New tools for children with Type 1 diabetes -

New tools for children with Type 1 diabetes - - Modern Medicine

HOT TOPICS: Cardiometabolic Disorders & Weight · Liability & Risk Management· Health Care IT

Normalization of blood glucose levels is the ultimate goal of diabetes treatment. But this goal must be balanced against the risk of hypoglycemia, which results when the body's insulin needs do not match the action of the insulin that has been delivered. In recent years, advances in recombinant DNA technology and medical device technology have helped us improve glycemic control while simultaneously decreasing the risk of hypoglycemia. These new technologies include insulin analogs and methods for delivering them, as well as improved glucose monitoring devices.

A little background

Table 1: HbA1c and glucose goals for age

The discovery and purification of insulin in 1921 created the first effective treatment for diabetes mellitus.¹ While this new therapy allowed patients to survive a previously fatal illness, additional complications became apparent. These included acute hypoglycemia and significant morbidity and mortality caused by long-term diabetes-associated microvascular and macrovascular complications. We now know that improved control of hyperglycemia decreases the risk of developing these complications.^2,3 Therefore, current treatment goals involve a tradeoff between normalized blood glucose levels and the risk of hypoglycemia. In younger children, it can be more difficult to identify hypoglycemia-the symptoms may be too subtle for caregivers, and the child may be less able to identify symptoms of hypoglycemia in themselves. Because of this, current guidelines recommend a higher goal for hemoglobin A1c (HbA1c) levels for younger children than for those who are older (TABLE 1).⁴

Insulin analogs

Pancreatic β-cells secrete insulin at a low basal rate that controls glucose levels in the fasting state; they also secrete increased amounts of insulin that control glucose levels after food intake. To normalize blood glucose levels in diabetics, administered insulin must replicate this endogenous basal-bolus pattern of insulin secretion.

Figure 1: Insulin requirements vs insulin action

Before insulins manufactured by recombinant DNA technology were developed, insulin regimens relied on a combination of regular insulin coupled with a longer-acting insulin such as neutral protamine Hagedorn (NPH). These regimens provided insulin action throughout the day with two or three shots. Unfortunately, the pharmacodynamics of these insulins did not match physiologic requirements, resulting in insufficient insulin action after meals and excess insulin action overnight and between meals (FIGURE 1).

Recombinant DNA technology allowed for structural modifications of insulin to alter its rate of absorption after subcutaneous injection. Thus, insulins could be designed with peaks and durations of action that would be better suited to provide either basal or bolus insulin needs.

Figure 2

BASAL INSULINS: LONG-ACTING INSULIN ANALOGS. The ideal basal insulin would have a long duration of action and no peak, providing a steady, low level of insulin action. Insulin glargine (Lantus) was the first insulin analog designed to provide basal insulin action: it was approved by the Food and Drug Administration (FDA) in 2000. The structure of insulin glargine differs from human insulin by only three amino acids (FIGURE 2). These modifications result in insulin glargine having a higher isoelectric point than that of human insulin. As a result, insulin glargine remains soluble at the acidic pH in the vial, and precipitates at the neutral pH of subcutaneous tissue once injected. It then slowly diffuses from this precipitated state.

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