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Diabetes Management
Progression from Basal to Pre-mixed or Rapid-acting Insulin—
Options for Intensification and the Use of Pumps
Morali D Sharma, MD
1
and Alan J Garber, MD, PhD
2
1. Associate Professor of Medicine; 2. Professor of Medicine, Biochemistry, and Molecular Biology, and Molecular and Cellular Biology,
Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine
Abstract
Initiating insulin therapy is an important step in the management of patients with type 2 diabetes. The insulin regimen prescribed should be
physiological and designed to control fasting and post-prandial glucose levels. The primary goals of therapy are achieving and maintaining tight
glycemic control. The optimal insulin regimen should be patient-specific, taking the patient’s lifestyle into consideration. As their diabetes
progresses, an increasing number of patients require insulin therapy. An initial approach is to add basal insulin to oral hypoglycemic agents.
When this regimen fails to achieve glycemic control, it should be intensified by either adding a rapid-acting insulin analog to control post-
prandial hyperglycemia or switching to pre-mixed insulin injection initiated once daily and subsequently up to three times daily. More tools are
now available, including injection devices, insulin pens, glucose monitoring devices, and insulin pumps, to overcome the barriers to initiating
and intensifying insulin therapy. With new insulin analogs it is possible to intensify insulin therapy to achieve glycemic control targets without
increasing the risk for hypoglycemia or causing excessive weight gain.
Keywords
Insulin therapy, basal insulin, pre-mixed insulin, insulin analogs, glycemic control
Disclosure: Morali D Sharma, MD, is a member of the speaker’s bureau of Bristol-Myers Squibb and AstraZeneca and has received research funding from Daiichi-Sankyo. Alan J
Garber, MD, PhD, has received grants and research support from Bristol-Myers Squibb, GlaxoSmithKline, Novo Nordisk, sanofi-aventis, Merck, Sankyo, Metabasis, and Roche, is a
consultant to GlaxoSmithKline, Merck, Novo Nordisk, and Roche, and is a member of the speaker’s bureau of GlaxoSmithKline, Merck, Novo Nordisk, and Sankyo.
Received: October 12, 2009 Accepted: December 17, 2009
Correspondence: Alan J Garber, MD, PhD, Professor of Medicine, Biochemistry, and Molecular Biology, and Molecular and Cellular Biology, Division of Diabetes, Endocrinology,
and Metabolism, Baylor College of Medicine, 1709 Dryden, Suite 1000, Houston, TX 77030. E: agarber@bcm.edu
Support: The publication of this article is supported by Novo Nordisk, Inc. The views and opinions expressed are those of the authors and not necessarily those of Novo Nordisk.
Type 2 diabetes is a progressive disease in which beta-cell function Importance of Glycemic Control in
continually declines, and most patients will eventually require insulin Type 2 Diabetes
therapy to control hyperglycemia. In type 2 diabetes such treatment Cardiovascular disease is the major cause of morbidity and mortality in
usually commences with oral antidiabetes drugs (OADs), but as beta- patients with diabetes.
8,9
In experimental models, prolonged exposure to
cell function declines, basal insulin is added to this regimen.
1
hyperglycemic glucose levels has been shown to result in glucotoxicity
10
Subsequently, as diabetes progresses, this treatment often requires and oxidative stress,
11–13
culminating in beta-cell failure. In patients with
augmentation with bolus or prandial dosing. An increasing body of diabetes, microvascular complications include retinopathy, nephropathy,
evidence suggests that early intensive glycemic control reduces and neuropathy; macrovascular complications include heart disease,
long-term vascular complications and potentially may improve beta- stroke, and peripheral vascular disease.
13,14
Thus, tight glycemic control is
cell function.
2,3
The importance of good glycemic control to reduce a crucial therapeutic goal in the management of type 2 diabetes. Evidence
the risk for the microvascular complications of hyperglycemia is suggests that early glycemic control substantially reduces the risk for
well established.
4–7
both microvascular and macrovascular events; it also delays the onset
and decreases progression of these events.
4–7
Results from the UK
This review considers how the use of pre-mixed (bi-phasic) insulin Prospective Diabetes Study (UKPDS) showed that aggressive glycemic
preparations, rapid-acting analogs, and insulin pumps as part of the control using sulfonylureas or insulin in 3,867 patients newly diagnosed
intensification process can establish better glycemic control over with type 2 diabetes significantly reduced the risk for microvascular
existing therapeutic approaches, thereby minimizing vascular complications compared with conventional treatment (relative risk [RR]
complications, improving quality of life, and achieving improved cost- reduction 25%; p=0.0099).
4
In this study, however, there was no
effectiveness in treatment. significant difference in macrovascular risk among those treated
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