Serum zonulin as parameter of intestinal permeability in longstanding type 2 diabetes: correlations with metabolism parameter and renal function

Abstract

Background: The raised permeability of the intestinal barrier (IB) is a factor of major pathogenetic relevance for the development of type-1 and type-2 diabetes. Little is known about the extent to which an impaired function of the IB is still detectable even after a relatively long duration of diabetes and which correlations are present between such an impairment and clinical parameters. We investigated these correlations by measuring serum zonulin levels as a parameter of the IB function in people with a longer history of type-2 diabetes. Methods: In 63 diabetic patients (mean history of diabetes 13 years) and 19 non diabetic controls, the serum zonulin concentrations were measured alongside metabolism parameters (HbA1c, insulin resistance, lipids) and renal function (estimated glomerular filtration rate [eGFR], urinary albumin/creatinine ratio [UACR]). In addition, we also re¬corded the patients’ demographic parameters and drug therapy details. Results: More than one half of diabetic patients (58%) exhibited elevated serum zonulin levels compared to nondiabetic controls. Regression analyses showed a significant positive correlation of zonulin concentrations to BMI and HbA1c, but not to insulin resistance or lipids. A significant positive correlation was found between zonulin and eGFR, alongside a significantly negative correlation to proteinuria (UACR). Taking several confounders into consideration, UACR remained an independent factor of influence on the zonulin concentration. Conclusion: An impaired IB was found in the majority of the diabetic patients even after a long-term duration of the disorder. Whether the detected positive associations between the zonulin concentration and HbA1c as well as BMI are reasons or consequences of the impaired IB must be investigated further in longitudinal studies. The correlations between circulating zonulin and parameters of kidney function demonstrated here for the first time may indicate that zonulin has effects in other organs too that have to be clarified in further studies.