Abstract
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.
Highlights
Individuals with obesity had 4-fold risk and type 2 diabeticpatients do have higher risk of dying from cirrhosis than the general population .[1,2] Vica-versa in the Insulin Resistance Atherosclerosis Study (IRAS) elevated ALT was independently associated with insulin resistance and other findings are consistent with the role of liver fat in diabetes pathogenesis.[3,4]Dipeptidyl peptidase-4 (DPP-4) inactivates both incretin hormones (GIP, GLP-1), DPP-4 inhibitors are used in the treatment of type 2 diabetes.[5]
Higher serum DPP-4 activity was found in patients with chronic C-virus hepatitis, which infectious disease is well known to be associated with diabetes mellitus and insulin resistance.[8,9]
Serum DPP-4 enzyme activity and HOMA2-IR Fifteen patients out of 39 in the non-alcoholic fatty liver disease (NAFLD) group had abnormal glucose metabolism: 11 NAFLD patients presented with type 2 diabetes mellitus and 4 NAFLD patients had (‘‘prediabetes’’) either impaired fasting glucose levels or impaired glucose tolerance at the OGTT (75 gCH)
Summary
Dipeptidyl peptidase-4 (DPP-4) inactivates both incretin hormones (GIP, GLP-1), DPP-4 inhibitors are used in the treatment of type 2 diabetes.[5] The prevalence of fatty liver disease in a population based study was 34% over 90% of which was due to non-alcoholic causes (NAFLD) that is generally asymptomatic, frequently associated with obesity, type 2 diabetes and metabolic syndrome.[6,7]. 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 naıve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD) and in healthy controls (CNTRL)
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