# Using technology to define and mitigate risk of impaired awareness of hypoglycemia in patients with type 1 diabetes

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $858,003

## Abstract

PROJECT SUMMARY/ ABSTRACT
Severe hypoglycemia remains a common and life-threatening issue for patients living with type 1 diabetes
(T1D). Research has consistently shown that patients with impaired awareness of hypoglycemia (IAH), which
typically coexists with a diminished counterregulatory response (CRR), are at the highest risk for severe
hypoglycemia. However, we currently do not have clinically available tools to identify patients with IAH, and
even if identified, we lack interventions to reduce their risk. The ultimate goal of this research is to address
these large, unmet needs. Specifically, we plan to utilize continuous glucose monitoring (CGM) to identify
which CGM metrics are associated with IAH and a diminished CRR (AIM 1). We will then determine if modern
T1D management with hybrid closed loop (HCL) systems can restore hypoglycemia awareness (AIM 2).
AIM 1: Identify the CGM metrics associated with hypoglycemia awareness
Our first hypothesis is that time below range (TBR) by CGM will inversely correlate with epinephrine AUC
during a hypoglycemic clamp. This hypothesis is strongly supported by our preliminary data detailed in our
research strategy. To test this hypothesis, we propose that the consortium enroll a total of 112 subjects with
T1D. Subjects will wear a blinded CGM for 10 days prior to a hypoglycemic clamp. Data to be collected will
include counterregulatory hormones during hypoglycemia, hypoglycemia symptom scores (Edinburgh), and
hypoglycemic awareness questionnaires (Clarke, Gold, Pederson, and hypo A-Q) as we have previously done.
CGM metrics will be correlated with CRR, symptom scores, and currently used questionnaires to define
awareness. The study design will determine which CGM metrics predict hypoglycemia awareness and CRR.
AIM 2: Determine if hypoglycemia awareness can be restored in individuals with T1D using up-to-date
management of diabetes
Our second hypothesis is that reducing TBR using modern diabetes management with HCL systems will
improve awareness of hypoglycemia and the CRR. To test this hypothesis, all 112 subjects will be randomized
1:1 to either a control arm or a hypoglycemia reduction arm for 2 years. In the control arm, all insulin delivery
methods will be allowed and CGM targets will follow current standards of care that allow up to 4% TBR (~1
hour/day). The hypoglycemia avoidance arm will provide all patients with a HCL system and target <1% TBR.
Hypoglycemic clamps will be conducted at baseline and months 3, 6, 12, 18, and 24 with 10 days of blinded
CGM prior to each clamp. The primary outcome will be the difference in epinephrine AUC during
hypoglycemic clamp between study arms. This study design will determine if up-to-date T1D management can
restore the CRR and hypoglycemia awareness.

## Key facts

- **NIH application ID:** 10708141
- **Project number:** 5U01DK135121-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Jeremy H Pettus
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $858,003
- **Award type:** 5
- **Project period:** 2022-09-25 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10708141

## Citation

> US National Institutes of Health, RePORTER application 10708141, Using technology to define and mitigate risk of impaired awareness of hypoglycemia in patients with type 1 diabetes (5U01DK135121-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10708141. Licensed CC0.

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