# Early myocardial remodeling and progressive kidney function decline in type 1 diabetes

> **NIH NIH R01** · JOSLIN DIABETES CENTER · 2024 · $778,620

## Abstract

SUMMARY
A large proportion of the excess CVD morbidity and mortality experienced by individuals with T1D occur in
conjunction with diabetic kidney disease (DKD), which is associated with a striking increase in the risk of
coronary artery disease (CAD) and heart failure. The latter is frequently due to the development of diabetic
cardiomyopathy – a diabetes-specific alteration of the myocardium. The etiologic links between DKD and
cardiomyopathy are not clear, but preliminary data from our group suggest a pivotal role of the kidney function
decline component of DKD rather than albuminuria. Specifically, using an MRI-derived marker of
cardiomyocyte size, we have observed that patients with T1D who are losing kidney function but still have
preserved GFR have subclinical signs of myocardial remodeling, as indicated by a larger cardiomyocyte
size and a reduction of myocardial fiber shortening during systole as compared to T1D patients with
stable kidney function. The overall goal of this collaborative proposal, which is in response to RFA-HL-21-014,
is to take advantage of the latest developments in cardiac imaging and biomarker platforms to characterize the
cardiac involvement in patients with T1D and DKD, focusing on the initial events in the development of diabetic
cardiomyopathy. “GFR Decliners” (GFR loss in the previous 3-6 years ≥3 ml/min/year, n=100) and “GFR Non-
Decliners” (n=100) with T1D and CKD stage 1-3A, along with Non-diabetic controls (n=100) of similar age and
CKD stage, will undergo a gadolinium-enhanced cardiac magnetic resonance (CMR) and a gated cardiac CT
scan to quantify coronary artery calcium (CAC). Through these studies, we will address the following Specific
Aims: 1. To evaluate the presence and severity of myocardial remodeling among T1D patients and
assess its relationship with early progressive kidney function decline. Cardiomyocyte size (τic) and
interstitial fibrosis (measured as extracellular volume [ECV]) will be quantified by CMR and compared among
GFR Decliners, GFR Non-Decliners, and Non-Diabetic subjects, and also related to albuminuria and presence
and severity of CAD. 2. To assess the relative contribution of cardiomyocyte hypertrophy and interstitial
fibrosis to impaired cardiac function among T1D patients. Indices of cardiac function and myocardial strain
will be derived from the CMR data and evaluated for their association with cardiomyocyte size (τic) and
interstitial fibrosis (ECV), in relation to the severity of concomitant CAD. 3. To gain insights into the disease
processes involved in the etiology of myocardial remodeling and assess whether these overlap with
those involved in the progressive kidney function decline. In targeted studies, we will focus on serum
proteins implicated in heart failure or previously associated with increased risk of GFR loss. In untargeted
studies, we will leverage the latest developments in multiplexed assays to evaluate serum protein profiles in a
systematic fashion. With th...

## Key facts

- **NIH application ID:** 10744757
- **Project number:** 5R01HL161858-03
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** Alessandro Doria
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $778,620
- **Award type:** 5
- **Project period:** 2021-12-24 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10744757

## Citation

> US National Institutes of Health, RePORTER application 10744757, Early myocardial remodeling and progressive kidney function decline in type 1 diabetes (5R01HL161858-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10744757. Licensed CC0.

---

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