Insulin sensitivity determines the effectiveness of dietary macronutrient composition on weight loss in obese women

OBJECTIVE: To determine whether macronutrient composition of a hypocaloric diet can enhance its effectiveness and whether insulin sensitivity (Si) affects the response to hypocaloric diets. RESEARCH METHODS AND PROCEDURES: Obese nondiabetic insulin-sensitive (fasting insulin < 10 microU/mL; n = 12) and obese nondiabetic insulin-resistant (fasting insulin > 15 microU/mL; n = 9) women (23 to 53 years old) were randomized to either a high carbohydrate (CHO) (HC)/low fat (LF) (60% CHO, 20% fat) or low CHO (LC)/high fat (HF) (40% CHO, 40% fat) hypocaloric diet. Primary outcome measures after a 16-week dietary intervention were: changes in body weight (BW), Si, resting metabolic rate, and fasting lipids. RESULTS: Insulin-sensitive women on the HC/LF diet lost 13.5 +/- 1.2% (p < 0.001) of their initial BW, whereas those on the LC/HF diet lost 6.8 +/- 1.2% (p < 0.001; p < 0.002 between the groups). In contrast, among the insulin-resistant women, those on the LC/HF diet lost 13.4 +/- 1.3% (p < 0.001) of their initial BW as compared with 8.5 +/- 1.4% (p < 0.001) lost by those on the HC/LF diet (p < 0.04 between two groups). These differences could not be explained by changes in resting metabolic rate, activity, or intake. Overall, changes in Si were associated with the degree of weight loss (r = -0.57, p < 0.05). DISCUSSION: The state of Si determines the effectiveness of macronutrient composition of hypocaloric diets in obese women. For maximal benefit, the macronutrient composition of a hypocaloric diet may need to be adjusted to correspond to the state of Si.     

Racial differences in insulin secretion and sensitivity in prepubertal children: role of physical fitness and physical activity

OBJECTIVE: To investigate in prepubertal children whether physical fitness and/or physical activity are: 1) associated with insulin secretion and sensitivity and 2) account for racial differences in insulin secretion and sensitivity. RESEARCH METHODS AND PROCEDURES: Subjects included 34 African American and 34 white nondiabetic children aged 5 to 11 years. Data were divided into two sets according to the availability of VO2max and physical activity data. Body composition was measured by dual-energy X-ray absorptiometry. Subcutaneous abdominal adipose tissue and intra-abdominal adipose tissue were examined by computed tomography. Insulin sensitivity (S1) and acute insulin response (AIR) were determined by a frequently sampled intravenous glucose tolerance test. An all-out, progressive treadmill exercise test was used for measuring VO2max. Physical activity data were collected by questionnaire. RESULTS: African American children had lower SI and higher AIR than white children, after adjusting for total body fat mass. African Americans reported higher levels of physical activity (hours/wk) than whites, but had a lower VO2max. In multiple linear regression analysis, hours/wk of activity and hours/wk of vigorous activity, but not moderate activity, were independently related to SI and AIR after adjusting for race, total body fat mass or fat distribution, and total lean tissue mass. VO2max was not related to AIR, and was inversely related to SI, after adjusting for body composition. Race remained significantly associated with both SI and AIR, even after adjusting for body composition, fat distribution, and hours/wk of activity or hours/wk of vigorous activity. DISCUSSION: In summary, overall physical activity and, especially, vigorous activity were associated with insulin secretion and sensitivity. However, neither physical activity nor VO2max explained the racial difference in insulin secretion (higher in African Americans) and sensitivity (lower in African Americans). Thus, racial (African American to white) differences in aspects of insulin action seem to be due to factors other than body composition, fat distribution, cardiovascular fitness, and amount of physical activity.     

Comparison of regional fat distribution and health risk factors in middle-aged white and African American women: The Healthy Transitions Study

OBJECTIVE: Both ethnicity and menopause appear to influence intra-abdominal fat distribution. This study evaluated intra-abdominal fat distribution and obesity-related health risks in perimenopausal white and African American women. RESEARCH METHODS AND PROCEDURES: Baseline data from a longitudinal study of changes in body composition and energy balance during menopause are reported. Healthy women (55 African Americans and 103 whites) who were on no medication and had at least five menstrual cycles in the previous 6 months were recruited. Body composition was assessed by DXA, and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography scan. SAT was divided into deep and superficial layers demarcated by the fascia superficialis. RESULTS: African American women were slightly younger (46.7 +/- 0.2 vs. 47.7 +/- 0.2 years, p = 0.002) and fatter (42.4% +/- 1.0% vs. 39.4% +/- 0.8% body fat, p = 0.02) than white women. In unadjusted data, African Americans had significantly more total abdominal fat and total, deep, and superficial SAT than whites. After adjustment for percent body fat and age, only total and superficial SAT remained significantly higher in African Americans. VAT, although slightly less in African American women, did not differ significantly by race. In multiple regression analysis, VAT was the strongest predictor of serum lipids, glucose, and insulin in women of both races, although superficial SAT was significantly associated with fasting glucose in whites. CONCLUSIONS: Middle-aged African American women have larger SAT depots, adjusted for total body fatness, but do not differ from white women with regard to VAT. The complexity of the relationship between abdominal fat and metabolic risk is increased by ethnic differences in such associations.     

Anti-lipolytic effects of insulin in African American and white prepubertal boys

OBJECTIVE: Relative to whites, African Americans have lower circulating triglycerides (TG) and greater highdensity lipoprotein cholesterol. The metabolic basis for this difference is not known. This study was conducted to test the hypothesis that insulin-induced suppression of free fatty acids (FFA) results in lower serum TG in African American versus white prepubertal children. RESEARCH METHODS AND PROCEDURES: Insulin, FFA, and TG were determined at baseline and during a frequently sampled, intravenous glucose tolerance test in eight African American and eight white prepubertal males pair-matched for whole-body insulin sensitivity. RESULTS: Baseline TG was lower in African Americans (0.43 +/- 0.10 vs. 0.79 +/- 0.37 mM/L; mean +/- SD; p < 0.01). African Americans had higher peak insulin (218 +/- 102 vs. 100 +/- 30 pM/L; mean +/- SD; p < 0.01) and a greater acute insulin response (9282 +/- 4272 vs. 4230 +/- 1326 pM/L x 10 minutes; mean +/- SD; p < 0.05). FFA and TG values determined at the FFA nadir were lower in African Americans (0.26 +/- 0.02 vs. 0.30 +/- 0.03 mEq/L; mean +/- SD; p < 0.01 for FFA nadir and 0.49 +/- 0.07 vs. 0.77 +/- 0.33 mM/L; mean +/- SD; p < 0.05 for TG). Among all subjects, FFA nadir was correlated with peak insulin (r = -0.54; p < 0.05). After adjusting for FFA nadir, neither baseline nor postchallenge TG differed with ethnicity (p = 0.073 and 0.192, respectively). The ethnic difference in FFA nadir disappeared after adjusting for peak insulin (p = 0.073). DISCUSSION: These data suggest that hyperinsulinemiainduced suppression of FFA among African Americans is a determinant of lower TG in this group.     

The frequency of Trp64Arg polymorphism of the beta3-adrenergic receptor gene in healthy and obese Hungarian children and its association with cardiovascular risk factors

OBJECTIVE: To estimate the frequency of Arg64 allele of the beta(3)-adrenergic receptor (3-BAR) gene in healthy (H) and obese (O) Hungarian children, and to look for possible associations between this polymorphism and some clinical and metabolic characteristics of obese children. PATIENTS/METHODS: In all, 147 healthy (male: 68) and 295 obese (male: 168) children were examined. The average age of the children in the two groups was 12.4+/-1.7 vs 12.6+/-3.2, respectively. Exon 1 of 3-BAR was amplified by polymerase chain reaction and the fragments were digested with BstN1. In obese children, oral glucose tolerance test was carried out and blood pressure (BP) was checked. RESULTS: The frequency of Trp64Arg polymorphism in normal and obese Hungarian children was similar (H vs O: n=14/9.5% vs n=35/11.8%). Obese children carrying the Arg64 allele (n=35, male: 23) were compared to randomly chosen, obese children without the Arg64 allele (n=35, male: 20). A significant difference was found between the body weight (81.2+/-23.2 vs 75.6+/-17.7 kg; mean+/-s.d.; P<0.01), body fat (38.8+/-3.9 vs 36.5+/-2.3%; mean+/-s.d.; P<0.05), mean fasting insulin levels (31.4+/-16.7 vs 16.9+/-7.6 microIU/ml; P<0.001) and mean systolic BP values (125.2+/-10.1 vs 114.5+/-8.3 mmHg; P<0.001) of the two obese groups. CONCLUSIONS: The frequency of Trp64Arg polymorphism was similar in Hungary as compared to other European countries. Although the prevalence of this polymorphism was similar in H and O children, the presence of Arg64 allele seems to be associated with increased adiposity, elevated systolic BP and higher fasting insulin levels.     

Influence of leptin on changes in body fat during growth in African American and white children

OBJECTIVE: The aim of this study was to determine whether initial levels or temporal changes in fasting leptin were associated with longitudinal changes in body-fat mass in children. RESEARCH METHODS AND PROCEDURES: The study group consisted of 85 children (42 white and 43 African American) with a mean initial age of 8.1 +/- 0.1 years. The children had between three and six annual visits for repeated measurements of body composition by DXA and fasting leptin level. Fat mass and fasting leptin level were not normally distributed and were log-transformed. Data were analyzed using SAS Proc mixed growth models, with log fat as the dependent variable. RESULTS: Initial leptin level was a significant predictor of the change in fat mass over time (p < 0.0001), with high initial leptin levels resulting in increased fat gain, independent of initial fat levels. This relationship remained significant when the data were analyzed separately by race (whites, p < 0.0001; African Americans, p = 0.008). The relationship between the initial level of leptin and the change in fat mass was not modified by race, sex, or Tanner Stage. The rate of change in leptin during the study was significantly related to the rate of change in fat mass in African Americans (p = 0.008) but not in whites (p = 0.490). DISCUSSION: In conclusion, high fasting leptin level at the start of the study was significantly associated with increasing fat mass in this cohort, indicating that the children may be developing resistance to the effects of leptin.     

Liver-fat accumulation and insulin resistance in obese women with previous gestational diabetes

OBJECTIVE: We determined whether fat accumulation in the liver is associated with features of insulin resistance independent of obesity. RESEARCH METHODS AND PROCEDURES: We recruited 27 obese nondiabetic women in whom liver fat (LFAT) content was determined by proton spectroscopy, intra-abdominal and subcutaneous fat by magnetic resonance imaging, and insulin sensitivity by the euglycemic insulin clamp technique. The women were divided based on their median LFAT content (5%) to groups with low (3.2 +/- 0.3%) and high (9.8 +/- 1.5%) liver fat. The groups were almost identical with respect to age (36 +/- 1 vs. 38 +/- 1 years in low vs. high-LFAT), body mass index (32.2 +/- 0.6 vs. 32.8 +/- 0.5 kg/m(2)), waist-to-hip ratio, intra-abdominal, subcutaneous, and total fat content. RESULTS: Women with high LFAT had features of insulin resistance including higher fasting serum triglyceride (1.93 +/- 0.21 vs. 1.11 +/- 0.09 mM, p < 0.01) and insulin (14 +/- 3 vs. 10 +/- 1 mU/L, p < 0.05) concentrations than women with low LFAT. The group with high LFAT also had higher 24-hour blood pressures, and lower whole-body insulin sensitivity compared with the low-LFAT group. DISCUSSION: In obese women with previous gestational diabetes, LFAT, rather than any measure of body composition, is associated with features of insulin resistance.     

Serum magnesium and type-2 diabetes in African Americans and Hispanics: a New York cohort

OBJECTIVES: The aim of this study was to examine the relationship of serum Mg with stage of diabetes measured by fasting serum glucose in a cohort of 485 African American and Hispanic adults. METHODS: The cross sectional Rosetta study was designed to assess body composition in a multi-racial cohort of healthy adults living in New York City. The data utilized for the current analyses were collected during the years 1990 to 2000. Serum Mg and glucose were measured after a 10-12 hour fast. Dual-energy x-ray absorptiometry was used to measure fat mass (FM) and fat free mass (FFM). RESULTS: The mean age of the cohort was 53 +/- 16 years. Hispanics had significantly lower (p < 0.05) mean serum Mg levels (0.82 +/- 0.07 mmol/L vs. 0.85 +/- 0.07 mmol/L) and FFM (48.8 +/- 10.9 kg vs. 50.9 +/- 10.3 kg) compared to African Americans. In both race/ethnic groups, individuals classified as having diabetes had significantly (p < 0.001) lower serum concentrations of Mg (0.80 +/- 0.07 mmol/L) compared to the normal group (0.84 +/- 0.07 mmol/L). CONCLUSIONS: These results show that in African American and Hispanic adults, those with diabetes have lower serum Mg levels compared to those classified as pre-diabetic or those with normal fasting glucose levels.     

Role of dietary factors in ethnic differences in early risk of cardiovascular disease and type 2 diabetes

BACKGROUND: The disparity in the prevalence of cardiovascular disease and type 2 diabetes between African Americans and whites has been well established, and ethnic differences in several risk factors for these diseases are evident in childhood. OBJECTIVE: The current study explored whether dietary factors explain ethnic differences in serum lipids and insulin profiles in children, independent of body composition and social class background. DESIGN: The sample included 95 African American and white children (mean age: 10.0 y). Macronutrient and food group intakes were derived from three 24-h recalls. Cardiovascular disease and type 2 diabetes risk were determined on the basis of total cholesterol, triacylglycerol, insulin sensitivity (S(i)), and acute insulin response (AIR). Data were analyzed by using t tests, analysis of covariance, and multiple regression. RESULTS: African American children had lower triacylglycerol (P < 0.01), lower S(i) (P < 0.001), and higher AIR (P < 0.001) than whites. Intake of fruit and vegetables was significantly higher, and dairy intake lower, in African American than in white children after adjustment for social class and total energy intake. Several direct relations were observed between diet and insulin action: carbohydrate and fruit intakes were positively associated with S(i) (P = 0.02), and vegetable intake was negatively associated with AIR (P = 0.01). However, neither macronutrient nor food group intake accounted for the ethnic differences in triacylglycerol and AIR. CONCLUSIONS: The African American children in our sample showed a greater disease risk than did the white children, even after body composition, social class background, and dietary patterns were adjusted for.     

Growth of visceral fat, subcutaneous abdominal fat, and total body fat in children

OBJECTIVE: To examine the patterns of growth of visceral fat, subcutaneous abdominal fat, and total body fat over a 3- to 5-year period in white and African American children. RESEARCH METHODS AND PROCEDURES: Children (mean age: 8.1 +/- 1.6 years at baseline) were recruited from Birmingham, Alabama, and those with three or more repeated annual measurements were included in the analysis (N = 138 children and 601 observations). Abdominal adipose tissue (visceral and subcutaneous) was measured using computed tomography. Total body fat and lean tissue mass were measured by DXA. Random growth curve modeling was performed to estimate growth rates of the different body fat compartments. RESULTS: Visceral fat and total body fat both exhibited significant growth effects before and after adjusting for subcutaneous abdominal fat and lean tissue mass, respectively, and for gender, race, and baseline age (5.2 +/- 2.2 cm(2)/yr and 1.9 +/- 0.8 kg/yr, respectively). After adjusting for total body fat, the growth of subcutaneous abdominal fat was not significant. Whites showed a higher visceral fat growth than did African Americans (difference: 1.9 +/- 0.8 cm(2)/yr), but there was no ethnic difference for growth of subcutaneous abdominal fat or total body fat. There were no gender differences found for any of the growth rates. DISCUSSION: Growth of visceral fat remained significant after adjusting for growth of subcutaneous abdominal fat, implying that the acquisition of the two abdominal fat compartments may involve different physiologic mechanisms. In contrast, growth of subcutaneous abdominal fat was explained by growth in total body fat, suggesting that subcutaneous fat may not be preferentially deposited in the abdominal area during this phase of growth. Finally, significantly higher growth of visceral fat in white compared with African American children is consistent with cross-sectional findings.     

Metabolic markers in relation to nutrition and growth in healthy 4-y-old children in Sweden

BACKGROUND: The worldwide increase in overweight and obesity probably involves dietary factors, and early indicators of risk must be identified. OBJECTIVE: We aimed to analyze metabolic markers in relation to dietary intake and anthropometry in healthy 4-y-old children. DESIGN: A cross-sectional study of nutritional intake was performed in 95 children by use of 7-d food records. Fasting blood samples were analyzed for glucose, insulin, and lipids. RESULTS: The study population was representative of Swedish children except that more parents than the average had a university education. The boys' mean energy intake was higher (6.6 +/- 0.75 MJ) than the girls' (5.7 +/- 0.79 MJ). Significant associations were found between the percentage of energy from carbohydrates and that from fat (r = -0.91) and sucrose (r = 0.59). High body mass index was associated with a low percentage of energy from fat (r = -0.32). Serum triacylglycerol, insulin, and the HOMA (homeostatic model assessment) index were higher in girls than in boys. In girls, HOMA beta-cell function was significantly negatively associated with fat intake and serum fasting insulin, and HOMA insulin resistance indexes were significantly associated with the increment in z scores for height and weight from birth to age 4 y. Compared with children with fasting insulin concentrations below the group mean + SD, the children with concentrations above that value were smaller as newborns and had larger increments in growth z scores from birth to age 4 y. CONCLUSION: In healthy Swedish 4-y-olds from well-educated families, low fat intake was related to high body mass index. Upward weight and height percentile crossings were related to insulin resistance, especially in girls.     

共轭亚油酸对肥胖大鼠脂联素基因表达的影响

目的研究共轭亚油酸对饮食诱导肥胖大鼠脂联素基因表达的影响。方法选用雄性Wistar大鼠,随机分为对照组、高脂组、高脂+共轭亚油酸组(每100g饲料含共轭亚油酸分别为075g、150g、300g),每组动物10只,观察共轭亚油酸对肥胖大鼠胰岛素、血糖水平的影响,并应用RTPCR的方法检测脂联素、过氧化物酶体增殖物活性受体γ(PPARγ)的表达水平。结果高脂组大鼠血清胰岛素和血糖水平分别为(1111±273)μIU/ml,(509±066)mmol/L,075%、150%、300%剂量组胰岛素水平分别为(699±177)μIU/ml,(736±148)μIU/ml,(785±160)μIU/ml,血糖水平分别为(428±072)mmol/L,(418±055)mmol/L,(406±063)mmol/L,且共轭亚油酸可增加肥胖大鼠脂肪组织脂联素、PPARγmRNA的表达水平。结论共轭亚油酸可通过激活PPARγ上调脂联素基因的表达,改善肥胖大鼠的胰岛素抵抗。     

Effects of calcium and dairy on body composition and weight loss in African-American adults

OBJECTIVE: Our objective was to determine the effects of dairy consumption on adiposity and body composition in obese African Americans. RESEARCH METHODS AND PROCEDURES: We performed two randomized trials in obese African-American adults. In the first (weight maintenance), 34 subjects were maintained on a low calcium (500 mg/d)/low dairy (<1 serving/d) or high dairy (1200 mg Ca/d diet including 3 servings of dairy) diet with no change in energy or macronutrient intake for 24 weeks. In the second trial (weight loss), 29 subjects were similarly randomized to the low or high dairy diets and placed on a caloric restriction regimen (-500 kcal/d). RESULTS: In the first trial, body weight remained stable for both groups throughout the maintenance study. The high dairy diet resulted in decreases in total body fat (2.16 kg, p < 0.01), trunk fat (1.03 kg, p < 0.01), insulin (18.7 pM, p < 0.04), and blood pressure (6.8 mm Hg systolic, p < 0.01; 4.25 mm Hg diastolic, p < 0.01) and an increase in lean mass (1.08 kg, p < 0.04), whereas there were no significant changes in the low dairy group. In the second trial, although both diets produced significant weight and fat loss, weight and fat loss on the high dairy diet were approximately 2-fold higher (p < 0.01), and loss of lean body mass was markedly reduced (p < 0.001) compared with the low dairy diet. DISCUSSION: Substitution of calcium-rich foods in isocaloric diets reduced adiposity and improved metabolic profiles in obese African Americans without energy restriction or weight loss and augmented weight and fat loss secondary to energy restriction.     

Greater appetite control associated with an increased frequency of eating in lean males

Eight healthy males of age 22.9+/-4.2 years (mean+/-SD) and body weight 73.26+/-11.50 kg, with BMI of 23.11+/-2.84 kg/m(2)underwent two different eating meal frequency patterns on 2 separate days. On both days they were fed approximately 33.3% of their average daily energy requirements as a breakfast pre-load meal: served either as a single meal (SINGLE) or divided into five equal portions (served hourly) (MULTI). Five and a half hours after the initial meal, an ad libitum meal was served. Venous blood was tested to determine plasma glucose and serum insulin concentrations every hour until the ad libitum lunch, and at 15-, 45- and 75-min after lunch. Visual analogue scales (VAS) were completed every hour until the ad libitum lunch, and at 15-, 45- and 75-min after lunch as a measure to determine hunger, appetite and satiety indices. Although both groups were fed isocaloric and identical macronutrient "breakfast pre-loads" (3450+/-466 kJ), the SINGLE group consumed 26.6% more (p<0.02) energy in the ad libitum lunch (5111+/-1502 kJ vs. 3752+/-893 kJ) than the MULTI group did. The pre-load feeding pattern had no effect on blood glucose responses throughout the trial. Following the larger SINGLE pre-load, serum insulin concentration rose to a higher (p<0.01) level compared to the first of the MULTI pre-load meals (123.04+/-61.51 microIU/ml vs. 37. 30+/-26.65 microIU/ml SINGLE vs. MULTI, respectively). Serum insulin rose to a higher (p<0.01) level following the fifth and final of the MULTI pre-load meals compared to the serum insulin levels in the SINGLE group at the same time into the trial (74. 21+/-51.64 microIU/ml vs. 24.98+/-13.46 microIU/ml MULTI vs. SINGLE, respectively). Despite consuming more energy in the ad libitum lunch, the SINGLE group showed no difference in serum insulin concentration following the ad libitum lunch compared to the insulin response of the MULTI group. These data suggest that when the nutrient load was spread into equal amounts and consumed evenly through the day in lean healthy males, there was an enhanced control of appetite. This greater control of satiety when consuming smaller multiple meals may possibly be linked to an attenuation in insulin response although clearly both other physical (gastric stretch) and physiological (release of gastric hormones) factors may also be affected by the periodicity of eating.     

A carbohydrate-restricted diet alters gut peptides and adiposity signals in men and women with metabolic syndrome

Carbohydrate-restricted diets have been shown to enhance satiation- and other homeostatic-signaling pathways controlling food intake and energy balance, which may serve to reduce the incidence of obesity and metabolic syndrome. This study was designed as a correlational, observational investigation of the effects of a carbohydrate-restricted diet on weight loss and body fat reduction and associated changes in circulating leptin, insulin, ghrelin, and cholecystokinin (CCK) concentrations in overweight/obese patients (4 men and 16 women) with metabolic syndrome. Subjects received clinical instruction on the initiation and maintenance of the commercial South Beach Diet, consisting of 2 phases: Phase I (initial 2 wk of the study) and Phase II (remaining 10 wk). Participants showed a decrease (P < 0.05) in body weight (93.5 +/- 3.6 kg vs. 88.3 +/- 3.4 kg), BMI (33.9 +/- 1.3 kg/m(2) vs. 32.0 +/- 1.3 kg/m(2)), waist circumference (112.8 +/- 2.8 cm vs. 107.7 +/- 3.0 cm), and total percent body fat (40.2 +/- 1.5% vs. 39.2 +/- 1.5%) by study completion. Plasma fasting insulin and leptin concentrations decreased significantly from baseline concentrations (139.1 +/- 12.2 pmol/L and 44.1 +/- 4.5 microg/L, respectively) by the end of Phase I (98.6 +/- 2.6 pmol/L and 33.3 +/- 4.1 microg/L, respectively). Plasma fasting ghrelin concentrations significantly increased from baseline (836.7 +/- 66.7 ng/L) by Phase II (939.9 +/- 56.8 ng/L). The postprandial increase in plasma CCK concentrations (difference in plasma CCK concentrations from fasting to postprandial) after Phase I (2.4 +/- 0.3 pmol/L) and Phase II (2.5 +/- 0.4 pmol/L) was significantly greater than the postprandial increase at baseline (1.1 +/- 0.5 pmol/L). Collectively, these results suggest that in patients with metabolic syndrome, improved adiposity signaling and increased postprandial CCK concentrations may act together as a possible compensatory control mechanism to maintain low intakes and facilitate weight loss, despite an increase in fasting ghrelin concentrations and subjective measures of hunger.     

Hypoenergetic high-carbohydrate or high-fat parenteral nutrition induces a similar metabolic response with differential effects on hepatic IGF-I mRNA in dexamethasone-treated rats

The optimal level of energy for critically ill patients who require parenteral nutrition (PN) is unclear. Our objective was to determine whether 50% energy (50%E) restriction due to a reduction in carbohydrate or fat, with provision of adequate protein and micronutrients, ameliorates the detrimental effects of dexamethasone (Dex) on body protein catabolism, insulin resistance, and insulin-like growth factor-I (IGF-I) responses in rats administered PN. The experiment included 6 PN groups, adequate energy (AE) +/- Dex, 50% AE with high carbohydrate (50%E CHO) +/- Dex and 50% AE with high fat (50%E FAT) +/- Dex. There was a significant interaction between energy level and Dex such that the increase in body catabolism due to 50%E from CHO or FAT was reduced by approximately 50%, although the amount of body weight and nitrogen lost over 7 d was significantly greater with 50%E than with AE. AE+Dex induced a 60% increase in liver mass, whereas 50%E+Dex reduced the increase to 26%. AE+Dex induced a 5-fold increase in serum insulin level, whereas 50%E+Dex normalized the insulin to glucose ratio. Serum IGF-I levels were reduced 14-18% by Dex and 30% by 50%E. Hepatic immunoreactive IGF-I was significantly correlated with serum IGF-I and nitrogen balance. 50%E CHO and 50%E FAT had differential effects on hepatic IGF-I mRNA with a 40% decrease in IGF-I mRNA due to 50%E FAT+Dex. In summary,CHO or FAT hypoenergetic PN with adequate protein had similar effects in normalizing hyperinsulinemia, attenuating hepatomegaly, and reducing the increment, but not the total amount of body protein catabolism, induced by glucocorticoid excess.     

Increased dietary protein modifies glucose and insulin homeostasis in adult women during weight loss

Amino acids interact with glucose metabolism both as carbon substrates and by recycling glucose carbon via alanine and glutamine; however, the effect of protein intake on glucose homeostasis during weight loss remains unknown. This study tests the hypothesis that a moderate increase in dietary protein with a corresponding reduction of carbohydrates (CHO) stabilizes fasting and postprandial blood glucose and insulin during weight loss. Adult women (n = 24; >15% above ideal body weight) were assigned to either a Protein Group [protein: 1.6 g/(kg. d); CHO <40% of energy] or CHO Group [protein: 0.8 g/(kg. d); CHO >55%]. Diets were equal in energy (7100 kJ/d) and fat (50 g/d). After 10 wk, the Protein Group lost 7.53 +/- 1.44 kg and the CHO Group lost 6.96 +/- 1.36 kg. Plasma amino acids, glucose and insulin were determined after a 12-h fast and 2 h after a 1.67 MJ test meal containing either 39 g CHO, 33 g protein and 13 g fat (Protein Group) or 57 g CHO, 12 g protein and 14 g fat (CHO Group). After 10 wk, subjects in the CHO Group had lower fasting (4.34 +/- 0.10 vs 4.89 +/- 0.11 mmol/L) and postprandial blood glucose (3.77 +/- 0.14 vs. 4.33 +/- 0.15 mmol/L) and an elevated insulin response to meals (207 +/- 21 vs. 75 +/- 18 pmol/L). This study demonstrates that consumption of a diet with increased protein and a reduced CHO/protein ratio stabilizes blood glucose during nonabsorptive periods and reduces the postprandial insulin response.     

Effects of exercise on emerging and traditional cardiovascular risk factors

BACKGROUND: Common cardiovascular disease risk factors (e.g., insulin and aerobic fitness) are improved with exercise; however, few studies have addressed the potential for training to modify emerging cardiovascular disease risk factors such as homocysteine and high-sensitivity C-reactive protein. METHODS: Sedentary adults (n = 324, 48.9 +/- 8.4 years) were randomized to four groups differing in training intensity (moderate = 45-55% or high = 65-75% of heart rate reserve) and frequency (low = 3-4, 30-min sessions/week or high = 5-7, 30 min-sessions/week). RESULTS: Within-group changes in homocysteine, insulin, and aerobic fitness were significant (all P < 0.0125). Furthermore, homocysteine increased in the high-intensity-low-frequency (0.98 +/- 2.32 micromol/L) and high-intensity-high-frequency (0.93 +/- 2.56 micromol/L) groups, while aerobic fitness increased in the moderate-intensity-high-frequency (0.99 +/- 2.01 mL min(-1) kg(-1)) and high-intensity-high-frequency (1.77 +/- 2.97 mL min(-1) kg(-1)) groups (all P < 0.003). The change in aerobic fitness was greater in the high-intensity-high-frequency compared to the moderate-intensity-low-frequency group (1.77 +/- 2.97 vs. 0.36 +/- 2.10 mL min(-1) kg(-1), P = 0.0014) (effect size estimate = 0.60 mL min(-1) kg(-1)). The main effects for intensity, with respect to the change in insulin (effect size estimate = 0.46 microU/mL), and frequency, with respect to the change in aerobic fitness (effect size estimate = 0.38 mL min(-1) kg(-1)), were significant (P < 0.0125). CONCLUSION: Although frequent bouts of higher intensity exercise were particularly effective in reducing fasting insulin and improving fitness, they resulted in slightly increased homocysteine levels.     

Insulin adsorption to three-liter ethylen vinyl acetate bags during 24-hour infusion

Insulin adsorption to ethylen vinyl acetate, 3-liter bags injected with 10 insulin units, during 24-hr infusion has been studied. Three different infusions systems (A, B, and C) were tested and eight bags for each system were used. An elevated insulin adsorption resulted in each system. The maximal insulin recovery, expressed as percentage of the original theoretical 3333 microIU/ml insulin concentration, was 19.54% (at time 6), 20.93% (at time 4), and 16.95% (at time 22) for system A, B, and C, respectively. "Dismissed insulin amount" after 24-hr infusion was 1590 +/- 279.5 microIU, 1505.8 +/- 430.5 microIU, and 1253.3 +/- 369.8 microIU for system A, B, and C, respectively. Comparison of insulin concentration values at different times revealed significant differences only at time 18 (if compared with times 0,2.4,6,8,12,14,16) ant at time 20 (if compared with time 4,6,8,10) for system A, and at time 4 (if compared with time 12,14,16,18,20,22,24) for system B. We conclude that a constant but low insulin delivery can be achieved using 3-liter EVA systems and a 24-hr infusion.     

Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism

Protein tyrosine phosphatase 1B (PTPN1) affects the regulation of insulin signaling and energy metabolism. We studied whether polymorphisms in the PTPN1 gene impact body fat distribution in the HERITAGE Family Study cohort in 502 white and 276 black subjects. Insulin sensitivity index, glucose disappearance index, acute insulin response to glucose (AIR(glucose)), and the disposition index (DI) were obtained from the frequently sampled intravenous glucose tolerance test. White subjects with the G82G at the PTPN1 IVS6+G82A polymorphism had higher body fat levels (p = 0.031) and sum of eight skinfolds (p = 0.003) and highest subcutaneous fat on the limbs (p = 0.002). G82A subjects had the lowest AIR(glucose) (p = 0.005) and disposition index (p = 0.040). Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR(glucose) (p from 0.006 to 0.010). The variant PTPN1 Pro387Leu was associated with lower fasting insulin level (p = 0.035) and glucose disappearance index (p = 0.038). In summary, PTPN1 IVS6+G82G homozygotes showed higher levels of all measures of adiposity. G82 allele heterozygotes are potentially at higher risk for type 2 diabetes. Gene-gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. The PTPN1 Pro387Leu variant was associated with lower glucose tolerance.