Glucose sensor-augmented continuous subcutaneous insulin infusion in patients with diabetic gastroparesis: An open-label pilot prospective study

Abstract

Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in poorly controlled diabetes with gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24 week open-label pilot prospective study of CSII plus CGM. The primary safety outcome was combined numbers of mild, moderate, and severe hypoglycemic events at screening and 24 weeks treatment. Secondary outcomes included glycemic excursions on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal tolerance. Combined mild, moderate, and severe hypoglycemic events occurred similarly during the screening/run-in (1.9/week) versus treatment (2.2/week) phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and hemoglobin A1c decreased from 9.4±1.4% to 8.3±1.3% (P = 0.001) on CSII plus CGM. Symptom scores decreased from 29.3±7.1 to 21.9±10.2 with lower nausea/vomiting, fullness/early satiety, and bloating/distention scores (P≤0.001). Quality-of-life scores improved from 2.4±1.1 to 3.1±1.1 (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420±258 to 487±312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared to be safe with minimal risks of hypoglycemic events and associated improvements in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance in patients with poorly controlled diabetes and gastroparesis. This study supports the safety, feasibility, and potential benefits of improving glycemic control in diabetic gastroparesis.

Fig 1. Flowchart for the GLUMIT-DG study.

This figure shows the Flowchart for patient recruitment for the GLUMIT-DG study, which follows a non-randomized trial design. A TREND checklist accompanies this Flowchart as the S1 File in the Supplemental Information section.

Fig 2. Study design for GLUMIT-DG.

The study design is shown. After an initial screening phase (up to 3 visits over up to 8 weeks), a run-in phase (up to 4 visits over up to 8 weeks) was conducted. The formal treatment phase consisted of 6 study visits over 24 weeks when CSII and CGM were used together to optimize glycemic control.

Fig 3. Effects of CSII plus CGM on glycemic parameters are shown.

Treatment elicited significant reductions in hemoglobin A1c at 12 and 24 weeks of treatment compared to screening values (A). CGM readings revealed reductions in time in both hypo- and hyperglycemia with treatment at 24 weeks (blue) compared to the screening phase (orange) (B).