Artificially sweetened versus regular mixers increase gastric emptying and alcohol absorption

Background

Mixed alcoholic drinks are increasingly being consumed in “diet” varieties, which could potentially empty more rapidly from the stomach and thereby increase the rate of alcohol absorption when compared with “regular” versions containing sugar.

Methods

We studied 8 healthy males twice in randomized order. On each day, they consumed an orange-flavored vodka beverage (30 g ethanol in 600 mL), made with either “regular” mixer containing sucrose (total 478 kcal), or “diet” mixer (225 kcal).

Results

Gastric half-emptying time measured by ultrasound (mean ± standard deviation) was less for the “diet” than the “regular” drink (21.1 ± 9.5 vs 36.3 ± 15.3 minutes, P <.01). Both the peak blood ethanol concentration (0.053 ± 0.006 vs 0.034 ± 0.008 g%, P <.001) and the area under the blood ethanol concentration curve between 0 and 180 minutes (5.2 ± 0.7 vs 3.2 ± 0.7 units, P <.001) were greater with the “diet” drink.

Conclusions

Substitution of artificial sweeteners for sucrose in mixed alcoholic beverages may have a marked effect on the rate of gastric emptying and the blood alcohol response.     

High-intensity aerobic training improves endothelium-dependent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus

Background

The aim of this study is to compare the effect of physical exercise program on the endothelial function of patients with metabolic syndrome and type 2 diabetes mellitus.

Methods

Patients were randomized for high intensity aerobic training (HI: 80% maximum heart rate, n = 10), low intensity aerobic training (LI: 55% of maximum heart rate, n = 10) and control (n = 11). Before and after 6 weeks of training, subjects performed the maximal exercise test and a study of the endothelial function, through a high resolution ultrasound of the brachial artery, which was assessed after reactive hyperemia (endothelium dependent vasodilation) and nitrate administration (endothelium independent vasodilation).

Results

A total of 31 patients with metabolic syndrome and type 2 diabetes mellitus were studied, with mean age of 58 ± 6 years, The percentage diameter difference of the vessel after hyperemia was significantly higher for the high intensity group (HI before 2.52 ± 2.85% and after 31.81 ± 12.21%; LI before 3.23 ± 3.52% and after 20.61 ± 7.76%; controls before 3.56 ± 2.33% and after 2.43 ± 2.14%; p < 0.05).

Conclusions

High intensity aerobic training improved the functional capability and endothelium dependent vasodilator response, but it does not improve the endothelium independent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus.     

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome

Background and aim

Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n = 247) or absence (n = 883) of type 2 diabetes in ACS patients.

Methods and results

We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p = 0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [β (SE) = 0.17 (0.07), p = 0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not −786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the −786C/894G/4a and −786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus.

Conclusions

Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients.     

Vascular function is impaired early after the initiation of chronic cigarette smoking

Background

The aim of this study was to assess resistance artery function in short-term chronic cigarette smokers and non-smoking control subjects.

Methods

Reactive hyperemia was assessed in 19 cigarette smokers (age 23 ± 1 years) and 19 non-smokers (age 23 ± 1 years).

Results

Cigarette smokers demonstrated a 23% lower peak forearm blood flow response compared with non-smokers (15.81 ± 0.66 vs. 20.58 ± 1.26 mL/min/100 mL, p < 0.05) and a 22% lower area under the curve of the reactive hyperemia response (607 ± 51.57 vs. 775 ± 53.51 mL/min/100 mL × 3 min, p < 0.05).

Conclusions

These results indicate that smoking-induced impairments of vascular function occur early after the initiation of chronic cigarette smoking.     

Paradoxical Preservation of Vascular Function in Severe Obesity

Background

Obesity is associated with a high risk of coronary artery disease morbidity and mortality. Yet, postmortem studies have shown that severely obese subjects exhibit smooth coronary arteries, thus suggesting that they may be protected from atherosclerosis. We assessed vascular function and its possible determinants in a cohort of normal-weight to severely obese insulin-sensitive subjects (body mass index [BMI] 23.2-49 kg/m²).

Methods

Seventy-one healthy, insulin-sensitive subjects (Homeostasis Model Assessment of Insulin Resistance index <2.5), divided into normal-weight (n = 13; BMI = 23.2 ± 1.6), obese (n = 35; BMI = 32.6 ± 2.5), and severely obese (n = 23; BMI = 49.0 ± 7.9) groups, were enrolled. Vascular function was evaluated by flow-mediated dilation and carotid intima-media thickness. High-sensitivity C-reactive protein, leptin, adiponectin, vascular growth factors, and CD34+KDR+/CD133+ endothelial progenitor cells, known markers of vascular health/protection, also were measured.

Results

Flow-mediated dilation was higher in severely obese than in obese and normal-weight individuals (P = .019 and P = .011 respectively). Intima-media thickness was consistently lower in severely obese than in obese individuals (P = .040) and similar in severely obese and normal-weight individuals (P >.99). Levels of high-sensitivity C-reactive protein and leptin were higher in severely obese than in obese and normal-weight individuals (high-sensitivity C-reactive protein: P = .018 and P = .05, respectively; leptin: P <.001 for both comparisons). CD34+KDR+ endothelial progenitor cells were significantly higher in severely obese versus obese individuals (P = .039).

Conclusion

Our study demonstrates that vascular function is paradoxically better in severely obese than in obese subjects and similar to that found in normal-weight subjects. Despite higher levels of high-sensitivity C-reactive protein and leptin, severely obese individuals may be partially protected from atherosclerosis, possibly by a greater mobilization of endothelial progenitor cells.     

Indexes of β-cell function from the oral glucose tolerance test can modestly predict pancreatic β-cell area in Korean

Aims

Pancreatic β-cell function indexes have been suggested using the oral glucose tolerance test (OGTT). Here, we investigated whether β-cell function index from the OGTT reflects pancreatic β-cell area in Korean patients.

Methods

The study consisted of 45 patients who underwent pancreatectomies. Before operation, a 75-g OGTT was performed. Immunohistochemical staining was performed, and indexes of β-cell function from the OGTT data were compared with the pancreatic β-cell area.

Results

The β-cell area of the pancreas was 1.07 ± 0.33% in the normal glucose tolerance group, 1.71 ± 0.85% in the pre-diabetes group (impaired glucose tolerance and impaired fasting glucose), and 1.08 ± 0.57% in the diabetes group. The β-cell area of the pre-diabetes group was significantly higher than that of the diabetes group. Pancreatic β-cell area showed a significant correlation with a homeostasis model assessment of β-cell function (r = 0.358, P = 0.016), disposition index (r = 0.336, P = 0.024), fasting glucose (r = −0.359, P = 0.015), and the C-peptide/glucose 30 min ratio (r = 0.319, P = 0.035).

Conclusions

Some parameters of β-cell function from the OGTT showed a significant relationship with the β-cell area of pancreas.     

Platelet activation after stenting with heparin-coated versus noncoated stents

Background

In animal models, heparin coating reduces platelet accumulation induced by coronary stenting. However, reduced platelet activation has never been demonstrated in humans. The purpose of the current study was to investigate the effect of heparin coating on platelet activation after coronary artery stenting.

Methods

In a prospective, randomized, pilot study of 50 consecutive elective patients, platelet activation was analyzed by measuring aggregation and surface receptor expression before and at 2 hours, 24 hours, 5 days and 30 days after implantation of either heparin-coated or noncoated stents .

Results

There was less platelet activation after implantation of a heparin-coated stent, as indicated by reduced expression at 24 hours of active glycoprotein (GP) IIb/IIIa (10.3 ± 6.1 vs 6.7 ± 2.1, P = .014), and total GP IIb/IIIa (382 ± 101 vs 306 ± 88, P = .01). A trend at 30 days poststenting of lower total (383 ± 150 vs 296 ± 86, P = .07) and active GP IIb/IIIa expression (10.3 ± 6.9 vs 7.5 ± 2.9, P = .15) was also observed with the heparin-coated stent). Aggregation and stimulated p-selectin did not differ between stent types.

Conclusion

Use of a heparin-coated stent in this pilot study of elective patients was associated with primarily less early platelet expression of GP IIb/IIIa. These findings have implications on the risk of subacute thrombosis and deserve further investigation.     

Modified clopidogrel loading dose according to platelet reactivity monitoring in patients carrying ABCB1 variant alleles in patients with clopidogrel resistance

Objectives

The aim of the present study was to investigate the impact of a adjusted clopidogrel loading dose (LD) according to platelet reactivity index in carriers of ABCB1 mutant allele undergoing percutaneous coronary intervention (PCI).

Methods

All patients met the inclusion criteria were recruited in the present study. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index. High treatment platelet reactivity (HTPR) was determined by a cut-off value of > 50%. The genetic polymorphism of ABCB1 was determined by allele-specific polymerase chain reaction (PCR). In patients carrying ABCB1 and HTPR after a first 300-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 300-mg LDs to obtain a VASP index < 50%. The rate of major adverse cardiovascular events (MACE) and major or minor bleeding in one month were recorded.

Results

536 patients were included in the present study. One hundred seventy-two patients (32%) carried ABCB1 mutant allele (11 homozygotes [2%] and 161 heterozygotes [30%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild allele (65.5 ± 13.8% vs. 47.6 ± 21.8%; p < 0.001). Of the 172 ABCB1 mutant allele carriers, 130 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (66.9 ± 12.8% vs.50.2 ± 18.3%; < 0.001). Finally, dose adjustment according to platelet reactivity monitoring enabled 88% of ABCB1 mutant allele carriers and 91% of wild allele carriers exhibiting HTPR to reach a VASP index < 50%. The rate of MACE and major or minor bleeding in one-month follow-up between the wild allele carriers and the mutant allele carriers didn't differentiate significantly.

Conclusions

Increased and adjusted clopidogrel loading dose according to platelet reactivity monitoring attenuated clopidogrel resistance in carriers of ABCB1 mutant allele.     

Enhancement of ultrasonic thrombus imaging using novel liposomal bubbles targeting activated platelet glycoprotein IIb/IIIa complex—in vitro and in vivo study

Background

We developed perfluorocarbon gas-containing bubble liposomes (BL) with Arg-Gly-Asp (RGD) sequence-containing peptides, which bind to activated platelet glycoprotein IIb/IIIa complexes. The aim of this study was to examine the enhancing effects in ultrasonic thrombus imaging using these targeted BL in vitro and in vivo.

Methods

Liposomes composed of phosphatidylcholine and cholesterol were manufactured, and RGD peptide was attached by a covalent coupling reaction. Sonication was used to conjugate liposomes and perfluorocarbon gas, which formed targeted BL. In vitro, targeted BL were mixed with whole blood, which was allowed to coagulate while being shaken and rotated. In vivo, we administered targeted BL to 10 rabbits with acute thrombotic occlusions in the ilio-femoral artery. Thrombi were imaged using a 7.5-9 MHz linear transducer and a conventional ultrasound machine, and by scanning electron microscopy. Ultrasound images were digitized, and mean pixel gray-scale level (black = 0, white = 255) was measured.

Results

In vitro, mean pixel gray-scale level of the thrombi in targeted BL group was significantly higher than in control and non-targeted BL groups (93 ± 26 vs. 58 ± 16, 48 ± 9, p = 0.002, n = 10). Scanning electron microscopy revealed large amounts of targeted BL attached to the thrombi. In vivo, mean pixel gray-scale level of the thrombi with targeted BL was significantly higher (33.2 ± 6.4 vs. 24.8 ± 8.5, p = 0.0051, n = 10) than that before targeted BL administration.

Conclusions

Perfluorocarbon gas-containing BL with RGD peptide represent a novel echo contrast agent, which can markedly enhance ultrasonic thrombus imaging in vitro and in vivo, and may be useful for noninvasively diagnosing acute thrombotic vessel occlusion.     

24-hour antiplatelet effect of aspirin in patients with previous definite stent thrombosis

Objective

Once-daily aspirin is standard treatment, but recent studies point towards increased platelet function at the end of the dosing interval. Stent thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so we investigated if platelet inhibition by aspirin declines through 24 h in patients with previous definite ST. Furthermore, we explored whether increased levels of immature platelets and thrombopoietin are associated with a particularly rapid recovery of platelet function.

Methods

This case–control study included 50 patients with previous definite ST matched with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate^® Analyzer). Cyclooxygenase-1 activity, platelet activation, immature platelets, and thrombopoietin were measured.

Results

Platelet aggregation increased by 109 ± 150 (arachidonic acid) and 47 ± 155 (collagen) aggregation units per minute from 1 to 24 h after aspirin intake (p-values < 0.0001) with corresponding increases in thromboxane B₂ (5.6 ± 5.1 ng/ml, p < 0.0001) and soluble P-selectin (6.2 ± 15.5 ng/ml, p < 0.0001). Platelet aggregation increased equally in all groups, but patients with previous ST displayed the highest levels of platelet aggregation at 24 h (p-values ≤ 0.05) and the highest levels of immature platelets (p < 0.01) and thrombopoietin (p < 0.0001).

Conclusions

Platelet inhibition declined significantly during the 24-hour dosing interval in aspirin-treated patients with previous definite ST or stable coronary artery disease and in healthy individuals. Increased levels of immature platelets and thrombopoietin were observed in patients with previous definite ST.     

Rehabilitation: Periodic somatosensory stimulation increases arterial baroreflex sensitivity in chronic heart failure patients

Background

One of the beneficial effects of exercise training in chronic heart failure (CHF) is an improvement in baroreflex sensitivity (BRS), a prognostic index in CHF. In our hypothesis-generating study we propose that at least part of this effect is mediated by neural afferent information, and more specifically, by exercise-induced somatosensory nerve traffic.

Objective

To compare the effects of periodic electrical somatosensory stimulation on BRS in patients with CHF with the effects of exercise training and with usual care.

Methods

We compared in stable CHF patients the effect of transcutaneous electrical nerve stimulation (TENS, N = 23, LVEF 30 ± 9%) with the effects of bicycle exercise training (EXTR, N = 20, LVEF 32 ± 7%). To mimic exercise-associated somatosensory ergoreceptor stimulation, we applied periodic (2/s, marching pace) burst TENS to both feet. TENS and EXTR sessions were held during two successive days.

Results

BRS, measured prior to the first intervention session and one day after the second intervention session, increased by 28% from 3.07 ± 2.06 to 4.24 ± 2.61 ms/mm Hg in the TENS group, but did not change in the EXTR group (baseline: 3.37 ± 2.53 ms/mm Hg; effect: 3.26 ± 2.54 ms/mm Hg) (P(TENS vs EXTR) = 0.02). Heart rate and systolic blood pressure did not change in either group.

Conclusions

We demonstrated that periodic somatosensory input alone is sufficient and efficient in increasing BRS in CHF patients. This concept constitutes a basis for studies towards more effective exercise training regimens in the diseased/impaired, in whom training aimed at BRS improvement should possibly focus more on the somatosensory aspect.     

Targeting dietary fat or glycemic load in the treatment of obesity and type 2 diabetes: a randomized controlled trial

Aims

To compare the effects of lifestyle modification programs that prescribe low-glycemic load (GL) vs. low-fat diets in a randomized trial.

Methods

Seventy-nine obese adults with type 2 diabetes received low-fat or low-GL dietary instruction, delivered in 40-week lifestyle modification programs with identical goals for calorie intake and physical activity. Changes in weight, HbA_1c, and other metabolic parameters were compared at weeks 20 and 40.

Results

Weight loss did not differ between groups at week 20 (low-fat: −5.7 ± 3.7%; low-GL: −6.7 ± 4.4%, p = .26) or week 40 (low-fat: −4.5 ± 7.5%; low-GL: −6.4 ± 8.2%, p = .28). Adjusting for changes in antidiabetic medications, subjects on the low-GL diet had larger reductions in HbA_1c than those on the low-fat diet at week 20 (low-fat: −0.3 ± 0.6%; low-GL: −0.7 ± 0.6%, p = .01), and week 40 (low-fat: −0.1 ± 1.2%; low-GL: −0.8 ± 1.3%; p = .01). Groups did not differ significantly on any other metabolic outcomes (p ≥ .06).

Conclusions

Results suggest that targeting GL, rather than dietary fat, in a low-calorie diet can significantly enhance the effect of weight loss on HbA_1c in patients with type 2 diabetes.     

Incretin secretion is not restored by short-term strict glycaemic control in Korean hyperglycaemic patients with type 2 diabetes

Aims

To determine whether short-term strict glycaemic control could restore incretin secretion in type 2 diabetic patients. The factors associated with incretin levels were also investigated.

Methods

A meal tolerance test (MTT) was performed in eighteen poorly controlled (pDM) and fifteen well controlled (wDM) diabetic patients. Fourteen patients in the pDM group underwent follow-up MTT after strict glycaemic control. The secretions of intact glucagon-like peptide-1 (iGLP-1) and total glucose-dependent insulinotropic polypeptide (tGIP) during MTT were calculated by total and incremental area under the curve (TAUC and IAUC) values.

Results

Posttreatment HbA1c level was significantly improved in the pDM group (11.2 ± 0.9 to 7.9 ± 0.9%). However, the secretion of incretin hormones was not increased in the posttreatment pDM group (TAUCiGLP-1, 3612 ± 587 to 2916 ± 405 pmol/L min; TAUCtGIP, 9417 ± 1099 to 8338 ± 903 pmol/L min). IAUCiGLP-1 was negatively correlated (r = −0.446, P = 0.011) and independently associated (β = −137.2, P = 0.027) with insulin resistance assessed by homeostasis model assessment.

Conclusions

Incretin secretion is not restored by short-term strict glycaemic control. Decreased incretin secretion seems to develop early in the course of type 2 diabetes with increasing insulin resistance, but not to be influenced by glycaemic status.     

Impairment of autonomic reactivity is a feature of heart failure whether or not the left ventricular ejection fraction is normal

Background

Autonomic dysfunction (AD) is associated with morbidity and mortality in patients with systolic heart failure (SHF). The extent of AD when LV ejection fraction is preserved (HF-NEF), is unclear. Our objectives were: 1) quantitative assessment of autonomic function in SHF and HF-NEF; and 2) exploration of relationships among AD, symptoms and cardiac function.

Methods

This was an observational study of patients newly referred from primary care with a heart failure diagnosis; 21 SHF, 20 HF-NEF patients and 21 normal subjects were recruited. All subjects underwent clinical evaluation, 6-minute walk test (6MWT), Minnesota Questionnaire (MLWHFQ) and echocardiography. Autonomic assessment included haemodynamic responses to standing, deep breathing and handgrip. Concomitant blood pressure variability (BPV) and heart rate variability (HRV) parameters were also derived.

Results

There were significant differences in all haemodynamic responses between SHF, HF-NEF and normal. Log transformed (ln) low frequency spectral component of BPV was lower in SHF (4.1 ± 0.3) than HF-NEF (4.2 ± 0.4) and normal (4.4 ± 0.1; p = 0.001 SHF vs HF-NEF and vs normal). Ln LF/HF was greater in normal than HF-NEF and SHF (1.5 ± 0.7 vs 0.9 ± 1.0 vs 0.6 ± 0.6; p = 0.003). Autonomic modulations correlated negatively with severity of heart failure.

Conclusions

Autonomic responses in heart failure were blunted and the attenuation of responses correlated strongly with symptomatic and functional markers of disease severity. Autonomic dysfunction is a feature of the heart failure syndrome but is not dependent on ejection fraction.     

Effects of 2 different antiplatelet regimens with abciximab or tirofiban on platelet function in patients undergoing coronary stenting

Background

We sought to compare the antiplatelet effects of the glycoprotein IIb-IIIa receptor blockers abciximab or tirofiban, combined with an adjuvant therapy with clopidogrel and aspirin.

Study design and methods

Twenty patients undergoing coronary stenting were randomly assigned to receive either abciximab or tirofiban combined with aspirin and clopidogrel. Serial blood samples were taken to assess platelet aggregation, P-selectin expression, thrombin generation, and platelet-induced endothelial cell expression of MCP-1, uPAR, and ICAM-1.

Results and conclusions

The therapy with aspirin plus clopidogrel attenuated agonist-induced platelet aggregation and P-selectin surface exposure (P < .05 vs aspirin monotherapy). Both tirofiban and abciximab further reduced agonist-induced platelet aggregation (P < .05), and decreased thrombin generation but had no effect on platelet α-granule release. None of the antithrombotic strategies significantly affected platelet-induced endothelial cell activation. Since platelet adhesion/degranulation initiates an inflammatory/mitogenic response in the vascular wall, future therapeutic strategies will have to be aimed at the inhibition of platelet release reactions.     

Feasibility of group lifestyle intervention for diabetes prevention in Arab Americans

Aims

To assess the feasibility and acceptability of a community-based, culturally-specific, Diabetes Prevention Program (DPP)-adapted, group lifestyle intervention in Arab-Americans.

Methods

Overweight (BMI ≥ 27 kg/m²) Arab-Americans aged ≥30 years and without a history of diabetes were recruited to participate in a 24-week group lifestyle intervention. The DPP core-curriculum was culturally rewritten, translated into Arabic, and delivered in weekly sessions over a 12-week period. Follow-up was performed at week-24. The primary goals were to achieve ≥7% weight loss and ≥150 min/week of physical activity. An intent-to-treat analysis was performed.

Results

Of the 71 participants (mean age ± SD 47 ± 10 years, 38% males), 44% achieved ≥7% weight loss, 59% achieved ≥5% reduction in weight, and 78% reached the physical activity goal of ≥150-min/week. The mean ± SD weight loss was 5.2 ± 4.4 kg at week-24 (p < 0.0001), Marked reduction in body measurements, daily energy and fat intake were noted. Retention was high with 86% completing the intervention.

Conclusions

This trial demonstrates that a culturally-specific, DPP-adapted, group lifestyle intervention implemented in a community setting is feasible and effective in Arab-Americans.     

Evaluation of the Finnish Diabetes Risk Score as a screening tool for impaired fasting glucose, impaired glucose tolerance and undetected diabetes

Aim

To evaluate the performance of FINDRISC as a screening tool for prediabetes - impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and undetected diabetes (UDD) in subjects at risk of developing diabetes.

Subjects and methods

2169 subjects with at least one risk factor for diabetes completed the FINDRISC questionnaire and underwent an oral glucose tolerance test. FINDRISC performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC).

Results

56.6% of subjects demonstrated normal glucose tolerance (NGT), 14.5% - IFG, 11.4% - IGT and 17.5% - UDD. NGT group demonstrated mean FINDRISC 10.1 ± 3.4, IFG group - 13.8 ± 4.3 (p < 0.0001 vs. NGT), IGT group - 14.4 ± 5.4 (p < 0.0001 vs. NGT) and UDD group - 15.5 ± 4.8 (p < 0.0001 vs. NGT and IFG, p < 0.01 vs. IGT). The AUC-ROC was 0.70 (95% CI 0.67-0.73) for UDD and 0.71 (95% CI 0.69-0.73) for undetected prediabetes and diabetes. The FINDRISC cut-off value of 10 to identify both prediabetes and diabetes had sensitivity of 84% and specificity of 61%.

Conclusions

FINDRISC is a feasible, non-invasive and useful tool for identifying subjects at risk for undetected diabetes and prediabetes. Laboratory screening should be performed in subjects with FINDRISC higher than 10.     

Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients

Aim

Advanced research has radically changed both diagnosis and treatment of diabetes during last three decades; a number of classes of oral antidiabetic agents are currently available for better glycemic control. Present study aims to evaluate the effect of metformin on different stress and inflammatory parameters in diabetic subjects.

Methods

208 type 2 diabetes patients were randomly assigned for metformin and placebo.

Results

Reactive oxygen species generation, advanced oxidation protein products (179.65 ± 13.6, 120.65 ± 10.5 μmol/l) and pentosidine (107 ± 10.4, 78 ± 7.6 pmol/ml) were found to be reduced by metformin treatment compared to placebo. On the other hand metformin administration enhanced total thiol and nitric oxide level (p < 0.05). But nutrient level (Mg⁺², Ca⁺²) in plasma was not altered by the treatment. Significant restoration of C reactive protein (p < 0.05) was noticed after metformin therapy. Metformin administration also improved Na⁺K⁺ATPase activity (0.28 ± 0.08, 0.41 ± 0.07 μmol Pi/mg/h) in erythrocyte membrane.

Conclusions

This study explores that metformin treatment restores the antioxidant status, enzymatic activity and inflammatory parameters in type 2 diabetic patients. Metformin therapy improves the status of oxidative and nitrosative stress altered in type 2 diabetes. This study unfolds the cardio protective role of metformin as an oral hypoglycemic agent.     

Melatonin reduces night blood pressure in patients with nocturnal hypertension

Purpose

Nocturnal hypertension is associated with a high risk of morbidity and mortality. A blunted nocturnal surge in melatonin excretion has been described in nondipping hypertensive patients. We therefore studied the potency of melatonin to reduce nighttime blood pressure (BP) in treated hypertensive patients with nocturnal hypertension.

Patients and Methods

Thirty-eight treated hypertensive patients (22 males, mean age 64 ± 11 years) with confirmed nocturnal hypertension (mean nighttime systolic BP >125 mm Hg), according to repeated 24-hour ambulatory blood pressure monitoring (ABPM), were randomized in a double-blind fashion to receive either controlled release (CR)-melatonin 2 mg or placebo 2 hours before bedtime for 4 weeks. A 24-hour ABPM was then performed.

Results

Melatonin treatment reduced nocturnal systolic BP significantly from 136 ± 9 to 130 ± 10 mm Hg (P = .011), and diastolic BP from 72 ± 11 to 69 ± 9 mm Hg (P = .002), whereas placebo had no effect on nocturnal BP. The reduction in nocturnal systolic BP was significantly greater with melatonin than with placebo (P = .01), and was most prominent between 2:00 am and 5:00 am (P = .002).

Conclusions

Evening CR-melatonin 2 mg treatment for 4 weeks significantly reduced nocturnal systolic BP in patients with nocturnal hypertension. Thus, an addition of melatonin 2 mg at night to stable antihypertensive treatment may improve nocturnal BP control in treated patients with nocturnal hypertension.     

Does Vitamin D Modulate Asymmetric Dimethylarginine and C-Reactive Protein Concentrations?

Background

Vitamin D deficiency is associated with significant increases in the incidence of cardiovascular risk factors and mortality. However, the mechanisms underlying this association remain unclear. The current study evaluated the possible relationships among vitamin D status, endothelial dysfunction, and inflammation.

Methods

Plasma concentrations of 25-hydroxyvitamin D₃ were determined by radioimmunoassay in a normal population cohort (n = 253) aged 51 to 77 years (mean 63.4 ± 6 years). Asymmetric dimethylarginine, a marker/mediator of endothelial dysfunction, was assayed by high-performance liquid chromatography. High-sensitivity C-reactive protein levels were used as a marker of inflammatory activation.

Results

On univariate analyses, low 25-hydroxyvitamin D₃ levels were inversely correlated with asymmetric dimethylarginine concentrations, high-sensitivity C-reactive protein levels, and body mass index. Seasonal fluctuations in 25-hydroxyvitamin D₃ levels were associated with reciprocal asymmetric dimethylarginine concentration fluctuations. Hypertension and treatment with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker also were associated with low 25-hydroxyvitamin D₃ levels. On multiple linear analysis, both asymmetric dimethylarginine (β = −0.19, P = .003) and high-sensitivity C-reactive protein (β = −0.14, P = .03) concentrations were inversely correlated with plasma 25-hydroxyvitamin D₃ concentrations; other significant correlates were male gender (β = 0.19, P = .003), calcium levels (β = 0.14, P = .03), and use of angiotensin-converting enzyme inhibitor (β = −0.17, P = .007).

Conclusion

Low 25-hydroxyvitamin D₃ levels are associated with markers of endothelial dysfunction and inflammatory activation, representing potential mechanisms for incremental coronary risk.