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1.  Acanthosis nigricans in type 2 diabetes: prevalence, correlates and potential as a simple clinical screening tool - a cross-sectional study in the Caribbean 
Background
This study aimed to evaluate the role of acanthosis nigricans (AN) as a marker of Type 2 Diabetes Mellitus (T2DM) by studying its prevalence and relationship with age, ethnicity, anthropometry and other risk factors for T2DM in the Trinidadian population.
Methods
311 successive adult patients with T2DM were recruited at diabetic clinics and inpatient wards across Trinidad. The presence, severity and texture of AN at the neck were assessed. Demographic, clinical and anthropometric characteristics were also measured, and logistic regression was used to model their relationship with presence of AN.
Results
The mean (SD) age was 58.1 years (12.6). 55.6% were female. 61.1% were East Indian, 24.4% African and 14.5% mixed ethnicity. The mean (SD) BMI was 27.3 kg/m2 (6.0) and the mean (SD) waist circumference was 96.7 cm (14.2). Prevalence of AN was 52.7% (95% CI 47.2, 58.3).
There was a greater odds of AN among diabetic patients who were: younger (p < 0.001); female (OR 1.67; 95% CI 1.06, 2.62); or East Indian rather than African (0.45; 0.26, 0.77) or mixed (0.43; 0.22, 0.84) descendents. There was a greater age-, sex- and ethnicity-adjusted odds of AN among those: overweight (3.98; 2.10, 7.55) or obese (8.31; 3.84, 18.00) versus normal BMI; centrally obese (4.72; 2.65, 8.43); with history of hypertension (2.19; 1.27, 3.79) or history of hypercholesterolemia (1.72; 1.02, 2.90), but there was no evidence of this demographic-adjusted association (p > 0.4) between AN and history of previous MI or CVA, family history of T2DM, T2DM treatment regimen, duration of T2DM or random blood glucose.
On further multivariable analysis, only age, sex, ethnicity, BMI and waist circumference were independently associated with AN (p < 0.05) and the effect of BMI varied with ethnicity.
Conclusions
There was a high prevalence of AN both overall and across age, sex and ethnic groups of diabetic patients. AN exhibited much potential as a valuable addition to T2DM risk assessment in the Trinidadian and similar settings.
doi:10.1186/1758-5996-6-77
PMCID: PMC4099386  PMID: 25031628
Acanthosis nigricans; Type 2 diabetes mellitus; Prevalence; Obesity; Screening; Risk factor; Age; Sex; Ethnicity; BMI; Waist circumference
2.  Effect of glycemic variability on short term prognosis in acute myocardial infarction subjects undergoing primary percutaneous coronary interventions 
Objective
Glycemic variability (GV) still remains unclear whether acute glycemic excursion has the important prognostic significance in ST-segment elevation myocardial infarction (STEMI) patients undergoing p-PCI. So our aim is to assess the prognostic value of GV in STEMI patients undergoing p-PCI.
Methods
We studied 237 STEMI patients undergoing p-PCI, whose clinical and laboratory data were collected. We used a continuous glucose monitoring system (CGMS) to measure the fluctuations of blood glucose. Participants were grouped into diabetes group and non-diabetes group, and grouped into tertiles of mean amplitude of glycemic excursions (MAGE). The major adverse cardiac events (MACE) of patients was documented during in-hospital and 30-day follow-up. The relationship of MAGE and the incidence of MACE were analyzed.
Results
Data from 237 subjects were incorporated into the statistical analysis, a higher MAGE level was associated with the higher peak CK-MB values (r = 0.374, P <0.01), and the higher peak cTnI values (r = 0.410, P <0.01). The rate of composite MACE by MAGE tertiles (<2.37 mmol/l, 2.37-3.65 mmol/l and >3.65 mmol/l) was 7.5% vs. 14.1% vs. 22.8%, respectively (P = 0.025); STEMI patients with a higher MAGE level had a significantly higher non-IRA revascularization compared with those with lower MAGE levels (32% vs. 15% vs. 21%, P = 0.037). Moreover, diabetic patients with higher MAGE level had significantly higher incidence of composite MACE and non-IRA revascularization, non-diabetic subjects did not show the similar results. In multivariable logistic analysis, the independent predictors of MACE were: MBG, MAGE and LVEF in diabetic subjects and were MBG and MAGE in nondiabetic subjects. Other factors were not significantly associated with MACE.
Conclusions
Greater GV is associated with composite MACE and non-IRA revascularization during in-hospital and 30-day follow-up in unadjusted analyses, especially for diabetic subjects. After multivariable logistic analysis, GV remains an independent prognostic factor for composite MACE in STEMI patients undergoing p-PCI.
doi:10.1186/1758-5996-6-76
PMCID: PMC4091650  PMID: 25013458
Glycemic variability-GV; ST-segment elevation myocardial infarction-STEMI; Primary percutaneous coronary interventions-p-PCI; Mean amplitude of glycemic excursions-MAGE
3.  Does family history of metabolic syndrome affect the metabolic profile phenotype in young healthy individuals? 
Background
Early identification of high-risk individuals is key for the prevention of cardiovascular disease (CVD). The aim of this study was to assess the potential impact of a family history of metabolic syndrome (fhMetS) on the risk of metabolic disorders (abnormal body mass, lipid profile, glucose metabolism, insulin resistance, and blood pressure) in healthy young individuals.
Methods
We studied CVD risk factors in 90 healthy volunteers, aged 27–39 years; of these, 78 had fhMetS and 12 were without fhMetS (control group). Fasting serum lipids, glucose, and insulin levels were assayed, and anthropometric parameters and blood pressure using, an ambulatory blood pressure monitoring system, were measured. Nutritional and physical activity habits were assessed.
Results
Despite similar nutritional and physical activity habits, abnormal body mass was found in 53.2% of the fhMetS participants and 46.1% of the control participants (p = 0.54). The occurrence of obesity was 19.4% and 0%, respectively (p = 0.69). Compared to the control participants, fhMetS was associated with significantly higher total cholesterol (5.46 mmol/L vs. 4.69 mmol/L, p < 0.030), low-density lipoprotein cholesterol ( 3.28 mmol/L vs. 2.90 mmol/L, p < 0.032), and non-high-density lipoprotein cholesterol ( 3.74 mmol/L vs. 3.25 mmol/L, p < 0.016) levels, in addition to lower fasting glucose levels ( 4.51 mmol/L vs. 4.81 mmol/L, p < 0.042). A positive correlation between fasting glucose and insulin levels (r = 0.28; p < 0.015) was detected in the fhMetS participants. Higher mean daytime systolic blood pressure (121.5 mmHg vs. 113.3 mmHg, p < 0.035), mean daytime diastolic blood pressure ( 79.0 mmHg vs. 74.5 mmHg, p < 0.045), and mean nighttime diastolic blood pressure ( 64.0 mmHg vs. 59.5 mmHg, p < 0.019) were observed in the fhMetS group.
Conclusions
More than 50% of the fhMetS participants had excess weight or a lipid disorder, which may indicate an increased risk of cardiovascular disease and the need for regular ambulatory assessment of serum lipid concentrations in young people with a family history of MetS.
doi:10.1186/1758-5996-6-75
PMCID: PMC4096539  PMID: 25024747
Metabolic syndrome; Family history; Cardiovascular disease; Risk factors
4.  A standard ballroom and Latin dance program to improve fitness and adherence to physical activity in individuals with type 2 diabetes and in obesity 
Objective
To test the effectiveness of a dance program to improve fitness and adherence to physical activity in subjects with type 2 diabetes and obesity.
Research Design and Methods
Following a motivational interviewing session, 100 subjects with diabetes and/or obesity were enrolled either in a dance program (DP, n = 42) or in a self-selected physical activity program (SSP, n = 58), according to their preferences. Outcome measures were reduced BMI/waist circumference, improved metabolic control in type 2 diabetes (−0.3% reduction of HbA1c) and improved fitness (activity expenditure >10 MET-hour/week; 10% increase in 6-min walk test (6MWT)). Target achievement was tested at 3 and 6 months, after adjustment for baseline data (propensity score).
Results
Attrition was lower in DP. Both programs significantly decreased body weight (on average, −2.6 kg; P < 0.001) and waist circumference (DP, −3.2 cm; SSP, −2.2; P < 0.01) at 3 months, and the results were maintained at 6 months. In DP, the activity-related energy expenditure averaged 13.5 ± 1.8 MET-hour/week in the first three months and 14.1 ± 3.0 in the second three-month period. In SSP, activity energy expenditure was higher but highly variable in the first three-month period (16.5 ± 13.9 MET-hour/week), and decreased in the following three months (14.2 ± 12.3; P vs. first period < 0.001). At three months, no differences in target achievement were observed between groups. After six months the odds to attain the MET, 6MWT and A1c targets were all significantly associated with DP.
Conclusion
Dance may be an effective strategy to implement physical activity in motivated subjects with type 2 diabetes or obesity (Clinical trial reg. no.NCT02021890, clinicaltrials.gov).
doi:10.1186/1758-5996-6-74
PMCID: PMC4082296  PMID: 25045404
5.  Serum retinol-binding protein 4 levels are elevated but do not contribute to insulin resistance in newly diagnosed Chinese hypertensive patients 
Background
Insulin resistance (IR) is closely correlated with cardiovascular disease (CVD). Retinol-binding protein 4 (RBP4) is a novel adipokine that modulates the action of insulin in various diseases. This study addressed the relationship between RBP4 and IR in newly diagnosed essential hypertension.
Methods
Serum RBP4, anthropometric and metabolic parameters were determined in 267 newly diagnosed essential hypertensive patients not taking antihypertensive medications. The patients along with 64 control (NC) normotensive and lean subjects paired by age and sex were divided into two groups depending on body mass index (BMI), hypertension with obesity (HPO) and hypertension without obesity (HP).
Results
A striking difference was observed in RBP4 levels between the HP and NC groups. Significantly higher levels were noted in the HP group compared with the NC group; slightly, but not significantly, lower levels were observed in the HPO group compared with the HP group. After adjusting for BMI, WC and WHR, a modestly linear relationship was observed between RBP4 levels and SBP (r = 0.377; p = 0.00), DBP (r = 0.288; p = 0.00) and HOMA-β(r = 0.121; p = 0.028). Multiple stepwise regression analysis showed that SBP, WHR and drinking were independently related with serum RBP4 levels.
Conclusions
The results of this study indicated that RBP4 levels were increased in naive hypertensive patients; however, no differences were observed in obese or non-obese hypertensive subjects. Our data suggest for the first time that RBP4 levels are significantly increased but do not contribute to the development of IR in newly diagnosed hypertensive Chinese patients.
doi:10.1186/1758-5996-6-72
PMCID: PMC4058001  PMID: 24932224
Retinol-binding protein 4; Insulin resistance; Obesity; Essential hypertension
6.  A systematic review and mixed-treatment comparison of dapagliflozin with existing anti-diabetes treatments for those with type 2 diabetes mellitus inadequately controlled by sulfonylurea monotherapy 
Background
To compare the first-in-class sodium glucose co-transporter 2 (SGLT2) inhibitor, dapagliflozin, with existing type 2 diabetes mellitus (T2DM) treatment options available within the European Union (EU) for add-on therapy to sulfonylureas (SUs).
Methods
A systematic review was conducted to identify randomised controlled trials (RCTs) in T2DM patients inadequately controlled by SU monotherapy. Direct meta-analysis, Bucher indirect comparisons and Bayesian network meta-analysis (NMA) were conducted on studies meeting predefined inclusion criteria. Sufficient data were available to assess three clinical endpoints at 24 (+/- 6) weeks follow-up: mean change in HbA1c from baseline, mean change in weight from baseline, and the proportion of patients experiencing at least one episode of hypoglycaemia. The effect of confounding baseline factors was explored through covariate analyses.
Results
The search identified 1,901 unique citations, with 1,870 excluded based on title/abstract. From reviewing full-texts of the remaining 31 articles, 5 studies were considered eligible for analysis. All studies were comparable in terms of baseline characteristics, including: HbA1c, age and body mass index (BMI). In addition to dapagliflozin, sufficient data for meta-analysis was available for three dipeptidyl peptidase-4 (DPP-4) inhibitors and one glucagon-like peptide-1 (GLP-1) analogue. Based on fixed-effect NMA, all treatment classes resulted in statistically significant decreases in HbA1c at follow-up compared to placebo. Dapagliflozin treatment resulted in significantly decreased weight at follow-up compared to placebo (-1.54 kg; 95% CrI -2.16, -0.92), in contrast to treatment with GLP-1 analogues (-0.65 kg; 95% CrI -1.37, 0.07) and DPP-4 inhibitors (0.57 kg; 95% CrI 0.09, 1.06). The odds of hypoglycaemia were similar to placebo for dapagliflozin and DPP-4 inhibitor add-on treatment, but significantly greater than placebo for GLP-1 analogue add-on treatment (10.89; 95% CrI 4.24, 38.28). Assessment of NMA model heterogeneity was hindered by the small size of the network.
Conclusions
Dapagliflozin, DPP-4 inhibitors and GLP-1 analogues, in combination with SU, all provided better short-term glycaemic control compared to SU monotherapy. Dapagliflozin was the only add-on therapy that had both a favourable weight and hypoglycaemia profile compared to the other classes of treatment evaluated.
doi:10.1186/1758-5996-6-73
PMCID: PMC4085736  PMID: 25006351
Diabetes; Dapagliflozin; Mixed treatment comparison; Systematic review; Network meta-analysis
7.  Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study 
Background
The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes.
Methods
A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes.
Results
After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients.
Conclusions
The prevalence and risk of lower limb atherosclerotic plaque in the ketosis-onset diabetes were remarkably higher than in the control subjects without diabetes. The features and risk factors of lower limb atherosclerotic lesions in the ketosis-onset diabetes resembled those in the non-ketotic type 2 diabetes, but different from those in the type 1 diabetes. Our findings provide further evidences to support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes rather than idiopathic type 1 diabetes.
doi:10.1186/1758-5996-6-71
PMCID: PMC4054910  PMID: 24926320
Type 1 diabetes; Ketosis-onset diabetes; Type 2 diabetes; Lower limb arteries; Atherosclerosis
8.  Effects of high-fat diet and the anti-diabetic drug metformin on circulating GLP-1 and the relative number of intestinal L-cells 
Background
Elevated serum free fatty acids (FFAs) contribute to the pathogenesis of type-2-diabetes (T2D), and lipotoxicity is observed in many cell types. We recently showed that simulated hyperlipidemia induces lipoapoptosis also in GLP-1-secreting L-cells in vitro, while metformin confers lipoprotection.
The aim of this study was to determine if a high fat diet (HFD) reduces the number of enteroendocrine L-cells and/or GLP-1 plasma levels in a rodent model, and potential effects thereupon of metformin treatment.
Methods
C57/Bl6 mice received control/HFD for 12-weeks, and oral administration of metformin/saline for the last 14 days. Blood glucose, glycosylated hemoglobin and plasma insulin and GLP-1 were determined before and after treatment with metformin using ELISAs. GLP-1-immunopositive cells in intestinal tissue sections were quantified using immunohistochemistry.
Results
A HFD increased blood glucose, glycosylated hemoglobin, and fasting plasma insulin (33%, 15% and 70% increase, respectively), in conjunction with reduced oral glucose tolerance, indicating the manifestation of insulin resistance. Metformin counteracted these adverse effects, while also reducing prandial plasma FFAs. The number of GLP-1-positive cells was indicated to be reduced (55% reduction of the number of GLP-1-positive cells, p = 0.134), while there was a trend toward increased prandial plasma GLP-1 despite reduced food intake following a HFD.
Conclusion
HFD-fed mice rapidly develop insulin resistance. Metformin exerts beneficial glucose lowering effects, and is indicated to improve the incretin response. Albeit no significant effect, a HFD tends to reduce the number of GLP-1-positive cells. However, considering concurrent normal or increased plasma GLP-1, any reduction in the number of GLP-1-positive cells, probably does not contribute to development of the glucose intolerance, but may contribute to progression of the diabetic state through eventual loss of a functional incretin response.
doi:10.1186/1758-5996-6-70
PMCID: PMC4097088  PMID: 25028601
Metformin; Glucagon-like peptide-1; Insulinotropic; Lipotoxicity; L-cell
9.  Efficacy and safety of vildagliptin, Saxagliptin or Sitagliptin as add-on therapy in Chinese patients with type 2 diabetes inadequately controlled with dual combination of traditional oral hypoglycemic agents 
Background
The oral DPP-4 inhibitors are new incretin-based therapies for treatment of type 2 diabetes. To assess the efficacy and safety of three DPP-4 inhibitors (Saxagliptin, Sitagliptin and Vildagliptin) as add-on therapy to dual combination of traditional oral hypoglycemic agents in Chinese type 2 diabetes patients.
Methods
In this 24-week, randomized, open-label, parallel clinical trial, we enrolled inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ≥7.5% to ≤10%) patients with type 2 diabetes, who were treated by dual combination of metformin and another traditional oral hypoglycemic agent (glimepiride, acarbose or pioglitazone). 207 patients had been randomized to add-on 5 mg saxagliptin group or 100 mg sitagliptin once daily group, or 50 mg vildagliptin twice daily group for 24 weeks. HbA1c, fasting and postprandial blood glucose (FBG and P2hBG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated.
Result
After 24 weeks, HbA1c, FBG, and P2hBG of each group were significantly decreased. (saxagliptin vs vildagliptin vs sitagliptin: HbA1c: -1.2% vs -1.3% vs -1.1%; FBG: -1.8 mmol/l vs -2.4 mmol/l vs -1.5 mmol/l; P2hBG: -3.4 mmol/l vs -3.7 mmol/l vs -3.2 mmol/l). The changes of HbA1c and P2hBG among the three groups had no significance. However, vildagliptin-added group showed the greatest reduction (p < 0.001), while, sitagliptin-added group showed the lowest reduction (p < 0.001) in terms of FPG changes. Proportions of patients achieving HbA1c < 7% at the end were similar in three groups (saxagliptin 59%, vildagliptin 65%, sitagliptin 59%). Mild hypoglycemia was commonly reported among the three groups (saxagliptin 6%, vildagliptin 2%, sitagliptin 3%). No significant between-group difference was shown in other AEs.
Conclusion
The three gliptins showed almost similar glycemic control and incidence of adverse events. However, for FBG control, saxagliptin demonstrated superiority to sitagliptin, while, inferiority to vildagliptin.
doi:10.1186/1758-5996-6-69
PMCID: PMC4050987  PMID: 24917890
Type 2 diabetes mellitus; Glycemic control; DPP-4 inhibitors; OHAs
10.  Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil 
Background
To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D).
Methods
This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups.
Results
We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001).
Conclusions
Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.
doi:10.1186/1758-5996-6-67
PMCID: PMC4052842  PMID: 24920963
Type 1 diabetes; Chronic complications; Insulin regimens; Brazil
11.  Post-meal β-cell function predicts the efficacy of glycemic control in patients with type 2 diabetes inadequately controlled by metformin monotherapy after addition of glibenclamide or acarbose 
Background
This study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy.
Methods
Fifty-one patients (M/F: 25/26, mean age: 53.7 ± 8.2 years, mean glycated hemoglobin [HbA1c] 8.4 ± 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA-β, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index).
Results
At baseline, there was a significant inverse relationship between DI120 and HbA1c (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 ± 1.6% to 7.4 ± 1.2% (p < 0.001), and from 8.2 ± 0.8% to 7.5 ± 0.8% (p < 0.001), respectively. In the glibenclamide group, DI120 significantly increased from 51.2 ± 24.2 to 74.9 ± 41.9 (p < 0.05), and in the acarbose group, from 62.5 ± 31.4 to 91.7 ± 36.2 (p < 0.05), respectively. Multiple regression analyses showed that both baseline HbA1c and DI120 independently predicted reduction of HbA1c as well as final HbA1c after combination therapy.
Conclusions
In patients with T2DM inadequately controlled with metformin, add-on oral anti-diabetic agent with glibenclamide or acarbose resulted in the significant HbA1c reduction and improvement of β-cell function. Subjects with greater baseline β-cell function reserve displayed better glycemic response in the combination therapy of metformin with glibenclamide or acarbose.
Trial registration
This study was registered in the ClinicalTrials.gov with registration number of NCT00417729.
doi:10.1186/1758-5996-6-68
PMCID: PMC4057801  PMID: 24932223
Beta-cell function; Disposition index; Glycated hemoglobin; Glycemic control; Metformin
12.  The effect on fall rate of blood glucose testing at the time of falls in elderly diabetics 
Objective
To determine the pattern of blood sugar and HbA1c testing among supportive living residents with diabetes and whether, in those with diabetes, blood glucose measurement was done at the time of a fall.
Research design and methods
The management of diabetes in relation to falls in the supportive living sector is unknown. A cross-sectional questionnaire study in Edmonton Alberta, Canada of Designated Supportive Living (DSL) homes have places funded by Alberta Health Services and other homes (SL) that have no funded places. A questionnaire was distributed to Directors of Care/managers of supportive living homes, with telephone interview follow-up if required.
Results
Sixty responses from 61 of the 71 homes (86%) provided information. 21 were DSL and 39 were SL homes. DSL homes were significantly more likely than SL ones to report that residents with diabetes had blood glucose measurements as part of regular care, to be aware that glycosylated haemoglobin was measured, and to say that blood glucose was measured at the time of a fall. Regression analysis identified that facilities with a policy to measure blood glucose at the time of a fall had a lower rate of falls in residents with diabetes than facilities without such a policy (p < 0.05). No effect of this policy was seen in residents without diabetes.
Conclusion
Residents with diabetes were less likely to fall in homes that indicated that they had a policy to measure blood glucose at the time of a fall.
doi:10.1186/1758-5996-6-65
PMCID: PMC4051385  PMID: 24917889
Diabetes; Falls; Blood glucose; Supportive/assisted living
13.  Fiber intake and inflammation in type 1 diabetes 
Background
Higher intake of dietary fiber is associated with lower risk of coronary heart disease, the leading cause of mortality among people with type 1 diabetes. The protective effect includes the anti-inflammatory properties of some foods. Population-based studies have shown an inverse association between some nutritional habits and high sensitive -C-reactive protein (hs-CRP). This study aimed to ascertain the association between fiber intake and hs-CPR levels in patients with type 1 diabetes.
Methods
This cross-sectional study was conducted with 106 outpatients with type 1 diabetes; age 40 ± 11 years; diabetes duration of 18 ± 8.8 years. Dietary intake was evaluated by 3-day weighed-diet records. Patients were categorized in 2 groups, according to fiber intake (>20 g/day and <20 g/day).
Results
The group with fiber intake > 20 g/day had lower hs-CRP levels [median (25th-75th) 0.7 mg/dl (0.4-2.4) vs. 1.9 mg/dl (1.0-4.4); P = 0.002], than the other group. Controlled for HbA1c and energy intake, an inverse relation was observed between hs-CRP levels and total fiber [ß = − 0.030 (SE: 0.0120), P = 0.02], soluble fiber [ß = − 0.078 (SE: 0.0421), P = 0.06] and insoluble fiber [ß = − 0.039 (SE: 0.01761), P = 0.026]. Even, after additional adjustment fibers remained associated with lower hs-CRP levels. Total fibers were stratified in 4 groups: < 10 g/day, from 10 to < 20 g/day, from 20 to 30 g/day and > 30 g/day. Compared to the group who ingested < 10 g/day of total fiber (referent group), the group who consumed > 30 g/d had significantly lower hs-CRP levels [−2.45 mg/L, P = 0.012] independent of the HbA1c values.
Conclusions
The present study suggests that an increased consumption of dietary fiber > 30 g/day may play a role in reducing inflammation in individuals with type 1 diabetes.
doi:10.1186/1758-5996-6-66
PMCID: PMC4083349  PMID: 25002911
Type 1 diabetes; Fiber intake; Inflammation
16.  Increased serum C1q-binding adiponectin complex to total-adiponectin ratio in men with multi-vessel coronary disease 
Background
Adiponectin plays a role as a positive contributor to the stabilization of atherosclerotic plaques. Circulating total adiponectin (Total-APN) levels associates with the number of coronary vessels in men with coronary artery disease (CAD). We recently reported that adiponectin binds to C1q in human blood, and serum C1q-binding adiponectin (C1q-APN) /Total-APN levels are associated with CAD in type 2 diabetic subjects. The present study investigated the relationship between circulating C1q-APN levels and the number of angiographic coronary artery vessel in male subjects.
Methods
The study subjects were 53 male Japanese patients who underwent diagnostic coronary angiography. Blood total adiponectin (Total-APN), high-molecular weight adiponectin (HMW-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assays.
Results
Serum C1q-APN/Total-APN ratio significantly increased in subjects with single and multi-vessel coronary diseases (p = 0.029 for trend, the Kruskal-Wallis test). However, serum Total-APN, HMW-APN, C1q-APN and C1q levels did not correlate with number of diseased coronary vessels.
Conclusion
Serum C1q-APN/Total-APN ratio progressively increases in men with single and multi-vessel coronary disease.
Trial registration
UMIN000002997
doi:10.1186/1758-5996-6-64
PMCID: PMC4038830  PMID: 24883115
Adiponectin; C1q; C1q-binding adiponectin; Coronary artery disease; Angiographic coronary vessel
17.  Epicardial adipose tissue thickness and plasma homocysteine in patients with metabolic syndrome and normal coronary arteries 
Background
Increased epicardial adipose tissue thickness and plasma homocysteine levels are associated with Metabolic Syndrome (MS) and coronary artery disease. The majority of patients with MS have subclinical or manifest coronary artery disease. The aim of this study was to evaluate the relationship between MS and plasma homocysteine levels and epicardial adipose tissue thickness in subjects without epicardial coronary artery disease.
Methods
Patients who underwent coronary angiography due to angina or equivocal symptoms and/or abnormal stress test results and were found to have normal coronary arteries were evaluated for the presence of MS. The study group comprised 75 patients with normal coronary arteries and MS, and the control group included 75 age-gender matched subjects without coronary artery disease or MS.
Results
Epicardial adipose tissue thickness (5.8 ± 1.9 mm vs. 4.3 ± 1.6 mm, p <0.001) and plasma homocysteine levels (21.6 ± 6.1 μmol/L vs. 15.1 ± 5.8 μmol/L, p <0.001) were significantly higher in the MS group. Body mass index, triglyceride level, weight, age and waist circumference were positively and HDL cholesterol level were negatively correlated with both epicardial adipose tissue thickness and plasma homocysteine level. Epicardial adipose tissue thickness had the strongest correlation with plasma homocysteine level (r = 0.584, p < 0.001). For each 1 mm increase in epicardial adipose tissue thickness, an increase of 3.51 μmol/L (95% CI: 2.24-4.79) in plasma homocysteine level was expected.
Conclusions
We observed a close relationship between MS and epicardial adipose tissue thickness and plasma homocysteine levels, even in the absence of overt coronary artery disease.
doi:10.1186/1758-5996-6-62
PMCID: PMC4035667  PMID: 24872849
Angina pectoris; Coronary angiography; Epicardial fat; Homocysteine
18.  Precocious markers of cardiovascular risk and vascular damage in apparently healthy women with previous gestational diabetes 
Previous gestational diabetes mellitus (pGDM) indicates future risk for type 2 diabetes (T2DM). Insulin resistance (IR) may precede T2DM in many years and is associated with an increased risk for cardiovascular diseases.
Aim
This study aims to identify endothelial dysfunction and cardiovascular risk factors in women with pGDM.
Methods
This cross-sectional analysis included 45 non diabetic women, 20 pGDM and 25 controls, at least one year after delivery. Body mass index (BMI), abdominal circumference (AC), blood pressure, serum lipids, liver enzymes, uric acid, nonesterified fatty acids, C-reactive protein and plasma glucose, insulin, fibrinogen and plasminogen activator inhibitor 1 were measured. HOMA IR and β were calculated. Pre and post induced ischemia videocapillaroscopy was performed in hand nailfold to evaluate microvascular morphologic aspect and functional response.
Results
AC and fasting glucose were significantly higher in pGDM (p = 0.01 and p = 0.002 respectively). Women with pGDM and BMI < 25 kg/m2 had significantly higher levels of fasting insulin and HOMA IR than controls (p = 0.008 and 0.05 respectively). Abnormal morphologic findings were more frequent and papillae rectification were 3.3 times more prevalent in pGDM (p = 0.003). Other microvascular parameters did not differ between groups.
Conclusion
Cardiovascular risk factors and a microcirculation abnormality (papillae rectification) were significantly increased in young non-diabetic women with pGDM.
doi:10.1186/1758-5996-6-63
PMCID: PMC4064263  PMID: 24955136
Gestational diabetes; Cardiovascular risk; Microangiopathy
19.  Blood glucose lowering activity of aloe based composition, UP780, in alloxan induced insulin dependent mouse diabetes model 
Background
There are a few nutritional approaches to address the increased needs of managing diabetic conditions. Previously it has been reported that UP780, a standardized composition of aloe chromone formulated with an aloe polysaccharide, has a significant impact in reducing HbA1C, fasting blood glucose, fructosamine and plasma insulin level in humans and improved impaired glucose and insulin resistance in high-fat diet-induced and db/db non-insulin dependent diabetic mouse models. Here we describe activity of UP780 and its constituents to improve insulin sensitivity in alloxan induced insulin dependent diabetic mouse model.
Materials and method
Insulin dependent diabetes was induced by administering a single intraperitoneal injection of alloxan monohydrate at a dose of 150 mg/kg to CD-1 mice. Aloesin (UP394) was formulated with an Aloe vera inner leaf gel powder polysaccharide (Qmatrix) to yield a composition designated UP780. Efficacy of oral administration of UP780 at 2000 mg/kg and its constituents (aloesin at 80 mg/kg and Qmatrix at 1920 mg/kg) were evaluated in this model. Glyburide, a sulfonylurea drug used in the treatment of type 2 diabetes, was used at 5 mg/kg as a positive control. Effect of UP780 on non-diabetic normal mice was also addressed.
Results
Mice administered intraperitoneal alloxan monohydrate developed progressive type-1 diabetes like symptom. After 4 weeks of daily oral administration, reductions of 35.9%, 17.2% and 11.6% in fasting blood glucose levels were observed for UP780, the UP780 Aloe vera inner leaf gel polysaccharide preparation without chromone (Qmatrix), and Aloesin (UP394), treated animals respectively, compared to vehicle treated animals. UP780 has no impact on blood glucose level of non-diabetic healthy mice. UP780 showed statistically significant improvement for blood glucose clearance in oral glucose tolerance tests. Similarly, enhanced improvement in plasma insulin level and statistically significant reduction in triglyceride level was also observed for animals treated with the composition.
Conclusion
These findings suggest that UP780, a chromone standardized Aloe based composition, could possibly be used as a natural supplement alternative to facilitate maintenance of healthy blood glucose levels.
doi:10.1186/1758-5996-6-61
PMCID: PMC4041641  PMID: 24891878
Insulin resistance; Aloe vera; Chromones; Alloxan
20.  Diabetes and cardiovascular disease: from evidence to clinical practice – position statement 2014 of Brazilian Diabetes Society 
There is a very well known correlation between diabetes and cardiovascular disease but many health care professionals are just concerned with glycemic control, ignoring the paramount importance of controlling other risk factors involved in the pathogenesis of serious cardiovascular diseases. This Position Statement from the Brazilian Diabetes Society was developed to promote increased awareness in relation to six crucial topics dealing with diabetes and cardiovascular disease: Glicemic Control, Cardiovascular Risk Stratification and Screening Coronary Artery Disease, Treatment of Dyslipidemia, Hypertension, Antiplatelet Therapy and Myocardial Revascularization. The issue of what would be the best algorithm for the use of statins in diabetic patients received a special attention and a new Brazilian algorithm was developed by our editorial committee. This document contains 38 recommendations which were classified by their levels of evidence (A, B, C and D). The Editorial Committee included 22 specialists with recognized expertise in diabetes and cardiology.
doi:10.1186/1758-5996-6-58
PMCID: PMC4030272  PMID: 24855495
Diabetes; Glicemic control; Cardiovascular risk stratification; Screening coronary artery disease; Treatment of dyslipidemia; Hypertension; Antiplatelet therapy; Myocardial revascularization
21.  Angiotensin II receptor blocker telmisartan attenuates aortic stiffening and remodelling in STZ-diabetic rats 
Background
Prevention or attenuation of diabetic vascular complications includes anti-hypertensive treatment with renin-angiotensin system inhibitors on account of their protective effects beyond blood pressure reduction. The present study aimed to investigate the effects of telmisartan, an angiotensin II type 1 receptor blocker (ARB), on blood pressure, aortic stiffening, and aortic remodelling in experimental type 1 diabetes in rats.
Methods
Diabetes was induced by streptozotocin (STZ) (65 mg/kg) in male Wistar rats. One diabetic group was treated for 10 weeks with telmisartan (10 mg/kg/day p/o). Pressure-independent aortic pulse wave velocity (PWV) was measured under anaesthesia after intravenous infusion of phenylephrine and nitroglycerine. Aortic wall samples were collected for histomorphometrical analysis.
Results
Untreated diabetes imposed differential effects on aortic stiffening, as demonstrated by increased isobaric PWV over a range of high blood pressures, but not at lower blood pressures. This was associated with loss and disruption of elastin fibres and an increase in collagen fibres in the aortic media. Treatment with telmisartan decreased resting blood pressure, reduced aortic stiffness, and partially prevented the degradation of elastin network within the aortic wall.
Conclusions
Telmisartan improved the structural and functional indices of aortic stiffening induced by untreated STZ-diabetes, demonstrating the importance of ARBs in the therapeutic approach to diabetic vascular complications.
doi:10.1186/1758-5996-6-57
PMCID: PMC4035834  PMID: 24920962
Arterial stiffness; Collagen; Diabetes; Elastin; Pulse wave velocity; Streptozotocin; Telmisartan
22.  Effect of single tablet of fixed-dose amlodipine and atorvastatin on blood pressure/lipid control, oxidative stress, and medication adherence in type 2 diabetic patients 
Background
Oxidized low-density lipoprotein (LDL) plays central roles in the formation and progression of atherosclerotic lesions. Malondialdehyde (MDA)-modified LDL (MDA-LDL) is speculated to be generated as a result of oxidative stress in the human body. Because both amlodipine and atorvastatin have been reported to reduce oxidative stress, it is expected that both drugs would have a favorable influence to reduce oxidative stress.
Objective
The objective of this study was to investigate the effects of a single pill of amlodipine (5 mg)/atorvastatin (10 mg) on oxidative stress, blood pressure/lipid control and adherence to medication in patients with type 2 diabetes.
Methods
This combination tablet was administered to 29 patients (16 male), and MDA-LDL, blood pressure, lipid profile, renal/liver function, CPK, hs-CRP, adiponectin, BNP, and HbA1c were measured at baseline, 6, and 12 months, and baPWV and mean IMT were measured at baseline and 12 months. Medication adherence was examined using a questionnaire at 6 months.
Results
MDA-LDL was decreased significantly. LDL-C, TG, and Cr were significantly decreased at 6 and 12 months compared with baseline. eGFR was increased at 6 months, and urinary albumin/creatinine ratio was decreased at 12 months. BNP was decreased at 6 and 12 months, and adiponectin was increased at 12 months. Both mean IMT and baPWV were significantly decreased. The results of the questionnaire showed that 93% of patients were satisfied with this medication. No severe adverse event was observed.
Conclusion
This combination tablet controlled both hypertension and dyslipidemia well in type 2 diabetic patients. The deceases in mean IMT and baPWV might suggest the improvement of atherosclerosis by this medication, which could be caused by the reduction of oxidative stress measured by MDA-LDL. In addition, this medication is expected to improve medication adherence.
doi:10.1186/1758-5996-6-56
PMCID: PMC4032353  PMID: 24860622
Malondialdehyde-modified low-density lipoprotein; Oxidative stress; Amlodipine; Atorvastatin; Diabetes mellitus; Hypertension; Dyslipidemia; Atherosclerosis; Medication adherence; Combination tablet
23.  Predictors of epicardial adipose tissue in patients with type 2 diabetes mellitus 
Background
Epicardial adipose tissue (EAT), visceral fat depot of the heart, was found to be associated with coronary artery disease in cardiac and non-cardiac patients. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were introduced as potential markers to determine inflammation in various disorders. Recently, atherogenic index of plasma (AIP) was found to be closely associated with atherosclerosis in general population. Waist circumference is commonly used to assess the risk factors in various metabolic disorders. There has been a well known relation between inflammation and peripheral adipose tissue in diabetes mellitus. However, the data regarding EAT and inflammation is scant in this population. Hence, we aimed to determine the relationship between PLR, NLR, AIP, waist circumference and EAT in diabetic patients.
Methods
This was a cross-sectional study involving 156 patients with type 2 diabetes mellitus (87 females, 69 males; mean age, 53.62 ± 9.33 years) and 50 control subjects (35 females, 15 males; mean age, 51.06 ± 8.74 years). EAT was measured by using a trans-thoracic echocardiogram. Atherogenic index of plasma was calculated as the logarithmically transformed ratio of the serum triglyceride to high density lipoprotein (HDL)cholesterol. NLR and PLR were calculated as the ratio of the neutrophils and platelets to lymphocytes, respectively.
Results
Waist circumference, PLR, NLR, AIP and EAT measurements were significantly higher in diabetic patients when compared to control subjects. When diabetic patients were separated into two groups according to their median value of EAT (Group 1, EAT < 4.53 (n = 78) and group 2, EAT ≥4.53 (n = 78)), group 2 patients had significantly higher Body mass index (BMI), waist circumference, AIP, NLR and PLR levels. In the bivariate correlation analysis, EAT was positively correlated with PLR, NLR, AIP, BMI and waist circumference (r = 0.197, p = 0.014; r = 0.229, p = 0.004; r = 0.161, p = 0.044; r = 0.248, p = 0.002; r = 0.306, p < 0.001, respectively). Waist circumference was found to be independent variables of EAT.
Conclusions
Simple calculation of PLR and measurement of waist circumference were found to be associated with increased EAT in diabetic patients.
doi:10.1186/1758-5996-6-55
PMCID: PMC4018267  PMID: 24822086
Diabetes mellitus; Waist circumference; Platelet-to-lymphocyte ratio; Neutrophil-to-lymphocyte ratio; Epicardial adipose tissue; Atherogenic index of plasma
24.  Effect of repaglinide versus glimepiride on daily blood glucose variability and changes in blood inflammatory and oxidative stress markers 
Background
Hemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages.
Methods
Continuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide.
Results
Nine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment.
Conclusion
These results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress.
doi:10.1186/1758-5996-6-54
PMCID: PMC4026053  PMID: 24843385
Cardiovascular disease; Continuous glucose monitoring; MAGE; Glimepiride
25.  Statins use is associated with poorer glycaemic control in a cohort of hypertensive patients with diabetes and without diabetes 
Background
The US Federal and Drug Administration (FDA) recently revised statin drug labels to include the information that increases in fasting serum glucose and glycated haemoglobin levels have been reported with the use of statins. Yet in a survey, 87% of the doctors stated that they had never or infrequently observed increases in glucose or HbA1c levels in patients on statin. In this study we would like to determine the association between the use of statins and glycaemic control in a retrospective cohort of patients with hypertension.
Methods
A retrospective review of 1060 medical records of patients with hypertension at a primary care clinic was conducted. These records were selected using systematic random sampling (1:4). Data on patient socio-demographic factors; clinical profile; investigation results and prescribed medications were collected. Independent t-test was used for continuous variables while Pearson’s χ2 test was used for categorical variables. Logistic regression was done to adjust for confounders.
Results
810 (76.4%) patients with hypertension were on statins, out of which 792 (97.8%) were taking simvastatin 10 mg or 20 mg daily. Analysis of the whole group regardless of diabetes status showed that the statin user group had higher HbA1c and fasting blood glucose values. The difference in HbA1c levels remained significant (adjusted OR = 1.290, p = 0.044, 95% CI 1.006, 1.654) after adjustment for diabetes, diabetic medication and fasting blood glucose. In the study population who had diabetes, statin users again had significantly higher HbA1c level compared to statin non-users. This difference remained significant (adjusted OR 1.208, p = 0.037, 95% CI 1.012, 1.441) after adjustment for age and diabetic medications.
Conclusions
Statins use is associated with increased HbA1c levels among hypertensive patients and hypertensive patients with diabetes. Clinicians managing hypertensive patients on statins should consider monitoring the HbA1c level and ensure that those with diabetes have their hyperglycaemia kept under control.
doi:10.1186/1758-5996-6-53
PMCID: PMC4003286  PMID: 24782916
Hypertension; Diabetes mellitus; Statin; HbA1c

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