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Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study.

ABSTRACT: Sugar substitutes are important in the dietary management of diabetes mellitus. Erythritol is a non-caloric dietary bulk sweetener that reverses endothelial dysfunction in diabetic rats. We completed a pilot study to examine the effects of erythritol on vascular function in patients with type 2 diabetes mellitus. Participants (n = 24) consumed erythritol 36 g/day as an orange-flavored beverage for 4 weeks and a single dose of 24 g during the baseline and final visits. We assessed vascular function before and after acute (2 h) and chronic (4 weeks) erythritol consumption. Acute erythritol improved endothelial function measured by fingertip peripheral arterial tonometry (0.52 ± 0.48 to 0.87 ± 0.29 au, P = 0.005). Chronic erythritol decreased central pulse pressure (47 ± 13 to 41 ± 9 mmHg, P = 0.02) and tended to decrease carotid-femoral pulse wave velocity (P = 0.06). Thus, erythritol consumption acutely improved small vessel endothelial function, and chronic treatment reduced central aortic stiffness. Erythritol may be a preferred sugar substitute for patients with diabetes mellitus.

SUBMITTER: Flint N

PROVIDER: S-EPMC4037362 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study.

Flint Nir N Hamburg Naomi M NM Holbrook Monika M Dorsey Pamela G PG LeLeiko Rebecca M RM Berger Alvin A de Cock Peter P Bosscher Douwina D Vita Joseph A JA

Acta diabetologica 20131224 3

Sugar substitutes are important in the dietary management of diabetes mellitus. Erythritol is a non-caloric dietary bulk sweetener that reverses endothelial dysfunction in diabetic rats. We completed a pilot study to examine the effects of erythritol on vascular function in patients with type 2 diabetes mellitus. Participants (n = 24) consumed erythritol 36 g/day as an orange-flavored beverage for 4 weeks and a single dose of 24 g during the baseline and final visits. We assessed vascular functi ...[more]

PMID: 24366423

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Project description:Recent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors can potentially reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2DM). However, there is little or no information on the therapeutic effects of SGLT2 inhibitors on the progression of atherosclerosis. This dapagliflozin effectiveness on vascular endothelial function and glycemic control (DEFENCE) study was designed to determine the effects of dapagliflozin, a SGLT2 inhibitor, on endothelial function in patients with early-stage T2DM.DEFENCE is a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative clinical trial. Between October 2015 and August 2016, 80 T2DM patients treated with 750 mg of metformin (hemoglobin A1c ?6.0 and <8.0%, n = 80) were enrolled and randomized to receive either 1500 mg/day metformin (the metformin group, n = 40), or 750 mg/day metformin supplemented with 5 mg/day dapagliflozin (the dapagliflozin group, n = 40), for 16 weeks. The primary endpoint was a change in flow-mediated dilation (FMD) from baseline to the end of the 16-week treatment period. The secondary outcomes include changes in indexes of glycemic control, lipid metabolism, and oxidative stress, body composition, and safety evaluation.Although FMD tended to improve only in the dapagliflozin group, ?FMD was comparable between the two groups. Analysis of patients with HbA1c >7.0% showed significant improvement of FMD in the dapagliflozin group than metformin group (P < 0.05). HbA1c, fasting plasma glucose, plasma glucagon, and body weight significantly decreased in both groups. Interestingly, urine 8-hydroxy-2'-deoxyguanosin, a biomarker of oxidative stress, was significantly lower in the dapagliflozin group than metformin group at 16 weeks (P < 0.001).Dapagliflozin add-on therapy to metformin for 16 weeks improved endothelial function, as assessed by FMD, in patients with inadequately controlled early-stage T2DM. Improvement in oxidative stress may contribute to the improvement in FMD. Trial registration University Hospital Medical Information Network Clinical Trial Registry (UMIN000018754).

Project description:Endothelial dysfunction is considered as a risk factor for cardiovascular disease, which is a consistent finding in diabetic mellitus type 2 (DMT2). First-degree relatives of DMT2 patients have a higher risk of developing DMT2 later on the life. We aimed to investigate whether impaired endothelial function exists in siblings of DMT2 patients.As endothelial function markers, plasma E-selectin, soluble inter-cellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) were measured on 27 DMT2 patients (9 m/18f; mean age: 48.48 ± 6.75 years), 28 siblings of DMT2 patients (14 m/14f; mean age: 44.54 ± 7.10 years), and 30 control subjects (18 m/12f; mean age: 44.72± 7.56 years) without any family history of diabetes. All the groups were matched by gender, age, and body mass index (BMI).Plasma levels of ET-1, sICAM-1, and E-selectin were significantly higher in the DMT2 group compared to the control group (ET-1:0.79 ± 1.63 pg/ml vs. 0.33 ± 0.08 pg/ml; PCD = 0.049, sICAM-1: 71.15 ± 27.20 ng/ml vs. 34.57 ± 22.56 ng/ml; PCD = 0.001, E-selectin: 22.45 ± 11.57 ng/ml vs. 16.28 ± 7.50 ng/ml; PCD =0.026). There was a significant difference in sICAM-1 levels between siblings (62.08 ± 26.37 ng/ml) and controls (PCS = 0.002), but not between siblings and DMT2 patients (PSD = 0.411). Moreover, a significant difference was observed in ET-1 levels between siblings (0.75 ± 1.26 pg/ml) and controls (PCS = 0.031), but not between siblings and DMT2 patients (PSD = 0.751). There was also a significant difference in E-selectin levels between DMT2 patients and siblings (16.56 ± 8.71 ng/ml; PSD =0.028); however, the difference in E-selectin levels was not statistically significant between siblings and controls (PCS = 0.919).Endothelial function markers in the siblings of DMT2 patients are increased in comparision to the control group Therefore; family history in the DMT2 patients seems to be a risk factor for endothelial function. Furthermore, endothelial dysfunction is available very early in the DMT2 patients, even before overt hyperglycemia ensues (in siblings), and may play a key role in the etiopathology of the vasculopathy associated with DMT2.

Project description:IntroductionThe objective of this study was to compare differences in glucoregulation, frequency of hypoglycemic episodes, glucose variability and lipid profiles of inpatients with poorly regulated type 1 diabetes mellitus (T1DM) after evening versus morning glargine application.MethodsEighteen patients with poorly regulated T1DM, glycated hemoglobin (Hba1c) levels ≥7% and frequent nocturnal and/or morning hypoglycemic episodes were included in this study. There was a 12-week screening phase where patients continued their usual insulin regimen and were encouraged to achieve optimal glycemic control; however, all patients maintained HbA1c values ≥7% and continued to have frequent nocturnal and/or morning hypoglycemic events and were therefore transitioned to morning application of insulin glargine for 12 weeks. The primary outcome was to investigate changes in HbA1c values 12 weeks after the transition. The secondary outcome was to evaluate the effect of transition on glucose variability, incidence of hypoglycemic episodes, insulin doses, lipid profile and weight. Data were analyzed using paired Student's t test and Pearson correlation.ResultsAfter the transition, there was no significant change in total daily dose of basal insulin (p 0.114) and the average body weight remained unchanged, while significant reduction of HbA1c was present (8.02 ± 0.5 vs. 7.4 ± 0.3%) (p < 0.01) resulting in a decrease in nocturnal and daytime hypoglycemic episodes per month per person (p < 0.01). Parameters of glucose variability (glycemic standard deviations and J-index) were also improved after transition period (p < 0.01). As for the lipid profile, increase of high-density lipoprotein cholesterol and decrease of triglycerides (p < 0.01) were noticed, while other lipid parameters remained unaffected. Furthermore, insignificant association of basal insulin dose with HbA1c values regardless of the time of administration was observed.ConclusionIn patients with poorly regulated T1DM, transition to morning application of glargine improved glucoregulation (including a decrease in HbA1c, glucose variability and number of nocturnal hypoglycemic episodes), followed by favorable changes in lipid profile without affecting body weight. These effects were associated with the time of application, but not with the insulin dose.

Project description:BACKGROUND:We report relationships between cardiovascular disease risk factors and myocardial structure, function, and scar in patients with type 1 diabetes mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. METHODS AND RESULTS:Cardiac magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus. Gadolinium cardiac magnetic resonance was also obtained in 741 patients. The mean age was 49±7 years; 52% were men; and mean duration of diabetes mellitus was 28±5 years. Associations of cardiovascular disease risk factors with cardiac magnetic resonance parameters were examined with linear and logistic regression models. History of macroalbuminuria was positively associated with left ventricular mass (by 14.8 g), leading to a significantly higher ratio of left ventricular mass to end-diastolic volume (by 8%). Mean hemoglobin A(1c) levels over the preceding 22 years were inversely associated with end-diastolic volume (-3.0 mL per unit mean hemoglobin A(1c) percent) and stroke volume (-2.3 mL per unit mean hemoglobin A(1c) percent) and positively related to the ratio of elevated left ventricular mass to end-diastolic volume (0.02 g/mL per unit). The overall prevalence of myocardial scar was 4.3% by cardiac magnetic resonance and 1.4% by clinical adjudication of myocardial infarction. Both mean hemoglobin A(1c) (odds ratio, 1.5 [95% confidence interval, 1.0-2.2] per unit) and macroalbuminuria (odds ratio, 3.5 [95% confidence interval, 1.2-9.9]) were significantly associated with myocardial scar and traditional cardiovascular disease risk factors. CONCLUSIONS:In addition to traditional cardiovascular disease risk factors, elevated mean hemoglobin A(1c) and macroalbuminuria were significantly associated with alterations in left ventricular structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00360893 and NCT00360815.

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Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study.

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Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study.

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