Physiological effects of intraperitoneal versus subcutaneous insulin infusion in patients with diabetes mellitus type 1: A systematic review and meta-analysis

PLoS One. 2021 Apr 13;16(4):e0249611. doi: 10.1371/journal.pone.0249611. eCollection 2021.

Abstract

The intraperitoneal route of administration accounts for less than 1% of insulin treatment regimes in patients with diabetes mellitus type 1 (DM1). Despite being used for decades, a systematic review of various physiological effects of this route of insulin administration is lacking. Thus, the aim of this systematic review was to identify the physiological effects of continuous intraperitoneal insulin infusion (CIPII) compared to those of continuous subcutaneous insulin infusion (CSII) in patients with DM1. Four databases (EMBASE, PubMed, Scopus and CENTRAL) were searched beginning from the inception date of each database to 10th of July 2020, using search terms related to intraperitoneal and subcutaneous insulin administration. Only studies comparing CIPII treatment (≥ 1 month) with CSII treatment were included. Primary outcomes were long-term glycaemic control (after ≥ 3 months of CIPII inferred from glycated haemoglobin (HbA1c) levels) and short-term (≥ 1 day for each intervention) measurements of insulin dynamics in the systematic circulation. Secondary outcomes included all reported parameters other than the primary outcomes. The search identified a total of 2242 records; 39 reports from 32 studies met the eligibility criteria. This meta-analysis focused on the most relevant clinical end points; the mean difference (MD) in HbA1c levels during CIPII was significantly lower than during CSII (MD = -6.7 mmol/mol, [95% CI: -10.3 --3.1]; in percentage: MD = -0.61%, [95% CI: -0.94 -- 0.28], p = 0.0002), whereas fasting blood glucose levels were similar (MD = 0.20 mmol/L, [95% CI: -0.34-0.74], p = 0.47; in mg/dL: MD = 3.6 mg/dL, [95% CI: -6.1-13.3], p = 0.47). The frequencies of severe hypo- and hyper-glycaemia were reduced. The fasting insulin levels were significantly lower during CIPII than during CSII (MD = 16.70 pmol/L, [95% CI: -23.62 --9.77], p < 0.0001). Compared to CSII treatment, CIPII treatment improved overall glucose control and reduced fasting insulin levels in patients with DM1.

Publication types

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

MeSH terms

  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / pathology
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Infusions, Parenteral / methods*
  • Infusions, Subcutaneous / methods*
  • Insulin / administration & dosage*

Substances

  • Hypoglycemic Agents
  • Insulin

Grants and funding

The Norwegian Research Council (NRC) is funding the Double Intraperitoneal Artificial Pancreas project (project number 248872) (all authors) as part of Centre for Digital Life Norway (digitallifenorway.org). The study is also supported by a scholarship from the Central Norway Regional Health Authority (CNRHA) (grant no 2014/23166) (MKA). These grants support the development to create a safe and robust artificial pancreas for patients with diabetes. The funding bodies are not involved in any other aspect of this systematic review, such as the design of the review’s protocol and analysis plan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.