Changes in the arginine methylation of organ proteins during the development of diabetes mellitus

Aim

In this study, we examined changes in asymmetric dimethylarginine (ADMA), dimethylarginine dimethylaminohydrolase (DDAH), nitric oxide synthesis (NOS), and the arginine methylation of organ proteins during the development of diabetes in mice.

Methods

Db/db mice developed significant obesity and fasting hyperglycemia during diabetogenesis. During diabetogenesis, the expression of ADMA and nNOS was increased, while that of DDAH1 and protein-arginine methyltransferase 1 (PRMT1) was decreased. Additionally, arginine methylation in the liver and adipose tissue was altered during diabetogenesis.

Results

Changes were evident at 75, 60, and 52 kDa in liver tissue and at 38 and 25 kDa in adipose tissue. Collectively, DDAH and ADMA are closely associated with the development of obesity and diabetes, and the arginine methylation levels of certain proteins were changed during diabetes development.

Conclusion

Protein arginine methylation plays a role in the pathogenesis of diabetes.     

Contrasting cardiovascular risk profiles and prescribed cardio-protective therapies in newly-diagnosed type 2 diabetes identified through screening and standard practice

Aims

Screening for Type 2 diabetes mellitus (T2DM) may improve long-term outcomes by managing cardiovascular risk at an earlier stage of the disease. The cardiovascular risk profile of screen-detected (SD) T2DM is ill defined and has not been compared to conventional newly diagnosed (CD) cases.

Methods

Baseline data from SD (n = 337) and CD (n = 824) cohorts were compared. SD adopted mixed approaches to screening, population based (n = 214) and cardiovascular-risk factor targeted (n = 123). CD reflected UK primary care practice with cases referred within four weeks of diagnosis.

Results

People with SD T2DM were leaner, had a lower HbA1c(%) and lower triglyceride but were more hypertensive compared to people with CD T2DM. Fewer SD were on blood pressure lowering (46% vs. 60%, p < 0.0001), statin (30% vs. 41%, p < 0.0001) or anti-platelet (15% vs. 27%, p < 0.0001) therapies. Modelled 10 year cardiovascular disease (CVD) risk was actually greater in the SD group compared to CD (CVD: 20.8 vs. 17.2, p = 0.0001).

Conclusion

Individuals with SD T2DM are at high risk of CVD as a result of untreated hyperglycaemia, hypertension and dyslipidaemia. Those prescribed antihypertensive or lipid-lowering therapies frequently still had inadequate control. Identifying vascular risk by screening for latent glucose disease provides therapeutic opportunities for earlier intervention.     

Contribution of glimepiride to basal-prandial insulin therapy in patients with type 2 diabetes

Aim

To investigate the efficacy of continuing glimepiride in combination with basal-prandial insulin therapy in type 2 diabetes.

Methods

An open crossover study was performed with arms of discontinuation and continuation of glimepiride in 25 subjects with mean diabetes duration of 17 years and 5 years of insulin treatment combined with glimepiride plus metformin. At entry and at the end of each 3-month arm, meal tolerance tests were performed for measurements of blood glucose and C-peptide.

Results

In terms of between-treatment differences (discontinuation vs. continuation arm of glimepiride) during meal tolerance tests performed at the ends of arms, significant increases in plasma glucose were seen on the discontinuation arm at 0-, 30-, and 60-min, while significant decreases in serum C-peptide were observed at 60- and 120-min. A1C values of the discontinuation arm significantly increased (from 6.6 ± 0.6 at baseline to 7.7 ± 0.8 at 3-months, p < 0.0001). Increases in A1C were closely correlated with decreases in area under the curve of meal-stimulated serum C-peptide (r = −0.61, p < 0.0001).

Conclusions

Since endogenous insulin secretion is more physiological than subcutaneous insulin injection, continuing glimepiride may remain beneficial, partly through enhancing insulin secretion, in individuals with a long duration of diabetes and basal-prandial insulin therapy.     

Impact of gluten-free diet on cardiovascular risk factors. A retrospective analysis in a large cohort of coeliac patients

Background

Concerns have been raised on whether a gluten-free diet affects the cardiovascular risk profile of coeliac patients.

Aims

To assess changes of multiple cardiovascular risk factors in coeliac patients evaluated before and during a gluten-free diet.

Methods

Retrospective analysis of the effects of 1–5 years of gluten-free diet on indicators of cardiovascular risk and on distribution in cardiovascular risk categories in 715 coeliac patients.

Results

Compared to baseline, significant increases were found in body mass index (21.4 ± 3.4 vs. 22.5 ± 3.5; p < 0.0001), total cholesterol (171.2 ± 37.4 mg/dL vs. 181.4 ± 35.1 mg/dL; p < 0.0001), and γ-glutamyl transpeptidase (16.5 ± 14.9 vs. 19.5 ± 19.2 U/L; p < 0.0001). Significant reductions were found in serum triglycerides (87.9 ± 49.5 vs. 80.2 ± 42.8 mg/dL; p < 0.0001) and homocysteine (16.9 ± 9.6 vs. 13.3 ± 8.0 μmol/L; p = 0.018) during gluten-free diet. The proportion of patients included in an arbitrarily defined category of “lowest cardiovascular risk profile” decreased from 58% at baseline to 47% during gluten-free diet.

Conclusions

A gluten-free diet significantly affects cardiovascular risk factors in coeliac patients, but changes do not consistently point towards worse or better risk profiles, thus suggesting that the diet is unlikely to be atherogenic.     

Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease

Aims

Patients with diabetes mellitus (DM) are prone to atherosclerosis. Atherosclerosis activates platelets; activated platelets release serotonin, and therefore, evaluation of serotonin levels in blood could be a valuable biomarker for future risk of cardiovascular events.

Methods

Plasma serotonin levels obtained from patients with DM complicated with chronic kidney disease were measured using HPLC and were compared to serotonin levels of healthy control subjects. Patients with DM were classified into 2 subgroups of mildly (group 1) and moderately/severely (group 2) impaired renal function.

Results

Serotonin concentration in platelet-poor plasma for group 1 was significantly higher than that of healthy control subjects (p < 0.01), and was significantly higher than that of patients from group 2 (p < 0.05). The concentration of serotonin in whole blood for group 2 patients was significantly lower than that measured from healthy control subjects (p < 0.01). The ratio of the plasma to whole blood level was significantly elevated in both groups 1 and 2 compared with healthy controls (p < 0.01).

Conclusions

Our results indicate that platelets are activated to release serotonin into plasma in diabetic patients with mildly impaired renal function. When renal damage is advanced, platelets are over-activated to release serotonin.     

Increased antibody response to microbial antigens in patients with Crohn's disease and their unaffected first-degree relatives

Background

Antibodies directed towards bacterial antigens are considered as serological markers of Crohn's disease. Their role in disease pathogenesis is still under investigation.

Aim

Assess the serologic response towards microbial antigens in Crohn's disease patients, their unaffected first-degree relatives and healthy controls.

Methods

This retrospective study included 60 Crohn's disease patients, 86 unaffected first-degree relatives and 100 healthy controls. Their sera were tested for anti-chitobioside, anti-laminaribioside, anti-mannobioside, anti-Saccharomyces cerevisiae and anti-outer membrane porin C of Escherichia coli.

Results

The prevalence of anti-chitobioside and anti-laminaribioside was higher in Crohn's disease patients and their first-degree relatives than in healthy controls (51.67%, 61.63% and 8%, respectively, for anti-chitobioside and 76.17%, 88.37% and 23.00% for anti-laminaribioside; p < 0.0001).The cumulative semiquantitative immune response against all the tested antibodies was higher in unaffected relatives than in healthy controls (p < 0.001).The quantitative analysis revealed that serum levels of anti-chitobioside, anti-laminaribioside and anti-mannobioside were similar in first-degree relatives and Crohn's disease patients and higher than healthy controls (p < 0.001).

Conclusions

Both qualitative and quantitative analysis revealed that unaffected first-degree relatives have increased antibody response to microbial antigens. This impaired immunological response towards enteric microorganisms may result from a genetic predisposition.     

Primary percutaneous transluminal coronary angioplasty accelerates early myocardial reperfusion compared to thrombolytic therapy in patients with acute myocardial infarction

Background

Successful early reperfusion of the infarcted myocardium as indicated by complete resolution of ST-segment elevations has been shown to be associated with an improved outcome in patients with acute ST-elevation myocardial infarction (AMI). The aim of this study was to compare early ST resolution in patients treated with primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for AMI.

Methods

A total of 1379 patients with AMI whose symptoms began <6 hours previously were enrolled in the Evaluation of the Safety and Cardioprotective effects of eniporide in Acute Myocardial Infarction (ESCAMI) trial and treated with primary PTCA (n = 528) or thrombolytic therapy (n = 851). Twelve-lead electrocardiograms (ECG) were obtained at baseline, directly after PTCA and at 90 minutes after the initiation of thrombolytic therapy.

Results

There were no differences with respect to clinical or ECG baseline variables between the 2 groups. The time intervals between hospital admission and ECG 2 (obtained 0-30 min after PTCA and 90 min after start of thrombolysis) were 121 ± 62 minutes in the PTCA group and 137 ± 57 minutes in the thrombolysis group, respectively. In ECG 2, complete (≥70%) ST resolution was observed more often in the PTCA treated patients (35 vs 27%, P = .003). The incidence of congestive heart failure until 6 weeks was lower in the PTCA group (11.2% vs 17.6, P = .001). Mortality after 6 weeks (3.4% vs 5.6%, P = .07) and after 6 months (4.5% vs 7.1%, P = .06) tended to be lower in the PTCA group.

Conclusion

Primary PTCA compared to thrombolytic therapy is associated with an accelerated myocardial reperfusion within 90 minutes after the start of reperfusion therapy. This early advantage in myocardial reperfusion is associated with an improved clinical outcome.     

Glomerular filtration rate, albuminuria and risk of cardiovascular and all-cause mortality in type 2 diabetic individuals

Background and aims

To assess all-cause and cardiovascular mortality in type 2 diabetic individuals according to estimated glomerular filtration rate (eGFR) and albuminuria.

Methods and results

We followed 2823 type 2 diabetic outpatients for a median period of 6 years for the occurrence of all-cause and cardiovascular mortality. eGFR was estimated using the abbreviated Modification of Diet in Renal Disease study equation. At baseline, an eGFR <60 ml/min/1.73 m² and abnormal albuminuria were present in 22.5% and 26.0% of participants, respectively. During follow-up, a total of 309 patients died, 53% of deaths were secondary to cardiovascular causes. Risks of all-cause and cardiovascular mortality increased progressively with decreasing eGFR and increasing albuminuria. After adjustment for age, sex, body mass index, smoking, hypertension, diabetes duration, hemoglobin A1c, plasma lipids, medications use (hypoglycemic, anti-hypertensive, anti-platelet or lipid-lowering drugs) and albuminuria, the hazard ratios of all-cause and cardiovascular mortality per 1-SD decrease in eGFR were 1.53 (95%CI 1.2-2.0; p < 0.0001) and 1.51 (95%CI 1.05-2.2; p = 0.023), respectively. A similar pattern in the risk of all-cause and cardiovascular mortality was seen for albuminuria (1.14, 1.01-1.3, p = 0.028 and 1.19, 1.01-1.4, p = 0.043 per 1-SD increase in albuminuria, respectively) after adjustment for eGFR and other potential confounders.

Conclusions

These findings suggest that both decreasing eGFR and rising albuminuria are associated with all-cause and cardiovascular mortality in type 2 diabetic individuals, independently of traditional risk factors and diabetes-related variables.     

Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant

Background and aims

Rare (611C) and common (1062V) variants of the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) display reduced activation of Wnt/ß-catenin signaling. The rare gene variant was associated with hypertension, metabolic abnormalities, and early coronary artery disease. We investigated whether the common 1062V LRP6 variant was related to carotid artery atherosclerosis (CAA) in hypertensive patients.

Methods and results

Retrospective study of 334 hypertensive patients (<65 years old) who underwent carotid artery ultrasonography. Hypertension, type 2 diabetes, dyslipidemia, glomerular filtration rate, and smoking habit were evaluated. CAA was defined by the presence of atherosclerotic plaques (focal intima-media thickness ≥1.3 mm). Logistic regression models were used to estimate the independent effect of 1062V allele. The relationship between LRP6 genotypes and LRP6 gene expression in carotid plaques was also investigated. No difference was observed between genotypes in clinical variables except for a slightly higher fasting glucose in 1062V carriers. The 1062V LRP6 variant was an independent risk factor for CAA in both unadjusted (OR 2.08, 95%CI 1.27-3.41, p = 0.003) and adjusted models (OR 1.92, 95%CI 1.09-3.39, p = 0.02). LRP6 was expressed in carotid atherosclerotic plaques at significantly lower levels (p = 0.015) in 1062V carriers.

Conclusion

Beside the role of established risk factors, 1062V variant of LRP6 and CAA are strongly associated in hypertensive patients, making LRP6 a novel relevant candidate gene for atherosclerosis in the presence of hypertension.     

Degree of control and delayed intensification of antihyperglycaemic treatment in type 2 diabetes mellitus patients in primary care in Spain

Objectives

Primary aim: to determine the degree of control of HbA_1c at the time of treatment intensification (TI) in T2DM patients. Secondary aims: fasting plasma glucose levels; estimation of the elapsed time between HbA_1c exceeding 7% and TI; antidiabetic combinations used, % patients with good cardiometabolic control (LDL-c < 100 mg/dL; SBP < 130 and DPB < 80 mmHg and HbA_1c < 7%).

Research design and methods

One-cohort, multicenter, retrospective, observational study conducted in Spain. Patients diagnosed with T2DM that had switched from monotherapy to combination antidiabetic therapy were evaluated at baseline and after one year of follow-up.

Results

A total of 1202 T2DM patients were analyzed. At the time of TI: mean HbA_1c 8.1%; median time of uncontrolled disease: 2.0 years. After one-year of TI: significant reduction in mean HbA_1c (8.1% vs.7.0%, p < 0.001) and a mean fasting plasma glucose levels reduction (181.1 mg/dL vs.144.1 mg/dL, p < 0.001) was also observed. The percentage of patients under glycemic control (HbA_1c < 7%) increased from 12.2% to 51.6% (p < 0.001). Most common antidiabetic combinations: metformin + sulfonylurea (44.1%) and metformin + thiazolidindione (15.9%).

Conclusions

In the population of T2DM patients analyzed, TI was carried out when HbA_1c values were above those recommended in clinical guidelines (≤7%), with a delay of two years to address the second step of therapy, despite the consensus recommendation of the ADA/EASD of 3 months. TI was shown to be effective since addition of a second antidiabetic drug led to an average reduction of HbA_1c of approximately 1%. Metformin was the drug most commonly used as monotherapy being the most frequent combination metformin + sulfonylurea.     

Sub-clinical organ damage in hypertension and obesity

Background

The development of sub-clinical organ damage precedes and predicts the occurrence of cardiovascular (CV) events in hypertensive as well as in obese patients.

Aim and methods

We investigated the prevalence and clinical correlates of organ damage (OD), namely carotid atherosclerosis (US scan) and urine albumin to creatinine ratio (three non-consecutive first morning samples) in a group of 164 obese patients and in an age- and gender-matched group of non-obese hypertensive patients.

Results

There was a significantly greater prevalence and severity of OD in obese patients as compared to non-obese hypertensive patients. In particular obese patients more frequently had microalbuminuria (16 vs7%, χ² 5.8, P = 0.0157) and carotid abnormalities (53 vs 10%, χ² 69.5, P < 0.0001) as well as higher urinary albumin excretion rate (−0.05 ± 0.52 vs −0.28 ± 0.43log ACR, P < 0.0001) and carotid intima-media thickness (0.955 ± 0.224 vs 0.681 ± 0.171, <0.0001). Notably, the coexistence of hypertension and obesity did not entail a greater prevalence and severity of OD. Moreover, after adjusting for potentially confounding factors including blood pressure levels, diagnosis of diabetes, and lipid profile, morbidly obese patients showed a 5-fold, and 22-fold higher risk of having microalbuminuria, and carotid atherosclerosis, respectively.

Conclusions

Sub-clinical OD is highly prevalent in obese patients, even in the absence of high blood pressure. Hypertension and obesity seem to exert an independent, possibly non-additive role on the occurrence of organ damage.     

Type 2 diabetes does not attenuate racial differences in coronary calcification

Aims

Coronary artery calcification (CAC) is a strong predictor of atherosclerotic cardiovascular disease (CVD). Whites appear to have a higher prevalence of CAC than African-Americans (AAs), but it is unknown if type 2 diabetes, a major cardiovascular risk factor, attenuates this difference. We investigated the relationship of race and CAC in a sample of patients with type 2 diabetes without clinical CVD.

Methods

Multivariable analyses of self-reported ethnicity and CAC scores, stratified by gender, in 861 subjects [32% AA, 66.9% male] with type 2 diabetes.

Results

AA race was associated with lower CAC scores in age-adjusted models in males [Tobit ratio for AAs vs. Whites 0.14 (95% CI 0.08-0.24, p < 0.001)] and females [Tobit ratio 0.26 (95% CI 0.09-0.77, p = 0.015)]. This persisted in men after adjustment for traditional, metabolic and inflammatory risk factors, but adjustment for plasma triglycerides [0.48 (95% CI 0.15-1.49, p = 0.201)] and HOMA-IR [0.28 (95% CI 0.08-1.03, p = 0.055)] partially attenuated the association in women.

Conclusions

Relative to African-Americans, White race is a strong predictor of CAC, even in the presence of type 2 diabetes. The relationship in women appears less robust possibly due to gender differences in metabolic risk factors.     

Are drugs a risk factor of post-ERCP pancreatitis?

Background

Pancreatitis is the most severe complication of ERCP. The aim of this study was to assess whether the use of potentially pancreatotoxic drugs is a risk factor for post-ERCP pancreatitis.

Methods

Risk factors for post-ERCP pancreatitis and all drugs taken during the month before ERCP were recorded retrospectively in a database. Patients with other causes of acute pancreatitis or chronic pancreatitis were excluded from the analysis. Post-ERCP pancreatitis was defined as abdominal pain and/or vomiting associated with amylase/lipase plasma levels equal to or greater than twice the upper normal value.

Results

A total of 173 patients (95 men, 78 women; mean age, 68 [16] years) were included. Post-ERCP pancreatitis occurred in 31 patients (18%). Several risk factors were identified in a multivariate analysis: difficulty in cannulation (p<0.001), endoscopic sphincterotomy (p<0.005), and female gender (p = 0.02). Having taken potent pancreatotoxic drugs increased the occurrence of post-ERCP pancreatitis: odds ratio 3.7: 95% confidence intervals [1.1,12.4], p = 0.04.

Conclusions

Use of pancreatotoxic drugs before or during ERCP significantly increased the risk of post-ERCP pancreatitis. Thus, discontinuation of the use of such drugs before ERCP seems justified whenever possible.     

Attribution of functional limitation to cancer decreases in the year following breast cancer diagnosis in older patients

Objectives

To examine the prevalence of self-reported functional limitations in a breast cancer population, identify whether these reported limitations are attributed to breast cancer versus other coexisting illnesses, and examine how this attribution changes over time from early in treatment to 9 months later.

Design

Longitudinal, observational study.

Setting

Community dwelling adults in Detroit metropolitan area.

Participants

2033 participants (1011 breast cancer patients, 1022 controls) aged 40-84 years.

Measurements

Participants were asked about each of 23 possible coexisting illnesses in addition to breast cancer and whether or not each illness, including breast cancer, caused any activity limitation.

Results

Of the 933 cancer patients who completed both baseline and follow-up evaluations, 45% were aged 65 years and older. At baseline, 56% of patients 65 years and older reported functional limitation compared with 50% of patients younger than 65 years (p = 0.005). Of those patients who reported limitation at baseline, 59% of older patients and 78% of younger patients attributed their limitation to breast cancer (p < 0.001). At follow-up, 53% of older and 37% of younger patients reported functional limitation (p < 0.001), with 27% of older patients compared with 57% of younger patients (p < 0.001) attributing limitation to breast cancer.

Conclusion

Self-reported functional limitations are common 3 months after breast cancer diagnosis, being attributed primarily to breast cancer. By 1 year after diagnosis, much of the limitation due to breast cancer resolves. Older women are less likely to have resolution of their limitations, which are most commonly due to other coexisting illnesses.     

Efficacy and safety of saxagliptin added to metformin in Asian people with type 2 diabetes mellitus: a randomized controlled trial

Aim

To assess efficacy and safety of saxagliptin added to metformin versus placebo plus metformin in Asian patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin alone.

Methods

Adults (HbA_1c 7.0-10.0%, on stable metformin ≥1500 mg/day) were randomized 1:1 to saxagliptin 5 mg daily plus metformin (n = 283) or placebo plus metformin (n = 287). The primary end point was HbA_1c change from baseline to Week 24.

Results

Saxagliptin plus metformin provided significant adjusted mean decreases versus placebo plus metformin (p ≤ 0.0052) in HbA_1c (−0.78% versus −0.37%), fasting plasma glucose (−1.14 mmol/L versus −0.58 mmol/L), and postprandial glucose area under the curve from 0 to 180 min (−315 mmol min/L versus −160 mmol min/L). Significantly more saxagliptin-treated patients achieved a therapeutic glycemic response (HbA_1c < 7.0%) (46.5% versus 30.5%; p = 0.0001). The proportion of patients experiencing adverse events (excluding hypoglycemia) was similar for saxagliptin plus metformin (42.8%) versus placebo plus metformin (40.8%). Hypoglycemic events were reported in 1.4% of patients in each group.

Conclusion

Saxagliptin added to metformin significantly improved glycemic control and was well tolerated in Asian patients with T2DM who had inadequate glycemic control with metformin and diet and lifestyle modification.     

Effect of gender on treatment outcomes in type 2 diabetes mellitus

Aim

To evaluate the effect of gender on clinical outcomes in people with type 2 diabetes mellitus (T2DM) receiving antidiabetes therapy.

Methods

This is a pooled analysis from nine similarly designed phase 3 and 4 randomized, controlled studies evaluating insulin glargine and an active comparator (NPH insulin, insulin lispro, premixed insulin, oral antidiabetes drugs, dietary intervention) in adults with T2DM. Impact of gender on outcomes including HbA1c, fasting plasma glucose (FPG), weight-adjusted insulin dose, and hypoglycemia incidence was evaluated after 24 weeks of treatment.

Results

Overall, 1651 male and 1287 female individuals were included; 49.8% and 50.2% were treated with insulin glargine or comparators, respectively. Females receiving insulin glargine were less likely than males to achieve a glycemic target of HbA1c ≤ 7.0% (53 mmol/mol) (54.3% vs 60.8%, respectively, p = 0.0162); there was no difference between females and males receiving comparators (52.7% vs 51.3%, respectively, p = 0.4625). Females had significantly greater reductions in FPG (3.1 mg/dL, p = 0.0458), required significantly higher insulin doses (0.03 IU/kg, p = 0.0071), and had significantly higher annual rates of symptomatic (p < 0.0001), glucose-confirmed (<50 and <70 mg/dL) symptomatic (p = 0.0005 and p < 0.0001), and severe hypoglycemia (p = 0.0020) than males.

Conclusions

Females in this analysis had smaller reductions in HbA1c and were less likely to reach glycemic goals despite higher insulin doses and more hypoglycemic events than males. Differences in gender responses to therapy should be considered when individualizing treatment for people with T2DM.     

Influence of glycosylated hemoglobin on sight-threatening diabetic retinopathy: a population-based study

Aim

To evaluate the role of glycosylated hemoglobin (HbA1c) on the occurrence of sight-threatening diabetic retinopathy (STDR) in urban Chennai, Tamil Nadu, India.

Methods

A total of 5999 individuals were enumerated from the Chennai metropolis. Of these, 1414 subjects with diabetes were included for data analysis in the study. STDR or non-STDR groups were classified based on the fundus photographs. HbA1c was measured (Bio-Rad DiaSTAT™ HbA1c Reagent Kit) by the liquid chromatography technique.

Results

A statistically significant difference (p < 0.05) was noted in the duration of diabetes, gender, body mass index, HbA1c, micro- and macro-albuminuria between both non-STDR and STDR groups as compared to the no-diabetic retinopathy (DR) group. On multivariate analysis, HbA1c (non-STDR: odd's ratio OR = 1.23; 95% confidence interval CI = 1.15-1.32; p < 0.0001; STDR: OR = 1.31 95% CI = 1.14-1.52; p < 0.0001) was found to be significantly associated with non-STDR and STDR when compared with the no-DR group. The Receiver Operating Characteristic analysis showed that the cut-off value of 8.0 had 75.6% sensitivity and 58.2% specificity with 64.9% maximum area under the curve.

Conclusion

HbA1c value >8.0% was significantly related with STDR. In a screening programme, the cut-off value of HbA1c >8.0% provided a maximum yield of STDR.     

Diabetes mellitus and oral mucosa alterations: prevalence and risk factors

Aims

To investigate the prevalence of oral mucosa alterations in patients with type 2 diabetes and to identify possible risk factors related to oral mucosa alterations.

Methods

146 patients with type 2 diabetes and 111 age- and gender-matched healthy controls subjects were consecutively recruited from Araraquara School of Dentistry to answer a structured questionnaire designed to collect demographic data as well as current and former history of diabetes. Clinical examination of the oral mucosa was carried out by a stomatologist.

Results

A higher prevalence of oral mucosa alterations was found in patients with diabetes than in patients without diabetes (p < 0.001), with significant difference to development conditions (p < 0.0001), potentially malignant disorders (p < 0.0001) and fungal infections (p < 0.05). In the multiple logistic regression, diabetes (odds ratio 9.9 IC 5.11-19.16) and smoking habit (odds ratio 3.17 IC 1.42-7.12) increased the odds of oral mucosa alterations significantly.

Conclusions

Patients with diabetes mellitus not only showed an increased prevalence of oral mucosa alterations but also a significant percentage of potentially malignant disorders. These findings elucidate the necessity of regular clinical examination to ensure early diagnosis and prompt management of oral mucosa lesions in patients with diabetes.     

Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24 week,double-blind,randomized Phase 3 trial

Background

Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy.

Methods

In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events ≥ 1%–<5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1­mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was ≥ 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.

Results

Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and 138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p < 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p < 0.0001). At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (< 2% and < 4% of alirocumab and ezetimibe patients, respectively).

Conclusions

Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.     

Inflammatory status, arterial stiffness and central hemodynamics in hypertensive patients with metabolic syndrome

Introduction

Inflammatory state is activated in metabolic syndrome and may explain part of the adverse prognosis of this entity. Arterial stiffness, central blood pressures and wave reflections are independent predictors of cardiovascular risk. This study investigates the relation between low-grade inflammation and arterial stiffness and central hemodynamics in patients with metabolic syndrome.

Methods

We studied 106 consecutive hypertensive patients with metabolic syndrome. Arterial stiffness was assessed by carotid-femoral (c-f) and carotid-radial (c-r) pulse wave velocity (PWV). Central blood pressures were evaluated by pulse wave analysis and heart rate corrected augmentation index (AIx₇₅) was used as a measure of wave reflections. White blood cell count (WBC), high sensitivity C-reactive protein (hsCRP) and fibrinogen were measured as inflammatory markers.

Results

In univariable analysis, PWVc-f correlated with both hsCRP (p < 0.01) and fibrinogen (p < 0.01), while PWVc-r correlated with hsCRP (p = 0.05). Regarding central blood pressures, aortic SBP correlated positively with hsCRP (p < 0.05) and marginally with fibrinogen (p = 0.06) and WBC (p = 0.08). Interestingly, no correlation was found between AIx₇₅ and any of these biomarkers. After adjustment for age, gender, smoking, mean arterial pressure, heart rate, waist circumference, glucose, total and HDL cholesterol, PWVc-f was independently related to hsCRP (p < 0.001) and fibrinogen (p < 0.01), while a marginal independent correlation was also found between PWVc-r and hsCRP (p = 0.06). Furthermore, aortic PP independently associated with fibrinogen (p < 0.05) whereas marginal associations demonstrated between aortic SBP and hsCRP and fibrinogen (p = 0.06 for both).

Conclusion

Inflammatory status is related to arterial stiffness and central blood pressures (but not to augmentation index) in hypertensives with metabolic syndrome. These findings may have implications for increased cardiovascular risk in these patients.