Type 1 diabetes mellitus: Complex interplay of oxidative stress, cytokines, gastrointestinal motility and small intestinal bacterial overgrowth

Eur J Clin Invest. 2018 Nov;48(11):e13021. doi: 10.1111/eci.13021. Epub 2018 Sep 19.


Background: Oxidative stress is risk factor in progression of diabetes. It can increase cytokine production via several different mechanisms. Inflammation can affect gut neural apparatus that may lead to dysmotility which may exaggerate occurrence of bacterial overgrowth in intestine. Thus, a study was planned to understand the complex interplay of oxidative stress, inflammatory cytokines, gut motility and small intestinal bacterial overgrowth in type 1 diabetes mellitus (T1DM) patients.

Materials and methods: Seventy-five T1DM patients and 75 healthy controls were enrolled. Small intestinal bacterial overgrowth (SIBO) and orocecal transit time (OCTT) were measured using noninvasive glucose and lactulose hydrogen breath tests, respectively. Plasma levels of interleukin-6 (IL-6), tissue necrosis factor-alfa (TNF-α) and interleukin-10 (IL-10) were measured in all subjects by ELISA. Oxidative stress and anti-oxidant parameters were measured by standard methods.

Results: Out of 75 T1DM patients, 36 were males with Mean ± SD age 22.3 ± 5.2 years, IL-6, TNF-α and IL-10 were significantly higher (P < 0.05) in T1DM patients as compared to controls. Lipid peroxidation (LPO) was significantly increased (P < 0.001), while reduced glutathione (GSH) significantly decreased (P < 0.01), whereas superoxide dismutase (SOD) and catalase significantly higher (P < 0.05) in T1DM patients as compared to controls. Positive correlation was observed between glycated haemoglobin (HbA1c) levels with LPO and negative correlation with GSH. Further, there was positive correlation between LPO and inflammatory cytokines (IL-6 & IL-10). OCTT was delayed and SIBO significantly higher in patients as compared to controls. On comparison of T1DM based on duration of disease, effect of all parameters was more pronounced in disease duration ≥5 years.

Conclusion: This study indicates that there is association between hyperglycaemia, oxidative stress (LPO), anti-oxidants (GSH, SOD and catalase), inflammatory cytokines, gut motility (OCTT), and small intestinal overgrowth in type 1 diabetes mellitus patients. This association is intensified as duration of disease increases.

Keywords: gastrointestinal motility; inflammatory cytokines; oxidative stress; small intestinal bacterial overgrowth; type 1 diabetes mellitus.

MeSH terms

  • Adolescent
  • Adult
  • Antioxidants / physiology
  • Case-Control Studies
  • Catalase / metabolism
  • Cytokines / metabolism*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Female
  • Gastrointestinal Microbiome / physiology
  • Gastrointestinal Motility / physiology*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hyperglycemia / complications
  • Intestine, Small / microbiology*
  • Lipid Peroxidation / physiology
  • Male
  • Microbiota / physiology
  • Oxidative Stress / physiology*
  • Superoxide Dismutase / metabolism
  • Young Adult


  • Antioxidants
  • Cytokines
  • Glycated Hemoglobin A
  • Catalase
  • Superoxide Dismutase