Ménière’s disease 5 years ago. Although she experiences the symptoms of tinnitus and vertigo very often she is not on any treatment. She denies deafness.
She was diagnosed with obstructive sleep apnoea 2 years ago and is managed with nocturnal nasal continuous positive airway pressure; however, she still has daytime somnolence and early-morning headaches.
She started gaining weight after commencing insulin therapy 15 years ago. She has previously attempted to lose weight, particularly through dieting, without much success. She has never attempted regular exercise.
Her medications in summary are metformin, insulin, nitrofurantoin, indapamide, cisapride, verapamil, salbutamol and thyroxine. She claims appropriate compliance with all her medications.
She is intolerant to sulfur-containing medications, which cause ‘dizziness’, the description of which suggests presyncope rather than vertigo.
She has never smoked. She was a heavy alcohol consumer 15 years ago when she drank 50 g/day of whisky for almost 2 years. She now consumes alcohol only on social occasions.
She lives with a female friend. She has been married three times before and the last partner she divorced 10 years ago. She has one daughter, aged 27, from her first marriage. She keeps in regular contact with her daughter, who is well and lives separately.
She is independent with the activities of self-care but requires assistance with shopping and housekeeping. Her friend provides help with these.
She lives in a villa with five steps at the entrance, which she finds difficult to negotiate due to her back pain and dyspnoea.
She works part-time as a social worker in the community. She does not drive and travels by public transport.
The dietary history I obtained suggests excessive joule intake in the form of lipids and carbohydrates, and she admits that she is not compliant with the diabetic dietary recommendations.
She also complains of depression and the associated vegetative symptom of initial insomnia, but denies any loss of appetite.
ON EXAMINATION
DP was alert and cooperative. She was obese, with an estimated body mass index of 35. Her blood pressure was 140/95 mmHg and there was a postural drop of 30 mmHg systolic and 10 mmHg diastolic. Her pulse was 90 beats per minute, and it was normal in rhythm, rate and character. There was no postural change in the pulse rate. Her respiratory rate was 30 per minute.
Cardiovascular examination showed no jugular venous pressure elevation. Her apex beat was not palpable. There were two heart sounds, which were normal, and there was mild pitting oedema bipedally.
Respiratory tract examination showed oropharyngeal crowding. There was decreased chest expansion bilaterally in the lower zones. Breath sounds were vesicular with bibasal crepitations.
Gastrointestinal examination showed abdominal obesity, with multiple injection scars and lipodystrophy in the abdominal wall. The abdomen was soft and non-tender. There was non-tender hepatomegaly with a smooth and regular edge. Bowel sounds were present.
In the neurological examination, the cranial nerve examination was unremarkable. Fundoscopy was difficult to perform due to bilateral pupillary meiosis secondary to topical meiotic therapy.
Motor and sensory examination of the upper limbs was normal.
Motor examination of the lower limbs was normal but there was impairment of all modalities of sensation to the level of the knee bilaterally. Coordination was normal bilaterally, in both the upper and lower limbs. Plantar response was flexor bilaterally.
Her gait examination showed excessive lumbar lordosis, and the Romberg’s test was positive.
Musculoskeletal examination showed nodal osteoarthritis of both hands, with Bouchard’s nodes and Heberden’s nodes present in the interphalangeal joints of all fingers bilaterally. There was no warmness to touch, tenderness or impairment of movement. Hand function was well preserved. There was midline tenderness to palpation in the lower cervical spine and the lumbar spine. Spinal mobility, however, was preserved.
Diabetic foot examination was unremarkable for any corns, callosities, ulcers or Charcot’s joints.
In summary, this is a 61-year-old, obese, diabetic woman presenting with dyspnoea and chest pain on a background of poor diabetic control, multiple complications of diabetes as well as hypertension, osteoarthritis, obstructive sleep apnoea, reflux oesophagitis, asthma, Ménière’s disease and hypothyroidism.
This woman’s main problem is her obesity. However, diagnosis and treatment of her coronary symptoms are of primary importance.
The other issues with this woman include coronary risk factor modification, better control of diabetes and the management of respiratory causes of dyspnoea.
She suffers from chest pain, with features highly suggestive of cardiac ischaemia. Also her dyspnoea and associated symptoms can suggest congestive cardiac failure. She runs the risk of having an acute myocardial infarction; therefore, her chest pain should be investigated and managed first.
First, I would like to see the result of a recent electrocardiogram, looking for evidence of cardiac ischaemia and left ventricular hypertrophy. I would like to see a recent chest X-ray, looking for evidence of pulmonary congestion and cardiomegaly. In addition I would like to see the results of a recent full blood count, looking for anaemia that can contribute to dyspnoea, a coagulation profile and the electrolyte profile, and renal function indices, looking for any renal failure.
Questions and answers
Q: Please interpret this electrocardiogram and describe this chest X-ray.
A: This ECG of DP done on (insert date) shows sinus rhythm with a left-axis deviation. There is a left bundle branch block and, in light of that, it is impossible to further interpret this ECG for any cardiac ischaemia. I would like to see previous ECGs to ascertain how recently this bundle branch block has developed.
This frontal-projection, posteroanterior view chest X-ray of DP done on (insert date) shows poor chest expansion, increased cardiothoracic ratio suggesting cardiomegaly, and increased vascular markings in the upper zones suggesting left ventricular failure and upper lobe diversion. I would like to follow up this X-ray with a nuclear medicine gated heart pool scan to ascertain left ventricular ejection fraction, and formal lung function tests to assess her lung physiology.
Q: Why do you want a gated heart pool scan?
A: Due to this woman’s body habitus, a transthoracic echocardiogram would not be very accurate in interpreting the ventricular function. I consider a gated heart pool scan to be more accurate and suitable in this setting.
Q: How would you approach the management of her ischaemic heart disease?
A: It is questionable whether this woman has been conclusively diagnosed with ischaemic heart disease, given that she is not on any anti-ischaemia therapy. But she is at extremely high risk of ischaemic heart disease considering her current symptomatology and the risk-factor profile. So I would like to perform a pharmacological stress-perfusion scan in the form of a dipyridamole-sestamibi scan to look for any coronary flow reserve.
Meanwhile, I would commence her on regular low-dose aspirin therapy and sublingual nitrate therapy, as needed, for her chest pain.
If the investigations prove the presence of reversible cardiac ischaemia, I would follow her up with coronary angiography in order to define coronary anatomy and decide on definitive revascularisation therapy.
Coronary reperfusion will considerably improve her cardiac function. But for now I will treat her with a diuretic such as frusemide and an angiotensin receptor inhibitor. An ACE inhibitor will help control her hypertension and protect her from progressive diabetic nephropathy. I would be cautious with using beta-blocker agents in this woman due to her history of asthma.
Then I would review her cardiac risk-factor profile with a view to optimising control. For this purpose I would check her fasting cholesterol profile, and if she has hypercholesterolaemia I would consider appropriate therapy.
Q: She has presented for optimisation of her blood sugar control. How would you go about doing that?
A: She needs better control of her diabetes as well as management of end-organ complications. Initially I would like to see her glycosylated haemoglobin level to ascertain her level of control of the blood sugar over the past 6 weeks. Lack of compliance with diabetic medications as well as the diabetic diet is a major cause for suboptimal control in the majority of patients. Therefore I would ensure regular medication and strict compliance with the diabetic diet while she is in hospital. I would initially observe her for 3 days to see whether her blood sugar control improved. If there was no significant improvement I would change her insulin regimen to a twice-daily dose of a combination long- and short-acting insulin to be given 15 minutes prior to the two main meals. I would commence her on a long- and short-acting 30/70 mixture given subcutaneously twice daily, with 30 units given before breakfast and 15 units before dinner. I would increase the metformin dose to 1 g three times daily. I would educate her on the diabetic diet in consultation with the diabetic educator and a specialist dietitian. I would encourage her to do low-impact exercise, such as walking or wading in a pool, for about half an hour each day.
Q: What is the rationale behind your therapeutic plan?
A: High doses of insulin can lead to further weight gain and worsening of insulin resistance. My objective is to break this vicious cycle by managing her on the lowest possible insulin regimen while increasing metformin, which is an agent that improves peripheral insulin sensitivity and is beneficial to the obese. Weight loss is of major importance in the management of diabetes in this woman, so I would initiate a definite plan of action with a view to losing 5–10 kg of body weight over a period of 3–6 months. If successful, this amount of weight reduction will help improve her blood sugar control too.
Q: How would you plan the weight reduction program? How easy or difficult do you think it will be?
A: It is certainly not going to be easy, but I am keen on trying it because she has not previously tried such a program. I would obtain a detailed dietary history to calculate her current level of joule intake and make necessary arrangements to restrict the amount of joules she consumes. I would plan a diet aimed at weight reduction in consultation with the dietitian. This diet would be rich in complex carbohydrates with a low glycaemic index and deficient in simple sugars and saturated fats. I would educate the patient in joule counting and encourage her to keep a record of her food intake. The diet will comprise 15% protein, 15% lipids (mainly in the form of mono- and polyunsaturated fats) and 70% carbohydrates. In addition, I would encourage her to take up regular low-impact exercise, such as walking or wading in a swimming pool, to be done for about half an hour each day. I would advise the patient’s GP to monitor her progress at regular intervals of 2 weeks.
Given her history of hypothyroidism, I would check her serum thyroid-stimulating hormone level and free T4 and T3 indices to exclude persistent hypothyroidism, which could very well contribute to her obesity.
Q: What are your goals in treating this woman’s diabetes?
A: I would aim to maintain her fasting blood sugar levels below 6.1 mmol/L and postprandial blood sugar levels below 7.8 mmol/L. I would aim at keeping her HbA1c level below 7%. To monitor this I would initially advise her to check her blood sugar level immediately before and 2 hours after each main meal.
Q: How would you monitor her for end-organ complications?
A: To evaluate the degree of renal involvement, I would like to see the latest renal function indices in the form of the blood urea and serum creatinine levels. In addition, I would like to see the results of a recent urinalysis, looking for proteinuria, and a spot urine test to calculate the albumin-to-creatinine ratio, looking for evidence of microalbuminuria. If there was frank proteinuria, I would proceed with a 24-hour urine collection for the purpose of quantification.
I would also perform a renal ultrasound scan, looking for diminished renal size.
Q: Her albumin to creatinine ratio is 3.6. How does this affect the management of this patient?
A: This signifies the presence of microalbuminuria and she is at very high risk of cardiovascular events such as myocardial infarction and stroke. I would repeat the test on two more occasions at 3-monthly intervals to confirm microalbuminuria. Meanwhile I would control her blood pressure at a level below 130/80 mmHg and ensure strict glycaemic control. Commencement of ACE inhibitor therapy would benefit her kidneys. I would commence her on a cholesterol-lowering statin agent regardless of her cholesterol level.
Q: If she has diabetic nephropathy with proteinuria, how would you manage her?
A: I would ensure strict control of her blood pressure and also place her on a protein restriction of 0.8 g/kg per day. I would ensure adequate hydration at all times and stop all potentially nephrotoxic drugs. I would ensure strict glycaemic control as much as possible. I would continue to monitor her renal function indices to ascertain the rate of progression and plan renal replacement therapy if indicated.
Q: What do you think her dyspnoea is due to?
A: Her dyspnoea could be multifactorial. It is possibly due to a combination of left heart failure due to ischaemia and hypertension, poorly controlled asthma and restrictive ventilatory defect secondary to obesity. Pulmonary embolisation is another contributory factor that should be considered. Pleural effusion associated with hypothyroidism is also a remote possibility. To further investigate this, I would like to see the results of arterial blood gases on room air, looking for hypoxia and hypercapnoea, and formal lung function studies, looking for a combination of obstructive and restrictive patterns together with impaired gas exchange. If there was significant hypoxia in the blood gas result I would also perform a ventilation-perfusion scan, looking for mismatch defects that would suggest pulmonary embolism.
Q: Why is she still complaining of daytime somnolence despite the treatment of her sleep apnoea?
A: She has multiple risk factors that contribute to obstructive sleep apnoea,including morbid obesity, oropharyngeal crowding and possible hypothyroidism. On the other hand, obstructive sleep apnoea can be contributing to many of the medical problems she currently suffers from, including poorly controlled hypertension, dyspnoea, depression and early-morning headaches. The persistence of daytime symptoms including somnolence despite nocturnal nasal continuous positive airway pressure may be due to poor technique, but I would like to confirm the diagnosis of obstructive sleep apnoea conclusively. She needs a repeat sleep study and assessment of her technique with the nocturnal continuous positive airway pressure machine. Once again, achievement of weight loss goals will certainly improve her prognosis in this respect.
Q: How would you manage hypercholesterolaemia that is not responding to the maximum available dose of the statin medication you have commenced?
A: If the fasting total cholesterol level remains above 4.0 mmol/L despite statin therapy at 40 mg/day for more than 3 months, I would add ezetimibe 10 mg to the regimen. This agent is known to reduce the cholesterol level by a further 15% over what is achieved with the maximal statin dose.
