Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE^-/-) and compared with wild-type littermates. Compared with wild-type littermates, ACE^-/- mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE^-/- mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE^-/- mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excrete in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE^-/- mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.

Television time and continuous metabolic risk in physically active adults

Purpose: Among Australian adults who met the public health guideline for the minimum health-enhancing levels of physical activity, we examined the dose-response associations of television-viewing time with continuous metabolic risk variables.

Methods: Data were analyzed on 2031 men and 2033 women aged >= 25 yr from the 1999-2000 Australian Diabetes, Obesity and Lifestyle study without clinically diagnosed diabetes or heart disease, who reported at least 2.5 h·wk-1 of moderate- to vigorous-intensity physical activity. Waist circumference, resting blood pressure, and fasting and 2-h plasma glucose, triglycerides, and high-density-lipoprotein cholesterol (HDL-C) were measured. The cross-sectional associations of these metabolic variables with quartiles and hours per day of self-reported television-viewing time were examined separately for men and for women. Analyses were adjusted for age, education, income, smoking, diet quality, alcohol intake, parental history of diabetes, and total physical activity time, as well as menopausal status and current use of postmenopausal hormones for women.

Results: Significant, detrimental dose-response associations of television-viewing time were observed with waist circumference, systolic blood pressure, and 2-h plasma glucose in men and women, and with fasting plasma glucose, triglycerides, and HDL-C in women. The associations were stronger in women than in men, with significant gender interactions observed for triglycerides and HDL-C. Though waist circumference attenuated the associations, they remained statistically significant for 2-h plasma glucose in men and women, and for triglycerides and HDL-C in women.

Conclusions: In a population of healthy Australian adults who met the public health guideline for physical activity, television-viewing time was positively associated with a number of metabolic risk variables. These findings support the case for a concurrent sedentary behavior and health guideline for adults, which is in addition to the public health guideline on physical activity.

Breaks in sedentary time

OBJECTIVE--Total sedentary (absence of whole-body movement) time is associated with obesity, abnormal glucose metabolism, and the metabolic syndrome. In addition to the effects of total sedentary time, the manner in which it is accumulated may also be important. We examined the association of breaks in objectively measured sedentary time with biological markers of metabolic risk.

RESEARCH DESIGN AND METHODS--Participants (n = 168, mean age 53.4 years) for this cross-sectional study were recruited from the 2004-2005 Australian Diabetes, Obesity and Lifestyle study. Sedentary time was measured by an accelerometer (counts/[minute^-1] < 100) worn during waking hours for seven consecutive days. Each interruption in sedentary time (counts/min [greater than or equal to] 100) was considered a break. Fasting plasma glucose, 2-h plasma glucose, serum triglycerides, HDL cholesterol, weight, height, waist circumference, and resting blood pressure were measured. MatLab was used to derive the breaks variable; SPSS was used for the statistical analysis.

RESULTS--Independent of total sedentary time and moderate-to-vigorous intensity activity time, increased breaks in sedentary time were beneficially associated with waist circumference (standardized ß = -0.16, 95% CI -0.31 to -0.02, P = 0.026), BMI (ß = -0.19, -0.35 to -0.02, P = 0.026), triglycerides (ß = -0.18, -0.34 to -0.02, P = 0.029), and 2-h plasma glucose (ß = -0.18, -0.34 to -0.02, P = 0.025).

CONCLUSIONS--This study provides evidence of the importance of avoiding prolonged uninterrupted periods of sedentary (primarily sitting) time. These findings suggest new public health recommendations regarding breaking up sedentary time that are complementary to those for physical activity.

Objectively measured sedentary time, physical activity, and metabolic risk the Australian diabetes, obesity and lifestyle tudy (AusDiab)

OBJECTIVE—We examined the associations of objectively measured sedentary time and physical activity with continuous indexes of metabolic risk in Australian adults without known diabetes.

RESEARCH DESIGN AND METHODS—An accelerometer was used to derive the percentage of monitoring time spent sedentary and in light-intensity and moderate-to-vigorous–intensity activity, as well as mean activity intensity, in 169 Australian Diabetes, Obesity and Lifestyle Study (AusDiab) participants (mean age 53.4 years). Associations with waist circumference, triglycerides, HDL cholesterol, resting blood pressure, fasting plasma glucose, and a clustered metabolic risk score were examined.

RESULTS—Independent of time spent in moderate-to-vigorous–intensity activity, there were significant associations of sedentary time, light-intensity time, and mean activity intensity with waist circumference and clustered metabolic risk. Independent of waist circumference, moderate-to-vigorous–intensity activity time was significantly beneficially associated with triglycerides.

CONCLUSIONS—These findings highlight the importance of decreasing sedentary time, as well as increasing time spent in physical activity, for metabolic health.

Dietary patterns, insulin resistance, and incidence of type 2 diabetes in the Whitehall II study

OBJECTIVE—We examined the associations of objectively measured sedentary time and physical activity with continuous indexes of metabolic risk in Australian adults without known diabetes.

RESEARCH DESIGN AND METHODS—An accelerometer was used to derive the percentage of monitoring time spent sedentary and in light-intensity and moderate-to-vigorous–intensity activity, as well as mean activity intensity, in 169 Australian Diabetes, Obesity and Lifestyle Study (AusDiab) participants (mean age 53.4 years). Associations with waist circumference, triglycerides, HDL cholesterol, resting blood pressure, fasting plasma glucose, and a clustered metabolic risk score were examined.

RESULTS—Independent of time spent in moderate-to-vigorous–intensity activity, there were significant associations of sedentary time, light-intensity time, and mean activity intensity with waist circumference and clustered metabolic risk. Independent of waist circumference, moderate-to-vigorous–intensity activity time was significantly beneficially associated with triglycerides.

CONCLUSIONS—These findings highlight the importance of decreasing sedentary time, as well as increasing time spent in physical activity, for metabolic health.

A comparison of subjective and objective measures of physical activity and fitness in identifying associations with cardiometabolic risk factors

Purpose
To compare the ability of alternative measures of physical activity and fitness to quantify associations with health outcomes.

Methods
Associations between a range of subjective and objective physical activity and fitness measures and cardiometabolic risk factors were examined using data from 1,631 Australians aged 26–36 years. Anthropometry, fitness, blood pressure, and fasting blood glucose, insulin, and lipids were measured at study clinics. Participants completed the International Physical Activity Questionnaire (IPAQ) and 7-day pedometer diaries; they also reported sedentary behavior (sitting, television viewing).

Results
In men and women, associations were strongest for fitness, with those in the highest (vs. lowest) fitness quarter having a 75% to 80% lower prevalence of two or more primary risk factors (waist circumference, high-density lipoprotein cholesterol, and insulin resistance). In men, a 60% to 70% reduced prevalence of two or more risk factors was observed across extreme quarters of IPAQ leisure, IPAQ vigorous, sitting duration, and pedometer measures. Similar reductions in prevalence were observed only across extreme quarters of pedometer activity and television viewing in women.

Conclusions
Associations between alternative measures and cardiometabolic risk were relatively independent, suggesting that a range of physical activity and fitness measures may be needed to most accurately quantify associations between physical activity and health.

Potential role of nitric oxide in contraction-stimulated glucose uptake and mitochondrial biogenesis in skeletal muscle

• 1. The present review discusses the potential role of nitric oxide (NO) in the: (i) regulation of skeletal muscle glucose uptake during exercise; and (ii) activation of mitochondrial biogenesis after exercise.
• 2. We have shown in humans that local infusion of an NO synthase inhibitor during exercise attenuates increases in skeletal muscle glucose uptake without affecting blood flow. Recent studies from our laboratory in rodents support these findings in humans, although rodent studies from other laboratories have yielded conflicting results.
• 3. There is clear evidence that NO increases mitochondrial biogenesis in non-contracting cells and that NO influences basal skeletal muscle mitochondrial biogenesis. However, there have been few studies examining the potential role of NO in the activation of mitochondrial biogenesis following an acute bout of exercise or in response to exercise training. Early indications are that NO is not involved in regulating the increase in mitochondrial biogenesis that occurs in response to exercise.
• 4. Exercise is considered the best prevention and treatment option for diabetes, but unfortunately many people with diabetes do not or cannot exercise regularly. Alternative therapies are therefore critical to effectively manage diabetes. If skeletal muscle NO is found to play an important role in regulating glucose uptake and/or mitochondrial biogenesis, pharmaceutical agents designed to mimic these effects of exercise may improve glycaemic control.

Local nitric oxide synthase inhibition reduces skeletal muscle glucose uptake but not capillary blood flow during in situ muscle contraction in rats

OBJECTIVE: We have previously shown in humans that local infusion of a nitric oxide synthase (NOS) inhibitor into the femoral artery attenuates the increase in leg glucose uptake during exercise without influencing total leg blood flow. However, rodent studies examining the effect of NOS inhibition on contraction-stimulated skeletal muscle glucose uptake have yielded contradictory results. This study examined the effect of local infusion of an NOS inhibitor on skeletal muscle glucose uptake (2-deoxyglucose) and capillary blood flow (contrast-enhanced ultrasound) during in situ contractions in rats.

RESEARCH DESIGN AND METHODS: Male hooded Wistar rats were anesthetized and one hindleg electrically stimulated to contract (2 Hz, 0.1 ms) for 30 min while the other leg rested. After 10 min, the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (arterial concentration of 5 µmol/l) or saline was infused into the epigastric artery of the contracting leg.

RESULTS: Local NOS inhibition had no effect on blood pressure, heart rate, or muscle contraction force. Contractions increased (P < 0.05) skeletal muscle NOS activity, and this was prevented by L-NAME infusion. NOS inhibition caused a modest significant (P < 0.05) attenuation of the increase in femoral blood flow during contractions, but importantly there was no effect on capillary recruitment. NOS inhibition attenuated (P < 0.05) the increase in contraction-stimulated skeletal muscle glucose uptake by ~35%, without affecting AMP-activated protein kinase (AMPK) activation.

CONCLUSIONS: NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment, suggesting that NO is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.

L-Arginine infusion increases glucose clearance during prolonged exercise in humans

Nitric oxide synthase (NOS) inhibition has been shown in humans to attenuate exercise-induced increases in muscle glucose uptake. We examined the effect of infusing the NO precursor L-arginine (L-Arg) on glucose kinetics during exercise in humans. Nine endurance-trained males cycled for 120 min at 72 ± 1% VO2 peak followed immediately by a 15-min "all-out" cycling performance bout. A [6,6-2H]glucose tracer was infused throughout exercise, and either saline alone (Control, CON) or saline containing L-Arg HCl (L-Arg, 30 g at 0.5 g/min) was coinfused in a double-blind, randomized order during the last 60 min of exercise. L-Arg augmented the increases in glucose rate of appearance, glucose rate of disappearance, and glucose clearance rate (L-Arg: 16.1 ± 1.8 ml·min–1·kg–1; CON: 11.9 ± 0.7 ml·min–1·kg–1 at 120 min, P < 0.05) during exercise, with a net effect of reducing plasma glucose concentration during exercise. L-Arg infusion had no significant effect on plasma insulin concentration but attenuated the increase in nonesterified fatty acid and glycerol concentrations during exercise. L-Arg infusion had no effect on cycling exercise performance. In conclusion, L-Arg infusion during exercise significantly increases skeletal muscle glucose clearance in humans. Because plasma insulin concentration was unaffected by L-Arg infusion, greater NO production may have been responsible for this effect.

Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions from the brown seaweed Ascophyllum nodosum

We screened seaweed species from Atlantic Canada for antidiabetic activity by testing extracts for α-glucosidase inhibitory effect and glucose uptake stimulatory activity. An aqueous ethanolic extract of Ascophyllum nodosum was found to be active in both assays, inhibiting rat intestinal α-glucosidase (IC50 = 77 μg/mL) and stimulating basal glucose uptake into 3T3-L1 adipocytes during a 20-minute incubation by about 3-fold (at 400 μg/mL extract). Bioassay-guided fractionation of the A. nodosum extract showed that α-glucosidase inhibition was associated with polyphenolic components in the extract. These polyphenolics, along with other constituents appeared to be responsible for the stimulatory activity on glucose uptake. However, attempts to further concentrate this activity through fractionation techniques were unsuccessful. A crude polyphenol extract (PPE), an enriched polyphenolic fraction (PPE-F1) and a polysaccharide extract (PSE) were prepared from commercial A. nodosum powder and administered to streptozotocin-diabetic mice for up to 4-weeks by daily gavage at 200 mg/kg body mass. PPE and PPE-F1 improved fasting serum glucose level in diabetic mice; however, the effect was only statistically significant at day 14. In addition, PPE-F1 was shown to blunt the rise in blood glucose after an oral sucrose tolerance test in diabetic mice. Mice treated with PPE and PPE-F1 had decreased blood total cholesterol and glycated serum protein levels compared with untreated diabetic mice, whereas PPE also normalized the reduction in liver glycogen level that occurred in diabetic animals. All 3 A. nodosum preparations improved blood antioxidant capacity.

On a établit une recherche d’un produit anti-diabétique, parmi les algues locales de la région Atlantique du Canada, en examinant la capacité d’un effet inhibiteur de l’enzyme α-glucosidase et une stimulation de l’incorporation cellulaire du glucose. Un extrait éthanol-aqueux de Ascophyllum nodosum nous a donné une activité positive chez les deux essais, une inhibition de l’α-glucosidase provenant de l’intestin du rat (IC50 = 77 μg/mL) et puis une stimulation triple, à une concentration de 400 μg/mL, de l’incorporation du glucose dans les adipocytes 3T3-L1 durant une période de 20 minutes. L’extrait de A. nodosum a été divisé, guidé par les résultats biologiques, et a ainsi démontré la présence d’éléments polyphénoliques associé à l’inhibition de l’α-glucosidase. Ces éléments polyphénoliques ainsi que d’autres semblent être responsables de l’incorporation stimulée du glucose. Il a été impossible de raffiner cette activité lors d’une division des composants. Un extrait brut polyphénolique (PPE), un extrait enrichi polyphénolique (PPE-F1) et puis un extrait polysaccharide (PSE) furent préparés d’une poudre commerciale de A. nodosum et utilisés dans une étude utilisant des souris, rendues diabétiques par injections de streptozotocin, traitées par un gavage journalier de l’extrait 200 mg/kg du poids corporel durant une période de 4 semaines. Le taux du glucose sanguin à jeun des souris fut moins élevé en présence des extraits qu’en leurs absence. Cependant, l’effet était seulement significatif au jour 14. Les résultats étant toutefois variables. En plus, lors d’un essai oral de la tolérance au sucrose chez la souris diabétique, l’extrait PPE-F1 a empêché l’augmentation du taux du glucose sanguin. Les extraits PPE et PPE-F1 ont réduit le taux de cholestérol sanguin et les niveaux de glycation des protéines en comparaison de ces niveaux en absence des extraits tandis que l’extrait PPE a présenté une réduction du niveau de glycogène du foie chez les souris diabétiques. Les trois extraits de A. nodosum ont tous amélioré la capacité antioxidante du sang.

Substrate utilization during exercise performed with and without glucose ingestion in female and male endurance trained athletes

Compared to males, females oxidize proportionately more fat and less carbohydrate during endurance exercise performed in the fasted state. This study was designed to test the hypothesis that there may also be gender differences in exogenous carbohydrate (CHOexo) oxidation during exercise. Healthy, young males (n = 7) and females (n = 7) each completed 2 exercise trials (90 min cycle ergometry at 60% VO[sub2peak]), 1 week apart. Females were eumenorrheic and were tested in the midfollicular phase of their menstrual cycle. Subjects drank intermittently either 8% CHOexo (1 g glucose ⋅ kg ⋅ h[sup-1]) enriched with U-13C glucose or an artificially sweetened placebo during the trial. Whole-body substrate oxidation was determined from PER, urinary urea excretion, and the ratio of 13C:12C in expired gas during the final 60 min of exercise. During the placebo trial, fat oxidation was higher in females than in males (0.42 ± 0.07 vs. 0.32 ± 0.09 g ⋅ min[sup-1] . kg LBM[sup-1] x 10[sup-2]) at 30 min of exercise (p < .05). When averaged over the final 60 min of exercise, the relative proportions of fat, total carbohydrate, and protein were similar between groups. During CHOexo ingestion, both the ratio of 13C: 12C in expired gas (p < .05) and the proportion of energy derived from CHOexo relative to LBM (p < .05) were higher in females compared to males at 75- and 90-min exercise. When averaged over the final 60 min of exercise, the percentage of CHOexo to the total energy contribution tended to be higher in females (14.3 + 1.2%) than in males (11.2 ± 1.2%; p = .09). The reduction in endogenous CHO oxidation with CHOexo intake was also greater in females (12.9 ± 3.1%) than in males (5.1 ± 2.0%; p = .05). Compared to males, females may oxidize a greater relative proportion of CHOexo during endurance exercise which, in turn, may spare more endogenous fuel. Based on these observations, ingested carbohydrate may be a particularly beneficial source of fuel during endurance exercise for females.

Intervening to improve health indicators among Australian farm families

The Sustainable Farm Families project (http://www.sustainablefarmfamilies.org.au/) was a 3-year demonstration and education project designed to influence farmer behavior with respect to family health and well-being among cropping and grazing farmers in Victoria, New South Wales, and South Australia, Australia. The project was conducted by the Western District Health Service, Hamilton, Australia, in partnership with farmers; Farm Management 500 (peer discussion group); the Victorian Farmers Federation; Royal Melbourne Institute of Technology; and Land Connect. During the 3 years of the project, 128 farmers—men (70) and women (58)—were enrolled. The project utilized a combination of small group workshops, individualized health action plans, and health education opportunities to encourage farm safety and health behavior changes and to elicit sustained improvements in the following health indicators: body mass index (BMI), total cholesterol, fasting blood glucose, and blood pressure. Mean changes in these health indicators were analyzed using repeated measures analysis of variance (ANOVA) and McNemar's test compared the proportion of individuals with elevated indicators. Among participants with elevated values at baseline, the following average reductions were observed: BMI 0.44 kg/m2 (p = .0034), total cholesterol 48.7 mg/dl (p < .0001), blood glucose 10.1 mg/dl (p = .0016), systolic blood pressure 12.5 mm Hg (p < .0001), and diastolic blood pressure 5.0 mm Hg (p = .0007). The proportion of participants with elevated total cholesterol at baseline decreased after 24 months (p < .001). Such findings suggest that proactive intervention by farmer associations, rural health services, and government agencies may be an effective vehicle for promoting voluntary farm safety and health behavior change while empowering farm families to achieve measurable reductions in important health risk factors.

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.

Dietary quality is associated with diabetes and cardio-metabolic risk factors1–3

In this study, our aim was to investigate the associations between diet quality and newly diagnosed diabetes, prediabetes, and cardio-metabolic risk factors. The analysis was based on 7441 participants of the Australian Diabetes, Obesity and Lifestyle study, a cross-sectional study of adults aged 25 y involving a 75-g oral glucose tolerance test. Diet quality was assessed via a dietary guideline index and FFQ data. Associations between diet quality and diabetes, prediabetes (impaired fasting glycemia, impaired glucose tolerance), and cardiovascular risk factors were investigated using linear and logistic regression adjusted for age, education, smoking, physical activity, sedentary behavior, and BMI. Higher diet quality was significantly associated with lower systolic and diastolic blood pressure among men, lower fasting plasma glucose among men and women, and lower systolic blood pressure, fasting plasma insulin, and 2-h plasma glucose and greater insulin sensitivity among women. Diet quality was inversely associated with abdominal obesity [odds ratio (OR) for top quartile: 0.68, 0.48–0.96], hypertension (OR: 0.50, 0.31–0.81), and type 2 diabetes (OR: 0.38, 0.18–0.80) among men. Lack of compliance with established dietary guidelines was associated with type 2 diabetes and cardio-metabolic risk factors. Further work is required to determine whether this dietary index has predictive validity for health in longitudinal studies.