Characteristics of basal insulin requirements by age and gender in Type-1 diabetes patients using insulin pump therapy

https://doi.org/10.1016/j.diabres.2004.11.005Get rights and content

Abstract

Establishment of appropriate basal insulin levels is an essential component of intensive insulin therapy. While the existence of a “dawn phenomenon” is widely recognized, the present study sought to establish whether diurnal basal insulin patterns exist in Type-1 diabetes, and whether these patterns vary by age and gender. Participant data was drawn from 322 Type-1 insulin pump users treated at a private diabetes education practice in suburban Philadelphia. All participants completed a battery of fasting tests designed to match basal insulin levels to endogenous glucose production and insulin sensitivity. Analysis of resultant basal patterns revealed significant differences between juvenile (age ≤20) and adult (age >20) basal insulin patterns. The younger group exhibited a more pronounced and sustained night-time peak; the older group exhibiting a briefer and less pronounced early-morning peak. Lower overall basal insulin requirements were found in the youngest (age ≤10) and oldest (age >60) groups. No noteworthy gender differences were found. Results can serve as a guide for clinicians when initiating and fine-tuning patients who utilize basal/bolus insulin therapy.

Introduction

Since the discovery of insulin in the 1920s [1], clinicians have been challenged to achieve euglycemia in their patients through the use of injectable insulin formulations. With the development of insulin analogs, such as aspart, lispro, glargine and detemir, basal/bolus insulin therapy has become a standard of care for people with Type-1 diabetes seeking near-normal blood glucose levels and lifestyle flexibility [2]. This form of therapy simulates the function of a healthy pancreas by providing a relatively low level of basal insulin continuously throughout the day and night to offset endogenous (hepatic) glucose production, along with larger “bolus” doses administered as needed to cover the glycemic rise induced by dietary carbohydrates [3].

With basal/bolus insulin therapy, the basal and bolus insulins are responsible for two separate elements of glycemic control. Basal insulin is responsible for the maintenance of euglycemia in the absence of food. Bolus insulin is responsible for metabolizing dietary carbohydrates and for reducing absolute values in blood glucose when in a hyperglycemic state.

While much attention has been given to the adjustment of bolus insulin doses based on carbohydrate consumption, physical activity and pre-meal blood glucose concentrations [4], [5], [6], [7], [8], [9], [10], [11], [12], little research exists regarding basal insulin requirements. Because basal insulin's role is the maintenance of blood glucose levels in the absence of food, it can be argued that proper basal insulin levels should be achieved prior to fine-tuning bolus insulin doses. Otherwise, patients may be at an increased risk of hypoglycemia and hyperglycemia with any changes in their regular meal schedule.

A number of options are available for providing basal insulin: the use of intermediate and long-acting insulins (NPH, Lente, Ultralente); use of basal insulin analogs (glargine, detemir); and continuous subcutaneous infusion of rapid-acting insulin (insulin pump therapy). Insulin pump therapy is unique in that it is the only system that permits the user to vary and adjust basal insulin levels in a tightly controlled manner. As a result, pump therapy has been shown to be more effective than traditional injection programs for achieving intensive blood glucose control [6], [13], [14], [15], [16], [17], [18], [19], [20]. However, inappropriate basal insulin levels can lead to recurrent and/or severe hypoglycemia as well as chronic hyperglycemia [21]. These, in turn, may contribute to the discontinuation of pump use [22], [23].

Appropriate basal insulin levels are critical to the safety and metabolic control of those using insulin pumps, as well as those using traditional injection therapy. Setting and fine-tuning basal insulin levels require a series of fasting tests under controlled conditions [24], [25]. It is only in the absence of exogenous variables (active bolus insulin, digesting food, exercise, acute stress) that basal insulin levels can be tested and properly adjusted. In a state of typical insulin sensitivity and endogenous glucose production (the “fasting” state), a basal insulin level that maintains steady/unchanging blood glucose concentrations is deemed appropriate. If blood glucose levels rise or fall significantly in a fasting state, the basal insulin level is considered to be inappropriate.

Performing fasting tests during all phases of the 24 h day, fine-tuning basal insulin, repeating the tests and tracking/documenting the results is a process that is cumbersome and complex for both patients and clinicians. Although the empirical testing of basal rates is recommended by insulin pump manufacturers, the use of these procedures appears to be limited by provider resources. In the case of pump users, many patients are simply given a single “flat” basal rate to use over a 24-h period [26], [27], followed by cursory adjustments based on blood glucose readings taken during the first few days or weeks of pump use. Of course, these readings can be affected by food (including the delayed effects of dietary fat), activity, stress, hormone production and countless environmental factors.

Basal insulin requirements typically vary throughout the day and night based on endogenous glucose output and peripheral insulin sensitivity [3], [28]. Insulin requirements are believed to increase during the night-time/early morning secondary to the dawn phenomenon [29], [30]; a decrease in insulin sensitivity caused by cortisol and growth hormone secretion [31], [38]. The magnitude of the dawn phenomenon has been shown to correlate positively with HbA1c level and counter-regulatory response to hypoglycemia, and inversely with duration of diabetes. However, no link has been established between age or gender and the magnitude of the blood glucose rise induced by the dawn phenomenon [30].

At present, the authors are not aware of any empirically derived data regarding basal insulin requirements for people with Type-1 diabetes. As a private practice specializing in intensive insulin therapy, our insulin pump users are routinely taken through a battery of fasting tests designed to establish basal insulin levels that maintain steady blood glucose levels in the absence of exogenous variables. By analyzing the basal insulin patterns of patients who have completed their basal testing/fine-tuning, we have managed to compile summary data concerning basal insulin peaks, timing, magnitude, duration and numbers of changes. Such data can serve as an effective guideline when starting patients on basal/bolus insulin therapy, particularly when resources are not available for taking each patient through the basal testing/fine-tuning process.

The questions addressed in the present study are:

  • (1)

    do basal insulin requirements vary significantly by age and/or gender?

  • (2)

    When do basal insulin requirements tend to “peak”? What is the magnitude and duration of the peak?

  • (3)

    How many “peaks” and different basal rate “segments” are usually required?

  • (4)

    What are “typical” basal insulin profiles for different age groups?

  • (5)

    How much variability exists between individuals within the same age groups?

Section snippets

Participants

Data was compiled from patients at Integrated Diabetes Services, a private diabetes education practice near Philadelphia. All individuals (N = 322: 150 men, 172 women) with Type-1 diabetes who completed the empirical testing and fine-tuning of their basal rates on their insulin pumps during the years 1997–2002 were included in the study. For each individual, data was collected at least 12 weeks following initiation of pump therapy, and was completed only after empirical basal testing and

Cumulative data

Overall average basal values varied from 0.0 to 3.5 units per hour. The average “non-peak” basal rate was 0.65 units/h, with an average “peak” basal rate of 0.96 units/h (a 48% increase over the non-peak average). Patients spent an average of 5.2 h at peak basal rates. More than 82.3% experienced one peak, 14.3% experienced no peaks, and 3.4% experienced two peaks. Patients required an average of 5.2 basal infusion rate changes through the 24-h period.

For juvenile subjects (age <21; N = 128), the

Discussion

With the growing popularity of basal/bolus insulin programs, greater attention needs to be placed on regulation of basal insulin. Improper basal insulin levels can cause unexpected hypoglycemia and/or hyperglycemia between meals and during sleep, undesired weight loss/gain, and difficulties achieving euglycemia during exercise. It can also interfere with efforts to calculate appropriate bolus insulin doses (insulin:carb formulas and blood sugar correction formulas). Our results indicate that it

Acknowledgements

The authors wish to thank Dr. Grafton Reeves and Dr. James Lenhard for reviewing earlier versions of the manuscript; Christine Shubin for her expert data entry; and Novo Nordisk Pharmaceuticals for their support of this research. (Supported by the American Association of Diabetes Educators/Novo Nordisk Pharmaceuticals Research Grant, 2003.)

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