Durability of glycemic control using U-500 insulin

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Abstract

Previous short-term studies evaluating U-500 insulin have reported improvements in glycemic control but with significant weight gain. This study was performed to examine the glycemic durability of U-500 insulin in highly insulin resistant subjects, and to determine if weight gain was continuous with use. Patients using U-500 insulin provided consent for chart reviews for up to 3 years prior to and 3 years after use of U-500 insulin. Charts were reviewed for physical and metabolic data from 53 subjects using U-500 insulin of which 20 used U-500 insulin for 3 years. Use of U-500 insulin led to an approximate 1% decrease in HbA1c within 3–6 months of use which was sustained for up to 3 years. Patients required increased insulin doses (by ∼80%) over the first 6–12 months with a corresponding weight gain (∼10 lbs) and a spike in hypoglycemia symptoms, but then insulin doses and body weight, as well as glycemic control and hypoglycemic symptoms, stabilized over subsequent follow up. Use of U-500 insulin in a clinical diabetes practice leads to sustained improvements in glycemic control following a period of insulin titration and weight gain. Despite the weight gain, glycemic control was sustained for up to 3 years.

Introduction

U-500 insulin is a 5-fold concentrated form of regular (U-100) insulin that is often used in individuals with extreme insulin resistance, commonly defined as insulin requirements >200 units/day. Due to its concentration, 100 units of insulin can be administered in an injection volume of 0.2 ml, as compared to 1.0 ml of U-100 insulin, thereby facilitating the administration of large amounts of insulin in smaller and/or fewer shots. In parallel with the obesity epidemic, there have been an increasing number of publications on U-500 insulin use in recent years (for review see [1]). Most studies are short term studies demonstrating efficacy of U-500 insulin in attaining glycemic control; however, several studies have reported weight gain [2], [3], [4], [5]. We previously published a report on the outcomes in body weight, glycemic control, insulin doses, hypoglycemia, and patient satisfaction in 40 subjects using U-500 insulin for 3 months, 36 using it for 6 months and 24 using it for one year. Within 6 months of transitioning to U-500 insulin subjects had an average 1.4% decrease in HbA1c, but at the expense of increased insulin doses and a 10–12 pound weight gain [3]. This weight gain has the potential to exacerbate insulin resistance, and could set up a vicious cycle of increased weight leading to increased insulin resistance, leading to increased insulin requirements, leading to further increases in weight. The purpose of this study is to report outcomes after 2–3 years of U-500 insulin use.

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Materials and methods

The subjects and methods have been previously described [3]. Subjects attending diabetes clinics at the University of Kentucky or the Lexington, Kentucky Veterans Affairs Medical Center who had been using U-500 insulin for at least 3 months (initiated by their diabetes care provider) were invited to participate. All subjects provided informed consent as approved by the Institutional Review Board and Research and Development Committee of the University of Kentucky and the Lexington, Kentucky

Results

A total of 53 subjects provided consent to participate in this observational study. Of these 53, six died during the 3 year follow-up (all from pre-existing medical conditions), 7 discontinued use of U-500 insulin (1 due to prolonged illnesses requiring prolonged inpatient admission; 2 due to decreased insulin needs following development of end stage renal disease and initiation of hemodialysis; 1 following liver transplantation; 1 following significant weight loss after lap band surgery; 1 due

Discussion

We and others have previously reported that the use of U-500 insulin can lead to improvements in glycemic control but at the expense of increased weight gain [2], [3], [4], [5]. This raises the concern that the use of U-500 insulin may initiate a vicious cycle whereby weight gain leads to increased insulin resistance requiring more insulin that contributes to more weight gain, or impairing glycemic control. To address this, we studied the physical and metabolic changes in a group of subjects

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgement

This work was supported in part by grant UL1RR033173.

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