A study on serum advanced glycation end products and its association with oxidative stress and paraoxonase activity in type 2 diabetic patients with vascular complications

ObjectivesEnhanced formation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions has been linked to diabetes mellitus (DM) associated complications. We investigated the clinical relevance of estimating AGEs and their relationship with oxidative stress (OS) and paraoxonase (PON1) activity in type 2 DM (T2DM) in relation to development of vascular complications.Design and MethodsSerum AGEs along with PON1 activity, protein carbonyl (PCO), advanced oxidation protein products (AOPP), lipid peroxidation (MDA), and total thiol (T-SH) were determined in 157 T2DM patients (DM without complications n = 57, DM micro-vascular complications n = 53, DM macro-vascular complications n = 47) and 40 healthy controls.ResultsSerum AGE level increased significantly in various study groups in following manner: healthy control < DM without complications < DM-macro < DM-micro. Logistic regression analysis using diabetic complications as dependent variable showed significant association with AGE level and PON1 activity even after adjustment for confounding factors. Receiver-operating-characteristics curve analysis showed that 2-fold increased in glycation and 50% decrease in PON1 activity may lead to development of vascular complications in diabetic subjects. PCO, AOPP and MDA were higher and PON1 activity was lower in T2DM with complications than those without complications. Among diabetic patients AGEs showed significant positive correlation with HbA_1C, MDA, AOPP, and negative correlation with PON1 activity and T-SH.ConclusionHigh serum AGE concentration and low PON1 activity may be considered as additional risk factor for development of vascular complications in T2DM. AGE formation plays significant role in induction of OS in diabetes.     

The plasma levels of relaxin-2 and relaxin-3 in patients with diabetes

ObjectivesRelaxin-2 has been found to alleviate fibrosis in experimental diabetic cardiomyopathy. In addition, the levels of serum relaxin-3 were increased and correlated with all the component traits of metabolic syndrome. We investigated the levels of plasma relaxin-2 or relaxin-3 and their relationship to component traits in patients with diabetes.Design and methodsWe studied 33 newly diagnosed type 2 diabetes patients and 38 age-matched healthy subjects. Blood samples were taken at study entry, and relaxin-3, relaxin-2, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, serum insulin and hemoglobin A_1c (HbA_1c) levels were measured.ResultsRelaxin-2 levels were significantly lower in patients with diabetes than in controls: the median plasma relaxin-2 concentration was 34.68 pg/mL (range, < 29.00–50.81 pg/mL) in patients with diabetes and 45.80 pg/mL (range, < 37.42–54.46 pg/mL) in controls (p = 0.0150). However, no differences in relaxin-3 levels were observed between the diabetes group and controls (p = 0.6550). The plasma levels of relaxin-2 or relaxin-3 were not correlated with systolic blood pressure (BP), diastolic BP, total cholesterol, LDL-C, HDL-C, triglyceride, fasting blood glucose, fasting insulin and HbA_1c in patients with diabetes. Additionally, there was no correlation between the plasma concentrations of relaxin-2 and relaxin-3 in patients with diabetes (r_s = 0.225; p = 0.208).ConclusionsWe conclude that the plasma levels of relaxin-2 in diabetes patients were lower than in controls, however, there are no difference in plasma relaxin-3 concentrations between controls and patients with diabetes. Relaxin-2 or relaxin-3 levels are not related to component traits in patients with diabetes.     

Usefulness of glycated albumin as an indicator of glycemic control status in patients with hemolytic anemia

BackgroundIn patients with hemolytic anemia (HA), glycated hemoglobin (HbA_1C) presents lower values in relation to glycemia because the lifespan of erythrocytes is shortened, whereas glycated albumin (GA) is not affected. In the present study, we examined the usefulness of GA as an indicator of glycemic control status in patients with HA.MethodsWe enrolled 21 patients with HA. A total of 202 patients with type 2 diabetes mellitus (T2DM) without complications were used as controls.ResultsWe identified a significant correlation between GA and HbA_1C in the patients with HA. However, in a comparison between the patients with HA and those with T2DM, the regression line showed a leftward shift in the former group. There was a significant positive correlation between hemoglobin (Hb) and HbA_1C in the patients with HA (R = 0.541, p = 0.025), although there was no significant correlation between Hb and GA. There was an inverse correlation between Hb levels and GA/HbA_1C ratio (R = ? 0.710, p = 0.001). The measured HbA_1C levels were lower than the HbA_1C levels estimated from mean plasma glucose levels, whereas the GA/3 levels were close to the estimated HbA_1C levels.ConclusionsGA is a useful indicator of glycemic control status in patients with HA.     

The evaluation of IL-12 concentration,PAF-AH,and PLA2 activity in patients with type 1 diabetes treated with intensive insulin therapy

ObjectivesThe aim of the study was to evaluate the concentration of interleukin 12 (IL-12), the activity of phospholipase A₂ (PLA₂), and platelet-activating factor acetylhydrolase (PAF-AH) in type 1 diabetes (DM1) patients treated with intensive insulin therapy.Design and methodsStudied parameters were measured in 81 patients, who were subdivided according to the HbA₁c value, hsCRP concentration, and presence or absence of late complications.ResultsPAF-AH activity was higher in the DM1 patients versus the control group (P = 0.042). IL-12 concentration was the highest in subgroup with ≥ 3 mg/L hsCRP (P < 0.05). Negative correlations were found for the IL-12 and age of patients and for apo A–I in the subgroup with poor metabolic control. In addition, positive correlation for hsCRP and PAF-AH activity in the subgroup with ≥3 mg/L CRP (P < 0.05) was also found.ConclusionsPAF-AH and IL-12 appear to be implicated in the development of a chronic inflammation in DM1. In addition, our results emphasize a protective role of apo A–I against an increase in IL-12 production.     

Relationship between genetic polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase as risk factors for type 2 diabetes in Tunisian patients

Background/aimsThe role of methylenetetrahydrofolate reductase (MTHFR) and angiotensin-converting enzyme (ACE) gene polymorphisms as being risk factors for diabetes is still controversial. The aim was to investigate the distribution of ACE and MTHFR genotypes as well as to evaluate the role of plasmatic total homocysteine levels (tHcy) and ACE activity in Tunisian patients with type 2 diabetes mellitus (T2DM).Design and methods115 T2DM patients compared to 116 healthy volunteers.ResultsThe ACE I/D polymorphism was significantly associated with diabetes (p < 0.0001). The DD genotype and D allele were more frequent in patients compared to control group [DD: OR = 4.93; p < 0.0001; 95 % CI: 2.71–8.97; D: OR = 3.08, 95% CI: 2.09–4.51 p < 0.0001]. MTHFR allele and genotype frequencies did not differ between patients and controls. The susceptibility to diabetes in individuals with genotypes DD +vTT was 13.39 and in the individuals with DD + CT was 6.57 times that of the controls. However, individuals with genotypes ID + CC or II + CT have a protective effect against diabetes. The DD and TT genotypes were associated with significantly higher ACE activity and tHcy levels in diabetics.ConclusionOur data suggest that ACE ID polymorphism may act synergistically with MTHFR C677T polymorphism to assess diabetes risk.     

Plasma visfatin and retinol binding protein-4 levels in patients with type 2 diabetes mellitus and their relationship to adiposity and fatty liver

ObjectivesWe investigated whether plasma visfatin and binding protein-4 (RBP-4) levels correlate with obesity and type 2 diabetes mellitus (T2DM).Design and methodsTwo groups were enrolled: Group 1: 40 patients with T2DM and Group 2: 40 age- and gender-matched healthy controls. Both groups were subdivided according to body mass index (BMI) into non-obese (BMI < 25 kg/m²) and obese subjects (BMI ≥ 30 kg/m²) (20 each).ResultsPlasma visfatin and RBP-4 levels were significantly increased in T2DM patients compared with controls with similar BMI values (for both p < 0.001). Plasma visfatin and RBP-4 concentrations correlated with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin resistance (HOMA_IR). Visfatin and RBP-4 correlated with visceral fat and liver fat in diabetic patients (for both p < 0.001).ConclusionVisfatin level was increased in T2DM, possibly related to hyperglycemia. Plasma RBP-4 correlated positively with liver fat and HOMA_IR which may reflect its effects on hepatic insulin sensitivity.     

HDL 2 Particles are associated with hyperglycaemia,lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients

ObjectivesIn this study we examined the relationship of oxidative stress and hyperglycaemia to antioxidative capacity of high-density cholesterol (HDL-C) particles in type 2 diabetes mellitus (DM).Design and methodsOxidative stress status parameters (superoxide anion (O₂^?), superoxide dismutase (SOD) activity and paraoxonase (PON1) status were assessed in 114 patients with type 2 DM and 91 healthy subjects. HDL particle diameters were determined by non-denaturing polyacrylamide gradient (3–31%) gel electrophoresis.ResultsPatients had significantly higher concentrations of oxidative stress parameter O₂^?(p < 0.001) and antioxidative defence, SOD activity (p < 0.001). Paraoxonase activity was significantly lower in diabetics (p < 0.001). The PON1₁₉₂ phenotype distribution among study groups was not significantly different. HDL 3 phenotype was significantly prevalent among patients (p < 0.001). Paraoxonase activity was significantly lower in patients with predominantly HDL 2 particles than in controls.ConclusionsThe results of our current study indicate that the diabetic HDL 2 phenotype is associated with hyperglycaemia, lower PON1 activity and elevated oxidative stress.     

Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance

ObjectivesThe aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance.Design and methodsWe studied 112 patients with T2DM and 80 age- and gender-matched control subjects.ResultsSerum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5 ± 5.2 ng/mL vs. 20.0 ± 7.3 ng/mL, P < 0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males (P < 0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) (ρ = 0.458, P < 0.05) and HOMA-R (ρ = 0.444, P < 0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI (F = 5.294, P < 0.05) in female patients with diabetes.ConclusionsThese findings suggest that BDNF may contribute to glucose metabolism.     

Association of vascular indices with novel circulating biomarkers as prognostic factors for cardiovascular complications in patients with type 2 diabetes mellitus

BackgroundThe pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The association of vascular indices with circulating biomarkers of inflammation and insulin resistance and their role in the long-term cardiovascular prognosis in T2DM patients were currently investigated.Patients and methodsPatients with T2DM and poor glycemic control without known cardiovascular diseases (n = 119) at baseline were enrolled and followed for about 9 years. The end-point was the occurrence of any cardiovascular event (coronary heart disease, stroke, peripheral artery disease or cardiovascular death). Aortic pulse wave velocity (PWV), augmentation index (AIx), brachial flow-mediated dilation (FMD), hsCRP, Chitinase-3-like protein 1 (YKL-40), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Fatty Acid Binding Protein (FABP-4) were assessed.ResultsHigher YKL-40 and NGAL were associated with higher PWV, while higher YKL-40 and FABP-4 were related to higher AIx (p < 0.05 for all). In univariate Cox regression analysis, PWV > 10 m/s, YKL-40 > 78 ng/ml and NGAL > 42 ng/ml were associated with cardiovascular events (p < 0.05 for all). In multivariate analysis, after adjusting for classical risk factors and glycemic control, increased NGAL, YKL-40 and PWV and decreased FMD (i.e. ≤ 2.2%) (p < 0.05 for all) were independently associated with cardiovascular events.ConclusionIn T2DM patients without established cardiovascular disease, novel indices of vascular inflammation (NGAL and YKL-40) were associated with subclinical atherosclerosis (arterial stiffness) but also with adverse clinical prognosis. Arterial stiffness and endothelial dysfunction were also independently related to adverse prognosis.     

Correlations of creatine and six related pyrimidine metabolites and diabetic nephropathy in Chinese type 2 diabetic patients

ObjectivesThe assessment of the clinical significance of creatine, cytosine, cytidine, uridine, thymine, thymidine, and 2′-deoxyuridine concentrations in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between pyrimidine metabolites and disease.Design and methodsThe study group consisted of 119 subjects, which were divided to three groups: control (n = 31), type 2 diabetes without nephropathy (DM, n = 23), and with nephropathy (DN, n = 65). Levels of related metabolites were measured in plasma of all participants.ResultsThere is a significant increase in levels of cytosine (P < 0.001), cytidine (P < 0.001), and thymidine (P = 0.016) with DN compared to DM. The levels of uridine, thymine, 2′-deoxyuridine, and creatine did not change.ConclusionsThe levels of cytosine, cytidine, and thymidine may be useful for monitoring the progression of DM and evaluating the treatment.     

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.Design and methodsThe MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP.ResultsThe possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p = 0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p = 0.027, and p = 0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p < 0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR = 4.73, p = 0.01).ConclusionBoth MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.     

Gingival crevicular fluid PGE2, IL-1beta, t-PA, PAI-2 levels in type 2 diabetes and relationship with periodontal disease

ObjectivesTo evaluate if type 2 diabetes mellitus increase gingival crevicular fluid (GCF) levels of prostaglandin E₂ (PGE₂), interleukin-1beta (IL-1ß), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-2 (PAI-2).Design and methodsSeventeen type 2 diabetic patients with periodontal disease (DM), 17 otherwise healthy periodontally diseased patients (PD) and 17 systemically and periodontally healthy control subjects (H) were enrolled. Clinical periodontal measurements were recorded at six sites/tooth. GCF samples were analyzed by ELISA. Data were tested by statistical tests.ResultsDM group revealed lower IL-1ß levels than PD group (p < 0.01). PGE₂, t-PA and PAI-2 levels were similar in DM and PD groups (p > 0.05). PGE₂, t-PA levels were higher in DM and PD groups than H group (p < 0.05). PAI-2 level was higher in DM group than H group (p < 0.05). GCF total amount of PGE₂ in DM group exhibited significant correlations with all clinical periodontal measurements (p < 0.05).ConclusionType 2 diabetes in this study seems not to increase GCF levels of the evaluated inflammatory mediators.     

Plasma advanced glycation endproduct,methylglyoxal-derived hydroimidazolone is elevated in young,complication-free patients with Type 1 diabetes

ObjectivesElevated advanced glycation endproducts (AGEs) are implicated in diabetic complications. Methylglyoxal-derived hydroimidazolone (MG-H) is one of the most abundant AGEs in vivo. Our objective was to develop a time-saving, specific method to measure free MG-H in plasma and determine its levels in complication-free young individuals with Type 1 diabetes (T1DM). The relationship of plasma free MG-H to hemoglobin A1C (A1C) and plasma methylglyoxal levels was also determined.Design and methodsA solid phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, and free plasma MG-H levels were measured in 40 T1DM patients (DM group), aged 6–21 years, and 11 non-diabetics (ND group), 6–22 years. Methylglyoxal was measured using LC-MS/MS and A1C by a Tosoh G7 high-performance liquid chromatograph.ResultsOur method showed high recovery, sensitivity and short run-time. Plasma free MG-H (nmol/L) was higher (p < 0.001) in the DM group (1318 ± 569; mean ± standard deviation) as compared to the ND group (583 ± 419). Within the DM group, plasma free MG-H did not correlate with plasma methylglyoxal or A1C.ConclusionsOur LC-MS/MS method to measure free MG-H in plasma may be useful for future clinical application. The increased levels of free MG-H observed in individuals with TIDM are not merely the result of short term changes in glucose or methylglyoxal, but may reflect long-term alterations to tissue proteins.     

Increased large VLDL and small LDL particles are related to lower bilirubin in Type 2 diabetes mellitus

ObjectivesBilirubin may protect against atherosclerotic cardiovascular disease by virtue of its anti-oxidative properties, but lower bilirubin may also be associated to atherogenic lipoprotein abnormalities. We determined associations of plasma (apo)lipoproteins and lipoprotein subfractions in subjects with and without type 2 diabetes mellitus (T2DM).Design and methodsPlasma (apo)lipoproteins, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and serum total bilirubin levels were determined in 53 T2DM patients and in 53 non-diabetic subjects.ResultsTriglycerides, large VLDL, small LDL and small HDL particles were increased (all p < 0.05), whereas HDL cholesterol, apoA-I and large HDL particles were decreased (all p < 0.05), coinciding lower bilirubin levels in T2DM (p < 0.001). In age- and sex-adjusted analysis, total cholesterol, non-HDL cholesterol, triglycerides, apoB, apoE, large VLDL and small LDL were negatively correlated with bilirubin, but HDL cholesterol was positively correlated with bilirubin in T2DM (p < 0.05 to p < 0.001). Multivariable linear regression analyses demonstrated that in all subjects combined total cholesterol, non-HDL cholesterol, triglycerides and apoE were negatively associated with bilirubin after adjustment for age, sex, T2DM, body mass index and alanine aminotransferase (all p < 0.05). Further multivariable linear regression analysis showed that large VLDL and small LDL particles were negatively associated with bilirubin, whereas large HDL particles were associated positively with bilirubin (p < 0.05).ConclusionsIncreased triglycerides, as well as large VLDL and small LDL particles are associated negatively, whereas HDL cholesterol is associated positively with bilirubin in T2DM. The proposed pro-atherogenic effects of low bilirubin could in part be attributed to relationships with abnormalities in (apo)lipoproteins and lipoprotein subfraction characteristics.     

Design features of the Diabetes and Periodontal Therapy Trial (DPTT): A multicenter randomized single-masked clinical trial testing the effect of nonsurgical periodontal therapy on glycosylated hemoglobin (HbA1c) levels in subjects with type 2 diabetes and chronic periodontitis

BackgroundEvidence suggests that periodontitis is associated with prevalent and incident type 2 diabetes mellitus (T2DM), raising the question of whether periodontitis treatment may improve glycemic control in patients with T2DM. Meta-analyses of mostly small clinical trials suggest that periodontitis treatment results in a modest reduction in glycosylated hemoglobin (Hb) A1c.PurposeThe purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if periodontal treatment reduces HbA1c in patients with T2DM and periodontitis.MethodsDPTT was a phase-III, single-masked, multi-center, randomized trial with a planned enrollment of 600 participants. Participants were randomly assigned to receive periodontal treatment immediately (Treatment Group) or after 6 months (Control Group). HbA1c values and clinical periodontal measures were determined at baseline and 3 and 6 months following randomization. Medication usage and dosing were assessed at each visit. Periodontal treatment consisted of scaling and root planing for a minimum of two 90-minute sessions, plus the use of an antibacterial mouth rinse for at least 32 days afterwards. The primary outcome was change in HbA1c from baseline to 6 months and the trial was powered to detect a between-group difference of 0.6%. Secondary outcomes included changes in periodontal clinical measures, fasting plasma glucose, the Homeostasis Model Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy.ConclusionDental and medical researchers collaborated to recruit, treat and monitor participants with two chronic diseases to determine if treatment of one condition affects the status of the other.     

Insertion/insertion genotype of α2B-adrenergic receptor gene polymorphism is associated with silent myocardial ischemia in patients with type 2 diabetes mellitus

ObjectivesWe investigated whether α₂-adrenergic receptor (AR) polymorphisms (α_2A-AR, α_2B-AR and α_2C-AR gene) affected silent myocardial ischemia (SMI) in patients with type 2 diabetes mellitus (T2DM).Design and methodsGenetic polymorphisms were determined in 321 patients with T2DM and coronary artery disease (CAD). Among them, 129 patients experienced transient asymptomatic ST-depression during 24-hour ambulatory electrocardiogram (SMI group), and the remaining 192 patients who had ambulatory electrocardiogram-symptom matching angina were categorized as angina group.ResultsThe genotype distribution and allele frequencies of α_2B-AR gene polymorphism (insertion [I]/deletion[D]) exhibited significant difference between SMI group and angina group (both P < 0.05), with genotype II (34.9%) being higher in SMI group than in angina group (19.8%)(P < 0.01). Multivariable logistic regression analysis revealed that duration of diabetes and genotype II of α_2B-AR gene polymorphism were independently associated with SMI.ConclusionsHomozygote for I allele of α_2B-AR gene polymorphism is associated with SMI in T2DM patients with CAD.     

Effects of Buddhist walking meditation on glycemic control and vascular function in patients with type 2 diabetes

ObjectiveTo investigate and compare the effects of Buddhist walking meditation and traditional walking on glycemic control and vascular function in patients with type 2 diabetes mellitus.MethodsTwenty three patients with type 2 diabetes (50–75 years) were randomly allocated into traditional walking exercise (WE; n = 11) or Buddhism-based walking meditation exercise (WM; n = 12). Both groups performed a 12-week exercise program that consisted of walking on the treadmill at exercise intensity of 50–70% maximum heart rate for 30 min/session, 3 times/week. In the WM training program, the participants performed walking on the treadmill while concentrated on foot stepping by voiced “Budd” and “Dha” with each foot step that contacted the floor to practice mindfulness while walking.ResultsAfter 12 weeks, maximal oxygen consumption increased and fasting blood glucose level decreased significantly in both groups (p < 0.05). Significant decrease in HbA1c and both systolic and diastolic blood pressure were observed only in the WM group. Flow-mediated dilatation increased significantly (p < 0.05) in both exercise groups but arterial stiffness was improved only in the WM group. Blood cortisol level was reduced (p < 0.05) only in the WM group.ConclusionBuddhist walking meditation exercise produced a multitude of favorable effects, often superior to traditional walking program, in patients with type 2 diabetes.     

Impact of mulberry leaf extract on type 2 diabetes (Mul-DM): A randomized,placebo-controlled pilot study

AimsMulberry leaves have been used anecdotally in Asia to treat many disease states, including glucose abnormalities. Animal and human studies illustrate potential benefit of mulberry leaf extract (MLE) in type 2 diabetes mellitus (DM2). The purpose of this study is to evaluate the glycemic and safety effects of MLE in patients with DM2.Materials & methodsThis randomized, double-blind, placebo-controlled pilot study evaluated MLE (1000 mg standardized) versus matching placebo given three times daily with meals. Patients (n = 24) were included if they had DM2 on single or combination oral therapy with a stable hemoglobin A1C (A1C). A 2-week placebo run-in (baseline) was followed by initiation of randomized medication for 3 months. Primary endpoints were change in A1C and self-monitoring blood glucoses (SMBG). Safety was also evaluated.ResultsOf 24 patients enrolled, 17 patients completed the study. Post-prandial SMBG was significantly decreased at 3 months in the MLE group versus baseline (16.1%; p < 0.05). This improvement in post-prandial SMBG persisted when compared to placebo (18.2%; p < 0.05). A1C decreased from 7.30% at baseline to 6.94% in the MLE group but did not reach statistical significance (p = 0.079). There was no difference in A1C between MLE and placebo. A significant 15% increase occurred in serum creatinine when the MLE group was compared to baseline or placebo (p < 0.05 for both). There was no significant effect on weight, fasting SMBG, blood pressure, hypoglycemia, or other safety evaluation markers.ConclusionsThese results suggest that mulberry leaf extract may be a useful complementary mealtime glucose option for patients with DM2.ClinicalTrials.gov Identifier NCT00795704.     

GSTM1-null and GSTT1-null genotypes are associated with essential arterial hypertension in patients with type 2 diabetes

ObjectiveTo evaluate whether the genetic polymorphisms of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1), Ile105Val of the GSTP1 (rs947894), and the Val16Ala polymorphism of the MnSOD (rs4880) are associated with essential arterial hypertension (EAH) in Caucasians with type 2 diabetes.Design and methods1015 Slovenian subjects (Caucasians) with type 2 diabetes with/without EAH were enrolled in the cross-sectional study. Genotypes were determined by multiplex PCR amplification and PCR-restriction fragment length polymorphism method.ResultsIn the cross-sectional study, GSTM1-null genotype and GSTT1-null genotype were associated with EAH in subjects with type 2 diabetes (59.0% vs. 50.3%, p = 0.007; 28.5% vs. 20.7%, p = 0.008; consequently).ConclusionAfter adjustment for age, body mass index, and hsCRP level, GSTM1-null and GSTT1-null genotypes were found to be independent risk factors for the development of EAH in Slovenian patients with type 2 diabetes.