Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals

Abstract

BackgroundA high-fat diet promotes postprandial systemic inflammation and metabolic endotoxemia. We investigated the effects of three consecutive high-fat meals on endotoxemia, inflammation, vascular function, and postprandial lipid metabolism in patients with type 1 diabetes.MethodsNon-diabetic controls (n = 34) and patients with type 1 diabetes (n = 37) were given three high-caloric, fat-containing meals during one day. Blood samples were drawn at fasting (8:00) and every two hours thereafter until 18:00. Applanation tonometry was used to assess changes in the augmentation index during the investigation day.ResultsThree consecutive high-fat meals had only a modest effect on serum LPS-activity levels and inflammatory markers throughout the day in both groups. Of note, patients with type 1 diabetes were unable to decrease the augmentation index in response to the high-fat meals. The most profound effects of the consecutive fat loads were seen in chylomicron and HDL-metabolism. The triglyceride-rich lipoprotein remnant marker, apoB-48, was elevated in patients compared to controls both at fasting (p = 0.014) and postprandially (p = 0.035). The activities of the HDL-associated enzymes PLTP (p < 0.001), and CETP (p = 0.007) were higher and paraoxonase (PON-1) activity, an anti-oxidative enzyme bound to HDL, decreased in patients with type 1 diabetes (p = 0.027).ConclusionsIn response to high-fat meals, early signs of vascular dysfunction alongside accumulation of chylomicron remnants, higher augmentation index, and decreased PON-1 activity were observed in patients with type 1 diabetes. The high-fat meals had no significant impact on postprandial LPS-activity in non-diabetic subjects or patients with type 1 diabetes suggesting that metabolic endotoxemia may be more central in patients with chronic metabolic disturbances such as obesity, type 2 diabetes, or diabetic kidney disease.

Intestinal alkaline phosphatase at the crossroad of intestinal health and disease – a putative role in type 1 diabetes

“…Chronic low-grade inflammation, dyslipidaemia and metabolic endotoxaemia have been associated with the development of diabetic nephropathy [10,11]. In our recent study, patients with type 1 diabetes exhibited signs of vascular dysfunction and adverse changes in postprandial lipid and lipoprotein balance in response to high-fat meals [12]. Because serum inflammatory markers were increased without direct evidence of endotoxinmediated cytokine production from circulating leucocytes [13], we hypothesized that the subsequent increase in postprandial blood cytokine concentrations could result from local inflammation in peripheral tissues.…”

“…On the investigation day, participants were given three energy-rich meals (2600 kcal in total): breakfast (at 8:00 h -965 kcal, 58% of total energy (E%) from fats), lunch (12:00 h -870 kcal, 44 E% fats) and dinner (16:00 h -779 kcal, 46 E% fats) [12]. Blood samples were drawn after overnight fasting at 8:00 h and every 2 h until 18:00 h. A 24-h urine collection was carried out during the research day.…”

“…Serum lipids (triglycerides, total cholesterol, HDL cholesterol), apolipoproteins (apoA-I, apoB-100, apoB-48, apoE) and the major lipid transfer proteins PLTP and CETP were measured as previously reported [12]. Serum LPS activity was measured kinetically from 1 : 5 diluted serum samples with the Limulus amoebocyte lysate assay (LAL, Hycult, Uden, the Netherlands) as described earlier [12].…”

Mediators between oral dysbiosis and cardiovascular diseases

“…Metabolic endotoxemia results in a status with chronic low‐grade proinflammation and pro‐oxidative stress , which may contribute to vasodilation and increased vascular and intestinal permeability. The inflammation associated with endotoxemia may partly explain its previously shown associations with clinical outcomes, such as CVD , progression of renal disease in diabetic subjects , and metabolic disorders, such as diabetes , obesity , metabolic syndrome , and non‐alcoholic fatty liver disease . Serum LPS activity is indirectly associated with serum HDL cholesterol concentrations and directly with triglyceride, cholesterol, CRP , fasting glucose, insulin, and HbA1c concentrations, as well as with body mass index , especially with the mass of visceral fat .…”

The effect of standardized food intake on the association between BMI and 1H-NMR metabolites

“…It would be valuable using both studies with fasted and non-fasted samples in meta-analyses of the association between metabolites and disease (risk factors). Previously, some studies have investigated the effect of different meals on metabolite levels78910. However, the intra-individual effects of standardized food intake on the association between metabolites and a disease risk factor have not yet been tested.…”