# Glucose Homeostasis and Beta Cell Function in Pseudohypoparathyroidism

> **NIH NIH R03** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $85,000

## Abstract

PROJECT SUMMARY
Pseudohypoparathyroidism type 1A (PHP1A) is a rare, genetic disorder caused by impaired stimulatory G-
protein signaling due to heterozygous mutations in the gene, GNAS. The most severe form of the disease,
PHP1A occurs when a GNAS mutation is inherited on the preferentially expressed maternal allele. A less
severe form of the disease, pseudopseudohypoparathyroidism (PPHP), occurs when a GNAS mutation is
inherited on the paternal allele. Clinically, PHP1A is characterized by multi-hormone resistance, cognitive
impairment and early-onset obesity while PPHP has a mild phenotype without multi-hormone resistance. It is
increasingly recognized that PHP1A is associated with an increased risk of type 2 diabetes but the mechanism
is unknown. Glucose homeostasis and diabetes risk has not been studied in PPHP. As part of the parent K23
award, we investigated glucose tolerance in children with PHP1A. In contrast to the adult literature, we found
that children with PHP1A had greater insulin sensitivity than matched controls. When challenged with an oral
glucose load, however, children with PHP1A had persistent hyperglycemia and 25% met criteria for impaired
glucose tolerance. The goal of this proposal is to quantify β-cell function in PHP1A. It is plausible that these
individuals have a) impaired β-cell function, b) differences in insulin sensitivity, and c) impaired incretin
function. Thus, in this pilot study we will definitively assess one of these, β-cell function, using the frequently
sampled intravenous glucose tolerance test in patients with PHP1A and PPHP (aim 1). We will also assess
oral glucose tolerance over time by bringing back children and young adults with PHP1A from our original
cohort for repeat glucose tolerance testing (aim 2). The ultimate goal is to rigorously define glucose
homeostasis defects in PHP1A in order to design and conduct an intervention study for glucose intolerance
and type 2 diabetes in PHP1A.

## Key facts

- **NIH application ID:** 9869896
- **Project number:** 5R03DK119733-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Ashley Hall Shoemaker
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $85,000
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869896

## Citation

> US National Institutes of Health, RePORTER application 9869896, Glucose Homeostasis and Beta Cell Function in Pseudohypoparathyroidism (5R03DK119733-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9869896. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*