Microvascular Disease and Risk of Cardiovascular Events and Death From Intensive Treatment in Type 2 Diabetes: The ACCORDION Study

ObjectiveTo assess whether the presence of microvascular complications modifies the effect of intensive glucose reduction on long-term outcomes in patients with type 2 diabetes.Patients and MethodsUsing ACCORD and ACCORDION study data, we investigated the risk of the primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) or death in relation to the prerandomization type and extent of microvascular complications. Interaction terms were fitted in survival models to estimate the risk of both outcomes across levels of an overall microvascular disease score (range 0 to 100) and its individual components: diabetic nephropathy, retinopathy, and neuropathy.ResultsDuring a mean follow-up of 7.7 years, 1685 primary outcomes and 1806 deaths occurred in 9405 participants. The outcome-specific microvascular score was ≤30 in 97.9% of subjects for the primary outcome and in 98.5% for death. For participants with scores of 0 and 30, respectively, the 10-year absolute risk difference between intensive glucose control and standard treatment ranged from ?0.8% (95% CI, ?2.6, 1.1) to ?3.0% ?7.1, 1.1) for the primary outcome and from ?0.5% (?2.1, 1.1) to 0.7% (?4.2, 5.6) for mortality. Retinopathy was associated with the largest effects, with a 10-year absolute risk difference of ?6.5% (?11.1 to ?2.0) for the primary outcome and ?3.9% (?7.8 to 0.1) for mortality.ConclusionThis hypothesis-generating study identifies diabetic retinopathy as predictor of the beneficial effect of intensive glucose control on the risk of cardiovascular disease and possibly death. Further long-term studies are required to confirm these findings.     

Biochemical Urine Testing of Medication Adherence and Its Association With Clinical Markers in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT)

OBJECTIVETo assess adherence to the three main drug classes in real-world patients with type 2 diabetes using biochemical urine testing, and to determine the association of nonadherence with baseline demographics, treatment targets, and complications.RESEARCH DESIGN AND METHODSAnalyses were performed of baseline data on 457 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT) study. Adherence to oral antidiabetics (OADs), antihypertensives, and statins was determined by analyzing baseline urine samples using liquid chromatography–tandem mass spectrometry. Primary outcomes were microvascular and macrovascular complications and treatment targets of LDL cholesterol, HbA_1c, and blood pressure. These were assessed cross-sectionally at baseline.RESULTSOverall, 89.3% of patients were identified as adherent. Adherence rates to OADs, antihypertensives, and statins were 95.7%, 92.0%, and 95.5%, respectively. The prevalence of microvascular (81.6% vs. 66.2%; P = 0.029) and macrovascular complications (55.1% vs. 37.0%; P = 0.014) was significantly higher in nonadherent patients. The percentage of patients who reached an LDL cholesterol target of ≤2.5 mmol/L was lower (67.4% vs. 81.1%; P = 0.029) in nonadherent patients. Binary logistic regression indicated that higher BMI, current smoking, elevated serum LDL cholesterol, high HbA_1c, presence of diabetic kidney disease, and presence of macrovascular disease were associated with nonadherence.CONCLUSIONSAlthough medication adherence of real-world type 2 diabetes patients managed in specialist care was relatively high, the prevalence of microvascular and macrovascular complications was significantly higher in nonadherent patients, and treatment targets were reached less frequently. This emphasizes the importance of objective detection and tailored interventions to improve adherence.     

Mucormycosis at a tertiary care centre in Gujarat,India

The prevalence of mucormycosis is reportedly high in India, although the studies are mainly from north and south India only. We analysed the mucormycosis cases at tertiary care centres of West India. We retrieved the clinical details of all the patients with probable and proven mucormycosis diagnosed at Sterling Hospital and ID clinic at Ahmedabad, Gujarat over the period from 1 January 2013 through 30 April 2015. The data were analysed to determine demography, risk factors, underlying diseases, site of infection and outcome of these patients. A total of 27 patients with the median age of 50 (16‐65) years were diagnosed with mucormycosis during the period. Rhino‐orbital‐cerebral mucormycosis was the most common (51.9%) presentation. Majority (55.6%) of the patients had uncontrolled diabetes with or without ketoacidosis; 25.9% patients had no underlying disease and most of them (85.7%) had cutaneous mucormycosis. In this group, the mortality was 25.9% and an equal percentage of patients were lost to follow up; 14 (51.9%) patients could complete 6 weeks of amphotericin B therapy. All patients who completed antifungal therapy survived except one. Like other parts of India, uncontrolled diabetes was the predominant risk factor for mucormycosis in our group. Patients completing 6 weeks of amphotericin B treatment were likely to survive.     

Predicting hospital stay,mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation

Aims/hypothesis

Hospital admissions for hypoglycaemia represent a significant burden on individuals with diabetes and have a substantial economic impact on healthcare systems. To date, no prognostic models have been developed to predict outcomes following admission for hypoglycaemia. We aimed to develop and validate prediction models to estimate risk of inpatient death, 24 h discharge and one month readmission in people admitted to hospital for hypoglycaemia.

Methods

We used the Hospital Episode Statistics database, which includes data on all hospital admission to National Health Service hospital trusts in England, to extract admissions for hypoglycaemia between 2010 and 2014. We developed, internally and temporally validated, and compared two prognostic risk models for each outcome. The first model included age, sex, ethnicity, region, social deprivation and Charlson score (‘base’ model). In the second model, we added to the ‘base’ model the 20 most common medical conditions and applied a stepwise backward selection of variables (‘disease’ model). We used C-index and calibration plots to assess model performance and developed a calculator to estimate probabilities of outcomes according to individual characteristics.

Results

In derivation samples, 296 out of 11,136 admissions resulted in inpatient death, 1789/33,825 in one month readmission and 8396/33,803 in 24 h discharge. Corresponding values for validation samples were: 296/10,976, 1207/22,112 and 5363/22,107. The two models had similar discrimination. In derivation samples, C-indices for the base and disease models, respectively, were: 0.77 (95% CI 0.75, 0.80) and 0.78 (0.75, 0.80) for death, 0.57 (0.56, 0.59) and 0.57 (0.56, 0.58) for one month readmission, and 0.68 (0.67, 0.69) and 0.69 (0.68, 0.69) for 24 h discharge. Corresponding values in validation samples were: 0.74 (0.71, 0.76) and 0.74 (0.72, 0.77), 0.55 (0.54, 0.57) and 0.55 (0.53, 0.56), and 0.66 (0.65, 0.67) and 0.67 (0.66, 0.68). In both derivation and validation samples, calibration plots showed good agreement for the three outcomes. We developed a calculator of probabilities for inpatient death and 24 h discharge given the low performance of one month readmission models.

Conclusions/interpretation

This simple and pragmatic tool to predict in-hospital death and 24 h discharge has the potential to reduce mortality and improve discharge in people admitted for hypoglycaemia.

     

Lipidomic changes in rat liver after long-term exposure to ethanol

Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD.     

Screening for the metabolic syndrome using simple anthropometric measurements in south Asian and white Europeans: A population-based screening study. The Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) Study

AimsTo estimate the prevalence of metabolic syndrome in a general population sample of south Asians and white Europeans and compare predictors of metabolic syndrome, using ethnic specific definitions of obesity.Methods3099 participants (71.4% white European, 28.6% south Asian) aged 40–75 years were screened using a 75 g oral glucose tolerance test. Metabolic syndrome was defined using National Cholesterol Education Programme and International Diabetes Federation definitions. We compared sensitivity, specificity and area under the curve of waist circumference, body mass index and waist–hip ratio.ResultsThe prevalence of metabolic syndrome using the definitions above was 29.9% (29.2% south Asian, 30.2% white European), and 34.4% (34.2% south Asian, 34.5% white European), respectively. Using the National Cholesterol Education Programme definition, waist circumference was significantly more predictive of metabolic syndrome than body mass index or waist–hip ratio. The area under the curve for waist circumference was 0.75 (95% CI: 0.69–0.80) and 0.76 (0.72–0.81) for south Asian men and women; 0.83 (0.80–0.85) and 0.80 (0.77–0.82) for white European men and women.ConclusionsThe prevalence of metabolic syndrome is high in both south Asian and white European populations. Waist circumference is a simple and effective measure for predicting metabolic syndrome in different populations.     

Should glycated haemoglobin (HbA1c) be used to detect people with type 2 diabetes mellitus and impaired glucose regulation?

There is a need to simplify screening tests for type 2 diabetes mellitus (T2DM) so patients can be identified earlier and more efficiently. Glycated haemoglobin (HbA1c) has been recommended by some international organisations as a diagnostic tool for detecting T2DM and impaired glucose regulation (IGR, also termed prediabetes and includes impaired fasting glucose and/or impaired glucose tolerance). The HbA1c cut-point of ≥6.5% (48 mmol/mol) has been selected as diagnostic for T2DM, while the cut-points for IGR are debated by the different international organisations: an International Expert Committee has suggested using HbA1c 6.0-6.4% (42-46 mmol/mol); however, the American Diabetes Association has recommended using HbA1c 5.7-6.4% (39-46 mmol/mol). Some countries will adopt a new method of reporting HbA1c values in millimoles per mole (mmol/mol). Use of HbA1c has some logistical advantages over using an oral glucose tolerance test (OGTT). As patients do not need to fast, appointments do not need to be limited to the morning. The HbA1c result reflects longer term glycaemia and is less affected by recent physical/emotional stress. However, there is some debate as to whether HbA1c should replace fasting plasma glucose or the OGTT. As the two tests detect different people, some individuals with diabetes detected on OGTT will no longer be classified as having T2DM using HbA1c ≥6.5% criteria. Furthermore, some medical conditions can result in HbA1c assay measurements not reflecting glycaemic control over the last 2-3 months; these include haematological disorders, renal failure, and chronic excess alcohol consumption.     

Reduction of Petroleum Hydrocarbons and Toxicity in Refinery Wastewater by Bioremediation

The aim of the study was to investigate petroleum waste remediation and toxicity reduction by five bacterial strains: Ralstonia picketti SRS (BP-20), Alcaligenes piechaudii SRS (CZOR L-1B), Bacillus subtilis (I'-1a), Bacillus sp. (T-1), and Bacillus sp. (T'-1), previously isolated from petroleum-contaminated soils. Petroleum hydrocarbons were significantly degraded (91%) by the mixed bacterial cultures in 30 days (reaching up to 29% in the first 72 h). Similarly, the toxicity of the biodegraded petroleum waste decreased 3-fold after 30 days. This work shows the influence of bacteria on hydrocarbon degradation and associated toxicity, and its dependence on the specific microorganisms present. The ability of these mixed cultures to degrade hydrocarbons and reduce toxicity makes them candidates for environmental restoration applications at other hydrocarbon-contaminated environments.