Water intake, thirst, and copeptin responses to two dehydrating stimuli in lean men and men with obesity.

Objective: Physiological systems responsible for water homeostasis and energy metabolism are interconnected. This study hypothesized altered responses to dehydration including thirst, ad libitum water intake, and copeptin in men with obesity.

Methods: Forty-two men (22 lean and 20 with obesity) were stimulated by a 2-hour hypertonic saline infusion and a 24-hour water deprivation.

Type 2 diabetes after gastric bypass: remission in five models using HbA1c, fasting blood glucose, and medication status.

Background: The remission rates of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB) vary according to the glycosylated hemoglobin A1c (HbA1c), fasting blood glucose (FG), and medication status. Our objectives were to describe remission using the American Diabetes Association standards for defining normoglycemia and to identify the factors related to the preoperative severity of T2DM that predict remission to normoglycemia, independent of weight loss, after RYGB. The setting was an urban not-for-profit community hospital.

Short-term isocaloric manipulation of carbohydrate intake: effect on subsequent ad libitum energy intake.

Background: Isocaloric manipulation of carbohydrate or fat intake could alter subsequent ad libitum food intake.

Methods: In a controlled inpatient study, we investigated whether isocaloric manipulation of carbohydrate or fat would alter subsequent ad libitum energy intake. Eighteen non-diabetic subjects (age range 19-53 years.

Effect of paternal diabetes on pre-diabetic phenotypes in adult offspring.

Objective: Paternal and maternal type 2 diabetes, exclusive of gestational diabetes, may influence risk factors in the offspring differently (through possible epigenetic effects of parental diabetes) and are difficult to identify without accurate dates of diagnosis. We aimed to examine a metabolic phenotype in three different groups of offspring to see distinct paternal versus maternal effects.

Research Design And Methods: We examined body composition and insulin action (M) in nondiabetic subjects and insulin secretion tested via acute insulin response (AIR) in normal glucose-tolerant full-heritage Pima Indian adults categorized by disparate parental diabetes status: 1) offspring of fathers with early-onset diabetes (age <35 years) and nondiabetic mothers (ODF; n = 10), 2) offspring of mothers with early-onset diabetes (age <35 years), not exposed to diabetes in utero with nondiabetic fathers (OMED; n = 11), and 3) a control group of offspring of parents without diabetes until >50 years of age (CON; n = 15).

Assessment of non-insulin-mediated glucose uptake: association with body fat and glycemic status.

In the fasting state, approximately 83% of glucose uptake occurs via non-insulin-mediated mechanisms. A widely accepted static rate for NIMGU is 1.62 mg kg(-1)·min(-1).

Childhood predictors of adult acute insulin response and insulin action.

Objective: Because declines in acute insulin response (AIR) and insulin action (M) predict development of type 2 diabetes, we sought to determine childhood factors that predict insulin action and AIR using longitudinal data from young Pima Indian adults with normal glucose regulation.

Research Design And Methods: Predictors of adult M, measured by the euglycemic-hyperinsulinemic clamp, and AIR, measured after a 25-g glucose bolus, were assessed in 76 individuals from a set of childhood data (BMI, systolic blood pressure [sBP] and diastolic blood pressure, cholesterol, fasting and 2-h insulin, and glucose levels during an oral glucose tolerance test).

Results: After adjustment for sex, adult percent body fat, adult and childhood age, childhood BMI, and sBP were negative and independent predictors of adult M.

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.

Distribution of subcutaneous fat predicts insulin action in obesity in sex-specific manner.

The pattern of adipose tissue (AT) distribution is an important predictor of metabolic risk. The aim of this study was to analyze the association of peripheral (insulin-mediated glucose disposal--M) and hepatic (suppression of endogenous glucose production--EGP) insulin action with abdominal (subcutaneous abdominal AT-SAAT intraabdominal AT-IAAT) and thigh AT depots in obese individuals. Fifty-seven Pima Indians with normal glucose tolerance underwent magnetic resonance imaging (MRI) and euglycemic-hyperinsulinemic clamp.

Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals.

Background: Enlargement of adipocytes from subcutaneous abdominal adipose tissue (SAT), increased intrahepatic lipid content (IHL), intramyocellular lipid content (IMCL), and low circulating adiponectin concentrations are associated with insulin resistance.

Objective: Because adiponectin increases fat oxidation in skeletal muscle and liver, and the expression of the adiponectin gene in SAT is inversely associated with adipocyte size, we hypothesized that hypoadiponectinemia links hypertrophic obesity with insulin resistance via increased IMCL and IHL.

Design: Fifty-three obese Pima Indians with a mean (+/-SD) age of 27 +/- 8 y, body fat of 35 +/- 5%, and normal glucose regulation (normal fasting and 2-h glucose concentration per WHO 1999 criteria) underwent euglycemic-hyperinsulinemic clamp, biopsies of SAT and vastus lateralis muscle, and magnetic resonance imaging of the abdomen.

Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals.

Background: Thyroid hormones (TH) may influence glucose metabolism. Hyperthyroid subjects have higher insulin secretion rates when compared with euthyroid individuals.

Objective: To evaluate the association between TH concentrations and insulin secretion in euthyroid, healthy Pima Indian adults (n=55, 29+/-7 years, females/males 36/19) with normal glucose tolerance (NGT) admitted to a Clinical Research Unit.

Palmitate action to inhibit glycogen synthase and stimulate protein phosphatase 2A increases with risk factors for type 2 diabetes.

Recent studies have suggested that abnormal regulation of protein phosphatase 2A (PP2A) is associated with Type 2 diabetes in rodent and human tissues. Results with cultured mouse myotubes support a mechanism for palmitate activation of PP2A, leading to activation of glycogen synthase kinase 3. Phosphorylation and inactivation of glycogen synthase by glycogen synthase kinase 3 could be the mechanism for long-chain fatty acid inhibition of insulin-mediated carbohydrate storage in insulin-resistant subjects.

The effect of insulin on net lipid oxidation predicts worsening of insulin resistance and development of type 2 diabetes mellitus.

Suppression of lipid oxidation (L(ox)) by insulin is impaired in obesity and type 2 diabetes mellitus (T2DM). Here we tested whether high L(ox) represents a primary or acquired characteristic in the pathogenesis of T2DM. Hood-indirect calorimetry was performed under postabsorptive conditions and during a two-step hyperinsulinemic euglycemic clamp (insulin infusion rates in mU.

Glucose response to an oral glucose tolerance test predicts weight change in non-diabetic subjects.

Objective: Glucose exerts a dual action in the regulation of energy balance, consisting of inhibition of energy intake and stimulation of energy expenditure. Whether blood glucose affects long-term regulation of body weight in humans remains to be established. We sought to test the hypothesis that the post-challenge glucose response is a predictor of weight change.

11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective changes in body weight and insulin resistance.

Objective: Increased mRNA and activity levels of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non-diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)].

Research Methods And Procedures: Prospective analyses were performed in 20 subjects (two whites and 18 Pima Indians) who had baseline measurements of 11betaHSD1 mRNA and activity in whole AT (follow-up, 0.

Acute insulin response is an independent predictor of type 2 diabetes mellitus in individuals with both normal fasting and 2-h plasma glucose concentrations.

Background: Earlier prospective studies have identified insulin action and secretion as predictors of T2DM in populations with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) (2-h OGTT < 7.8 and 7.8-11 mmol/L, respectively).

Higher fasting plasma concentrations of glucagon-like peptide 1 are associated with higher resting energy expenditure and fat oxidation rates in humans.

Background: Glucagon-like peptide 1 (GLP-1) is a gut hormone that decreases appetite and promotes satiety. Its role in energy metabolism regulation is still poorly understood.

Objective: The aim of the study was to investigate the relation of fasting plasma GLP-1 concentrations to rates of energy expenditure (EE) and substrate oxidation-ie, respiratory quotient (RQ).

Lower total fasting plasma adiponectin concentrations are associated with higher metabolic rates.

Context: The possible role of adiponectin, a protein uniquely produced by the adipose tissue and significantly reduced in obesity and other insulin-resistant states, in the regulation of energy expenditure (EE) is still poorly understood.

Objective: The objective of the study was to investigate the relationship between total fasting plasma adiponectin concentrations and the various components of EE measured in a metabolic chamber in Pima Indians and to test whether body fat distribution may have a role in this association.

Design: This was a cross-sectional study.

Serum gamma-glutamyl transpeptidase is a determinant of insulin resistance independently of adiposity in Pima Indian children.

Context: Elevated activities of serum enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT), have been associated with obesity and insulin resistance (IR). ALT is an independent predictor of type 2 diabetes mellitus (T2DM) in adult Pima Indians, and GGT predicts T2DM in other adult populations.

Objective: Our aim was to establish whether independent relationships exist between either adiposity or IR and hepatic enzymes in a group of Pima Indian children.

Intrauterine exposure to diabetes is a determinant of hemoglobin A(1)c and systolic blood pressure in pima Indian children.

Context/objective: Given the increasing rates of both childhood obesity and type 2 diabetes (T2DM), we investigated whether maternal diabetes status during pregnancy is a determinant of risk factors associated with T2DM or cardiovascular disease in offspring during childhood.

Design/participants: Forty-two Pima Indians, aged 7-11 yr, were identified retrospectively from maternal oral glucose tolerance tests as offspring of a diabetic pregnancy (22 ODM, eight males, 14 females) or offspring born before the mother developed diabetes (20 PRE, 12 males, eight females). SETTING/MAIN OUTCOME MEASURES: Weight, height, body mass index, percent body fat, blood pressure, and fasting concentrations of glucose, insulin, hemoglobin A1c (HbA1c), total cholesterol, triglycerides, and high-density lipoprotein-cholesterol were measured while staying in an in-patient clinical research unit and compared in cross-sectional analyses.

Weight, adiposity, and physical activity as determinants of an insulin sensitivity index in pima Indian children.

Objective: To determine whether measures of physical activity are related to an insulin sensitivity index ([ISI] 10(4)/fasting insulin x glucose) independent of weight or adiposity in children.

Research Design And Methods: We conducted a longitudinal study of 90 Pima Indian children (39 boys and 51 girls) at 5 and 10 years of age measuring adiposity (dual-energy X-ray absorptiometry), physical activity behavior (questionnaire: number of activities per week [ACT], average hours per week [TIME]), and energy expenditure (doubly labeled water: physical activity level [PAL]).

Results: In cross-sectional analyses, ACT was correlated with ISI at 5 years of age (r = 0.

Cross-sectional and prospective relationships of fasting plasma ghrelin concentrations with anthropometric measures in pima Indian children.

Ghrelin, a recently discovered GH secretagogue with orexigenic effects, is proposed to be a regulator of energy balance. To test whether fasting plasma ghrelin concentrations predict future gain in body weight or adiposity, we measured weight, height, body mass index (BMI), percentage of body fat (by dual energy x-ray absorptiometry), and fasting plasma concentrations of ghrelin, insulin, and glucose in 10-yr-old Pima Indians (n = 40; 13 males and 27 females) and subsequent weight, height, and BMI 1.7 +/- 0.

High circulating ghrelin: a potential cause for hyperphagia and obesity in prader-willi syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder occurring in 1 of 10,000-16,000 live births and is characterized by excessive appetite with progressive massive obesity as well as short stature and mental retardation. Most patients have GH deficiency and hypogonadotropic hypogonadism. The causes of the hyperphagia and abnormal GH secretion are unknown.

Plasma adiponectin concentrations in children: relationships with obesity and insulinemia.

Adiponectin, a novel adipokine with anti-inflammatory and insulin-sensitizing properties, has been found to have independent negative associations with obesity and hyperinsulinemia/insulin resistance in adults. We measured fasting plasma adiponectin and insulin concentrations and body composition (dual-energy x-ray absorptiometry or doubly labeled water) in 30 5-yr-old (11 boys and 19 girls) and 53 10-yr-old (17 boys and 36 girls) Pima Indian children. A subgroup of 20 children (5 boys and 15 girls) had all measurements at both 5 and 10 yr of age.