Type 1 Diabetes Mellitus

Type 1 diabetes (T1DM) formerly know as “childhood," "juvenile," or "insulin-dependent" diabetes is characterized by high glucose levels secondary to auto-immune destruction of the insulin-producing beta cells of the islets of Langerhans of the pancreas leading to a deficiency of insulin. Insulin is the hormone that drives blood glucose into the cells where it can be used for fuel, heat production and other metabolic processes. T1DM is lethal unless chronic treatment with exogenous insulin replaces the missing hormone. While T1DM was previously considered to be primarily a childhood problem, it is now known that it may have its onset at any age which is why "Type 1" is the preferred term.

Diabetes mellitus in poorly controlled patients is associated with significant morbidity and mortality due to long term microvascular and macrovascular complications such as retinopathy, neuropathy, nephropathy, myocardial infarction and stroke. A large prospective trial, The Diabetes Control and Complications Trial (DCCT) clearly demonstrated the benefits of intensive glycemic control for preventing or delaying the development and progression of both microvascular as well as macrovascular long term complications in patients with T1DM. Therefore, maintaining plasma glucose concentrations within levels as close to the normal (nondiabetic) range as possible has become the fundamental treatment goal of comprehensive diabetes care. However, the DCCT also demonstrated that intensive insulin therapy used to optimize glycemic control is associated with an increased incidence of hypoglycemia (low blood glucose). The potential for hypoglycemia in patients with T1DM is increased because patients with long-standing diabetes lose their protective mechanisms against hypoglycemia and because of pharmacokinetic and pharmacodynamic imperfections of current insulin based treatment regimens. Iatrogenic (drug-induced) hypoglycemia is the most common adverse effect associated with treatment of T1DM and it is a major barrier, from the perspective of both patients and physicians, to the implementation of intensive insulin treatment to improve outcomes.

Although blood glucose levels in patients with T1DM are often low during sleep, routine measurement has been uncommon until the recent advent of non-invasive continuous glucose monitors (CGM). CGM has demonstrated that the average patient with T1DM has hypoglycemia for about 10% of the day with nocturnal hypoglycemia accounting for more than 50% of all hypoglycemic episodes On the less severe spectrum of effects, nocturnal hypoglycemia may cause sleep disturbances (vivid dreams or nightmares) daytime fatigue or mood changes. Frequent episodes of mild hypoglycemia are known to lessen the ability of patients with T1DM to sense their hypoglycemia, thereby putting them at risk for increasingly severe episodes. Thus, a vicious circle of recurrent severe hypoglycemia is created. Severe episodes of nocturnal hypoglycemia may cause life-threatening events such as seizure, coma, stroke-like effects, or sudden cardiac death, known as “dead in bed syndrome“. An estimated 2-4% of deaths of people with T1DM have been attributed to hypoglycemia.