The Rationale for Timing of the premeal insulin administration - In type 1 diabetes, very little, if any, endogenous insulin is available to handle the carbohydrate load which very rapidly enters the circulation after the start of a meal. In non diabetic individuals, a complex array of physiological events occurs prior to eating (often called the cephalic phase of insulin secretion) which prepares the pancreas for immediate release of preformed insulin when any meal related increase in blood glucose occurs. This rapid insulin secretion prepares the tissues (primarily muscle and liver) to take up glucose very rapidly and thereby prevent severe hyperglycemia in the postprandial state. Since significant absorption of all short acting insulins (e.g. insulin lispro, aspart, or glulisine) from the subcutaneous tissue does not occur for 15 minutes following injection (26), this delay often results in postprandial hyperglycemia. If the patient happens to be hypoglycemic prior to the meal, this delay can be advantageous, but if he/she is hyperglycemic, then severe postprandial hyperglycemia may result. A rationale solution to this problem would be to time the short acting insulin injection based on the premeal blood glucose, but aside from our one pilot study addressing this strategy, no clinical study has been published supporting this approach. Our grant application is designed to correct this deficiency and provide the scientific data to support this addition to intensive insulin therapy.