Procollagen-III peptide identifies adipose tissue-associated inflammation in type 2 diabetes with or without nonalcoholic liver disease

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A marker for monitoring liver fibro-inflammation in Type 2 diabetes patients

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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that affects the body’s ability to metabolize sugar. Often associated with overweight or obese subjects with a sedentary lifestyle, it generally appears during adulthood. It is characterized either by organ “resistance” to the normal effects of insulin, or by insulin production that is too low to maintain normal glucose levels. The worldwide prevalence of Type 2 diabetes has increased dramatically: the number of diabetic patients was multiplied by a factor of 4 in 30 years, according to the World Health Organization. It is no longer a disease specific to Western countries and is now spreading rapidly in middle- and low-income countries.
If diet and exercise are not enough to manage blood sugar levels, diabetes medications or insulin therapy must be prescribed to patients. Also, the disease causes damage to many organs, such as the heart, kidney, lung, and liver by promoting micro- and macro-vascular complications and metabolic disorders. This results in a chronic inflammatory state with tissue remodeling and organ dysfunction. Furthermore, treated patients require close follow-up.
Many studies have revealed a strong relationship between Type 2 diabetes mellitus and chronic hepatopathies such as non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). In this article, Ilaria Barchetta conducted a clinical study on a cohort of T2DM patients. By using a set of biological markers, from general liver enzymes to inflammatory cytokines and the circulating Procollagen type III aminoterminal Propeptide (PIIINP), she was able to better characterize the biomarker landmarks in T2DM patients, with or without NAFLD. Interestingly, she showed how PIIINP could be correlated with adipose tissue (AT) expansion and inflammation in the liver.
This brings further controversy to discussions about the direct relationship of PIIINP levels with NAFLD. However, it also clearly demonstrates the added value of this biomarker in early investigation and routine follow-up of patients suffering from T2DM and dysmetabolic conditions. PIIINP is the best biomarker candidate for fibro-inflammation assessment in the liver, and likely also in many other organs!


Procollagen-III peptide (PIIINP) is a marker of fibrosis associated with increased cardiometabolic risk and progression of chronic liver diseases such as nonalcoholic fatty liver disease (NAFLD) and steatohepatitis; its association with type 2 diabetes mellitus (T2DM) has not been elucidated yet. The aim of this study was to investigate the relationship among circulating PIIINP levels, metabolic traits, and body fat distribution in subjects with T2DM with or without NAFLD.
Data from 62 T2DM subjects recruited in our diabetes outpatient clinics at Sapienza University of Rome, Italy, were analysed. Participants underwent metabolic and inflammatory profiling (CRP, TNFα, IL-6, IL-8, WISP1, and adiponectin) and magnetic resonance imaging for diagnosing NAFLD on the basis of hepatic fat fraction (≥5.5%) and quantifying visceral and subcutaneous adipose tissue (AT) areas. Serum PIIINP was measured by human-PIIINP ELISA kits.
Higher PIIINP levels correlated with greater BMI and visceral AT area and were associated with systemic signatures of AT-associated inflammation-ie, higher WISP-1, IL-8, and lower adiponectin levels; conversely, PIIINP did not differ significantly between T2DM patients with or without NAFLD and were not associated with hepatic fat fraction, Fatty Liver Index, FIB-4, or transaminases.
Elevated circulating PIIINP levels specifically identify T2DM individuals with AT expansion and systemic proinflammatory profile suggestive for AT dysfunction; our results point toward a new role of PIIINP as a marker of fibro inflammation in dysmetabolic conditions, likely related to AT expansion.


Diabetes/ Metabolism Research and Reviews. 2018 Jul;34(5): e2998.

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