# A Role for Glycemic Variation in Optimizing Management of Diabetes and Vascular Complications

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2020 · $122,816

## Abstract

PROJECT SUMMARY/ABSTRACT
A role for glycemic variation in optimizing management of diabetes and vascular complications
It is well demonstrated that high glucose levels lead to more rapid development of macrovascular and
microvascular complications in people with diabetes. However, there is less consistent evidence that lowering
glucose levels to near normal levels prevent or slows vascular complications, particularly in more advanced
stages of type 2 diabetes. The recent VADT, ACCORD, and ADVANCE trials demonstrated that intensive efforts
to lower glucose had only modest effects on the rate of vascular complications. Why glycemic control strategies
that focused on reduction of glucose levels and HbA1c did not have the anticipated success in reducing vascular
outcomes is not clear. This has raised the possibility that (1) there are glycemic metrics beyond those that reflect
average glucose control, such as HbA1c, that can explain this paradox, and (2) there exists heterogeneous
treatment effects of intensive glycemic therapy for macrovascular and microvascular complications, with
subgroups of patients who do less well with intensive treatment counter-balancing those that do respond. In
recent reports we have demonstrated long-term glycemic variability was associated with risk of cardiovascular
disease (CVD) events, even after adjusting for traditional markers of glycemic control. Importantly, this appeared
most relevant to those receiving intensive glycemic control. These preliminary findings support careful
examination of determinants and consequences of glycemic variability. In this proposal, we therefore propose to
(a) evaluate and compare the importance of glycemic variation, both short-term measured by 1,5-anhydroglucitol
and long-term in the development of macro and microvascular complications; (b) to study whether intensive
treatment is beneficial in preventing vascular outcomes when glycemic variation is constrained; (c) genetic
variants associated with glycemic variation in T2D patients will explain additional risk in progression to vascular
complications beyond the genetic variants associated with mean glycemic levels.

## Key facts

- **NIH application ID:** 10040813
- **Project number:** 1R21HL150374-01A1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Peter D Reaven
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,816
- **Award type:** 1
- **Project period:** 2020-08-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040813

## Citation

> US National Institutes of Health, RePORTER application 10040813, A Role for Glycemic Variation in Optimizing Management of Diabetes and Vascular Complications (1R21HL150374-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10040813. Licensed CC0.

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