Management strategies for brittle diabetes.

Type 1 diabetes is an intrinsically unstable condition. However, the term "brittle diabetes" is reserved for those cases in which the instability, whatever its cause, results in disruption of life and often recurrent and/or prolonged hospitalization. It affects 3/1000 insulin-dependent diabetic patients, mainly young women. Its prognosis is poor with lower quality of life scores, more microvascular and pregnancy complications and shortened life expectancy. Three forms have been described: recurrent diabetic ketoacidosis, predominant hypoglycemic forms and mixed instability. Main causes of brittleness include malabsorption, certain drugs (alcohol, antipsychotics), defective insulin absorption or degradation, defect of hyperglycemic hormones especially glucocorticoid and glucagon, and above all delayed gastric emptying as a result of autonomic neuropathy. Psychosocial factors are very important and factitious brittleness may lead to a self-perpetuating condition. The assessment of brittle diabetes requires quantification of the variability of blood glucose levels. To quantify instability, measures which have been developed, include Mean Amplitude of the largest Glycemic Excursions (MAGE), Mean Of Daily Differences (MODD), Lability Index (LI), Low Blood Glucose Index (LBGI), Clarke's score, Hyposcore, and continuous blood glucose monitoring. Once psychogenic problems have been excluded, therapeutic strategies require firstly, the treatment of underlying organic causes of the brittleness whenever possible and secondly optimising standard insulin therapy using analogues, multiple injections and consideration of Continuous Subcutaneous Insulin Infusion. Alternative approaches may still be needed for the most severely affected patients. Isolated islet transplantation (IIT), which restores glucose sensing, should be considered in cases of hypoglycaemic unawareness and/or lability especially if the body mass index is < 25, but with current immunosuppressive protocols patients must have normal renal function and preferably no plans for pregnancy. Implantable pumps have advantages for patients who either weigh more than 80 kgs or have abnormalities of kidney or liver function or are highly sensitised.