Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake

Abstract

Objective: Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide are incretin hormones, secreted in response to meal ingestion. The incretin hormones stimulate insulin secretion and are essential for the maintenance of normal plasma glucose concentrations. Both incretin hormones are metabolized quickly by the enzyme dipeptidyl peptidase-IV (DPP-IV). It is well known that type-2 diabetic patients have an impaired incretin effect. Therefore, the aim of the present study was to investigate plasma DPP-IV activity in the fasting and the postprandial state in type-2 diabetic patients and control subjects. Design: The study included two protocols. Protocol one involved 40 fasting type-2 diabetic patients (28 men); age 61G1.4 (meanGS.E.M.) years; body mass index (BMI) 31G0.6 kg/m 2 ; HbAlc 7.2G0.2%; and 20 matched control subjects (14 men) were studied. Protocol two involved eight type-2 diabetic patients (six men); age 63G1.2 years; BMI 33G0.5 kg/m 2 ; HbAlc 7.5G0.4%; eight matched control subjects were included. Methods: In protocol one, fasting values of DPP-IV activity were evaluated and in protocol two, postprandial DPP-IV activity during a standard meal test (566 kcal) was estimated. Results: Mean fasting plasma DPP-IV activity (expressed as degradation of GLP-1) was significantly higher in this patient group compared with the control subjects (67.5G1.9 vs 56.8G2.2 fmol GLP-1/h (meanGS.E.M.); PZ0.001). In the type-2 diabetic patients, DPP-IV activity was positively correlated to FPG and HbAlc and negatively to the duration of diabetes and age of the patients. No postprandial changes were seen in plasma DPP-IV activity in any of the groups. Conclusions: Plasma DPP-IV activity increases in the fasting state and is positively correlated to FPG and HbAlc levels, but plasma DPP-IV activity is not altered following meal ingestion and acute changes in plasma glucose. 155 485-493 European Journal of Endocrinology

Decreased active GLP-1 response following large test meal in patients with type 1 diabetes using bolus insulin analogues

“…Hence, the increased DDP-IV activity in the patients studied by Vilsbøll et al should result in lower p-active GLP-1 levels relative to those in our patients, but the p-active GLP-1 levels were actually higher than those seen in our patients [2]. Furthermore, the p-active GLP-1 levels may increase when patients have hypoglycemia, as in patients with type 2 diabetes [9], but no patients with hypoglycemia participated in either study. Therefore, glycemic state may be not directly related to these differences between the studies.…”

“…Hyperglycemia evaluated by HbA1c levels increases DPP-IV activity in patients with type 1 diabetes [8]. Moreover, serum DPP-IV activity is positively correlated to fasting plasma glucose and HbAlc levels in patients with type 2 diabetes [9]. Hence, the increased DDP-IV activity in the patients studied by Vilsbøll et al should result in lower p-active GLP-1 levels relative to those in our patients, but the p-active GLP-1 levels were actually higher than those seen in our patients [2].…”

Plasma dipeptidyl peptidase 4 activity correlates with body mass index and the plasma adiponectin concentration in healthy young people

“…Pala et al reported that oral glucose loading did not induce DPP4 activation in normal, impaired glucose tolerance, or type 2 diabetes subjects [21]. In addition, Ryskjaer et al reported that plasma DPP4 activity is not altered following meal ingestion or acute changes in the plasma glucose level [10]. Taking these findings together, we assume that DPP4 biosynthesis is correlated with longterm exposure to a high glucose concentration.…”

“…1). The correlations between DPP4 activity and BMI (r = 0.24, p = 0.0017) and total cholesterol (r = 0.27, p = 0.0006) remained significant after adjusting for age and sex (Table 3), but not found to increase [9,10] and decrease [11][12][13] in patients with type-2 diabetes. Moreover, it has been reported that the degree of plasma DPP4 activity was significantly higher in obese subjects than in lean subjects [14,15]; however, the DPP4 hyperactivity in obese individuals did not seem to be affected by their degree of overweightedness [14].…”

“…In this study, plasma DPP4 activity was not correlated with the fasting blood glucose level in healthy young subjects. Clinical studies have been reported that DPP4 activity showed significant correlations with plasma glucose and HbA1c levels in diabetic patients [9,10]. Moreover, an in vitro study determined that exposure to high levels of glucose enhanced the biosynthesis of DPP4 in human glomerular endothelial cells [20].…”