Preamble

Prevention of type 1 diabetes currently resides at around the same level as peace on earth: eminently desirable, theoretically possible, not as yet demonstrated. Jay Skyler has ably summarised the evidence that p-cell function can be influenced by therapies introduced at the time of diagnosis of type v diabetes. The immune intervention most convincingly shown to prolong p-cell function following diagnosis is cyclosporine, but its effects are usually transient and the risk of nephrotoxicity disqualifies it from further consideration. Nicotinamide is not known to affect immune function, but animal studies suggest that it can help p-cells to survive in a hostile environment. Its effects in humans following diagnosis are measurable, but clinically unimportant. The most evidence-based means of preserving p-cell function after diagnosis would be the introduction of intensified insulin therapy from the time of diagnosis. The Diabetes Control and Complications Trial demonstrated reciprocal benefit in those with high residual p-cell cell function - intensified therapy protects endogenous insulin secretion, and endogenous insulin secretion permits better control with less hypoglycaemia1. These effects may extend for six year following diagnosis, but it is doubtful whether lasting p-cell survival can be achieved beyond this point2.

Clinicians are sometimes accused of spending more time speculating about the possible benefits of untried therapies than in implementing what is already known. There is certainly reluctance to attempt strict glucose control in those newly diagnosed, partly based on a reasonable wish not to add to the burden of diabetes at this early stage of the disease. The culture of diabetes care varies more between countries than the reader of a text on evidence-based medicine might imagine, but there is something quintessentially British about the desire not to provoke anxiety about future unpleasantness until the opportunity of doing anything useful to prevent it has lapsed. Further investigation of the feasibility, costs and benefits of early aggressive insulin therapy from diagnosis would clearly be justified. It is also clear that trials of immune intervention need to be carefully standardised for glucose control - a powerful reason for insisting on blinded trials wherever feasible in this situation.

The important message from all this is that useful numbers of p-cell are present in many new-onset patients, that it is possible to influence their survival over a matter of years, and that this has the potential to reduce both the risk of long-term complications and the fear of hypoglycaemia. These observations cannot be ignored, and provide justification for a variety of immune interventions currently planned or in trial, as described in Chapter 4. They do not, however, offer a means of disease prevention.

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