Background In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4) and the insulin resistance index (HOMA2-IR) in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD) and in healthy controls (CNTRL).Methods and Findings sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs) and 82 type 2 diabetes (F/M:48/34, 62.8 yrs) patients and 26 (F/M:14/12, 35.3 yrs) controls. Definition of T2D group as patients with type 2 diabetes but without clinically obvious liver disease created non-overlapping study groups. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD patients: 24-NGT, 4-IGT or IFG (“prediabetes”), 11-type 2 diabetes. HOMA2-IR: CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests); NAFLD(NGTonly): 3.23 (p = 0.0013 vs CNTRL); NAFLD(IFG/IGT/type 2 diabetes): 3.82 (p<0.001 vs CNTRL, p = 0.049 vs 2TD group). sDPP-4 activity was higher in NAFLD both with NGT (mean:33.08U/L) and abnormal glucose metabolism (30.38U/L) than in CNTRL (25.89U/L, p<0.001 and p = 0.013) or in T2D groups (23.97U/L, p<0.001 and p = 0.004). Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and γGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and γGT: r = 0.4128,p = 0.0210.Conclusions The fasting serum DPP-4 activity was not increased in T2D provided that patients with liver disease were intentionally excluded. The high serum DPP-4 activities in NAFLD were correlated with liver tests but not with the fasting plasma glucose or HbA1C supporting that the excess is of hepatic origin and it might contribute to the speedup of metabolic deterioration. The correlation among γGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and HOMA2-IR in NAFLD strongly suggests that serum DPP-4 activity should be considered as a novel liver disease biomarker.
Dipeptidyl peptidase-4 (DPP-4) is involved in the metabolism of peptide hormones, T-cell activation and proliferation. In type 1 diabetes mellitus (T1DM) β-cell destruction involves a number of dysregulated T-cells. Our aim was to assess the serum DPP-4 activity and the lymphocyte membrane bound CD26 expression in patients with type 1 diabetes and healthy controls. Ninety-eight (T1DM: 48, F/M = 20/28, mean age: 34.4y; control: 50, F/M = 39/11 mean age: 32,4y) individuals were included. Fasting serum DPP-4 enzymatic activity, plasma glucose (FPG), CD26 expression on CD3+, CD4+ and CD8+ lymphocytes, HbA1c and body mass index (BMI) were assessed. ICA and GAD antibodies were assessed in the T1DM group. DPP-4 enzymatic activity was determined by kinetic enzyme assay, ICA and GAD were assessed by ELISA. Determination of the CD26 expression on CD3+, CD4+ and CD8+ lymphocytes was performed by flow-cytometric analysis. We found higher serum DPP-4 activity (Mean: T1DM: 30.069 U/L, control: 22.62 U/L, p < 0.0001) and decreased CD26 lymphocyte expression on all lymphocyte subpopulations in T1DM. Fasting serum DPP-4 activity was independent from the ICA or GAD status of patients with T1DM. Here we first present that the serum DPP-4 activity is increased and the lymphocyte membrane bound CD26 expression is decreased in type 1 diabetes. Decreased lymphocyte membrane bound CD26 expression in T1DM might be a novel part of the T-lymphocyte regulatory dysfunction observed in type 1 diabetes mellitus. These results might provide some basis for the clinical implication of DPP-4 inhibition in patients with T1DM.
A dipeptidil-peptidáz-4 enzim -amely azonos a T-lymphocyta membránfelszínhez kötött CD26 molekulával -az inkretin hormonok bontásával jelentős szerepet játszik a szénhidrát-anyagcsere szabályozásában. Célkitűzés: Vizsgálatunk célja az volt, hogy meghatározzuk az éhomi és postprandialis szérum-DPP-4 enzimaktivitását 41 1-es, 87 2-es típusú cukorbetegben, valamint 25 egész-séges személyben. Módszer: A szérum-DPP-4-enzimaktivitás meghatározása microplate-alapú kinetikus eljárással történt éhomi, majd étkezést követően 60 és 120 perces időszakokban. Eredmények: A DPP-4-enzimaktivitás mind éhomi, mind postprandialis állapotban szignifi kánsan magasabb volt az 1-es típusú diabetesben szenvedőknél, mint a 2-es típusú diabeteses vagy a kontrollszemélyekben. Nem találtunk változást az enzimaktivitásban egyik csoporton belül sem a postprandialis és az éhomi állapot között. Nem volt korreláció sem az éhomi plazmaglükóz-és a szérum-DPP-4-enzimaktivitás, sem a HbA 1c és a szérum-DPP-4-enzimaktivitás között. Következtetés: Eredményeink felvetik annak a valószínűségét, hogy a DPP-4-gyel kapcsolatba hozható vércukorszint-válto-zás nem a szérumban mérhető DPP-4-aktivitás-változás következménye, hanem parakrin módon ható DPP-4-hatásként jelentkezik. Az 1-es típusú diabetesben észlelhető emelkedett DPP-4-enzimaktivitás ugyanakkor a pancreas autoimmun folyamatára utalhat, de hormonális feed-back mechanizmust, esetleg célszervkárosodást is jelezhet.Kulcsszavak: dipeptidil-peptidáz-4, glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, 1-es típusú cukorbetegség, 2-es típusú cukorbetegség, autoimmunitás Elevated serum dipeptidyl peptidase-4 activity in type 1 diabetes mellitus: a direct comparisonDipeptidyl peptidase-4 (DPP-4) has an important role in the carbohydrate metabolism with the degradation of incretin hormones. Aim: We assessed the serum DPP-4 activity both in fasting and postprandial condition in patients with type 1-, type 2 diabetes and healthy controls. Methods: Serum DPP-4 activities were determined at fasting sate and at 60 and 180 minutes after test meal. DPP-4 activity was measured by microplate-based kinetic assay in 41 type 1-, and in 87 type 2 diabetic patients and in 25 healthy volunteers. Results: Serum DPP-4 activities were found signifi cantly higher both in fasting and postprandial state in patients with type 1 diabetes than in type 2 and control subjects. No change in the enzyme activities was found after test meal. Correlation was neither detected between the fasting plasma glucose nor between the HbA 1C and the DPP-4 values in any of the groups studied. Conclusions: Results suggest that it is not the hyperglycemia, rather the type of diabetes which determinates the serum DPP-4 enzymatic activity. The exact background of this phenomenon is not yet clear, however, increased serum DPP-4 enzyme activity in type 1 diabetes mellitus may refer to pancreatic autoimmune process, concomitant autoimmune diseases, hormonal feed back mechanism, or even target organ damage.Keywords: dipeptidyl peptida...
Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β-cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.
There are differences in the time course of evolution and in predictors of morphological and functional changes in arteries in type 1 diabetes mellitus.
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