# Skeletal Fragility in Type 1 Diabetes: Glycemic Control and Bone Strength

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $298,001

## Abstract

Patients with type 1 diabetes (T1D) display a high risk of fragility fractures, yet the skeletal pathophysiology of
T1D is incompletely understood. Decreases in areal BMD (aBMD) are well-established, but the magnitude of
the aBMD deficit explains only 20% of the observed increase in T1D fracture risk. Rather, deficits in bone
microarchitecture, turnover and material composition likely predispose to the high fracture risk. In type 2
diabetes (T2D), we have shown reduced bone material strength index (BMSi) using a novel impact
microindentation device, which, we found, also correlated with long-term glycemia as reflected by a skin
autofluorescence measure of tissue advanced glycation endproduct (AGE) levels. Despite reduced BMSi in
T2D, skeletal microarchitecture was found to be intact, as assessed by high resolution peripheral quantitative
computed tomography (HR-pQCT). In contrast, in T1D, primary deficits reside in altered microarchitecture and
we find reduced trabecular thickness. However, we have little information on effects of T1D on trabecular
morphology, biomechanical properties and bone material strength. Importantly, the onset of T1D is generally
before attainment of peak bone mass, yet there is little natural history data to demonstrate how bone accrual is
impacted. It is also unknown whether glycemic control and variability predict bone deficits. In order to
understand the pathogenesis of T1D bone disease, it is thus imperative that we understand the time course of
skeletal deficits in T1D, and specifically, how they might progress as a function of glycemic control. Together,
these observations underscore our central hypothesis: T1D, in contrast to T2D, is primarily associated with
decrements in bone strength due to disrupted microarchitecture occurring during peak bone mass accrual, and
that this disruption arises from hyperglycemia and glycemic variability. Thus, the overall goals of this
application are: 1) to understand the relationship between glycemic control and bone strength in long-standing
T1D adults versus controls using HR-pQCT-based estimates of bone strength (including trabecular and cortical
components and trabecular morphology); 2) to elucidate the effects of T1D (including glycemic control and
variability by continuous glucose monitoring) on the peak accrual of bone mass by following HR-pQCT-based
estimates of bone strength over 2 years in T1D children versus controls; and 3) to examine the relationship
between bone material strength by microindentation and AGE accumulation by skin autofluorescence in long-
standing T1D adults versus controls. The research will provide comprehensive data about the effects of T1D
on the elements of bone that contribute to strength and fracture resistance. The effects of glycemic control on
cross-sectional measures and prospective bone acquisition will determine whether skeletal fragility, like other
complications of T1D, is associated with poor glycemic control. The results should help u...

## Key facts

- **NIH application ID:** 10017182
- **Project number:** 5R01DK122564-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MISHAELA R RUBIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $298,001
- **Award type:** 5
- **Project period:** 2019-09-12 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017182

## Citation

> US National Institutes of Health, RePORTER application 10017182, Skeletal Fragility in Type 1 Diabetes: Glycemic Control and Bone Strength (5R01DK122564-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10017182. Licensed CC0.

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