2-hour Postload Glucose Research Articles

Occurrence and Predictors of Persistent Impaired Glucose Tolerance After Acute Ischemic Stroke or Transient Ischemic Attack

Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, orpersistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to identify patients at risk of persistent impaired glucose tolerance. Patients admitted to the stroke unit or TIA clinic of the Erasmus Medical Center with ischemic stroke or TIA and impaired glucose tolerance (2-hour postload glucose level of 7.8-11.0mmol/L) were consecutively enrolled between July 2009 and June 2012. The oral glucose tolerance test was repeated after 3months and patients were classified as having transient impaired glucose tolerance or persistent impaired glucose tolerance. We developed a prediction model by means of a multivariable logistic regression model. We calculated the area under the receiver operating characteristic curve (AUC) to quantify the performance of the model and the internal validity by bootstrapping. Of the 101 patients included, 53 (52%) had persistent impaired glucose tolerance or progression to diabetes. These patients were older and more often had hypertension and used statins. A prediction model including age, current smoking, statin use, triglyceride, hypertension, previous ischemic cardiovascular disease, body mass index, and fasting plasma glucose accurately predicted persistent impaired glucose tolerance (bootstrapped AUC, .777), with statin use, triglyceride, and fasting plasma glucose as the most important predictors. Half of the patients with impaired glucose tolerance after a TIA or ischemic stroke have persistent impaired glucose tolerance. We provide a prediction model to identify patients at risk of persistent impaired glucose tolerance, with statin use, triglyceride, and fasting plasma glucose as the most important predictors, which after external validation might be used to optimize secondary prevention.

BMI and waist circumference are associated with impaired glucose metabolism and type 2 diabetes in normal weight Chinese adults

AimsTo examine the associations of BMI and waist circumference with glucose metabolism and (pre)diabetes among adults with BMI<25kg/m2. MethodsWe conducted a cross-sectional study in a nationally representative sample (10,098 men and 17,454 women) of Chinese adults aged ≥20years with BMI<25kg/m2. Glucose levels after at least 10hours of overnight fasting, at 30minutes and at 120minutes after a standard 75-g oral glucose load were measured. Associations of BMI and waist circumference with outcomes were examined by general linear models for continuous outcomes and by logistic regression models for dichotomous outcomes. ResultsAmong those with BMI<25kg/m2, 18.8% of men and 17.1% of women had abnormal glucose metabolism, including 4.9% of men and 3.8% of women with undiagnosed type 2 diabetes. For each SD increase in BMI (2.1kg/m2) and waist circumference (8.3cm), fasting glucose levels increased by 0.128 and 0.170mmol/L in men, and by 0.112 and 0.167mmol/L in women, respectively; the corresponding increases for 2-hour post-load glucose levels were 0.121 and 0.217mmol/L in men, and 0.241 and 0.362mmol/L in women. When simultaneously included in the same model, these associations with waist circumference were stronger than with BMI. ConclusionObesity measures are associated with abnormal glucose metabolism and diabetes, with central obesity playing a more prominent role than general obesity in Chinese population with BMI<25kg/m2. Chinese diabetes prevention and treatment programs should incorporate targeting of normal weight adults with central obesity.

Lack of Racial Disparity in Incident Prediabetes and Glycemic Progression Among Black and White Offspring of Parents With Type 2 Diabetes: The Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) Study

Although the incidence of type 2 diabetes (T2D) among persons with prediabetes is well known (∼10%/y), the incidence of prediabetes among normoglycemic persons is unclear. Also, in the Diabetes Prevention Program, no racial/ethnic differences were seen in diabetes incidence, whereas marked racial/ethnic disparities are reported in the prevalence of T2D. We aimed to obtain estimates of incident prediabetes and determine whether racial disparities manifest during transition to prediabetes. We enrolled 376 (217 black, 159 white) nondiabetic offspring of parents with T2D (mean age 44.2 y) and followed them up quarterly for 5.5 years. Assessments included anthropometry, body composition, oral glucose tolerance test, biochemistries, energy expenditure, insulin sensitivity, and insulin secretion. The primary outcome was progression to impaired fasting glucose and/or impaired glucose tolerance (or diabetes). Of 343 participants with evaluable data, 101 subjects (49 white, 52 black) developed prediabetes, and 10 (4 white, 6 black) developed diabetes during a mean follow-up of 2.62 years. There was no significant racial difference in the cumulative incidence of prediabetes (32.7% white, 30% black) or combined prediabetes/diabetes (35% white, 30% black). Significant predictors of prediabetes included age, gender, trunk fat, 2-hour postload glucose (2hrPG), insulin sensitivity, and insulin secretion. In a Cox proportional-hazards model, with adjustment for age and sex, the 2hrPG and abdominal obesity were independent predictors of incident prediabetes/diabetes [relative hazards (95% confidence interval [CI]) for the 90th vs 10th percentile: trunk fat mass 2.90 (95% CI 1.74-4.82), P < .0001; 2hrPG 2.54 (95% CI 1.46-4.40), P = .0009]. Having the trunk fat mass and the 2hrPG at the 90th percentile conferred a 7-fold hazard of prediabetes compared with persons at the 10th percentile for both measures. Black and white offspring of parents with type 2 diabetes develop prediabetes at a similar high rate of approximately 11% per year. Therefore, close surveillance, with prompt intervention to prevent dysglycemia, is warranted in persons with parental diabetes.

Thresholds of various glycemic measures for diagnosing diabetes based on prevalence of retinopathy in community-dwelling Japanese subjects: the Hisayama Study

BackgroundThere has been controversy over the diagnostic thresholds of hemoglobin A1c (HbA1c) for diabetes. In addition, no study has examined the thresholds of glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) for diagnosing diabetes using the presence of diabetic retinopathy (DR). We examined the optimal thresholds of various glycemic measures for diagnosing diabetes based on the prevalence of DR in community-dwelling Japanese subjects.MethodsA total of 2,681 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test, measurement of HbA1c, GA, and 1,5-AG, and an ophthalmic examination in 2007-2008. The associations of glycemic measures with DR status were examined cross-sectionally. DR was assessed by an examination of the fundus photograph of each eye and graded according to the International Clinical Diabetic Retinopathy Disease Severity Scale. We divided the values of glycemic measures into ten groups on the basis of deciles. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold of each glycemic measure for detecting the presence of DR.ResultsOf the subjects, 52 had DR. The prevalence of DR increased steeply above the ninth decile for fasting plasma glucose (FPG) (6.2-6.8 mmol/l), for 2-hour postload glucose (PG) (9.2-12.4 mmol/l), for HbA1c (5.9-6.2% [41-44 mmol/mol]), and for GA (16.2-17.5%), and below the second decile for 1,5-AG (9.6-13.5 μg/mL). The ROC curve analysis showed that the optimal thresholds for DR were 6.5 mmol/l for FPG, 11.5 mmol/l for 2-hour PG, 6.1% (43 mmol/mol) for HbA1c, 17.0% for GA, and 12.1 μg/mL for 1,5-AG. The area under the ROC curve (AUC) for 2-hour PG (0.947) was significantly larger than that for FPG (0.908), GA (0.906), and 1,5-AG (0.881), and was marginally significantly higher than that for HbA1c (0.919). The AUCs for FPG, HbA1c, GA, and 1,5-AG were not significantly different.ConclusionsOur findings suggest that the FPG and HbA1c thresholds for diagnosing diabetes in the Japanese population are lower than the current diagnostic criterion, while the 2-hour PG threshold is comparable with the diagnostic criterion. 2-hour PG had the highest discriminative ability, whereas FPG, HbA1c, GA, and 1,5-AG were similar in their ability.

Glucose homeostasis in Egyptian children and adolescents with β-Thalassemia major: Relationship to oxidative stress.

Background:Oxidative stress in children with β-thalassemia may contribute to shortened life span of erythrocytes and endocrinal abnormalities.Aim:This study was aimed to evaluate glucose homeostasis in Egyptian children and adolescents with β-thalassemia major and its relation to oxidative stress.Materials and Methods:Sixty children and adolescents with β-thalassemia major were studied in comparison to 30 healthy age and sex-matched subjects. Detailed medical history, thorough clinical examination, and laboratory assessment of oral glucose tolerance test (OGTT), serum ferritin, alanine transferase (ALT), fasting insulin levels, plasma malondialdehyde (MDA) as oxidant marker and serum total antioxidants capacity (TAC) were performed. Patients were divided into two groups according to the presence of abnormal OGTT.Results:The prevalence of diabetes was 5% (3 of 60) and impaired glucose tolerance test (IGT) was 8% (5 of 60). Fasting blood glucose, 2-hour post-load plasma glucose, serum ferritin, ALT, fasting insulin level, homeostatic model assessment for insulin resistance index (HOMA-IR) and MDA levels were significantly elevated while TAC level was significantly decreased in thalassemic patients compared with healthy controls (P < 0.001 for each). The difference was more evident in patients with abnormal OGTT than those with normal oral glucose tolerance (P < 0.001 for each). We also observed that thalassemic patients not receiving or on irregular chelation therapy had significantly higher fasting, 2-h post-load plasma glucose, serum ferritin, ALT, fasting insulin, HOMA-IR, oxidative stress markers OSI and MDA levels and significantly lower TAC compared with either those on regular chelation or controls. HOMA-IR was positively correlated with age, serum ferritin, ALT, MDA, and negatively correlated with TAC.Conclusions:The development of abnormal glucose tolerance in Egyptian children and adolescents with β--thalassemia is associated with alteration in oxidant-antioxidant status and increase in insulin resistance.Recommendation:1- Glucose tolerance tests, HOMA-IR, and MDA should be an integral part of the long-term follow-up of children and adolescents with β-thalassemia major. 2- Regular iron chelation and antioxidant therapy should be advised for thalassemic patients to improve glucose hemostasis.

Body Mass Index, Waist-circumference and Cardiovascular Disease Risk Factors in Iranian Adults: Isfahan Healthy Heart Program

Considering the main effect of obesity on chronic non-communicable diseases, this study was performed to assess the association between body mass index (BMI), waist-circumference (WC), cardio-metabolic risk factors and to corroborate whether either or both BMI and WC are independently associated with the risk factors in a sample of Iranian adults. This cross-sectional study was performed on data from baseline survey of Isfahan Healthy Heart Program (IHHP). The study was done on 12,514 randomly-selected adults in Isfahan, Najafabad and Arak counties in 2000-2001. Ages of the subjects were recorded. Fasting blood glucose (FBG), 2-hour post-load glucose (2hpp), serum lipids, systolic and diastolic blood pressure (SBP and DBP), BMI, WC, smoking status, and total daily physical activity were determined. Increase in BMI and WC had a significant positive relation with the mean of FBG, 2hpp, SBP, DBP, serum lipids, except for HDL-C (p<0.001 for all). After adjustment for age, smoking, physical activity, socioeconomic status (SES), and BMI, the highest odds ratio (OR) (95% CI) for diabetes mellitus (DM) according to WC was 3.13 (1.93-5.08) and 1.99 (1.15-3.44) in women and men respectively. Moreover, the highest ORs based on BMI with adjustment for age, smoking, physical activity, SES, and WC were for dyslipidaemia (DLP) [1.97 (1.58-2.45) in women and 2.96 (2.41-3.63) in men]. The use of BMI or WC alone in the models caused to enhance all ORs. When both BMI and WC were entered in the model, the ORs for all risk factors, in men, according to BMI, were more compared to WC. However, in women, ORs for DM and hypertension (HTN) in WC quartiles were more than in BMI quartiles. BMI is the better predictor of DM, HTN, and DLP in men compared to WC. Conversely, in women, WC is a superior predictor than BMI, particularly for DM and HTN. Furthermore, the measurement of both WC and BMI in Iranian adults may be a better predictor of traditional risk factors of CVDs compared to BMI or WC alone.

Prevalence of Prediabetes and Newly Diagnosed Diabetes in Patients with a Transient Ischemic Attack or Stroke

Background: Patients with a transient ischemic attack (TIA) or stroke and prediabetes or newly diagnosed diabetes are at high risk of recurrent stroke or cardiovascular events. This underlines the importance of accurate screening for impaired glucose metabolism in clinical practice. Fasting plasma glucose levels are currently the most commonly measured glycemic parameter to detect prediabetes or diabetes, even if 2-hour postload glucose and glycosylated hemoglobin levels can be used as well. We assessed the prevalence of prediabetes and newly diagnosed diabetes with different screening methods, including fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin levels in consecutive patients with recent TIA, ischemic stroke or intracerebral hemorrhage admitted to the stroke unit or visiting the specialized TIA outpatient clinic in the Erasmus Medical Center, Rotterdam, The Netherlands. Methods: We measured fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin levels in 269 patients with a TIA, 374 with ischemic stroke and 57 with intracerebral hemorrhage, all without a history of diabetes mellitus. Prediabetes was defined as fasting plasma glucose levels of 5.6-6.9 mmol/l and/or 2-hour postload glucose levels of 7.8-11.0 mmol/l and/or glycosylated hemoglobin levels of 5.7-6.4%. Newly diagnosed diabetes was defined as fasting plasma glucose levels of ≥7.0 mmol/l and/or 2-hour postload levels of ≥11.1 mmol/l and/or glycosylated hemoglobin levels of ≥6.5%. The diagnosis was based on a one-time measurement. Results: Based on fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin levels combined, 365 patients (52%) were identified as prediabetics and 188 (27%) as having newly diagnosed diabetes. Patients with intracerebral hemorrhage had more often newly diagnosed diabetes compared with patients with an ischemic stroke or a TIA [27 (47%) and 161 (25%), respectively; p < 0.001]; the prevalence of prediabetes was similar. Newly diagnosed diabetes was identified more frequently by 2-hour postload glucose levels (n = 162; 23%) than by fasting plasma glucose (n = 49; 7%) or glycosylated hemoglobin levels (n = 36; 5%). About one third of the patients with normal fasting glucose levels has impaired glucose tolerance or elevated glycosylated hemoglobin levels. Conclusions: Prediabetes and newly diagnosed diabetes are highly prevalent in patients with a TIA or stroke. The majority of these patients would not have been identified by fasting plasma glucose levels alone. Both 2-hour postload glucose and glycosylated hemoglobin levels identify more patients with a disturbed glucose metabolism.

Serum electrolyte levels in relation to macrovascular complications in Chinese patients with diabetes mellitus

BackgroundThe prevalence of diabetes in China is increasing rapidly. However, scarce data are available on serum electrolyte levels in Chinese adults with diabetes, especially in those with cardiovascular complications. This study measured serum electrolyte levels and examined their relationship with macrovascular complications in Chinese adults with diabetes.MethodsThe three gender- and age-matched groups were enrolled into this analysis, which were 1,170 subjects with normal glucose regulation (NGR), 389 with impaired glucose regulation (IGR) and 343 with diabetes. Fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2hPG), glycosylated hemoglobin A1c (HbA1c) and serum electrolyte levels were measured. Data collection included ankle brachial index results.ResultsSerum sodium and magnesium levels in the diabetes group were significantly decreased compared to the NGR group (sodium: 141.0 ± 2.4 vs. 142.1 ± 2.0 mmol/l; magnesium: 0.88 ± 0.08 vs. 0.91 ± 0.07 mmol/l, all P < 0.01), while the serum calcium level was significantly increased (2.36 ± 0.11 vs. 2.33 ± 0.09 mmol/l, P < 0.01). Multiple linear regression showed that serum sodium and magnesium levels in the diabetes group were negatively correlated with FPG, 2hPG and HbA1c (sodium: Std β = −0.35, -0.19, -0.25; magnesium: Std β = −0.29, -0.17, -0.34, all P < 0.01), while the serum calcium level was positively correlated with HbA1c (Std β = 0.17, P < 0.05). In diabetic subjects, serum sodium, magnesium and potassium levels were decreased in the subjects with the elevation of estimated glomerular filtration rates (P < 0.05). ANCOVA analysis suggested that serum magnesium level in subjects with diabetic macrovascular complications was significantly decreased compared with diabetic subjects without macrovascular complications after the effect of some possible confounding being removed (P < 0.05).ConclusionsSerum sodium and magnesium levels were decreased in Chinese subjects with diabetes, while the observed increase in calcium level correlated with increasing glucose level. Diabetic patients with macrovascular complications had lower serum magnesium level than those with no macrovascular complications.

Association of Serum Uric Acid with 2-Hour Postload Glucose in Chinese with Impaired Fasting Plasma Glucose and/or HbA1c

ObjectiveTo examine whether serum uric acid (SUA) is associated with 2-hour postload glucose (2-h PG) in Chinese with impaired fasting plasma glucose (IFG) and/or HbA1c (IA1C).Research Design and MethodsAnthropometric and biochemical examinations, such as SUA concentration, were performed in 3763 individuals from all the villages in Baqiao County, China. A 75-g oral glucose tolerance test (OGTT) was conducted in 1197 Chinese with prediabetes as having IFG (110≤ fasting plasma glucose [FPG] <126 mg/dl and HbA1c <6.5%), IA1C (5.7% ≤ HbA1c <6.5% and FPG <126 mg/dl), or both.ResultsThe present study included 1197 participants with IFG and/or IA1C (mean age 56.5±10.3 years; 50.6% men). In multivariate linear regression, after adjustment for gender, age, smoking and drinking, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), lipid profiles, logarithmic transformed C-reactive protein (log-CRP), estimated glomerular filtration rate (e-GFR), FPG and HbA1c, with a 1-mg/dl increment of SUA, 2-h PG increased by 5.04±0.72 (P<0.001), 3.06±1.08 (P = 0.001), 5.40±1.26 (P<0.001), and 2.34±2.16 mg/dl (P = 0.056) in all participants, in participants with normal glucose tolerance (NGT), with impaired glucose tolerance (IGT), and with 2-h newly diagnosed diabetes (2-h NDM, with 2-h PG ≥200 mg/dl), respectively. In both men and women, 2-h PG increased progressively and significantly from the lower to the upper SUA tertiles (P<0.001). Moreover, in multivariate logistic regression, 1-standard deviation (SD; 1.53 mg/dl) increment of SUA was significantly associated with a 36% higher risk for 2-h NDM (Odds ratio [CI 95%]: 1.36 [1.09–1.99]; P = 0.03).ConclusionsSUA is significantly associated with 2-h PG in Chinese with IFG and/or IA1C.

Prevalence of Glucose Abnormalities and Diagnostic Value of Fasting Glucose and Fasting Insulin in Urban Hispanics

The prevalence of glucose abnormalities (GAs) and the diagnostic value of fasting plasma glucose and insulin in detecting impaired glucose tolerance (IGT) and diabetes mellitus (DM) were determined in urban Latin Americans. An oral glucose tolerance test was conducted in 592 subjects after administration of 75 g of glucose. Employing American Diabetes Association (ADA) and World Health Organization guidelines, GAs were found in 34% of the subjects, defined as impaired fasting glucose (IFG) (13.3%), IGT (6.9%), combined IFG + IGT (7.8%), and newly diagnosed type-2-DM (6.5%). All newly diagnosed diabetics had 2-hour glucose levels ≥200 mg/dL, but only 46.1% had fasting glucose ≥126 mg/dL. In addition, nearly half of the subjects with IGT (47%) had fasting glucose levels <100 mg/dL. The sensitivity, specificity, positive and negative predictive values of IFG in predicting IGT was 52.9%, 83%, 36.8%, and 90.4 %, respectively. Fasting insulin levels were not sensitive for differentiating glucose tolerant, from IFG and IGT; only the subjects with combined IFG + IGT had increased fasting insulin levels (22% above IFG) (P < 0.01). Two-hour insulin was increased by 30% in IGT and newly diagnosed diabetics, and by 46% in the subjects with combined IFG + IGT. In summary, the very high prevalence of undetected GA encountered in "healthy" subjects living in Caracas, Venezuela, requires immediate sanitary attention. With 50% of diabetic patients being unaware of their condition, half of IGT and DM not detected by ADA guidelines, and the poor sensitivity/specificity of fasting glucose in predicting 2-hour abnormalities, we recommend that 2-hour postload glucose be included when screening for GAs. Measurements of fasting and/or postload insulin are not cost effective for the diagnosis of GA, because they provide little additional clinical information in this context.

Impaired glucose homeostasis in non-diabetic Greek hypertensives with diabetes family history. Effect of the obesity status

Arterial hypertension (AH) and diabetes mellitus (DM) are established cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM family history identify individuals at risk for type 2 DM in whom preventive interventions are necessary. The aim of this study was to determine the glycemic profile in non-diabetic Greek adult hypertensive men and women according to DM family history and the obesity status. Diabetes family history, obesity markers (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and 2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c; fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA; quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH prevalence were determined in a large cohort of 11,540 Greek hypertensives referred to our institutions. Positive DM family history was associated with elevated fasting glucose (98.6 ± 13.1 vs 96.5 ± 12.3 mg/dL), HbA1c (5.58% ± 0.49% vs 5.50% ± 0.46%), fasting insulin (9.74 ± 4.20 vs 9.21 ± 3.63 μU/mL) and HOMA (2.43 ± 1.19 vs 2.24 ± 1.01) values, lower QUICKI (0.342 ± 0.025 vs 0.345 ± 0.023), Bennett (0.285 ± 0.081 vs 0.292 ± 0.078) and McAuley (6.73 ± 3.43 vs 6.95 ± 3.44) values, and higher IGH prevalence (45.3% vs 38.7%); P < .01 for all comparisons. The difference in the prevalence of IGH according to DM family history was significant (P < .01) in both genders and every WHR and BMI subgroup (except for women with BMI <20 kg/m2). Non-diabetic hypertensives with positive DM family history present with higher IGH prevalence and worse glycemic indices levels compared with those with negative family history, especially in the higher WHR/BMI subgroups.

Screen Viewing and Diabetes Risk Factors in Overweight and Obese Adolescents

Sedentary behavior has been associated with deleterious cardiometabolic health indicators in adults, but very little research has examined this relationship in youth. To examine the association between the duration and type of sedentary screen behavior with diabetes risk factors (fasting glucose, insulin, homeostasis model-insulin resistance [HOMA-IR], 2-hour postload glucose, hemoglobin A1c) in a sample of overweight and obese adolescents. A cross-sectional study of 307 overweight or obese adolescents aged 14-18 years (90 boys, 217 girls) assessed at baseline of a lifestyle intervention for weight control conducted from 2005 to 2010. Sedentary screen behaviors, defined as hours per day spent watching TV, playing seated video games, recreational computer use, and total screen time were measured by self-report. Data were analyzed using linear regression analyses in 2012. TV viewing was the only type of sedentary screen behavior associated with elevated diabetes risk factors before and after adjustment for confounders. Specifically, TV viewing remained positively associated with fasting insulin (adjusted r=0.11, β=0.10, p=0.048) and HOMA-IR (adjusted r=0.11, β=0.10, p=0.05) after adjustment for age, gender, waist-to-hip ratio, caloric intake, percentage of intake in carbohydrates, physical activity duration, and physical activity intensity. TV watching may be independently associated with an increase in diabetes risk factors in a high-risk sample of overweight and obese adolescents. These findings provide support for interventions designed to reduce time spent watching TV as a possible means to attenuating diabetes risk factors in this high-risk population.

Safety and FeasibiLity of Metformin in Patients with Impaired Glucose Tolerance and a Recent TIA or Minor Ischemic Stroke (LIMIT) Trial – A Multicenter, Randomized, Open-Label Phase II Trial

We aimed to assess the safety, feasibility, and effects on glucose metabolism of treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment. Patients with TIA or minor ischemic stroke in the previous six months and impaired glucose tolerance (2-hour post-load glucose levels of 7.8-11.0 mmol/l) were randomized to metformin, in a daily dose of 2 g, or no metformin, for three months. Primary outcome measures were safety and feasibility of metformin, and the adjusted difference in 2-hour post-load glucose levels at three months. This trial is registered as an International Standard Randomized Controlled Trial Number 54960762. Forty patients were enrolled; 19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3-10 weeks. Treatment with metformin was associated with a significant reduction in 2-hour post-load glucose levels of 0·97 mmol/l (95% CI 0·11-1·83) in the on-treatment analysis, but not in the intention-to-treat analysis (0·71 mmol/l; 95% CI -0·36 to 1·78). Treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance is safe, but leads to minor side effects. If tolerated, it may lead to a significant reduction in post-load glucose levels. This suggests that the role of metformin as potential therapeutic agent for secondary stroke prevention should be further explored.

2-Hour postload serum glucose levels and maternal blood pressure as independent predictors of birth weight in "appropriate for gestational age" neonates in healthy nondiabetic pregnancies.

Introduction. Increased neonatal birth weight (NBW), often associated with diabetic pregnancies, is a recognized indicator of childhood obesity and future metabolic risk. Predictors of NBW in healthy non-diabetic pregnancies are not yet established. Here, we investigated the association of maternal parameters of healthy non-diabetic mothers with NBW of their “appropriate-for-gestational age” neonates. Methods. The study involved 36 healthy mother/infant pairs. Examined parameters included NBW, maternal age, first and last trimester (BMI), weight gain, fasting serum lipids and glucose, 2-hour postload glucose levels and blood pressure. Results. Postload-glucose levels were significantly higher in mothers of heavier neonates. ANOVA results indicated that 15% increase in postload-glucose levels corresponded to more than 0.5 Kg increase in NBW in the third tertile. NBW correlated positively with postload glucose levels, and negatively with systolic blood pressure. Regression analysis showed that the main predictors of NBW were postload-glucose levels (B = 0.455, P = 0.003), followed by systolic blood pressure (B = −0.447, P = 0.004), together predicting 31.7% NBW variation. Conclusion. This study highlights that increased maternal postload sugar levels and blood pressure, within the normal range, highly predicts NBW of healthy mothers. These findings may provide focus for early dietary intervention measures to avoid future risks to the mother and baby.

Validity of diabetes self-reports in the Saku diabetes study.

BackgroundDiabetes is an important risk factor for cardiovascular disease, certain types of cancer, and death, and self-reports are one of the most convenient methods for ascertaining diabetes status. We evaluated the validity of diabetes self-reports among Japanese who participated in a health checkup.MethodsSelf-reported diabetes was cross-sectionally compared with confirmed diabetes among 2535 participants aged 28 to 85 years in the Saku cohort study. Confirmed diabetes was defined as the presence of at least 1 of the following: fasting plasma glucose (FPG) level of 126 mg/dL or higher, 2-hour post-load glucose (2-hPG) level of 200 mg/dL or higher after a 75-gram oral glucose tolerance test, glycated hemoglobin (HbA1c) level of 6.5% or higher, or treatment with hypoglycemic medication(s).ResultsOf the 251 participants with self-reported diabetes, 121 were taking hypoglycemic medication(s) and an additional 69 were classified as having diabetes. Of the 2284 participants who did not self-report diabetes, 80 were classified as having diabetes. These data yielded a sensitivity of 70.4%, a specificity of 97.3%, a positive predictive value of 75.7%, and a negative predictive value of 96.5%. The frequency of participants with undiagnosed diabetes was 3.0%. Of these, 64.2% had FPG within the normal range and were diagnosed by 2-hPG and/or HbA1c.ConclusionsOur findings provide additional support for the use of self-reported diabetes as a measure of diabetes in epidemiologic studies performed in similar settings in Japan if biomarker-based diagnosis is difficult.

Hemoglobin A1c and Arterial and Ventricular Stiffness in Older Adults

ObjectiveArterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE) are implicated in this stiffening pathophysiology. We examined the association between HbA1c, an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes.Research Design & MethodsBaseline HbA1c was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA1c and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG) with like measures.ResultsHbA1c was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both) and positively associated with greater body-mass index and black race. In adjusted models, HbA1c was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP), carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM). FG levels were positively associated with systolic, diastolic and PP and LVM.ConclusionsIn this sample of older adults without diabetes, HbA1c was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers.

Association Between Glucose Tolerance Level and Cancer Death in a General Japanese Population: The Hisayama Study

The authors examined the associations of glucose tolerance status and fasting and 2-hour postload glucose levels with the risk of cancer death in a 19-year follow-up study of 2,438 Japanese subjects aged 40-79 years who underwent a 75-g oral glucose tolerance test (1988-2007). During follow-up, 229 subjects died of cancer. The risk of cancer death was significantly higher in subjects with fasting plasma glucose levels of ≥5.6 mmol/L or 2-hour postload glucose levels of ≥11.1 mmol/L than in those with the lowest fasting or 2-hour postload glucose levels, after adjustment for potentially confounding factors. According to glucose tolerance status, not only diabetes but also impaired fasting glycemia and impaired glucose tolerance were significant risk factors for cancer death (for impaired fasting glycemia, multivariable-adjusted hazard ratio (HR) = 1.49 (95% confidence interval (CI): 1.05, 2.11); for impaired glucose tolerance, HR = 1.52 (95% CI: 1.05, 2.22); and for diabetes, HR = 2.10 (95% CI: 1.41, 3.12)). With regard to site-specific cancers, elevated fasting or 2-hour postload glucose levels were associated with the risks of death from stomach, liver, and lung cancer. These findings suggest that both prediabetic hyperglycemia and diabetes are significant risk factors for cancer death in the general Japanese population.

Clinical Effects of Colesevelam in Hispanic Subjects with Primary Hyperlipidemia and Prediabetes

Objective: To evaluate the efficacy and safety of colesevelam in Hispanic subjects with primary hyperlipidemia and prediabetes. Materials and Methods: A 16-week, randomized, double–blind, placebo–controlled, multinational study evaluating colesevelam in participants with primary hyperlipidemia (low–density lipoprotein cholesterol [LDL–C] level ≥ 100 mg/dL) and prediabetes (fasting plasma glucose level ≥ 110 to ≤ 125 mg/dL, or 2-hour postload glucose level ≥ 140 to < 200 mg/dL during an oral glucose tolerance test) was conducted between January 14, 2008 and April 3, 2009. Participants were randomized 1:1 to colesevelam 3.75 g/day or placebo. The primary efficacy endpoint was mean change from baseline in LDL–C level with colesevelam compared with placebo. Participants who self–identified as Hispanic during enrollment were included in this exploratory analysis evaluating the efficacy of colesevelam in Hispanics with primary hyperlipidemia and prediabetes. Results: From a total of 216 subjects with primary hyperlipidemia and prediabetes, 153 Hispanics were included in this post hoc analysis; 77 subjects were randomized to colesevelam and 76 subjects were randomized to placebo. At week 16, LDL–C levels were significantly reduced with colesevelam compared with placebo (mean treatment difference, −19.4%; P < 0.0001). Achievement of LDL–C level < 100 mg/dL was more frequent with colesevelam than with placebo (27% vs 11%; P = 0.002). In addition, significant mean reductions in non–high–density lipoprotein cholesterol, total cholesterol, and apolipoprotein B levels (P ≤ 0.0002 for all), and a significant median increase in triglyceride levels (P = 0.003), were seen with colesevelam compared with placebo. At study end, there was a significant mean reduction in glycated hemoglobin levels and median reduction in fasting plasma glucose levels with colesevelam compared with placebo (P ≤ 0.02 for both). A fasting plasma glucose level < 100 mg/dL was achieved in 44% of colesevelam recipients compared with 23% of placebo recipients (P < 0.05). Overall, colesevelam was well tolerated. Conclusion: Colesevelam may be a treatment option for Hispanic subjects with primary hyperlipidemia and prediabetes, mainly to reduce LDL–C levels, with added beneficial effect on glucose levels.

Diabetes and pre-diabetes as determined by glycated haemoglobin A1c and glucose levels in a developing southern Chinese population.

BackgroundThe American Diabetes Association and World Health Organization have recently adopted the HbA1c measurement as one method of diagnostic criteria for diabetes. The change in diagnostic criteria has important implications for diabetes treatment and prevention. We therefore investigate diabetes using HbA1c and glucose criteria together, and assess the prevalent trend in a developing southern Chinese population with 85 million residents.MethodsA stratified multistage random sampling method was applied and a representative sample of 3590 residents 18 years of age or above was obtained in 2010. Each participant received a full medical check-up, including measurement of fasting plasma glucose, 2-hour post-load plasma glucose, and HbA1c. Information on history of diagnosis and treatment of diabetes was collected. The prevalence of diabetes obtained from the present survey was compared with the data from the survey in 2002.ResultsThe prevalence of diabetes based on both glucose and HbA1c measurements was 21.7% (95% CI: 17.4%–26.1%) in 2010, which suggests that more than 1 in 5 adult residents were suffering from diabetes in this developing population. Only 12.9% (95% CI: 8.3%–17.6%) of diabetic residents were aware of their condition. The prevalence of pre-diabetes was 66.3% (95% CI: 62.7%–69.8%). The prevalence of diabetes and pre-diabetes which met all the three diagnostic thresholds (fast plasma glucose, 2 hour post-load plasma glucose, and HbA1c) was 3.1% and 5.2%, respectively. Diabetes and pre-diabetes as determined by HbA1c measurement had higher vascular risk than those determined by glucose levels. The prevalence of diabetes increased from 2.9% (95% CI: 2.0%–3.7%) in 2002 to 13.8% (95% CI: 10.2%–17.3%) in 2010 based on the same glucose criteria.ConclusionsOur results show that the diabetes epidemic is accelerating in China. The awareness of diabetes is extremely low. The glucose test and HbA1c measurement should be used together to increase detection of diabetes and pre-diabetes.

Prevalence of Atherosclerosis-Related Risk Factors and Diseases in the Philippines

BackgroundWe conducted a survey in 2008 to measure the prevalence of lifestyle-related diseases and risk factors in Philippine adults.MethodsStratified multistage sampling was used to cover the entire Philippine population of adults aged 20 years or older. Using health questionnaires, anthropometric measurements, and blood examinations, the prevalences of atherosclerosis-related risk factors and diseases were determined. Survey results were compared with those obtained in 2003.ResultsOut of 7700 eligible subjects, 64% to 93.7% responded to different survey items. Age-adjusted hypertension prevalence was 24.6% at a single visit and 20.6% when corrected for true prevalence. The prevalence of diabetes was 3.9% on the basis of fasting blood glucose (FBG), 5.2% by FBG and history, and 6.0% when 2-hour post-load plasma glucose level was determined. The prevalence of dyslipidemia was 72.0% and the prevalence of smoking was 31%. The prevalence of obesity was 4.9% by body mass index (BMI), and 10.2% and 65.6% by waist-hip ratio (WHR) in men and women, respectively. The prevalences of coronary, cerebrovascular, and peripheral arterial diseases were 1.1%, 0.9%, and 1.0%, respectively.ConclusionsThe prevalences of risk factors for atherosclerosis were higher in 2008 than in 2003, although the increase in diabetes was not significant and smoking decreased. These findings indicate a need for active collaborative intervention by all government agencies and medical societies in the Philippines.