Diurnal variations to proinflammatory markers in individuals with diabetes compared to healthy controls: protocol for a systematic review and meta-analysis

Jun 3, 2026BMJ open

Daily changes in inflammation markers in people with diabetes compared to healthy individuals

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Abstract

This review evaluates the impact of diabetes on daily variations in proinflammatory markers.

Diabetes mellitus is linked to chronic, low-grade inflammation.
The relationship between diabetes and disruptions in circadian rhythms is of increasing interest.
This review aims to synthesize clinical evidence regarding how diabetes may affect daily patterns of proinflammatory markers.
Proinflammatory markers will be compared between individuals with diabetes and healthy controls using defined diurnal variations.
A meta-analysis will be conducted if sufficient comparable data is available.

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INTRODUCTION: Diabetes mellitus is a highly prevalent metabolic disorder associated with chronic, low-grade inflammation. Of recent interest is the association between diabetes and circadian rhythm disruption. The aim of this review is to evaluate and synthesise clinical evidence for whether diabetes affects homeostatic diurnal patterns to proinflammatory markers in the human body. This could inform the optimal timing of immune-targeted therapies over the course of the day.

METHODS AND ANALYSIS: This systematic review will include primary clinical research studies reporting on diurnal variations, defined as an afternoon/evening (PM) minus a morning (AM) value, within a timeframe of 12±4 hours, for predefined proinflammatory markers, in individuals with diabetes (type 1 or type 2) compared with healthy controls. A search of online databases (Cochrane CENTRAL, Ovid MEDLINE and Ovid Embase) will be performed. Grey literature searches will be performed in clinical trial registries. Two review authors will independently screen retrieved citation records at the title/abstract and full-text levels. Study quality will be assessed using an appropriate National Institute of Health quality assessment tool. A meta-analysis will be performed if more than one study reports equivalent data for any outcome. Statistical heterogeneity will be assessed using the χtest. Where a meta-analysis is not possible or unlikely to be meaningful, a narrative synthesis of the findings will be provided. 2

ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review as no original data will be collected. The results will be disseminated through peer-reviewed publication and conference presentations.

PROSPERO REGISTRATION NUMBER: CRD420251115780.

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Diurnal variations to proinflammatory markers in individuals with diabetes compared to healthy controls: protocol for a systematic review and meta-analysis

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