Complex Assessment of Metabolic Effectiveness of Insulin Pump Therapy in Patients with Type 2 Diabetes Beyond HbA1c Reduction

Rudolf Chlup, Sarah Runzis, Javier Castaneda, Scott W Lee, Xuan Nguyen, Ohad Cohen, Rudolf Chlup, Sarah Runzis, Javier Castaneda, Scott W Lee, Xuan Nguyen, Ohad Cohen

Abstract

Background: This prospective single-center study recruited insulin-resistant continuous subcutaneous insulin infusion (CSII) therapy-naive patients with type 2 diabetes (T2D) using insulin analog-based multiple daily injections (MDI) therapy and metformin.

Methods: A total of 23 individuals with T2D (70% male), aged a mean ± standard deviation 57.2 ± 8.03 years, with body mass index of 36.2 ± 7.02 kg/m2, diabetes duration of 13.3 ± 4.64 years, and HbA1c of 10.0% ± 1.05% were randomly assigned to a CSII arm or an MDI continuation arm to explore glucose control, weight loss, total daily insulin dose (TDD), and insulin resistance. Insulin dosing was optimized over a 2-month run-in period.

Results: At 6 months, patients assigned to the CSII arm achieved a significant mean HbA1c reduction of -0.9% (95% confidence interval [CI] = -1.6, -0.1), while reducing their TDD by -29.8 ± 28.41 U/day (33% of baseline [92.1 ± 20.35 U/day]) and achieving body mass (BM) reduction of -0.8 ± 5.61 kg (0.98% of baseline [104.8 ± 16.15 kg]). MDI patients demonstrated a nonsignificant HbA1c reduction of -0.3% (95% CI = -0.8, 0.1) with a TDD reduction of 5% from baseline (99.0 ± 25.25 U/day to 94.3 ± 21.25 U/day), and a BM reduction of -1.0 ± 2.03 kg (0.99% of baseline [108.9 ± 20.55 kg]). After 6 months, the MDI arm crossed over to CSII therapy. At 12 months, patients continuing CSII demonstrated an additional mean 0.7% HbA1c reduction with 54.6% achieving HbA1c<8%. The final TDD reduction was -9.7 U/day in comparison to baseline; BM increased by 1.1 ± 6.5 kg from baseline. The MDI patients that crossed to CSII showed an HbA1c reduction of -0.5% ± 1.04%, HbA1c response rate of 27.3%, a TDD reduction of -17.4 ± 21.06 U/day, and a BM reduction of -0.3 ± 3.39 kg. Diabetic ketoacidosis or severe hypoglycemia did not occur in either arm.

Conclusion: CSII therapy safely and significantly improved metabolic control with less insulin usage, with no sustainable reduction of BM, blood pressure, and lipid profile, in insulin-resistant T2D patients. Treatment adherence and satisfaction in these patients were excellent.

Trial registration: ClinicalTrials.gov NCT01182493.

Keywords: Body mass; HbA1c; Insulin aspart; Insulin pump; Self-monitoring.; Type 2 diabetes.

Conflict of interest statement

S.R., J.C., S.W.L., O.C., X.N., and T.L.C. are employees of Medtronic.

Figures

FIG. 1.
FIG. 1.
HbA1c and insulin total daily dose during the course of the study. HbA1c and TDD during the course of the study. The HbA1c (top) and TDD (bottom) in the MDI/CSII arm (N = 11, closed symbols) and the CSII/CSII arm (N = 11, open symbols) are shown. Symbols and bars show the mean and 95% CI, respectively. CI, confidence interval; CSII, continuous subcutaneous insulin infusion; MDI, multiple daily injections; TDD, total daily insulin dose.
FIG. 2.
FIG. 2.
Mean daily hypoglycemia exposure during the study. The mean time (in minutes) of hypoglycemia (≤70 mg/dL, ≤3.9 mmol/L) exposure per day is shown for the MDI/CSII arm (N = 11, closed symbols) and the CSII/CSII arm (N = 10, open symbols) at baseline (Visit 1), 6 months (Visit 5), and 12 months (Visit 10, end of study). While hypoglycemia exposure was reduced in the MDI arm that transitioned to CSII therapy by end of study (Visit 10), this was NS when compared to baseline. For the CSII/CSII arm, hypoglycemia exposure was increased from Visit 5 to end of study (NS, compared to baseline). Symbols and bars show the mean and 95% CI, respectively. NS, not significant.

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