B. Mukhopadhyay, J. Geddes, M. Fisher
Department of Diabetes, Glasgow Royal Infirmary, Glasgow
Correspondence to: M Fisher, Consultant Physician, Department of Diabetes, Glasgow Royal Infirmary, Glasgow Tel: 0141 211 4182 Fax: 0141 211 4080 Email: miles.fisher@northglasgow.scot.nhs.uk
SMJ 2005 50(3): 127-128
Abstract
We report diagnostic difficulties in a case of diabetes mellitus presenting as acute on chronic renal failure with normoglycaemia. A renal biopsy indicated diabetic nephropathy; she developed hyperglycaemia following the institution of haemodialysis. It is important to remember that diabetic patients may have normal blood glucose concentrations in renal failure. In a patient with undiagnosed diabetes mellitus presenting with acute on chronic renal failure, choice of diagnostic biochemical test for diabetes may be difficult.
Key words: normoglycaemia, diabetes mellitus, renal failure.
Case report
A 55-year-old Caucasian woman was admitted as an emergency to hospital in December 2003 by her general practitioner after a fall. She had had diarrhoea for a week and facial swelling, which he suspected was caused by a drug reaction to Diclofenac sodium; this had been prescribed for left leg pain one week prior to her admission. She was a non-smoker, and drug therapy on admission to hospital consisted of ferrous sulphate 200mg tid, simvastatin 40 mg od, diclofenac 50mg tid and loperamide 2mg prn.
Clinical examination on arrival to hospital revealed that she was hypothermic (temperature 34 degree C) and bradycardic at 47 bpm, with a blood pressure of 144/72 mmHg. She had widespread peripheral oedema. Heart sounds were noted to be quiet. There were bilateral pleural effusions on respiratory examination. Electrocardiogram revealed sinus bradycardia, low-voltage complexes and increased QT interval (QTc 0.54 sec). Chest radiograph demonstrated cardiomegaly and evidence of fluid overload, with bilateral pleural effusions.
Admission biochemistry results (Table 1) were suggestive of acute renal failure with metabolic acidosis, normocytic anaemia, hypocalcaemia and hyperphosphataemia; the presence of anaemia and hypocalcaemia indicated the possibility of underlying chronic renal disease. Urinalysis revealed moderate degrees of blood and protein, but no glycosuria. Her random serum glucose was 6.2 mmol/l. The renal failure was suspected to be either secondary to the nonsteroidal anti-inflammatory drug or rapidly progressive glomerulonephritis. Her renal immunology, complement levels and myeloma screen were normal. A renal ultrasound demonstrated unobstructed kidneys, 9.4 cm on the right and 8.4 cm on left. She remained oliguric and developed pulmonary edema unresponsive to treatment with diuretics. An echocardiogram revealed a hypertrophied left ventricle with good function. There were no obvious regional wall motion abnormalities, no valvular dysfunction and mild mitral regurgitation. She was therefore started on haemodialysis and ultrafiltration.
Her old medical notes became available at this stage after considerable delay. Her recent medical history included anaemia and deteriorating renal function for which she had attended the general medical outpatient clinic in June 2003; at that point her serum creatinine was 150 µmol/l (normal range 75 – 130 µmol/l, estimated creatinine clearance 33 ml/ min). In the clinic, she had denied any osmotic symptoms, her general clinical examination including neurology was unremarkable, blood pressure was 165/95 mmHg and apart from abnormal renal function and normochromic, normocytic anaemia (Hb 10.5 gm/dl) routine blood tests were normal. Her random blood glucose was 12 mmol/l; thereafter a fasting blood glucose was 5.0 mmol/l. Subsequently she failed to attend the clinic for follow up. She also had a past medical history of hysterical paraparesis since 1984 and hyperlipidaemia.
As the cause of her renal failure remained unclear, a renal biopsy was performed two weeks after admission following correction of her coagulopathy. This demonstrated nodular sclerosis with features similar to diabetic nephropathy (Figures 1a and 1b). Subsequently two fasting blood glucose concentrations were normal (5.1 and 5.6 mmol/l) and glycosylated haemoglobin (HbA1c) was 5.1%. After a period of haemodialysis, her appetite improved and blood glucose concentrations began to increase up to 25 mmol/l, requiring treatment with oral sulphonylureas. At this point she was screened for other complications of diabetes, and fundoscopy through dilated pupils revealed pre proliferative diabetic retinopathy in the right eye and a dense cataract in the left, substantiating a diagnosis of longstanding undiagnosed diabetes mellitus.
After two months of treatment as an inpatient she was well enough to come off haemodialysis (creatinine 220 µmol/l) and was discharged home. She was however readmitted three weeks later with vomiting and worsening of renal function, perhaps due to gastroparesis as suggested at gastroscopy. There was no postural hypotension or other evidence of autonomic neuropathy. During her second admission she suffered a cardiac arrest, which she did not survive.
Discussion
Type 2 diabetes is on the rise and in Scotland at least one in 40 people have the disease. Type 2 diabetes can present to a variety of health care professionals; to the podiatrist with foot problems, to the optician or ophthalmologist with retinopathy, to the dermatologist with skin lesions, to the general physician with dyslipidaemia, to name but a few. In the United Kingdom Prospective Diabetes Study (UKPDS), 21% of newly diagnosed patients had evidence of retinopathy and 18% had an abnormal electrocardiogram at presentation.1
However, it is uncommon for patients with diabetes to present with advanced renal failure. In the United Kingdom Prospective Diabetes Study, only two subjects out of 3232 (0.06%) newly diagnosed patients presented with serum creatinine > 175 µmol/l . In the same study only 3% patients had elevated creatinine at presentation although it is not clear whether they had diabetic nephropathy. In a recent survey from a tertiary clinic in a developing country, 7.5% of all newly registered patients had signs of nephropathy as judged by elevated serum creatinine (>176mmol/L), frank proteinuria or oedema.2 In diabetic patients, blood sugar levels tend to be lower in renal failure. Such patients are predisposed to hypoglycaemic attacks. This is due to a combination of factors including reduced clearance of insulin, loss of renal neoglucogenesis and reduced calorie intake as a result of anorexia. There have been previous reports of euglycaemia in patients presenting with overt microvascular disease3. The normal blood sugar level at presentation in our case is perhaps explained by her poor appetite and renal failure. As her appetite improved with haemodialysis, she became hyperglycaemic requiring treatment with an oral sulphonylurea.
This case also highlights the dilemma about which diagnostic test to choose for diabetes - fasting blood glucose or glucose response to an oral glucose load (OGTT). The WHO criteria of 2 hour post-prandial blood glucose level had been used for the diagnosis of diabetes. In 1997 the American Diabetes Association (ADA) adopted the revised fasting blood glucose (FBG) level 7.0 mmol/L, as this was predictive of developing microvascular complications4. But the DECODE study demonstrated that among patients thought to have diabetes by the WHO criteria, 52% had a FBG < 7 mmol/l, whereas in the ADA group diagnosed on the basis of fasting blood glucose level, 59 % of patients failed to reach the two hour diagnostic value of > 11 mmol/L5. In cases of diagnostic dilemma, expert opinion is currently in favour of the OGTT, as this involves measuring both fasting and two hour glucose.
It is likely that a formal OGTT would have revealed the diagnosis earlier in our patient. Also earlier fundoscopy could have provided useful diagnostic information. Needless to say, on this occasion, neither would perhaps have changed the natural history of her illness, which was in an advanced stage at presentation. She had chronic renal failure secondary to diabetes; dehydration due to diarrhea precipitated acute renal failure.
Although unusual, diabetes should be considered in the differential diagnosis of someone presenting with renal failure. One should be aware that such patients may not be hyperglycaemic, and a normal blood sugar measured under such circumstances does not rule out a diagnosis of diabetes mellitus. In cases of doubt a formal oral glucose tolerance test is recommended and one should screen for microvascular complications of diabetes, which could be diagnostic.
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