Latent autoimmune diabetes in the young
Editor – Latent autoimmune diabetes in the young (LADY) incorporates an increasing number of young patients with an initial insulin independent period. This is similar to latent autoimmune diabetes in adults (LADA), which masquerades as type 2 diabetes. The UK Prospective Diabetes Study estimated that 10–15% of patients with type 2 diabetes have latent autoimmune diabetes and that 58% of these patients require insulin within six years of diagnosis, irrespective of age.1 The recent finding that early insulin therapy has favourable outcomes on β-cell function and glycaemic remission compared with oral hypoglycaemic agents in patients with newly diagnosed type 2 diabetes is an exciting prospect.2
With reference to the recent lesson of the month (Clin Med October 2008 pp 552–3), taking into consideration the asymptomatic 15-year-old girl's body mass index of 21.4 kg/m2, consistent with ketonuria and raised blood glucose, favours the initiation of insulin treatment. It is of concern that the patient's β-cell function may have been left to deteriorate on sulphonylureas. In light of Weng et al's finding a low-dose insulin regime may have been a better option to preserve β-cell function and prevent catastrophic outcomes such as diabetic ketoacidosis.2
It would be interesting to know the HbA1c of the patient as Stene and colleagues demonstrated that normal but increasing HbA1c may predict progression from islet immunity to overt type 1 diabetes, whereas random plasma glucose levels are less predictive.3 Further, the human leukocyte antigen (HLA) status of the patient is not stated which could predict disease progression. The DAISY study implies that DR3/4 and the DQ8 genotype are predictive of disease progression. However 50% of genetic risk for type 1 diabetes is attributable to HLA region, including the insulin gene, CTLA-4, IL4/13 which all demonstrate a strong association.4 Autoantibody testing is highly favourable in such patients as there is a strong association with progression to type 1 diabetes.5 However, autoantibodies such as GAD65 must be repeated more than once to rule out false or transient positive results. In addition to existing markers of autoimmunity, data on a novel autoantibody ZnT8 suggest that this autoantibody may need to be tested to diagnose latent autoimmune diabetes.6
The possibility that LADY represents a growing proportion of cases seen in clinical practice, together with limited evidence to guide health professionals in treatment options, makes research into glycaemic control and preservation of β-cell function relevant in these patients. Screening and early detection of such patients may lead to a less severe onset and a milder clinical course following diagnosis.7
- © 2009 Royal College of Physicians
Reference
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- ↵Weng J, Li Y, Xu W et al. Effect of intensive insulin therapy on β-cell function and glyacemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 2008; 371:1573–60.
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- ↵Steck AK, Bugawan TL, Valdes AM et al. Association of non-HLA genes with type 1 diabetes autoimmunity. Diabetes 2005;54(8)2482–6.doi:10.2337/diabetes.54.8.2482
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- ↵Wenzlau JM, Juhl K, Yu L et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci USA 2007; 104:17040–45.doi:10.1073/pnas.0705894104
- ↵Barker JM, Goehrig SH, Barriga K et al. Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up. Diabetes Care 2004;27(6)1399–404.doi:10.2337/diacare.27.6.1399
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