Clinical Experience with Insulin Glargine in Type 1 Diabetes

Barbara Davis Campus for Childhood Diabetes, University of Colorado-Denver, 1775 Aurora Court, Aurora, CO 80045, USA.
Diabetes Technology & Therapeutics (Impact Factor: 2.11). 10/2010; 12(11):835-46. DOI: 10.1089/dia.2010.0135
Source: PubMed


The Diabetes Control and Complications Trial (DCCT) demonstrated the importance of optimal glycemic control achieved through intensive insulin therapy in reducing the microvascular complications associated with type 1 diabetes. However, the DCCT, which was conducted prior to the availability of insulin analogs, also reported a significant increase in severe hypoglycemia with intensive versus conventional therapy. Insulin analogs were developed to aid patients in achieving better diabetes control by providing insulins with optimized pharmacokinetic and pharmacodynamic characteristics. Insulin glargine was the first long-acting insulin analog with a 24-h duration of action, offering once-daily injection, and has now been in clinical use for over 10 years. The authors performed a systematic search of EMBASE, MEDLINE, and Web of Science (Science Citation Index) to determine the efficacy of insulin glargine in type 1 diabetes in basal-bolus insulin regimens. Randomized controlled trials have demonstrated that glycemic control with insulin glargine is at least comparable to that with neutral protamine Hagedorn (NPH) insulin in adults and in children and adolescents, and with continuous subcutaneous insulin infusion in adults. However, these same trials show a significantly lower risk for hypoglycemia with insulin glargine compared with NPH insulin in adults.

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    • "Glargine also shows lower intrasubject variability compared to NPH, as measured by the coefficient of variation for the 24-h glucose infusion rate – 48% for glargine versus 68% for NPH [19]. As a result, glargine used in the general population leads to glycemic control that is at least comparable to that of NPH, but with significantly lower risk for hypoglycemia [20]. While there are numerous reports on the off-label use of glargine in pregnant women, there are no randomized clinical trials assessing its safety during pregnancy [17]. "
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    ABSTRACT: Abstract Pregnancies affected by type 1 diabetes (T1D) carry a major risk for poor fetal, neonatal, and maternal outcomes. Achieving normoglycemia while minimizing the risk of hypoglycemia is a major goal in the management of T1D as this can greatly reduce the risk of complications. However, maintaining optimal glucose levels is challenging because insulin requirements are not uniform throughout the course of the pregnancy. Over the past decade, there has been significant improvement in the methods for glucose monitoring and insulin administration, accompanied by an increase in the number of treatment options available to pregnant patients with T1D. Through study of the scientific literature and accumulated evidence, we review advances in the management of T1D in pregnancy and offer advice on how to achieve optimal care for the patient.
    Full-text · Article · Nov 2013 · The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
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    • "It is not surprising that after one month of insulin treatment blood glucose levels of the diabetic rats were not lowered/corrected, since insulin directly treats diabetes on a daily basis—as a short-term and not a long-term treatment. Insulin glargine may be expected to lower the blood glucose levels since it is a long-acting insulin; however, the duration of its action does not reach 24 hours with some recipients, which may be reflected by hyperglycemia [23]. Although not significant, Exendin-4 treatment showed slight improvement in the blood glucose levels. "
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    ABSTRACT: This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary endothelium (CE) and cardiomyocytes (CMs) of type 1 diabetic male Sprague-Dawley rats. The groups assessed are normal (N), streptozotocin-induced diabetic (D), Insulin treated (DI), Exendin-4 treated (DE), Aliskiren treated (DA), cotreated with Insulin and Aliskiren (DIA) and cotreated with exendin-4 and Aliskiren (DEA). Heart perfusion with (125)I-GLP-1 was performed to estimate GLP-1 binding affinity (τ = 1/k-n) to its receptor in the heart. Western Blotting was assessed to determine the expression variation of GLP-1 receptor in the heart. Plasma GLP-1 levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Diabetes decreased the τ value on CE and increased it on CMs compared to normal. The combination of Exendin-4 with Aliskiren showed a normalizing effect on the binding affinity of GLP-1 at the coronary endothelium, while at the cardiomyocyte level Exendin-4 treatment alone was the most effective.
    Full-text · Article · Jun 2011 · Experimental Diabetes Research
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    ABSTRACT: The attributes of a perfect basal insulin should include: the ability to provide basal glucose levels at target range; once-daily injection; suitable to be injected at any time of day and still cover the intervening period (up to 48 h); cause no hypoglycemia, weight gain or other serious side effects such as cancer; be consistent in its action; and be inexpensive. Following protamine zinc insulin, neutral protamine Hagedorn was introduced approximately 60 years ago. protamine zinc insulin''s highly variable action was reduced, but not eliminated, by neutral protamine Hagedorn. A total of 10 years ago, insulin glargine was introduced to the American market. It quickly gained market share due the relative lack of a peak action and therefore its lower risk of hypoglycemia, and also due to its long duration of action of 24 h or longer, at least in some patients. Then, 5 years ago, insulin detemir was introduced. Although it still may be questioned as to whether its duration of action is 24 h, it appears to have less variability in action and results in less weight gain than insulin glargine. Can we say that these insulins are the perfect basal insulin? The answer is no, and this article will discuss their shortcomings.
    No preview · Article · Jun 2011 · Expert Review of Endocrinology & Metabolism
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