Usefulness of the plasma glucose concentration-to-HbA1c ratio in predicting clinical outcomes during acute illness with extreme hyperglycaemia

AimsTo evaluate the correlation between the plasma glucose-to-glycated haemoglobin ratio (GAR) and clinical outcome during acute illness.MethodsThis retrospective observational cohort study enrolled 661 patients who visited the emergency department of our hospital between 1 July 2008 and 30 September 2010 with plasma glucose concentrations > 500 mg/dL. Systolic blood pressure, heart rate, white blood cells, neutrophils, haematocrit, blood urea nitrogen, serum creatinine, liver function and plasma glucose concentration were recorded at the initial presentation to the emergency department. Data on glycated haemoglobin over the preceding 6 months were reviewed from our hospital database. The glucose-to-HbA_1c ratio (GAR) was calculated as the plasma glucose concentration divided by glycated haemoglobin.ResultsThe GAR of those who died was significantly higher than that of the survivors (81.0 ± 25.9 vs 67.6 ± 25.0; P < 0.001). There was a trend towards a higher 90-day mortality rate in patients with higher GARs (log-rank test P < 0.0001 for trend). On multivariate Cox regression analysis, the GAR was significantly related to 90-day mortality (hazard ratio [HR] for 1 standard deviation [SD] change: 1.41, 95% confidence interval [CI]: 1.22–1.63; P < 0.001), but not to plasma glucose (HR: 0.89, 95% CI: 0.70–1.13; P = 0.328). Rates of intensive care unit (ICU) admission and mechanical ventilator use were also higher in those with higher GARs.ConclusionGAR independently predicted 90-day mortality, ICU admission and use of mechanical ventilation. It was also a better predictor of patient outcomes than plasma glucose alone in patients with extremely high glucose levels.     

Circulating PCSK9 levels in acute coronary syndrome: Results from the PC-SCA-9 prospective study

BackgroundSerum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear.ObjectiveThis study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS).MethodsIn this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters.ResultsA total of 174 patients (mean age: 59 ± 14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P < 0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho = 0.226, P = 0.017) and apolipoprotein B (rho = 0.282, P = 0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho = 0.239, P = 0.009), but not in the statin-treated group (P = NS). This association was maintained after adjusting for LDL-C (P = 0.014) and major CV risk factors (P = 0.008).ConclusionSerum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS.     

Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: Associations with inflammatory and cardiometabolic markers in 4391 subjects

AimThis study aimed to compare concentrations of serum 25-hydroxy vitamin D and inflammatory markers in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and to determine whether the relationship between vitamin D levels and both cardiometabolic and inflammatory markers differs between MHO and MUO.MethodsThis cross-sectional study comprised 4391 obese subjects aged > 18 years. A panel of cardiometabolic and inflammatory markers, including anthropometric variables, glycaemic indices, lipid profiles, liver enzymes, homocysteine, C-reactive protein (CRP), fibrinogen and serum 25-hydroxy vitamin D levels, was investigated. All cardiometabolic and inflammatory markers in MHO and MUO as well as in vitamin D deficiency were compared.ResultsPrevalence of MHO was 41.9% in our obese subjects using International Diabetes Federation criteria. Considering insulin resistance and inflammation, the prevalence of MHO was 38.4%. Individuals with MHO had significantly higher vitamin D concentrations compared with MUO, and this difference in vitamin D status persisted after accounting for BMI and waist circumference. Subjects with MHO had significantly better metabolic status, lower liver enzymes, lower inflammatory markers and higher serum 25-hydroxy vitamin D than those with MUO. Associations between vitamin D levels and inflammatory and cardiometabolic markers differed according to MHO/MUO status. Among MUO subjects, vitamin D deficiency was associated with higher liver marker and homocysteine levels. Serum vitamin D was negatively associated with fasting plasma glucose and HbA_1c in MHO only.ConclusionSerum 25-hydroxy vitamin D levels were lower in MUO vs MHO, and reduced vitamin D concentrations were more strongly associated with cardiometabolic and inflammatory markers in MUO than in MHO subjects. These findings suggest that a deficiency in vitamin D could be a key component of MUO.     

Association between serum uric acid (SUA) levels and metabolic syndrome (MetS) components in personnel of Shahroud University of Medical Sciences

AimsSerum uric acid level has been suggested to be associated with metabolic syndrome risk factors. However, the association between metabolic syndrome and serum uric acid is still controversial and challenging. This study was aimed to investigate the association between serum uric acid levels and metabolic syndrome components in personnel of the Shahroud University of Medical Sciences.Material and methodsThis case–control study was conducted on 499 personnel aged 30–60 years old who were working in Shahroud University of Medical Sciences, in 2015. MetS was defined according to the National Cholesterol Education Program (NCEP) criteria. The relationship between serum UA level and the number of metabolic components was determined by linear regression analysis.ResultIn this study, the mean concentration of serum uric acid in men with the syndrome was higher than that in women. Mean serum UA level increased as the number of metabolic factors increased. The mean serum uric acid levels was 4.98 ± 1.64 in patients with metabolic syndrome and 4.5 ± 1.28 in non-patients (p = 0.005). Subject with abnormal uric acid were almost 2.62 times more likely than other subject to develop the syndrome.ConclusionsThe results of this study showed that only hypertriglyceridemia is a component which increases the risk of hyperuricemia. In addition, hyperuricemia increases the risk of metabolic syndrome by more than two fold. It seems that high uric acid can be considered as a predisposing factor for metabolic syndrome; thus, it is recommended to measure serum uric acid in routine tests.     

Prevention of acute renal failure

Acute renal failure (ARF) comprises a family of syndromes that is characterized by an abrupt and sustained decrease in the glomerular filtration rate. In the ICU, ARF is most often due to sepsis and other systemic inflammatory states. ARF is common among the critically ill and injured and significantly adds to morbidity and mortality of these patients. Despite many advances in medical technology, the mortality and morbidity of ARF in the ICU continue to remain high and have not improved significantly over the past 2 decades. Primary strategies to prevent ARF still include adequate hydration, maintenance of mean arterial pressure, and minimizing nephrotoxin exposure. Diuretics and dopamine have been shown to be ineffective in the prevention of ARF or improving outcomes once ARF occurs. Increasing insight into mechanisms leading to ARF and the importance of facilitating renal recovery has prompted investigators to evaluate the role of newer therapeutic agents in the prevention of ARF.     

Panvascular disease – Diagnosis and management

Panvascular disease (PVD) increases significantly the risk for cardiovascular events (myocardial infarction, stroke and cardiovascular death); the more sites affected, the greater the risk of a major cardiac event. Despite its high incidence and severe cardiovascular prognosis, PVD has still not been well studied. History of risk factors and co-morbidities, as well as a detailed physical examination, are mandatory in the initial screening and diagnostic work-up. The ankle-brachial index and various non-invasive imaging methods such as duplex ultrasound, computed tomography or magnetic resonance angiography are used for the diagnosis of atherosclerosis in various vascular beds, while digital subtraction angiography is currently used almost exclusively in association with endovascular procedures. Appropriate utilization of techniques is based on international guidelines and a multidisciplinary discussion for each case.Management of a patient diagnosed with PVD can be very complex. Secondary preventive measures and aggressive medical treatment are needed to reduce excess cardiovascular risk. Whether routine screening for atherosclerosis at various sites in the arterial tree in all or selected patients may alter treatment to improve outcome in these patients has not been shown.In the lack of hard evidence, individualized decision-making is needed with the collaboration of many specialties in a multidisciplinary approach. In general, the more symptomatic lesion or the lesion with the strongest prognostic impact should be treated first. In selected cases combined interventions can be done. Perioperative cardiovascular complications are common in patients with PVD, thus preoperative targeted screening may be needed.Clinical studies are needed to identify more effective approaches to diagnose and treat these patients. A single trial performed so far failed to demonstrate a panvascular screening in patients with severe coronary artery disease. Meanwhile, a multidisciplinary team is often needed to optimize short- and long-term prognosis.     

Basal insulin treatment intensification in patients with type 2 diabetes mellitus: A comprehensive systematic review of current options

AimAs type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium–glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin.MethodsMEDLINE, EMBASE and EBSCOhost were searched for English-language articles, and all those captured were original articles (case studies and narrative reviews were omitted). Data on study design, population demographics, interventions and outcomes were tabulated. The extracted outcome data included changes in glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), as well as body weight and safety data.ResultsA total of 88 publications were deemed relevant. All treatments reduced HbA_1c and FPG. The most pronounced reductions in PPG, an unmet need in patients not controlled by basal insulin, were seen following administration of RAIs and short-acting GLP-1 RAs, although data for this outcome are generally lacking. Body weight benefits were observed with GLP-1 RAs and SGLT-2 inhibitors. However, as only articles in English were included, the result was a possible publication bias, while the diversity of study designs and drug combinations limited comparisons between studies.ConclusionThe evidence supports effectiveness of the available add-on treatments to basal insulin. However, other factors, such as potential body-weight increases, convenience/compliance and adverse events, particularly hypoglycaemia, should be considered on a patient-by-patient basis to optimalize treatment outcomes.