Diabetes Research and Clinical Practice - Articles in Press

Microinflammation is a common risk factor for progression of nephropathy and atherosclerosis in Japanese patients with type 2 diabetes - Corrected Proof

2010-02-08

Abstract: Aim: This study aimed to evaluate the change of serum levels of proinflammatory molecules in patients with type 2 diabetes and clarify the involvement of these molecules in diabetic nephropathy and atherosclerosis.Methods: Sixty-six Japanese type 2 diabetic patients (T2DM) and 39 healthy control subjects were enrolled. We assessed clinical parameters, urinary albumin excretion rate (AER), brachial-ankle pulse wave velocity (baPWV), intima media thickness (IMT) and serum levels of proinflammatory molecules.Results: Serum levels of IL-6, IP-10 and MCP-1 were significantly higher in T2DM than in control subjects. In T2DM, serum levels of high-sensitivity (hs) CRP, IP-10, hsTNF-α, VCAM-1 and E-selectin were positively correlated with AER. Serum levels of IP-10, hsTNF-α and VCAM-1 were positively correlated with baPWV. Serum levels of hsCRP, IL-6, IP-10 and hsTNF-α were positively correlated with IMT. Multiple linear regression analysis revealed that serum levels of hsTNF-α were independently associated with AER (β=0.235, P=0.038) and serum levels of IP-10 were independently associated with baPWV (β=0.209, P=0.047) and IMT (β=0.303, P=0.032).Conclusion: Our results suggest that low-grade inflammation, microinflammation, may be a common risk factor for diabetic nephropathy and atherosclerosis in Japanese type 2 diabetic patients.

Diabetes research and clinical practice Junior Research Prize: Conference report, 2009 - Corrected Proof

Katherine Pinnick — 2010-02-08

October 2009 saw the arrival of the global diabetes community in Montreal, Canada, for the 20th World Diabetes Congress. Nearly 18 months earlier I participated in the 2nd Elsevier/OCDEM Junior Research Competition, an event for DPhil students and junior researchers at the Oxford Centre for Diabetes, Endocrinology and Metabolism. Having recently completed my DPhil studies I submitted an abstract outlining the key findings from my thesis entitled “Pancreatic fat accumulation and effects on beta cell function”. Five abstracts, including mine, were selected for oral presentations which we delivered to a panel of judges and an audience of OCDEM researchers. To my surprise the judges selected my presentation and as the recipient of the Elsevier/OCDEM Junior Research Prize 2008, Elsevier kindly funded my registration, accommodation and travel to the World Diabetes Congress, allowing me to join the 12000 international delegates attracted to the 5-day conference.

Prescription of physical activity is not sufficient to change sedentary behavior and improve glycemic control in type 2 diabetes patients - Corrected Proof

2010-02-08

Abstract: Objective: To assess the impact of personalized exercise prescription on habitual physical activity and glycemic control in sedentary, insulin treated type 2 diabetes patients during a 2-y intervention period.Research design and methods: 74 patients were randomized to the intervention (n=38) or control (n=36) group. The intervention group was stimulated to increase daily physical activity through regular, structured, and personalized exercise prescription by a physical therapist over the 2-y intervention period.Results: Physical activity levels at work or in leisure time were not modulated by the exercise prescription intervention. In accordance, no changes in body composition, glycemic control, medication use or risk factors for cardiovascular disease were observed.Conclusions: Long-term behavioral intervention programs, providing individualized exercise prescription, are not sufficient to change sedentary behavior and/or improve glycemic control in insulin treated, type 2 diabetes patients.

Type 2 diabetes mellitus impairs bone healing of dental implants in GK rats - Corrected Proof

2010-02-08

Abstract: Type 2 diabetes is an increasingly prevalent disease with oral health manifestations. In this study, titanium implants were placed in the femora of 10 type 2 diabetic and 10 age-matched normal rats. We compared the results of bone histomorphometry around the dental implants at 4 and 8 weeks postsurgery.

Glucose control in patients with type 2 diabetes based on frequency of insulin glargine administration - Corrected Proof

Audrey K. Housel, Robert F. Shaw, Nancee V. Waterbury — 2010-02-08

Abstract: Glucose control and predictors of a switch from once to twice daily administration of insulin glargine in patients with type 2 diabetes was investigated. A mean decrease in %A1c of 0.52±0.12 (p=0.14) resulted, indicating clinical relevance. Daily dose was the only significant predictor of twice daily therapy.

Increased plasma adiponectin closely associates with vascular endothelial dysfunction in type 2 diabetic patients with diabetic nephropathy - Corrected Proof

2010-02-08

Abstract: Several studies found that adiponectin, an adipokine withstands atherosclerosis in vivo, is significantly increased in subjects with diabetic nephropathy (DN), but its clinical meaning remains unclear. For its structural similarity to complement C1q and collagen, we performed this study to explore the relationship between adiponectin and the vascular endothelial function alterations in DN patients. 50 type 2 diabetic patients without clinical cardiovascular complications were assigned to control group, microalbuminuria group (Micro-MA), and macroalbuminuria group (Macro-MA) according to the Mogensen's criteria. Plasma adiponectin and soluble vascular cell adhesion molecule-1 (sVCAM-1) were detected. Flow-mediated dilatation (FMD), nitroglycerin-induced dilatation (NID) and cardiologic parameters were measured by ultrasound cardiogram. Plasma adiponectin level was significantly and gradually increased in agreement with the amount of urine albumin excretion. sVCAM-1 was higher in Micro-MA and Macro-MA patients than in the controls, but it was comparable between the former 2 groups. FMD and NID were both remarkably decreased in Macro-MA group compared with Micro-MA and control group. For the whole subjects, plasma adiponectin was negatively related to FMD (r=−0.397, P<0.01) and NID (r=−0.413, P<0.01). These results suggest that increased plasma adiponectin may predict co-existing vascular endothelial dysfunction in DN patients.

Three novel mutations in MODY and its phenotype in three different Czech families - Corrected Proof

2010-02-04

Abstract: Aims/hypothesis: MODY (Maturity Onset Diabetes of the Young) is an autosomal dominant inherited type of diabetes with significant genetic heterogeneity. New mutations causing MODY are still being found. A genetically confirmed diagnosis of MODY allows application of individualized treatment based on the underlying concrete genetic dysfunction. Detection of novel MODY mutations helps provide a more complete picture of the possible MODY genotypes.Materials and methods: We tested 43 adult Czech patients with clinical characteristics of MODY, using direct sequencing of HNF1A (hepatocyte nuclear factor 1-alpha), HNF4A (hepatocyte nuclear factor 4-alpha) and GCK (glucokinase) genes.Results: In three Czech families we identified three novel mutations we believe causing MODY—two missense mutations in HNF1A [F268L (c.802T>C) and P291S (c.871C>T)] and one frame shift mutation in GCK [V244fsdelG (c.727-728delG)]. Some of the novel HNF1A mutation carriers were successfully transferred from insulin to gliclazide, while some of the novel GCK mutation carriers had a good clinical response when switched from insulin or oral antidiabetic drugs to diet.Conclusion: We describe three novel MODY mutations in three Czech families. The identification of MODY mutations had a meaningful impact on therapy on the mutation carriers.

Microvascular complications are associated with low levels of maternal sE-selectin and sVCAM-1 in pregnancy complicated with pregestational diabetes mellitus - Corrected Proof

Agnieszka Zawiejska, Ewa Wender-Ożegowska, Jacek Brązert — 2010-02-03

Abstract: Pregestational diabetes with vasculopathy in pregnant women is still associated with increased risk for severe maternal and foetal complications and their pathomechanism remains unclear. We investigate endothelial function in diabetic pregnant women with and without vascular disease, measured as changes in concentrations of soluble E-selectin and VCAM-1 throughout pregnancy. 121 pregnant women with PGDM and singleton pregnancy (30 participants with vasculopathy, 91 without vasculopathy) were enrolled into the prospective study. Control group consisted of 20 nondiabetic pregnant women in uncomplicated gestation, sampled cross-sectionally in early pregnancy and at term. We demonstrated lower concentrations of circulating sE-selectin both in early and in late diabetic gestation, irrespective of a concomitant vasculopathy. We also found reduced concentrations of sVCAM-1 in late gestation in diabetic pregnancies both with and without vascular disease, and reduced increase in its levels with gestation. We report significantly elevated concentrations of sVCAM-1 in early pregnancy in diabetic participants with retinopathy and nephropathy comparing with patients with retinopathy only and nondiabetic pregnant controls. We noted a general pattern of pregestational diabetes associated with reduced levels of cell adhesion molecules in early pregnancy with a further reduction during gestation, except for participants with combined retino- and nephropathy.

Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes - Corrected Proof

Hong-Yan Pan, Lin Guo, Qiang Li — 2010-02-03

Abstract: Aims: To assay the levels of serum omentin-1 in subjects with different levels of glucose regulation and to analyze the relationship between serum omentin-1 levels and body mass index (BMI), glycoslated hemoglobin (HbA1c), plasma glucose, insulin resistance index (HOMA-IR), TNF-α and IL-6 levels.Methods: Forty-six patients with impaired glucose regulation (IGR), 55 patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM), and 50 subjects with normal glucose tolerance (NGT) were enrolled in this study. The levels of serum omentin-1 and plasma glucose at fasting and at 2h after glucose load and fasting serum levels of TNF-α, IL-6, insulin, and HbA1c were measured. HOMA-IR was calculated.Results: The levels of serum omentin-1 were lower in the IGR and T2DM groups than in the NGT group. Within groups, omentin-1 levels were no significant difference before and after glucose load. The level of serum omentin-1 was negatively correlated to BMI, HOMA-IR, fasting insulin, TNF-α, IL-6, plasma glucose. HOMA-IR and BMI were independent related factors that influenced the levels of serum omentin-1.Conclusions: Serum omentin-1 levels were decreased in impaired glucose regulation subjects. Lack of omentin-1 may contribute to the development of insulin resistance and T2DM.

Nurse diabetes case management interventions and blood glucose control: Results of a meta-analysis - Corrected Proof

Garry Welch, Jane Garb, Sofija Zagarins, Irina Lendel, Robert A. Gabbay — 2010-02-01

Abstract: We conducted a meta-analysis of studies reporting diabetes case management interventions to examine the impact of case management on blood glucose control (HbA1c). Databases used for the search included Medline, PubMed, Cochrane EPOC, Cumulative Index to Nursing & Allied Health Literature database guide (CINAHL), and PsychInfo. A composite estimate of effect size was calculated using a random effects model and subgroup analyses were conducted. Twenty-nine salient studies involving 9397 patients had sufficient data for analysis. Mean patient age was 63.2 years, 49% were male, and ethnicity/race was 54% White. Type 2 diabetes was the focus in 91% of studies. Results showed a large overall effect size favoring case management intervention over controls or baseline values on HbA1c (ES=0.86, 95%CI: 0.52–1.19, Z=5.0, p<0.001). This corresponds to a mean HbA1c reduction of 0.89 (95%CI: 0.63–1.15). Subgroup analyses showed clinical setting, team composition, and baseline HbA1c were important predictors of effect size, but not diabetes self-management education which was poorly described or absent in most diabetes case management interventions examined. Nurse-led case management provides an effective clinical strategy for poorly controlled diabetes based on a meta-analysis of clinical trials focusing on blood glucose control.

A case of insulinoma following total gastrectomy—Effects of an alpha-glucosidase inhibitor on suppressing GIP and GLP-1 elevations - Corrected Proof

2010-02-01

Abstract: A 61-year-old woman with fasting hypoglycemia following total gastrectomy was diagnosed as insulinoma. GIP and GLP-1 levels after a mixed meal were extremely increased. Administration of miglitol, an alpha-glucosidase inhibitor, suppressed the GIP and GLP-1 elevations.

Fat mass threshold associated with a significant deterioration of insulin sensitivity in postmenopausal women - Corrected Proof

2010-02-01

Abstract: The aim of this study was to establish a cut-off value of percentage of fat mass (%FM) at which insulin sensitivity (IS) is significantly altered in sedentary postmenopausal women. Our results suggest that maintaining a %FM below 41% would minimize the deterioration of IS and its associated risks.

Serum MMP-7 is increased in diabetic renal disease and diabetic diastolic dysfunction - Corrected Proof

2010-01-25

Abstract: Circulating matrix metalloproteinase (MMP) levels may correlate with diabetic complications. Whether they are changed in early diabetic cardiomyopathy is not known and was examined in this study. TIMP-1 and collagen degradation products were also measured. Results from subjects with and without diastolic dysfunction were compared with those obtained for patients with varying stages of diabetic renal disease.Patients with type 2 diabetes with or without diastolic dysfunction with varying degrees of renal disease were recruited for this study. Age-matched non-diabetic subjects served as controls. MMPs (-1, -3 and -7) and TIMP-1 were measured by ELISA, MMP-2 and -9 by zymography and collagen degradation products by radioimmunoassay.Differences in the pattern of MMPs/TIMPs and collagen degradation products were observed. The most consistent change was in totalMMP-7, which was increased in those with diastolic dysfunction and those with macroalbuminuria. MMP-7 correlated with cardiac function (p<0.05 vs control, in those with diastolic dysfunction), and renal filtration function (p<0.05 vs control).In summary, we have identified novel relationships between serum MMP-7 and diabetic complications specifically in renal disease and in diastolic dysfunction. How increased circulating MMP-7 is associated with these diabetic microvascular complications and the significance of these findings will require prospective studies.

Lack of preservation of insulin gene expression by a Glucagon-Like Peptide 1 agonist or a Dipeptidyl Peptidase 4 inhibitor in an in vivo model of glucolipotoxicity - Corrected Proof

2010-01-22

Abstract: Prolonged exposure of pancreatic beta-cells to elevated levels of glucose and fatty acids adversely affects insulin secretion and gene expression.Aim: To examine whether the GLP-1 agonist exenatide or the inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase 4 (DPP-4) sitagliptin rescue insulin gene expression in rats infused for 72h with glucose+Intralipid, independently from their glucose-lowering action.Methods: Wistar rats were infused alternatively with glucose or Intralipid for cycles of 4h each for a total of 72h. The animals received exenatide (5μg/kg/day IV) or sitagliptin (5mg/kg/day IV) continuously starting 4 days prior to and continuing throughout the 3-day infusion period.Results: Plasma glucose, fatty acids, insulin and C-peptide levels were unaffected by exenatide or sitagliptin treatment during the infusion period. Insulin mRNA levels increased in response to the glucose infusion, but this increase was abolished in islets from rats receiving glucose+Intralipid. Neither exenatide nor sitagliptin administration rescued insulin mRNA in glucose+Intralipid infused rats.Conclusions: Neither a GLP-1 agonist nor a DPP-4 inhibitor, at doses that do not alter blood glucose levels, prevented the inhibition of insulin gene expression in this in vivo model of glucolipotoxicity.

Waist circumference has heterogeneous impact on development of diabetes in different populations: Longitudinal comparative study between Australia and Iran - Corrected Proof

2010-01-22

Abstract: Aims: Comparing waist circumference (WC) role in diabetes risk prediction and diagnosis of metabolic syndrome (MS) in different populations.Methods: Population-based samples from Australia (n=9026) and Iran (n=8259) were studied in 2000 and followed for ∼4 years. Follow-up attendance was ∼58% and mean age was 51 vs. 47. Pearson correlations calculated between WC and other MS components. ROC for the role of WC in the prediction of incident diabetes was used.Results: Prevalences of MS (48% vs. 28%), an increased WC (58.5% vs. 54.5%), low HDL-C (35% vs. 11.2%), high triglyceride (52.2% vs. 29.6%) were significantly higher in Iran. Fasting glucose ≥5.6mmol/L was higher in Australia (26% vs. 23%). Hypertension was no different (∼38%). Pearson correlations between WC and other MS components were stronger in Australians: FPG (0.32 vs. 0.2), HDL (0.47 vs. 0.16), TG (0.38 vs. 0.30) and SBP (0.38 vs. 0.36). Among women, area under ROC curve for WC as a predictor for diabetes was significantly higher for Australians (0.76 vs. 0.68, p<0.001) with no difference among men (0.69 vs. 0.71, p=0.4).Conclusion: WC was more strongly related to other components of MS in Australia. Association between WC and MS or incident diabetes varies between ethnicities.

Normal range of alanine aminotransferase concentration is associated with carotid atherosclerosis - Corrected Proof

2010-01-22

Abstract: Objective: To investigate whether alanine aminotransferase (ALT), even within the reference range, is associated with atherosclerotic burden in apparently healthy adults.Methods: This was an observational study performed on 830 healthy individuals with normal ALT concentration (≤40U/L). Atherosclerotic burden was assessed by carotid arterial intima-media thickness (IMT). All subjects were divided according to the quartile based on their ALT concentrations.Results: Despite all subjects having a normal ALT concentration, ultrasonographic liver steatosis was observed in 48.4% and 36.7% of men and women, respectively. In both genders, subjects in the highest quartile of ALT concentration had a significantly higher waist circumference, triglyceride concentration, HOMA-IR, a higher prevalence of metabolic syndrome, and a greater severity of ultrasonographic liver steatosis than did those in the lower quartiles. In women, the carotid IMT increased significantly with increasing quartiles of ALT concentration (0.62±0.14mm, 0.66±0.15mm, 0.69±0.15mm, vs. 0.72±0.24mm; P for trend<0.001). Based on multivariate regression analysis, the serum ALT, even within the normal range, was associated with the carotid IMT in both men and women, and independently of traditional cardiovascular risk factors.Conclusions: ALT concentrations, albeit within the reference range, were associated with atherosclerotic burden in healthy adults.

Prevalence of the metabolic syndrome among extremely obese adolescents in Italy and Germany - Corrected Proof

2010-01-22

Abstract: Juvenile metabolic syndrome (MetS) is a growing major medical problem in industrialised countries. We estimated its prevalence among two similar clinic-based sequentially recruited cohorts of extremely obese adolescents (age: 12–18 years) from Italy (N=665, males=271, females=394) and Germany (N=661, males=261, females=400) using the recent IDF paediatric criteria. The prevalence of the MetS was 23.3% among the Italians and 40.4% among the Germans. A multivariate logistic regression revealed an increased risk related to age (adjusted odd ratio (AOR): 2.24; 95% confidence interval (CI): 1.59–3.16; p<0.001), BMI SDS (AOR: 3.61; 95% CI: 2.33–5.60; p<0.001), male gender (AOR: 2.36; 95% CI: 1.80–3.10; p<0.001), and in German adolescents (AOR: 2.56; 95% CI: 1.98–3.31; p<0.001). Among Italian adolescents having the MetS, 83% had 3 abnormalities, 16% had 4 abnormalities while less than 1% had all the 5 abnormalities. In the German cohort, 67%, 28% and 5% of affected individuals had 3, 4 and 5 abnormalities, respectively. These results indicate that MetS is highly prevalent among extremely obese adolescents, and suggest that (besides age, obesity and gender) national sociocultural factors, as alimentary trends, could be important. Further tools should be developed to understand international epidemiological differences concerning obesity and its comorbidities in relation to lifestyles in the countries of European Union.

Impact of ENPP1 and MMP3 gene polymorphisms on aortic calcification in patients with type 2 diabetes in a Korean population - Corrected Proof

2010-01-21

Abstract: Aims: We investigated whether gene polymorphisms of Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and matrix metalloproteinase 3 (MMP3) are associated with increased vascular calcification in patients with type 2 diabetes (T2D) and evaluated whether serum MMP3 and osteoprotegerin (OPG) levels are related to calcification.Methods: This study included 464 subjects: 269 patients with T2D and 195 healthy controls in South Korea. We genotyped subjects for four single nucleotide polymorphisms (SNPs): ENPP1 K121Q, ENPP1 A/G+1044TGA, MMP3 −709A>G and MMP3 −1475G>A. The presence or absence of calcifications in the aortic arch was assessed by plain chest radiography.Results: The SNPs ENPP1 K121Q and MMP3 −709A>G showed significant associations with T2D (P=0.001 and P=0.004). The SNP ENPP1 K121Q showed a significant association with aortic arch calcification in T2D (P=0.036). Serum OPG levels were significantly higher in T2D patients than in the control group (P<0.001). However, serum MMP3 levels were significantly lower in T2D patients than in the control group (P<0.001).Conclusions: Our study demonstrates that the ENPP1 K121Q and MMP3 −709A>G polymorphisms are associated with T2D, and that the ENPP1 Q allele is associated with increased aortic arch calcification in a Korean population.

Inverse associations of serum bilirubin with high sensitivity C-reactive protein, glycated hemoglobin, and prevalence of type 2 diabetes in middle-aged and elderly Japanese men and women - Corrected Proof

2010-01-18

Abstract: Aim: The aim of this study was to examine the association of serum bilirubin, an endogenous antioxidant, with serum high sensitivity C-reactive protein (hs-CRP) level, HbA1c, and the prevalence of type 2 diabetes in middle-aged and elderly Japanese men and women (n=12,400).Methods: Analysis of covariance and logistic regression analysis were used to estimate geometric means of hs-CRP and HbA1c and odds ratios of prevalent diabetes according to bilirubin concentrations, respectively, with statistical adjustment for behavioral factors and liver enzymes.Results: Geometric means of hs-CRP and HbA1c were progressively lower with increasing concentrations of serum bilirubin in men and women each. An inverse association between serum bilirubin and HbA1c was slightly attenuated after adjustment for hs-CRP, but still remained highly significant (trend P=0.0004 in men and trend P=10−5 in women). Multivariate-adjusted odds ratios of prevalent diabetes for the lowest to highest quintiles of serum total bilirubin were 1.00, 1.00, 0.73, 0.80, and 0.73 (trend P=0.002), without adjustment for hs-CRP, and 1.00, 1.04, 0.76, 0.86, and 0.79 (trend P=0.01), with adjustment for hs-CRP.Conclusions: Higher concentrations of serum bilirubin probably confer protection against the development of type 2 diabetes.

Hyperglycemia on admission predicts larger infarct size in patients undergoing percutaneous coronary intervention for acute ST-segment elevation myocardial infarction - Corrected Proof

2010-01-18

Abstract: Aims: To determine if hyperglycemia on admission correlates to infarct size measured by single-photon emission computed tomography (SPECT) in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).Methods: We evaluated 347 STEMI patients who underwent primary PCI. Infarct size was determined by SPECT on Day 5. The population was divided into: hyperglycemia (glycemia on admission >11mmol/L) or non-hyperglycemia (≤11mmol/L) regardless of diabetic status.Results: 61 (17.6%) patients presented with hyperglycemia on admission. There were no significant differences in baseline characteristics or in PCI characteristics between the two groups. Final TIMI 3 flow was achieved in 81.7% of patients with hyperglycemia vs 85.7% of patients with non-hyperglycemia (p=0.43). The infarct size was larger in the hyperglycemia group (6 [2–14]% vs 8.5 [3–18.25]%; p=0.016). A multivariate linear regression analysis showed that hyperglycemia on admission was an independent predictor of infarct size at Day 5 post-MI (p=0.004).Conclusion: In patients with STEMI treated with primary PCI, hyperglycemia on admission is associated with larger infarct size determined by SPECT.

A survey of oral health education provided by certified diabetes educators - Corrected Proof

Hon K. Yuen, Georgiana Onicescu, Elizabeth G. Hill, Carolyn Jenkins — 2010-01-15

Abstract: The purpose of this study was to investigate certified diabetes educators’ (CDEs) perceptions of the adequacy of their diabetes education curricula in providing oral health information. A questionnaire was mailed to all CDEs with a mailing address in South Carolina (SC), United States (US). Of the 130 respondents, between 50%–60% indicated that they adequately addressed frequent dental visits, daily brushing and flossing, and importance of good oral hygiene. Almost all (93.8%) reported that their curricula did not include an oral health module; the two predominant reasons were: not having enough time (61.0%), and not knowing enough about oral health and its relationship to diabetes (37.0%). Respondents who expressed that they did not know enough about oral health and its relationship to diabetes were less likely to provide adequate ‘oral-health-related information’ (p=0.008), especially information about the effect of periodontal disease on diabetes (p=0.016). This study indicates that SC CDEs do not routinely provide comprehensive oral health education to people with diabetes primarily due to lack of time and knowledge related to oral health. To better serve their patients, CDEs should integrate oral health education in the diabetes education curriculum.

Automated detection of hypoglycemia-induced EEG changes recorded by subcutaneous electrodes in subjects with type 1 diabetes—The brain as a biosensor - Corrected Proof

2010-01-15

Abstract: Aims: Hypoglycemia unawareness is a common condition associated with increased risk of severe hypoglycemia. We test the hypothesis that specific changes in the electroencephalogram (EEG) during hypoglycemia can be recorded by subcutaneous electrodes and processed by a general mathematical algorithm, and that hypoglycemia associated EEG changes appear before the development of severe hypoglycemia.Methods: Fifteen patients with type 1 diabetes were exposed to insulin-induced hypoglycemia and EEG was recorded. The cognitive function was evaluated by repeated cognitive testing. Insulin infusion was terminated when plasma glucose reached 1.8mmol/l or when the subjects showed obvious signs of cognitive dysfunction. EEG was analyzed by an automated mathematical algorithm with a predefined threshold of hypoglycemia.Results: Hypoglycemia associated EEG changes were detected by the mathematical algorithm in all subjects. Plasma glucose at the time of EEG changes above the threshold value ranged from 2.0 to 3.4mmol/l and occurred 29±28min (range 3–113min) before termination of insulin infusion.Conclusions: Hypoglycemia associated EEG changes could be detected by an automated mathematical algorithm in all subjects exposed to insulin-induced hypoglycemia. In 12 of 15 patients, EEG changes occurred before severe hypoglycemia as evaluated by the cognitive testing.

The effects of vigorous physical activity on intra-abdominal fat levels: A preliminary study of middle-aged Japanese men - Corrected Proof

2010-01-14

Abstract: Aim: To examine the effects of vigorous physical activity (PA) on intra-abdominal fat (IF) levels in obese men.Methods: Thirty-seven obese men (mean age: 47.6±8.6 years) engaged in a 12-week aerobic exercise program on a regular basis (3 days/week). We divided them into low volume of vigorous PA group (n=19) or high volume of vigorous PA group (n=18), based on the median time spent (34.3min/week) in vigorous PA (over 6.1 metabolic equivalents assessed by a single-axis accelerometer) throughout the program.Results: Regular exercise reduced IF levels (measured by computed tomography) from 188.1±53.9cm2 to 170.3±46.6cm2 for the low volume of vigorous PA group and from 167.9±44.3cm2 to 137.9±40.6cm2 for the high volume of vigorous PA group. Two-way (time×group) ANOVA revealed no significant interactions for the IF level. However, correlation analysis for all participants showed that time spent in vigorous PA throughout the program significantly correlated to IF reductions after adjusting for initial levels of IF, vigorous PA and weight changes (r=−0.42, P=0.02).Conclusion: This study suggests that vigorous PA may affect IF reductions in obese men.

Factors predicting the need for insulin therapy in patients with gestational diabetes mellitus - Corrected Proof

2010-01-13

Abstract: Aim: To determine the possible factors predicting the insulin requirement in pregnancies complicated by gestational diabetes mellitus (GDM).Method: A total of 294 patients with GDM diagnosed by the 100-g/3-h oral glucose tolerance test (OGTT) were studied. The following factors were analyzed: maternal age, nulliparity, family history of diabetes, prepregnancy BMI, prior GDM, prior fetal macrosomia, multiple pregnancy, polyhydramnios, gestational age at diagnosis of GDM, smoking, hypertension, number of abnormal 100-g/3-h OGTT values, and glycated hemoglobin (HbA1c). The association between each factor and the need for insulin therapy was then analyzed individually. The performance of these factors to predict the probability of insulin therapy was estimated using a logistic regression model.Results: Univariate analysis showed a positive correlation between insulin therapy and prepregnancy BMI, family history of diabetes, hypertension, prior GDM, prior fetal macrosomia, number of abnormal 100-g/3-h OGTT values, and HbA1c (P<0.05). Prepregnancy BMI, family history of diabetes, number of abnormal 100-g/3-h OGTT values and HbA1c were statistically significant variables in the logistic regression model.Conclusions: The probability of insulin therapy can be estimated in pregnant women with GDM based on prepregnancy BMI, family history of diabetes, number of abnormal 100-g/3-h OGTT values, and HbA1c concentration.

Effect of age and race/ethnicity on HbA1c levels in people without known diabetes mellitus: Implications for the diagnosis of diabetes - Corrected Proof

Mayer B. Davidson, David L. Schriger — 2010-01-11

Abstract: Aims: To determine if age and race/ethnicity affect HbA1c levels independent of glycemia.Methods: We analyzed 2712 individuals from the NHANES III population 40–74 years old without diabetes history.Results: HbA1c levels increased by 0.10% per decade in people with NGT and 0.07% in those with IFG and/or IGT, independent of fasting and 2-h glucose on OGTT's. Compared to non-Hispanic whites, HbA1c levels increased by 0.12% (NGT) and 0.10% (IFG/IGT) in Mexican-Americans and 0.21% (NGT) and 0.35% (IFG/IGT) in non-Hispanic blacks, independent of glycemia. At HbA1c levels of ≥6.5%, ≥7.0% and 6.5–6.9%, diabetes diagnosed by current FPG/OGTT criteria occurred in 82%, 94% and 65%, respectively. In non-Hispanic blacks with HbA1c levels of 6.5–6.9%, 68% of those 40–74 years old and 87% of those over 64 years old would not have diabetes by FPG/OGTT criteria. Over 90% of all race/ethnicity groups would have diabetes with HbA1c levels ≥7.0%.Conclusions: Because many people, especially older non-Hispanic blacks, with HbA1c levels of 6.5–6.9% would not have diabetes by current FPG/OGTT criteria and clinical retinopathy and nephropathy are very unusual in patients whose HbA1c levels are kept <7.0%; we recommend an HbA1c level of ≥7.0% to diagnose diabetes.

Glycemic control and its correlates in patients with diabetes in Venezuela: Results from a nationwide survey - Corrected Proof

2010-01-08

Abstract: Aims: To determine the prevalence of inadequate glycemic control and its correlates in a large multicenter survey of Venezuelan patients with diabetes.Methods: A cross-sectional study in a sample of adult patients with diabetes, attending health centers in Venezuela. Information about diabetes, current medications, complications, and diet were obtained by trained interviewers, using a standardized questionnaire. HbA1c was measured by high-performance liquid chromatography in a central laboratory. Patients with HbA1c≥7% were considered to have inadequate glycemic control.Results: Overall 4075 patients were surveyed, 349(8.6%) with type 1 diabetes (T1D) and 3726(91.4%) with type 2 diabetes(T2D). Subjects’ mean age was 58 years, and 65% were female. The prevalence of inadequate glycemic control was 76%. Poor glycemic control was more common in T1D patients (87%) than in those with T2D(75%), p<10−4. Satisfaction with current diabetes treatment was associated with improved glycemic control among non-insulin-treated patients with T2D, but gender, multi-professional care, and participation in a diabetes education program were not.Conclusions: Despite clinical evidence supporting tight control of diabetes, few diabetic patients in Venezuela met recommended glycemic control targets. This may contribute to increased rates of diabetic complications. Our findings support the public health message of implementation of early, aggressive management of diabetes.

Effects of short-term therapy with different insulin secretagogues on glucose metabolism, lipid parameters and oxidative stress in newly diagnosed Type 2 Diabetes Mellitus - Corrected Proof

2010-01-08

Abstract: Aim: To compare effects of three different insulin secretagogues on early-phase insulin secretion, metabolism of glucose and lipids, and lipid peroxidation in newly diagnosed Type 2 Diabetes Mellitus (T2DM).Methods: Totally 60 newly diagnosed T2DM outpatients were randomized to three groups with 1-month monotherapy of repaglinide (Rg), glimepiride (Gm) or gliclazide MR (Gli), respectively. Some indexes of early-phase insulin secretion, glucose, lipids, and lipid peroxidation were inspected.Results: Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and fructosamine (FA) were improved in all groups similarly (p>0.05). Rg group was with the highest early-phase insulin secretion index (ΔI30/ΔG30) (p=0.026), lower mean amplitude of glycaemic excursion (MAGE) (p<0.05), lowest mean peak value of post-lunch glucose (p=0.043), and lowest postprandial triglyceride (TG) (p=0.039). Postprandial free fatty acid (FFA) was lower after Rg and Gli treatment (p<0.05). Serum 8-iso prostaglandin F2α (8-iso PGF2α) was improved in all groups, but the improvement showed statistically significant only in Rg group (p=0.04).Conclusion: Rg, Gm and Gli can all decrease blood glucose effectively in newly diagnosed T2DM patients, while Rg performs outstandingly in the aspects of improving early-phase insulin secretion, glucose excursion, postprandial lipids and 8-iso PGF2α.

The effect of mosapride (5HT-4 receptor agonist) on insulin sensitivity and GLUT4 translocation - Corrected Proof

2010-01-08

Abstract: Aims: We investigated the effect of mosapride, 5HT-4 (5-hydroxytryptamine) agonist, on blood glucose level and insulin sensitivity in subjects with impaired glucose tolerance (IGT) and conducted an in vitro study to evaluate the action mechanism.Methods: Thirty IGT patients were randomly assigned to receive either mosapride or placebo for 2 weeks. Biochemical profiles and insulin sensitivity index from euglycemic hyperinsulinemic clamp test were assessed before and after treatment. In cultured myotubes from human skeletal muscle cells, insulin- and mosapride-induced GLUT4 translocation and tyrosine phosphorylation of IRS-1 were determined.Results: After 2 weeks of treatment with mosapride, glucose disposal rates were significantly increased up to those of control (mosapride 5.47±1.72 vs 7.06±2.13, P=0.004, placebo 5.42±1.85 vs 5.23±1.53mgkg−1min−1). Fasting plasma glucose (FPG) and insulin levels were decreased. Mosapride increased the contents of GLUT4 in plasma membrane representing the increased recruitment of glucose transporters from intracellular pool. While insulin treatment on human skeletal muscle cell resulted in an increased tyrosine phosphorylation of IRS-1, mosapride did not have any effect.Conclusions: Mosapride is effective in decreasing FPG without stimulating insulin secretion in IGT subjects, possibly by inducing GLUT4 translocation in skeletal muscles.

C358A missense polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) and insulin resistance in patients with diabetes mellitus type 2 - Corrected Proof

D.A. de Luis, M. Gonzalez Sagrado, R. Aller, O. Izaola, R. Conde, E. Romero — 2010-01-07

Abstract: Background: The polymorphism 385 C/A of FAAH has been associated with overweight and obesity. The aim of our study was to investigate the relationship of polymorphism (cDNA 385 C→A) of FAAH gene on obesity parameters in patients with diabetes mellitus type 2.Design: A population of 70 patients with diabetes mellitus type 2 was analyzed. An anthropometric and biochemical nutritional assessment was performed. The statistical analysis was performed for the combined C358A and A358A as a group and wild type C358C as second group.Results: Fifty-five patients (78.7%) had genotype C358C (wild type group) and 15 (21.3%) patients C358A (14 patients, 20.6%) or A358A (1 patient, 0.7%) (mutant group). BMI (38.9±6.4 vs. 39.2±5.7, p<0.05), weight (96.8±17.6kg vs. 102.5±16.8kg, p<0.05), fat mass (42.1±16.1kg. vs. 46.9±11.1kg, p<0.05), waist circumference (115.9±12.8cm vs. 121.3±12.8cm, p<0.05), insulin (22.5±18.8mUI/L vs. 33.9±17.1UI/L, p<0.05) and TNF-alpha (6.1±3.4pg/mL vs. 8.4±3.2pg/mL, p<0.05) were higher in mutant type group than wild type. Adiponectin levels (33.3±20.8ng/mL vs. 22.3±10.8ng/mL, p<0.05) were higher in wild type group than mutant type group.Conclusion: There is an association of the mutant type group A358C and A358A of FAAH with a worse cardiovascular profile (weight, body mass index, waist circumference, insulin,TNF-alpha and adiponectin levels) than wild type group.

Genetic association of the neuropilin-1 gene with type 1 diabetes in children: Neuropilin-1 expression in pancreatic islets - Corrected Proof

2010-01-06

Abstract: Minor alleles of two SNPs in intron 9 of the NRP1 gene, which encodes neuropilin-1, were found to be associated with type 1 diabetes (T1D) in children. Neuropilin-1 peptides were confined to islets in human pancreas. This suggests neuropilins-1 could influence the development of some cases of T1D in children.

Impact of type 2 diabetes mellitus on prescription medication burden and out-of-pocket healthcare expenses - Corrected Proof

2010-01-04

Abstract: Aims: The number of prescription medications and out-of-pocket expenses of individuals with type 2 diabetes mellitus (T2DM) were evaluated to assess the economic burden of diabetes.Methods: The self-reported number of prescription medications and out-of-pocket healthcare expenses were evaluated from respondents of the United States SHIELD study with and without a diagnosis of T2DM. Medications included monotherapy and combination therapy; combination tablets were counted as one agent. Analysis of variance and multivariate linear regression models adjusted for age, gender, prescription insurance coverage, and household income.Results: Of the T2DM respondents (n=3551), 40% were on 1 prescription antidiabetic agent (7% insulin alone), 26% were on 2 agents, 8% were on ≥3 agents, with a mean of 1.3 antidiabetic agents. After adjusting for age, gender, insurance coverage, and income, respondents with T2DM had a significantly larger total number of prescriptions (6.2) and higher out-of-pocket expenses for both annual medical ($1158) and monthly prescription ($144) expenses, compared with respondents without T2DM (n=8686) (4.1 prescriptions, $925 annual medical, $118 monthly prescription) (p<0.01).Conclusions: Increased out-of-pocket medical and medication costs in T2DM are due to the use of both antidiabetic agents and other medications for treatment of comorbid conditions.

Leisure-time physical activity and risk of type 2 diabetes in patients with established vascular disease or poorly controlled vascular risk factors - Corrected Proof

2010-01-04

Abstract: Aim: To investigate the effect of leisure-time physical activity on the incidence of type 2 diabetes (T2DM) in patients with manifest arterial disease, or poorly controlled risk factors.Methods: We examined 3940 patients with manifest arterial disease, hypertension or hyperlipidemia, aged 55.2±12.2 years. Leisure-time physical activity was measured by a questionnaire and metabolic equivalent (MET) hours per week (h/wk) were calculated. Incident T2DM was evaluated by a specific diabetes questionnaire.Results: Most patients (65%) were physically inactive (0METh/wk), 12% were insufficiently physically active (0–10.5METh/wk) and 23% were sufficiently physically active (≥10.5METh/wk). During a mean follow-up of 4.7 years, 194 (5%) incident cases of T2DM occurred. Sufficiently physically active patients had a lower incidence of diabetes (hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.37–0.83). Patients who were physically active and not-obese (BMI<30kg/m2) were at the lowest risk for developing T2DM (HR 0.18, 95% CI 0.12–0.28) compared with patients who were physically inactive and obese.Conclusions: Leisure-time physical activity is associated with a decreased risk of T2DM in patients with manifest arterial disease, or poorly controlled risk factors. The combination of physical activity and non-obesity is associated with an even lower risk of the development of type 2 diabetes than the sum of their independent, protective effect.

Transcription factor, SP1, in epiretinal membranes of patients with proliferative diabetic retinopathy - Corrected Proof

2010-01-04

Abstract: SP1 mRNA was highly expressed in the epiretinal membranes of proliferative diabetic retinopathy (PDR), and the SP1 protein was mainly co-localized with vascular endothelial growth factor. SP1 might play an important role in the angiogenesis of PDR by regulating the promoter activity and expression of genes encoding angiogenesis-related factors.

Effects of Glimepiride on metabolic parameters and cardiovascular risk factors in patients with newly diagnosed type 2 diabetes mellitus - Corrected Proof

2010-01-04

Abstract: Background: To investigate the effects of Glimepiride on blood glucose in patients with newly diagnosed type 2 diabetes mellitus (T2DM) in connection with plasma lipoproteins and plasminogen activity.Methods: A total of 565 T2DM patients were received Glimepiride (n=333) or Glibenclamide (n=232) for 12 weeks. We observed the level of blood glucose (BG), glycated hemoglobin (HbA1C), the insulin resistance (IR) state, plasma lipoproteins, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type I (PAI-1) before and after a 12 weeks of treatment.Results: After 12 weeks with Glimepiride treatment, significant reductions were observed in fasting blood glucose (FBG) and 2-h postprandial BG(PBG), HbA1C (from 8.60±3.10 to 7.10±1.60%) and HOMA-IR (from 4.11±0.85 to 2.42±0.91%). The level of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly decreased, whereas that of high-density lipoprotein (HDL) was increased markedly with statistical significance. In addition, there was an obvious improvement in t-PA activity (from 0.225±0.11 to 0.457±0.177IU/ml); whereas the PAI-1 activity was decreased significantly (from 0.898±0.168 to 0.533±0.215AU/ml). No significant changes were observed in plasma lipoprotein profiles and plasminogen activity in Glibenclamide receiving group.Conclusions: Glimepiride can rapidly and stably improve glycemic control and lipoprotein metabolism, significantly alleviate insulin resistance and enhance fibrinolytic activity.

Seasonal fluctuations of glycated hemoglobin levels in Japanese diabetic patients - Corrected Proof

Hiroshi Sakura, Yasutomi Tanaka, Yasuhiko Iwamoto — 2010-01-04

Abstract: Aims: We examined whether glycated hemoglobin (HbA1C) levels of Japanese diabetic patients showed seasonal fluctuations.Methods: Subjects included 2511 diabetic patients who regularly visited a single diabetic outpatient clinic for 10 years. A total of 253,477 HbA1C measurements, as well as sex, age, BMI, type of diabetes, and mode of therapy were extracted from a hospital-based database. For the cross-sectional and longitudinal analyses, average monthly HbA1C values of subjects and amplitudes of seasonal fluctuations were calculated. For the time-series analysis, seasonal adjustment factors of each subject were classified as complete, incomplete, or no fluctuation.Results: Subjects showed a clear seasonal fluctuation of HbA1C levels, with highest levels in March (7.69%) and lowest levels in August (7.46%; p<0.001). The amplitudes of the seasonal fluctuations were associated with the mean HbA1C levels. The time-series analysis showed that 78.3% of patients had complete or incomplete seasonal fluctuations. HbA1C levels were highest in winter–spring and lowest in summer–autumn in most patients; however, some patients showed a reverse pattern.Conclusions: Seasonal fluctuations of HbA1C levels were recognized in most of the Japanese diabetic patients. Physiological or metabolic factors related to temperature may be the main cause of seasonal fluctuations in HbA1C levels.

Start improving the quality of care for people with type 2 diabetes through a general practice support program: A cluster randomized trial - Corrected Proof

2010-01-04

Abstract: Aims: To evaluate the effectiveness of a two-arm quality improvement program (QIP) to support general practice with limited tradition in chronic care on type 2 diabetes patient outcomes.Methods: During 18 months, we performed a cluster randomized trial with randomization of General Practices. The usual QIP (UQIP: 53 GPs, 918 patients) merged standard interventions including evidence-based treatment protocol, annual benchmarking, postgraduate education, case-coaching for GPs and patient education. The advanced QIP (AQIP: 67 GPs, 1577 patients) introduced additional interventions focussing on intensified follow-up, shared care and patient behavioural changes. Main outcomes were HbA1c, systolic blood pressure (SBP), and low density lipoprotein cholesterol (LDL-C), analyzed by generalized estimating equations and linear mixed models.Results: In UQIP, endpoints improved significantly after intervention: HbA1c −0.4%, 95% CI [−0.4; −0. 3]; SBP −3mmHg, 95% CI [−4; −1]; LDL-C −13mg/dl, 95% CI [−15; −11]. In AQIP, there were no significant additional improvements in outcomes: HbA1c −0.4%, 95% CI [−0.4; −0.3]; SBP −4mmHg, 95% CI [−5; −2]; LDL-C −14mg/dl, 95% CI [−15; −11].Conclusions: A multifaceted program merging standard interventions in support of general practice induced significant improvements in the quality of diabetes care. Intensified follow-up in AQIP with focus on shared care and patient behaviour changes did not yield additional benefit.

Diabetic kidney disease: Act now or pay later - Corrected Proof

2009-12-31

In 2003, the International Society of Nephrology and the International Diabetes Federation launched a booklet called “Diabetes and Kidney Disease: Time to act” to highlight the global pandemic of type 2 diabetes and diabetic kidney disease. It aimed to alert governments, health organisations, providers, doctors and patients to the increasing health and socio-economic problems due to diabetic kidney disease and its sequelae, end stage kidney disease requiring dialysis and cardiovascular death. Seven years later, the same message has become even more urgent. World Kidney Day 2010, under the auspices of the International Society of Nephrology (ISN) and the International Federation of Kidney Foundations (IFKF), together with the International Diabetes Federation (IDF), provides yet another chance to underline the importance of diabetic kidney disease, stress its lack of awareness at both public and government levels and emphasise that its management involves prevention, recognition and treatment of its complications. Primary prevention of type 2 diabetes will require massive lifestyle changes in the developing and developed world supported by strong governmental commitment to promote lifestyle and societal change.

Using anthropometric indices to predict cardio-metabolic risk factors in Australian Indigenous populations - Corrected Proof

Ming Li, Robyn A. McDermott — 2009-12-25

Abstract: Aims: To compare the predictive power of anthropometric indices (BMI, waist circumference (WC), waist-to-hip ratio (WHpR) and waist-to-height ratio (WHtR)) for diabetes, hypertension and dyslipidemia in Australian Aboriginal and Torres Strait Islander (TSI) adults.Methods: Cross-sectional study of 2862 Indigenous Australians aged over 15 living in rural communities in Far North Queensland during 1999–2001. The predictive values of anthropometric indices for cardio-metabolic disorders were compared using receiver operating characteristic (ROC) analysis.Results: BMI was the poorest predictor while WHpR was the best among the four measures. The optimal WHtR and WHpR cut-off points for the cardio-metabolic risks in both women and men in the two Indigenous populations were 0.5–0.6 and 0.9 respectively. Optimal BMI cut-offs for diabetes, hypertension, and dyslipidemia were much lower in Aborigines than the recommended WHO BMI cut-offs, while those in TSIs were around WHO BMI criteria. The optimal WC cut-points varied by gender and ethnicity.Conclusions: BMI was not a good discriminator of cardio-metabolic risk factors in Australian Indigenous populations compared with other anthropometric indices. WHpR is more closely associated with the risk of cardio-metabolic in these high-risk populations.

Plasma sRAGE is independently associated with high sensitivity C-reactive protein in type 2 diabetes without coronary artery disease - Corrected Proof

Xiao-Fei An, Yue Zhao, Jiang-Yi Yu, Jing-Shun Liu, Wan-Jian Gu, Feng Gao — 2009-12-25

Abstract: Our studies suggest that plasma soluble advanced glycation end products (sRAGEs) has significantly negative association with high sensitivity C-reactive protein (hs-CRP) in 245 type 2 diabetes patients without diagnosed coronary artery disease (CAD). sRAGE maybe act as a novel biomarker for predicting the atherosclerosis in diabetes at the early stage.

Time lag characterization of two continuous glucose monitoring systems - Corrected Proof

Satish K. Garg, Mary Voelmle, Peter A. Gottlieb — 2009-12-21

Abstract: Aim: To evaluate the system time lag associated with subcutaneous interstitial glucose (IG) sensing and venous blood glucose (BG) of two continuous glucose monitoring (CGM) systems, the SEVEN® (DexCom™, San Diego, CA) and the Navigator® (Abbott Diabetes Care, Alameda, CA), in adults with type 1 diabetes.Methods: Fourteen subjects wore both CGM systems concurrently during the 15-day study. Reference YSI (Yellow Springs, OH) and CGM data from the in-clinic sessions, conducted on day 5, 10 and 15 of the study were evaluated. The system time lag of CGM system was estimated using various regression method related statistical estimators.Results: The estimated time lags based on different statistical measures are similar within each CGM system. The time lag based on correlation coefficient criteria is estimated as 4.5±5min (median±IQR) for the SEVEN®, and 15±7min for the Navigator®. The ranges of these estimators of two CGM systems were different (2–6min for SEVEN® and 14–15min for Navigator®).Conclusions: The study findings suggest that commonly accessible statistics, such as correlation statistics, offer estimates that are comparable to complicated approaches. Different time lags were observed with two CGM systems.

Molecular pathology of oxidative stress in diabetic angiopathy: Role of mitochondrial and cellular pathways - Corrected Proof

Zhirajr Mokini, M. Loredana Marcovecchio, Francesco Chiarelli — 2009-12-21

Abstract: Diabetes mellitus is characterized by chronic hyperglycaemia and a significant risk of developing micro- and macrovascular complications. Growing evidence suggests that increased oxidative stress, induced by several hyperglycaemia-activated pathways, is a key factor in the pathogenesis of endothelial dysfunction and vascular disease.Reactive oxidant molecules, which are produced at a high rate in the diabetic milieu, can cause oxidative damage of many cellular components and activate several pathways linked with inflammation and apoptosis. Among the mechanisms involved in oxidative stress generation, mitochondria and uncoupling proteins are of particular interest and there is growing evidence suggesting their pivotal role in the pathogenesis of diabetic complications. Other important cellular sources of oxidants include nicotinamide adenine dinucleotide phosphate oxidases and uncoupling endothelial nitric oxide synthase. In addition, diabetes is associated with reduced antioxidant defences, which generally contrast the deleterious effect of oxidant species. This concept underlines a potential beneficial role of antioxidant therapy for the prevention and treatment of diabetic vascular disease. However, large scale trials with classical antioxidants have failed to show a significant effect on major cardiovascular events, thus underlying the need of further investigations in order to develop therapies to prevent and/or delay the development of micro- and macrovascular complications.

Vital sign triage to rule out diabetic ketoacidosis and non-ketotic hyperosmolar syndrome in hyperglycemic patients - Corrected Proof

2009-12-21

Abstract: Aims: To develop a prediction algorithm to rule out diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar syndrome (NKHS) based on vital signs for early triage of patients with diabetes.Methods: The subjects were consecutive adult diabetic patients with hyperglycemia (blood glucose ≥250mg/dl) who presented at an emergency department. Based on a derivation sample (n=392, 70% of 544 patients at a hospital in Okinawa), recursive partitioning analysis was used to develop a tree-based algorithm. Validation was conducted using the other 30% of the patients in Okinawa (n=152, internal validation) and patients at a hospital in Tokyo (n=95, external validation).Results: Three risk groups for DKA/NKHS were identified: a high-risk group of patients with glucose >400mg/dl or systolic blood pressure <100mmHg; a low risk group of patients with glucose ≤400mg/dl and normal vital signs (systolic blood pressure ≥100mmHg, pulse ≤90/min, and respiratory rate ≤20/min); and an intermediate risk group. The prevalences of DKA/NKHS were 2% (derivation set), 0% (internal validation set), and 0% (external validation set) in the low risk group, respectively.Conclusions: Our algorithm may help DKA/NKHS triage and patients with normal vital signs can be initially triaged as low risk for DKA/NKHS.

Serum fatty acid composition and insulin resistance are independently associated with liver fat markers in elderly men - Corrected Proof

Helena Petersson, Johan Ärnlöv, Björn Zethelius, Ulf Risérus — 2009-12-18

Abstract: Aim: To investigate the relationships of serum fatty acid (FA) composition and estimated desaturase activities with the liver fat marker alanine aminotransferase (ALT).Methods: 546 Swedish elderly men of a population-based cohort participated in this cross-sectional study. FA composition was assessed in serum cholesterol esters to determine dietary fat quality (e.g. linoleic) and desaturation products (e.g. dihomo-γ-linolenic acid). Desaturase indices, including stearoyl coenzymeA desaturase-1 (SCD-1), were calculated by FA product-to-precursor ratios.Results: In linear regression analyses adjusting for lifestyle, abdominal obesity and insulin sensitivity, the dietary biomarker linoleic acid (n-6), but not n-3 FAs, was inversely related to ALT. Desaturation products including palmitoleic, oleic, γ-linolenic and dihomo-γ-linolenic acids, and Δ6-desaturase and SCD-1 indices were directly related to ALT (all p<0.05). After further adjustment for factors previously linked to fatty liver (i.e. serum lipids, adiponectin concentrations), SCD-1 index (p=0.004) and insulin resistance (p<0.0001) were independent determinants of ALT activity, whereas waist circumference, triglycerides, non-esterified FA and adiponectin were not.Conclusion: A low dietary intake of linoleic acid and elevated SCD-1 index may contribute to higher ALT activity in elderly men, even independently of obesity and insulin resistance.

A novel glucokinase gene mutation and its effect on glycemic/C-peptide fluctuations in a patient with maturity-onset diabetes of the young type 2 - Corrected Proof

Lindsey A. Loomba-Albrecht, Maryam Jame, Andrew A. Bremer — 2009-12-16

Abstract: Maturity-onset diabetes of the young (MODY) is a group of disorders accounting for 2–5% of diabetes; MODY2 is caused by inactivating GCK mutations. We report a case of MODY2 caused by a novel GCK mutation and demonstrate differential glycemic/C-peptide responses to treatment with insulin, no medication, and an oral sulfonylurea.

Prevalence of non-diabetic renal disease in patients with type 2 diabetes - Corrected Proof

2009-12-14

Abstract: It is important to differentiate proteinuria from non-diabetic renal diseases (NDRD) or diabetic nephropathy in diabetic patients. The purpose of our study was to evaluate the prevalence of NDRD. A retrospective analysis was performed on diabetic patients who had undergone renal biopsy during a 6-year period. Our study revealed a high prevalence of NDRD in the diabetic population. Sixty-nine patients were investigated, 52.2% were diagnosed as NDRD and 47.8% as DN. Focal segmental glomerulosclerosis was the most common lesion found in patients with NDRD. We found a relationship between DN and fasting blood glucose level, systolic blood pressure, diastolic blood pressure, LVMI, intima-media thickening (IMT), and the presence of carotid plaques. Patients with NDRD had a lower incidence of diabetic retinopathy (DR). The absence of DR to differentiate NDRD had a sensitivity of 72.7%, a specificity 91.7%, and an ROC=0.822. Fasting blood glucose level had a sensitivity and specificity of 93.9% and 75%, respectively. Similarly, the use of IMT had sensitivity and specificity of 90% and 75.8%, respectively. In this study, we determined that the absence of DR, a lower fasting blood glucose level, and IMT is useful in differentiating NDRD from DN in diabetic patients with overt proteinuria.

Impact of metabolic syndrome, diabetes and prediabetes on cardiovascular events: Tehran Lipid and Glucose Study - Corrected Proof

Farzad Hadaegh, Gita Shafiee, Asghar Ghasemi, Parvin Sarbakhsh, Fereidoun Azizi — 2009-12-09

Abstract: Aims: To compare the cardiovascular disease (CVD) risk associated with the metabolic syndrome (MetS) and dysglycemia, independent of each other during a median follow-up of 6.7 years.Methods: Study population included 4018 Iranian subjects≥40 years, free of CVD or coronary heart disease (CHD) at baseline. Incidence rates and hazard ratio (HR) were estimated by the presence or absence of MetS and dysglycemia. Considering the glycemic status, the ability of MetS in prediction of CVD after adjustment for age, sex and CVD risk factors was assessed.Results: The prevalence of MetS, impaired fasting glucose or impaired glucose tolerance (IFG/IGT) and diabetes were 51.4%, 27.3%, and 18.7%, respectively. The addition of MetS to diabetes did not change the CVD risk compared to diabetic subjects without MetS (reference group) after adjustment for age and sex [HR: 1.62 (95% CI 0.93–2.81)] and CVD risk factors [HR: 1.49 (95% CI 0.86–2.60)]. However, addition of MetS to IFG/IGT increased the risk of CVD by 2.5 times compared to those with IFG/IGT without MetS (the risk factor adjusted HR: 2.45 (95% CI 1.32–4.55)).Conclusions: In Iranian population, MetS did not add to diabetes to predict incident CVD however, IFG/IGT was a significant predictor only in the presence of MetS.

Comorbidity in the elderly with diabetes: Identification of areas of potential treatment conflicts - Corrected Proof

2009-11-18

Abstract: Aims: To investigate the prevalence of comorbid conditions in the elderly with diabetes and the prescribing of potentially inappropriate medicines or treatment conflicts.Methods: A cross-sectional study of diabetics aged ≥65 years, using prescription dispensing data from the Australian Department of Veterans’ Affairs. Comorbidities were determined using the comorbidity index Rx-Risk-V. Potentially inappropriate prescribing or treatment conflicts specific for the elderly were determined from guidelines or reference compendia, in addition to the 2003 updated Beers criteria.Results: Of 18,968 diabetics, the median number of comorbidities was 5 (IQR 3–8). Diabetes and associated cardiovascular medicines accounted for 41.9% of all medicine use. Associated cardiovascular diseases were highly prevalent comorbidities. 46% had gastro-oesophageal reflux disease, 25% depression, 20% chronic airways disease or chronic pain and 15% also had heart failure or inflammation-pain. At least 16% were dispensed a medicine associated with adverse effects in patients with diabetes and 22.7% were dispensed at least one potentially inappropriate medicine.Conclusion: Significant comorbid conditions in elderly diabetic patients with potential for inappropriate prescribing or treatment conflicts include arthritis, heart failure, chronic airways diseases and diseases treatable with systemic corticosteroids. Appropriate management of comorbidity should be included in guidelines for the elderly with diabetes.

Beneficial effect of physical activity on blood pressure and blood glucose among Japanese male workers - Corrected Proof

Kazuko Ishikawa-Takata, Hirofumi Tanaka, Keiji Nanbu, Toshiki Ohta — 2009-11-02

Abstract: Aims: To examine the appropriate type and frequency of physical activity for the beneficial effect on hypertension and hyperglycemia.Methods: The incidence of hypertension and hyperglycemia was assessed using the results of annual physical checkups over 4 years for 5843 male employees aged 18–57 years old. Associations of different types of physical activity with the incidence of these two risk factors were examined with Cox proportional-hazard models.Results: There was a progressive reduction in the hazards ratios of hypertension with increasing total daily activity (hazards ratio of 0.65 (95% CI, 0.45–0.93) in subjects who walked >8000 steps/day vs. <4000 steps/day). Subjects who exercised >3 times/week also showed a significantly lower risk (0.35; 0.13–0.96) of developing hypertension vs. those who exercised <3 times/week. The only physical activity factor associated with a lower incidence of hyperglycemia was weekend (Saturday and Sunday) physical activity (0.66; 0.43–0.99, very active vs. sedentary on weekends).Conclusion: Increasing daily and leisure time physical activities had a beneficial effect on hypertension independent from physical activity at weekend, while only doing physical activity on weekends affects an elevation of blood glucose independent of daily and leisure time physical activity.