The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals.

The protein encoded by the PPARGC1A gene is expressed at high levels in metabolically active tissues and is involved in the control of oxidative stress via reactive oxygen species detoxification. Several recent reports suggest that the PPARGC1A Gly482Ser (rs8192678) missense polymorphism may relate inversely with blood pressure. We used conventional meta-analysis methods to assess the association between Gly482Ser and systolic (SBP) or diastolic blood pressures (DBP) or hypertension in 13,949 individuals from 17 studies, of which 6,042 were previously unpublished observations. The studies comprised cohorts of white European, Asian, and American Indian adults, and adolescents from South America. Stratified analyses were conducted to control for population stratification. Pooled genotype frequencies were 0.47 (Gly482Gly), 0.42 (Gly482Ser), and 0.11 (Ser482Ser). We found no evidence of association between Gly482Ser and SBP [Gly482Gly: mean = 131.0 mmHg, 95% confidence interval (CI) = 130.5-131.5 mmHg; Gly482Ser mean = 133.1 mmHg, 95% CI = 132.6-133.6 mmHg; Ser482Ser: mean = 133.5 mmHg, 95% CI = 132.5-134.5 mmHg; P = 0.409] or DBP (Gly482Gly: mean = 80.3 mmHg, 95% CI = 80.0-80.6 mmHg; Gly482Ser mean = 81.5 mmHg, 95% CI = 81.2-81.8 mmHg; Ser482Ser: mean = 82.1 mmHg, 95% CI = 81.5-82.7 mmHg; P = 0.651). Contrary to previous reports, we did not observe significant effect modification by sex (SBP, P = 0.966; DBP, P = 0.715). We were also unable to confirm the previously reported association between the Ser482 allele and hypertension [odds ratio: 0.97, 95% CI = 0.87-1.08, P = 0.585]. These results were materially unchanged when analyses were focused on whites only. However, statistical evidence of gene-age interaction was apparent for DBP [Gly482Gly: 73.5 (72.8, 74.2), Gly482Ser: 77.0 (76.2, 77.8), Ser482Ser: 79.1 (77.4, 80.9), P = 4.20 x 10(-12)] and SBP [Gly482Gly: 121.4 (120.4, 122.5), Gly482Ser: 125.9 (124.6, 127.1), Ser482Ser: 129.2 (126.5, 131.9), P = 7.20 x 10(-12)] in individuals <50 yr (n = 2,511); these genetic effects were absent in those older than 50 yr (n = 5,088) (SBP, P = 0.41; DBP, P = 0.51). Our findings suggest that the PPARGC1A Ser482 allele may be associated with higher blood pressure, but this is only apparent in younger adults.

Optimal H∞ insulin injection control for blood glucose regulation in diabetic patients

The theory of H/sup /spl infin// optimal control has the feature of minimizing the worst-case gain of an unknown disturbance input. When appropriately modified, the theory can be used to design a "switching" controller that can be applied to insulin injection for blood glucose (BG) regulation. The "switching" controller is defined by a collection of basic insulin rates and a rule that switches the insulin rates from one value to another. The rule employed an estimation of BG from noisy measurements, and the subsequent optimization of a performance index that involves the solution of a "jump" Riccati differential equation and a discrete-time dynamic programming equation. With an appropriate patient model, simulation studies have shown that the controller could correct BG deviation using clinically acceptable insulin delivery rates.

Blood glucose meters : an independent head to head comparison

A new generation of blood glucose meters is now available for use by people with diabetes and health professionals, but little independent evaluation data is available. Previous models are prone to a variety of errors. We compared the accuracy, precision and features of the six latest meters available in Australia as of 1996. Meters studied were the Mini-Accutrend and Advantage (Boehringer Mannheim), Precision QID and Companion 2 (MediSense), Glucometer Elite (Bayer) and Lynx (National Diagnostic Products). We measured the blood glucose levels of 50 people with diabetes with these meters, and compared them to a reference method (YSI glucose analyser). Error grid analysis confirmed that accuracy of all meters was sufficient for their intended use as patient monitors. Precision was assessed using 25 samples from control solutions provided for each meter, and the coefficient of variation calculated. Improvements in strip and meter technology in some models have increased ease of use and reduced the likelihood of user error. This study, when considered with individual preferences for various features and price should assist patients in choosing a new blood glucose meter.

Beneficial associations of physical activity with 2-h, but not fasting, blood glucose in Australian adults

OBJECTIVE--We examined the associations of physical activity with fasting plasma glucose (FPG) and with 2-h postload plasma glucose (2-h PG) in men and women with low, moderate, and high waist circumference.

RESEARCH DESIGN AND METHODS--The Australian Diabetes, Obesity and Lifestyle (AusDiab) study provided data on a population-based cross-sectional sample of 4,108 men and 5,106 women aged [greater than or equal to] 25 years without known diabetes or health conditions that could affect physical activity. FPG and 2-h PG were obtained from an oral glucose tolerance test. Self-reported physical activity level was defined according to the current public health guidelines as active ([greater than or equal to] 150 min/week across five or more sessions) or inactive (<150 min/week and/or less than five sessions). Sex-specific quintiles of physical activity time were used to ascertain dose response.

RESULTS--Being physically active and total physical activity time were independently and negatively associated with 2-h PG. When physical activity level was considered within each waist circumference category, 2-h PG was significantly lower in active high-waist circumference women ([beta] -0.30 [95% CI -0.59 to -0.01], P = 0.044) and active low-waist circumference men ([beta] -0.25 [-0.49 to -0.02], P = 0.036) compared with their inactive counterparts. Considered across physical activity and waist circumference categories, 2-h PG levels were not significantly different between active moderate-waist circumference participants and active low-waist circumference participants. Associations between physical activity and FPG were nonsignificant.

CONCLUSIONS--There are important differences between 2-h PG and FPG related to physical activity. It appears that 2-h PG is more sensitive to the beneficial effects of physical activity, and these benefits occur across the waist circumference spectrum.

Should capillary blood glucose measurements be used in population surveys?

Objective
To determine the accuracy and appropriateness of capillary blood glucose testing in population surveys.
Materials and methods
Capillary blood glucose using the Rochec ACCU-CHEK instrument and Advantage 11 Test Strips was compared to a laboratory instrument. Three independent cross-sectional risk factor surveys (n=1432) and baseline individuals from the Greater Green Triangle Diabetes Prevention Project (n=341) provided both fasting plasma and capillary blood glucose measurements. Accuracy of capillary glucoses was assessed using the ISO 15197 standard. The median age of the participants was 71years, ranging from 25 to 84years. There were 799 males and 974 females.
Results
Capillary glucose method had poorer precision at lower concentrations (CV: 9.50%, mean=3.09mmol/L, CV: 4.90%, mean=16.78mmol/L, n=233 replicates). Individual discrepancies were seen across the measuring range (2.8–19.9mmol/L, n=1773). In total, 94.5% of results fell within the minimum acceptable accuracy standards. This was slightly short of the 95% of results required to meet the ISO 15197 standard. The prevalence of diabetes in the study population using glucose 7.0mmol/L was 2.4% (95%CI 1.8–3.3%) according to fasting plasma glucose and 2.8% (2.1–3.8%) according to fasting capillary glucose. The lower WHO-defined cut-off of 6.1mmol/L for capillary blood glucose testing gave a prevalence of 10.7% (9.0–12.5%).
Conclusions
This study of matched capillary and plasma glucose results concludes that while it is appropriate to use fasting capillary glucose levels to determine the prevalence of diabetes in populations, it should not be used to reliably diagnose diabetes in individuals.

Simulation of a device concept for noninvasive sensing of blood glucose levels

This paper introduces a method of modeling noninvasive glucose sensing for patients who suffer from diabetes mellitus. The proposed technique involves simulation of light propagation through biological tissue with an embedded photonic crystal. The proposed detection technique is Raman spectroscopy and the use of the photonic crystal enables the enhancement of Raman scattering by engineering the photon density of states. Further enhancement can be achieved using noble metal clusters which result in surface enhanced Raman scattering and has the ability to provide enhancements of up to a million times.

Effect of increased blood glucose availability on glucose kinetics during exercise

This study examined the effect of increased blood glucose availability on glucose kinetics during exercise. Five trained men cycled for 40 min at 77 ± 1% peak oxygen uptake on two occasions. During the second trial (Glu), glucose was infused at a rate equal to the average hepatic glucose production (HGP) measured during exercise in the control trial (Con). Glucose kinetics were measured by a primed continuous infusion ofd-[3-3H]glucose. Plasma glucose increased during exercise in both trials and was significantly higher in Glu. HGP was similar at rest (Con, 11.4 ± 1.2; Glu, 10.6 ± 0.6 μmol ⋅ kg−1 ⋅ min−1). After 40 min of exercise, HGP reached a peak of 40.2 ± 5.5 μmol ⋅ kg−1 ⋅ min−1in Con; however, in Glu, there was complete inhibition of the increase in HGP during exercise that never rose above the preexercise level. The rate of glucose disappearance was greater (P < 0.05) during the last 15 min of exercise in Glu. These results indicate that an increase in glucose availability inhibits the rise in HGP during exercise, suggesting that metabolic feedback signals can override feed-forward activation of HGP during strenuous exercise.

Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo

We previously used Gene Expression Signature technology to identify methazolamide (MTZ) and related compounds with insulin sensitizing activity in vitro. The effects of these compounds were investigated in diabetic db/db mice, insulin-resistant diet-induced obese (DIO) mice, and rats with streptozotocin (STZ)-induced diabetes. MTZ reduced fasting blood glucose and HbA1c levels in db/db mice, improved glucose tolerance in DIO mice, and enhanced the glucose-lowering effects of exogenous insulin administration in rats with STZ-induced diabetes. Hyperinsulinemic-euglycemic clamps in DIO mice revealed that MTZ increased glucose infusion rate and suppressed endogenous glucose production. Whole-body or cellular oxygen consumption rate was not altered, suggesting MTZ may inhibit glucose production by different mechanism(s) to metformin. In support of this, MTZ enhanced the glucose-lowering effects of metformin in db/db mice. MTZ is known to be a carbonic anhydrase inhibitor (CAI); however, CAIs acetazolamide, ethoxyzolamide, dichlorphenamide, chlorthalidone, and furosemide were not effective in vivo. Our results demonstrate that MTZ acts as an insulin sensitizer that suppresses hepatic glucose production in vivo. The antidiabetic effect of MTZ does not appear to be a function of its known activity as a CAI. The additive glucose-lowering effect of MTZ together with metformin highlights the potential utility for the management of type 2 diabetes.

Self-monitoring of blood glucose versus self-monitoring of urine glucose in adults with newly diagnosed Type 2 diabetes receiving structured education: a cluster randomized controlled trial.

AIMS: To compare the effectiveness and acceptability of self-monitoring of blood glucose with self-monitoring of urine glucose in adults with newly diagnosed Type 2 diabetes. METHODS: We conducted a multi-site cluster randomized controlled trial with practice-level randomization. Participants attended a structured group education programme, which included a module on self-monitoring using blood glucose or urine glucose monitoring. HbA1c and other biomedical measures as well as psychosocial data were collected at 6, 12 and 18 months. A total of 292 participants with Type 2 diabetes were recruited from 75 practices. RESULTS: HbA1c levels were significantly lower at 18 months than at baseline in both the blood monitoring group [mean (se) -12 (2) mmol/mol; -1.1 (0.2) %] and the urine monitoring group [mean (se) -13 (2) mmol/mol; -1.2 (0.2)%], with no difference between groups [mean difference adjusted for cluster effect and baseline value = -1 mmol/mol (95% CI -3, 2); -0.1% (95% CI -0.3, 0.2)]. Similar improvements were observed for the other biomedical outcomes, with no differences between groups. Both groups showed improvements in total treatment satisfaction, generic well-being, and diabetes-specific well-being, and had a less threatening view of diabetes, with no differences between groups at 18 months. Approximately one in five participants in the urine monitoring arm switched to blood monitoring, while those in the blood monitoring arm rarely switched (18 vs 1% at 18 months; P < 0.001). CONCLUSIONS: Participants with newly diagnosed Type 2 diabetes who attended structured education showed similar improvements in HbA1c levels at 18 months, regardless of whether they were assigned to blood or urine self-monitoring.

The Accuracy of National Body Fat Cutoff Levels in the Prediction of Elevated Blood Pressure among Brazilian Male Adolescents

Objective: To assess viability of the development of percentage body fat cutoffs based on blood pressure values in Brazilian adolescents.Methods: A cross-sectional study was conducted with a sample of 358 male subjects from 8 to 18 years old. Blood pressure was measured by the oscilometric method, and body composition was measured by dual-energy X-ray absorptiometry (DXA).Results: For the identification of elevated blood pressure, these nationally developed body fat cutoffs presented relative accuracy. The cutoffs were significantly associated with elevated blood pressure [odds ratio = 5.91 (95% confidence interval: 3.54-9.86)].Conclusions: Development of national body fat cutoffs is viable, because presence of high accuracy is an indication of elevated blood pressure.