# Elucidating Determinants of Gestational Beta-Cell Adaptation and Failure

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $199,953

## Abstract

Elucidating Determinants of Gestational Beta-Cell Adaptation and Failure
The candidate is an M.D. trained in clinical endocrinology who will undertake a five-year
mentored research and career development program in the genetics, physiology, and
endocrinology of glucose metabolism in pregnancy at Massachusetts General Hospital (MGH).
The candidate will complete the proposed program under the mentorship of prominent
researchers with complementary areas of expertise: 1) Dr. Jose C. Florez, Chief of the MGH
Diabetes Unit and world-recognized leader in translational investigation of type 2 diabetes
genetics and 2) Dr. Ravi Thadhani, Chief of the MGH Nephrology Division and expert in
translational investigation of medical disorders in pregnancy. The candidate will undertake
coursework, receive mentorship, and gain practical experience in physiologic investigation,
longitudinal and genetic data analysis, advanced techniques to profile human plasma, and safe,
ethical conduct of research in the obstetric population. This program will uniquely equip the
candidate with the skills necessary to become an independent physician-scientist investigating
endocrine and metabolic disease in pregnancy. Indeed, during pregnancy, there are profound
changes in glucose metabolism. By late gestation, maternal pancreatic beta cells must
dramatically increase insulin secretion in the face of marked pregnancy-induced insulin
resistance. In 5-10% of pregnant women, this beta-cell adaptation fails, resulting in gestational
diabetes mellitus (GDM). GDM is associated with costly adverse perinatal outcomes and a high
risk of future maternal type 2 diabetes. It is unclear to what extent GDM results from maternal
beta-cell defects that preceded pregnancy or from an imbalance of circulating hormones that
stimulate the beta cell during gestation. The scientific goal of the proposed research is to assess
the contribution of maternal genetics and circulating gestational hormones to beta-cell
adaptation and failure in pregnancy. In Aim 1, the candidate will determine the primary
physiologic mechanism(s) by which maternal genetic variants alter the risk of GDM. In Aim 2,
the candidate will test whether the plasma of pregnant women contains endogenous beta-cell
stimulatory activity which is deficient in GDM. To accomplish these aims, the candidate will
study pregnant women in two cohorts: one established, with cross-sectional physiologic data
and one actively enrolling, with longitudinal physiologic data. The proposed research may define
key pathways leading to hyperglycemia in pregnancy which can be targeted in novel pregnancy-
specific prevention and treatment strategies for GDM.

## Key facts

- **NIH application ID:** 10166833
- **Project number:** 5K23DK113218-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Camille Elise Powe
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $199,953
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-01-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166833

## Citation

> US National Institutes of Health, RePORTER application 10166833, Elucidating Determinants of Gestational Beta-Cell Adaptation and Failure (5K23DK113218-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166833. Licensed CC0.

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