Insulin Resistance is Associated with Gut Permeability Without the Direct Influence of Obesity in Young Adults

Abstract

Objective: Recent findings have associated insulin resistance and obesity with increased gut permeability. However, it still remains unclear whether obesity may be the underlining factor for the association between gut permeability and insulin resistance. This study investigated the relationship between gut permeability, measures of obesity, and markers of insulin resistance in young adults.

Materials and methods: A cross-sectional quantitative study which enrolled 151 young South African adults was conducted. Anthropometric measurements were performed to assess obesity. Adiponectin, leptin, and zonulin, a marker for gut permeability, were assayed. Insulin and fasting glucose were assayed and used to determine insulin resistance (HOMA-IR), insulin sensitivity (%S) and beta cell function (%B).

Results: Decreased adiponectin and increased leptin were associated (p<0.05) with obesity. HOMA-IR inversely correlated (p<0.05) with adiponectin but positively with leptin to adiponectin (Lept/ADP) ratio (p<0.05) in females. Markers of insulin resistance were not associated (p>0.05) with obesity. Overweight/obese (O/O) females had a significantly (p<0.01) higher zonulin concentration than lean females. Zonulin positively associated (p<0.05) with body mass index and visceral fat, as well as with HOMA-IR and insulin concentration. Lept/ADP ratio, an inflammatory marker, was associated with risk of insulin resistance. Increased insulin, a maker for insulin resistance, was associated with risk of gut permeability.

Conclusion: Insulin resistance was associated with gut permeability without a direct influence by obesity in young adults. The lack of relationship between obesity and insulin resistance was possibly mediated by the contribution of obesity to gut permeability. This finding suggests that gut permeability may be a potential independent risk factor for the development of insulin resistance in healthy obese young adults.

Keywords: gut permeability; inflammation; insulin resistance; obesity.

Conflict of interest statement

The authors report no conflicts of interest for this work.

© 2020 Mkumbuzi et al.

Figures

Figure 1

Plasma adiponectin level between overweight/obese and lean subjects. Data is expressed as mean ± standard error of the mean. p≤0.05 was considered statistically significant, *p

Figure 2

Plasma leptin level between overweight/obese and lean subjects. Data is expressed as mean ± standard error of the mean. p≤0.05 was considered statistically significant, *p

Figure 3

Leptin to adiponectin ratio between overweight/obese and lean subjects. Data is expressed as mean ± standard error of the mean. p≤0.05 was considered statistically significant, ***p

Figure 4

Plasma zonulin between lean and overweight/obese subjects. Data is expressed as mean ± standard error of the mean. p≤0.05 was considered statistically significant, **p

Figure 5

Mediation effect and summary of findings. (A) Mediation effect of gut permeability on the relationship between obesity and insulin resistance. The numeric figures represent the coefficient of relationship; X: Independent variable, Y: Dependent variable and M: Mediator variable. (B) Schematic summary of findings. A: Metabolically healthy obesity in young adults promote gut and systemic inflammation; B: Inflammation in the gut promotes gut permeability; C: Gut permeability leads to insulin resistance; D: Systemic inflammation promotes insulin resistance; E: Metabolically healthy obesity in young adults is associated with gut permeability; F: Metabolically healthy obesity in young adults is not associated with insulin resistance.