The effects of Chronic Lycopene Supplementation on Exercise-Induced Oxidative Stress and Glucose Homeostasis.

Lycopene can exert antioxidant effects against peripheral and cellular oxidative stress and may be associated with reduced diabetic risk. Conversely, exercise-induced free radicals are thought to underpin many of the desirable whole-body adaptations following training and the use of antioxidants within the exercise model remains debatable. PURPOSE: To investigate the effect of lycopene supplementation on oxidative stress and glucose homeostasis following acute aerobic exercise. METHOD: Twenty-eight (n=28) apparently healthy male volunteers were recruited (age 24 ± 4 years; weight 78 ± 10 kg; height 178 ± 8 cm; 2max 40 ± 7 ml·kg-1 ·min-1 ) in a randomised, single blind, placebo-controlled study. Participants were required to attend the Laboratory on two occasions: prior to and following 6 weeks of supplementation of either 10mg lycopene (LG; n=15) or placebo (PG; n=13) followed by a bout of acute exercise for one hour at 65% 2max. Exogenous glucose oxidation was then measured on an isotope ratio mass spectrometer in a sub-group of participants (n=14) following exercise, by administration of a standard oral glucose tolerance test (OGTT; 75g glucose). Venous blood samples were drawn for measurement of oxidative stress parameters, plasma glucose and insulin. RESULTS: Plasma lycopene increased in LG only (0.01 ± 0.004 vs.0.02 ± 0.007 µmol/L; P <0.05) following supplementation and remained elevated post exercise compared to PG (0.01 ± 0.004 vs. 0.02 ± 0.009 µmol/L; P <0.05). There were no changes in other markers of oxidative stress (SOD, LOOHs, F2 ISP and Alkoxyl radical) either between or within the trials, (P >0.05, respectively). A main effect for an increase in insulin was observed two hours post OGTT in the sub-groups (Pooled data, P <0.05) but trends in the HOMA scores were evident with a 57% increase for LG (2.20 ± 1.84 vs. 5.14 ± 2.5; P >0.05) and an 11% decrease for PG (2.17 ± 1.06 vs. 1.94 ± 1.53; P >0.05). No change in plasma glucose was detected at any point, or after the OGTT (P >0.05). CONCLUSION: In healthy males, lycopene supplementation had no effect on post exercise levels of ROS or markers of lipid peroxidation, despite an increase in plasma lycopene. However, lycopene supplementation may affect post exercise insulin sensitivity in response to glucose consumption, but further parallel research is required.

Effect of dietary supplementation of different oils during the first or second half of pregnancy on the glucose tolerance of the sow

Poor glucose tolerance may be an under-researched contributory factor in the high (10% to 20%) pre-weaning mortality rate observed in pigs. Insulin resistance commences at around week 12 of gestation in the sow, although there are conflicting reports in the literature about the extent to which insulin resistance is modulated by maternal diet. The aim of the study was to determine the effects of supplementing the maternal diet with different dietary oils during either the first half or the second half of gestation on the glucose tolerance of the sow. Sows were offered the control (C: n = 5) diet as pellets or the C diet plus 10% extra energy (h = 16 per group) derived from either. (i) extra pellets; (ii) palm oil; (iii) olive oil; (iv) sunflower oil; or (v) fish oil. Experimental diets were fed during either the first (G1) or second (G2) half of gestation. A glucose tolerance test (GTT) was conducted on day 108 of gestation by administering 0.5g/kg glucose i.v. Blood samples were taken every 5 to 10 min for 90 min post administration. The change in body weight and backfat thickness during gestation was similar but both type and timing of dietary supplementation influenced litter size and weight. With the exception of the sunflower oil group, supplementing the maternal diet in G1 resulted in larger and heavier litters, particularly in mothers offered palm oil. Basal blood glucose concentrations tended to be more elevated in G1 than G2 groups, whilst plasma insulin concentrations were similar Following a GTT, the adjusted area under the curve was greater in G1 compared to G2 sows, despite no differences in glucose clearance. Maternal diet appeared to influence the relationship between glucose curve characteristics following a GTT and litter outcome. In conclusion, the degree of insulin sensitivity can be altered by both the period during which maternal nutritional supplementation is offered and the fatty acid profile of the diet.

Intergenerational effects of birth weight on glucose tolerance and reproductive performance

Women who were themselves small-for-gestational age (SGA) are at a greater risk of adulthood diseases such as non-insulin-dependent diabetes mellitus (NIDDM), and twice at risk of having an SGA baby themselves. The aim of this study was to examine the intergenerational pig. Low (L) and normal (N) birth weight female piglets were followed throughout their first pregnancy (generation 1 (0)). After they had given birth, the growth and development of the lightest (I) and heaviest (n) female piglet from each litter were monitored until approximately 5 months of age (generation 2 (G2)). A glucose tolerance test (GTT) was conducted on G1 pig at similar to 6 months of age and again during late pregnancy; a GTT was also conducted on G2 pigs at similar to 4 months of age. G1 L offspring exhibited impaired glucose metabolism in later life compared to their G1 N sibling but in the next generation a similar scenario was only observed between I and n offspring born to G1 L mothers. Despite G1 L mothers showing greater glucose intolerance in late pregnancy and a decreased litter size, average piglet birth weight was reduced and there was also a large variation in litter weight; this suggests that they were, to some extent, prioritising their nutrient intake towards themselves rather than promoting their reproductive performance. There were numerous relationships between body shape at birth and glucose curve characteristics in later life, which can, to some extent, be used to predict neonatal outcome. In conclusion, intergenerational effects are partly seen in the pig. It is likely that some of the intergenerational influences may be masked due to the pig being a litter-bearing species.

Physical activity and television viewing in relation to risk and undiagnosed abnormal glucose metabolism in adults

OBJECTIVE--The goal of this study was to assess the associations of physical activity time and television (TV) time with risk of "undiagnosed" abnormal glucose metabolism in Australian adults.

RESEARCH DESIGN AND METHODS--This population-based cross-sectional study using a stratified cluster design involving 42 randomly selected Census Collector Districts across Australia included 8,299 adults aged 25 years or older who were free from new type 2 diabetes and self-reported ischemic disease and did not take lipid lowering or antihypertensive drugs. Abnormal glucose metabolism (impaired fasting glycetnia [IFG], impaired glucose tolerance [IGT], or new type 2 diabetes) was based on an oral glucose tolerance test Self reported physical activity time and TV time (previous week) were assessed using interviewer administered questionnaires.

RESULTS--Alter adjustment for known confounders and TV time, the odds ratio (OR) of having abnormal glucose metabolism was 0.62 (95% CI 0.41-0.96) in men and 0.71 (0.501.00) in women for those engaged in physical activity [greater than or equal to] 2.5 h/week compared with those who were sedentary (0 h/week). The ORs of having abnormal glucose metabolism were 1.16 (0.791.70) in men and 1.49 (1.12-1.99) in women who watched TV > 14 h/week compared with those who watched [less than or equal to] 7.0 h/week. Higher TV viewing (> 14 h/week) was also associated with an increased risk of new type 2 diabetes in men and women and IGT in women compared with those watching < 14 h/week. Total physical activity of [greater than or equal to] 2.5 h/week was associated with a reduced risk of IFG, IGT, and new type 2 diabetes in both sexes: however, only the association with IGT in women was statistically significant.

CONCLUSIONS--These findings suggest a protective effect of physical activity and a deleterious effect of TV time on the risk of abnormal glucose metabolism in adults. Population strategies to reduce risk of abnormal glucose metabolism should focus on reducing sedentary behaviors such as TV time, as well as increasing physical activity.

Association of television viewing with fasting and 2-h postchallenge plasma glucose levels in adults without diagnosed diabetes

OBJECTIVE—We examined the associations of television viewing time with fasting plasma glucose (FPG) and 2-h postchallenge plasma glucose (2-h PG) levels in Australian adults.

RESEARCH DESIGN AND METHODS—A total of 8,357 adults aged >35 years who were free from diagnosed diabetes and who attended a population-based cross-sectional study (Australian Diabetes, Obesity and Lifestyle Study [AusDiab]) were evaluated. Measures of FPG and 2-h PG were obtained from an oral glucose tolerance test. Self-reported television viewing time (in the previous week) was assessed using an interviewer-administered questionnaire. Homeostasis model assessment (HOMA) of insulin sensitivity (HOMA-%S) and ß-cell function (HOMA-%B) were calculated based on fasting glucose and insulin concentrations.

RESULTS—After adjustment for confounders and physical activity time, time spent watching television in women was positively associated with 2-h PG, log fasting insulin, and log HOMA-%B and inversely associated with log HOMA-%S (P < 0.05) but not with FPG. No significant associations were observed with glycemic measures in men. The ß-coefficients across categories of average hours spent watching television per day (<1.0, 1.0–1.9, 2.0–2.9, 3.0–3.9, and ≥4.0) for 2-h PG in women were 0 (reference), 0.009, 0.047, 0.473, and 0.501, respectively (P for trend = 0.02).

CONCLUSIONS—Our findings highlight the unique deleterious relationship of sedentary behavior (indicated by television viewing time) and glycemic measures independent of physical activity time and adiposity status. These relationships differed according to sex and type of glucose measurement, with the 2-h PG measure being more strongly associated with television viewing. The findings suggest an important role for reducing sedentary behavior in the prevention of type 2 diabetes and cardiovascular disease, especially in women.

Objectively measured light-intensity physical activity is independently associated with 2-H plasma glucose

Objective: We examined the associations of objectively measured sedentary time, light-intensity physical activity, and moderate- to vigorous-intensity activity with fasting and 2-h postchallenge plasma glucose in Australian adults.

Research Design and Methods: A total of 67 men and 106 women (mean age ± SD 53.3 ± 11.9 years) without diagnosed diabetes were recruited from the 2004–2005 Australian Diabetes, Obesity, and Lifestyle (AusDiab) study. Physical activity was measured by Actigraph  accelerometers worn during waking hours for 7 consecutive days and summarized as sedentary time (accelerometer counts/min <100; average hours/day), light-intensity (counts/min 100-1951), and moderate- to vigorous-intensity (counts/min ≥1,952). An oral glucose tolerance test was used to ascertain 2-h plasma glucose and fasting plasma glucose.

Results: After adjustment for confounders (including waist circumference), sedentary time was positively associated with 2-h plasma glucose (b = 0.29, 95% CI 0.11–0.48, P = 0.002); light-intensity activity time (b = –0.25, –0.45 to –0.06, P = 0.012) and moderate- to vigorous-intensity activity time (b = –1.07, –1.77 to –0.37, P = 0.003) were negatively associated. Light-intensity activity remained significantly associated with 2-h plasma glucose following further adjustment for moderate- to vigorous-intensity activity (b = –0.22, –0.42 to –0.03, P = 0.023). Associations of all activity measures with fasting plasma glucose were nonsignificant (P > 0.05).

Conclusions: These data provide the first objective evidence that light-intensity physical activity is beneficially associated with blood glucose and that sedentary time is unfavorably associated with blood glucose. These objective data support previous findings from studies using self-report measures, and suggest that substituting light-intensity activity for television viewing or other sedentary time may be a practical and achievable preventive strategy to reduce the risk of type 2 diabetes and cardiovascular disease.

Effects of chronic treatment with arabose on glucose and lipid metabolism in obese diabetic wistar rats

Aims: The effect of chronic treatment with acarbose on fasting plasma glucose, insulin, triglyceride, cholesterol and free fatty acid (FFA) concentrations, as well as on the glucose and insulin excursions during oral glucose tolerance test (OGTT), in obese diabetic Wistar (WDF) rats was investigated. Methods: Forty-five mature male WDF rats were randomly distributed to one of the three treatment groups (no acarbose, 20 mg and 40 mg of acarbose/100 g of chow, respectively). After 3.5, 7.5 and 11.5 months, animals were tested for glucose tolerance by means of an OGTT, and their respective metabolic profiles were determined. Control determinations were done in obese and age-matched lean animals before the start of the trial. Results: The WDF rats exhibit higher body weight and fasting blood glucose, insulin, triglyceride and cholesterol concentrations compared to lean animals. Moreover, they show marked glucose intolerance as indicated by the glucose and insulin excursions during OGTT. Interestingly, in both treated and untreated animals, a reversion of the hyperglycaemic state as well as an improvement of the glucose tolerance is observed. However, whereas in the group receiving no acarbose this is accounted for by dramatic increases in fasting plasma insulin concentrations and insulin secretion during OGTT (as indicated by the ΔInsulin area), in rats treated with acarbose the reversion of the diabetic state takes place without increments in hormone concentration. In addition, rats treated with acarbose for 3.5 and 7.5 months show lower plasma triglyceride and FFA concentrations, and the same was observed for cholesterol at the highest dosage of the drug. Conclusions: Chronic treatment with acarbose of WDF rats improves the glycaemic and lipidic control as well as the glucose tolerance, with a lower demand of pancreatic insulin than in untreated rats. This data suggests that the long-term modulation of glucose and insulin excursions after meals improves the insulin sensitivity in this rat strain.

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.

Association between impaired glucose metabolism and quality of life

Aims
We examined the association of quality of life with glucose tolerance status in an Australian population to determine the stage in the development of diabetes that quality of life is impaired.

Methods
The Australian Diabetes, Obesity and Lifestyle study (AusDiab) was a population-based study of 11,247 people from randomly selected areas of Australia. As part of the study, participants underwent an oral glucose tolerance test and completed the SF-36 quality of life questionnaire.

Results
Previously diagnosed diabetes was associated with a significantly greater risk of being in the lowest quartile of each dimension of the SF-36 scale (except for mental health) and this association was only partially attenuated by adjustment for age, sex, body mass index (BMI), physical activity and treatment for hypertension and lipid abnormalities (adjusted odds ratios [95% CI]: bodily pain, 1.51 [1.18–1.94]; general health, 2.20 [1.64–2.95]; physical functioning, 1.50 [1.10–2.05]; role limitation (emotional), 1.43 [1.07–1.91]; role limitation (physical), 1.57 [1.13–2.18]; social functioning, 1.93 [1.46–2.54] and vitality, 2.24 [1.56–3.22]. Among those with newly diagnosed diabetes (NDM) and impaired glucose tolerance (IGT), there was also evidence of reduced quality of life on some dimensions of the SF-36 scale (NDM, general health, physical functioning and role limitation (physical); IGT, physical functioning and social functioning) after adjustment for confounders.

Conclusion
These findings show that diabetes is associated with a reduced quality of life and that this is evident in the early stage of the disease, particularly in relation to the ability to perform physical activities.

Screening for type 2 diabetes and impaired glucose metabolism – the Australian experience

OBJECTIVE--To assess the Australian protocol for identifying undiagnosed type 2 diabetes and impaired glucose metabolism.

RESEARCH DESIGN AND METHODS--The Australian screening protocol recommends a stepped approach to detecting undiagnosed type 2 diabetes based on assessment of risk status, measurement of fasting plasma glucose (FPG) in individuals at risk, and further testing according to FPG. The performance of and variations to this protocol were assessed in a population-based sample of 10,508 Australians.

RESULTS--The protocol had a sensitivity of 79.9%, specificity of 79.9%, and a positive predictive value (PPV) of 13.7% for detecting undiagnosed type 2 diabetes and sensitivity of 51.9% and specificity of 86.7% for detecting impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). To achieve these diagnostic rates, 20.7% of the Australian adult population would require an oral glucose tolerance test (OGTT). Increasing the FPG cut point to 6.1 mmol/l (110 mg/dl) or using Hb[A.sub.1c], instead of FPG to determine the need for an OGTT in people with risk factors reduced sensitivity, increased specificity and PPV, and reduced the proportion requiring an OGTT. However, each of these protocol variations substantially reduced the detection of IGT or IFG.

CONCLUSIONS--The Australian screening protocol identified one new case of diabetes for every 32 people screened, with 4 of 10 people screened requiring FPG measurement and 1 in 5 requiring an OGTT. In addition, 1 in 11 people screened had IGT or IFG. Including Hb[A.sub.1c] measurement substantially reduced both the number requiring an OGTT and the detection of IGT or IFG.

Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet

The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-α, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-β, and PPAR-γ) and BT (C/EBP-β), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-γ genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.

Are barriers to physical activity similar for adults with and without abnormal glucose Metabolism?

Purpose The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status.
Methods The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged ≥25 years. AGM was identified through an oral glucose tolerance test. The previous week’s physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity.
Results Of the 7088 participants (47.5 ± 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P < .001). Key barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity.
Conclusions Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.

Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse.

RATIONALE: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on the use of high fat-fed rodent models and typically involve the determination of muscle glucose uptake under insulin-stimulated conditions. While insightful, they do not necessarily reflect the physiology of the postprandial state. In addition, most studies do not examine aspects of glucose metabolism beyond the uptake process. Here we present an approach to study rodent muscle glucose and intermediary metabolism under the dynamic and physiologically relevant setting of the oral glucose tolerance test (OGTT). METHODS AND RESULTS: In vivo muscle glucose and intermediary metabolism was investigated following oral administration of [U-(13)C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring (13)C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates via gas chromatography-mass spectrometry. While no dietary effects were noted in the glycolytic pathway, muscle from mice fed a high fat diet (HFD) exhibited a reduction in labelling in TCA intermediates. Interestingly, this appeared to be independent of alterations in flux through pyruvate dehydrogenase. In addition, our findings suggest that TCA cycle anaplerosis is negligible in muscle during an OGTT. CONCLUSIONS: Under the dynamic physiologically relevant conditions of the OGTT, skeletal muscle from HFD fed mice exhibits alterations in glucose metabolism at the level of the TCA cycle.

The intravenous glucose tolerance and postprandial glucose tests may present different responses in the evaluation of obese dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

THE ASSESSMENT OF ZINC STATUS BY THE ZINC TOLERANCE-TEST IN THYROID-DISEASE

Zinc status was evaluated in 12 hyperthyroid and in 7 hypothyroid patients in comparison with 8 euthyroid individuals by the oral zinc tolerance test and by the determination of urinary zinc excretion. Hyperthyroid patients presented a basal serum concentration similar to that of euthyroid individuals but greater urinary zinc excretion, indicating the occurrence of zinc depletion from tissues to the blood stream caused by the catabolism inherent in the hyperthyroid state. Hyperthyroidism also caused lower zinc assimilation by tissues after zinc ingestion. Hypothyroid individuals present lower basal zinc levels in serum than euthyroid and hyperthyroid individuals and urinary zinc excretion similar to that of euthyroid individuals. No changes in the parameters measured were observed after zinc load, suggesting reduced or delayed intestinal absorption and zinc assimilation by tissues. The present data are indicative of zinc deficiency, the lower intestinal zinc absorption probably being one of the contributing factors.