Paediatrics: Type 1 diabetes mellitus

Type 1 diabetes mellitus

This is the most common form of diabetes mellitus in children and adoles-cents (90% of cases). It is an autoimmune disorder characterized by T-cell mediated destruction and progressive loss of pancreatic B-cells leading to eventual insulin deficiency and hyperglycaemia.

Epidemiology 

The incidence of Type 1 diabetes mellitus (T1DM) has been increasing, but shows marked geographical variation. In Europe the highest incidence rates are seen in the Nordic countries (Finland, Sweden). During childhood there are two peaks in presentation, one between ages 5 and 7yrs and the other, larger peak, just before or at the onset of puberty. Seasonal variation in presentation of T1DM is also observed with a peak seen in the winter months.

Aetiology

The cause of T1DM involves both genetic and environmental factors. Over 20 different T1DM susceptibility genes have been identified. The insulin-dependent diabetes mellitus (IDDM1) gene locus, which represents the human leukocyte antigen (HLA) DR/DQ locus on the major histocom-patibility complex, accounts for the greatest susceptibility.

The role of various environmental interactions and triggers is controversial.

Pathophysiology

T1DM is a chronic autoimmune condition.

·  Immune tolerance is broken and antibodies against specific B-cell autoantigens are generated (e.g. anti-islet cell; anti-insulin; anti-GluAD; anti-IA2 antibodies).

·  T-cell activation leads to B-cell inflammation (‘insulitis’) and to subsequent cell loss through apotosis.

·  The rate of B-cell loss varies (months–years) and the timing and presentation of symptomatic diabetes may depend on factors that increase insulin requirements (e.g. puberty).

Clinical presentation

The onset of symptoms evolves over a period of weeks. Symptoms are a reflection of insulin deficiency resulting in increased catabolism and hyper-glycaemia. In the majority, first presentation is usually made in the early symptomatic phase with:

·  weight loss;

·  polyuria/polydipsia;

·  nocturia/nocturnal enuresis.

Other less common symptoms include:

·  candida infection (e.g. oral thrush, balanitis, vulovaginitis);

·  skin infections.

Failure to recognize these symptoms will result in delayed or late diagnosis of T1DM and possible presentation with DKA. The risk of first presentation of T1DM with DKA is increased when non-specific symptoms of diabetes may go unrecognized:

·intercurrent/febrile illness;

·infants and preschool age child.

Assessment of new patient

Emphasis should be put on:

·History: duration of symptoms.

·Family history: of diabetes/other autoimmune disease.

·Examination: weight/BMI; signs of DKA.

Diagnosis and investigations

The diagnosis is readily established in a symptomatic child with a random blood glucose level >11.1mmol/L. Other investigations:

·U&E.

·Blood pH (to exclude DKA).

·Diabetes-related autoantibodies: islet cell antibody (ICA)/anti-insulin antibody (IAA)/anti-GluAD antibody (GluAD)/anti-IA-2.

·Other autoimmune disease screen: thyroid function test/thyroid antibodies; coeliac disease antibody screen.