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Type 1 diabetes typically presents with acute osmotic symptoms or diabetic decompensation. It is seldom diagnosed solely as the result of a blood test.
A woman of 23 consulted her general practitioner because of 'flu-like symptoms, sore throat and lethargy. There was a strong family history of type 1 diabetes (including a brother and a first cousin) and her mother had checked her blood glucose with a meter. The reading was 13.4 mmol/L 2 hours after food. On examination her temperature was 37.4°C and she had mild tender submandibular lymphadenopathy and tonsillar erythema. She was slim, with a body mass index of 23.
She had never experienced any osmotic or other symptoms suggestive of diabetes. In the fasting state, urine was negative for glucose and ketones and plasma glucose was 5.9 mmol/L. Further blood tests showed a normal full blood count, including differential, and normal renal, liver and thyroid function. A monospot test was positive, and infectious mononucleosis was thought the likely cause of her symptoms. She was advised to rest, and to test her blood sugar occasionally, fasting and 2 hours after meals. Postprandial hyperglycaemia continued with blood sugars on her meter ranging from 9 to 14 mmol/L. Urine remained negative for ketones and glucose. An oral glucose tolerance test (OGTT) pointed to diabetes and she was referred to the hospital diabetes clinic. Blood sugars continued at 4-7 mmol/L before meals and up to 14 mmol/L postprandially. She was now symptom-free, having recovered from her bout of infectious mononucleosis. There was no evidence of diabetic complications. Glycated haemoglobin indicated good control at 6.7%. Glutamic acid decarboxylase-65 antibody (GAD65) and islet cell antibody (ICA) markers for type 1 diabetes were strongly positive. An OGTT three months after the first showed no change (Table 1). Six months after diagnosis she is taking repaglinide 0.5 mg with meals and has good postprandial glycaemic control. She has been offered lowdose preprandial insulin but prefers to use oral medication for as long as possible.
The Diabetes Prevention Trial Investigators have described a group of patients who are diagnosed with type 1 diabetes on the basis of OGTT alone1. The study involved screening all ICA-positive relatives of a cohort of type 1 diabetic patients with OGTT to determine glycaemic status and intravenous GTT to determine first-phase insulin response. Of 585 relatives screened, 73% had normal glucose tolerance, 14.9% had impaired glucose tolerance and 10.4% had diabetes. Amongst the diabetic cohort, diabetes was diagnosed generally on the basis of postprandial hyperglycaemia rather than fasting hyperglycaemia. In addition, these patients had an impaired first-phase insulin response to a glucose load and high-risk diabetes HLA haplotypes were common in this group. All were symptom-free and the age range was 3-45 years. The fact that they are young and ICA-positive, have a first-degree relative with type 1 diabetes, and possess high-risk HLA haplotypes makes it very likely they have true type 1 diabetes and will eventually develop symptomatic disease requiring insulin.
This newly described subset gives some clue as to the natural history of type 1 diabetes before it becomes clinically apparent. The impaired first-phase response to a glucose load suggests that the earliest manifestation of beta cell failure is loss of acute insulin response to a glucose load, leading to postprandial hyperglycaemia. The viral illness in our patient may or may not have influenced her glycaemic status, but we note that glucose tolerance was unaltered after recovery. An unanswered question is whether ‘resting’ the beta-cells with low-dose insulin or immunomodulatory therapies such as cyclosporin will prevent or delay progression to full-blown diabetes2.