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The increasing understanding of the processes leading to symptomatic type 1 diabetes has resulted in a consensus model in individuals who have a genetic susceptibility and comprises 3 stages (Figure 6.9). Stage 1 individuals have positive autoantibodies but normal glucose tolerance. As mentioned above, increasing numbers of islet autoantibodies and increasing titres represent disease progression. Stage 2 is reached as β cell loss results in glycaemic responses to a glucose challenge becoming abnormal, but there is no universal agreement as to what the glucose stimulus should be or what threshold of blood glucose (or HbA1c) would define ‘dysglycaemia’. Both the presence of impaired fasting glucose or glucose intolerance (see Chap 3) following a 75g OGTT and a 20% increase in baseline HbA1c have a positive predictive value (PPV) of 98% for symptomatic type 1 diabetes within 5 years in prospective studies in high risk individuals, and it is known that the first phase insulin response to intravenous glucose declines rapidly 18–6 months before diabetes symptoms. Stage 3 is the development of symptomatic diabetes.