Type 1 Diabetes Treatment

Individuals with T1D must rely on exogenous insulin delivered subcutaneously (subq) either by periodic injection or by continuous pumpassisted infusion to control the hyperglycemia and ketonemia. Two types of therapeutic injection regimens are currently used, standard and intensive. [Note: Pump delivery is also considered intensive therapy.]
1. Standard versus intensive treatment: Standard treatment is typically two to three daily injections of recombinant human insulin. Mean blood glucose levels obtained are typically 225–275 mg/dl, with a glycated hemoglobin (HbA1c) level  of 8%–9% of the total hemoglobin (blue arrow in Fig. 1). [Note: The rate of formation of HbA1c is proportional to the average blood glucose concentration over the previous 3 months. Thus, HbA1c provides a measure of how well treatment has normalized blood glucose over that time in a patient with diabetes.] In contrast to standard therapy, intensive treatment seeks to more closely normalize blood glucose through more frequent monitoring and subsequent injections of insulin, typically ≥4 times a day. Mean blood glucose levels of 150 mg/dl can be achieved, with HbA1c ~7% of the total hemoglobin (see red arrow in Fig. 1). [Note: Normal mean blood glucose is ~100 mg/dl, and HbA1c is ≤6% (see black arrow in Fig.1).] Therefore, normalization of glucose values (euglycemia) is not achieved even in intensively treated patients. Nonetheless, patients on intensive therapy show a ≥50% reduction in the long-term microvascular complications of diabetes (that is, retinopathy, nephropathy, and neuropathy) compared with patients receiving standard care. This confirms that the complications of diabetes are related to an elevation of plasma glucose.

Figure 1: Correlation between mean blood glucose and percent hemoglobin A1c in patients with type 1 diabetes receiving intensive or standard insulin therapy. [Note: Nondiabetic individuals are included for comparison.]
2. Hypoglycemia: One of the therapeutic goals in cases of diabetes is to decrease blood glucose levels in an effort to minimize the development of long-term complications of the disease . However, appropriate dosage of insulin is difficult to achieve. Hypoglycemia caused by excess insulin is the most common complication of insulin therapy, occurring in >90% of patients. The frequency of hypoglycemic episodes, seizures, and coma is particularly high with intensive treatment regimens designed to achieve tight control of blood glucose (Fig. 2). In normal individuals, hypoglycemia triggers a compensatory secretion of counterregulatory hormones, most notably glucagon and epinephrine, which promote hepatic production of glucose . However, patients with T1D also develop a deficiency of glucagon secretion. This defect occurs early in the disease and is almost universally present 4 years after diagnosis. Therefore, these patients rely on epinephrine secretion to prevent severe hypoglycemia. However, as the disease progresses, T1D patients show diabetic autonomic neuropathy and impaired ability to secrete epinephrine in response to hypoglycemia. The combined deficiency of glucagon and epinephrine secretion creates a symptom-free condition sometimes called “hypoglycemia unawareness.” Thus, patients with long-standing T1D are particularly vulnerable to hypoglycemia.
Hypoglycemia can also be caused by strenuous exercise. Because exercise promotes glucose uptake into muscle and decreases the need for exogenous insulin, patients are advised to check blood glucose levels before or after intensive exercise to prevent or abort hypoglycemia.

Figure 2: Effect of tight glucose control on hypoglycemic episodes in a population of patients on intensive therapy or standard therapy.
3. Contraindications for tight control: Children are not put on a program of tight control of blood glucose before age 8 years because of the risk that episodes of hypoglycemia may adversely affect brain development. Elderly people typically do not go on tight control because hypoglycemia can cause strokes and heart attacks in this population. Also, the major goal of tight control is to prevent complications many years later. Tight control, then, is most worthwhile for otherwise healthy people who can expect to live at least 10 more years. [Note: For most nonpregnant adults with diabetes, the individual treatment strategies and goals are based on the duration of diabetes, age/life expectancy, and known comorbid conditions.]

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