Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity

Abstract

ObjectiveGiven that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH)-infected subjects are more insulin sensitive than STH-uninfected subjects.DesignWe performed a cross-sectional study on Flores island, Indonesia, an area with high prevalence of STH infections.MethodsFrom 646 adults, stool samples were screened for Trichuris trichiura by microscopy and for Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, and Strongyloides stercoralis by qPCR. No other helminth was found. We collected data on body mass index (BMI, kg/m2), waist-to-hip ratio (WHR), fasting blood glucose (FBG, mmol/L), insulin (pmol/L), high sensitive C-reactive protein (ng/ml) and Immunoglobulin E (IU/ml). The homeostatic model assessment for insulin resistance (HOMAIR) was calculated and regression models were used to assess the association between STH infection status and insulin resistance.Results424 (66%) participants had at least one STH infection. STH infected participants had lower BMI (23.2 vs 22.5 kg/m2, p value = 0.03) and lower HOMAIR (0.97 vs 0.81, p value = 0.05). In an age-, sex- and BMI-adjusted model a significant association was seen between the number of infections and HOMAIR: for every additional infection with STH species, the HOMAIR decreased by 0.10 (p for linear trend 0.01). This effect was mainly accounted for by a decrease in insulin of 4.9 pmol/L for every infection (p for trend = 0.07).ConclusionSTH infections are associated with a modest improvement of insulin sensitivity, which is not accounted for by STH effects on BMI alone.

Filarial Infection or Antigen Administration Improves Glucose Tolerance in Diet-Induced Obese Mice

“…Accordingly, prevalence of lymphatic filariasis was significantly lower in diabetic subjects than nondiabetic subjects in Chennai, India [15]. Moreover, a recent study in Flores Island, Indonesia, revealed that people with soil-transmitted helminth infections have an improved insulin sensitivity compared to uninfected individuals [17]. A cross-sectional study in Australian aborigines further suggested that a history of Strongyloides stercoralis infection reduces the risk to develop T2D [18].…”

“…Recent cross-sectional studies in India, Indonesia, rural China, and in aborigines in Australia revealed that the prevalence of helminth infections in T2D patients is significantly lower than in nondiabetic controls, independent of socioeconomic differences in income and nutrition, suggesting that helminth infections may indeed prevent or delay the onset of T2D [15,16,17,18]. Possible helminth-mediated protective mechanisms include the downregulation of proinflammatory immune responses that are associated with T2D, the induction of type 2 immune responses, the promotion of fatty acid uptake, or a stronger expression of genes that are associated with insulin sensitivity.…”

Cardiovascular disease and type 2 diabetes in evolutionary perspective: A critical role for helminths?

“…Reports include minimal clinical atherosclerosis in patients with schistosomal hepatic fibrosis [113], lower levels of T2DM with lymphatic filariasis [114], and lower blood glucose, glycated hemoglobin (HbA1c), insulin resistance, triglycerides and LDL with prior Schistosomiasis japonicum infection [115]. The Indonesian ImmunoSPIN project, detailed in ‘Ende of Flores Island’ section, has found that helminth infections are associated with greater insulin sensitivity [116]. An autopsy study of 319 cadavers in the Khanty-Mansiisk region of Russia measured both Opisthochis felineus worm burden and area of atherosclerotic lesions in the thoracic and aortic arteries [117].…”

“…In the rural and semi-urban Nangapanda area of Flores Island, Indonesia, Maria Yazdanbakhsh, Aprilianto Wiria and colleagues have studied the role of helminths on immune function and chronic disease among Ende farmers as part of the ImmunoSPIN project [116, 120, 168] (Fig. 2a).…”

“…Moreover, having more helminth co-infections is associated with lower BMI, WHR and total cholesterol among those infected. Each additional helminth co-infection is associated with 4.9 pmol/l lower insulin, independently of their inverse relationship with BMI [116]. Higher IgE is also associated with lower HDL, total cholesterol and fasting blood glucose.…”