Postprandial whole-body glycolysis is similar in insulin-resistant and insulin-sensitive non-diabetic humans.

AIMS/HYPOTHESIS: Insulin resistance is characterised by impaired glucose utilisation when measured by a euglycaemic-hyperinsulinaemic clamp. We hypothesised that, in response to postprandial conditions, non-diabetic individuals would have similar intracellular glycolytic and oxidative glucose metabolism independent of the degree of insulin resistance. METHODS: Fourteen (seven male) sedentary, insulin-sensitive participants (mean ± SD: BMI 25 ± 4 kg/m²; age 39 ± 10 years; glucose disposal rate 9.4 ± 2.1 mg [kg estimated metabolic body size]⁻¹ min⁻¹) and 14 (six male) sedentary, non-diabetic, insulin-resistant volunteers (29 ± 4 kg/m²; 34 ± 13 years; 5.3 ± 1.2 mg [kg estimated metabolic body size]⁻¹ min⁻¹) received after a 10 h fast 60 g glucose plus 15 g [6,6-²H2]glucose. Serum glucose and insulin concentrations, plasma ²H enrichment and whole-body gas exchange were determined before glucose ingestion and hourly thereafter for 4 h. Plasma ²H2O production is an index of glycolytic disposal. On day 2, participants received a weight-maintenance diet. On day 3, a euglycaemic-hyperinsulinaemic clamp was performed. RESULTS: Insulin-resistant individuals had about a twofold higher postprandial insulin response than insulin-sensitive individuals (p = 0.003). Resting metabolic rate was similar in the two groups before (p = 0.29) and after (p = 0.33-0.99 over time) glucose ingestion, whereas a trend for blunted glucose-induced thermogenesis was observed in insulin-resistant vs insulin-sensitive individuals (p = 0.06). However, over the 4 h after the 75 g glucose ingestion, glycolytic glucose disposal was the same in insulin-sensitive and insulin-resistant individuals (36.5 ± 3.7 and 36.2 ± 6.4 mmol, respectively; p = 0.99). Similarly, whole-body carbohydrate oxidation did not differ between the groups either before or after glucose ingestion (p = 0.41). CONCLUSIONS/INTERPRETATION: Postprandial hyperinsulinaemia and modest hyperglycaemia overcome insulin resistance by enhancing tissue glucose uptake and intracellular glucose utilisation.

Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of Type 2 diabetes.

AIMS/HYPOTHESIS: The recent discovery of two adiponectin receptors (AdipoR1 and AdipoR2) will improve our understanding of the molecular mechanisms underlying the insulin-sensitising effect of adiponectin. The aim of this study was to determine for the first time whether skeletal muscle AdipoR1 and/or AdipoR2 gene expression levels are associated with insulin resistance. METHODS: Using RT-PCR and northern analysis we measured AdipoR1 and AdipoR2 gene expression in skeletal muscle from healthy Mexican Americans with normal glucose tolerance who had (n=8) or did not have (n=10) a family history of Type 2 diabetes. RESULTS: Gene expression profiling indicated that the AdipoR1 and AdipoR2 isoforms are highly expressed in human skeletal muscle, unlike in mice where AdipoR2 expression was highest in the liver, and AdipoR1 was highest in skeletal muscle. In the study subjects, the expression levels of AdipoR1 (p=0.004) and AdipoR2 (p=0.04), as well as plasma adiponectin concentration (p=0.03) were lower in people with a family history of Type 2 diabetes than in those with no family history of the disease. Importantly, the expression levels of both receptors correlated positively with insulin sensitivity (r=0.64, p=0.004 and r=0.47, p=0.048 respectively). CONCLUSIONS/INTERPRETATION: Collectively, these data indicate that both isoforms of the adiponectin receptor play a role in the insulin-sensitising effect of adiponectin.

Low plasma leptin concentration and low rates of fat oxidation in weight-stable post-obese subjects.

OBJECTIVE: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post-obese adults (2 males and 6 females; 48.9 +/- 12.2 years; body mass index [BMI]: 24.5 +/- 1.0 kg/m2; body fat 33 +/- 5%; mean +/- SD) who lost 27.1 +/- 21.3 kg (16 to 79 kg) and had maintained this weight loss for > or =2 months (2 to 9 months) to eight age- and BMI-matched control never-obese subjects (1 male and 7 females; 49.1 +/- 5.2 years; BMI 24.4 +/- 1.0 kg/m2; body fat 33 +/- 7%). RESEARCH METHODS AND PROCEDURES: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10-hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48-hour period in free living conditions. RESULTS: After adjustment for fat mass and fat-free mass, post-obese subjects had, compared with controls, similar levels of physical activity (4185 +/- 205 vs. 4295 +/- 204 counts) and similar RMR (1383 +/- 268 vs. 1430 +/- 104 kcal/day) but higher RQ (0.86 +/- 0.04 vs. 0.81 +/- 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat-free mass, was lower in post-obese than in control subjects (4.5 +/- 2.1 vs. 11.6 +/- 7.9 ng/mL, p < 0.05). DISCUSSION: The low fat oxidation and low plasma leptin concentrations observed in post-obese individuals may, in part, explain their propensity to relapse.

Daily energy expenditure in Mexican and USA Pima indians: low physical activity as a possible cause of obesity.

BACKGROUND: Obesity is caused by an imbalance between energy intake and energy expenditure. However, it is unknown whether increased physical activity protects susceptible populations against the development of obesity and type 2 diabetes. OBJECTIVE: To investigate the potential protective role of environment and physical activity against obesity by measuring total energy expenditure in Mexican and USA Pima Indians. METHODS: We compared the physical activity level of 40 (17 female and 23 male; 37+/-11 y, 66+/-13 kg) Mexican Pima Indians from a remote, mountainous area of Northwest Mexico, with 40 age-and-sex matched (17 female and 23 male; 37+/-12 y, 93+/-22 kg) Pima Indians from the Gila River Indian Community in Arizona, USA. We measured total energy expenditure (TEE) by doubly labeled water and calculated physical activity by different methods: physical activity level (PAL) as the ratio of TEE on resting metabolic rate (RMR), TEE adjusted for RMR by linear regression, activity energy expenditure adjusted for body weight (AEE), and activity questionnaire. RESULTS: Physical activity was higher in Mexican Pima Indians when compared with USA Pima Indians as assessed by PAL (1.97+/-0.34 vs 1.57+/-0.16, P<0.0001), TEE adjusted for RMR (3289+/-454 vs 2671+/-454 kcal/day, P<0.0001) and AEE adjusted for body weight (1243+/-415 vs 711+/-415 kcal/day, P<0. 0001). Questionnaires revealed more time spent on occupational activities among Mexican Pima compared with USA Pima (23.9+/-13.3 vs 12.6+/-13.9 h/week, P<0.001). CONCLUSION: These data support a significant role for physical activity in the prevention of obesity in genetically susceptible populations. International Journal of Obesity (2000)24, 55-59

Plasma leptin concentrations in Pima Indians living in drastically different environments.

OBJECTIVE: Plasma leptin, an important signal for the regulation of energy stores, is known to be influenced by many hormonal factors, but may also be affected by behavioral and environmental factors. The purpose of this study was to investigate the impact of lifestyle (diet composition, level of physical activity) on plasma leptin concentrations among Pima Indians living in drastically different environments. RESEARCH DESIGN AND METHODS: We studied 224 Mexican Pima Indians (115 women, 109 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 418 U.S. Pima Indians (281 women, 137 men) living a North American lifestyle on the Gila River Indian Reservation in Arizona. We hypothesized that the absolute value of leptin would be lower in Mexican Pima Indians because of their lower percent body fat, but could be further influenced by their lifestyle, independent of body composition. RESULTS: Leptin concentration (enzyme-linked immunosorbent assay [ELISA]) was strongly correlated with percent fat (bioimpedance) in Mexican Pima Indians (r = 0.83, P < 0.0001) and U.S. Pima Indians (r = 0.86, P < 0.0001). Among U.S. Pima Indians, independent of percent fat, subjects with type 2 diabetes had lower leptin than nondiabetic subjects (difference = 6.9 +/- 1.0 ng/ml, P < 0.002). Among nondiabetic subjects, Mexican Pima Indians had lower absolute leptin concentrations than U.S. Pima Indians, but higher after adjustment for percent body fat, waist circumference, age, and sex. In a subset of 70 pairs of subjects matched for sex and percent body fat, leptin concentration was 4.4 +/- 1.0 ng/ml (P < 0.0001) higher in Mexican Pima Indians versus U.S. Pima Indians. CONCLUSIONS: These results suggest that independent of body composition, leptin concentration may be increased by environmental factors, such as a high-carbohydrate diet and a high level of physical activity.

Is a low leptin concentration, a low resting metabolic rate, or both the expression of the "thrifty genotype"? Results from Mexican Pima Indians.

BACKGROUND: The high prevalence of obesity and type 2 diabetes in some populations is believed to be the expression of a "thrifty genotype," which conferred survival advantages during periods of harsh environmental conditions, but has become a liability in industrialized environments of abundance. Low plasma leptin concentrations and a low metabolic rate may be the phenotypic expression of this genotype. OBJECTIVE: We hypothesized that plasma leptin concentrations and resting metabolic rate would be lower in Mexican Pima Indians not yet exposed to an affluent lifestyle than in non-Pima Mexicans living in the same environment. DESIGN: We studied 208 nondiabetic Pima Indians (105 women and 103 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 183 nondiabetic non-Pima Mexicans (90 women and 93 men) living in the same environment. A subset of 40 (17 women and 23 men) Pima Indians and 40 (19 women and 21 men) non-Pima Mexicans was selected for studies of energy metabolism with a ventilated-hood system. RESULTS: Leptin concentrations were strongly correlated with percentage body fat in both groups (r = 0.83, P < 0.0001). There was no significant difference in plasma leptin concentration between groups in absolute value (P = 0.90) or after adjustment for percentage body fat, waist circumference, age, and sex (P = 0.40). Similarly, there was no significant difference in resting metabolic rate between groups in absolute value (P = 0.27) or after adjustment for fat-free mass (P = 0.32). CONCLUSIONS: These results do not support the hypothesis that hypoleptinemia, a relatively low resting metabolic rate, or both are expressions of the thrifty genotype.

Low levels of physical activity in 5-year-old children.

As the prevalence of obesity in Western societies has increased to disturbing levels, interest in the role of physical inactivity in promoting this trend has increased. We assessed physical activity energy expenditure (AEE) in 127 5-year-old children, 43 of whom were white children and 84 Pima Indian children; the latter group represents a population with an extremely high prevalence of obesity. Total energy expenditure (TEE) and resting metabolic rate (RMR) were measured by the doubly labeled water method and indirect calorimetry, respectively. From these measured values, different indexes of physical activity were calculated, including AEE = TEE-(RMR + 0.1 x TEE) and physical activity level (PAL = TEE/RMR). By the age of 5 years, Pima Indian children were significantly heavier (23.0 +/- 5.3 kg vs 19.1 +/- 2.6 kg) and fatter (30 +/- 7% vs 21 +/- 5% body fat) than white children (p < 0.0001), whereas TEE (5996 +/- 1005 kJ/day vs 5690 +/- 760 kJ/day) and RMR (4431 +/- 625 kJ/day vs 4236 +/- 534 kJ/day) were similar in the 2 groups in both absolute values and after adjustment for fat-free mass, fat mass, and sex. Both white and Pima Indian children had physical activity levels 20% to 30% lower (PAL = 1.35 +/- 0.13) than currently recommended by the World Health Organization (1.7 to 2.0). However, the different calculated indexes of physical activity were comparable in the two racial groups. Differences in TEE or AEE are unlikely to explain the obesity seen in Pima Indian children at a later age, suggesting that excess food intake is likely to play a major role in the cause of obesity in this obesity-prone population. However, both white and Pima Indian children have surprisingly low levels of physical activity, a condition that portends poorly for the prevention of obesity in adulthood.

Effects of a traditional lifestyle on obesity in Pima Indians.

OBJECTIVE: The Pima Indians of Arizona have the highest reported prevalences of obesity and non-insulin-dependent diabetes mellitus (NIDDM). In parallel with abrupt changes in lifestyle, these prevalences in Arizona Pimas have increased to epidemic proportions during the past decades. To assess the possible impact of the environment on the prevalences of obesity and NIDDM, data were collected on members of a population of Pima ancestry (separation 700-1,000 years ago) living in a remote mountainous location in northwestern Mexico, with a lifestyle contrasting markedly with that in Arizona. RESEARCH DESIGN AND METHODS: Pima heritage was established by history and by use of Pima language. Measurements of weight, height, body fat (bioimpedance), blood pressure, plasma levels of glucose, cholesterol, and HbA1c were obtained in 19 women (36 +/- 13 years of age) and 16 men (48 +/- 14 years of age) and compared with sex-, age- and diabetes status-matched Pimas living in Arizona (10 Arizona Pimas for each Mexican Pima). RESULTS: Mexican Pimas were lighter (64.2 +/- 13.9 vs. 90.2 +/- 21.1 kg, P < 0.0001; means +/- SD) and shorter (160 +/- 8 vs. 164 +/- 8 cm, P < 0.01) with lower body mass indexes (24.9 +/- 4.0 vs. 33.4 +/- 7.5 kg/m2, P < 0.0001) and lower plasma total cholesterol levels (146 +/- 30 vs. 174 +/- 31 mg/dl, P < 0.0001) than Arizona Pimas. Only two women (11%) and one man (6%) had NIDDM, contrasting with the expected prevalences of 37 and 54% in female and male Arizona Pimas, respectively. CONCLUSIONS: This preliminary investigation shows that obesity, and perhaps NIDDM, is less prevalent among people of Pima heritage living a "traditional" lifestyle than among Pimas living in an "affluent" environment. These findings suggest that, despite a similar potential genetic predisposition to these conditions, a traditional lifestyle, characterized by a diet including less animal fat and more complex carbohydrates and by greater energy expenditure in physical labor, may protect against the development of cardiovascular disease risk factors, obesity, and NIDDM.

Daily energy expenditure by five-year-old children, measured by doubly labeled water.

Current recommendations for daily energy requirements in 5-year-old children (90 kcal/kg per day) are based on energy intake associated with normal growth. It is not known, however, how these recommendations compare with total free-living energy expenditure (TEE) and how much of TEE is related to physical activity. The TEE and the resting metabolic rate (RMR) were measured in 28 white children, aged 5 years (15 boys, 13 girls; mean (+/- SD) weight 20.1 +/- 3.4 kg; height 113 +/- 6 cm; fat 20% +/- 5%). The TEE was calculated during a 7-day period from urinary elimination rates of deuterium (2H) and heavy oxygen (18O) by using a modification of the two-point slope-intercept method; RMR was measured by a ventilated-hood indirect calorimeter. Physical activity indexes were also collected from questionnaires completed by the parents. Measured TEE was considerably lower than the recommended dietary allowances (1370 +/- 222 kcal/day vs 1807 +/- 310 kcal/day; p < 0.0001), whereas measured RMR was slightly higher than predicted RMR (1001 +/- 119 kcal/day vs 952 +/- 78 kcal/day; p < 0.001). The energy cost of physical activity accounted for only 16% +/- 7% of TEE. An index of activity, assessed as the difference between the measured TEE and the predicted TEE, correlated positively with past-year sport-leisure activity assessed by questionnaire (r = 0.40; p < 0.05). We conclude that measured TEE in 5-year-old children yields lower values (approximately 400 kcal/day) than current estimates. A minute part of this difference (20 to 30 kcal/day) is related to the changes in energy stores during growth, but most seems due to lower-than-expected levels of physical activity. This might be related to increased television viewing, which replaces activities requiring energy.