OBJECTIVE Insulin increases glucose disposal in part by enhancing microvascular blood flow (MBF) and substrate delivery to myocytes. Insulin’s microvascular action is impaired with insulin resistance and type 2 diabetes. Resistance training (RT) improves glycemic control and insulin sensitivity, but whether this improvement is linked to augmented skeletal muscle microvascular responses in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS Seventeen (11 male and 6 female; 52 ± 2 years old) sedentary patients with type 2 diabetes underwent 6 weeks of whole-body RT. Before and after RT, participants who fasted overnight had clinical chemistries measured (lipids, glucose, HbA1c, insulin, and advanced glycation end products) and underwent an oral glucose challenge (OGC) (50 g × 2 h). Forearm muscle MBF was assessed by contrast-enhanced ultrasound, skin MBF by laser Doppler flowmetry, and brachial artery flow by Doppler ultrasound at baseline and 60 min post-OGC. A whole-body DEXA scan before and after RT assessed body composition. RESULTS After RT, muscle MBF response to the OGC increased, while skin microvascular responses were unchanged. These microvascular adaptations were accompanied by improved glycemic control (fasting blood glucose, HbA1c, and glucose area under the curve [AUC] during OGC) and increased lean body mass and reductions in fasting plasma triglyceride, total cholesterol, advanced glycation end products, and total body fat. Changes in muscle MBF response after RT significantly correlated with reductions in fasting blood glucose, HbA1c, and OGC AUC with adjustment for age, sex, % body fat, and % lean mass. CONCLUSIONS RT improves OGC-stimulated muscle MBF and glycemic control concomitantly, suggesting that MBF plays a role in improved glycemic control from RT.
The purpose of this article was to examine metabolic risk factors for type 2 diabetes in children and adolescents as a function of maternal versus paternal family history of type 2 diabetes and to examine whether differences in these risk factors emerge during adolescent growth.A total of 247 overweight Latino children (baseline age = 11.1 +/- 1.7 years) with a parental history of type 2 diabetes were followed annually for 5 years (2.2 +/- 1.2 observations/child) with measures of insulin sensitivity, acute insulin response to glucose, and disposition index. Longitudinal linear mixed-effects modeling was used to evaluate the influence of maternal versus paternal family history of type 2 diabetes on changes in diabetes risk factors over age.Insulin sensitivity and the disposition index decreased over age (beta = -0.052 and beta = -0.033, P < 0 0.01). Acute insulin response to glucose and fasting and 2-h glucose increased (beta = 0.019, beta = 0.002, and beta = 0.003, P < 0.01). Declines in insulin sensitivity were significantly greater in participants whose maternal grandmothers had a history of type 2 diabetes (beta = -0.03, P = 0.03). Declines in the disposition index (beta = -0.02, P = 0.04) and increases in fasting glucose were significantly influenced by a maternal history of type 2 diabetes (beta = 0.60, P < 0.05).Maternal but not paternal family history for diabetes may have a significant impact on insulin dynamics, becoming more pronounced during growth in overweight Latino adolescents. Further research is clearly warranted.
PURPOSE: There is an ongoing debate as to the relative impact of fat and sugar on health outcomes. We tested the influence of dietary factors on insulin sensitivity in an animal model of metabolic syndrome. METHODS: Starting at 2 months of age for 2 months, female Fischer rats were fed either standard low-fat, complex-carbohydrate (LFCC) chow, or diets containing increased fat (high in saturated and monounsaturated fat, primarily from lard plus a small amount of corn oil, HFCC), sucrose (LFS), or both (HFS). An additional group fed HFS performed treadmill exercise training 5 days/week (HFS + exercise). RESULTS: Compared to LFCC controls (mean±SE, 12.15±1.24 mg/dL * uU/mL * min2 *10-7), consumption of LFS (20.30±1.07 mg/dL * uU/mL * min2 *10-7; p<0.001), but not HFCC (14.45±0.89 mg/dL * uU/mL * min2 *10-7), increased glucose x insulin area under the curve (AUCglucose*insulin) during an intravenous glucose tolerance test (IVGTT). HFS (30.05±0.81 mg/dL * uU/mL * min2 *10-7) elicited greater AUCglucose*insulin than all other diets (all p“0.001). When insulin sensitivity was estimated by the Matsuda insulin sensitivity index (ISI), relationships were generally similar, except that the HFCC group exhibited lower ISI (9.53±1.17) than LFCC (15.76±1.97; p<0.01), LFS (6.73±0.79) was similar to HFCC, and HFS (4.25±0.56) was similar to LFS. Exercise partially ameliorated the insulin resistance-inducing effects of HFS diet consumption (HFS + exercise: 22.13±0.03 mg/dL * uU/mL * min2 *10-7, p<0.001). Estimates based on fasting glucose and insulin were generally similar, but not as sensitive as insulin sensitivity from the IVGTT. CONCLUSION: Although refined sugar and fat both induce insulin resistance in rats, refined-sugar tended to induce insulin resistance more than fat when each was consumed in isolation. The combination elicited the greatest degree of insulin resistance. Exercise training partially ameliorated, but did not normalize the effects of the HFS diet. Finally, the method of estimation of insulin resistance may impact study findings and interpretation.
The aim of the present study was to analyze the effects of age on cardiorespiratory fitness (CRF), muscle strength and heart rate (HR) response to exercise adaptation in women in response to a long-term twice-weekly combined aerobic and resistance exercise program. 85 sedentary women, divided into young (YG; n=22, 30.3±6.2 years), early middle-aged (EMG; n=28, 44.1±2.5 years), late middle-aged (LMG; n=20, 56.7±3.5 years) and older (OG; n=15, 71.4±6.9 years) groups, had their CRF, muscle strength (1-repetition maximum test) and HR response to exercise (graded exercise test) measured before and after 12 months of combined exercise training. Exercise training improved CRF and muscle strength in all age groups (P<0.05), and no significant differences were observed between groups. Exercise training also improved resting HR and recovery HR in YG and EMG (P<0.05), but not in LMG and OG. Maximal HR did not change in any group. Combined aerobic and resistance training at a frequency of 2 days/week improves CRF and muscle strength throughout the lifespan. However, exercise-induced improvements in the HR recovery response to exercise may be impaired in late middle-aged and older women.
The present study was designed to examine the effects of a short‐term diet/exercise program on markers of metabolic health and serum lipomics. 33 overweight children (15 boys, 18 girls, age 12.3±0.4 yr), were placed on an ad libitum, high‐fiber, low‐fat diet and daily exercise (2–2.5 hr) regimen in the Pritikin Longevity Center 2‐wk program. Fasting serum was taken pre‐ and post‐intervention for determination of glucose, lipids, metabolic risk markers, and lipomic analysis by gas chromatography. After 2 wks subjects lost weight (73.0±6.2 post vs. 75.7±6.5 kg pre) but remained overweight/obese (BMI: 27.2±1.7 vs. 28.2±1.8 kg/m 2 ). Despite remaining overweight, no subjects had metabolic syndrome post‐ compared with 8 pre‐intervention. RHR and BP decreased significantly, p<0.005. Serum TG, Total‐C, LDL (p<0.0001), PAI‐1, resistin, leptin (p<0.001), HDL, IL‐8, amylin and insulin (p<0.05) decreased significantly. Serum IL‐10 (p=0.14) and IL‐1ra (p=0.29) increased and VEGF (p=0.07) decreased non‐significantly. Lipomic analysis revealed decreases in total lipids (79% of baseline), saturated fatty acids (14:0, 82%, 18:0, 87% and 20:0, 33%), and increases in 20:1 (125%), 22:6 (144%) and 18:1/18:0 (114%), all p<0.05. These results indicate changes in multiple indices of metabolic health and serum lipomics with short‐term, rigorous lifestyle modification, even in the face of remaining overweight/obese. This study was supported by a grant from the L‐B Research/Education Foundation and funding from UCLA.
0991 PURPOSE: Testosterone supplementation increases muscle mass and strength and regulates other physiological processes, however the effects of testosterone on cardiovascular risk is controversial. METHODS: To prospectively determine the effects of graded doses of testosterone on 8-isoprostane PGF-2α (8-ISO), soluble intracellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1), 121 eugonadal men, (61, 18–35 yr and 60, 60–75 yr) were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 weeks. Energy and protein intakes were standardized. RESULTS: The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl, in the younger men and 176, 274, 852, 1784 and 3286 ng/dl in the older men at the 25-, 50-, 125-, 300-, and 600- mg doses, respectively. Using a multiple regression model for marker change which includes terms for baseline atherogenic marker level, change in testosterone level, age group, interaction between age group and testosterone level, and testosterone dose group, for 8-ISO, the baseline value was significantly negatively correlated with 8-ISO change (p < 0.0001) and age group was significant (p = 0.03, older group had a larger decline). For sICAM-1, there were no significant effects (p > 0.05 in all cases). For MCP-1, baseline MCP-1 was negatively correlated with MCP-1 change (p < 0.02). That is, the larger the baseline MCP-1 level, the greater the decline in MCP-1. CONCLUSIONS: These data provide evidence against potential adverse cardiovascular effects of androgens. Long-term studies are needed to determine whether testosterone supplementation of older men with low testosterone levels affects atherosclerosis progression.
We examined the impact of strength fitness and body weight on the redox properties of high-density lipoprotein (HDL) and associations with indices of vascular and metabolic health. Ninety young men were categorized into three groups: 1) overweight untrained (OU; n = 30; BMI 30.7 ± 2.1 kg/m(2)); 2) overweight trained [OT; n = 30; BMI 29.0 ± 1.9; ≥4 d/wk resistance training (RT)]; and 3) lean trained (LT; n = 30; BMI 23.7 ± 1.4; ≥4 d/wk RT). Using a novel assay on the basis of the HDL-mediated rate of oxidation of dihydrorhodamine (DOR), we determined the functional (redox) properties of HDL and examined correlations between DOR and indices of vascular and metabolic health in the cohort. DOR was significantly lower in both trained groups compared with the untrained group (LT, 1.04 ± 0.49; OT, 1.39 ± 0.57; OU, 1.80 ± 0.74; LT vs. OU P < 0.00001; OT vs. OU P = 0.02), however, DOR in the OT group was not significantly different from that of the LT group. DOR was negatively associated with HDL-cholesterol (R = -0.64), relative strength (R = -0.42), sex hormone-binding globulin (R = -0.42), and testosterone (R = -0.35) (all P ≤ 0.001); whereas DOR was positively associated with triglycerides (R = 0.39, P = 0.002), oxidized low-density lipoprotein (R = 0.32), body mass index (R = 0.43), total mass (R = 0.35), total fat mass (R = 0.42), waist circumference (R = 0.45), and trunk fat mass (R = 0.42) (all P ≤ 0.001). Chronic RT is associated with improved HDL redox activity. This may contribute to the beneficial effects of RT on reducing cardiovascular disease risk, irrespective of body weight status.
Current cell-based assays for determining the functional properties of high-density lipoproteins (HDL) have limitations. We report here the development of a new, robust fluorometric cell-free biochemical assay that measures HDL lipid peroxidation (HDLox) based on the oxidation of the fluorochrome Amplex Red. HDLox correlated with previously validated cell-based (r = 0.47, p<0.001) and cell-free assays (r = 0.46, p<0.001). HDLox distinguished dysfunctional HDL in established animal models of atherosclerosis and Human Immunodeficiency Virus (HIV) patients. Using an immunoaffinity method for capturing HDL, we demonstrate the utility of this novel assay for measuring HDLox in a high throughput format. Furthermore, HDLox correlated significantly with measures of cardiovascular diseases including carotid intima media thickness (r = 0.35, p<0.01) and subendocardial viability ratio (r = -0.21, p = 0.05) and physiological parameters such as metabolic and anthropometric parameters (p<0.05). In conclusion, we report the development of a new fluorometric method that offers a reproducible and rapid means for determining HDL function/quality that is suitable for high throughput implementation.
The efficacy of exercise training systems designed to be used in the home on cardiometabolic outcomes remains largely unknown. This investigation included two studies. Study 1 tested the effects a multi-exercise pulley system (NordicTrack Fusion CST with video trainer) and Study 2 an incline trainer (NordicTrack X22i with video trainer), both combined with daily food provision, for 12-weeks on indices of cardiometabolic health. Study 1 enrolled 27 adults (11 men, 16 women, 33.8±4.4 years of age) and Study 2 enrolled 29 adults (11 men, 18 women, 40.8±12.5 years of age). Pre- and post-intervention measurements were performed for body weight, fat mass, lean tissue mass, and visceral fat by dual energy x-ray absorptiometry, blood pressure, aerobic fitness and body circumferences. For Study 1, there were significant decreases in body weight, fat mass, visceral fat, diastolic blood pressure (DBP), resting heart rate (RHR), and all circumference sites, while there was an increase in aerobic fitness (all p<0.001). Both males and females exhibited significant improvement in all these outcomes. For Study 2, there were significant decreases in body weight, fat mass, visceral fat, DBP, RHR, all circumference sites (all p<0.001), and lean tissue mass (LTM) (p=0.006), and an increase in aerobic fitness (p<0.001). Both males and females exhibited significant changes in all these outcomes, except LTM which did not change in females. Both studies exhibited high exercise session attendance and high dietary adherence. Overall these data indicate the potential efficacy of home-based training systems, when combined with diet, on selected cardiometabolic outcomes.
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