Repeatability and reproducibility of the hyperinsulinemic-euglycemic clamp and the tracer dilution technique in a controlled inpatient setting.

The objective of the study was to evaluate the reproducibility and repeatability of the combined use of the hyperinsulinemic-euglycemic (H-E) clamp and tracer dilution techniques. Ten nondiabetic men underwent a low-dose (40 mU/[m(2) min]) H-E clamp that was repeated within 3 to 4 days using porcine or human insulin in a double-blinded, randomized, crossover design. Coefficients of variation (CVs) for intraindividual differences and repeatability coefficient were calculated to evaluate reproducibility and repeatability. The Bland and Altman method was used to quantify repeatability. The CVs for intraindividual differences were 5.7% +/- 3.5% for steady-state (SS) insulin; 6.7% +/- 6.2% and 54.2 +/- 38.3% for basal and SS endogenous glucose product (EGP), respectively; and 10.3% +/- 8.5% for total insulin-stimulated glucose disposal (M) values. Basal EGP, SS EGP, and SS glucose and insulin concentrations were similar for the 2 clamps; but glucose infusion rate (P = .02) and M (borderline significant, P = .06) were higher in the first clamp than the second clamp. No significant correlations between mean of differences and average of basal and SS EGP, SS insulin concentration, and M between the 2 clamps were observed. We also found that the different values were less than the repeatability coefficients of these parameters and that the 95% limits of agreement and the interval of repeatability coefficient of these parameters were similar. There were no differences in metabolic responses between clamps when compared by the type of insulin (porcine vs human) infused. Our findings indicate that, although SS EGP has a high CV, the clamp, which measures insulin action (ie, SS insulin, M), and the tracer dilution technique for assessing basal EGP are repeatable and reproducible. Decreased glucose infusion rate and M over a short period in the second clamp may reflect an accumulative effect of continued physical inactivity.

Elevated concentrations of linoleic acid in erythrocyte membrane phospholipids in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), is a disorder characterized by diffuse inflammation of the gastrointestinal tract. The immune response and inflammation are mediated by polyunsaturated fatty acids and influenced by dietary fats and lipid metabolism. This study examined the qualitative and quantitative fat intake of IBD patients and healthy controls on plasma phospholipid and erythrocyte membrane phospholipid (EMP) fatty acid content. Measurement of the fatty acid composition of plasma phospholipid and EMP were performed in 29 UC patients, 20 CD patients, and 31 healthy controls. Anthropometric characteristics and data on dietary intake were also collected. We observed significantly lower lipid intake in UC and CD patients vs controls. The UC and CD patients had significantly higher levels of linoleic acid in their EMP than did controls. There were no significant differences in the levels of n-3 polyunsaturated fatty acids, but there were significantly higher levels of the n-6 in the EMP of UC and CD patients compared with controls. The significant differences persisted after the data were adjusted for potential confounders and lipid intake. Higher levels of linoleic acids and n-6 fatty acids, which are involved in production of proinflammatory mediators, were found in IBD patients compared with controls, thereby implicating n-6 fatty acids in the pathophysiology of the disease.

The association of plasma fibrinogen concentration with diabetic microvascular complications in young adults with early-onset of type 2 diabetes.

AIMS: Diabetic nephropathy is an important risk factor for cardiovascular diseases (CVD). The underlying etiology is not fully understood but may be related to changes in inflammatory and hemostatic markers with kidney disease. We investigated the associations of the markers with microvascular complications in Pima Indians (PI) with early-onset type 2 diabetes (T2DM). METHODS: C-reactive protein, interleukine-6, fibrinogen, D-dimer, plasmin-antiplasmin complex and plasminogen activator inhibitor-1 were measured in 104 PI (age: 32+/-4 y) with diabetes and 59 (32+/-4 y) with fasting glucose <110 mg/dl and 2-h glucose <140 mg/dl. Urine albumin to creatinine ratio (ACR) was used as marker of nephropathy. Severity of retinopathy was classified in the worse eye by direct ophthalmoscopy as none, background and proliferative. RESULTS: Of these markers, only fibrinogen was associated with ACR (r=0.25, p<0.01). After adjustment for age, sex, percentage Pima heritage, smoking status, diabetes duration, blood pressure and use of aspirin, antihypertensive and antihyperglycemic agents, general linear models (with natural log-transformed values of fibrinogen and ACR as dependent and independent variables, respectively) revealed that a one percent increase in ACR would yield a 0.02% increase in the fibrinogen (beta=0.02, p<0.05). Plasma fibrinogen was also significantly increased with severity of diabetic retinopathy (p<0.05). CONCLUSIONS: Increased plasma fibrinogen concentration was associated with diabetic microvascular disease, in particular with nephropathy. This may help to explain the etiologic link between nephropathy and CVD.

Postprandial glucagon-like peptide-1 (GLP-1) response is positively associated with changes in neuronal activity of brain areas implicated in satiety and food intake regulation in humans.

Postprandial glucagon-like peptide-1 (GLP-1) secretion can act as a meal termination signal in animals and humans. We tested the hypothesis that the postprandial changes in plasma GLP-1 concentrations are associated with changes in the human brain activity in response to satiety by performing a post-hoc analysis of a cross-sectional study of neuroanatomical correlates of hunger and satiation using (15)O-water positron-emission tomography (PET). Forty-two subjects (22M/20F, age 31+/-8 years) spanning a wide range of adiposity (body fat: 7-44%) were included in this analysis. Outcome measures included changes in PET-measured regional cerebral blood flow (rCBF) and plasma concentrations of GLP-1, glucose, insulin, and free-fatty acids (FFA), elicited by the administration of a satiating amount of a liquid formula meal. The peak postprandial increases in plasma GLP-1 concentrations were correlated with increases in rCBF in the left dorsolateral prefrontal cortex (including the left middle and inferior frontal gyri), previously implicated in PET studies of human satiation, and the hypothalamus, previously implicated in the regulation of food intake in animal and human studies, both before and after adjustment for sex, age, body fat, and changes in plasma glucose, insulin, and serum FFA concentrations. The postprandial GLP-1 response is associated with activation of areas of the human brain previously implicated in satiation and food intake regulation.

Relationships between plasma leptin concentrations and human brain structure: a voxel-based morphometric study.

We have previously demonstrated that obese people have reduced grey matter (GM) in several brain areas, including regions implicated in the regulation of taste (i.e., inferior frontal operculum and postcentral gyrus), reward (i.e., putamen), and behavioural processing (i.e., middle frontal gyrus), compared with their lean counterparts. It is well established that the brain may serve as a direct target for adiposity signals, one of the most important being leptin. We investigated the relationships between fasting plasma leptin concentrations and brain tissue composition in a group of 32 young adult Caucasians (12M/20F, age 32+/-1 years, body fat 29+/-1%, mean+/-S.E.) with normal glucose tolerance by using voxel-based morphometry of magnetic resonance imaging scans. Fasting plasma leptin concentrations were positively correlated with GM volumes of the left cerebellum and left inferior temporal gyrus and negatively associated with GM volumes of the left inferior frontal operculum, left postcentral gyrus, and right putamen (P<0.001, uncorrected for multiple comparisons) after adjustment for sex, percent body fat, age, fasting plasma insulin concentrations (i.e., the major determinants of plasma leptin), and global GM volume (thus allowing for an assessment of regional effects only). This study showed an independent, negative correlation between fasting plasma leptin concentrations, which are increased in obesity, and the volumes of GM in brain areas where obese people have reduced GM compared to their lean counterparts. These relationships may explain some of the abnormalities in brain morphology recently found to be associated with excess body fatness.

Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity.

BACKGROUND: In an exploratory positron emission tomography study of postprandial regional cerebral blood flow, which is a marker of neuronal activity, obese men differed from lean men in several brain regions, including the prefrontal cortex. The subjects received a meal proportional to their body size; therefore, the meal volume was different for each person. OBJECTIVE: We investigated whether differences in the brain responses of obese and lean men to a meal represent satiety or feelings of gastric distension. DESIGN: We studied 9 lean (x +/- SD body fat: 15 +/- 5%; age: 33 +/- 10 y) and 9 obese (body fat: 31 +/- 4%; age: 32 +/- 10 y) men given a fixed amount (400 mL) of a liquid meal. We compared their results with those in 11 lean (body fat: 16 +/- 5%; age: 35 +/- 8 y) and 11 obese (body fat: 33 +/- 5%; age: 28 +/- 5 y) previously studied men given a meal proportional to their body size. We performed analyses by using a two-level, random-effects approach in the STATISTICAL PARAMETRIC MAPPING software package and a significance level of P < or = 0.001, uncorrected for multiple comparisons. RESULTS: Compared with lean men, obese men had consistently less postprandial activation in the left dorsolateral prefrontal cortex, irrespective of meal size. CONCLUSION: Because the dorsolateral prefrontal cortex has been implicated in the inhibition of inappropriate behavior, satiety, and meal termination, differential responses of neuronal activity to food intake in this area may contribute to a propensity for obesity or to the difficulty in losing weight experienced by obese men.

Brain abnormalities in human obesity: a voxel-based morphometric study.

Obesity is accompanied by damage to several tissues. Overweight is a risk factor for Alzheimer's disease and other neurodegenerative disorders. Whether structural abnormalities associated with excess body fat may also occur in the brain is unknown. We sought to determine to what extent excess body fat is associated with regional alterations in brain structure using voxel-based morphometry (VBM), a whole-brain unbiased technique based upon high-definition 3D magnetic resonance imaging (MRI) scans normalized into a common standard space and allowing for an objective assessment of neuroanatomical differences throughout the brain. We studied 24 obese (11 male, 13 female; age: 32 +/- 8 years; body mass index [BMI]: 39.4 +/- 4.7 kg/m2) and 36 lean (25 male, 11 female; mean age: 33 +/- 9 years; BMI: 22.7 +/- 2.2 kg/m2) non-diabetic Caucasians. In comparison with the group of lean subjects, the group of obese individuals had significantly lower gray matter density in the post-central gyrus, frontal operculum, putamen, and middle frontal gyrus (P < 0.01 after adjustment for sex, age, handedness, global tissue density, and multiple comparisons). BMI was negatively associated with GM density of the left post-central gyrus in obese but not lean subjects. This study identified structural brain differences in human obesity in several brain areas previously involved in the regulation of taste, reward, and behavioral control. These alterations may either precede obesity, representing a neural marker of increased propensity to gaining weight, or occur as a consequence of obesity, indicating that also the brain is affected by increased adiposity.

Obesity is associated with increased risk of allergy in Vietnamese adolescents.

BACKGROUND: The prevalence of allergic diseases has remarkably increased in the last decades in tandem with the number of obese individuals. Results of studies on obesity and allergic diseases are controversial, and most of them are related to asthma and asthma-like symptoms. OBJECTIVE: In our study, we evaluated the association of several obesity indices and the prevalence of allergic diseases, including bronchial asthma, allergic rhino-conjunctivitis, atopic dermatitis and food allergy. DESIGN: Cross-sectional study. RESULTS: From a total of 1185 adolescents (49.3% boys) aged 12 to 17 y old, 19.3% reported a physician-diagnosed allergic disease, and 35.3% reported undiagnosed allergic symptoms. Logistic regression analysis revealed a higher risk of allergy in children of middle (OR = 2.02, CI: 1.12-3.64) and high (OR = 2.40, CI: 1.25-4.61) compared to low socioeconomic status, in subjects reporting industrial emissions in the neighborhood (OR = 2.19, CI: 1.40-3.41), and in adolescents with parental history of allergy (OR = 1.92, CI: 1.26-2.92). Body mass index (BMI) and percentage of body fat (%BF) were significantly related to allergy (OR = 1.16, CI: 1.01-1.34 for BMI; OR = 1.03, CI: 1.01-1.06 for %BF). After controlling for socioeconomic status, industrial emissions and parental history of allergy, only %BF remained statistically significant (OR = 1.03, CI: 1.01-1.06). Food allergy was not related to obesity in our study population, and when adolescents with food allergy were excluded from the analysis, the odds of having allergy increased 28% with each increase in SD of BMI (OR = 1.28, CI: 1.05-1.57) and 5% for each unit increase in the percentage of body fat (OR = 1.05, CI: 1.01-1.08). CONCLUSION: In conclusion, being overweight was associated with an increased risk of allergy in our study population. Our results point towards an association between being overweight and rhino-conjunctivitis, but not food allergy. No association was observed with other allergic diseases.