Dipeptidyl peptidase-4 levels are increased and partially related to body fat distribution in patients with familial partial lipodystrophy type 2

Abstract

BackgroundDipeptidyl peptidase-4 (DDP4) is an enzyme responsible for glucagon-like peptide-1 inactivation and plays an important role in glucose metabolism.ObjectiveThe aim of this study was to evaluate DPP4 levels in patients with familial partial lipodystrophy type 2 (FPLD2) and correlate it with body fat distribution.MethodsFourteen patients with FPLD2 were selected to participate in this study and matched to a healthy control group (n = 8). All participants had anthropometrical data registered. Body adiposity index (BAI) was used to evaluate fat distribution in this population. Body fat content and distribution were analyzed by dual X-ray absorptiometry (DXA). Biochemical exams, including DPP4 levels, were performed in all individuals.ResultsDespite the same body mass index, lipodystrophic patients had a significant lower hip (median 92.0 vs 94.5; p = 0.028), HDL cholesterol (42.6 ± 10.4 vs 66.1 ± 16.0; p < 0.01) and BAI (24.1 ± 2.8 vs 29.0 ± 3.7; p = 0.02), suggesting that BAI was able to catch differences in fat distribution between groups. On the other hand, patients with FPLD2 presented significant higher levels of insulin (median 11.2 vs 5.3; p = 0.015), triglycerides (184.9 ± 75.4 vs 89.1 ± 51.0; p < 0.01) and DPP4 (4.89 ± 0.92 vs 3.93 ± 1.08; p = 0.04). A trend toward an inverse statistical significance was observed between DPP4 levels and BAI (r = −0.38; p = 0.072). In the lipodistrophic group, a significant correlation was found between DPP4 levels and percentage of total body fat (r = 0.86; p = 0.0025) and android fat (r = 0.78; p = 0.014).ConclusionsPatients with FPLD2 exhibit an increase in DDP4 levels in comparison to a healthy control group. The increase in the levels of this enzyme does not seem to be related to the diagnosis of diabetes and might be associated with an increase in central fat (estimated using BAI and measured using DXA). These results might be used to reinforce the concept that DDP4 is an adipokine related to central fat distribution.

Insulin secretory defect in familial partial lipodystrophy Type 2 and successful long-term treatment with a glucagon-like peptide 1 receptor agonist

“…In addition to the expected insulin resistance, we identified a defect of first-phase insulin secretion in the woman, which may explain the efficacy of the GLP-1 receptor agonist; however, this has not been directly confirmed. Our findings may be related to the increased levels of dipeptidyl peptidase-4 found in familial partial lipodystrophy type 2, as recently reported [6]. The effectiveness of liraglutide has also been demonstrated in a retrospective case-control study of patients with HIV-associated lipodystrophy; however, in that case, the effects on glycaemia were small and probably secondary to weight loss, which was different from our case [7].…”

“…Our findings may be related to the increased levels of dipeptidyl peptidase-4 found in familial partial lipodystrophy type 2, as recently reported [6]. In addition to the expected insulin resistance, we identified a defect of first-phase insulin secretion in the woman, which may explain the efficacy of the GLP-1 receptor agonist; however, this has not been directly confirmed.…”

Effect of Adding Vildagliptin to Metformin on Antioxidant State, Inflammatory, and Atherothrombotic Markers in Newly Diagnosed Patients with Type 2 Diabetes Mellitus

“…These findings are in consistence with previous studies [42,43]. Regarding the central obesity, Valerio et al demonstrated a positive correlation between DPP-4 enzyme levels and central fat distribution in patients with familial partial lipodystrophy type 2 [44]. Thus, inhibition of DPP-4 enzyme may be associated with central fat redistribution and waist circumference reduction.…”

Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

“…A link between obesity or underlying diseases like diabetes mellitus, which both can affect DPP4 expression levels [48], and the risk of fatal outcome of MERS-CoV infection has been made [49]. Moreover, alanine scanning mutagenesis identified DPP4 residues critical for MERS-CoV entry, including K267, L294, I295, R317 and R336 [50,51]. However, the impact of natural-occurring variations on host cell entry of MERS-CoV has not been addressed so far.…”