New study shows DPP-4 improves Endothelial Function

Heart Vessels. 2018 Feb 9. doi: 10.1007/s00380-018-1136-2. [Epub ahead of print]

Comparison of the effects of linagliptin and voglibose on endothelial function in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, pilot study (EFFORT).

Koyama T1, Tanaka A2, Yoshida H3, Oyama JI4, Toyoda S5, Sakuma M5, Inoue T5, Otsuka Y1, Node K6.

Author information

1
Department of Cardiology, Fukuoka Wajiro Hospital, Fukuoka, Japan.
2
Department of Cardiovascular Medicine, Saga University, 5-5-1 Nabeshima, Saga, Japan. tanakaa2@cc.saga-u.ac.jp.
3
Clinical Research Center, Saga University, Saga, Japan.
4
Department of Cardiovascular Medicine, Saga University, 5-5-1 Nabeshima, Saga, Japan.
5
Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Japan.
6
Department of Cardiovascular Medicine, Saga University, 5-5-1 Nabeshima, Saga, Japan. node@cc.saga-u.ac.jp.

Abstract

Endothelial dysfunction contributes to poor cardiovascular prognosis in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). The effect of dipeptidyl peptidase-4 inhibitors on endothelial function remains controversial. We sought to compare the effects of linagliptin and voglibose on endothelial function, as assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT). Sixteen patients with newly diagnosed T2DM and CAD were randomized 1:1 to linagliptin (5 mg, once-daily) or voglibose (0.9 mg, thrice-daily). The RH-PAT and laboratory parameters, including 75 g oral glucose tolerance test, were measured at baseline and 3 months.
Linagliptin increased serum levels of active glucagon-like peptide-1 and high-molecular-weight adiponectin. Age-, sex-, and baseline-adjusted changes in logarithmic RH-PAT index (LnRHI) after 3 months were significant between groups (linagliptin, 0.135 ± 0.097; voglibose, – 0.124 ± 0.091; P = 0.047). In the linagliptin group, change in LnRHI was positively correlated with change in high-density lipoprotein cholesterol and negatively correlated with changes in both urine albumin-to-creatinine ratio and high-sensitivity C-reactive protein. Furthermore, linagliptin treatment for 3 months reduced serum levels of both glucose and insulin at 2 h, relative to voglibose, in the age-, sex-, and baseline-adjusted model. Linagliptin improved endothelial function relative to voglibose, accompanied by amelioration of glycemic, renal, and cardiometabolic parameters, in patients with newly diagnosed T2DM and CAD.Trial registration Unique Trial Number, UMIN 000029169.

KEYWORDS:

Coronary artery disease; Endothelial function; Linagliptin; Type 2 diabetes mellitus; Voglibose

Incretins_and_DPP_4_inhibitors.svg.png
Heart Vessels. 2018 Feb 1. doi: 10.1007/s00380-018-1128-2. [Epub ahead of print]

Microvasc Res. 2018 Feb 2. pii: S0026-2862(17)30233-9. doi: 10.1016/j.mvr.2018.02.001. [Epub ahead of print]

Attenuated cutaneous microvascular function in healthy young African Americans: Role of intradermal l-arginine supplementation.

Kim K1, Hurr C2, Patik JC3, Matthew Brothers R4.

Author information

1
Department of Pathology, The University of Alabama at Birmingham, United States.
2
Department of Pharmacology and Physiology, George Washington University, United States.
3
Department of Kinesiology, The University of Texas at Arlington, United States.
4
Department of Kinesiology, The University of Texas at Arlington, United States. Electronic address: matthew.brothers@uta.edu.

Abstract

It has been established that endothelial function in conduit vessels is reduced in young African Americans (AA) relative to Caucasian Americans (CA). However, less is known regarding endothelial function in microvasculature of young AA. We hypothesized that microvascular function in response to local heating of skin is attenuated in young AA relative to age-matched CA due largely to the lack of NO bioavailability, which is in turn improved by intradermal l-arginine supplementation and/or inhibition of arginase. Nine AA and nine CA adults participated in this study. Participants were instrumented with four microdialysis membranes in the cutaneous vasculature of one forearm and were randomly assigned to receive 1) lactated Ringer’s solution as a control site; 2) 20 mM NG-nitro-l-arginine (l-NAME) to inhibit NO synthase activity; 3) 10 mM l-arginine to local supplement l-arginine; or 4) a combination of 5.0 mM (S)-(2‑boronoethyl)-l-cysteine-HCL (BEC) and 5.0 mM Nω-hydroxy-nor-l-arginine (nor-NOHA) at a rate of 2.0 μl/min to locally inhibit arginase activity. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C heating plus sodium nitroprusside administration. The response during the 42 °C local heating plateau was blunted in the AA at the control site (CA: 84 ± 12 vs. AA: 62 ± 6 vs. %CVCmax; P < 0.001). This response was improved in AA at the l-arginine site (Control: 62 ± 6 vs. l-arginine: 70 ± 18%CVCmax; P < 0.05) but not in the arginase inhibited site (Control: 62 ± 6 vs. Arginase inhibited: 62 ± 13%CVCmax; P = 0.91). In addition, the AA group had an attenuated NO contribution to the plateau phase during 42 °C local heating relative to the CA group (CA: 56 ± 14 vs. AA: 44 ± 6 Δ %CVCmax; P < 0.001).

These findings suggest that 1) cutaneous microvascular function in response to local heating is blunted in young AA when compared to age-matched young CA; 2) this attenuated response is partly related to decrease in NO bioavailability in young AA; and 3) a local infusion of l-arginine, but not arginase inhibition, improves cutaneous microvascular responses to local heating in young AA relative to CA.

KEYWORDS:

African American; Blood flow; Microvascular function; Nitric oxide

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