Biomedical subjects

Michael D Jensen

Publications and source records attributed to Michael D Jensen.

At least 19 recordsLinked to original sources

PubMed2007

Insulin dose response analysis of free fatty acid kinetics.

Insulin regulation of free fatty acid (FFA) release is an important aspect of metabolic function; however, FFA release is exquisitely sensitive to insulin, which complicates the design and analysis of dose response experiments. We measured FFA ([(3)H]palmitate) and glucose ([(3)H]glucose) kinetics in 7 nonobese men, 7 nonobese women, 7 obese men, and 7 obese women by using a two-step insulin clamp (0.25 and 2.5 mU/kg fat-free mass per minute). Obese men and women were characterized as having a BMI of 28 or greater and body fat of 28% and 40% or greater for men and for women, respectively. Nonobese men and women had 22% and 35% or less body fat, respectively. All volunteers were Caucasian. Glucose disposal increased in a linear fashion with plasma insulin concentrations. The nonlinear suppression of plasma palmitate flux and concentrations could be linearized by logarithmically transforming both the insulin concentration and palmitate axes, except in nonobese men. We repeated the studies in 7 nonobese and 7 obese men, using 1.0 mU/kg fat-free mass per minute as the second insulin dose, which linearized the log-transformed lipolysis measures. The indices of insulin regulation of lipolysis predicted using 2 points (basal and second insulin dose) vs 3 points (basal, low, and high dose) were not different provided the proper second dose was selected. The EC(50) for insulin suppression of lipolysis correlated linearly with plasma triglycerides (r = 0.52, P < .001) and exponentially with insulin sensitivity(glucose) (r = 0.70, P < .001). We conclude that log transformation of insulin dose response data for FFA permits straightforward data analysis and simplifies the estimation of metabolically relevant parameters.

Adult↗

PubMed2006

Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics.

The ability of growth hormone (GH) to stimulate lipolysis and cause insulin resistance in skeletal muscle may be causally linked, but the mechanisms remain obscure. We investigated the impact of GH on the turnover of FFA and VLDL-TG, intramuscular triglyceride content (IMTG), and insulin sensitivity (euglycemic clamp) in nine healthy men in a randomized double-blind placebo-controlled crossover study after 8 days treatment with (A) Placebo+Placebo, (B) GH (2 mg daily)+Placebo, and (C) GH (2 mg daily)+Acipimox (250 mgx3 daily). In the basal state, GH (B) increased FFA levels (P<0.05), palmitate turnover (P<0.05), and lipid oxidation (P=0.05), but VLDL-TG kinetics were unaffected. Administration of acipimox (C) suppressed basal lipolysis but did not influence VLDL-TG kinetics. In the basal state, IMTG content increased after GH (B; P=0.03). Insulin resistance was induced by GH irrespective of concomitant acipimox (P<0.001). The turnover of FFA and VLDL-TG was suppressed by hyperinsulinemia during placebo and GH, whereas coadministration of acipimox induced a rebound increase FFA turnover and VLDL-TG clearance. We conclude that these results show that GH-induced insulin resistance is associated with increased IMTG and unaltered VLDL-TG kinetics; we hypothesize that fat oxidation in muscle tissue is an important primary effect of GH and that circulating FFA rather than VLDL-TG constitute the major source for this process; and the role of IMTG in the development of GH-induced insulin resistance merits future research.

Adult↗

PubMed2006

Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study.

BACKGROUND: Rimonabant, a selective cannabinoid type 1 receptor blocker, reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients. The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas. METHODS: 1047 overweight or obese type 2 diabetes patients (body-mass index 27-40 kg/m2) with a haemoglobin A1c (HbA1c) concentration of 6.5-10.0% (mean 7.3% [SD 0.9] at baseline) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity, and randomly assigned placebo (n=348), 5 mg/day rimonabant (360) or 20 mg/day rimonabant (339) for 1 year. Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis. The primary endpoint was weight change from baseline after 1 year of treatment. Analyses were done on an intention-to-treat basis. This trial is registered at ClinicalTrials.gov, number NCT00029848. FINDINGS: 692 patients completed the 1 year follow-up; numbers in each group after 1 year were much the same. Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group (placebo: -1.4 kg [SD 3.6]; 5 mg/day: -2.3 kg [4.2], p=0.01 vs placebo; 20 mg/day: -5.3 kg [5.2], p<0.0001 vs placebo). Rimonabant was generally well tolerated. The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group, mainly due to depressed mood disorders, nausea, and dizziness. INTERPRETATION: These data indicate that 20 mg/day rimonabant, in combination with diet and exercise, can produce a clinically meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas.

Adolescent↗

PubMed2006

DHEA in elderly women and DHEA or testosterone in elderly men.

BACKGROUND: Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown. METHODS: We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life. RESULTS: As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter (9.2 micromol per liter) in men and by 3.8 microg per milliliter (10.3 micromol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects. CONCLUSIONS: Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov].).

Adult↗

PubMed2006

Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people.

BACKGROUND & AIMS: Peptide YY (PYY) levels are reported to be decreased in obesity. The relation between gastric functions, satiation, and gut hormones in obesity is incompletely understood. The aim of this study was to compare gastric volumes, emptying, maximum tolerated volumes, postchallenge symptoms, and selected gut hormones in normal, overweight, or obese healthy volunteers. METHODS: In 73 nonbulimic normal, overweight, or obese participants weighing less than 137 kg, we measured gastric emptying of solids and liquids by scintigraphy (gastric emptying half-time [GE t(1/2)]); gastric volumes by single-photon emission computed tomography; maximum tolerated volumes and symptoms by satiation test; and plasma leptin, ghrelin, insulin, glucagon-like peptide 1, and PYY levels. Groups were compared using 1-way analysis of covariance adjusted for sex. Univariate associations among measured responses were assessed using Spearman correlations. Multiple linear regression models, adjusting for weight and sex, assessed the independent ability of gastric functions and hormones to predict satiation volume. RESULTS: Obese and overweight subjects had significantly lower postprandial gastric volumes, higher fasting and postprandial insulin and leptin levels, and lower fasting ghrelin and lower postprandial reduction in ghrelin levels. PYY levels were not different in obese or overweight subjects compared with controls. The GE t(1/2) was correlated inversely with postprandial PYY; increased body weight was associated with faster GE t(1/2) of solids (r(s) = 0.33, P = .005) and liquids (r(s) = 0.24, P = .04). Postprandial changes in gastric volume and PYY were independent predictors of satiation (both P = .01). CONCLUSIONS: Overweight or obesity are associated with lower postprandial gastric volumes and normal PYY levels. Gastric emptying influences postprandial PYY levels. Postprandial PYY and gastric volume independently predict satiation volume in nonbulimic people across a wide body mass index range.

Adolescent↗

PubMed2006

Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease.

Secretory phospholipase A2-IIA (sPLA2-IIA) is an inflammatory protein known to play a role in the pathogenesis of many inflammatory diseases. Although this enzyme has also been implicated in the pathogenesis of neurodegenerative diseases, there has not been a direct demonstration of its expression in diseased human brain. In this study, we show that sPLA2-IIA mRNA is up-regulated in Alzheimer's disease (AD) brains as compared to non-demented elderly brains (ND). We also report a higher percentage of sPLA2-IIA-immunoreactive astrocytes present in AD hippocampus and inferior temporal gyrus (ITG). In ITG, the majority of sPLA2-IIA-positive astrocytes were associated with amyloid beta (Abeta)-containing plaques. Studies with human astrocytes in culture demonstrated the ability of oligomeric Abeta1-42 and interleukin-1beta (IL-1beta) to induce sPLA2-IIA mRNA expression, indicating that this gene is among those induced by inflammatory cytokines. Since exogenous sPLA2-IIA has been shown to cause neuronal injury, understanding the mechanism(s) and physiological consequences of sPLA2-IIA upregulation in AD brain may facilitate the development of novel therapeutic strategies to inhibit the inflammatory responses and to retard the progression of the disease.

Journal Article↗

PubMed2006

Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns.

Anatomically separate fat depots differ in size, function, and contribution to pathological states, such as the metabolic syndrome. We isolated preadipocytes from different human fat depots to determine whether the basis for this variation is partly attributable to differences in inherent properties of fat cell progenitors. We found that genome-wide expression profiles of primary preadipocytes cultured in parallel from abdominal subcutaneous, mesenteric, and omental fat depots were distinct. Interestingly, visceral fat was not homogeneous. Preadipocytes from one of the two main visceral depots, mesenteric fat, had an expression profile closer to that of subcutaneous than omental preadipocytes, the other main visceral depot. Expression of genes that regulate early development, including homeotic genes, differed extensively among undifferentiated preadipocytes isolated from different fat depots. These profiles were confirmed by real-time PCR analysis of preadipocytes from additional lean and obese male and female subjects. We made preadipocyte strains from single abdominal subcutaneous and omental preadipocytes by expressing telomerase. Depot-specific developmental gene expression profiles persisted for 40 population doublings in these strains. Thus, human fat cell progenitors from different regions are effectively distinct, consistent with different fat depots being separate mini-organs.

Adipose Tissue↗

PubMed2006

Acute hyperinsulinemia inhibits intramyocellular triglyceride synthesis in high-fat-fed obese rats.

Hyperinsulinemia is common in obesity, but whether it plays a role in intramyocellular triglyceride (imcTG) buildup is unknown. In this study, hyperinsulinemic-euglycemic clamp experiments were performed in overnight-fasted lean and high-fat-fed obese rats, awake, to determine the effect of insulin on imcTG synthesis (incorporation of [(14)C]glycerol, [(14)C]glucose, and [(3)H]oleate). Insulin infusion at 25 (low insulin) and 100 (high insulin) pmol/kg/min increased plasma insulin by 5- and 16-fold, respectively, whereas plasma and intramyocellular glycerol, FFAs, triglycerides, and glucose levels were maintained at their basal levels by co-infusion of exogenous glycerol, FFAs, and triglycerides at fixed rates and glucose at varying rates. In obese rats, insulin suppressed incorporation of glycerol into the imcTG-glycerol moiety dose dependently (P < 0.01-P < 0.001) in gastrocnemius and tibialis anterior, but only the high insulin suppressed it in soleus (P < 0.05). The low insulin suppressed glucose incorporation into imcTG-glycerol in all three muscles (P = 0.01-P < 0.01). However, the low insulin did not affect (P > 0.05) and the high insulin suppressed (P < 0.05-P < 0.01) fatty acid incorporation into imcTG in all three muscles. Insulin also suppressed glycerol incorporation in lean rats (P < 0.01-P < 0.04). On the other hand, imcTG pool size was not affected by insulin (P > 0.05). These observations suggest that acute hyperinsulinemia inhibits imcTG synthesis and thus does not appear to promote imcTG accumulation via the synthetic pathway, at least in the short term.

Acute Disease↗

PubMed2006

Energy expenditure, insulin, and VLDL-triglyceride production in humans.

Hypertriglyceridemia is considered a cardiovascular risk factor in diabetic and nondiabetic subjects. In this study, we aimed to determine potential regulators of very low density lipoprotein-triglyceride (TG) production. VLDL-TG kinetics were measured in 13 men and 12 women [body mass index [mean (range)]: 24.8 (20.2-35.6) kg/m(2)]. VLDL-TG production was assessed from the plasma decay of a bolus injection of ex vivo labeled VLDL particles ([1-(14)C]triolein-VLDL-TG). Similar VLDL-TG production (micromol/min) was found in men and women. VLDL-TG production was not significantly correlated with palmitate flux ([9,10-(3)H]palmitate) (r = 0.09, P = 0.67) or palmitate concentration (r = -0.29, P = 0.2) but was correlated significantly with fasting insulin concentration (r = 0.46, P < 0.05) and resting energy expenditure (REE) (r = 0.45, P < 0.05). The latter correlation improved when adjusted for sex. The best multivariate model with VLDL-TG production as the dependent variable and REE, body composition, hormones, and substrate levels as independent variables included fasting insulin (P = 0.02) and REE (P = 0.02) (r(2) = 0.32, P < 0.001). We conclude that VLDL kinetics are similar in men and women and that REE and plasma insulin are significant independent predictors of VLDL-TG production. FFA availability and body fat distribution are unrelated to VLDL production. We suggest that REE plays a greater role in VLDL-TG production than previously anticipated. REE and insulin should be taken into account when VLDL-TG production comparisons between groups are made.

Body Composition↗

PubMed2006

Sex-specific differences in leg fat uptake are revealed with a high-fat meal.

The mechanism(s) by which sex specific differences in regional body fat distribution develop are not known. We assessed the effects of a high-fat (HF) meal on fatty acid oxidation and uptake into regional fat depots using isotopic tracers and adipose biopsies. Thirty men (BMI 23.6 +/- 0.3 kg/m(2)) and 29 women (BMI 22.4 +/- 0.3 kg/m(2)) received a meal containing [(3)H]triolein. Twelve of the men and 13 of the women received an additional 80 g of triolein in the meal (HF) and the remainder received a normal-fat (NF) meal. Adipose tissue lipoprotein lipase (LPL) activity was measured in the fed and fasted state. After 24 h, meal fatty acid uptake into subcutaneous adipose tissue was assessed. The efficiency of meal fat uptake into upper body subcutaneous fat was similar in both sexes, but women had a greater leg fat uptake, especially in response to a HF meal (P < 0.0001). A correlation between fed-state LPL activity and meal fat uptake was found in both upper and lower body fat (P < 0.0001, r = 0.69). These studies show that, in times of net fat storage, women preferentially increase uptake in leg adipose tissue, and this is likely mediated by fed-state LPL activity.

Adult↗

PubMed2006

Diet/Exercise versus pioglitazone: effects of insulin sensitization with decreasing or increasing fat mass on adipokines and inflammatory markers.

BACKGROUND: Plasma adipokine concentrations are variably related to fatness/insulin resistance and may act via endocrine mechanisms. We assessed the relationship among plasma adipokine concentrations and their relationship with insulin sensitivity and body composition in obese adults before and after insulin sensitization accomplished using diet/exercise or pioglitazone. METHODS: Plasma adipokine concentrations, insulin sensitivity, and body composition were assessed in 39 upper-body obese insulin-resistant, nondiabetic adults before and after 19 wk of diet/exercise or 30 mg/d pioglitazone. RESULTS: Diet/exercise reduced body fat and visceral fat and improved insulin sensitivity parameters; pioglitazone improved insulin sensitivity to a similar degree but increased body fat. Adiponectin increased more after pioglitazone (4770 +/- 487 vs. 8351 +/- 693.6 ng/ml, P < 0.001) than after diet/exercise (4704 +/- 367 to 5426 +/- 325.3 ng/ml, P < 0.01), whereas TNFalpha, IL-6, and resistin did not change. C-reactive protein decreased with diet/exercise. Adipokine concentrations were not correlated with each other at baseline or after insulin sensitization, except TNFalpha and IL-6 (r = 0.43, P < 0.05); IL-6 was inversely correlated with resistin. Only adiponectin was correlated (P < 0.05) with indices of insulin sensitivity. Adiponectin concentrations were inversely correlated with visceral fat and with sc fat depots in men but positively correlated with sc fat in women. CONCLUSION: Plasma adipokine concentrations were not consistently interrelated, and only adiponectin displayed the expected relationship with insulin sensitivity and sensitization. These findings do not support an endocrine role for resistin, TNFalpha, and IL-6 in mediating changes in insulin resistance after diet/exercise or pioglitazone.

Absorptiometry, Photon↗

PubMed2006

Thematic review series: patient-oriented research. Free fatty acid metabolism in human obesity.

Adipose tissue lipolysis provides circulating FFAs to meet the body's lipid fuel demands. FFA release is well regulated in normal-weight individuals; however, in upper-body obesity, excess lipolysis is commonly seen. This abnormality is considered a cause for at least some of the metabolic defects (dyslipidemia, insulin resistance) associated with upper-body obesity. "Normal" lipolysis is sex-specific and largely determined by the individual's resting metabolic rate. Women have greater FFA release rates than men without higher FFA concentrations or greater fatty acid oxidation, indicating that they have greater nonoxidative FFA disposal, although the processes and tissues involved in this phenomenon are unknown. Therefore, women have the advantage of having greater FFA availability without exposing their tissues to higher and potentially harmful FFA concentrations. Upper-body fat is more lipolytically active than lower-body fat in both women and men. FFA released by the visceral fat depot contributes only a small percentage of systemic FFA delivery. Upper-body subcutaneous fat is the dominant contributor to circulating FFAs and the source of the excess FFA release in upper-body obesity. We believe that abnormalities in subcutaneous lipolysis could be more important than those in visceral lipolysis as a cause of peripheral insulin resistance. Understanding the regulation of FFA availability will help to discover new approaches to treat FFA-induced abnormalities in obesity.

Adipose Tissue↗

PubMed2006

High-precision isotopic analysis of palmitoylcarnitine by liquid chromatography/electrospray ionization ion-trap tandem mass spectrometry.

Single quadrupole gas chromatography/mass spectrometry (GC/MS) has been widely used for isotopic analysis in metabolic investigations using stable isotopes as tracers. However, its inherent shortcomings prohibit it from broader use, including low isotopic precision and the need for chemical derivatization of the analyte. In order to improve isotopic detection power, liquid chromatography/electrospray ionization ion-trap tandem mass spectrometry (LC/ESI-itMS2) has been evaluated for its isotopic precision and chemical sensitivity for the analysis of [13C]palmitoylcarnitine. Over the enrichment range of 0.4-10 MPE (molar % excess), the isotopic response of LC/ESI-itMS2 to [13C]palmitoylcarnitine was linear (r = 1.00) and the average isotopic precision (standard deviation, SD) was 0.11 MPE with an average coefficient of variation (CV) of 5.6%. At the lower end of isotopic enrichments (0.4-0.9 MPE), the isotopic precision was 0.05 MPE (CV = 8%). Routine analysis of rat skeletal muscle [13C4]palmitoylcarnitine demonstrated an isotopic precision of 0.03 MPE for gastrocnemius (n = 16) and of 0.02 MPE for tibialis anterior (n = 16). The high precision enabled the detection of a small (0.08 MPE) but significant (P = 0.01) difference in [13C4]palmitoylcarnitine enrichments between the two muscles, 0.51 MPE (CV = 5.8%) and 0.43 MPE (CV = 4.6%), respectively. Therefore, the system demonstrated an isotopic lower detection limit (LDL) of < or =0.1 MPE (2 x SD) that has been impossible previously with other organic mass spectrometry instruments. LC/ESI-itMS2 systems have the potential to advance metabolic investigations using stable isotopes to a new level by significantly increasing the isotopic solving power.

Animals↗

PubMed2006

Assessment and preparation of patients for bariatric surgery.

The number of bariatric surgical procedures performed in the United States has increased steadily during the past decade. Currently accepted criteria for consideration of bariatric surgery include a body mass index (calculated as weight in kilograms divided by the square of height in meters) of 40 kg/m2 or greater (or >35 kg/m2 with obesity-related comorbidities), documented or high probability of failure of nonsurgical weight loss treatments, and assurance that the patient is well informed, motivated, and compliant. Appropriate patient selection is important in achieving optimal outcomes after bariatric surgery. In this article, we review our approach to the medical and psychological assessment of patients who want to undergo bariatric surgery. The medical evaluation is designed to identify and optimally treat medical comorbidities that may affect perioperative risks and long-term outcomes. The psychiatric and psychological assessment identifies factors that may influence long-term success in maintaining weight loss and prepares the patient for the lifestyle changes needed both before and after surgery.

Bariatric Surgery↗

PubMed2006

Is visceral fat involved in the pathogenesis of the metabolic syndrome? Human model.

OBJECTIVE: To review the evidence for and against the role of visceral adipose tissue as a major contributor to the metabolic complications of obesity through abnormal regulation of lipolysis. RESEARCH METHODS AND PROCEDURES: Data from investigators in the field who have studied visceral adiposity and metabolic health and/or regional and systemic free fatty acid (FFA) release were considered. RESULTS: Although visceral fat mass was positively correlated with adverse health consequences and excess FFA availability, visceral fat was not the source of excess systemic FFA availability. Upper body non-visceral fat contributes the majority of FFAs in lean, obese, diabetic, and non-diabetic humans. Increasing amounts of visceral fat probably result in greater hepatic FFA delivery. DISCUSSION: Systemic, as opposed to hepatic, insulin resistance is unlikely to be caused by high rates of visceral adipose tissue lipolysis.

Fatty Acids, Nonesterified↗

PubMed2006

Potential role of new therapies in modifying cardiovascular risk in overweight patients with metabolic risk factors.

The serotonin, norepinephrine, dopamine, and endocannabinoid systems, as well as a host of other systems, mediate hunger and satiety signals. Weight loss agents that modulate appetite through pure central nervous system pathways (e.g., APD356, a selective serotonin receptor agonist) and peripheral signals to central nervous system pathways (e.g., cholecystokinin receptor agonists and ghrelin receptor antagonists) are in preclinical or early phase studies. Both devices and pharmacological compounds that facilitate weight loss and/or target multiple components of metabolic risk also are in development. One of the medications that has completed extensive phase III clinical trials and may become available in the foreseeable future is rimonabant, a selective cannabinoid 1-receptor antagonist. Drugs that improve adipose tissue function or fatty acid metabolism (e.g., AOD9604) also are in clinical trials. Some currently available medications may reduce metabolic complications without treating obesity per se (e.g., acipimox, pioglitazone). Surgically implanted gastric pacemaker systems that modulate vagus nerve activity and delay gastric emptying are under study.

Anti-Obesity Agents↗

PubMed2006

Weekly changes in basal metabolic rate with eight weeks of overfeeding.

OBJECTIVE: The contribution of basal metabolic rate (BMR) to weight gain susceptibility has long been debated. We wanted to examine whether BMR changes in a linear fashion with overfeeding. Our hypothesis was that BMR does not increase linearly with 1000-kcal/d overfeeding in lean healthy subjects over 8 weeks. The null hypothesis states that BMR increases linearly with 1000-kcal/d overfeeding in lean healthy subjects. RESEARCH METHODS AND PROCEDURES: Initially, 16 lean healthy sedentary subjects completed 2 weeks of weight maintenance feeding at the General Clinical Research Center. The subjects were then overfed by 1000 kcal/d over 8 weeks. BMR was measured under standard conditions each week using indirect calorimetry. RESULTS: Baseline BMR was 1693 +/- 154.5 kcal/d. BMR increased from 1711 +/- 201.3 kcal/d at week 1 of overfeeding to 1781 +/- 171.65 kcal/d at the second week of overfeeding (p = 0.05). BMR fell during the third week of overfeeding to 1729 +/- 179.5 kcal/d (p = 0.05). After 5 weeks of overfeeding, BMR reached a plateau. Thereafter, there was no further change. Comparison of BMR with weeks of overfeeding was significantly different compared with the linear model (p < 0.05). DISCUSSION: Increases in BMR in lean sedentary healthy subjects with 1000-kcal/d overfeeding are not linear over 8 weeks. There seems to be a short-term increase in BMR in the first 2 weeks of overfeeding that is not representative of longer-term changes.

Adiposity↗

PubMed2006

Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes.

OBJECTIVE: Pioglitazone, a peroxisome proliferator-activated receptor agonist and glipizide, an insulin secretagogue, are commonly used to treat type 2 diabetes. Our study was designed to examine the effects of pioglitazone versus glipizide on body water, body composition, and hemodynamic parameters in the presence of comparable glycemic control between groups. RESEARCH DESIGN AND METHODS: We studied 19 diabetic subjects randomly assigned to either 45 mg pioglitazone (n = 8) or 10 mg (median dose) glipizide (n = 11) for 12 weeks. Body water content was measured with deuterated water, body composition by dual-energy X-ray absorptiometry and computed tomography, and cardiac output and systemic vascular resistance by acetylene rebreathing technique both before and after therapy. RESULTS: Pioglitazone increased (P < 0.001 from baseline) total body water (+2.4 +/- 0.5 l) accounting for 75% of the total weight gain (+3.1 +/- 2.0 kg) but did not alter vascular endothelial growth factor concentrations. Total abdominal (-32.2 +/- 19 cm(2)) and visceral fat area (-16.1 +/- 8 cm(2)) tended to decrease with pioglitazone but increased (P < 0.02 for differences between groups) with glipizide (+38.4 +/- 17 cm(2) abdominal; +19.1 +/- 9 cm(2) visceral). Pioglitazone tended to reduce (P = 0.05) diastolic (-8.4 +/- 4 mmHg) and mean (-9.5 +/- 5 mmHg; P = 0.08) blood pressure and reduced (P < 0.001) systemic vascular resistance (2,785 +/- 336 vs. 2,227 +/- 136 dynes/s per m(2)), while there were no differences in these parameters with glipizide. Neither therapy altered circulating catecholamine concentrations. CONCLUSIONS: When pioglitazone and glipizide are given in doses sufficient to achieve equivalent glycemic control in people with type 2 diabetes, pioglitazone increases total body water, thereby accounting for the majority of weight gain, tended to decrease visceral and abdominal fat content and blood pressure, and reduces systemic vascular resistance.

Adult↗