Abstract

Objective:Emerging evidence from animal models suggests that translocation of bacterial debris across a leaky gut may trigger low-grade inflammation, which in turn drives insulin resistance. The current study set out to investigate this phenomenon, termed ‘metabolic endotoxemia', in Gambian women.Methods:In a cross-sectional study, we recruited 93 age-matched middle-aged urban Gambian women into three groups: lean (body mass index (BMI): 18.5–22.9 kg m−2), obese non-diabetic (BMI: ⩾30.0 kg m−2) and obese diabetic (BMI: ⩾30.0 kg m−2 and attending a diabetic clinic). We measured serum bacterial lipopolysaccharide (LPS) and endotoxin-core IgM and IgG antibodies (EndoCAb) as measures of endotoxin exposure and interleukin-6 (IL-6) as a marker of inflammation.Results:Inflammation (IL-6) was independently and positively associated with both obesity and diabetes (F=12.7, P<0.001). LPS levels were highest in the obese-diabetic group compared with the other two groups (F=4.4, P<0.02). IgM EndoCAb (but not total IgM) was highly significantly reduced in the obese (55% of lean value) and obese diabetic women (30% of lean; F=21.7, P<0.0001 for trend) compared with lean women.Conclusion:These data support the hypothesis that gut-derived inflammatory products are associated with obesity and diabetes. Confirmation of these findings and elucidation of the role of the microbiota, gut damage and the pathways for translocation of bacterial debris, could open new avenues for prevention and treatment of type 2 diabetes.

Highlights

  • Obesity is the leading risk factor for metabolic syndrome, insulin resistance and type 2 diabetes, not all obese individuals go on to develop disease.[1]

  • Type 2 diabetes is a heterogeneous condition with aetiologies reflecting a complex interaction between genes and environment, including diet, physical activity and factors operating in early life

  • Animal studies have allowed for experiments into the causal nature of this association

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Summary

Evidence for metabolic endotoxemia in obese and diabetic Gambian women

S Hawkesworth[1], SE Moore[1,2], AJC Fulford[1,2], GR Barclay[3], AA Darboe[2], H Mark[2], OA Nyan[4] and AM Prentice[1,2]

OBJECTIVE
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
Obesity Obesity adj for diabetes Diabetes adj for obesity
DISCUSSION

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