Clinical Study Suggests Low Glucose Suspend is Safe in Individuals with Hypoglycemia Unawareness

Hypoglycemia is a common and serious complication of insulin therapy in children and adults with T1D. Sleep poses a particular risk, and severe hypoglycemia is more frequent overnight especially in those individuals who have hypoglycemia unawareness. The advent of the low-glucose suspend (LGS) function in the Medtronic Paradigm Veo System, allowing insulin to be automatically suspended for up to 2 hours when sensor glucose falls below a preset threshold, has the potential to reduce the duration of hypoglycemia and is a significant first step toward a closed-loop artificial pancreas for patients with T1D.

This study reports experience of the Veo system in children and adults enrolled as part of an intervention trial in individuals with hypoglycemia unawareness. The data were obtained from a subset of participants from the larger trial, which is still ongoing. Here the team focused on an analysis of the blood glucose profiles following the full 2-hour pump suspension and also the different patterns of use among patients and their behavioral responses to alarms. The team found that the LGS function was frequently activated but that most of these events were short and that the patient had overridden pump suspension and resumed insulin delivery. Almost 40% of all LGS events occurred overnight, and one in three events lasted the full 2-h duration. LGS events, including multiple activations, were not associated with severe hypoglycemia or diabetic ketoacidosis. For overnight suspend events where the patient did not wake up the initial fall in glucose levels was arrested promptly and rose steadily during the 2-hour suspended period. The mean glucose level at the end of the 2-hour suspend event was 99 mg/dL, which is a near-normal value. The mean first-morning fingerstick blood glucose value was 185 mg/dL and there was no associated ketosis. These analyses suggest that 2-hour insulin suspension overnight is unlikely to be associated with adverse outcomes. Following 6 months of using the LGS function, there was no deterioration in A1c level and overall hypoglycemia unawareness scores were found to be improved. These findings, however, are preliminary, and the final results will be reported at the end of the trial.

Reference:

Ly TT, Nicholas JA, Retterath A, Davis EA, Jones TW. Analysis of Glucose Responses to Automated Insulin Suspension With Sensor-Augmented Pump Therapy. Diabetes Care. July 2012;35(7):1462-5.

Investigators and Institutions:

Trang Ly1,2,3, Jennifer Nicholas1,2, Adam Retterath2, Elizabeth Davis1,2,3, Timothy Jones1,2,3

1Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; 2Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia; and the 3School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.

Ramifications for Individuals with Type 1 Diabetes:

Severe hypoglycemia is a major barrier to tight glucose control in people with diabetes. LGS systems have been shown to reduce hypoglycemia exposure without a deterioration in A1c a major step forward. Furthermore, previous research has shown that people who have hypoglycemia unawareness can become aware again of low blood sugars by avoiding frequent lows. Preventing all lows for two weeks resulted in increased symptoms of a low blood sugar and a return to nearly normal symptoms after 3 months. A pump that suspends insulin delivery when glucose levels fall to a pre-set low threshold may provide significant benefit to individuals who have hypoglycemia unawareness. This study suggests that LGS is safe and unlikely to result in adverse outcomes in this patient population. At the conclusion of this ongoing study we will better understand the potential utility of LGS in preventing hypoglycemia unawareness and whether it can prevent loss of the critical warning symptoms in individuals who suffer from this T1D complication. The Veo System is not currently approved for use in the US.

JDRF Involvement:

Dr. Trang Ly is the recipient of a JDRF postdoctoral fellowship and Dr. Tim Jones, her mentor, is receiving JDRF funding to assess biochemical measures of hypoglycemia unawareness in a subset of the participants in this trial. Dr. Tim Jones is a member of the JDRF artificial pancreas consortium.