Glucose intolerance: postprandial hyper glucose, risk factor for diabetic macroangiopathy

Major prospective studies about diabetes showed simply improving glucose control is not sufficient to prevent diabetes macroangiopathy. Hence, postprandial hyperglycemia is focused as new risk factor of diabetes macroangiopathy. It is getting common that IGT (impaired glucose tolerance) is a major risk of cardiovascular disease. Our previous data suggest that the risk of macroangiopathy is not postprandial hyperglycemia itself but pathophysiology of causing postprandial hyperglycemia; reducing insulin sensitivity and/or delayed and hyper insulin level. To prevent postprandial hyperglycemia, there are three strategies according to pathophysiology. Improving insulin sensitivity of liver, delaying glucose flux to portal vein and reviving fast insulin secretion. Recent study shows each strategy can reduce risk of diabetes macroangiopathy.     

Use of the diabetes risk score for opportunistic screening of undiagnosed diabetes and impaired glucose tolerance: the IGLOO (Impaired Glucose Tolerance and Long-Term Outcomes Observational) study

OBJECTIVE: To evaluate an opportunistic screening strategy addressed to individuals with one or more cardiovascular risk factor, based on the Diabetes Risk Score (DRS) as the initial instrument, for the identification of individuals with type 2 diabetes or impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: The DRS, a simple self-administered questionnaire, was completed by individuals identified by general practitioners and presenting with one or more cardiovascular risk factor. All patients underwent a 2-h oral glucose tolerance test (OGTT). The optimal DRS cutoff was calculated by applying the receiver-operating characteristic curve. RESULTS: Overall, 1,377 individuals aged between 55 and 75 years received an OGTT and completed the DRS. Mean DRS values showed a marked variation according to glucose metabolism categories, as follows: 8.7 +/- 3.0 in normoglycemic individuals, 9.5 +/- 3.1 in individuals with impaired fasting glucose, 9.9 +/- 3.3 in individuals with IGT, and 12.0 +/- 3.5 in individuals with type 2 diabetes. The receiver-operating characteristic curve showed that, with a cutoff of 9, the sensitivity of DRS in detecting individuals with glucose abnormalities (type 2 diabetes or IGT) was 77% and the specificity 45%. The use of the DRS as an initial screening instrument, followed by the measurement of fasting blood glucose in individuals with a score > or =9 and by the OGTT in individuals with a fasting blood glucose between 5.6 and 6.9 mmol/l, would lead to the identification of 83% of the case subjects with type 2 diabetes and 57% of the case subjects with IGT, at a cost of an OGTT in 38% of the sample and a fasting blood glucose in 64%. CONCLUSIONS: The DRS can represent a valid inexpensive instrument for opportunistic screening and a useful alternative to indiscriminate fasting blood glucose measurement, not readily available in general practice.     

Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes study

OBJECTIVE: Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk categories for type 2 diabetes. This study compared both categories with respect to the degree of insulin secretion abnormalities and insulin resistance. RESEARCH DESIGN AND METHODS: This is a crossover comparison of a population at high risk for type 2 diabetes. The subjects were recruited from the Risk Factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study. They underwent a 75-g oral glucose tolerance test, with measurement of specific insulin, C-peptide, proinsulin, and free fatty acids at baseline and every 30 min after load for 2 h. Factor analysis was performed to evaluate the importance of insulin resistance and secretion abnormalities in both categories. RESULTS: All categories of prediabetic hyperglycemia had a higher cardiovascular risk factor level when adjusted for sex, age, and BMI compared to control subjects with normal glucose tolerance. Subjects with isolated IFG were more insulin resistant than those with IGT. By contrast, subjects with isolated IGT exhibited a more severe deficit in early- and late-phase insulin secretion versus IFG subjects. As shown with factor analysis, in IFG the insulin resistance factor explained 28.4% of the variance, whereas in IGT the insulin secretion factor was dominant, explaining 31.1% of the total variance. CONCLUSIONS: Our cross-sectional data from the RIAD study demonstrate that isolated IFG and isolated IGT are different with respect to the degree of insulin resistance and anomalies in insulin secretion, and that subjects with IGT exhibit a deficit in the early and late phases of insulin secretion. This finding may be important for a differential approach in primary prevention of type 2 diabetes.     

Diabetes Screening in Canada (DIASCAN) Study: prevalence of undiagnosed diabetes and glucose intolerance in family physician offices

OBJECTIVE--To assess the prevalence of undiagnosed diabetes and glucose intolerance in individuals > or =40 years of age who contacted their family physician for routine care. RESEARCH DESIGN AND METHODS--The study used a stratified randomized selection of family physicians across Canada that was proportional to provincial and urban/rural populations based on Statistics Canada Census data (1996). Consecutive patients > or =40 years of age were screened for diabetes. If a casual fingerprick blood glucose was >5.5 mmol/l, the patient returned for a fasting venous blood glucose test. If the fasting blood glucose was 6.1-6.9 mmol/l, a 2-h 75-g post-glucose load venous blood glucose was obtained. Results of these tests were used to classify patients in diagnostic categories. RESULTS--Data were available for 9,042 patients. Previously undiagnosed diabetes was discovered in 2.2% of the patients, and new glucose intolerance was found in an additional 3.5% of patients. Overall, 16.4% of patients had previously known diabetes. The decrease in fasting plasma glucose criterion from 7.8 to 7.0 mmol/l resulted in a 2.2% versus a 1.6% prevalence of new diabetes. Several risk factors were reported in a significantly greater proportion of patients with new glucose intolerance and either new and known diabetes compared with the normal glucose tolerance group of patients. CONCLUSIONS--Routine screening for diabetes by family physicians is justified in patients > or =40 years of age, given the finding of previously undiagnosed diabetes in 2.2% of these patients and newly diagnosed glucose intolerance in an additional 3.5% of these patients. Another 16.4% of primary care patients > or =40 years of age have known diabetes. This has important implications regarding health resources and physician education.     

Endothelial cells (ECs) for vascular tissue engineering: venous ECs are less thrombogenic than arterial ECs

Primary endothelial cells (ECs) are the preferred cellular source for luminal seeding of tissue‐engineered (TE) vascular grafts. Research into the potential of ECs for vascular TE has focused particularly on venous rather than arterial ECs. In this study we evaluated the functional characteristics of arterial and venous ECs, relevant for vascular TE. Porcine ECs were isolated from femoral artery (PFAECs) and vein (PFVECs). The proliferation rate was comparable for both EC sources, whereas migration, determined through a wound‐healing assay, was less profound for PFVECs. EC adhesion was lower for PFVECs on collagen I, measured after 10 min of arterial shear stress. Gene expression was analysed by qRT–PCR for ECs cultured under static conditions and after exposure to arterial shear stress and revealed differences in gene expression, with lower expression of EphrinB2 and VCAM‐1 and higher levels of vWF and COUP‐TFII in PFVECs than in PFAECs. PFVECs exhibited diminished platelet adhesion under flow and cell‐based thrombin generation was delayed for PFVECs, indicating diminished tissue factor (TF) activity. After stimulation, prostacyclin secretion, but not nitric oxide (NO), was lower in PFVECs. Our data support the use of venous ECs for TE because of their beneficial antithrombogenic profile. Copyright © 2012 John Wiley & Sons, Ltd.     

Aggregate National Early Warning Score (NEWS) values are more important than high scores for a single vital signs parameter for discriminating the risk of adverse outcomes

IntroductionThe Royal College of Physicians (RCPL) National Early Warning Score (NEWS) escalates care to a doctor at NEWS values of ≥5 and when the score for any single vital sign is 3.MethodsWe calculated the 24-h risk of serious clinical outcomes for vital signs observation sets with NEWS values of 3, 4 and 5, separately determining risks when the score did/did not include a single score of 3. We compared workloads generated by the RCPL's escalation protocol and for aggregate NEWS value alone.ResultsAggregate NEWS values of 3 or 4 (n = 142,282) formed 15.1% of all vital signs sets measured; those containing a single vital sign scoring 3 (n = 36,207) constituted 3.8% of all sets. Aggregate NEWS values of either 3 or 4 with a component score of 3 have significantly lower risks (OR: 0.26 and 0.53) than an aggregate value of 5 (OR: 1.0). Escalating care to a doctor when any single component of NEWS scores 3 compared to when aggregate NEWS values ≥5, would have increased doctors’ workload by 40% with only a small increase in detected adverse outcomes from 2.99 to 3.08 per day (a 3% improvement in detection).ConclusionsThe recommended NEWS escalation protocol produces additional work for the bedside nurse and responding doctor, disproportionate to a modest benefit in increased detection of adverse outcomes. It may have significant ramifications for efficient staff resource allocation, distort patient safety focus and risk alarm fatigue. Our findings suggest that the RCPL escalation guidance warrants review.     

Reliability of the Home Falls and Accidents Screening Tool (HOME FAST) for identifying older people at increased risk of falls

Purpose : The Home Falls and Accidents Screening Tool (HOME FAST) was designed as part of a comprehensive health assessment instrument to measure falls risk for older people within their home environment. This paper describes the evaluation of the inter-rater reliability of the HOME FAST.

Method : Forty home visits were undertaken, in urban and rural settings of the UK, by pairs of raters, one of whom was an expert rater. Occupational therapists, occupational therapy assistants and a social worker rated each home using the HOME FAST concurrently with an expert rater. The kappa statistic was used to determine the degree of agreement between pairs of raters.

Results : The overall kappa value for the checklist was 0.62, indicating a fair to good level of agreement between raters. 'Hazardous outside paths' was the only item that demonstrated poor agreement (kappa=0.30). The expert rater consistently identified more hazards than the other raters, and the level of agreement was stable between raters irrespective of the number of hazards present in the homes visited.

Conclusions : Definitions of non-applicable household features and improving the objectivity of the operational definitions for recognizing hazards that demand more qualitative judgements will enhance the reliability of the HOME FAST.     

Obstructive Sleep Apnea,Glucose Tolerance,and β-Cell Function in Adults With Prediabetes or Untreated Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study

OBJECTIVEObstructive sleep apnea (OSA) is associated with insulin resistance and has been described as a risk factor for type 2 diabetes. Whether OSA adversely impacts pancreatic islet β-cell function remains unclear. We aimed to investigate the association of OSA and short sleep duration with β-cell function in overweight/obese adults with prediabetes or recently diagnosed, treatment-naive type 2 diabetes.RESEARCH DESIGN AND METHODSTwo hundred twenty-one adults (57.5% men, age 54.5 ± 8.7 years, BMI 35.1 ± 5.5 kg/m²) completed 1 week of wrist actigraphy and 1 night of polysomnography before undergoing a 3-h oral glucose tolerance test (OGTT) and a two-step hyperglycemic clamp. Associations of measures of OSA and actigraphy-derived sleep duration with HbA_1c, OGTT-derived outcomes, and clamp-derived outcomes were evaluated with adjusted regression models.RESULTSMean ± SD objective sleep duration by actigraphy was 6.6 ± 1.0 h/night. OSA, defined as an apnea-hypopnea index (AHI) of five or more events per hour, was present in 89% of the participants (20% mild, 28% moderate, 41% severe). Higher AHI was associated with higher HbA_1c (P = 0.007). However, OSA severity, measured either by AHI as a continuous variable or by categories of OSA severity, and sleep duration (continuous or <6 vs. ≥6 h) were not associated with fasting glucose, 2-h glucose, insulin sensitivity, or β-cell responses.CONCLUSIONSIn this baseline cross-sectional analysis of the RISE clinical trial of adults with prediabetes or recently diagnosed, untreated type 2 diabetes, the prevalence of OSA was high. Although some measures of OSA severity were associated with HbA_1c, OSA severity and sleep duration were not associated with measures of insulin sensitivity or β-cell responses.     

Influence of alcohol use, ethnicity, age, gender, BMI and smoking on the serum transferrin glycoform pattern: implications for use of carbohydrate-deficient transferrin (CDT) as alcohol biomarker

BACKGROUND: An alcohol-induced change in the serum transferrin glycoform pattern, carbohydrate-deficient transferrin (CDT), is used as a biomarker for detection and follow-up of heavy alcohol consumption. Besides studying the effects of drinking, this study evaluated any baseline differences in the transferrin pattern in relation to ethnicity, age, gender, body mass index (BMI) and smoking, as these could be confounders causing bias in CDT testing. METHODS: The transferrin glycoform pattern was determined in 1387 sera (68% men, 32% women) collected in Australia, Brazil, Canada, Finland and Japan from subjects classified as non-drinkers, light/moderate drinkers, or heavy drinkers by use of the WHO/ISBRA Interview Schedule. The iron-saturated glycoforms were separated by an HPLC candidate reference method, and the relative amounts of individual glycoforms to total transferrin were determined. RESULTS: In non-drinkers, the differences in the serum transferrin glycoform pattern in relation to ethnicity, age, gender and BMI were small and mostly not statistically significant. A higher disialotransferrin level in smokers compared with non-smokers could largely be explained by a higher alcohol intake in smokers. In the drinking subgroups, the main CDT glycoform disialotransferrin showed a positive correlation (r=0.80) with asialotransferrin, and disialo- and asialotransferrin a negative correlation with tetrasialotransferrin, that was dependent on the alcohol consumption level. CONCLUSIONS: With respect to CDT testing, the results indicated that adjustment of reference intervals for disialotransferrin and CDT in relation to ethnicity, age, gender, BMI and smoking is not required.     

Effect of abnormal fasting plasma glucose level on all-cause mortality in older patients with acute myocardial infarction: results from the Beijing Elderly Acute Myocardial Infarction Study (BEAMIS)

OBJECTIVE: To assess whether the relationship between abnormal fasting plasma glucose (FPG) levels and patient outcomes holds for both older men and older women with acute myocardial infarction (AMI).PATIENTS AND METHODS: From April 1, 2004, to October 31, 2006, a total of 2016 consecutive older patients (age ≥65 years) presenting with AMI were screened. Of these patients, 1854 were consecutively enrolled in the study. Patients were categorized into 4 groups: the hypoglycemic group (FPG, ≤90.0 mg/dL [to convert to mmol/L, multiply by 0.0555]; n=443, 23.9%), the euglycemic group (FPG, 90.1-126.0 mg/dL; n=812, 43.8%), the mildly hyperglycemic group (FPG, 126.1-162.0 mg/dL; n=308, 16.6%), and the severely hyperglycemic group (FPG, ≥162.1 mg/dL; n=291, 15.7%). The primary outcomes were rates of in-hospital and 3-year mortality.RESULTS: Female patients were older and had a higher incidence of diabetes mellitus but lower rates of smoking and use of invasive therapy. Men tended to have a higher frequency of hypoglycemia, whereas women tended to have a higher frequency of hyperglycemia. No significant difference was found in in-hospital (10.9% vs 9.1%; P=.36) or 3-year (24.5% vs 24.5%; P=.99) mortality between male and female patients, and FPG-associated mortality did not vary significantly by sex.CONCLUSION: An increased FPG level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased FPG levels at admission could predict higher mortality rates regardless of sex. There was a striking U-shaped relationship between FPG levels and in-hospital and 3-year mortality. The effect of abnormal FPG level on outcomes among older patients with AMI did not vary significantly by sex.AMI = acute myocardial infarction; BEAMIS = the Beijing Elderly Acute Myocardial Infarction Study; CABG = coronary artery bypass grafting; CI = confidence interval; DM = diabetes mellitus; FPG = fasting plasma glucose; PCI = percutaneous coronary interventionMany primary and secondary prevention strategies for acute myocardial infarction (AMI) shown to be efficacious in randomized controlled trials have been implemented by physicians and health care systems, resulting in improved control of cardiovascular risk factors in several populations.^1-5 Although better management of risk factors is an important quality benchmark, reductions in the incidence of myocardial infarction and mortality are better measures of quality. Previous studies of mortality associated with AMI have often focused on selected subgroups in populations with limited diversity with respect to coexisting conditions, and most have not examined differences due to sex, although management and outcomes differ markedly.^6-9 Several studies have reported that acute hyperglycemia in patients with AMI is related to a higher incidence of mortality.^10-16 No studies have evaluated the relationship between abnormal fasting plasma glucose (FPG) levels and outcomes separately for men and women. The aim of this study, therefore, was to assess whether the relationship between FPG levels and all-cause mortality is different for men and women among older patients with AMI by analyzing data from BEAMIS (the Beijing Elderly Acute Myocardial Infarction Study).     

Women are more than twice as likely to die from burns as men in Australia and New Zealand: An unexpected finding of the Burns Evaluation And Mortality (BEAM) Study

While the risk of death after nonthermal trauma and sepsis may be higher for men, sex differences in outcome after burns are inconsistently reported. The Burns Evaluation And Mortality Study examined the outcomes of all patients admitted after thermal injury to the intensive care unit (ICU) at 8 of 9 burn referral centers in Australia and New Zealand between January 1, 2005, and December 31, 2011. There were 348 women and 1367 men treated for acute burns. Women were older, had more extensive burns, and higher severity of illness scores. Women spent longer in hospital and in ICU than men. Mortality among women was higher than in men (21% vs 8.3%, P < .001). Trends toward a survival disadvantage for women were seen across all ages, at all levels of severity of illness, at every proportion of body surface area burnt, and across all centers. After adjusting for confounding factors, women had more than double the risk of death compared with men (odds ratio, 2.35; 95% confidence interval, 1.38-4.01; P = .002). Our study conclusively shows worse outcomes for women with burns admitted to ICUs in Australia and New Zealand. Further research is required to determine why this is happening.     

Dietary fat intake as risk factor for the development of diabetes: multinational,multicenter study of the Mediterranean Group for the Study of Diabetes (MGSD)

OBJECTIVE: To investigate the role of dietary factors in the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: In the context of the Multinational MGSD Nutrition Study, three groups of subjects were studied: 204 subjects with recently diagnosed diabetes (RDM), 42 subjects with undiagnosed diabetes (UDM) (American Diabetes Association criteria-fasting plasma glucose [FPG] > or =126 mg/dl), and 55 subjects with impaired fasting glucose (IFG) (FPG > or =110 and <126 mg/dl). Each group was compared with a control group of nondiabetic subjects, matched one by one for center, sex, age, and BMI. Nutritional habits were evaluated by a dietary history method, validated against the 3-day diet diary. In RDM, the questionnaire referred to the nutritional habits before the diagnosis of diabetes. Demographic data were collected, and anthropometrical and biochemical measurements were taken. RESULTS: Compared with control subjects, RDM more frequently had a family history of diabetes (49.0 vs. 14.2%; P < 0.001), exercised less (exercise index 53.5 vs. 64.4; P < 0.01), and more frequently had sedentary professions (47.5 vs. 27.4%; P < 0.001). Carbohydrates contributed less to their energy intake (53.5 vs. 55.1%; P < 0.05), whereas total fat (30.2 +/- 0.5 vs. 27.8 +/- 0.5%; P < 0.001) and animal fat (12.2 +/- 0.3 vs. 10.8 +/- 0.3%; P < 0.01) contributed more and the plant-to-animal fat ratio was lower (1.5 +/- 0.1 vs. 1.8 +/- 0.1; P < 0.01). UDM more frequently had a family history of diabetes (38.1 vs. 19.0%; P < 0.05) and sedentary professions (58.5 vs. 34.1%; P < 0.05), carbohydrates contributed less to their energy intake (47.6 +/- 1.7 vs. 52.8 +/- 1.4%; P < 0.05), total fat (34.7 +/- 1.5 vs. 30.4 +/- 1.2%; P < 0.05) and animal fat (14.2 +/- 0.9 vs. 10.6 +/- 0.7%; P < 0.05) contributed more, and the plant-to-animal fat ratio was lower (1.6 +/- 0.2 vs. 2.3 +/- 0.4; P < 0.05). IFG differed only in the prevalence of family history of diabetes (32.7 vs. 16.4%; P < 0.05). CONCLUSIONS: Our data support the view that increased animal fat intake is associated with the presence of diabetes.     

Using HbA(1c) to improve efficacy of the american diabetes association fasting plasma glucose criterion in screening for new type 2 diabetes in American Indians: the strong heart study

OBJECTIVE: To find an optimal critical line in the fasting plasma glucose (FPG)-HbA(1c) plane for identifying diabetes in participants with impaired fasting glucose (IFG) and thereby improve the efficacy of using FPG alone in diabetes screening among American Indians. RESEARCH DESIGN AND METHODS: We used FPG, 2-h postload glucose (2hPG), and HbA(1c) measured in the 2,389 American Indians (aged 45-74 years, without diabetes treatment or prior history of diabetes) in the Strong Heart Study (SHS) baseline (second) examination. Participants were classified as having diabetes if they had either FPG > or =126 mg/dl or 2hPG > or =200 mg/dl, as having IFG if they had 110 < or = FPG < 126 mg/dl, and as having normal fasting glucose (NFG) if they had FPG <110, according to the American Diabetes Association (ADA) definition. Logistic regression models were used for identifying diabetes (2hPG > or =200 mg/dl) in IFG participants. The areas under the receiver operating characteristic (ROC) curves generated by different logistic regression models were evaluated and compared to select the best model. A utility function based on the best model and the cost-to-benefit ratio was used to find the optimal critical line. The data from the second examination were used to study the effect of the time interval between the successive diabetes screenings on both the FPG criterion and the optimal critical line. RESULTS: A total of 37% of all subjects with new diabetes at baseline and 55.2% of those in the second exam had 2hPG > or =200 but FPG <126. There was a very large portion of IFG participants with diabetes (19.3 and 22.9% in the baseline and second exam, respectively). Among the areas under the ROC curves, the area generated by the logistic regression model on FPG plus HbA(1c) is the largest and is significantly larger than that based on FPG (P = 0.0008). For a cost-to-benefit ratio of 0.23888, the optimal critical line that has the highest utility is: 0.89 x HbA(1c) + 0.11 x FPG = 17.92. Those IFG participants whose FPG and HbA(1c) were above or on the line were referred to take an oral glucose tolerance test (OGTT) to diagnose diabetes. The optimal critical line is lower if a successive diabetes screening will be conducted 4 years after the previous screening. CONCLUSIONS: FPG > or =126 and 2hPG > or =200, as suggested by the ADA, are used independently to define diabetes. The FPG level is easy to obtain, and using FPG alone is suggested for diabetes screening. It is difficult to get physicians and patients to perform an OGTT to get a 2hPG level because of the many drawbacks of the OGTT, especially in those patients who already have FPG <126. It is also impractical to conduct an OGTT for everyone in a diabetes screening. Our data show that 37% of all subjects with new diabetes in the SHS baseline exam and 55.2% of those in the second exam have 2hPG > or =200 but FPG <126. These cases of diabetes cannot be detected if FPG is used alone in a diabetes screening. Therefore, although the small portion of diabetes in the NFG group (4.7% in the baseline and 6.9% in the second exam) may be ignored, those cases of diabetes among IFG participants ( approximately 20% in our data) need further consideration in a diabetes screening. It may be worthwhile for those IFG participants identified by the optimal critical line to take an OGTT. The optimal critical line and time interval between successive diabetes screenings need further study.