Changes in glycemia, insulin and gut hormone responses to a slowly ingested solid low-carbohydrate mixed meal after laparoscopic gastric bypass or band surgery.

OBJECTIVE: To evaluate early changes in glycemia, insulin physiology and gut hormone responses to an easily tolerated and slowly ingested solid, low-carbohydrate mixed meal test (MMT) following laparoscopic adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery. SUBJECTS/METHODS: This was a prospective non-randomized study. Plasma glucose, insulin and c-peptide (to estimate hepatic insulin extraction; %HIE), incretins (GIP, aGLP-1) and pancreatic polypeptide (PP) responses to the MMT were measured at 4-8 weeks before and after surgery in obese, metabolically healthy patients (RYGB=10F or LAGB =7F/1M). Supplementary clamp data on basal endogenous glucose production (EGP) and peripheral insulin action (Rd=rate of glucose disposal) and metabolic clearance rates of insulin (MCR-INS) were available in five of the RYGB patients. Repeated measures were appropriately accounted for in the analyses. RESULTS: Following LAGB surgery, C-peptide and insulin MMT profiles (P=0.004 and P=0.0005, respectively) were lower with no change in %HIE (P=0.98). In contrast, in RYGB subjects, both fasting glucose and insulin (Δ=-0.66 mmol l-1, P⩽0.05 and Δ=-44.4 pmol l-1, P⩽0.05, respectively) decreased, and MMT glucose (P<0.0001) and insulin (P=0.001) but not c-peptide (P= 0.69) decreased. Estimated %HIE increased at fasting (Δ=8.4%, P⩽0.05) and during MMT (P=0.0005). Early (0-20 min) prandial glucose (0.27±0.26 versus 0.006±0.21 mmol l-1, P⩽0.05) and insulin (63(48, 66) versus 18(12, 24) pmol l-1, P⩽0.05) responses increased after RYGB. RYGB altered the trajectory of prandial aGLP-1 responses (treatment × trajectory P=0.02), and PP was lower (P<0.0001). Clamp data in a subset of RYGB patients showed early improvement in basal EGP (P=0.001), and MCR-INS (P=0.015). CONCLUSION: RYGB results in distinctly different changes in plasma glucose, insulin and gut hormone response patterns to a solid, slowly ingested low-carbohydrate MMT versus LAGB. Altered nutrient delivery, along with indirect evidence for changes in hepatic and peripheral insulin physiology, are consistent with the greater early improvement in glycemia observed after RYGB versus LAGB surgery.

Salsalate has no effect on insulin secretion but decreases insulin clearance: a randomized, placebo-controlled trial in subjects without diabetes.

To elucidate whether increased insulin concentration after salsalate treatment (3 g/day for 7 days) is attributable to an increased insulin secretion rate (ISR) or to reduced metabolic clearance of endogenous insulin (MCI) during stepped glucose infusion (SGI). The analysis was performed in obese subjects who participated in a randomized double-blind, parallel, placebo-controlled clinical trial. A total of 27 participants (16 on salsalate, 11 on placebo) completed baseline and follow-up SGI. During SGI in the salsalate group, C-peptide concentrations were reduced by 11%, while plasma insulin concentrations were increased by 30%, corresponding to a 30% reduction in MCI (p < 0.0001). At molar increments of glucose, insulin concentrations were increased by 27% (p = 0.02), but ISR was unchanged. Salsalate did not alter insulin secretion, but lowered MCI, indicating that a reduction in insulin clearance is the principal mechanism for increased insulin levels after salsalate administration.

mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action.

OBJECTIVE: To determine whether the mRNA concentrations of inflammation response genes in isolated adipocytes and in cultured preadipocytes are related to adipocyte size and in vivo insulin action in obese individuals. DESIGN: Cross-sectional inpatient study. SUBJECTS: Obese Pima Indians with normal glucose tolerance. MEASUREMENTS: Adipocyte diameter (by microscope technique; n=29), expression of candidate genes (by quantitative real-time PCR) in freshly isolated adipocytes (monocyte chemoattractant protein (MCP) 1 and MCP2, macrophage inflammatory protein (MIP) 1alpha, MIP1beta and MIP2, macrophage migration inhibitory factor (MIF), tumor necrosis factor alpha, interleukin (IL) 6 and IL8; n=22) and cultured preadipocytes (MCP1, MIP1alpha, MIF, IL6 and matrix metalloproteinase 2; n=33) from subcutaneous abdominal adipose tissue (by aspiration biopsy, n=34), body fat by dual-energy X-ray absorptiometry, glucose tolerance by 75 g oral glucose tolerance test and insulin action by euglycemic-hyperinsulinemic clamp (insulin infusion rate 40 mU m(-2) min(-1)) (all n=34). RESULTS: MIF was the only gene whose expression in both freshly isolated adipocytes and cultured preadipocytes was positively associated with adipocytes diameter and negatively associated with peripheral and hepatic insulin action (all P<0.05). In multivariate analysis, the association between adipocyte MIF mRNA concentrations and adipocytes diameter was independent of the percentage of body fat (P=0.03), whereas adipocyte MIF mRNA concentrations, but not adipocyte diameter, independently predicted peripheral insulin action. The mRNA expression concentrations of the MIF gene in adipocytes were not associated with plasma concentrations of MIF, but were negatively associated with plasma adiponectin concentrations (P=0.004). In multivariate analysis, adipocyte MIF RNA concentrations (P=0.03) but not plasma adiponectin concentrations (P=0.4) remained a significant predictor of insulin action. CONCLUSIONS: Increased expression of MIF gene in adipose cells may be an important link between obesity characterized by enlarged adipocytes and insulin resistance in normal glucose tolerant people.

The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study.

AIM/HYPOTHESIS: Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. METHODS: The study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI >or= 30 kg/m(2). The intervention was salsalate (3 g/day, n = 28) or identical placebo (n = 26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal (R (d)) by euglycaemic-hyperinsulinaemic clamp (insulin infusion rate 40 mU m(-2) min(-1)) and glucose tolerance by 75 g OGTT. RESULTS: The study was completed by 47 participants, of which 40 were analysed (salsalate n = 22, placebo n = 18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p = 0.001) and glucose AUC during the OGTT (p = 0.01), and in increased R (d) (20 [8] vs 18 [6] micromol [kg estimated metabolic body size](-1) min(-1), p = 0.002), while there was no significant change in these variables with placebo (p > 0.3 for all). The effect of salsalate on R (d) disappeared (p = 0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p < 0.0001) measured during the clamp. No side effects of salsalate were observed during the study. CONCLUSIONS/INTERPRETATION: The glucose-lowering potential of salicylates appears to be due to effects on insulin concentration rather than improved insulin action. Salicylate-based compounds may be useful for the treatment and prevention of type 2 diabetes.

Comparison of plasma insulin levels after a mixed-meal challenge in children with and without intrauterine exposure to diabetes.

BACKGROUND: The diabetic intrauterine environment is a known risk factor for the development of diabetes in the offspring. OBJECTIVE: We compared anthropometric and metabolic characteristics of 41 nondiabetic children whose mothers developed diabetes either before (ODM, n = 19, 9.3 +/- 1.1 yr) or after (OPDM, n = 22, 9.5 +/- 1.3 yr) the pregnancy of interest. Maternal diabetes status was established from OGTT results before, during, and after the pregnancy of interest. DESIGN: After consuming a standardized diet for 2 d, a mixed-meal breakfast was given after an overnight fast. Fasting concentrations and responses of plasma glucose and insulin were evaluated using linear regression analyses to assess potential independent determinants of plasma insulin concentration at each time point. RESULTS: After adjustment for age and sex, there were no differences between ODM and OPDM children for maternal age at diagnosis, height, weight, body mass index, BMI z score, or percent body fat (dual energy x-ray absorptiometry). After adjusting for age, sex, percent body fat, and the corresponding glucose level at each time point, ODM had a lower plasma insulin level at the 15-min time point during the meal test than OPDM (P = 0.01). CONCLUSION: A lower initial insulin response to a standard mixed-meal challenge can be detected in nondiabetic ODM compared with OPDM children as early as 9 yr of age. This response may be another indicator for an attenuated early insulin response and explain the increased risk for diabetes in these children.

Resistance exercise training is associated with decreases in serum low-density lipoprotein cholesterol levels in premenopausal women.

BACKGROUND: Aerobic exercise training is associated with reduced serum concentrations of triglycerides, increased concentrations of high-density lipoprotein cholesterol, and minimal changes in serum levels of total cholesterol or low-density lipoprotein cholesterol. There are few data on the effects of resistance exercise on blood lipid levels. METHODS: Premenopausal women were randomly assigned to a supervised resistance exercise training program (n = 46) or a control group (n = 42) for 5 months. Serum was analyzed for levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Body composition and dietary intake were also measured. RESULTS: The exercise group showed a 0.33 +/- 0.03-mmol/L (mean +/- SE) decrease in total cholesterol level and a 0.36 +/- 0.001-mmol/L decrease in low-density lipoprotein cholesterol level that was significantly different from the control group. No significant changes were noted in serum high-density lipoprotein cholesterol or triglyceride levels in either group. Changes in body composition showed no significant correlations with changes in total cholesterol or low-density lipoprotein cholesterol. There were no significant differences in nutrient intake between the groups. CONCLUSION: In healthy, premenopausal women, with normal baseline lipid profiles, 5 months of resistance exercise training was associated with significant decreases in serum total cholesterol and low-density lipoprotein cholesterol concentrations.

Effects of arginine/lysine supplementation and resistance training on glucose tolerance.

The purpose of this study was to evaluate and compare the effects of arginine/lysine supplementation (AL) and resistance training (RT) on changes in glucose tolerance and to determine whether alterations were associated with changes in selected hormonal parameters. The study involved 30 physically active college males, ages 20-30 yr, randomly assigned to one of four groups: placebo/control (P/C, n = 7), P/RT (n = 8), AL/C (n = 7), or AL/RT (n = 8). An AL supplement at a daily morning dose of 132 mg/kg fat-free body mass or placebo was administered orally to controls and training groups. During the 10-wk program, exercise subjects participated in a progressive resistance training program stressing all major muscle groups. Three-hour oral glucose tolerance (OGT) tests were performed on each subject before and after the 10-wk intervention to evaluate resting levels and responses of glucose, insulin, and glucagon. OGT parameters did not significantly change after intervention. It was concluded that neither AL supplementation nor RT had a significant effect on OGT.

The maximally accumulated oxygen deficit as an indicator of anaerobic capacity.

Recently, a procedure has been established for the determination of the maximally accumulated oxygen deficit (MAOD) (Medbo et al., J. Appl. Physiol. 64:50-60, 1988) as an indicator of anaerobic capacity. We hypothesized that, if MAOD were a valid indicator of anaerobic capacity, it should distinguish between aerobically and anaerobically trained athletes and correlate with other existing anaerobic testing measures. Subjects were four distance and five middle distance runners, three sprinters, and four controls. The subjects ran for 2-3 min at 125-140% of VO2max until exhaustion, and the accumulated O2 deficit for that run was calculated by an extrapolation procedure. Subjects also performed the Wingate cycle ergometer test and runs of 300, 400, and 600 m. (Only athletes performed the runs.) Post-exercise blood lactates were obtained following the supramaximal treadmill run. MAOD (in O2 equivalents-ml.kg-1) was higher for the sprinters (78) and middle distance runners (74) than for the long distance runners (56) and control subjects (56) (P less than or equal to 0.05), indicating a greater anaerobic capacity for the former two groups. Consequently, the relative anaerobic contribution was larger for the sprinters (39%) and middle distance runners (37%) than for the long distance runners (30%; P less than or equal to 0.05). Significant correlations were found between MAOD and both Wingate power and treadmill work for all subjects and between Wingate power, Wingate capacity, treadmill work, and 300 m time for the athletes, suggesting that relationships do exist among MAOD and other anaerobic test measures. Potential use of MAOD as an indicator of anaerobic capacity is therefore promising and should be further explored.

Variation in bone mineral content and estimated body fat in young adult females.

This study was designed to determine whether variability in bone mineral content (BMC) at the lumbar vertebrae (L2-4), radius shaft (RS), femoral neck, and distal radius can significantly contribute to the variability observed in body density (Db) among 89 females (age = 25.1 +/- 5.3 yr) of varying activity levels and menstrual status. Theoretical differences in Db were calculated at +/- 1 and +/- 2 standard deviations of BMC (SDBMC) for the population as well as for the subgroups: eumenorrheic inactive controls (C), recreational runners (RR), collegiate runners (CR), body builders (BB), swimmers (S), and amenorrheic runners (AR). Multiple regression to predict Db yielded significant coefficients (b) for BMC at L2-4 (b = 0.0190, P less than 0.001) and RS (b = 0.0425, P less than 0.01) when added separately to the sum of four skinfolds (subscapula, abdomen, thigh, calf). The differences in % BFHW at +/- 1 and +/- 2 SDBMC for the sample mean for RSBMC were +/- 1.0% and +/- 2.0%, respectively. Variability in L2-4 contributed differences of +/- 1.3% and +/- 2.6% at +/- 1 and +/- 2 SDBMC. The subgroup % BFHW differences (due to L2-4 and RS combined) ranged from an average overestimation of 1.3% for the AR to an average underestimation of 1.4% for the BB. Estimated mean errors for remaining groups were less than or equal to 0.5%. Individual differences ranged from a 3.3% underestimation (BB) to a 3.0% overestimation (AR).(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic actions of estradiol: significance for acute and chronic exercise responses.

Although estradiol (E2) is considered primarily for its role in reproduction, it can exert numerous physiological actions on a variety of tissues. However, there are several difficulties in isolating these actions and determining its impact for in vivo situations. Despite the limitations, it does appear that E2 can alter, under certain conditions, resting and acute exercise metabolism and blood glucose regulation. Specifically, E2 can increase lipid availability and utilization and decrease gluconeogenesis and glycogenolysis. Development of glucose intolerance as a result of insulin insensitivity has also been documented. The mechanisms of E2 may be through direct alterations in key enzyme activity and membrane permeability or indirectly via changes in insulin:glucagon, cortisol, hGH, and catecholamine levels or sensitivity. Future research should focus on understanding the effects of exercise and diet on chronic E2 status and the resulting impact for a variety of conditions that include reproductive and skeletal integrity and predisposing metabolic risk factors for CAD and diabetes. In order to make meaningful correlations between E2 levels and physiological measurements such as bone mineral content, lipid profiles, glucose intolerance, etc., there needs to be a standard guideline for determining and defining one's "estrogen status." Finally, in order to identify underlying mechanisms, an understanding of and appreciation for the interrelationships among the numerous compositional, metabolic, and (neuro)endocrine factors involved is needed. A general model is presented, along with specific applications, to study these interactions.

Impact of total body water fluctuations on estimation of body fat from body density.

The purpose was to investigate the possibility that variability in body weight in females due to water retention causes differences in body density (Db) values determined by hydrostatic weighing (HW). Determination of total body water (TBW) and Db were concurrently measured in seven females who experienced considerable fluctuations in body weight (1.5-4.5 kg) and seven males, ages 19-24. Females were measured when they felt they were at their lowest (LO) and highest (HI) body weights (BW) during a menstrual cycle. Males were randomly tested approximately 3 wk apart. Mean values of selected variables were compared in the LO vs HI testing sessions by paired t-tests. Significant mean differences were found in the females (P less than 0.01) for the following variables: BW (kg) (LO = 58.9, HI = 61.1), Db (g.cc-1) (LO = 1.0430, HI = 1.037), and percent body fat (%BF) as determined by HW alone (LO = 24.8%, HI = 27.6%). Variables significant at the P less than 0.05 level were TBW(l) (LO = 33.6, HI = 35.1) and %TBW of the fat-free body (LO = 74.5, HI = 75.9). However, changes in TBW could not entirely account for observed changes in Db. Only mean BW (kg) was significant (P less than 0.01) in the males (LO = 74.3, HI = 74.6). It is concluded that changes in TBW can in part result in significantly different Db values obtained from HW in females who did experience perceptible changes in BW during a menstrual cycle. The remaining differences may be due to changes in fat and protein content or methodological errors.

Comparison of estradiol and testosterone levels during and immediately following prolonged exercise in moderately active and trained males and females.

Estradiol (E2) and testosterone (T) levels were compared among 28 subjects, ages 21-30, classified as male controls (MC), male runners (MR), female controls (FC) or female runners (FR). Serial blood samples were drawn from an indwelling venous catheter during rest (2 hrs), treadmill exercise (1 hr at 60% VO2max), and immediate recovery (15 min). Two-way ANOVA resulted in expected sex differences (p less than .01) in resting levels of E2 (M = 43.2 +/- 26.4; F = 142.4 +/- 72.8 pg/ml) and T (M = 4.8 +/- 1.2; F = 0.6 +/- 0.4 ng/ml). Significant (p less than .01) percent (%) and absolute (ABS) increases in E2 were observed in all subjects. Exercise increases in T were only significant in the MRs. ABS and % changes were compared among groups during exercise and during recovery. Training-related differences were found in the nature of the steroid responses. Runners exhibited greater ABS and % increases in T and E2 during recovery while the controls' greatest increases occurred during exercise. It was concluded that the greater (and more rapid) exercise responses of E2 in the MCs and T in the FCs as compared to the MRs and FRs, respectively were due to increased adrenal stimulation. The greater (and more delayed) recovery responses of the runners were due to gonadal production or differences in gonadal blood flow dynamics immediately post-exercise. The significance of this training difference may be relevant for steroidal induction of anabolic processes that lead to training adaptations.

Sex and training differences in human growth hormone levels during prolonged exercise.

Human growth hormone (hGH) levels were measured during rest, prolonged treadmill exercise at 60% maximum O2 uptake (VO2max), and immediate recovery in four groups of subjects (n = 7/group), ages 21-30 yr, classified as male runners (MR), female runners (FR), male controls (MC), and female controls (FC) to determine whether sex differences in the hGH response are related to resting 17 beta-estradiol (E2) and/or cardiorespiratory endurance (CRE). Glucose (Glc), E2, and hGH levels were determined from serial blood samples taken from an intravenous catheter. Glc did not change significantly during exercise, but different trends for the runners (increases) vs. controls (decreases) resulted in higher (P less than 0.01) postexercise levels in the runners. Resting hGH was higher (P less than 0.05) in the FRs and FCs than the MRs and MCs, respectively, and continued to be higher in the FCs (vs. MCs) during the first 30 min of exercise. The MRs achieved higher peak hGH levels and exhibited higher values than the MCs throughout exercise and recovery. There were no statistically significant training differences in the females. The strongest predictors for peak hGH were absolute work load and group (runners vs. controls), both of which combined accounted for 32-36% of the variability (P less than 0.01) in hGH response. Significant sex-related variables (sex, resting E2) accounted for 11-19% of the variability in peak or percent change in hGH, with E2 having a positive effect at rest but a negative effect during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal alterations due to exercise.

The study of hormonal alterations due to exercise is of growing interest because of the implications for adaptation, performance, and health. The influence of the sympathoadrenal response on energy metabolism and fluid and electrolyte balance has been of primary interest in past research. Interpretation of results, however, is difficult because of the numerous factors which need to be controlled. Limitations in the interpretation of hormone levels exist because of changes in plasma volume and/or clearance rate and the influences of timing and method of blood sampling. Other factors which must be considered are the design of exercise protocols, and various subject characteristics (sex, age, fitness level, training history, diet, emotional status, diurnal and menstrual variations). Hormonal alterations during acute exercise occur primarily because of sympathoadrenal secretion of the catecholamines which initiate mobilisation of glucose and free fatty acids. This response, in turn, stimulates other endocrine glands and cells (anterior and posterior pituitary, adrenal cortex, thyroid, parathyroid, liver, pancreas, kidney) to secrete secondary hormones which potentiate fuel mobilisation and regulate water and electrolyte concentrations. As duration of exercise increases, nutrient and ion concentrations also influence hormonal responses. In recent years, research has focused on the effect of exercise-induced hormonal alterations on reproductive functioning and various endocrine-related diseases (hypopituitarism, diabetes, osteoporosis, cardiovascular disease). These topics, as well as a better understanding of mechanisms of action via receptor activity, influences on training adaptations, and implications (if any) of hormonal alterations for the growth and development of children, provide challenges for future research.