Decision aids for people with Type 2 diabetes mellitus: an effectiveness rapid review and meta-analysis.

AIMS: To perform a rapid review and meta-analysis of randomized controlled trials (RCTs) evaluating patient decision aids (PtDAs) for people with Type 2 diabetes mellitus. METHODS: We searched Medline and the Cochrane Library for RCTs assessing PtDAs in people with Type 2 diabetes. PtDAs were defined as tools designed to help people engage in decision-making about healthcare options, such as making treatment choices or setting therapeutic goals. The study selection process was facilitated by an automated screening tool to identify RCTs. We classified outcomes into seven domains and conducted meta-analyses using random effects models. RESULTS: We included a total of 15 studies, nine of which were cluster RCTs, that evaluated 10 PtDAs. Thirteen trials compared a PtDA with usual care or usual care plus educational material, whereas two RCTs compared individually tailored vs. non-tailored PtDAs. Meta-analyses showed a favourable effect of PtDAs compared with usual care in reducing decisional conflict [weighted mean difference (WMD) -4.66, 95% confidence interval (CI) -7.93 to -1.39] and in improving knowledge (WMD 20.46, 95% CI 9.13 to 3.77). Use of PtDAs resulted in more active involvement in decision-making during the consultation, although no effect was evident in terms of glycaemic control or self-reported medication adherence. CONCLUSIONS: PtDAs for people with Type 2 diabetes can improve the quality of decision-making and increase knowledge transfer. Interpretation of our findings is attenuated due to limitations related to the rapid review approach, including searching only two databases and performing data extraction and risk of bias assessment by a single reviewer.

Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the efficacy and safety of recently approved once-weekly glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 RA licensed for once-weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate. RESULTS: In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was -0.66% [six studies; 95% confidence interval (CI) -1.14 to -0.19; I(2) = 88%] with albiglutide, and -1.18% (seven studies; 95% CI -1.34 to -1.02; I(2) = 65%) with dulaglutide. Based on data from placebo-controlled trials, we did not detect statistically significant weight-sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once-weekly GLP-1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c-lowering (mean differences -0.40%; 95% CI -0.66 to -0.14; I(2) = 85%, -0.44%; 95% CI -0.58 to -0.29; I(2) = 40% and -0.28; 95% CI -0.45 to -0.10; I(2) = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions. CONCLUSIONS: Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.

Investigating the role of Natural Killer T-cells in Gram negative infections of patients with type 2 diabetes mellitus.

BACKGROUND: Invariant Natural Killer T (iNKT) cells belong to innate immunity and combine T-cell receptor specificity with Natural Killer surface markers. They can produce cytokines immediately after stimulation and direct immunity to either Th1 or Th2 cytokine production. iNKT cells participate in a variety of immune responses, such as microbial infections, autoimmunity, and cancer. Type 2 Diabetes Mellitus (T2DM) has been associated with activated innate immunity and certain cytokine profile during microbial infections. This study aimed to evaluate whether iNKT cells have a role in the immune response of T2DM patients during infections with gram-negative bacteria. METHOD: The T2DM group consisted of patients (n =11) who had a diagnosis of T2DM for at least six months and febrile illness for three days, while the control group consisted of patients (n =11) who had not T2DM, but were febrile for three days. All patients were infected by gram-negative bacteria. Physical examination was performed, and peripheral blood was drawn on days three and six of febrile illness. Flow cytometry was utilized for iNKT cell identification with monoclonal antibodies Phycoerythrin (PE) - Cyanin (CY) 5 anti-Human CD3, Fluorescein isothiocyanate (FITC) anti-Human CD4, PE anti-human invariant NKT T-Cell Receptor. For intracellular staining, we used Alexa Fluor anti-Human interferon-γ (IFN-γ) and Allophycocyanin (APC) anti-human interleukin-4 (IL-4). The variables processed were: CD3+IL-4+iNKT+ , CD4+IL-4+iNKT+, CD3+IFNγ+iNKT+, CD4+IFNγ+iΝΚΤ+, CD3+iNKT+, CD4+iNKT+ ,CD3+IL4+, CD4+IL-4+, CD3+IFNγ+, CD4+IFNγ+ on days three and six of febrile illness (CD3+, CD4+: T lymphocyte surface markers, iNKT+: invariant Natural Killer T- Cell Receptor, IL4+: interleukin 4, IFNγ+: interferon γ). RESULTS: Comparisons between T2DM patients and controls revealed no statistically significant difference in any of the study's variable. Regarding within T2DM patients comparisons CD4+IL4+iNKT+, CD3+IL4+iNKT+, CD4+IFN+iNKT+, CD3+IFN+iNKT+, and CD3+iNKT+  decreased, whereas CD3+IL4+ was increased at day six compared to day three. Within control group CD4+IL4+iNKT+, CD3+IL4+iNKT+, and CD3+iNKT+ were decreased, whereas CD4+IFN+, CD3+IFN+ were increased at day six compared to day three. CONCLUSION: The absence of statistical difference between T2DM patients and controls implies that the role of iNKT cells is virtually the same in both groups of patients during the course of gram-negative infections and that there is no numerical variance of this cell population between the two groups. Despite the small sample size, we notice that all iNKT parameters (both IL4/IFNγ) are suppressed in the T2DM group during the later phase, but only those concerning IL4+iNKT+ in the control group, suggesting that IFNγ production remains elevated in the controls. A compensatory anti-inflammatory type-response could provide an explanation for the prevalence of IL4 production during the later phase of infection in T2DM and the sustained production of IFNγ in controls. Hippokratia 2015; 19 (3): 231-234.

Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis.

AIM: To assess the efficacy and safety of the novel sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin compared with placebo or other antidiabetic agents in patients with type 2 diabetes. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials. We searched Medline, Embase and the Cochrane Library through December 2013 and grey literature. Two reviewers working independently extracted relevant data and carried out risk-of-bias assessments. We synthesized results using random-effects models and computed weighted mean differences (WMDs) and odds ratios (ORs). RESULTS: We included 10 studies with 6203 participants. Compared with placebo, mean changes in haemoglobin A1c were -0.62% [95% confidence interval (CI) -0.68 to -0.57%] for empagliflozin 10 mg and -0.66% (-0.76 to -0.57%) for empagliflozin 25 mg. Empagliflozin 25 mg daily had glycaemic efficacy similar to metformin or sitagliptin (WMD -0.11%; 95% CI -0.25 to 0.03%), without increasing risk for hypoglycaemia. It was also associated with body weight loss (WMD -1.84; 95% CI -2.30 to -1.38 kg vs. placebo) and had a favourable effect on blood pressure. Incidence of hypoglycaemia with empagliflozin was similar to placebo (OR 1.10; 95% CI 0.87 to 1.39); nevertheless we noted an increased risk for genital tract infections (OR 3.31; 95% CI 1.55 to 7.09). Findings were similar for the 10-mg dosing regimen. CONCLUSIONS: Empagliflozin effectively lowers blood glucose and provides additional clinical benefits including body weight and blood pressure reduction. Ongoing trials will elucidate the long-term safety and effect of empagliflozin on cardiovascular outcomes.

Large- and small-for-gestational-age neonates born by women with gestational diabetes mellitus diagnosed by the new IADPSG criteria: a case-control study of 289 patients and 1 108 controls.

BACKGROUND: The primary aim of this case-control study was to compare women whose pregnancy was complicated with gestational diabetes mellitus (GDM), diagnosed by the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, with a control group of healthy, pregnant women in terms of incidence of large- (LGA) and small-for-gestational-age (SGA) neonates. Our secondary aim was to compare intrauterine growth of fetuses between the same 2 populations. PATIENTS AND METHODS: The study included 289 women diagnosed as having GDM in the current pregnancy and 1 108 pregnant controls. Women were followed-up every 2 (GDM group) or 4 weeks (control group). The main metabolic parameters recorded were body mass index, fasting plasma glucose, home blood glucose and glycated hemoglobin A1c. The main ultrasonographic parameters were estimated fetal weight (EFW), head (HC) and abdominal circumferences (AC). Decisions on treatment modification in the GDM group were based on both metabolic and ultrasonographic parameters. RESULTS: There was no evidence for a difference in the incidence of LGA (9.9 vs. 9.2%, Chi-square, p=0.745) or SGA (10.5 vs. 9.0%, p=0.524) in GDM and in control group, respectively. No significant differences were found in EFW or AC between GDM and control groups during the second and third trimester. CONCLUSIONS: Incidence of LGA and SGA neonates is similar among healthy pregnant women and women with GDM, diagnosed by the new IADPSG criteria and treated according to both metabolic and ultrasonographic parameters.

Is deferasirox implicated in multiple organ failure in a patient with homozygous ß-thalassemia?

We herein report a case of a thalassemic-patient who was on deferasirox chelation therapy and admitted to the emergency department because of fever, diffuse abdominal pain and altered mental status. Despite the appropriate treatment he died two days later due to cardiac arrest. As we failed to recognize any etiology and the patients' relatives denied a post mortem examination due to religious reasons, we cannot provide any additional data. However, we are wondering whether this incident might be related to deferasirox.

Glycemia and cardiovascular risk: challenging evidence based medicine.

Optimal glycemic control is well known to reduce effectively the risk of micro vascular complications both in type 1 and type 2 diabetes mellitus. However the role of glycemic control in decreasing the risk of myocardial infarction and ischemic stroke, the leading causes of death in patients with diabetes, has been so far controversial. In this review, based on data recently reported from large interventional studies, we discuss the possible causal relationship between glycemia and cardiovascular outcomes in type 1 and type 2 diabetes. Strict glycemic control right from the diagnosis of the disease may be effective in reducing long term incidence of cardiovascular (CV) disease in both T1 and T2 diabetics. Nevertheless such a strategy could be potentially harmful for T2 diabetics with long duration of sub optimal glycemic control and already established CV complications. Treatment targets in these patients should be individualized taking into account other aspects of glycemic control and diabetes complications such as hypoglycemia and autonomic neuropathy.

Gestational diabetes mellitus: why screen and how to diagnose.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Women with GDM and their offspring have an increased risk of developing type 2 diabetes mellitus in the future. The global incidence of GDM is difficult to estimate, due to lack of uniform diagnostic criteria. Various diagnostic criteria have been proposed. The benefit of treating GDM has also been controversial. The clinical significance of treating maternal hyperglycemia was made evident in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The HAPO study demonstrated that there is a continuous association of maternal glucose levels with adverse pregnancy outcomes and served as the basis for a new set of diagnostic criteria, proposed in 2010 by the International Association of Diabetes and Pregnancy Groups (IADPSG). According to these criteria the diagnosis of GDM is made if there is at least one abnormal value (≥92, 180 and 153 mg/dl for fasting, one-hour and two-hour plasma glucose concentration respectively), after a 75 g oral glucose tolerance test (OGTT).

Glycaemic control is correlated with well-being index (WHO-5) in subjects with type 2 diabetes.

UNLABELLED: The aim of this study was to examine the potential correlation of WHO-5 well-being index with glycaemic control and chronic complications in subjects with type 2 diabetes. The study included 156 subjects (73 men, mean age 64.05+/-9.11 years, mean diabetes duration 12.22+/-5.61 years). Well-being was assessed by the WHO-5 score via a validated questionnaire comprising 5 questions (Q1-Q5). HbA (1c) showed a significant negative correlation with overall WHO-5 score (r (s)=-0.248, p=0.002) and individual Q1-Q4 scores (r (s)=-0.262, p=0.001; r (s)=-0.248, p=0.002; r (s)=-0.207, p=0.009 and r (s)=-0.169, p=0.035 respectively). Subjects with adequate glycaemic control (HbA (1c) < 7%, n=67) had a significantly higher WHO-5 score in comparison to those with inadequate glycaemic control (HbA (1c) >or= 7%, n=89) (mean+/-SD: 19.69+/-5.47 vs. mean+/-SD: 17.11+/-6.38, p=0.011). Finally, WHO-5 score was significantly (p=0.013) lower in subjects with neuropathic pain than in those without neuropathic pain. CONCLUSIONS: In type 2 diabetic subjects, glycaemic control shows a significant correlation with well-being, while neuropathic pain is associated with lower well-being score.

Association between BBS6/MKKS gene polymorphisms, obesity and metabolic syndrome in the Greek population.

OBJECTIVE: To investigate the relationship between MKKS gene variations, obesity-related traits and features of the metabolic syndrome (MS) in the Greek population. DESIGN AND SUBJECTS: Genotype and haplotype analysis was carried out for six known MKKS gene polymorphisms (534C>T, 985+16T>G, 985+33C>G, 986-29A>T, 1161+58A>G and 1595G>T) in 220 obese subjects (body mass index > or =30 kg/m(2)) and 330 non-obese controls. RESULTS: Genotype frequencies of the 985+16T>G, 986-29A>T and 1595G>T SNPs were significantly different between obese and non-obese individuals (P=0.0016, 0.0196 and 0.0069, respectively). Obese carriers of the risk alleles of the above three polymorphisms had a significantly increased prevalence of arterial hypertension. Furthermore, obese carriers of the G allele for the 985+16T>G polymorphism had an increased prevalence of type 2 diabetes mellitus and of MS component traits. A new polymorphism was detected, namely a C to T substitution at position 1129 (1129C>T or N377N). Frequency of the T allele for the 1129C>T polymorphism was significantly higher in control individuals than in obese subjects (P=0.0253). Haplotype TGTGT was more prevalent in obese than in controls (P=0.0002) and was associated with increased prevalence of the MS in obese subjects (P<0.0001). CONCLUSION: Our results suggest that genetic variation in the MKKS gene may play a role in the development of obesity and the metabolic syndrome.

N of 1 trials in diabetes: making individual therapeutic decisions.

N of 1 trials are single-subject, randomised, crossover studies, in which the patient serves as their own control to compare the efficacy of a treatment. They offer an alternative to large, randomised clinical trials, which have limited applicability, and empirical testing, which is arbitrary in nature. N of 1 trials are regarded as providing the highest strength of evidence for individual subject decisions. They rely upon the patient expressing preferences and making shared decisions for determining the future therapy, and may therefore lead to the successful implementation of lifestyle interventions. N of 1 trials are an optimal approach for making therapeutic decisions in chronic diseases like diabetes mellitus, where decision-making is often reliant upon arbitrary criteria and clinical judgement.