The role of innate lymphoid cells and T helper cell activation in type 2 diabetic patients: a protocol for a systematic review and meta-analysis

Syst Rev. 2019 Sep 3;8(1):229. doi: 10.1186/s13643-019-1144-z.


Background: Persistent levels of low-grade inflammation and T lymphocyte activation are associated with insulin resistance and type 2 diabetes that eventually lead to the development of cardiovascular diseases. Interestingly, increasing studies report on an emerging role of innate lymphoid cells in the development of both type 2 diabetes and cardiovascular disease. This systematic review will provide a comprehensive synthesis of available studies reporting on the role of innate lymphoid cells and associated T helper cell function in type 2 diabetic patients. It will further provide insight into the association of innate lymphoid cell activation and cardiovascular risk in adults living with type 2 diabetes.

Methods: This systematic review protocol has been prepared in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines. The protocol has been registered with PROSPERO (CRD42018106159). This systematic review and meta-analysis will include published randomised clinical trials, observational studies, and case-control studies. We will also include grey literature. A search strategy will be developed with the help of subject librarian using Medical Subject Heading (MeSH) words for MEDLINE. This will then be adapted for the Embase database. Two independent reviewers VM and BBN will screen all studies using prespecified inclusion and exclusion criteria. The Downs and Black checklist will be used to assess the quality of individual studies. Predefined relevant data items will be extracted using sheets, and all study tables will be created using Review Manager V.5.3. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the strength of evidence.

Ethics and dissemination: The review will include publicly available data. The findings of this review will be disseminated through publications.

Keywords: Anti-hyperglycemic; Glucose metabolism; Hyperglycaemia; Inflammation; Innate lymphoid cells; Natural killer cells; T helper cells.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / immunology
  • CTLA-4 Antigen / immunology
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / epidemiology
  • Cholesterol / blood
  • Cytokines / immunology
  • Diabetes Mellitus, Type 2 / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Hyaluronan Receptors / immunology
  • Inflammation / immunology*
  • Killer Cells, Natural / immunology*
  • Lipoproteins, LDL / blood
  • Lymphocyte Activation / immunology*
  • Lymphocyte Count
  • Lymphocyte Subsets / immunology*
  • Lymphocytes / immunology
  • Programmed Cell Death 1 Receptor / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Triglycerides / blood


  • CTLA-4 Antigen
  • Cytokines
  • Histocompatibility Antigens Class II
  • Hyaluronan Receptors
  • Lipoproteins, LDL
  • Programmed Cell Death 1 Receptor
  • Triglycerides
  • Cholesterol