# University of Minnesota Clinical Center for the Restoration of Impaired Awareness of Hypoglycemia in Type 1 Diabetes

> **NIH NIH U01** · UNIVERSITY OF MINNESOTA · 2022 · $387,494

## Abstract

Hypoglycemia (HG) is common in the lives of people with type 1 diabetes (T1D) and may prevent them from
achieving the benefits associated with optimal glycemic control. Recurrent HG over a few days to weeks may
lead to the condition of impaired awareness of HG (IAH) where the first sign of a low blood sugar is confusion or
unconsciousness. Avoiding HG is associated with a reduced risk of IAH and when strictly done, may restore HG
in some but not all patients with IAH. The reason for this heterogeneity in response remains uncertain.The
purpose of this application is to apply to become part of a consortium that will implement a protocol designed to
restore awareness of HG in persons with T1D and IAH. As instructed by the FOA, we address the following
objectives in our application:
1. Determine if diabetes care with use of the most up-to-date management strategies with T1D and IAH.
2. Determine the physiological factors that are associated with restoration of HG awareness, including but not
limited to age, duration of diabetes and metrics of glycemia.
3. Determine the association of the current self-report questionnaires (or develop new questionnaires or
metrics) for identification of IAH with measurement of CRR using "state of the art" metabolic assessments.
To meet objective 1, we propose the consortium enroll 650 subjects with T1D and IAH into a randomized clinical
trial where a 12-month intervention of HG avoidance education and use of a hybrid closed loop system for insulin
infusion is compared to standard care (which includes HG avoidance education, insulin administration via regular
pump or injections, and CGM usage). With epinephrine response during the hypoglycemic clamp at 12 months
as our primary outcome variable, we will test the hypothesis that subjects in the closed loop intervention
arm will have a greater epinephrine response during the hypoglycemic clamp at 12 months of follow-
up than will subjects in the control arm.
To meet objective 2, we will collect information about glycemic variability, food quality and quantity, physical
activity, sleep, stress, mood, and feelings about HG as well as patient characteristics such as HG induced
glucagon secretion, residual C-peptide secretion, and diabetes duration. This information will then be explored
using machine learning techniques to see what exposures and experiences correlate with IAH restoration.
To meet objective three, we will compare the concordance of the Clarke, Gold, and Hypo-AQ questionnaires at
categorizing subjects into IAH and NAH groups. The scores on each of the questionnaires will also be correlated
with objective measures of the counterregulatory response.

## Key facts

- **NIH application ID:** 10599602
- **Project number:** 1U01DK135130-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** ELIZABETH R. SEAQUIST
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $387,494
- **Award type:** 1
- **Project period:** 2022-09-25 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599602

## Citation

> US National Institutes of Health, RePORTER application 10599602, University of Minnesota Clinical Center for the Restoration of Impaired Awareness of Hypoglycemia in Type 1 Diabetes (1U01DK135130-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10599602. Licensed CC0.

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