Effects of uncomplicated vaginal delivery and epidural analgesia on fetal arterial acid–base parameters at birth in gestational diabetes

Aim

To investigate the effects of uncomplicated vaginal delivery and epidural analgesia on fetal acid–base parameters in women with gestational diabetes (GDM) compared with controls.

Methods

A retrospective case–control study of 142 women with gestational diabetes and 284 controls. To evaluate the effect of diabetes and analgesia on acid–base status correcting for potential confounders we used ordered logistic equations including quartiles of fetal arterial acid–base parameters collected at birth as outcomes and categories of diabetes and epidural analgesia as explanatory variables.

Results

In the GDM group cord base deficit (−2.63 mmol/l, interquartile range [IQR] = 4.2 to −0.65 mmol/l vs. −1.9 mmol/l, IQR = −3.3 to −0.2  mmol/l, p = 0.009, odds ratio (OR) = 1.51, 95% confidence interval (CI) = 1.04–2.18) was lower and concentration of calcium higher (1.49 mmol/l, IQR = 1.42–1.56 mmol/l vs. 1.47 mmol/l, IQR = 1.41–1.51 mmol/l, p = 0.009, OR = 1.69, 95% CI = 1.12–2.56) compared with controls. Epidural analgesia in the GDM group was associated with reduced cord concentration of glucose (84.0 mg/dl [4.7 mmol/l], IQR = 70–103.3 mg/dl vs. 92.5 mg/dl [5.1 mmol/l], IQR = 76.5–121.8 mg/dl, p = 0.004), lactate (2.65 mmol/l (IQR = 1.80–4.20) vs. 3.70 mmol/l (IQR = 2.90–5.55 mmol/l), p = 0.002) and less pronounced base deficit (−2.05 mmol/l, IQR = −3.90 to −0.17 mmol/l vs. −2.8, IQR = −5.57 to −1.05 mmol/l, p = 0.01, OR = 0.7, 95% CI = 0.49–0.99).

Conclusions

In uncomplicated pregnancies and deliveries, well-controlled gestational diabetes mellitus has potentially significant detrimental effects on fetal acid–base status at birth. Epidural analgesia reduces cord arterial glucose and lactates.     

Effect of glycemic control on intact parathyroid hormone level in end stage renal disease patients on maintenance hemodialysis

Aims

We evaluated the relationship between iPTH levels and glycemic control in patients with diabetes and end stage renal disease (ESRD) on maintenance hemodialysis (MHD).

Methods

The study included 98 subjects with ESRD and type 2 diabetes aged 30–75 years who were on MHD. These were divided into two groups – patients with HbA1c >7.0 (53 mmol/mol) (poor glycemic control group) and patients with HbA1c <7.0 (53 mmol/mol) (good glycemic control group). All patients had been on regular bicarbonate haemodialysis for more than 6 months using polysulfone membrane dialyzer; 4 h per episode 3 times/week, with a dialysis fluid of 3.0 mEq/L of calcium concentration. 1-α-(OH)D3 and calcium carbonate were used routinely in all patients. The contribution of each relevant biological parameter to serum iPTH level was assessed using multiple regression test.

Results

Poor glycemic control was associated with reduced serum iPTH level and good glycemic control with higher serum iPTH. The serum HbA1c level was significantly correlated with the serum iPTH level (p = 0.0003).

Conclusions

Glycemic control is a significant determinant of iPTH level in diabetic ESRD patients on MHD.     

Clinical factors associated with absolute and relative measures of glycemic variability determined by continuous glucose monitoring: An analysis of 480 subjects

Aim

Factors associated with absolute and relative measures of glycemic variability have not been determined by continuous glucose monitoring (CGM) and concurrent measurement of fasting C-peptide levels.

Methods

We analyzed CGM data for subjects with type 1 diabetes (T1D; n = 81) and type 2 diabetes (T2D; insulin-treated, n = 168; not insulin-treated, n = 231) who underwent CGM between October 2009 and September 2011 at Samsung Medical Center. Correlations between clinical factors and both standard deviation (SD) and coefficient of variance (CV) in CGM were analyzed by multiple regression.

Results

Regardless of the type of diabetes and insulin therapy, higher CV, but not SD, was significantly associated with a minimum glucose level of <70 mg/dL (3.9 mmol/l) in CGM (p < 0.001). In T1D, fasting C-peptide levels inversely correlated with SD while BMI inversely correlated with CV, and duration of diabetes, and HDL levels positively correlated with CV. Use of pre-mixed insulin increased both SD and CV. In insulin-treated T2D, fasting C-peptide levels inversely correlated with both SD and CV while HbA1c correlated with SD, and duration of diabetes positively correlated with CV. In T2D without insulin therapy, age, BMI, HbA1c, HDL, triglyceride levels and use of sulfonylurea positively correlated with SD while HDL levels and use of sulfonylurea positively correlated with CV, and LDL levels inversely correlated with CV.

Conclusions

Relative glycemic variability (CV) was determined by factors different from those that affect absolute glycemic variability (SD). Some of these factors were indicators of higher insulin sensitivity and residual insulin secretion.     

Ethnic disparities in the association of impaired fasting glucose with the 10-year cumulative incidence of type 2 diabetes

Aims

Evidence of ethnic disparities in the conversion of prediabetes to type 2 diabetes is scarce. We studied the association of impaired fasting glucose (IFG) and fasting plasma glucose (FPG) with the 10-year cumulative incidence of type 2 diabetes in three ethnic groups.

Methods

We analyzed data for 90 South-Asian Surinamese, 190 African-Surinamese, and 176 ethnic Dutch that were collected in the periods 2001–2003 and 2011–2012. We excluded those with type 2 diabetes or missing FPG data. We defined baseline IFG as FPG of 5.7–6.9 mmol/L. We defined type 2 diabetes at follow-up as FPG ≥ 7.0 mmol/L, HbA1c ≥ 48 mmol/mol (6.5%), or self-reported type 2 diabetes.

Results

10-Year cumulative incidences of type 2 diabetes were: South-Asian Surinamese, 18.9%; African-Surinamese, 13.7%; ethnic Dutch, 4.5% (p < 0.05). The adjusted association of baseline IFG and FPG with the 10-year cumulative incidence of type 2 diabetes was stronger for South-Asian Surinamese than for African-Surinamese and ethnic Dutch. The IFG (compared to normoglycaemia) ORs were 11.1 [3.0–40.8] for South-Asian Surinamese, 5.1 [2.0–13.3] for African-Surinamese, and 2.2 [0.5–10.1] for ethnic Dutch.

Conclusions

The 10-year cumulative incidence of type 2 diabetes was higher and associations with baseline IFG and FPG were stronger among South-Asian Surinamese and African-Surinamese than among ethnic Dutch. Our findings confirm the high risk of type 2 diabetes in South-Asians and suggest more rapid conversion in populations of South-Asian origin and (to a lesser extent) African origin than European origin.     

Impact of glycemic variability and hypoglycemia on adverse hospital outcomes in non-critically ill patients

Aims

To determine if glycemic variability is associated with hospitalization outcomes in non-critically ill patients, and if this association remains after controlling for hypoglycemia.

Methods

A retrospective review was performed on 1276 medical admissions (801 patients) in which insulin was given, ≥6 point of care glucose (POCG) measurements and length of stay (LOS) 2–30 days. Coefficient of variation (%CV) was used to measure glycemic variability. Outcomes included LOS and a composite outcome based on ICU transfer, hospital acquired infections, and acute renal failure (ARF).

Results

There were a median of 18.5 POCG measurements per admission with a mean %CV 34.2 ± 11.1. Hypoglycemia (POCG ≤70 mg/dl [3.9 mmol/l]) occurred in 35.0% of admissions. ICU transfer occurred in 3.3%, hospital acquired infections 4.8%, ARF 8.3%, and composite outcome 13.5%. Adjusting for age, sex, race and Charlson score, every 10 unit increase in %CV was associated with an increase in LOS of 0.27 days (p = 0.004), while there was no association between %CV and the composite outcome. For LOS, there was a significant interaction between %CV and hypoglycemia (p = 0.07). While there was a non-significant correlation in patients without hypoglycemia, LOS correlated negatively with %CV in patients with hypoglycemia. When considered simultaneously with %CV, hypoglycemia was associated with increased odds of the composite outcome [OR 2.03 (95% CI 1.36–3.01), p = <0.001] and an increase of 2 days in LOS for those with average %CV.

Conclusions

Hypoglycemia, compared to glycemic variability, is more strongly associated with adverse outcomes in hospitalized, non-critically ill patients.     

Impaired response or insufficient dosage?—Examining the potential causes of “inadequate response” to allopurinol in the treatment of gout

Objectives

Gout is one of the most common forms of arthritis. It is well established that urate-lowering therapy that aims for a serum urate less than at least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate-lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol; these patients can be considered to have “inadequate response” to allopurinol. Herein, we examine the potential mechanisms and implications of inadequate response to allopurinol.

Methods

The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol.

Results

The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be “partially resistant” to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and/or function such that oxypurinol is rendered less effective and/or drug interactions.

Conclusions

It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician towards making a therapeutic choice that is more likely to result in achieving the serum urate target.     

International noninterventional study of acarbose treatment in patients with type 2 diabetes mellitus

Aim

To obtain data on efficacy, safety and tolerability of acarbose monotherapy or combination therapy during daily-life treatment.

Methods

This prospective, non-controlled, observational study enrolled patients with type 2 diabetes, whose physician decided that acarbose treatment was appropriate, from China, Middle East, Indonesia, Morocco, Pakistan, Philippines, Poland and Taiwan. The observation period included an initial visit and up to three follow-up visits; an extension of 2 years was realized in Pakistan and Poland.

Results

Of 14,574 patients enrolled, 14,418 comprised the intent-to-treat population. At the initial visit, 74.1% of patients had been treated with a glucose-lowering agent. Fasting blood glucose was reduced from 175.2 mg/dL at the initial visit to 133.7 mg/dL at the last visit (mean of 11.3 weeks after initial visit; P < 0.0001). Mean 2-h postprandial blood glucose decreased from 244.7 mg/dL to 172.4 mg/dL (P < 0.0001). HbA1c reduced from 8.4% to 7.4% (P < 0.0001). Glycemic efficacy was maintained over the 2-year extension period. There were 432 adverse events in 293 patients (2.03%), mainly gastrointestinal. Physicians assessed efficacy as “very good”/“good” in 85.1% of patients, and were “very satisfied”/“satisfied” with acarbose therapy in 94.3% of cases.

Conclusion

Acarbose therapy was efficacious and well tolerated in daily life in patients with type 2 diabetes.     

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.     

Le ressenti des patients vis-à-vis d’une corticothérapie orale prolongée influence l’adhérence déclarée à ce traitement

Background

In patients treated with systemic glucocorticoids (GCs), it is unknown if beliefs about the treatment are associated with level of reported adherence.

Patients and methods

Cross-sectional study conducted in two departments of internal medicine during a six-month period. All patients receiving long-term GCs therapy were asked to fill in a questionnaire regarding their beliefs about (specific scale of the Beliefs about Medicines Questionnaire) and their adherence to (four-item Morisky-Green scale) GCs. Logistic regression analysis was used to assess association between beliefs about GCs and adherence to treatment.

Results

One hundred and eighty one questionnaires were analysed (women: 79%, median age [IQR]: 47 [33–61] years, median duration of treatment: 18 [7–72] months, median daily dosage of prednisone equivalent: 10 [6–20] mg). Among these 181 patients, 83 (46%) reported a “concern” score equal to or higher than the “necessity” score. Nineteen percent of patients reported a low adherence level. In multivariate analysis, these patients were significantly younger (OR: 0.96 [0.93–0.98] per increasing year of age, P = 0.002) and reported more frequently a “concern” score higher than a “necessity” score (OR: 3.08 [1.27–7.46], P = 0.01) as compared to patients reporting a high adherence level.

Conclusion

Informing patients about the “necessity” of GCs and taking into account their “concerns” about adverse events or their fear of becoming dependent on the medication may improve their adherence to treatment.     

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.     

Canagliflozin,a sodium glucose co-transporter 2 inhibitor,reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial

Objective

Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin.

Materials/Methods

Patients (N = 37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B–D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period.

Results

A single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B–D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC_0–2h, − 7.5% for B vs A; − 18.5% for C vs A; − 12.0% [P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC_0–2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated.

Conclusions

These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg.     

Acute kidney injury and long-term risk of stroke after coronary artery bypass surgery

Background

Acute kidney injury (AKI) is associated with death, end-stage renal disease, and heart failure in patients with coronary heart disease. This study investigated the association between AKI and long-term risk of stroke.

Methods and results

50,244 patients who underwent coronary artery bypass grafting (CABG) in Sweden between 2000 and 2008 were identified from the SWEDEHEART registry. After exclusions 23,584 patients without prior stroke who underwent elective, primary, isolated, CABG were included. AKI was categorized according to absolute increases in postoperative creatinine values compared with preoperative values: stage 1, 0.3–0.5 mg/dL (26–44 μmol/L); stage 2, 0.5–1.0 mg/dL (44–88 μmol/L); and stage 3, > 1.0 mg/dL (≥ 88 μmol/L). Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for stroke. There were 1156 (4.9%) strokes during a mean follow-up of 4.1 years. After adjustment for confounders, HRs (95% CIs) for stroke in AKI stages 1, 2 and 3 were 1.12 (0.89–1.39), 1.31 (1.04–1.66) and 1.31 (0.92–1.87), respectively, compared with no AKI. This association disappeared after taking death into account in competing risk analysis. There was a significant association between AKI and stroke in men (HR: 1.26 [1.05–1.50]) but not in women (HR: 1.07 [0.75–1.53]), and in younger (< 65 years; HR: 1.57 [1.12–2.22]), but not elderly patients (HR: 1.17 [0.98–1.40]).

Conclusions

The long-term risk of stroke is weakly associated with AKI after primary isolated CABG, but this association is attenuated and not significant when considering death as a competing risk.     

Glucagon-like peptide-1 receptor agonists and pancreatitis: A meta-analysis of randomized clinical trials

Aims

Several randomized trials with metabolic outcomes have reported that glucagon like peptide-1 receptor agonists (GLP-1 RA) could be associated with an increased risk of pancreatitis. The present meta-analysis aimed to examine this hypothesis.

Methods

An extensive Medline, Embase, and Cochrane Database search for “exenatide”, “liraglutide”, “albiglutide”, “taspoglutide”, “dulaglutide”, “lixisenatide”, and “semaglutide” was performed up to March 31st, 2013. Inclusion criteria: (i) randomized trials, (ii) duration ≥12 weeks; (iii) on type 2 diabetes; and (iv) comparison of GLP-1RA with placebo or active drugs. Mantel–Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for pancreatitis.

Results

80 eligible trials were identified. Of these, 39 had not disclosed their findings or did not report any information on pancreatitis. The remaining 41 trials enrolled 14,972 patients, with a total exposure of 14,333 patient × years (8353 and 5980 patient × years for GLP-1 receptor agonists and comparators, respectively). The overall risk of pancreatitis was not different between GLP-1RA and comparators (MH-OR: 1.01[0.37; 2.76]; p = 0.99).

Conclusions

The present meta-analysis does not suggest any increase in the risk of pancreatitis with the use of GLP-1RA. However, it should be recognized that the number of observed cases of incident pancreatitis is very small and the confidence intervals of risk estimates are wide.     

Low HDL-cholesterol: a strong predictor of glycemic response to glitazone treatment in patients with type 2 diabetes

We performed a study in 102 people with type 2 diabetes aiming to determine “easy-to-use” predictive factors for glycemic response to glitazones. We found that low baseline HDL-cholesterol (<40 mg/L [1.04 mmol/L] in males, <50 mg/L [1.30 mmol/L] in females) was a strong independent predictor of glycemic response to glitazones (OR = 2.67 [2.02-3.52], p = 0.0004).     

Alteration in fasting glucose after prolonged treatment with a thiazide diuretic

Aims

Thiazide diuretics are recommended as first line antihypertensive treatment, but may contribute to new onset diabetes. We aimed to describe change in fasting glucose (FG) during prolonged thiazide treatment in an observational setting.

Methods

We conducted an observational, non-randomized, open label, follow-up study of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 studies. We enrolled previous participants from the PEAR or PEAR-2 studies with at least 6 months of continuous treatment with either hydrochlorothiazide (HCTZ) or chlorthalidone. Linear regression was used to identify associations with changes in FG after prolonged thiazide and thiazide-like diuretic treatment.

Results

A total of 40 participants were included with a mean 29 (range 8–72) months of thiazide treatment. FG increased 6.5 (SD 13.0) mg/dL during short-term thiazide treatment and 3.6 (SD 15.3) mg/dL FG during prolonged thiazide treatment. Increased FG at follow-up was associated with longer thiazide treatment duration (β = 0.34, p = 0.008) and lower baseline FG (β = −0.46, p = 0.02). β blocker treatment in combination with prolonged thiazide diuretic treatment was also associated with increased FG and increased 2-h glucose obtained from OGTT.

Conclusions

Our results indicate that prolonged thiazide treatment duration is associated with increased FG and that overall glycemic status worsens when thiazide/thiazide-like diuretics are combined with β blockers.     

Motivational interviewing in inflammatory bowel disease patients: A useful tool for outpatient counselling

Background

Most inflammatory bowel disease patients miss follow-up visits and are non-adherent to therapy due to the lack of an engaging patient–physician relationship. Motivational interviewing is a patient-centred counselling method used to elicit/strengthen motivation towards change. The aim of this study was to assess the role of motivational interviewing in patients affected by inflammatory bowel disease.

Methods

The study included consecutive patients with inflammatory bowel disease presenting for the first consultation (June 2012–February 2013). All consultations were carried out applying the motivational interviewing approach. After each consultation, patients filled out a questionnaire asking demographic data, and their past and current experience.

Results

Overall, 23 males (51.1%) and 22 females (48.9%), mean age 36.1 ± 15.2 years, were enrolled. Before and after experiencing the motivational interviewing approach (mean visit duration 41.5 ± 8.7 min) “overall satisfaction rate”, “physician's communication skills”, and “perceived empathy” were 60% vs 100%, 40% vs 95.6%, and 40% vs 100%, respectively. Satisfaction was lower in patients affected by indeterminate colitis (p = 0.004), and of younger age (p = 0.02).

Conclusion

The motivational interview approach is appreciated by inflammatory bowel disease patients. Despite being time-consuming, the motivational interview appears considerably worthwhile at the first visit and in younger patients. Motivational interviewing can help physicians to deal with their patients, moving from “cure” to “care”.     

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.     

Interventions to maintain cardiac risk control after discharge from a cardiovascular risk reduction clinic: A randomized controlled trial

Aims

To evaluate the efficacy of two maintenance strategies compared to usual care after discharge from a pharmacist-led cardiovascular risk reduction clinic (CRRC).

Methods

Open-label, randomized-controlled trial of 200 consecutive CRRC patients that met clinic discharge criteria (HbA1c ≤7% (53 mmol/mol); blood pressure ≤140/80 mmHg for those with diabetes and ≤140/90 mmHg for those without diabetes; and an LDL-cholesterol ≤2.59 mmol/l). Participants were randomized to either [1] quarterly group medical visits or [2] quarterly CRRC individual clinic visits, or [3] a usual care control arm with the standard primary care alone first in a 1:1:1 ratio, followed by a 2:2:1 ratio after first 100 patients. Primary outcome measures were time to failure for guideline recommended goals of HbA1c and blood pressure over 12-months.

Results

Of the 200 participants randomized, 89% had diabetes and were similar in other cardiovascular risk factors. After 1-year, the HbA1c failure rate was 0.36 [95% CI, 0.28–0.47] per quarter for the group medical visit arm, 0.24 [95% CI, 0.18–0.33] per quarter for the quarterly CRRC individual arm and, 0.82 [95% CI, 0.69–0.96] per quarter for the usual care control arm, p < 0.001. The rate of failure for blood pressure was 0.31 [95% CI, 0.23–0.41] per quarter for the group medical visit arm, 0.22 [95% CI, 0.16–0.30] per quarter for the CRRC individual arm and, 0.53 [95% CI, 0.40–0.71] per quarter the control arm, p < 0.001.

Conclusion

After discharge from a CRRC program, both individual and group interventions are more effective in maintaining glycemia and blood pressure control for patients with diabetes than usual care after 1-year of follow-up.     

Higher vaspin levels in subjects with obesity and type 2 diabetes mellitus: A meta-analysis

Aims

Visceral adipose tissue-derived serpin (vaspin) was identified as a new adipocytokine. Many studies reported vaspin concentrations in obese subjects and type 2 diabetes mellitus (T2DM) patients. However, large variation in levels of vaspin seen in different studies may be attributable to differences of sample size. The aim of this study is to establish an accurate confidence interval of vaspin levels in obese subjects and T2DM patients using a large-scale meta-analysis.

Methods

Publications of the association between vaspin and obesity and T2DM in the databases of Medline, PubMed and EMBase were collected. The keywords included “vaspin” and “visceral adipose tissue-derived serpin”. Review manager 5.0 was used to process the data.

Results

For the analysis of obesity, 6 studies with 1826 participants were included in our meta-analysis; the level of vaspin was 0.52 ng/ml [95% confidence interval (CI)](0.10–0.93, P = 0.02) higher in obese subjects than that in non-obese healthy controls. Eleven studies with 1570 patients were included for the analysis of T2DM; the level of vaspin was 0.36 ng/ml [95%CI] (0.23–0.49, P < 0.00001) higher compared with that in healthy controls.

Conclusions

Significantly higher levels of serum vaspin were observed in obese subjects and T2DM patients.     

Clampless off-pump surgery reduces stroke in patients with left main disease

Background

Surgical revascularization is the most appropriate therapy for patients with significant left main coronary-artery disease (LMD). An incidence of perioperative stroke remains an issue when compared to the early outcomes to percutaneous coronary intervention (PCI). This study evaluates the safety and impact of standardized “clampless” OPCAB techniques, composed of either complete in situ grafting or “clampless” device enabled techniques for stroke reduction in patients undergoing surgical revascularization for LMD.

Methods

Between 1999 and 2009, 1031 patients with LMD underwent myocardial-revascularization at our institution. Of these, 507 patients underwent “clampless” OPCAB and 524 patients underwent conventional on-pump CABG (ONCABG). Data-collection was performed prospectively and a propensity-adjusted regression-analysis was applied to balance patient characteristics. LMD was defined as a stenosis > 50% and endpoints were mortality, stroke, a cardiac-composite (including death, stroke and myocardial-infarction); a non-cardiac composite and complete-revascularization.

Results

In OPCAB patients, the cardiac composite (3.0% vs. 7.8%; propensity-adjusted (PA)OR = 0.27; CI95% 0.12–0.65; p = 0.003) as well as the occurrence of stroke (0.4% vs. 2.9%; PAOR = 0.04; CI95% 0.003–0.48; p = 0.012) were significantly lower while the mortality-rate was well comparable between groups (1.8% vs. 2.5%; PAOR = 0.44; CI95% 0.11–1.71; p = 0.24). The non-cardiac composite was also significantly decreased after OPCAB (8.9% vs. 19.7%; PAOR = 0.55; CI95% 0.34–0.89; p = 0.014) and complete revascularization was achieved for similar proportions in both groups (95.1% vs. 93.7%; p = 0.35).

Conclusions

This study shows the superiority of OPCAB for patients with LMD with regards to risk-adjusted outcomes other than mortality. A “clampless OPCAB strategy”, effectively reduces stroke yielding similar early outcomes as PCI.