Acute Elevations of Plasma Asymmetric Dimethylarginine and Impaired Endothelial Function in Response to a High-Fat Meal in Patients With Type 2 Diabetes

Context: Postprandial dysmetabolism is emerging as an important cardiovascular risk factor. Augmentation index (AIx) is a measure of systemic arterial stiffness and independently predicts cardiovascular outcome. Objective: The objective of this study was to assess the effect of a standardized high-fat meal on metabolic parameters and AIx in 1) lean, 2) obese nondiabetic, and 3) subjects with type 2 diabetes mellitus (T2DM). Design and Setting: Male subjects (lean, n = 8; obese, n = 10; and T2DM, n = 10) were studied for 6 h after a high-fat meal and water control. Glucose, insulin, triglycerides, and AIx (radial applanation tonometry) were measured serially to determine the incremental area under the curve (iAUC). Results: AIx decreased in all three groups after a high-fat meal. A greater overall postprandial reduction in AIx was seen in lean and T2DM compared with obese subjects (iAUC, 2251 ± 1204, 2764 ± 1102, and 1187 ± 429% · min, respectively; P < 0.05). The time to return to baseline AIx was significantly delayed in subjects with T2DM (297 ± 68 min) compared with lean subjects (161 ± 88 min; P < 0.05). There was a significant correlation between iAUC AIx and iAUC triglycerides (r = 0.50; P < 0.05). Conclusions: Obesity is associated with an attenuated overall postprandial decrease in AIx. Subjects with T2DM have a preserved, but significantly prolonged, reduction in AIx after a high-fat meal. The correlation between AIx and triglycerides suggests that postprandial dysmetabolism may impact on vascular dynamics. The markedly different response observed in the obese subjects compared with those with T2DM was unexpected and warrants additional evaluation.

Download Full-text

Adiponectin is expressed in the pancreas of high-fat-diet-fed mice and protects pancreatic endothelial function during the development of type 2 diabetes

Diabetes & Metabolism ◽

10.1016/j.diabet.2014.05.004 ◽

2014 ◽

Vol 40 (5) ◽

pp. 363-372 ◽

Cited By ~ 6

Author(s):

X.-X. Liu ◽

K.-Y. Liu ◽

P. Li ◽

S. Han ◽

X.-D. Peng ◽

...

Keyword(s):

Type 2 Diabetes ◽

Endothelial Function ◽

High Fat Diet ◽

High Fat

Download Full-text

Serum Phospholipid Transfer Protein Activity After a High Fat Meal in Patients with Insulin-Treated Type 2 Diabetes

Lipids ◽

10.1007/s11745-010-3384-5 ◽

2010 ◽

Vol 45 (2) ◽

pp. 129-135 ◽

Cited By ~ 2

Author(s):

Axel Schlitt ◽

Bernhard Schwaab ◽

Kirsten Fingscheidt ◽

Karl J. Lackner ◽

Gunnar H. Heine ◽

...

Keyword(s):

Type 2 Diabetes ◽

Phospholipid Transfer Protein ◽

High Fat ◽

Serum Phospholipid ◽

Protein Activity ◽

Transfer Protein ◽

Phospholipid Transfer ◽

Fat Meal

Download Full-text

Oxidative stress and endothelial dysfunction are associated with reduced cognition in type 2 diabetes

Diabetes and Vascular Disease Research ◽

10.1177/1479164119848093 ◽

2019 ◽

Vol 16 (6) ◽

pp. 577-581 ◽

Cited By ~ 3

Author(s):

Onno N Groeneveld ◽

Esther van den Berg ◽

Odd Erik Johansen ◽

Sven Schnaidt ◽

Karin Hermansson ◽

...

Keyword(s):

Type 2 Diabetes ◽

Endothelial Function ◽

Asymmetric Dimethylarginine ◽

Prostaglandin F2α ◽

Regression Coefficients ◽

Psychomotor Speed ◽

Mental Flexibility ◽

Cardiovascular Outcome Trial ◽

Factor Α

Objective: Type 2 diabetes is associated with cognitive dysfunction, but the mechanisms are unknown. We assessed the relationships of biomarkers of oxidation, endothelial function and inflammation with cognition in participants of the CAROLINA® trial (CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes). Methods: Baseline circulating biomarkers of oxidation (8-iso-prostaglandin F2α), endothelial function (asymmetric dimethylarginine, endothelin-1) and inflammation (C-reactive protein, interleukin-6, tumour necrosis factor-α), based on linear regression, were related to cognition on five domains, as measured with an automated battery. Results: In 37 patients (mean age 66.7 ± 8.7 years, median HbA1c 6.9%/52 mmol/mol), 8-iso-prostaglandin F2α was associated with reduced mental flexibility and attention (standardised regression coefficients −0.47, −0.34), whereas asymmetric dimethylarginine was associated with reduced psychomotor speed and attention (standardised regression coefficients −0.39, −0.34). No significant associations were observed between biomarkers of inflammation and cognition. Conclusion: Elevated biomarkers of oxidation and endothelial function are associated and may play a role in reduced psychomotor speed, mental flexibility and attention in type 2 diabetes.

Download Full-text

Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes

Diabetes ◽

10.2337/db06-1687 ◽

2007 ◽

Vol 56 (8) ◽

pp. 2046-2053 ◽

Cited By ~ 49

Author(s):

Leonie K. Heilbronn ◽

Søren Gregersen ◽

Deepali Shirkhedkar ◽

Dachun Hu ◽

Lesley V. Campbell

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Fat Oxidation ◽

High Fat ◽

History Of ◽

Fat Meal

Download Full-text

Type 2 diabetes progression differently affects endothelial function and vascular contractility in the aorta and the pulmonary artery

Scientific Reports ◽

10.1038/s41598-021-85606-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Bernardete F. Melo ◽

Jesus Prieto-Lloret ◽

Marlene D. Cabral ◽

Fatima O. Martins ◽

Inês B. Martins ◽

...

Keyword(s):

Type 2 Diabetes ◽

Endothelial Dysfunction ◽

Pulmonary Artery ◽

Endothelial Function ◽

Pulmonary Disease ◽

Systemic Circulation ◽

Diabetic Rats ◽

High Fat ◽

Vascular Contractility

AbstractType 2 diabetes (T2D) is associated with cardiovascular and pulmonary disease. How T2D affects pulmonary endothelial function is not well characterized. We investigated the effects of T2D progression on contractility machinery and endothelial function in the pulmonary and systemic circulation and the mechanisms promoting the dysfunction, using pulmonary artery (PA) and aorta. A high-fat (HF, 3 weeks 60% lipid-rich diet) and a high-fat/high-sucrose (HFHSu, combined 60% lipid-rich diet and 35% sucrose during 25 weeks) groups were used as prediabetes and T2D rat models. We found that T2D progression differently affects endothelial function and vascular contractility in the aorta and PA, with the contractile machinery being altered in the PA and aorta in prediabetes and T2D animals; and endothelial function being affected in both models in the aorta but only affected in the PA of T2D animals, meaning that PA is more resistant than aorta to endothelial dysfunction. Additionally, PA and systemic endothelial dysfunction in diabetic rats were associated with alterations in the nitrergic system and inflammatory pathways. PA dysfunction in T2D involves endothelial wall mineralization. The understanding of the mechanisms behind PA dysfunction in T2D can lead to significant advances in both preventative and therapeutic treatments of pulmonary disease-associated diabetes.

Download Full-text