Diabetes Research and Clinical Practice - Articles in Press

Coronary calcium score, albuminuria and inflammatory markers in type 2 diabetic patients: Associations and prognostic implications - Corrected Proof

2012-05-17

Abstract: Aims: To investigate the relationship of coronary artery calcium (CAC) scores with common carotid artery intima media thickness (CCA-IMT), albuminuria and inflammatory factors in type 2 diabetes.Methods and results: 128 asymptomatic type 2 diabetic patients, with at least one cardiovascular risk factor in addition to diabetes, were included in the study. CAC scores, carotid arteries plaque formation and CCA-IMT were assessed. The patients were followed for a mean period of 36.6±3.3 months. Linear regression analysis identified the logarithmically transformed (Ln) albuminuria (β=0.32, P=0.007), age (β=0.04, P=0.001) and the uric acid (β=0.13, P=0.04) as independent determinants of the CAC score. During follow-up period, cardiovascular events occurred in 18 out of 46 patients with CAC score ≥100 compared with 5 out of 82 patients with CAC score <100 (log rank, P<0.0001). Multivariate Cox proportional hazards analysis identified LnCAC score (P<0.0001), LnAlbuminuria (P=0.01) and uric acid (P=0.03) as independent predictors for cardiovascular events.Conclusions: There was a significant relationship between CAC score, albuminuria and inflammation in patients with type 2 diabetes. LnCAC score together with LnAlbuminuria and uric acid were identified as independent predictors of cardiovascular events in these patients.

All-cause in-hospital mortality and comorbidity in diabetic and non-diabetic patients with stroke - Corrected Proof

2012-05-16

Highlights: ► There is no significant difference in all-cause in-hospital mortality between diabetic and non-diabetic patients with stroke. ► Diabetic patients more frequently present with hypertension, CAD, PAD, albuminuria and an IRF. ► There is no difference in rapid diagnostic and therapeutic intervention between diabetic and non-diabetic patients with stroke.Abstract: Introduction: The aim of this study was to compare diabetic and non-diabetic patients with stroke with regard to their all-cause in-hospital mortality and possible differences regarding their comorbidities.Methods: All patients of the Munich Stroke Registry (2003–2004, n=537) were assessed. Hospital mortality in diabetic (n=160, 29.8%) and non-diabetic (n=377, 70.2%) patients was compared. Pre-existing comorbidities such as hypertension, coronary artery disease (CAD), peripheral arterial disease (PAD), albuminuria and impaired renal function (IRF) were noted.Results: Regarding all-cause in-hospital mortality, no significant differences were found between diabetic and non-diabetic patients. Overall 71 patients (13.2%) died of whom 27 (16.9%) where diabetic and 44 (11.7%) non-diabetic patients (n.s.). Hypertension, CAD, PAD, albuminuria and IRF were more frequent in diabetic patients (p<0.05).Conclusion: Despite multiple comorbidities and risk factors no significant difference in all-cause in-hospital mortality was seen in diabetic patients as compared to non-diabetic patients. Improved treatment strategies and early intervention may compensate for their poorer prognosis.

Association of KCNJ11 E23K gene polymorphism with hypoglycemia in sulfonylurea-treated Type 2 diabetic patients - Corrected Proof

Georgia Ragia, Anna Tavridou, Ioannis Petridis, Vangelis G. Manolopoulos — 2012-05-16

Abstract: Aims: In addition to sulfonylurea-induced severe hypoglycemia, which however is not common in T2DM patients treated solely with oral hypoglycemic drugs, mild hypoglycemia is a frequent adverse event affecting many patients treated with oral hypoglycemic drugs and has a serious impact in patient adherence to therapy and everyday clinical practice. The aim of the present study was to investigate the possible association of KCNJ11 E23K polymorphism with incidence of sulfonylurea-induced mild hypoglycemic events.Methods: 176 T2DM patients receiving sulfonylurea were included in the study, including 92 that had experienced drug-associated hypoglycemia and 84 that had never experienced hypoglycemia while on sulfonylurea treatment. KCNJ11 E23K polymorphism was detected by use of PCR-RFLP method.Results: Frequencies of KCNJ11 E23K genotypes and alleles were not different between hypoglycemic and non-hypoglycemic T2DM patients (p=0.35 and p=0.47, respectively). In logistic regression analysis before and after adjustment for other factors known to affect this condition (age, body mass index, sulfonylurea mean daily dose, duration of T2DM, renal function and CYP2C9 genotype) KCNJ11 E23K polymorphism did not affect hypoglycemia risk.Conclusions: KCNJ11 E23K polymorphism is not associated with increased risk of mild hypoglycemia in sulfonylurea-treated T2DM patients.

Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus - Corrected Proof

2012-05-16

Abstract: Aims: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM).Methods: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months.Results: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01–1.66) and 1.36 (1.06–1.74), respectively (additive model) versus 1.45 (1.01–2.08) and 1.56 (1.06–2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05–1.18, p=0.00016 after adjustment for age and ethnicity).Conclusions: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results.

Higher magnification lenses versus conventional lenses for evaluation of diabetic neuropathy by corneal in vivo confocal microscopy - Corrected Proof

2012-05-14

Abstract: We tested agreement for small fibre morphology using corneal in vivo confocal microscopy between the recently available higher-magnification 300μm2 and the conventional 400μm2 field-of-view lenses. We found insignificant bias for corneal nerve fibre length indicating that either lens could reasonably be applied to research and clinical screening for diabetic neuropathy.

Increase of INS-1 cell apoptosis under glucose fluctuation and the involvement of FOXO–SIRT pathway - Corrected Proof

2012-05-14

Abstract: Aims: Variations of blood glucose level have been reported to be more harmful than sustained high glucose, but the effects on pancreatic β-cells have not yet been clarified. FOXO transcription factors are important for cell fate. We tried to clarify the effect of glucose variability on INS-1 cells, and the potential mechanisms related with FOXO–SIRT pathway.Methods: INS-1 cells were exposed to control, SHG (sustained high glucose) or IHG (intermittent high glucose) alternating every 12h for 5days.Results: INS-1 cells in SHG showed lower apoptosis and higher GSIS than IHG. Deacetylated FOXO and binding with SIRT were higher in SHG than IHG. Administration of PI3K inhibitor and/or SIRT inhibitor increased apoptosis and decreased Mn-SOD and Bcl-2 in SHG.Conculsions: IHG was more harmful to INS-1 cells than SHG. The degree of phosphorylation and acetylation of FOXO transcription factors were different between SHG and IHG, which might be one mechanism of increased INS-1 cell apoptosis in IHG.

Association of the DDAH2 gene polymorphism with type 2 diabetes and hypertension - Corrected Proof

2012-05-14

Abstract: Aims: The aim of this study was to investigate whether the polymorphism of DDAH2 is associated with type 2 diabetes and hypertension in Korean population.Methods: Total 605 subjects were included in this study: 403 patients with type 2 diabetes and 202 non-diabetic control subjects. The SNP rs805304 and rs2272592 in DDAH2 were analyzed. We examined the association of SNP rs805304 and rs2272592 in DDAH2 with type 2 diabetes and hypertension.Results: SNP rs2272592 was significantly associated with type 2 diabetes (P<0.001) while SNP rs805304 was not (P=0.716). We observed that the prevalence of the AG+GG genotypes were significantly greater than AA homozygotes in type 2 diabetes (AA vs AG+GG; OR 20.74, 95% CI 6.48–66.35, P<0.001). Significance was maintained after adjusting for age, sex, BMI, DBP and BUN (OR 21.03, 95% CI 2.83–151.14, P=0.003). Both SNP rs805304 and rs2272592 in DDAH2 were not significantly associated with hypertension.Conclusions: In the present study, we found that SNP rs2272592 in DDAH2 is associated with type 2 diabetes but SNP rs805304 in DDAH2 is not. DDAH2 SNP rs2272592 AG+GG genotypes are associated with genetic susceptibility to type 2 diabetes in Korean population.

The development and feasibility of a web-based intervention with diaries and situational feedback via smartphone to support self-management in patients with diabetes type 2 - Corrected Proof

2012-05-14

Abstract: Aims: The aim of the study was to develop and test the feasibility of a three months web-based intervention, delivered by a smartphone to support self-management in patients with type 2 diabetes.Methods: The intervention included use of a smartphone enabling access to daily web-based diaries and individualized written situational feedback. The participants registered their eating behavior, medication taking, physical activities and emotions three times daily using the mobile device. They also registered their fasting blood glucose level in the morning diary. A therapist had immediate access to submitted diaries and used the situational information to formulate a personalized feedback based on Acceptance Commitment Therapy. The purpose of the diaries and the situational feedback was to stimulate self-management.Results: Eleven of the fifteen participants included in the study completed the intervention, which was evaluated as supportive and meaningful. Most of the participants reported positive life style changes. The response rate to the daily registration entries was good and few technical problems were encountered.Conclusions: The described intervention is feasible and should be tested out in a large-scale study. The developed smartphone application seems a promising tool for supporting patients with type 2 diabetes to make important life style changes.

Association between blood glucose levels and high-sensitivity cardiac troponin T in an overt cardiovascular disease-free community-based study - Corrected Proof

Jin Zheng, Ping Ye, Leiming Luo, Wenkai Xiao, Ruyi Xu, Hongmei Wu — 2012-05-14

Abstract: Aim: To investigate the relationship between blood glucose levels and high-sensitivity cardiac troponin T (hs-cTnT) in an overt cardiovascular disease-free community-based study.Methods: Cardiac troponin T levels were measured using a highly sensitive assay in 1365 individuals, aged 45 years or older, without overt cardiovascular disease in a community-based, cross-sectional study, in Beijing, China. All participants underwent anthropometric measurements, biochemical analysis and an oral glucose tolerance test.Results: Both the prevalence of detectable hs-cTnT (≥3.0pg/mL) and elevated hs-cTnT (≥13.3pg/mL) were significantly higher in patients with diabetes mellitus (DM) than in patients with normal glucose tolerance (NGT), and those with impaired glucose regulation (IGR). After adjustment for multiple factors, the prevalence of detectable hs-cTnT (adjusted OR=1.22) and elevated hs-cTnT (adjusted OR=1.29) in the DM group were still significantly higher than in the NGT group. hs-cTnT was related to multiple risk factors for cardiovascular events, and fasting blood glucose level was an independent predictor of hs-cTnT.Conclusions: hs-cTnT showed a varied distribution in a community-based population with different blood glucose levels. Both the prevalence of detectable hs-cTnT and elevated hs-cTnT were increased significantly in the diabetic population. hs-cTnT was related to multiple risk factors for cardiovascular events, and fasting blood glucose level was an independent predictor of hs-cTnT.

Promoting the use of DPP-4 inhibitors in Asia - Corrected Proof

Kasia J. Lipska, David Beran — 2012-05-09

DPP-4 inhibitors are a newer class of oral anti-hyperglycemic agents for which there are some pre-clinical data, small mechanistic studies, and post hoc analyses of randomized clinical trials suggesting possible beneficial effect on cardiovascular risk. However, the relationship between DPP-4 inhibition and actual patient outcomes, including cardiovascular events, remains unknown. Therefore, most clinical guidelines do not support DPP-4 inhibitors as first- or second-line agents. Mu et al. erroneously state that the NICE guidelines recommend these agents as second-line options (they should be considered only for patients already on metformin who are at high risk for serious hypoglycemia or who have contraindications to sulfonylureas ). Despite the uncertainty with respect to patient-important outcomes, these agents are increasingly used in the U.S. with substantial financial implications for individual and health system spending . If, indeed, as Mu et al. suggest we should “overcome the obstacles” and widely apply these agents in Asia, we may in fact contribute to the growing trend of catastrophic medical spending in developing countries . The use of expensive therapies with unproven impact on rates of diabetic complications cannot be justified in health systems lacking other essential elements for diabetes care such as patient education, diagnostic tools and trained healthcare workers . Indeed, it is worth noting that all of the authors of the paper have significant conflicts of interest with respect to the maker of DPP-4 inhibitors, Boehringer Ingelheim – a conflict which should have precluded publication in Diabetes Research in Clinical Practice, the peer-reviewed Journal of the International Diabetes Federation, among whose missions are to “develop and encourage best practice in diabetes policy, management and education” .

Association of the PTPN22 gene (+1858C/T, −1123G/C) polymorphisms with type 1 diabetes mellitus: A systematic review and meta-analysis - Corrected Proof

Songtao Tang, Wenjia Peng, Changjiang Wang, Haiqin Tang, Qiu Zhang — 2012-05-09

Abstract: Objective: A meta-analysis was conducted to evaluate the association of PTPN22 gene (+1858C/T −1123G/C) polymorphism with T1DM susceptibility.Methods: Electronic databases were used to identify published studies before September 2011. We adopted the most appropriate genetic model. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed.Results: Totally, 25 case–control studies including 8613 T1DM cases and 10,133 healthy controls (24 studies containing 8129 cases and 9641 controls for PTPN22 +1858C/T, 5 studies including 1460 cases and 1609 controls for PTPN22 −1123G/C) were identified as eligible and analyzed. The most appropriate co-dominant model was adopted. A significant association of PTPN22 +1858C/T gene polymorphism was found in overall population. When stratified by race, significance was observed in Europe and America, but not in Asia. We did not detect any association for PTPN22 −1123G/C polymorphism.Conclusions: Our study indicated that T1DM is associated with PTPN22 +1858C/T gene polymorphism, and targeting this promoter polymorphism should be dependent on ethnicity. Whether −1123G/C polymorphism is a susceptibility locus for T1DM, further studies with well-designed among different ethnicity populations are required.

Type 2 diabetes or …? Still looking for a better name - Corrected Proof

Andrew J. Krentz — 2012-05-07

Two decades have passed since the Lancet published an editorial that questioned the diabetes nomenclature of the day. Titled ‘Type 2 diabetes or NIDDM: Looking for a better name’ the article summarized knowledge and uncertainties about the overlap of these terms with lesser degrees of glucose intolerance, insulin resistance, and the metabolic syndrome .

Exendin-4 directly improves endothelial dysfunction in isolated aortas from obese rats through the cAMP or AMPK–eNOS pathways - Corrected Proof

Lina Han, Yerong Yu, Xiaodong Sun, Ben Wang — 2012-05-07

Abstract: Aims: To determine whether exendin-4 might directly improve endothelial dysfunction in aorta isolated from high-fat diet-induced obese rats.Methods: Wistar rats were randomly divided into control and obesity (OB) groups and fed. Vascular segments of obese rats were incubated in organ bath in the presence or absence of exendin-4. Nitric oxide (NO) production and nuclear transcription factor kappa B expression in vascular rings were measured. The aortic rings of the obese rats were then incubated in an organ bath with exendin-4 in the presence or absence of the following inhibitors: the AMPK, the adenylate cyclase and the NO synthase inhibitor.Results: The maximum endothelium-dependent vasodilatation (EDV) value was severely reduced in the OB group. Exendin-4 treatment significantly increased the NO level, improved endothelium-dependent vasodilatation and reduced expression of NF-κB in the obese group. The beneficial effect of exendin-4 on EDV in obese rats was partly attenuated in the presence of the specific inhibitors.Conclusion: Exendin-4 directly improves impaired EDV of aortae from obese rats. The beneficial effect of exendin-4 appears to be mediated in part via stimulation of cAMP/AMPK-related signalling pathways and enhancement of endothelial nitric oxide synthase activity.

Accuracy and durability of Semmes–Weinstein monofilaments: What is the useful service life? - Corrected Proof

2012-05-07

Abstract: Objective: To evaluate the accuracy and effective service life of commercially available Semmes–Weinstein monofilaments with repetitive loading.Methods: We obtained 6 brands of Semmes–Weinstein monofilaments (SWM) from commercial vendors identified from the Internet and the federal registry. Five monofilaments of each brand were subjected to repeat loading cycles, allowed to rest over night and loaded again the next day. First, sets of five monofilaments were loaded 25 times for each of five days. Then sets of five monofilaments were subjected to 200 loading cycles a day for 15 days. A testing jig ensured each SWM was loaded perpendicular to a digital pressure plate. The buckling force was measured via the pressure plate to determine failure loads. Several statistical techniques were used to examine the behavior of the monofilaments over repeated loadings: time series analysis, ANOVA and nonparametric comparisons of load distributions.Results: The monofilaments tested were neither precise nor accurate. The plasticity of filaments increased with repeated loadings resulting in lower bending forces. Individual and average bending forces varied widely both within and between monofilament brands. All monofilaments showed a typical material failure pattern. Initially the bending force was high but rapidly decreased and then leveled out at levels 1–2g lower than the starting values. After resting over night, the initial bending force was again high but usually not as high as the previous day and bending forces decreased and then leveled out. Most monofilaments did not start at the accepted 10-g buckling force but varied by up to 30% (p<0.01). At best, monofilaments starting at the accepted 10±1g buckling force would remain within a usable range (9–11g) for 7–9 days or to evaluate 70–90 patients.Conclusion: Commercially available SWM have significant variability within and between devices from different manufacturers. Their actual bending force varies widely from their designated 10g value. When used they have a short service life where the instrument is within 10% of their initial bending force which is not usually the stated 10g of force.

Diabetes medications and cancer: A way out of uncertainty - Corrected Proof

Marco Gallo, Katherine Esposito, Dario Giugliano — 2012-05-04

Compared with non-diabetic people, people with type 2 diabetes have an increased risk of developing a wide range of common tumors and also have a poorer prognosis . Both obesity and the metabolic syndrome, two disorders strongly linked with and major risk factors for type 2 diabetes, are associated with an increased risk of malignant disease in both sexes (Giugliano et al., unpublished data ). Although it has been shown since 2005 that diabetes is associated with an increased risk of colorectal cancer (30% increased risk) and pancreas cancer (82% increased risk) compared with the non-diabetic population , this relationship attracted relatively little attention among diabetes researchers and health care providers, whose focus has been on the dominant role of cardiovascular disease. Ironically, the awakening of the clinical relevance of the link between diabetes and cancer was generated by safety concerns associated with the use of some diabetes medications, in particular in 2009 with the publication of a series of observational reports suggesting an association between insulin glargine and a possible increase in tumor risk . However these reports stimulated considerable debate among diabetes clinicians, oncologists, and epidemiologists, leading to the issuing of a consensus report from the American Cancer Society and the American Diabetes Association . A number of epidemiological studies and meta-analyses have tried to shed more light on this topic, with conflicting results. Large population-based studies failed to confirm an association between insulin glargine and malignancy risk in general . On the other hand, several analyses were unable to rule out the possibility of an increased risk of breast cancer among women treated with glargine, in comparison with users of human insulin .

Serum allograft inflammatory factor-1 is a novel marker for diabetic nephropathy - Corrected Proof

2012-05-04

Abstract: Aims: Recent studies have identified macrophage-mediated injury as an important component in the development of diabetic nephropathy. The aim of this study was to investigate the correlations between serum allograft inflammatory factor-1 (AIF-1) concentration, which is a marker of activated macrophages, and diabetic nephropathy.Methods: Serum AIF-1 concentrations were measured in 284 patients with type 2 diabetes. We evaluated relationships of serum AIF-1 concentrations to degree of urinary albumin excretion (UAE) or estimated glomerular filtration rate (eGFR) in univariate and multivariate linear regression analyses.Results: Serum AIF-1 concentrations positively correlated with logarithm of UAE (r=0.260, P<0.0001), whereas serum AIF-1 concentrations inversely correlated with eGFR (r=−0.312, P<0.0001). Mean serum AIF-1 concentration was higher in patients with macroalbuminuria than that in patients with normoalbuminuria (P=0.0001) or that in patients with microalbuminuria (P=0.0093). In multivariate linear regression analyses, serum AIF-1 concentrations were independently correlated with logarithm of UAE (β=0.213, P=0.0120) and with eGFR (β=−0.286, P=0.0011).Conclusions: Serum AIF-1 concentration correlated with albuminuria and eGFR in patients with type 2 diabetes and it could be a marker of diabetic nephropathy as well as activated macrophages.

A comparison of cost per case detected of screening strategies for Type 2 diabetes and impaired glucose regulation: Modelling study - Corrected Proof

2012-05-03

Abstract: Background: To determine a cost per case detected for different screening strategies for both Type 2 diabetes alone and in combination with impaired glucose regulation.Methods: Bayesian framework modelling study using data from the ADDITION-Leicester screening study in UK multi-ethnic primary care setting. There were 5794 people aged 40–75 years (77.4% white European; 22.6% south Asian) without previously known diabetes. We compared 212 screening strategies including blood tests, a computer practice data score and a risk score, as part of a multi-stage process that all used an oral glucose tolerance test as the diagnostic test. Simulation models were created using sensitivity estimates for the expected cost per case.Results: The estimated costs per case identified for the 18 most sensitive strategies varied from £457 to £1639 (€526–1886, for £1=€1.15) for diabetes and £148–913 (€170–1050) for both diabetes and impaired glucose regulation. The lowest costing diabetes strategies ranged from £457 to £523 (€526–601) involving a two-stage screening strategy, a non-invasive risk stratifying tool followed by a blood test, producing sensitivities ranging from 67.1 to 82.4%.Conclusion: Screening a population using a non-invasive risk stratification tool followed by a screening blood test is the most cost-effective method of screening for diabetes and abnormal glucose tolerance.

The association between Problem Areas in Diabetes Scale scores and glycemic control is modified by types of diabetes therapy: Diabetes Distress and Care Registry in Tenri (DDCRT 2) - Corrected Proof

2012-05-03

Abstract: Aim: To evaluate the joint association of Problem Areas in Diabetes (PAID) Scale scores and glycemic control with diabetes therapy.Methods: We used 3479 patients’ data with type 1 and type 2. Modified Poisson regression analysis was used to estimate relative risks (RRs) for poor glycemic control (HbA1c≥7.0%) across quartiles of PAID scores.Results: Compared with the 1st quartile of PAID score, multivariable-adjusted RRs for poor glycemic control were 0.99 (95%CI, 0.87–1.11), 1.05 (95%CI, 0.93–1.18), and 1.12 (95%CI, 1.00–1.27), respectively, for 2nd to 4th quartiles, and we observed significant trend (p for trend=0.03). We observed significant interaction of PAID score and HbA1c with diabetes therapy (p=0.0469). In patients receiving diet only therapy, the RRs for poor glycemic control were 1.38 (95%CI, 0.93–2.05), 1.18 (95%CI, 0.51–5.13), and 1.81 (95%CI, 1.16–2.79), respectively for 2nd to 4th quartiles of PAID score compared with the 1st quartile (p for trend=0.025); while we did not observe significant association between PAID and poor glycemic control in patients receiving medication therapy.Conclusions: Diabetes distress measured by PAID survey was associated with poor glycemic control, and this association was modified by diabetes therapy.

Diabetic foot osteomyelitis: Bone markers and treatment outcomes - Corrected Proof

2012-04-30

Abstract: Aims: Novel bone turnover markers could help with the diagnosis and monitoring of osteomyelitis patients. We compared levels of two bone turnover markers, serum amino-terminal telopeptides (NTx) and bone alkaline phosphatase (BAP), in diabetic patients with and without osteomyelitis.Methods: Matched case–control study was conducted with diabetic patients with and without osteomyelitis. Cases not undergoing immediate amputation were followed with repeat measurements after osteomyelitis treatment and for outcome determination.Results: Analysis included 54 subjects, 27 cases and 27 controls. Median BAP levels were similar between cases and controls at enrollment (p=.55) as were median NTx levels (p=.43). Cases with follow-up data (n=18) had similar bone marker levels at enrollment and 6 weeks. No significant differences in BAP or NTx levels at enrollment or follow-up were seen between cases with poor versus favorable outcomes.Conclusions: No differences in NTx or BAP levels were seen between cases and controls. Cases with follow-up data had similar levels at enrollment and 6 weeks. Lack of difference may be due to small sample size, small areas of bone involved in foot osteomyelitis, or limitations of these specific markers. More research is needed.

Medication-related problems occurring in people with diabetes during an admission to an adult teaching hospital: A retrospective cohort study - Corrected Proof

Kate Claydon-Platt, Elizabeth Manias, Trisha Dunning — 2012-04-27

Abstract: Aims: To examine the characteristics of medication-related problems occurring in people with diabetes admitted to hospital and to identify risk factors for medication-related problems.Methods: A retrospective cohort study of medication-related problems occurring in patients admitted to an adult, inner-city Australian teaching hospital was conducted over two-years. The risk factors associated with medication-related problems were identified using random effect logistic regression.Results: There were 9530 admissions of people with diabetes involving 5205 individuals over a two-year period. Medication-related problems were associated with 686 (7.2%) admissions involving 571 individuals (11.0%). The most common medication-related problems were medication errors (64.1%) associated with hypoglycaemia and unintentional overdose. Five factors were significantly associated with medication-related problems: female gender [odds ratio (OR) 1.30, 95% confidence intervals (CI) 1.11–1.52], age of 18–50 years (OR 2.32, CI 1.85–2.91), single marital status (OR 1.46, CI 1.24–1.74), mental and behavioural problems (OR 1.74, 1.43–2.11), and a comorbidity index score of at least one (OR 1.35–1.67).Conclusions: Five significant risk factors were associated with medication-related problems in people with diabetes admitted to hospital. These risks need to be considered when developing care plans and interventions to prevent medication-related problems for individuals with diabetes.

A prospective evaluation of neonatal hypoglycaemia in infants of women with gestational diabetes mellitus - Corrected Proof

2012-04-26

Abstract: Objective: To analyse first-day-of-life glucose levels in infants of women with gestational diabetes (GDM) and the influence of maternal, gestational and peripartum factors on the development of neonatal hypoglycaemia.Study design: Prospective cohort study including newborns of GDM mothers. Capillary blood glucose (CBG) was measured serially on the first day of life. CBG values were defined as normal (≥2.5mmol/l), mild hypoglycaemia (2.2–2.4mmol/l), moderate hypoglycaemia (1.6–2.1mmol/l) and severe hypoglycaemia (<1.6mmol/l).Results: One hundred and ninety infants were included: 23 (12.1%) presented mild, 20 (10.5%) moderate and only 5 (2.6%) severe hypoglycaemia. Hypoglycaemic infants were more frequently large-for-gestational-age (29.3% vs 11.3%, p=0.003), had lower umbilical cord pH (7.28 vs 7.31, p=0.03) and their mothers had more frequently been hyperglycaemic during labour (18.8% vs 8.5%, p=0.04). In multivariate analysis Pakistani origin (OR: 2.94; 95% CI: 1.14–7.55) and umbilical cord venous pH (OR: 0.04, 95% CI: 0.261–0.99) were significantly and independently associated with hypoglycaemia.Conclusions: Mild and moderate neonatal hypoglycaemias were common although severe episodes were unusual in infants of women with GDM. Hypoglycaemia is mainly influenced by ethnicity and cord blood pH, although maternal peripartum glycaemic control and large-for-gestational-age condition may also play a role.

Clinical implications of pathologic diagnosis and classification for diabetic nephropathy - Corrected Proof

2012-04-23

Abstract: Aim: The usefulness of renal pathologic diagnosis in type II DM (diabetes mellitus) remains debate.Methods: We grouped the pathologic diagnoses as pure DN (diabetic nephropathy), NDRD (non-diabetic renal disease), and NDRD mixed with DN (Mixed). We classified pure DN as the criteria suggested by Tervaert. We compared the accuracy of clinical parameters to predict DN and usefulness of pathology to predict renal prognosis.Results: Among 126 enrolled patients, there were 50 pure DN, 65 NDRN, and 11 Mixed. The sensitivity and specificity for predicting DN with the presence of retinopathy were 77.8–73.6% and, with a cut-off value of 7.5 years of diabetic duration, the sensitivity and specificity were 64.5–67.2%. ESRD (end stage renal disease) occurred in 44.0% of DN, 18.2% of Mixed, and 12.3% of NDRD (p<0.001). Among pure DN, Class IV showed the lowest estimated glomerular filtration rate (eGFR). We estimated the 5-year renal survival rate as 100.0% in Classes I and IIa, 75.0% in Class IIb, 66.7% in Class III, and 38.1% in Class IV (p=0.002).Conclusions: Nephropathy of type II DM was diverse and could not be completely predicted by clinical parameters. The renal pathologic diagnosis was a good predictor for renal prognosis in type II DM.

Association of the PPARG Pro12Ala polymorphism with type 2 diabetes and incident coronary heart disease in a Hong Kong Chinese population - Corrected Proof

2012-04-20

Abstract: Aims: We examined the risk association between single nucleotide polymorphisms (SNPs) in eleven candidate genes with type 2 diabetes (T2D). T2D-associated polymorphisms were also examined for prediction of incident CHD.Methods: 113 tagging SNPs were genotyped in stage 1 (467 T2D cases, 290 controls), and 15 SNPs were analyzed in the final cohort (1462 T2D cases, 600 controls). Three T2D-associated SNPs were further tested for prediction of CHD within a subset of 1417 T2D cases free of CHD at enrolment.Results: In the case–control analysis, PPARG rs1801282 (Pro12Ala) (OR=1.48 (1.02–2.16)), ADIPOQ rs1063539 (OR=1.17 (1.01–1.35)), and HNF4A rs1884614 (OR=1.16 (1.00–1.32) were associated with T2D (Pallelic<0.05). Joint analysis of rs1801282-C, rs1063539-G, and rs1884614-T risk alleles showed an additive dosage effect (P for trend=0.001). Moreover, carriers with two PPARG rs1801282-C risk alleles were associated with an increased risk of incident CHD (HR=4.38 (1.03–18.57), P=0.045) in T2D patients in the prospective analysis.Conclusions: Genetic variants of PPARG, ADIPOQ and HNF4A were individually and jointly associated with T2D in Hong Kong Chinese. The PPARG Pro12 risk allele contributed to increased risk for both T2D and CHD.

Diabetes and depressive symptoms among Korean American older adults: The mediating role of subjective health perceptions - Corrected Proof

Yuri Jang, Nan Sook Park, Soyeon Cho, Soonhee Roh, David A. Chiriboga — 2012-04-20

Abstract: Purpose: In recognition of the impact of chronic diseases on mental health and the lack of research on Asian American subgroups, the present study examined subjective perceptions of health as a potential mediator in the association between diabetes and depressive symptoms in Korean American older adults.Methods: Multivariate analysis with data from 672 Korean American older adults in Florida explored the mediation model of health perceptions.Results: The presence of diabetes was associated with negative perceptions of health and elevated symptoms of depression. The proposed mediation model was also supported: negative perceptions of health served as an intervening step between diabetes and depressive symptoms.Conclusions: The intervening role of health perceptions yields implications for developing health promotion interventions targeting older individuals with diabetes. Results suggest that even in the presence of chronic health conditions, mental well-being of older adults can be maintained by having optimistic beliefs and positive attitudes towards their own health.

Diabetes Australia position statement. A new language for diabetes: Improving communications with and about people with diabetes - Corrected Proof

J. Speight, J. Conn, T. Dunning, T.C. Skinner, on behalf of Diabetes Australia — 2012-04-18

Abstract: Diabetes is the fastest growing chronic condition in Australia, affecting 1.7 million Australians, requiring daily self-care, and known to reduce quantity and quality of life. On average, people with diabetes experience greater emotional distress than those without diabetes. One source of distress can be the language used to refer to diabetes, its management and the person with diabetes. The way verbal and written language is used reflects and shapes people's thoughts, beliefs and behaviours. Language has the power to persuade, change or reinforce beliefs and stereotypes – for better or worse. Words do more than reflect people's reality: they create reality and affect how people view the world and their diabetes. Language needs to engage people with diabetes and support their self-care efforts. Importantly, language that de-motivates or induces fear, guilt or distress needs to be avoided and countered. Diabetes Australia believes optimal communication increases the motivation, health and well-being of people with diabetes, and that careless or negative language can be de-motivating, is often inaccurate, and can be harmful. Diabetes Australia developed this position statement to encourage greater awareness of the language surrounding diabetes and provide recommendations for more careful and positive language use.

Option for diabetic patients with multi-vessel coronary disease: Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG): A meta-analysis - Corrected Proof

Fan Zhang, Yuan Yang, Dayi Hu, Han Lei, Yang Wang — 2012-04-18

Abstract: Diabetes is prevalent in patients with coronary artery disease. In diabetic patients with multi-vessel coronary disease, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) were widely used for revascularization. We aimed to compare the effectiveness and safety of PCI and CABG in these patients. Nine randomized controlled trials were identified in which a total of 1047 diabetic patients were randomly assigned to PCI and 1054 diabetic patients were assigned to CABG. Results showed that five-year mortality was significantly higher in diabetic patients after PCI than after CABG (risk difference (RD) of 7%; P<0.001); repeated revascularization was more common after PCI than after CABG (one-year RD of 13%; P<0.001); major adverse cardiac and cerebrovascular events were also more frequent after PCI (one-year RD of 12%; P<0.001); however, the cerebrovascular accident rate was lower in the PCI group than the CABG group (one-year RD of −2%; P=0.004). Conclusively, in diabetic patients with multi-vessel coronary disease, CABG was not only more effective than PCI in reducing mortality but also led to fewer repeated revascularizations and fewer major adverse cardiac and cerebrovascular events. Despite these benefits, CABG did put diabetic patients at higher risk for cerebrovascular accident than did PCI.

The effect of various intensities of physical activity and chronic inflammation in men and women by diabetes status in a national sample - Corrected Proof

2012-04-17

Abstract: Moderate-to-vigorous physical activity (MVPA) has been shown to be inversely associated with C-reactive protein (CRP); however, the association between light intensity physical activity (LPA), and CRP is unknown. Our findings suggest that focusing on increasing MVPA, relative to LPA, may have a greater impact on inflammation regardless of diabetes status.

Adiponectin improves endothelial dysfunction caused by elevated FFAs levels, partially through cAMP-dependent pathway - Corrected Proof

Ben Wang, Yerong Yu, Lina Han — 2012-04-16

Abstract: Aims: To determine whether adiponectin can attenuate endothelial dysfunction caused by elevated free fatty acids (FFAs) concentration, and if so, to explore the underlying mechanism.Methods: Male Sprague-Dawley rat thoracic aortas were isolated then cut into four vascular rings, incubated in organ bath containing Krebs–Henseleit buffer with different agents separately: 800μmol/L Palmic acid (FFA, n=14), 800μmol/L Palmic acid+2μg/mL adiponectin (FFA+gAd, n=14), 800μmol/L Palmic acid+2μg/mL adiponectin+200μmol/L adenylate cyclase inhibitor dideoxyadenosine (FFA+gAd+ddAdo, n=7), blank control (NC, n=10). The endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIV) were assessed by acetylcholine (Ach) induced contraction of the aortas. Nuclear transcription factor kappa B (NF-κB) expression in rat aortic section was evaluated immunohistochemically.Results: Ach caused a concentration dependent vascular relaxation in all pre-constricted aortic rings. PA treatment impaired the Ach induced EDV which was significantly attenuated by pretreatment with adiponectin. Dideoxyadenosine partly abolished the vascular protective effect of adiponectin. Sodium nitroprusside (SNP) had no significant effect on the vasodilatation among four groups. Increased NF-κB expression was noted in FFA group. Pretreatment with adiponectin partly decreased NF-κB expression when compared with FFA group.Conclusion: Adiponectin may independently mitigate endothelial dysfunction caused by elevated FFAs concentration through the cross talk between cAMP and NF-κB signaling pathway.

Diabetic cardiomyopathy and diastolic heart failure – Difficulties with relaxation - Corrected Proof

C. Teupe, C. Rosak — 2012-04-16

Abstract: Diabetic patients carry a four- to five-fold increased risk of heart failure. Hyperglycaemia plays a central role in the pathogenesis of diabetic cardiomyopathy. Diabetic cardiomyopathy represents a distinct structural and functional disorder of the myocardium characterized by cardiac hypertrophy and an increased myocardial stiffness. At an early stage, diabetic cardiomyopathy is manifested by diastolic heart failure with preserved ejection fraction. In some patients, diastolic dysfunction may progress to heart failure with reduced ejection fraction and result in overt systolic heart failure. Diastolic dysfunction can accurately be diagnosed by echocardiography and BNP measurement in daily clinical practice. Early treatment is prognostically important. Optimal control of blood glucose levels and blood pressure is beneficial. So far metformin is the only antidiabetic agent not associated with harm in diabetic patients with heart failure. Incretin-based therapies potentially provide cardiovascular benefits. ACE inhibitors, angiotensin-1 receptor antagonists and beta-blockers should be preferred in heart failure therapy.

Self-monitoring of blood glucose in type 2 diabetes: Is the debate (finally) ending? - Corrected Proof

Antonio Ceriello — 2012-04-16

The usefulness of the self-monitoring of blood glucose (SMBG) in the management of type 2 diabetes not on insulin therapy is still a matter of debate, and in my opinion, of confusion. For example, in a very recent meta-analysis the authors conclude “Evidence from this meta-analysis of individual patient data was not convincing for a clinically meaningful effect of clinical management of non-insulin treated type 2 diabetes by self-monitoring of blood glucose levels compared with management without self-monitoring, although the difference in HbA1c level between groups was statistically significant” . Even the conclusions of the authors of this meta-analysis could be anyhow questionable (a significant reduction of HBA1c is not clinically relevant?), in this meta-analysis no one of the study evaluating structured SMBG has been included. As underlined in the review by Parkin in this issue of the journal, performing a structured SMBG makes the difference: the difference is in how the data coming from the SMBG are used. It is clear that only when a consistent action follows the data coming from the SMBG an improvement of the metabolic control can be achieved.

The protective effect of resveratrol on islet insulin secretion and morphology in mice on a high-fat diet - Corrected Proof

2012-04-13

Abstract: The aim of this study was to investigate the effect of resveratrol on beta cells in male C57BL/6J mice fed a high-fat diet and the possible mechanisms. Male C57BL/6J mice were randomly divided into three groups: normal control (NC) group, high-fat diet (HF) group and high-fat diet and resveratrol treatment (HFR) group (15 in each group). HFR group was fed with high fat diet for 8 weeks and then orally administered resveratrol at 400mg/kg daily. Twenty-four weeks later, the function of insulin secretion in vivo and in vitro was improved robustly in HFR group compared with HF group. The levels of glucose and lipid metabolism, beta cell mass, lipid content, and oxidative stress were lower in HFR group than in HF group. Simultaneously, resveratrol administration promoted the expression of SIRT1 in islets, while the expression of uncoupling protein 2 (UCP2) was restrained. Resveratrol, as well, also had a beneficial effect on the ratios of expressions of Bcl-2/Bax and levels of malondialdehyde/glutathione peroxidase. Resveratrol can protect islets from abnormal insulin secretion and morphological changes induced by a high-fat diet. The effect might be partly related to activated SIRT1 signal pathway, improved oxidative stress induced damage and incidence of apoptosis.

Use of thiazolidinedione and cancer risk in Type 2 diabetes: The Hong Kong diabetes registry - Corrected Proof

2012-04-13

Abstract: We examined possible anticancer effects of thiazolidinediones (TZDs) in 6074 Chinese with Type 2 diabetes free of cancer at enrolment. During a median follow-up of 4.93years, 270 patients developed cancer. Use of TZDs was associated with reduced risk of cancer in a dose–response manner in multivariable analysis.

A gastroretentive gabapentin formulation for the treatment of painful diabetic peripheral neuropathy: Efficacy and tolerability in a double-blind, randomized, controlled clinical trial - Corrected Proof

David Sandercock, Marilou Cramer, Victor Biton, Verne E. Cowles — 2012-04-13

Abstract: Aims: A randomized, double-blind, placebo-controlled study was conducted in 147 patients to determine the efficacy and safety of a gastroretentive formulation of gabapentin (G-GR) in treating painful diabetic peripheral neuropathy (DPN).Methods: Diabetic patients with symmetrical painful symptoms in distal extremities for 1–5 years and a baseline average daily pain (ADP) score of ≥4 received G-GR 3000mg, as a single evening daily dose (G-GR-QD) or a divided dose (G-GR-DD, 1200mg AM/1800mg PM), or placebo for 4 weeks. G-GR was titrated from 300 to 3000mg/day over 2 weeks, followed by 2 additional weeks at 3000mg/day. Efficacy measures included changes from baseline to Week 4 in ADP score and average daily sleep interference score (SIS).Results: A significantly larger decrease in ADP score was observed in the G-GR-QD dose group compared with placebo (−2.50 versus −1.30; p=0.002). A ≥50% reduction in ADP score was achieved in 34.8% of G-GR-QD recipients compared with 7.8% of placebo recipients (p=0.001). Similar results were observed for changes in SIS. The incidences of dizziness and somnolence, commonly associated with gabapentin, were low.Conclusions: Once-daily G-GR was effective and well tolerated for the treatment of pain due to DPN.

Single-nucleotide polymorphisms and haplotypes in the adiponectin gene contribute to the genetic risk for type 2 diabetes in Tunisian Arabs - Corrected Proof

2012-04-12

Abstract: Adiponectin is an adipocyte-produced protein involved in regulating glucose, lipid, and energy metabolism, and is encoded by ADIPOQ (APM1) gene. ADIPOQ polymorphisms were previously associated with type 2 diabetes (T2DM) in Caucasian and non-Caucasian populations. We investigated the contribution of 13 polymorphisms in the promoter, coding regions, and 3′untranslated region of ADIPOQ gene to T2DM in 917 patients and 748 normoglycemic control subjects. ADIPOQ genotyping was done by allelic discrimination method. Of the 13 ADIPOQ variants analyzed, higher minor allele frequency of rs16861194 (P<0.001), rs17300539 (P<0.001), rs266729 (P<0.001), rs822396 (P=0.02), rs2241767 (P=0.03), and rs1063538 (P=0.02) were seen in T2DM cases. Varied association of ADIPOQ genotypes with T2DM was seen according to the genetic model used: rs17300539 and rs266729 were significantly associated with T2DM under the three models, while rs16861194 was association with T2DM under additive and dominant models, and rs822396, rs2241766, and rs1063538 were associated with T2DM under the dominant models only. Haploview analysis revealed low linkage disequilibrium between the ADIPOQ variants, resulting in high haplotype diversity, and two blocks were identified, each differentially associated with T2DM. These results support a significant association of ADIPOQ gene polymorphism with T2DM in Tunisian Arabs.

Impact of smoking cessation on incidence of diabetes mellitus among overweight or normal-weight Japanese men - Corrected Proof

2012-04-12

Abstract: Aims: To assess the impact of smoking cessation on incidence of diabetes among overweight or normal-weight Japanese men.Methods: This 9.2-year cohort study included 2070 men aged 40–69 years without diabetes. We classified them according to smoking status as non-smokers, past smokers (>9, 6–9, 3–5 and <3 years) and current smokers. Participants were followed up until diabetes developed or the end of 2006. The incidence of diabetes was determined from fasting and random plasma glucose levels, HbA1c levels or being under medical treatment for diabetes.Results: During 18,963 person-years of follow-up, 246 of the participants developed diabetes. The risk for diabetes peaked within 3 years of quitting (HR: 2.98, 95% CI: 1.38–6.27) and persisted at 5 years after quitting smoking (HR, 2.49; 95% CI, 1.18–5.26) among overweight individuals. Moreover, this study identified a high risk for diabetes among past smokers who had quit >9 years in both normal weight and overweight.Conclusions: Cigarette smoking predicts incidence of diabetes, but smoking cessation leads to higher short-term risk in overweight and long-term risk in both. Preventing smoking is superior to smoking cessation, and is very important for avoiding diabetes.

Links among type 2 diabetes, cancer and metformin use: What have we learned? - Corrected Proof

Y.-J. Sheen, Wayne H.-H. Sheu — 2012-04-12

Recent studies conducted among various ethnic populations have confirmed the universal observation that patients with type 2 diabetes are at a high risk of developing, and have a poor prognosis for certain cancers (pancreas, liver, colon and rectum, breast, bladder and endometrium) . These findings extend to subjects with prediabetes and asymptomatic hyperglycemia, who are associated with premature death from cancer . The proposed underlying mechanisms in these subjects, to name a few, are hyperinsulinemia, hyperglycemia and associated chronic inflammation . Insulin has metabolic and mitogenic effects, which in combination cause increased cell proliferation, including that of cancer cells . Most cancer cells express both insulin and insulin-like growth factor (IGF) receptors and, upon stimulation, enhance insulin-mediated mitogenesis . The relationship between hyperinsulinemia and cancer may also be manifested through the hormone-dependent pathway by a decrease in the concentration of circulating sex hormone-binding globulin and a subsequent increase in the level of bioactive estrogen, which might in turn increase the risk of cancer in the breast and endometrium . Malignant cell growth is strongly dependent on increased glucose uptake and metabolism, which may be due to the higher expression levels of glucose transporters in cancer cells compared to normal cells . In addition, many cancers express highly effective insulin-independent glucose uptake mechanisms because ATP generation by glycolysis requires far more glucose than oxidative phosphorylation in these cells . Results from epidemiologic studies also supported the association of hyperglycemia and cancer incidence . On the other hand, malignant disease may cause abnormal glucose metabolism with so-called “reverse causality” in case of pancreases cancer . It is widely acknowledged that type 2 diabetes and related metabolic disorders (obesity, hyperlipidemia) may facilitate cancer progression through mechanisms such as increased inflammation and oxidative stress. Adipose tissues produce certain amounts of inflammatory cytokines (free fatty acids, interleukin-6, plasminogen activator inhibitor-1, leptin, and tumor necrosis factor), which have been shown to modulate malignant cell transformation or cancer progression .

Plasminogen activator inhibitor-1 is associated with renal dysfunction independent of BMI and serum lipid levels in patients with type 2 diabetes - Corrected Proof

2012-04-12

Abstract: We investigated a possible association between serum plasminogen activator inhibitor-1 (PAI-1) levels and renal dysfunction in 124 type 2 diabetes patients. Multiple linear regression analyses indicated that the PAI-1 levels were significantly inversely correlated with estimated glomerular filtration rate (eGFR) independent of albuminuria, BMI, LDL-C, and triglyceride.

Resource utilisation and clinical data before and after switching between short-acting human insulin and rapid-acting insulin analogues in patients with type 2 diabetes: The SWING study - Corrected Proof

2012-04-09

Abstract: Aim: SWING was a prospective, observational study conducted in nine European countries primarily to assess direct treatment costs when switching from short-acting human insulins to rapid-acting insulin analogues (H-A) or vice versa (A-H) in patients with type 2 diabetes.Methods: Data were collected at a baseline visit (time of switch) and at approximately 3, 6 and 12months post-switch.Results: In total, 2389 patients switched from H-A (n=2203) or A-H (n=186); another 603 were enrolled but ineligible. Mean (SD) direct diabetes-related costs (pro-rated to account for variable visit schedules) were €548.7 (865.8) 6months prior to switch, €625.6 (1474.9) at 0–6months and €568.6 (590.7) 6–12months following switch for H-A, and €544.5 (421.0), €481.0 (301.5) and €461.6 (335.0) for A-H, respectively. Mean (SD) HbA1c decreased over 12months by 1.08 (1.53)% units H-A and 1.17 (1.45)% units A-H. A small decline in hypoglycaemia occurred over time, but there were no clinically meaningful changes in mean PROs.Conclusions: There were small changes in mean direct diabetes-related costs (following adjustment for time interval) in patients switching in either direction. Improvements in mean HbA1c and incidence of hypoglycaemia cannot necessarily be attributed to therapeutic switch.

Type 2 diabetes mellitus patients manifest characteristic spatial EMG potential distribution pattern during sustained isometric contraction - Corrected Proof

Kohei Watanabe, Toshiaki Miyamoto, Yoji Tanaka, Kazuhito Fukuda, Toshio Moritani — 2012-04-09

Abstract: Aim: The purpose of the present study is to investigate spatial surface electromyography (SEMG) potential distribution pattern in type 2 diabetes mellitus (T2DM) patients.Methods: Nine T2DM patients and nine age-matched healthy men (CON) performed a sustained isometric knee extension at 10% of maximal voluntary contraction for 120s. Multi-channel SEMG was recorded from the vastus lateralis muscle by means of 64 electrodes. To characterize spatial SEMG potential distribution pattern, modified entropy and correlation coefficients between same electrode locations were calculated at 15, 60 and 120s for the root mean square values.Results: At 60 and 120s, modified entropy in T2DM was significantly lower than those in CON (p<0.05). Correlation coefficients for T2DM were significantly higher than those for CON at 60 and 120s (p<0.05).Conclusion: From these results, we suggested that T2DM patients continue to recruit limited and same motor units during the sustained contraction at low force level.

The effect of insulin therapy on biomechanical deterioration of bone in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats - Corrected Proof

Nurten Erdal, Serkan Gürgül, Can Demirel, Altan Yildiz — 2012-04-09

Abstract: Aims: To investigate the effect of insulin therapy on biomechanical properties of bone in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) in rats.Methods: A total of 28 male Wistar-Albino rats (12-week-old; 210–300g) were divided into 4 groups (n=7 for each) including control [C; no treatment], sham [Sh; distilled water i.p., for 8 weeks], diabetes [T1DM; 65mg/kg of STZ, single i.p.] and diabetes+insulin treatment [T1DM+I; 65mg/kg of STZ, single i.p.+insulin; 2–4UI/day/rat, i.p., for 8 weeks] groups. Body weight, blood glucose levels (BGLs), bone mineral density (BMD) and geometric/mechanical properties of bone tissue were evaluated.Results: BGLs in diabetic rats were significantly increased compared to non-diabetic rats, while the body weights were decreased (p<0.05). Femur length and cross-sectional area of femur were significantly decreased in both T1DM and T1DM+I groups (p<0.05). The significant reduction obtained in BMD in T1DM rats compared with C and Sh (p<0.05) groups was reversed by insulin treatment (p<0.05). Displacement, absorbed energy, maximum load, ultimate stress and toughness were significantly decreased inT1DM and T1DM+I groups compared to C and Sh groups (p<0.05).Conclusions: In conclusion, insulin treatment seems to be ineffective in restoration of biomechanical deterioration of bone specific to STZ-induced T1DM.

Results that matter: Structured vs. unstructured self-monitoring of blood glucose in type 2 diabetes - Corrected Proof

Christopher G. Parkin, Ann Buskirk, Deborah A. Hinnen, Matthias Axel-Schweitzer — 2012-04-05

Abstract: Self-monitoring of blood glucose (SMBG) is one component of diabetes management. SMBG presents information about current glycemic status and provides the ability to obtain immediate feedback regarding the impact of behavioral and pharmacological interventions on glucose levels. However, SMBG is useful only when the glucose information is understood correctly, data are accurately interpreted, and results prompt appropriate therapeutic actions.The International Diabetes Federation (IDF) recently published guidelines for SMBG use in non-insulin treated people with diabetes, recommending that SMBG should be used only when patients and/or their clinicians possess the ability and willingness to incorporate SMBG monitoring and therapy adjustment into their diabetes care plan. If SMBG is used, the IDF also recommends that structured SMBG be performed utilizing defined regimens to meet individual needs.Structured SMBG can be performed as daily glucose profiles that are representative of daily glucose excursions. Measuring preprandial/postprandial blood glucose (bG) levels on consecutive or alternating days (“testing in pairs”) also provides impactful glucose information for daily diabetes management.This article reviews recent studies that appropriately utilized structured SMBG as an integral component of comprehensive diabetes management and discusses how their findings support the IDF recommendations. Our goal is to help clinicians make more informed decisions about the value and utility of SMBG in diabetes management.

Quantification of concordance and discordance between apolipoprotein-B and the currently recommended non-HDL-cholesterol goals for cardiovascular risk assessment in patients with diabetes and hypertriglyceridemia - Corrected Proof

O.P. Ganda, C.G. Jumes, M.J. Abrahamson, M. Molla — 2012-03-29

Abstract: Aims: In patients with diabetes and hypertriglyceridemia, LDL-cholesterol (LDL-C) provides an inaccurate reflection of LDL particle burden. The relative value of non-HDL-cholesterol (non-HDL-C) and apolipoprotein-B (Apo-B) in estimating cardiovascular risk is controversial. We assessed the discordance between non-HDL-C and Apo-B targets in patients with diabetes with TG 200–499mg/dl.Methods: Data from 1430 determinations of LDL-C, non-HDL-C, and Apo-B in ambulatory patients with diabetes were analyzed. Rates of discordance were calculated, based on the currently recommended LDL-C, non-HDL-C, and Apo-B goals.Results: In patients with non-HDL-C goal of <130mg/dl, there was a discordance with Apo-B level goal of <90mg/dl, in 31% of samples. In patients with non-HDL-C goal of <100mg/dl, 6% of samples had Apo-B ≥80 and 18% had Apo-B <80mg/dl. Using the Apo-B goal of <70mg/dl, these numbers were 37% and 3.5% respectively. There was also a significant gender difference, i.e. under-estimation of risk by suggested non-HDL-C cut-offs, in females, compared to males.Conclusions: In patients with diabetes and hypertriglyceridemia, a considerable discordance exists between non-HDL-C and Apo-B. Our data suggest a need for prospective studies to compare the relative merits of non-HDL-C and Apo-B targets in the assessment of cardiovascular risk.

Diabetes care: Opinions, needs and proposed solutions of Swiss patients and healthcare professionals: A qualitative study - Corrected Proof

I. Peytremann-Bridevaux, S. Lauvergeon, D. Mettler, B. Burnand — 2012-03-29

Abstract: Aims: To explore, both among patients with diabetes and healthcare professionals, opinions on current diabetes care and the development of the “Regional Diabetes Program”.Methods: We employed qualitative methods (focus groups – FG) and used purposive sampling strategy to recruit patients with diabetes and healthcare professionals. We conducted one diabetic and one professional FG in each of the four health regions of the canton of Vaud/Switzerland. The eight FGs were audio-taped and transcribed verbatim. Thematic analysis was then undertaken.Results: Results showed variability in the perception of the quality of diabetes care, pointed to insufficient information regarding diabetes, and lack of collaboration. Participants also evoked patients’ difficulties for self-management, as well as professionals’ and patients’ financial concerns. Proposed solutions included reinforcing existing structures, developing self-management education, and focusing on comprehensive and coordinated care, communication and teamwork. Patients and professionals were in favour of a “Regional Diabetes Program” tailored to the actors’ needs, and viewed it as a means to reinforce existing care delivery.Conclusions: Patients and professionals pointed out similar problems and solutions but explored them differently. Combined with coming quantitative data, these results should help to further develop, adapt and implement the “Regional Diabetes Program”.

Utility of HbA1c for diagnosis of gestational diabetes mellitus - Corrected Proof

Rajesh Rajput, YogeshYadav, Meena Rajput, Smiti Nanda — 2012-03-28

Abstract: Objective: To evaluate the utility of HbA1c in combination with OGTT for diagnosis of GDM.Materials and methods: 607 pregnant women with their estimated gestational age between 24 and 28 weeks were evaluated for GDM using OGTT based on ADA criteria. HbA1c was also done at the same time.Results: The mean HbA1c value in women with GDM was significantly higher than women without GDM (5.73±0.34% compared to 5.34±0.35%). The area under ROC curve of HbA1c to detect GDM was 0.805 and an HbA1c cutoff value of ≥5.95% had sensitivity of 28.6% and specificity of 97.2% in diagnosing GDM while an HbA1c cutoff value of ≥5.45% had sensitivity of 85.7% and specificity of 61.1% in diagnosing GDM. For women with an HbA1c value between 5.45% and 5.95%, an OGTT should be performed to correctly identify women with GDM. Using this methodology 85.7% of the GDM cases would have been detected and only 2.8% of normal women would have been wrongly labeled as having GDM. Also, this methodology would have obviated an OGTT in 61.8% women in our study.Conclusion: HbA1c in combination with OGTT can obviate the need of OGTT in almost two-thirds of women with GDM.

Barriers and opportunities of empowerment as applied in diabetes settings: A focus on health care professionals’ experiences - Corrected Proof

S. Scambler, P. Newton, A.J. Sinclair, K. Asimakopoulou — 2012-03-28

Abstract: This exploratory study examines the opportunities and barriers health care professionals (HCPs) working with diabetes patients face when they try to implement the rhetoric of patient empowerment in practice. A small sample of diabetes HCPs (N=13), from National Health Service (NHS) hospital, walk-in and general practitioner (GP) clinics in South-East England, was interviewed through in-depth semi-structured interviews. Interviews were recorded, transcribed verbatim and analysed thematically. The analysis showed that empowerment was seen as beneficial for patients and HCPs. Time and resources could be moved from successfully empowered patients and focussed on more complex patients, this was termed ‘selective empowerment’. The main barriers to empowerment were identified as a lack of resources, time and HCPs trained in empowerment techniques. Empowerment is a popular concept in theory, and presents HCPs with several opportunities but also important barriers in its practical, clinical implementation day-to-day.

Effect of the once-daily human GLP-1 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes - Corrected Proof

2012-03-27

Abstract: Aims: Liraglutide reduces bodyweight in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the mechanisms underlying this effect.Methods: The comparative effects of liraglutide, glimepiride and placebo on energy intake, appetite, nausea, gastric emptying, antral distension, bodyweight, gastrointestinal hormones, fasting plasma glucose and resting energy expenditure (REE), were assessed in subjects with T2DM randomised to treatment A (liraglutide–placebo), B (placebo–glimepiride) or C (glimepiride–liraglutide). Assessments were performed at the end of each 4-week treatment period.Results: Energy intake was less (NS) with liraglutide vs placebo and glimepiride, and 24-h REE was higher (NS) with liraglutide vs placebo and glimepiride. Fasting hunger was less (p=0.01) with liraglutide vs placebo and glimepiride, and meal duration was shorter with liraglutide (p=0.002) vs placebo. Paracetamol AUC0–60min and Cmax were less (p<0.01) and fasting peptide YY was lower (p≤0.001) after liraglutide vs placebo and glimepiride. Bodyweight reductions of 1.3 and 2.0kg were observed with liraglutide vs placebo and glimepiride (p<0.001). There were no differences on antral distension, nausea, or other gastro-intestinal hormones.Conclusion: Liraglutide caused decreased gastric emptying and increased reduction in bodyweight. The mechanisms of the liraglutide-induced weight-loss may involve a combined effect on energy intake and energy expenditure.

Changes in visfatin levels after oral glucose tolerance test in women with gestational diabetes mellitus - Corrected Proof

Liang Zhaoxia, Wu Ying, Chen Danqing — 2012-03-26

Abstract: Visfatin levels increased following an oral glucose tolerance test (OGTT) in normal pregnancy, and this increase correlated with metabolic indexes such as blood glucose, blood fat, and insulin resistance. Conversely, visfatin levels in women with gestational diabetes mellitus (GDM) increased to lesser extent than in normal pregnancy, which suggests a disorder in the relationship between visfatin, blood glucose and insulin.

Downregulation of chemerin and alleviation of endoplasmic reticulum stress by metformin in adipose tissue of rats - Corrected Proof

Lina Pei, Jing Yang, Jian Du, Huiqiang Liu, Na Ao, Yingyan Zhang — 2012-03-26

Abstract: Aims: To investigate whether metformin regulates chemerin expression in vivo by alleviating ER stress.Methods: Male Sprague-Dawley rats were fed a high-fat or normal diet for 10 weeks to induce insulin resistance. During the following 6 weeks, the rats were divided into four groups: normal diet without treatment (NC), normal diet with metformin treatment (NM), high-fat diet without metformin (HF), and high-fat diet with metformin (HM). Body weight, fasting glucose, basal insulin level, insulin sensitivity, chemerin expression in serum and adipose tissue, ER stress marker and its pathway were measured.Results: After 6 weeks treatment, metformin reduced the body weight gain and enhanced insulin sensitivity of high-fat fed rats. The basal insulin level in the HM group was lower than in the HF group. Metformin reduced chemerin expression in the HM group compared with HF. Metformin reduced the GRP78 mRNA expression in HM rats. Activation of IRE1 alpha was lower in the HM group than the HF group.Conclusions: Metformin treatment decreased the chemerin expression and alleviated the ER stress in the visceral adipose tissue of high-fat diet-induced insulin-resistant rats. These data may also provide a further rationale for exploring the use of metformin in the treatment of insulin resistance.

Assessment of glycemic control among diabetic residents in nursing homes - Corrected Proof

2012-03-26

Abstract: We assessed hemoglobin A1c (HbA1c) among 88 diabetic residents in three Italian nursing homes, and compared figures with current guidelines and reports in the literature. Mean HbA1c was 6.5%; this paper from Southern Europe confirms recent findings in nursing homes on HbA1c values well below recommended targets.

Circulating soluble tumor necrosis factor related apoptosis inducing-ligand (TRAIL) is decreased in type-2 newly diagnosed, non-drug using diabetic patients - Corrected Proof

A. Bisgin, A.D. Yalcin, R.M. Gorczynski — 2012-03-26

Abstract: We examined the association between serum sTRAIL measured by ELISA and HbA1C levels, pre/post-prandial blood glucose levels and body mass index in 22 newly diagnosed type-2 diabetic patients.A significant difference in sTRAIL levels was found between study group and controls.