Postchallenge Plasma Glucose Research Articles

A hospital-based cross-sectional study to develop an estimation formula for 2-h post-challenge plasma glucose for screening impaired glucose tolerance

AimsTo create and validate an estimation formula for 2-h post-challenge plasma glucose (2-hPG) as an alternative to oral glucose tolerance test (OGTT) for impaired glucose tolerance (IGT) screening. Methods380 Japanese subjects (57.6% males, aged 58.5 (14.0); mean (SD) years) undergoing OGTT were included in this hospital-based cross-sectional study mainly at Kyoto University Hospital between 2000 and 2011. We determined the main predictive variables of 2-hPG from clinical variables and separated the subjects randomly into two groups: a derivation group to construct an estimation formula of 2-hPG on the basis of predictive variables and a validation group to evaluate the accuracy of the formula. ResultsFasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were highly correlated with 2-hPG measured by OGTT. Multiple linear regression analysis showed that estimated 2-hPG (e2-hPG) was calculated by the formula: e2-hPG=1.66×FPG (mmol/l)+1.63×HbA1c (%)−10.11 (R2, coefficient of determination=60.2%). When the cut-off value was set to the diagnostic criteria of IGT, 7.8mmol/l of e2-hPG, sensitivity, specificity, and negative predictive value (NPV) were 83.3%, 44.1%, and 74.3%, respectively. When the cut-off value was set lower (7.2mmol/l), these values were 94.4%, 30.5%, and 85.7%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.68. ConclusionsThis high-sensitive estimation formula may be a useful alternative to OGTT for IGT screening. For the levels ≤7.2mmol/l, this formula may also be useful in cross-sectional study to identify people whose glucose tolerance is normal.

Influence of whey protein and its hydrolysate on prehypertension and postprandial hyperglycaemia in adult men

The effects of pre-meal consumption of whey protein isolate (WPI) and its hydrolysate (WPH) on blood pressure in pre-hypertensive and post-meal plasma responses in type 2 diabetic subjects were investigated. In a placebo-controlled double-blind randomised study, ten male patients with type 2 diabetes received dosages of WPI or WPH (0, 0.1, 0.2 and 0.4 g kg−1 body weight). Ingestion of 0.2 g kg−1 WPH or 0.4 g kg−1 WPI markedly promoted insulin secretion leading to a major reduction (p < 0.01) in post-challenge plasma glucose response. Plasma insulin concentration increased significantly (p < 0.05) only in the 0.4 g kg−1 WPH trial concomitant with returning the glucose level to the normal range 2 h after the meal. Neither WPH nor WPI (21 g day−1) caused a significant reduction (p > 0.05) in systolic blood pressure and diastolic blood pressure of pre-hypertensive subjects over the one-week administration.

Physical Activity is Strongly Inversely Related To Post-Challenge Plasma Glucose and Glycemic Spikes in a Risk Population for Type 2 Diabetes

To examine the relationship between physical activity (PA) and various cardiometabolic risk factors during an oral glucose tolerance test (OGTT), including glycemic spikes (PGS) in individuals at risk for type 2 diabetes. A total of 949 middle-aged subjects from the Risk factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) trial aged 40-70 years were included in the present cross-sectional analysis. Standard 75 g OGTT was performed and blood was collected every 30 min for 2 hours for measurements of plasma glucose (PG) and other cardiometabolic risk factors. PA was assessed using interviewer-administered questionnaire. Post-challenge PGS and maximal PG (PGmax) during OGTT were significantly lower in individuals with high PA vs. individuals with low PA even after body mass index (BMI) adjustment (p = 0.026 and p = 0.035, respectively). In univariate analysis post-challenge PG 30, 60, 90, and 120 minutes, PGS and PGmax during OGTT were significantly inversely correlated to PA. This correlation was attenuated but remained significant after adjustment for BMI. Fasting PG and glycosylated hemoglobin were not correlated to PA. Significantly higher fasting and post-challenge insulin levels were found among subjects with low vs. subjects with medium (p < 0.05) and high PA (p < 0.05). Post-challenge C-peptide and proinsulin levels were significantly lower in participants with high vs. participants with low PA (p < 0.05 for all). The relationship between 2-h PG and PA was observed also in lean subjects and in subjects with normal fasting glucose. In multivariate analysis PA was a significant independent determinant of 2-h PG. We found a strong inverse relationship between PA and various post-challenge cardiometabolic parameters during OGTT, including glycemic spikes, in a population at risk for diabetes. This relationship was only partially dependent on BMI.

Targets for Glycemic Control

Targets for Glycemic Control

Wrist Circumference as a Novel Predictor of Diabetes and Prediabetes: Results of Cross-Sectional and 8.8-Year Follow-up Studies

Our objective was to examine whether wrist circumference is associated with incident type 2 diabetes mellitus, independently of general (body mass index [BMI]) or central (waist circumference [WC]) adiposity measures in a cohort of an Iranian adult population. A total of 9330 subjects ≥ 20 years of age were included in the cross-sectional study. For prospective analysis, subjects with prevalent diabetes were excluded, leaving 6393 subjects (2716 males and 3677 females). The standard 2-hour postchallenge plasma glucose test was performed at baseline and during follow-up. Cox regression analysis was used to estimate the hazard ratio of diabetes for wrist circumference. During a mean follow-up of 8.8 years, 649 new cases of diabetes occurred. At baseline, using linear regression models, we showed significant linear associations between wrist circumference and diabetes risk factors in both genders, and this association remained significant after controlling for BMI or WC among females. In prospective evaluation, wrist circumference was significantly associated with incident diabetes (multivariable-adjusted hazard ratio = 1.17 [1.03-1.32] and 1.31 [1.18-1.45] for males and females, respectively). After controlling for the subjects' BMI or WC, wrist circumference was an independent predictor of diabetes only among females. Wrist circumference was an independent predictor of metabolic syndrome only among women even after adjustment for BMI, WC, or both. Wrist circumference is a significant predictor of diabetes in both genders of adult population. However, its predictability is independent of BMI or WC only among females. Because of its simple and easy-to-detect nature, wrist circumference could be considered as a new anthropometric assessment for prediction of type 2 diabetes and metabolic syndrome.

Isolated post-challenge hyperglycaemia and risk of cardiovascular events: Tehran Lipid and Glucose Study

To evaluate the risk of cardiovascular events in diabetes defined by isolated post-challenge hyperglycaemia (IPH). We followed 3794 subjects aged ≥40 years without known history of diabetes or cardiovascular disease (CVD) at baseline for CVD events. Participants were categorized as subjects without diabetes [fasting plasma glucose (FPG) < 126 mg/dL and 2-h post-challenge plasma glucose (2-hPG) < 200 mg/dL], IPH (FPG < 126 mg/dL and 2-h PG ≥ 200 mg/dL) and fasting hyperglycaemia (fasting blood glucose (FBS) ≥ 126 mg/dL). Hazard ratios (HRs) were calculated with the use of Cox proportional-hazards regression models to evaluate the risk of CVD events. At baseline, of 486 subjects with newly diagnosed diabetes, 190 (39%) had IPH. Over the next 8 years, age and sex-adjusted HR for incident CVD was 1.77 (95% confidence interval (CI): 1.19-2.64; p = 0.005) in subjects with IPH compared with subjects without diabetes. After further adjustment for potential confounders, the HR for CVD was not significant [1.32 (95% CI: 0.88-1.99; p = 0.2)]. IPH in middle-aged adults adds nothing for identifying CVD risks when other risk factors are taken into account. Associated metabolic risk factors seem to be more important than hyperglycaemia per se.

Elevated 1‐h plasma glucose following 75‐g oral glucose load is a predictor of arterial stiffness in subjects with normal glucose tolerance

The study aimed to investigate arterial stiffness in subjects with normal glucose tolerance. BMI, systolic blood pressure, fasting plasma glucose, lipid variables, ankle-brachial pressure index and brachial-ankle pulse wave velocity were measured in 2059 subjects from Takasaki city, located approximately 100 km north of Tokyo in Japan. Following a 75-g oral glucose tolerance test, only subjects with normal glucose tolerance were selected. One-hour post-challenge plasma glucose levels were correlated with brachial-ankle pulse wave velocity values (r = 0.340, P < 0.0001). When subjects with normal glucose tolerance were divided into three groups-group 1 (1-h plasma glucose < 8.56 mmol/l, n = 1595), group 2 (1-h plasma glucose ≥ 8.56 and < 10.17 mmol/l, n = 334) and group 3 (1-h plasma glucose ≥ 10.17 mmol/l, n = 130)-the brachial-ankle pulse wave velocity of group 3 (1473 ± 322 cm/s) was significantly higher than that of group 2 (1355 ± 252 cm/s) and brachial-ankle pulse wave velocity of group 2 was also significantly higher than that of group 1 (1275 ± 212 cm/s). We have identified that, in normal glucose tolerance, arterial stiffness is advanced in subjects with higher 1-h post-challenge plasma glucose in spite of the normal range for BMI, systolic blood pressure, fasting plasma glucose and lipid variables. Higher 1-h plasma glucose level is a risk factor for arterial stiffness in normal glucose tolerance.

Change in general and central adiposity measures in prediction of incident dysglycemia; Tehran Lipid and Glucose Study

ObjectivesTo examine the change in general and central adiposity measures as a predictor of incident dysglycemia during a 6-year follow-up. SubjectsA total of 4029 (2333 women and 1696 men) non-dysglycemic Iranians aged ≥20years, underwent standard fasting and 2-h post-challenge plasma glucose tests at baseline and follow-up. ResultsDuring follow-up, 458 new cases of dysglycemia occurred. In multivariable models including baseline values of each anthropometric measure, odds ratios (ORs) for dysglycemia incidence corresponding to a 1-SD increase in changes of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and hip circumference (HC), were 1.32, 1.56, 1.39, 1.51 and 1.39 for men and 1.59, 1.50, 1.37, 1.47, and 1.38, for women, respectively (all P<0.05). After controlling for weight change and WC change among men and women, respectively, HC change did not remain as a predictor. Using the paired homogeneity test, there was no superiority for changes in central obesity measures compared to changes in BMI to predict dysglycemia. ConclusionThe association between HC changes and incident dysglycemia was dependent upon changes in central and general adiposity measures, where the former did not have higher predictability than the latter in prediction of dysglycemia.

Non-linear contribution of glucose measures to cardiovascular diseases and mortality: Reclassifying the Framingham's risk categories: A decade follow-up from the Tehran lipid and glucose study

BackgroundWe investigated non-linear contribution of fasting plasma glucose (FPG) and 2-hour post-challenge plasma glucose (2h-PCPG) to the risk of CVD and mortality. We hypothesized that glucose measures improve risk-stratification made by the Framingham's general CVD risk algorithm. MethodsAmong participants aged ≥30 (n=8071), not taking glucose-lowering agents, 6169 (3477 women) remained eligible. Non-linear contribution of FPG and 2h-PCPG to incident CVD and mortality were assessed using Cox models incorporating restricted cubic splines functions. Risk reclassification improvement conferred by FPG and 2h-PCPG was examined using an extended version of net reclassification index (NRI) that takes into account the censoring nature of survival data. ResultsWe documented 465 incident CVD events (402 CHD), 212 deaths from any cause (94 CVD deaths). Excluding the contribution of the 2h-PCGP to mortality (that was linear) dose–response relationships between glucose measures and CVD and mortality were curvilinear with nadirs below which decreasing levels of glucose were unlikely to offer any benefit. These nadirs were assigned to FPG of 4.9–5.3 and 2h-PCPG of 6.0mmol.l−1. Glucose measures added to the predictive ability of the Framingham's general CVD risk algorithm with cutpoint-free NRIs ranging from 19 to 54%. ConclusionGlucose measures contributed to the risk of CVD and mortality in a curvilinear fashion, we observed increased risk below glucose thresholds currently used to define diabetes, supporting criteria for the diagnosis of impaired fasting glycemia and impaired glucose tolerance. Glucose measures were observed to add to predictive ability of the predictive model which included established cardiovascular risk factors.

Elevated A1C is associated with impaired early-phase insulin secretion rather than insulin resistance in Koreans at high risk for developing diabetes

The purpose of this study is to examine the association of A1C with beta-cell dysfunction, insulin resistance, and cardiovascular risk factors in Koreans with the relatively high risk for the future development of diabetes. This cross-sectional study recruited subjects from the pre-diabetic cohort of the Korea National Diabetes Program. Among study subjects (n = 616) aged 21-77 years with a history of hyperglycemia (fasting plasma glucose (FPG) ≥ 5.5 mmol/mL), analyses were conducted on 504 participants (296 women, 208 men) except for subjects with FPG ≥ 7.0 mmol/L or 120-min post-challenge plasma glucose ≥ 11.1 mmol/L or A1C ≥ 6.5 %. For insulin sensitivity and β-cell function classified by the categories of A1C levels, ∆Ins(30-0)/∆Glu(30-0) was lower in the highest quartile group than other groups. Although there was no significant difference in HOMA-IR according to the A1C categories, even lowest A1C group (≤ 5.3 %) already included many subjects with abnormal glucose tolerance. A1C showed a significant association with hsCRP, number of metabolic syndrome (MetS) components and ∆Ins(30-0)/∆Glu(30-0) after adjusting for age, gender, BMI, and medications whereas HOMA-IR was insignificantly associated with A1C. Stepwise regression analysis for A1C showed that A1C is independently and negatively associated with ∆Ins(30-0)/∆Glu(30-0), and positively associated with hsCRP. Our study showed that higher A1C was associated with impaired early-phase insulin secretion, MetS, and low grade inflammation in Koreans with the relatively high risk for the future development of diabetes.

Effects of Resistance Training on Adiposity and Metabolism after Spinal Cord Injury

This pilot work was conducted to evaluate the effects of neuromuscular electrical stimulation resistance training (RT) of the paralyzed knee extensor muscle groups on skeletal muscle and intramuscular fat (IMF) cross-sectional areas, trunk visceral adipose tissue (VAT), carbohydrate, and lipid profiles in men with spinal cord injury. Nine individuals with motor complete spinal cord injury were randomly assigned to an RT + diet group (n = 5) or a diet group (n = 4). The RT + diet underwent 12 wk of progressive RT, twice weekly, to the knee extensor muscle groups using neuromuscular electrical stimulation and ankle weights. Weekly feedback was provided to both groups to maintain a standard diet. Magnetic resonance imaging and a whole-body dual-energy x-ray absorptiometric images were obtained before and 1 wk after interventions. Participants underwent a metabolic study after a 12-h overnight fast to measure fasting and postchallenge plasma glucose, insulin, and lipid profiles. Skeletal muscle hypertrophy was detected in the whole thigh, knee extensors, and flexors in the RT + diet group compared with the diet group. VAT cross-sectional area, VAT/subcutaneous adipose tissue ratio at L5-S3, and percent IMF decreased significantly in the RT + diet group. Plasma insulin area under the curve decreased in the RT + diet group but not in the diet group. Fasting triglycerides and cholesterol/HDL decreased in the RT + diet group. Twice-weekly evoked RT to the paralyzed lower extremities resulted in significant skeletal muscle hypertrophy that was associated with reduction in VAT, VAT/subcutaneous adipose tissue ratio, and percent IMF. Significant improvements in insulin profile and lipid metabolism were noted in the RT + diet when compared with diet alone.

2-h postchallenge plasma glucose predicts cardiovascular events in patients with myocardial infarction without known diabetes mellitus

Background and purposeThe incidence of cardiovascular events remains high in patients with myocardial infarction (MI) despite advances in current therapies. New and better methods for identifying patients at high risk of recurrent cardiovascular (CV) events are needed. This study aimed to analyze the predictive value of an oral glucose tolerance test (OGTT) in patients with acute myocardial infarction without known diabetes mellitus (DM).MethodsThe prospective cohort study consisted of 123 men and women aged between 31–80 years who had suffered a previous MI 3–12 months before the examinations. The exclusion criteria were known diabetes mellitus. Patients were followed up over 6.03 ± 1.36 years for CV death, recurrent MI, stroke and unstable angina pectoris. A standard OGTT was performed at baseline.Results2-h plasma glucose (HR, 1.27, 95% CI, 1.00 to 1.62; P < 0.05) and smoking (HR, 3.56, 95% CI, 1.02 to 12.38; P < 0.05) proved to be independent predictors of CV events in multivariate statistical analysis after adjustments for age, sex, total cholesterol, and other baseline characteristics.ConclusionsIn this study population, with previous MI and without known DM, 2-h PG and smoking were significant predictors of CV death, recurrent MI, stroke and unstable angina pectoris, independent of baseline characteristics and medical treatment.

Association between an increment of 30-minute postchallenge plasma glucose and urine albumin excretion exists in postmenopausal women but not in premenopausal women

Usually, the increment of 30-minute postchallenge plasma glucose (ΔG30-0) represents the highest glucose spike in the population with normal glucose regulation (NGR). The aim of this study was to explore the differences in ΔG30-0 and urinary albumin excretion, a marker for widespread vascular damage, between premenopausal and postmenopausal women, and the relationship between ΔG30-0 and urinary albumin excretion. A population-based cross-sectional study, consisting of 5,289 participants aged 20 to 75 years from six different communities, was conducted in Shanghai between 2007 and 2008. We assessed postchallenge blood glucose and insulin at 0-, 30-, and 120-minute urinary albumin and creatinine. ΔG30-0 was calculated as 30-minute postchallenge glucose minus fasting plasma glucose, and the albumin-to-creatinine ratio (ACR) was used to reflect urinary albumin excretion. Among these, the data of 2,240 women with NGR were analyzed. (1) Postmenopausal women had higher ΔG30-0 and ACR than did premenopausal women (3.55 ± 1.52 mmol/L vs 3.21 ± 1.49 mmol/L and 6.92 [4.91-10.99] mg/g vs 6.18 [4.17-10.07] mg/g, respectively; all P < 0.001). (2) Multivariable logistic regression showed that ΔG30-0 was independently associated with increased ACR in postmenopausal women with NGR (odds ratio, 1.10; P = 0.048) but not in premenopausal women. (3) The main factor associated with ΔG30-0 was the early-phase glucose disposition index drawn from the multivariable linear regression, which explained approximately 19% and 28% of the variation of ΔG30-0 in premenopausal and postmenopausal women, respectively (both P < 0.001). In the NGR population, postmenopausal women have higher ΔG30-0 and ACR compared with premenopausal women. The relationship between ΔG30-0 and increased urine albumin excretion existed in postmenopausal women.

Effect of transjugular intrahepatic portosystemic shunt on glycometabolism in cirrhosis patients

Patients with liver cirrhosis suffer from hyperinsulinemia, hyperglucagonemia and a certain degree of insulin resistance, and portosystemic shunts may be involved in the etiology. A transjugular intrahepatic portosystemic shunt (TIPS) as a treatment for the complications of portal hypertension leads to hemodynamic changes. The objective of the present study is to evaluate whether TIPS can also affect glycometabolism in cirrhosis patients. Forty-six liver cirrhosis patients (experimental group [EG]) without diabetes who underwent TIPS were evaluated. Portal venous pressure (PVP), cardiac output (CO) and blood flow in the shunt (BFS) were measured or calculated before TIPS, after 15 minutes and, finally, after 90 days. Twenty-five liver cirrhosis patients without diabetes and without TIPS were included as the control group (CG). Oral glucose tolerance tests (OGTTs) were carried out at 0, 1, 7, 30 and 90 days after TIPS or after inclusion in the study. Indices related to glycometabolism and liver function, which included biochemical values, were also investigated. PVP changed immediately from 39.43 ± 1.29 cmH(2)O to 21.43 ± 1.42 cmH(2)O and remained stable thereafter. A pronounced increase in CO was observed after TIPS, while BFS did not change significantly. Also, glycosylated hemoglobin A(1c) (HbA(1c)), fasting plasma glucose (FPG), fasting plasma C-peptide (FPC), glucagon-like peptide-1 (GLP-1) and 2-h post-challenge plasma glucose (2 hPG) were non significantly increased after the shunt. Statistically significant hyperinsulinemia and hyperglucagonemia persisted for 90 days after TIPS. In addition, TIPS was followed by an increase in insulin resistance (IR) and β-cell function. Thirty-four patients in the EG and 15 in the CG were diagnosed with diabetes or prediabetes after 90 days. No significant differences in biochemical values were observed 90 days after the shunt. In addition to causing hemodynamic changes, TIPS augments hyperglucagonemia because of increased secretion and decreased clearance of glucagon in the liver, whereas IR deteriorates after the procedure. However, glycemic control does not worsen after TIPS, and the procedure is not associated with a higher risk of diabetes largely because of the simultaneous increase in insulin.

Increment of 30‐min post‐challenge plasma glucose is associated with urine albumin excretion in men with normal glucose regulation

The overwhelming majority of subjects with normal glucose regulation have the highest plasma glucose concentration at 30 minutes during oral glucose tolerance. We aimed to examine the association between increment of 30-min post-challenge glucose and albuminuria in participants with normal glucose regulation. A population-based cross-sectional study was conducted in six communities in Shanghai between 2007 and 2008. A total of 3508 subjects with normal glucose regulation had complete data and were enrolled into the analysis. Among the selected subjects, only 1525 individuals (581 men, 944 women) were examined for their serum insulin levels. We assessed post-challenge blood glucose and insulin at 0, 30 and 120 min, urinary albumin and creatinine. The 30-min post-challenge glucose increment (Δ) was calculated as 30-min post-challenge glucose minus fasting plasma glucose, and albumin/creatinine ratio was used to reflect urinary albumin excretion. Multivariable logistic regression analysis revealed that the Δ30-min post-challenge glucose was independently associated with increased albumin/creatinine ratio in men with normal glucose regulation (OR = 1.08, P = 0.025), but not in women. Furthermore, multivariable linear regression analysis revealed that early-phase glucose disposition index was the main factor responsible for Δ30-min post-challenge glucose and explained 14-20% of the variance of Δ30-min post-challenge glucose in the two subgroups (P < 0.05). Notably, men had higher Δ30-min post-challenge glucose and lower early-phase glucose disposition index than women (all P < 0.001). The 30-min post-challenge plasma glucose increment is associated with urine albumin excretion in men with normal glucose regulation.

Impact of hip circumference and height on incident diabetes: results from 6‐year follow‐up in the Tehran Lipid and Glucose Study

To investigate the effects of height and hip circumference, individually and in combination with waist circumference, on incident diabetes. A total of 1589 men and 2132 women, free of diabetes at baseline aged ≥ 20 years participated in a 6-year follow-up examination. The standard 2-h post-challenge plasma glucose test was performed at baseline and during follow-up. The Cox model was used to regress the hazard of diabetes on height and hip circumference individually and in combination with waist circumference. Median follow-up was 6 years, with a total of 9433 and 12,607 person-years follow-up among men and women, respectively. The incidence rate of diabetes (95% CIs) was 9.0 (7.6-11.5) and 11.0 (9.6--13.4) per 1000 persons per year in men and women, respectively. Among men, after multiple adjustments, the anthropometric measures were no longer associated with incident diabetes. Among women, the age-adjusted hazard ratio (95% CIs) of diabetes was 0.80 (0.61-1.04) for height, 1.39 (1.21-1.60) for hip circumference and 1.86 (1.59-2.17) for waist circumference. After further adjustment for waist circumference, the hazard ratios were 0.69 (0.53-0.90) for height and 0.76 (0.61-0.96) for hip circumference. These inverse associations resisted multiple adjustments. The hazard ratio for waist circumference increased by 7 and 54% when height and hip circumference were included in the models. We observed that height and hip circumference were inversely associated with incident diabetes among women and that these associations could be explored by considering the effect of waist circumference. The risk of diabetes attributable to waist circumference might be underestimated were the effects of height and hip circumference not considered.

Pharmacokinetic and Pharmacodynamic Properties of the Glucokinase Activator MK-0941 in Rodent Models of Type 2 Diabetes and Healthy Dogs

Glucokinase activators (GKAs) are small-molecule agents that enhance glucose sensing by pancreatic β cells and glucose metabolism by hepatocytes. There is strong interest in these agents as potential therapies for type 2 diabetes. Here, we report key pharmacokinetic and pharmacodynamic findings from preclinical studies of the GKA 3-[[6-(ethylsulfonyl)-3-pyridinyl]oxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (MK-0941). Incubated in vitro with recombinant human glucokinase, 1 μM MK-0941 lowered the S(0.5) of this enzyme for glucose from 6.9 to 1.4 mM and increased the maximum velocity of glucose phosphorylation by 1.5-fold. In 2.5 and 10 mM glucose, the EC(50) values for activation of GK by MK-0941 were 0.240 and 0.065 μM, respectively. Treatment of isolated rat islets of Langerhans and hepatocytes with 10 μM MK-0941 increased insulin secretion by 17-fold and glucose uptake up to 18-fold, respectively. MK-0941 exhibited strong glucose-lowering activity in C57BL/6J mice maintained on a high-fat diet (HFD), db/db mice, HFD plus low-dose streptozotocin-treated mice, and nondiabetic dogs. In both mice and dogs, oral doses of MK-0941 were rapidly absorbed and rapidly cleared from the blood; plasma levels reached maximum within 1 h and fell thereafter with a half-life of ~2 h. During oral glucose tolerance testing in dogs, MK-0941 reduced total area-under-the-curve postchallenge (0-2 h) plasma glucose levels by up to 48% compared with vehicle-treated controls. When administered twice daily to mice for 16 days, and once daily to the dog for 4 days, MK-0941 remained efficacious on successive days. These findings support further investigation of MK-0941 as a potential therapeutic agent for treatment of type 2 diabetes.

The Pre-diabetes Risk Education and Physical Activity Recommendation and Encouragement (PREPARE) programme study: are improvements in glucose regulation sustained at 2 years?

To determine whether improvements in glucose regulation following the PREPARE structured education programme were sustained at 24 months. Ninety-eight overweight or obese individuals with impaired glucose tolerance were randomized to receive: (1) advice leaflet, (2) 3-h structured education programme aimed at promoting physical activity, (iii) 3-h structured education with personalized pedometer use. The primary outcome was change in 2-h post-challenge plasma glucose. Seventy-three (74%) individuals were included for analysis at 24 months; age 65 ± 8 years, BMI 29.3 ± 4.8 kg/m(2), South Asian ethnicity 21%. A statistically significant reduction in 2-h glucose of -1.6 mmol/l (-0.4 to -2.7) was seen in the education-with-pedometer group compared with the control group. There is no significant difference in the education-only group. Improvements in glucose regulation following a pragmatic group-based structured education with pedometer use were sustained at 24 months.

Glycated Hemoglobin A1c, Fasting Plasma Glucose, and Two-Hour Postchallenge Plasma Glucose Levels in Relation to Carotid Intima-Media Thickness in Chinese with Normal Glucose Tolerance

The association between hyperglycemic markers and cardiovascular risk is not consistent in nondiabetic subjects. Even less are the data regarding the associations in subjects with normal glucose tolerance (NGT). Our objective was to assess the association of glycated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2-h postchallenge glucose with carotid intima-media thickness (CIMT) in subjects with NGT. This cross-sectional study included 1627 participants with NGT and aged 40 yr and above, who were randomly recruited from Songnan Community, Baoshan District, Shanghai. All participants received a 75-g oral glucose tolerance test, blood HbA1c assay, and CIMT measurements. Using multivariable linear regression, after adjustment for age, sex, smoking and drinking status, body mass index, blood pressure, and serum lipids, the increasing trend of CIMT was found in HbA1c quartiles (P = 0.016) rather than in FPG and postchallenge glucose quartiles. Furthermore, in a fully adjusted logistic model including FPG and postchallenge glucose as covariates, participants in the highest quartile of HbA1c, as compared with those in the lowest quartile, still conferred a 68% increased odds of elevated CIMT (≥ 0.70 mm). In the population of NGT, HbA1c is significantly associated with CIMT independent of conventional cardiovascular risk factors, FPG, and postchallenge glucose. The results implied that HbA1c could be more informative of cardiovascular risk as compared with FPG and postchallenge glucose in subjects with NGT.

Fasting glucose cutoff point: where does the risk terminate? Tehran lipid and glucose study

The aim of this study is to determine safe fasting plasma glucose (FPG) levels. We included data on 5,960 individuals aged ≥20 years at baseline with at least one follow-up examination. Diabetes was ascertained in accordance with American Diabetes Association criteria, using standard 2-h post-challenge plasma glucose test. Multivariate restricted cubic splines Weibull regression was implemented for interval-censored survival data on incident diabetes. We used Harrell's C statistic for discrimination, Nam-D'Agostino χ(2) for calibration, and Royston's R(2) for variations in the outcome explained by models. During a 6-year median follow-up, 369 incident cases of diabetes were ascertained. Family history of diabetes, systolic blood pressure, waist-to-height ratio, and triglyceride-to-high-density lipoprotein cholesterol ratio, independent of FPG and each other remained associated with incident diabetes. The cubic splines model achieved good calibration (χ(2) = 12.1) and discrimination (C = 0.828) and explained 75% of variation in the time until incident diabetes. A J-shaped FPG-diabetes relationship was observed. Descending arm of the dose-response relationship curve corresponded to increasing FPG levels up to 4.0 mmol l(-1), where it started increasing. The risk of incident diabetes decreased with decreasing levels of FPG down to 4.0 mmol l(-1), where the risk stopped decreasing. Multivariate-adjusted risk of incident diabetes was zero at FPG = 5.05 mmol l(-1). Although currently there is no firm evidence to show that early intervention among individuals with the elevated FPG levels could prevent or delay onset of diabetes, individuals with FPG levels below 5.05 mmol l(-1) could be safely reassured about their near-term risk of developing incident diabetes and screened on a less frequent basis.