Can a tool that automates insulin titration be a key to diabetes management?

Abstract

Background: Most patients who use insulin do not achieve optimal glycemic control and become susceptible to complications. Numerous clinical trials have shown that frequent insulin dosage titration is imperative to achieve glycemic control. Unfortunately, implementation of such a paradigm is often impractical. We hypothesized that the Diabetes Insulin Guidance System (DIGS™) (Hygieia, Inc., Ann Arbor, MI) software, which automatically advises patients on adjustment of insulin dosage, would provide safe and effective weekly insulin dosage adjustments.

Subjects and methods: In a feasibility study we enrolled patients with type 1 and type 2 diabetes, treated with a variety of insulin regimens and having suboptimal glycemic control. The 12-week intervention period followed a 4-week baseline run-in period. During the intervention, DIGS processed patients' glucose readings and provided insulin dosage adjustments on a weekly basis. If approved by the study team, the adjusted insulin dosage was communicated to the patients. Insulin formulations were not changed during the study. The primary outcome was the fraction of DIGS dosage adjustments approved by the study team, and the secondary outcome was improved glycemic control.

Results: Forty-six patients were recruited, and eight withdrew. The DIGS software recommended 1,734 insulin dosage adjustments, of which 1,731 (99.83%) were approved. During the run-in period the weekly average glucose was stable at 174.2±36.7 mg/dL (9.7±2.0 mmol/L). During the following 12 weeks, DIGS dosage adjustments resulted in progressive improvement in average glucose to 163.3±35.1 mg/dL (9.1±1.9 mmol/L) (P<0.03). Mean glycosylated hemoglobin decreased from 8.4±0.8% to 7.9±0.9% (P<0.05). Concomitantly, the frequency of hypoglycemia decreased by 25.2%.

Conclusions: The DIGS software provided patients with safe and effective weekly insulin dosage adjustments. Widespread implementation of DIGS may improve the outcome and reduce the cost of implementing effective insulin therapy.

Trial registration: ClinicalTrials.gov NCT01170208.

Figures

FIG. 1.

Capillary glucose levels during the study. (A) An example of a patient managed with the Diabetes Insulin Guidance System (DIGS) software in Group II. This was a 58-year-old woman with a 13-year history of type 2 diabetes, complicated with neuropathy and nephropathy. (Upper panel) Insulin dosage. (Lower panel) Weekly mean glucose and events of hypoglycemia. During the first 4 weeks the subject continued to follow her current insulin dosage. During the active phase of the study (Weeks 4–16), the DIGS software adjusted each component of the basal-bolus regimen. Her total daily insulin dosage increased by 19% (from 123 to 151 units/day), but its distribution considerably changed, that is, different components in the regimen were diametrically redirected according to glucose patterns. (B) Weekly mean glucose (and regression lines) in Groups I and II. (C) Weekly mean glucose in Group III (because of fewer data points, a regression line was not plotted). (D) Weekly mean glucose (and regression line) of patients with and without frequent hypoglycemia. During the active 12 weeks weekly mean glucose improved when possible. A1C, glycosylated hemoglobin.

FIG. 2.

Hypoglycemia during the study. (A) Histogram depicting frequency of hypoglycemic glucose readings per glucose value during the 12-week active phase and the 4-week run-in period. The histogram shows that glucose readings below 65 mg/dL (<3.6 mmol/L) during the active phase had different distribution than during the run-in period and were generally milder. (B) Frequency of minor hypoglycemia (glucose <65 mg/dL [<3.6 mmol/L]) during each quartile for all patients and patients with or without frequent hypoglycemia (>85 events per patient-year). (C) Total daily insulin in patients with frequent minor hypoglycemia. During the active 12-week period, the frequency and severity of hypoglycemia decreased.

FIG. 2.

Hypoglycemia during the study. (A) Histogram depicting frequency of hypoglycemic glucose readings per glucose value during the 12-week active phase and the 4-week run-in period. The histogram shows that glucose readings below 65 mg/dL (<3.6 mmol/L) during the active phase had different distribution than during the run-in period and were generally milder. (B) Frequency of minor hypoglycemia (glucose <65 mg/dL [<3.6 mmol/L]) during each quartile for all patients and patients with or without frequent hypoglycemia (>85 events per patient-year). (C) Total daily insulin in patients with frequent minor hypoglycemia. During the active 12-week period, the frequency and severity of hypoglycemia decreased.