# Investigating Causal Relationships of Diabetes and Obesity on Degenerative Rotator Cuff Tear

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY/ABSTRACT:
Degenerative rotator cuff tear (DCT) is among the most common causes of shoulder pain, yet little is known
about the genetic and physical risk factors for these tears. Contrary to prior belief that DCTs were fully
attributable to repetitive microtrauma, new evidence has emerged on intrinsic tendinous abnormalities that
could predispose DCT risk. Obesity and diabetes are common health conditions associated with intrinsic
tendinous changes (such as tendon fat and aberrant microstructural fiber composition, as well as increased
tendon cell death and abnormal nutrient vessel anatomy) and may contribute to predisposing conditions that
promote rotator cuff injury. Several epidemiologic studies link obesity and diabetes with cuff disease. However,
most are limited in their scope to establish causal links in part due to inconsistent definitions of cuff disease,
lack of temporality between exposure and outcome, and biases inherent to these studies. The objective of the
proposed work is to leverage several large international DNA and patient health databases, as well as an
ongoing prospective cohort, to evaluate causal roles of diabetes and obesity on DTCs, by incorporating
methods rooted in instrumental variable analysis (Mendelian Randomization [MR]) which can overcome
traditional challenges faced by previous studies. For my first aim, I will build, validate and compare two
algorithms to classify cases and non-cases of DCT. These algorithms will be appropriately matched and
applied to a variety of international biorepositories with genetic data that linked to electronic health records
(EHR). Using genome-wide association study (GWAS) data for DCT generated from these sources, and
GWAS data on obesity and diabetes traits from published studies, I will evaluate evidence for causal
relationships between diabetes and DCT (Aim 2), and obesity and DCT (Aim 3) using MR techniques.
Additionally, I will determine the potential mediating role of diabetes on the association between obesity and
rotator cuff tear using two-step MR methods. DCT is a debilitating condition with great long-term morbidity.
With the ever-increasing rates of diabetes and obesity in our population, conclusions drawn from this work (null
or otherwise) will be timely and impactful. Together, this work taps into unknown and understudied
musculoskeletal consequences of diabetes and obesity, and will inform approaches to mitigating risk of injury,
opening the door for future studies on treatment and prevention of DCT in these populations.

## Key facts

- **NIH application ID:** 10804612
- **Project number:** 5F31AR082662-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Simone Herzberg
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10804612

## Citation

> US National Institutes of Health, RePORTER application 10804612, Investigating Causal Relationships of Diabetes and Obesity on Degenerative Rotator Cuff Tear (5F31AR082662-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10804612. Licensed CC0.

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