Plasma interleukin-6 is associated with coagulation in poorly controlled patients with Type 2 diabetes.

AIMS: We investigated the relationship between interleukin (IL)-6 and coagulation, i.e. whether changes in the plasma IL-6 are associated with those in coagulation markers (D dimer and fibrinogen) after glycaemic control with sulphonylurea or insulin in poorly controlled patients with Type 2 diabetes. METHODS: We studied 42 patients with Type 2 diabetes, including 19 subsequently treated with sulphonylurea, 23 treated with insulin and 48 control subjects. All patients were in poor glycaemic control and were hospitalized for 3 weeks. At the beginning and end of treatment, we measured plasma concentrations of IL-6, fibrinogen, and D dimer. RESULTS: Plasma concentrations of IL-6 and D dimer were significantly higher in diabetic patients than in controls (P<0.0001 for both). In all patients with diabetes, the plasma concentration of IL-6 decreased significantly (P<0.001) after treatment. Changes in the plasma IL-6 during hospitalization were positively correlated with those in plasma D dimer and fibrinogen (r=0.664, P<0.0001; r=0.472, P=0.0042, respectively). Treatment with sulphonylurea or insulin caused a similar fall in the plasma IL-6 concentration with a concomitant decrease in the BMI and an equal improvement in glycaemia. CONCLUSIONS: In poorly controlled patients with Type 2 diabetes, plasma IL-6 concentrations were reduced significantly even by short-term metabolic control. As changes in the plasma concentrations of D dimer are related to plasma IL-6, plasma IL-6 may reflect a pro-coagulant as well as an inflammatory state in patients with Type 2 diabetes.     

Association between rs13266634 C/T polymorphisms of solute carrier family 30 member 8 (SLC30A8) and type 2 diabetes, impaired glucose tolerance, type 1 diabetes--a meta-analysis

Aims

To investigate the association of solute carrier family 30 member 8 (SLC30A8) rs13266634 C/T polymorphism with type 2 diabetes (T2DM), impaired glucose tolerance (IGT), and type 1 diabetes (T1DM).

Methods

We searched all the publications about the association between SLC30A8 and diabetes from PubMed, and evaluated the association between SLC30A8 rs13266634 C/T polymorphism and T2DM, IGT and T1DM, respectively, by meta-analysis of all the validated studies. Allelic and genotypic comparisons between cases and controls were evaluated.

Results

Thirty six studies were included in the meta-analysis: 31 studies were analysed for rs13266634 C/T polymorphism with T2DM, 3 studies with IGT and 4 studies with T1DM. The pooled odds ratios (ORs) for allelic and genotypic comparisons (including additive model, co-dominant model, dominant model and recessive model) showed that rs13266634 C/T polymorphism was significantly associated with increased T2DM risk: OR = 1.15, 95% confidence interval (CI) = 1.13-1.17, P < 0.001, P_{heterogeneity} = 0.041, OR = 1.34, 95% CI = 1.26-1.41, P < 0.001, P_{heterogeneity} = 0.908, OR = 1.20, 95% CI = 1.16-1.24, P < 0.001, P_{heterogeneity} = 0.699, and OR = 1.23, 95% CI = 1.17-1.30, P < 0.001, P_{heterogeneity} = 0.801, respectively. In subgroup analyses, we found that rs13266634 C/T polymorphism was associated with T2DM risk both in Asian and European subgroup (P < 0.001), but not in African (P > 0.05). And the pooled odds ratio (OR) for allelic frequency comparison showed that rs13266634 C/T polymorphism was also significantly associated with IGT: OR = 1.15, 95% CI = 1.06-1.26, P < 0.001, P_{heterogeneity} = 0.364. Meanwhile, our meta-analysis did not suggest that rs13266634 C/T polymorphism was associated with T1DM risk (P > 0.05): OR = 1.02, 95% CI = 0.98-1.06, P = 0.328, P_{heterogeneity} = 0.488 for allelic frequency comparison.

Conclusions

Our meta-analysis results revealed the significant association between rs13266634 C/T polymorphism and T2DM and IGT, but did not support the association between this polymorphism and T1DM.     

Altered Endothelial Function in Asymptomatic Male Adolescents with Type 1 Diabetes

Objective. While adult men and women with diabetes experience similar rates of cardiovascular disease, early microvascular complications show significant gender differences during adolescence. The goal of this study was to determine whether a gender contrast in a preclinical stage of atherosclerosis, or endothelial dysfunction, is present in pediatric diabetic patients. Methods. Reactive hyperemia‐peripheral arterial tonometry (RH‐PAT), a noninvasive method to assess endothelial dysfunction, was used. Measurements were performed at rest and after hyperemia in 20 diabetic subjects and 20 age‐ and gender‐matched nondiabetics, aged 12–16 years. Confounding risk factors for endothelial dysfunction, including smoking, obesity, and hypertension, were excluded. Results. RH‐PAT was lower for male diabetic subjects vs. controls (n = 12, 1.60 ± 0.32 vs. 1.92 ± 0.28, P < .001). RH‐PAT was similar in female diabetic patients vs. controls. Male and females with type 1 diabetes subjects had equivalent metabolic control (HbA1C 7.48 ± 1.0 vs. 7.51 ± 0.9) and lipid profiles. No difference was observed in age, HbA1C, and diabetes duration, between male and female diabetic subjects. However, diabetic female patients had a greater body mass index (24.2 ± 2.5 vs. 20.6 ± 2.0, P = .003) and were more mature in pubertal status as compared with diabetic male patients. Conclusion. Endothelial dysfunction was present in adolescent male diabetic subjects as measured using RH‐PAT. Considering that endothelial dysfunction is reversible, early detection of this process may have theurapeutic and prognostic implications in this young age group.     

Low bone mineral density is associated to poor glycemic control and increased OPG expression in children and adolescents with type 1 diabetes

Aims

To investigate early alterations on bone mineral density (BMD) and RANK, RANKL and OPG mRNA expression in peripheral blood leukocytes (PBL) in children and adolescents with type 1 diabetes (T1D) and the relationship with glycemic control and bone biomarkers.

Methods

This cross-sectional study included 75 children and adolescents with T1D and 100 individuals without diabetes (normoglycemic–NG) aged 6–20 years old. T1D individuals were considered to have good (T1DG) or poor (T1DP) glycemic control according to the values of HbA1c. Phosphorus, magnesium, total and ionized calcium, osteocalcin, alkaline phosphatase and tartaric-resistant acid phosphatase (TRAP) values were determined in blood samples. BMD was measured by DEXA. RANK, RANKL and OPG mRNA expression was measured in PBL by real-time PCR.

Results

Osteocalcin values were decreased in diabetic groups in comparison to NG group (p < 0.05), and a negative correlation with both serum glucose (r = −0.265, p < 0.01) and Hb1Ac (r = −0.252, p < 0.01) in T1D group was found. BMD was lower in diabetic groups in comparison with NG group (p < 0.05) and a negative correlation was observed between BMD and both serum glucose (r = −0.357, p < 0.01) and HbA1c (r = −0.351, p < 0.01) in T1D group. OPG mRNA expression was significantly increased in T1D and T1DP groups in comparison with NG group (p < 0.05). In conclusion, children and adolescents with early onset T1D presented low bone mineral density associated to unsatisfactory glycemic control, increased OPG mRNA expression and low osteocalcin concentration.     

Prevalence,correlates and management of type 2 diabetes mellitus in Lebanon: Findings from a national population-based study

Aims

This study aims to examine the prevalence, associated risk factors and complications of diabetes, as well management and preventive care in Lebanon, a small, middle-income country of the Mediterranean region.

Methods

Using a comprehensive multi-dimensional questionnaire, a cross-sectional national survey of 2195 Lebanese adults aged ≥25 years was conducted based on the WHO STEPwise guidelines. The outcome variable, diabetes, was self-reported. Measures for diabetes management included frequency of blood glucose testing and regular eye and foot exams. Macrovascular and microvascular complications were also recorded.

Results

The prevalence of type 2 diabetes was 8.5% (95%CI = 7.3–9.7). Factors associated with an increased risk of having diabetes were: being divorced or widowed (OR = 2.56; 95%CI = 1.07–5.42) compared to single, being obese (OR = 1.50, 95%CI = 1.00–2.57), and having a family history of diabetes (OR = 3.40;95%CI = 2.48–5.19). Vigorous physical activity significantly decreased the odds of diabetes (OR = 0.42; 95%CI = 0.24–0.72). Diabetes management and self-care goals were as follows: 82% were not measuring their blood sugar via dextro on a daily basis, 64.2% did not have a foot exam within the past year, and 52.4% did not obtain the recommended yearly eye exam. The most common complications included heart disease (27.8%) and retinopathy (16.6%).

Conclusions

Prevalence of diabetes in Lebanon was comparable to that found in the West, yet remained lower than estimates in other resource-rich neighboring countries. Adherence to management and self-care measures was sub-optimal resulting in high complication rates. Contextual factors play a role in increasing diabetes risk. Population-based interventions to enhance and promote self-management behaviors are essential to improve complication rates.     

l‐Methionine anti‐biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator,ivacaftor

Background

Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l ‐Methionine is an amino acid with reported biofilm‐inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co‐treatment with ivacaftor and l ‐methionine can reduce the formation of Pseudomonas aeruginosa biofilms.

Methods

P aeruginosa (PAO‐1 strain) biofilms were studied in the presence of l ‐methionine and/or ivacaftor. For static biofilm assays, PAO‐1 was cultured in a 48‐well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter‐Glo? assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs.

Results

l ‐Methionine (0.5 μM) significantly reduced PAO‐1 biofilm mass (32.4 ± 18.0%; n = 4; p < 0.001) compared with controls. Low doses of ivacaftor alone (4, 8, and 12 μg/mL) had no effect on biofilm formation. When combined with ivacaftor (4 μg/mL), a synergistic anti‐biofilm effect was noted at 0.05 μM and 0.5 μM of l ‐methionine (two‐way analysis of variane, p = 0.0415) compared with corresponding concentrations of l ‐methionine alone.

Conclusion

Ivacaftor enhanced the anti‐biofilm activity of l ‐methionine against the PAO‐1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l ‐methionine combinations for P aeruginosa sinusitis are planned.

     

Candida species and other yeasts in the oral cavities of type 2 diabetic patients in Cali,Colombia

Objective:

To determine the prevalence of Candida species and to study factors associated to oral cavity colonization in patients with type 2 diabetes mellitus.

Methods:

A total of 107 diabetics were classified into controlled and uncontrolled according to glycosylated hemoglobin values. Each patient was assessed for stimulated salivary flow rates, pH, and an oral rinse to search for yeast. The study also determined the state of oral health via Klein and Palmer CPO indexes for permanent dentition, dental plaque by O''Leary, and a periodontal chart.

Results:

We found yeasts in 74.8% of the patients. A total of 36 of the 52 subjects with controlled diabetes presented yeasts and 44 in the uncontrolled; no significant differences (p = 0.2) were noted among the presence of yeasts and the control of blood glucose. The largest number of isolates corresponded to C. albicans, followed by C. parapsilosis. Uncontrolled individuals presented a significantly higher percentage of yeast different from C. albicans (p = 0.049).

Conclusions:

We found a high percentage of Candida colonization and uncontrolled individuals had greater diversity of species. The wide range of CFU/mL found both in patients with oral candidiasis, as well as in those without it did not permit distinguishing between colonization and disease. We only found association between isolation of yeasts and the low rate of salivary flow.     

Validating an ontology-based algorithm to identify patients with Type 2 Diabetes Mellitus in Electronic Health Records

BackgroundImproving healthcare for people with chronic conditions requires clinical information systems that support integrated care and information exchange, emphasizing a semantic approach to support multiple and disparate Electronic Health Records (EHRs). Using a literature review, the Australian National Guidelines for Type 2 Diabetes Mellitus (T2DM), SNOMED-CT-AU and input from health professionals, we developed a Diabetes Mellitus Ontology (DMO) to diagnose and manage patients with diabetes. This paper describes the manual validation of the DMO-based approach using real world EHR data from a general practice (n = 908 active patients) participating in the electronic Practice Based Research Network (ePBRN).MethodThe DMO-based algorithm to query, using Semantic Protocol and RDF Query Language (SPARQL), the structured fields in the ePBRN data repository were iteratively tested and refined. The accuracy of the final DMO-based algorithm was validated with a manual audit of the general practice EHR. Contingency tables were prepared and Sensitivity and Specificity (accuracy) of the algorithm to diagnose T2DM measured, using the T2DM cases found by manual EHR audit as the gold standard. Accuracy was determined with three attributes – reason for visit (RFV), medication (Rx) and pathology (path) – singly and in combination.ResultsThe Sensitivity and Specificity of the algorithm were 100% and 99.88% with RFV; 96.55% and 98.97% with Rx; and 15.6% and 98.92% with Path. This suggests that Rx and Path data were not as complete or correct as the RFV for this general practice, which kept its RFV information complete and current for diabetes. However, the completeness is good enough for this purpose as confirmed by the very small relative deterioration of the accuracy (Sensitivity and Specificity of 97.67% and 99.18%) when calculated for the combination of RFV, Rx and Path. The manual EHR audit suggested that the accuracy of the algorithm was influenced by data quality such as incorrect data due to mistaken units of measurement and unavailable data due to non-documentation or documented in the wrong place or progress notes, problems with data extraction, encryption and data management errors.ConclusionThis DMO-based algorithm is sufficiently accurate to support a semantic approach, using the RFV, Rx and Path to define patients with T2DM from EHR data. However, the accuracy can be compromised by incomplete or incorrect data. The extent of compromise requires further study, using ontology-based and other approaches.     

Treatment non-adherence among patients with poorly controlled type 2 diabetes in ambulatory care settings in southwestern Nigeria

Background

Poor adherence to prescribed therapy among patients with chronic diseases is a growing concern which undermines the benefits of current medical care.

Objectives

To evaluate the pattern of treatment non-adherence among ambulatory patients with poorly controlled type 2 diabetes in southwestern Nigeria, and to determine the possible factor(s) that accounted for such non-adherence with a view to identifying areas of future intervention to improve outcome.

Methods

A prospective cross-sectional interview using the concept of RIM (Recognize, Identify and Manage) model was used to evaluate adherence to treatment recommendations among 176 consented patients recruited from the endocrinology out-patient clinics of two teaching hospitals in southwestern Nigeria between November, 2010 and January, 2011.

Results

Overlaps of non-adherence behavior were obtained. More than three-quarter (153; 88.4%) were not aware of indication for each of the prescribed medications, 26 (15.3%) correctly described regimen as prescribed. The factorsidentified as possible barriers to medication adherence include practical (145; 40.1%), knowledge (103; 28.5%), and attitudinal (114; 31.5%) barriers. Dietary non-adherence was mostly due to inappropriate guidance (62; 33.7%).

Conclusions

The arrays of non-adherence behavior among the cohort further emphasize the need for patient-centered approach as a reasonable strategy in resolving non-adherence problems in routine clinical practice.     

Alleles that increase risk for type 2 diabetes mellitus are not associated with increased risk for Alzheimer's disease

Although epidemiological studies suggest that type 2 diabetes mellitus (T2DM) increases the risk of late-onset Alzheimer's disease (LOAD), the biological basis of this relationship is not well understood. The aim of this study was to examine the genetic comorbidity between the 2 disorders and to investigate whether genetic liability to T2DM, estimated by a genotype risk scores based on T2DM associated loci, is associated with increased risk of LOAD. This study was performed in 2 stages. In stage 1, we combined genotypes for the top 15 T2DM-associated polymorphisms drawn from approximately 3000 individuals (1349 cases and 1351 control subjects) with extracted and/or imputed data from 6 genome-wide studies (>10,000 individuals; 4507 cases, 2183 controls, 4989 population controls) to form a genotype risk score and examined if this was associated with increased LOAD risk in a combined meta-analysis. In stage 2, we investigated the association of LOAD with an expanded T2DM score made of 45 well-established variants drawn from the 6 genome-wide studies. Results were combined in a meta-analysis. Both stage 1 and stage 2 T2DM risk scores were not associated with LOAD risk (odds ratio = 0.988; 95% confidence interval, 0.972–1.004; p = 0.144 and odds ratio = 0.993; 95% confidence interval, 0.983–1.003; p = 0.149 per allele, respectively). Contrary to expectation, genotype risk scores based on established T2DM candidates were not associated with increased risk of LOAD. The observed epidemiological associations between T2DM and LOAD could therefore be a consequence of secondary disease processes, pleiotropic mechanisms, and/or common environmental risk factors. Future work should focus on well-characterized longitudinal cohorts with extensive phenotypic and genetic data relevant to both LOAD and T2DM.