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Progression from Basal to Pre-mixed or Rapid-acting Insulin
intensively during the 10-year study period. The results of a 10-year post- may protect, and possibly restore, beta-cell function, and therefore alter
study follow-up on 3,277 of the patients remaining in the trial showed that the progressive course of diabetes.
21
the differences between treatment groups in terms of glycemic control
were eliminated during the first year, but the risk for microvascular events Initiating Insulin Therapy
and for myocardial infarction and death from any cause was reduced Insulin is clearly the most effective way to control hyperglycemia. There is
throughout the 10 years of post-trial follow-up. This demonstrated the recent evidence to suggest that healthcare providers generally wait to
long-term benefit of early glycemic control in the UKPDS population.
15
The initiate insulin therapy and that the HbA
1c
value at which they will start
Epidemiology of Diabetes Interventions and Complications (EDIC) study aggressive glucose-lowering action is 9% or higher.
23,24
This reluctance
originally compared intensive and conventional therapy in a population of may be due, in part, to concern about hypoglycemia and patient
1,441 patients with type 1 diabetes. In the 17-year follow-up of this study, willingness and/or ability to inject insulin. A variety of insulin analogs are
intensive treatment providing early glycemic control reduced the risk for now available that lower the risk for hypoglycemia and limit weight gain.
any cardiovascular disease event by 42% (p=0.02 versus conventional New insulin analogs more closely mimic the kinetic profile of endogenous
treatment) and reduced the risk for non-fatal myocardial infarction, insulin compared with the older human insulins. Both human insulin
stroke, or death from cardiovascular disease by 57% (p=0.02). and insulin analogs are now available in convenient pen devices that
Microalbuminuria and albuminuria were associated with a significant allow more flexible dosing.
25
Pens can provide more accurate dosing
increase in the risk for cardiovascular disease, but differences between compared with a vial/syringe, as well as providing more discreet dosing.
treatment groups remained significant (p≤0.05). It was concluded that They can also be easier to use/learn/teach.
26–28
intensive therapy has long-term beneficial effects on the risk for
cardiovascular disease in patients with type 1 diabetes.
7
In the past, a common approach to initiating insulin therapy in type 2
diabetes was to discontinue OADs and begin with a single morning dose
The level of glycemic control is gauged by fasting plasma glucose (FPG), of basal insulin.
29
An alternative approach was subsequently developed in
post-prandial plasma glucose (PPG), and glycated hemoglobin (HbA
1c
), which a single bedtime dose of basal insulin (initially intermediate-acting
which reflects glycemic exposure during a period of approximately three neutral protamine Hagedorn [NPH] and, more recently, long-acting insulin
months. PPG contributes significantly to the HbA
1c
value, especially as glargine or detemir) was added to the daytime OAD regimen. The
values approach target levels,
16
and post-prandial glucose excursions have intention behind this approach is to control FPG with basal insulin and to
recently been linked to vascular damage.
17
Control of PPG is crucial to control daytime and post-prandial hyperglycemia using OAD medications,
reaching the target HbA
1c
levels of 6.5% as recommended by the such as sulfonylureas or other oral secretagogues that augment prandial
American Association of Clinical Endocrinologists (AACE) and <7% as insulin secretion. However, evidence may be lacking to substantiate the
recommended by the American Diabetes Association (ADA).
18,19
Therefore, prandial benefit of sulfonylureas.
22
Alternatively, pre-mixed insulins can
treatment with basal insulin alone may be insufficient to achieve glycemic be an option to initiate insulin therapy. These are mixtures of insulin
control targets, and an intensified insulin regimen is often required to preparations containing fixed ratios of regular human insulin plus NPH or
achieve target HbA
1c
levels as the disease progresses. rapid-acting analogs plus a protaminated intermediate-acting form of
a rapid-acting analog. Thus, these mixtures provide control of fasting
Rationale for Early Initiation of Insulin Therapy plasma glucose and prandial plasma glucose in a single injection.
The Diabetes Prevention Program demonstrated that an intensive lifestyle Examples of pre-mixed analog preparations include a mixture containing
intervention was most effective at reducing progression to diabetes in 75% protamine-based intermediate-acting neutral protamine lispro (NPL)
high-risk individuals, followed by metformin therapy.
20
Similarly, early and 25% rapid-acting insulin lispro, and another example contains 70%
intervention with insulin may potentially protect beta-cell function.
21,22
A insulin aspart protamine suspension and 30% insulin aspart.
30
Pre-mixed
recent randomized, parallel-group study of 382 patients with newly analogs have been studied to initiate insulin once or twice daily.
31
diagnosed type 2 diabetes looked at the effects of intensive, short-term
insulin therapy on beta-cell function.
23
Patients were randomly assigned to Insulins with different pharmacodynamic profiles are available, allowing
treatment with continuous subcutaneous insulin therapy, multiple daily for three possible strategies in the initiation of insulin therapy: basal
injections (MDIs), or oral hypoglycemic agents. Once patients had achieved insulin, basal–bolus insulin (basal–bolus insulin can be used to initiate
and sustained on-therapy normoglycemia for two weeks, pharmacological therapy for patients with HbA
1c
levels >8.5%
32
), or pre-mixed insulin. For
treatment was stopped. Normoglycemia was attained by >95% of patients more detail, see Table 1 in the online version of this article at
in the insulin treatment groups compared with 84% of those receiving oral www.touchendocrinology.com. Typically, the first strategy to consider is
agents. Glycemic control, in terms of fasting blood glucose, was reached the addition of a basal insulin to an OAD regimen. Compared with NPH
significantly faster with insulin, and at one year after treatment 51% of insulin, both detemir and glargine have demonstrated comparable efficacy
those who had received continuous insulin and 45% of those who had for glycemic control, once-daily dosing, and less hypoglycemia.
33,34
In
received MDIs remained normoglycemic compared with 27% of patients addition, the new AACE guidelines recommend the use of insulin analogs
treated with oral hypoglycemic agents. Beta-cell function was measured at over human insulin formulations.
35
the end of therapy and after one year using homeostasis model
assessment of basal beta-cell function (HOMA B) and acute insulin The AACE recommends that treatment-naïve individuals whose initial
response. Patients treated with continuous insulin therapy had an increase HbA
19
1c
value is >10% be started on insulin therapy. A major challenge
in HOMA B of 160% compared with 105% for those treated with oral for primary care physicians when initiating insulin therapy is choosing
agents. The results of this study suggest that early insulin supplementation when to use each of the many insulins available today; these are
US ENDOCRINOLOGY 41
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