## 4 Discussion  
### Outcomes of Helminuths Infection and T2 DM Comorbidity in Experimental Animal Studies  
Type 2 diabetes mellitus is a chronic inflammatory metabolic disease which leads to chemokines and cytokines alterations, activation of different cell types and metabolic perturbations in different organs [2; 26]. Clinical manifestations of T2 DM are common in late adolescence and increase progressively into mid-life. Prevalence of inflammatory metabolic diseases such as T2 DM are relatively high, especially in the developed countries [25]. Apart from this being a lifestyle disease associated with sedentarism, it might also be due to limited exposure to helminth infections which has been postulated as one mechanism to explain the markedly high prevalence of T2 DM in developed countries [25; 27]. Previous studies have demonstrated that the prevalence of helminth infections was remarkably reduced in T2 DM individuals compared to non-diabetic controls, [22; 28] thus, confirming a protective effect of T2 DM against helmin infections. Both animal models and human studies have demonstrated that helminth infections can also protect against establishment or ameliorates T2 DM [29]. These observations are further collaborated by [PERSON] et al. [2], [PERSON] et al. [9] and [PERSON] et al. [30], who concluded that helminth infections protect against T2 DM by the alteration of host immune responses. A study by [PERSON] et al. [2], demonstrated that alterations in the gut microbiota modulates glucose intolerance and adipose tissue inflammation. Additionally, there are reports that helminth infection alters the gut microbiome during obesity and also modulate glucose uptake, inflammation and insulin sensitivity [2; 31], although the helminth infection and T2 DM interface seems to be counter-regulatory with the effects of helminths on diabetic status still to be fully explored.  
Findings from experimental animal studies have shown that chronic _S. mansoni_ infection provides protection against streptozotocin-induced T-cell-mediated pancreatitis [20]. However, the protection did not provide better peripheral glycemic control, thus, modulation of cytokine production could be responsible for the observed decreased peripheral glucose uptake by the diaphragm [20]. Another study by [PERSON] et al. [16] demonstrated that experimental infection with _S. muris_ showed a delay on the onset of hyperglycemia in fa/fa rats. It was also suggested that inflammatory cytokine production may activate the onset of hyperglycemia in this model. According to [PERSON] et al. [21], parasite-induced Th2 immune responses prevented T2 DM in KK-Ay/Tajcl mice. Intraperitoneal glucose tolerance test (IPGTT) was significantly improved on _H. polygyrus_ infection, suggesting that insulin sensitivity was recovered following _H. polygyrus_ infection [21]. It has also been reported that the elevation of Th2 T-helper cells induces alternatively activated macrophages (AAMacs), which inhibit inflammation by producing IL-10. Th2 cytokines are associated with the promotion of IgE and eosinophilic responses in atopy, and interleukin-10 has more of an anti-inflammatory response [21; 32]. AAMacs induction by Th2 T-helper cells might be one of the reasons underlying the improvement in the diabetic condition. Further studies still need to be reconsidered on the protective effect of helminth infection in T2 DM, in order to devise therapeutic strategies for the treatment of autoimmune diseases. To define the role of each of the immune cells during the interaction of the immunity and metabolic systems, it would also be necessary to assess the effect of Th2, AAMac(M2) or eosinophil depletion. Future investigations are needed to understand the underlying mechanism of the delayed onset of T2 DM in _S. muris_ infected fa/fa rats, and other parasitic infections especially the tissue-dwelling parasites to determine whether the onset of hyperglycemia in fa/fa rats is delayed.