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Biomedical subjects

C Bogardus

Publications and source records attributed to C Bogardus.

At least 109 records · Page 6Linked to original sources
PubMed1994

Linkage analysis of acute insulin secretion with GLUT2 and glucokinase in Pima Indians and the identification of a missense mutation in GLUT2.

The acute insulin response (AIR), a measure of pancreatic beta-cell function, aggregates in families and is a predictor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in insulin-resistant Pima Indians. To assess the genetic components of AIR and NIDDM, polymorphic dinucleotide repeat regions in two candidate genes, the liver/islet glucose transporter gene (GLUT2) and the glucokinase gene, were evaluated. Sib-pair linkage analyses were performed to determine if linkage exists between these marker loci and measurements of AIR and NIDDM. No linkage was found between glucokinase and either AIR or NIDDM. Robust sib-pair linkage analyses suggest linkage between GLUT2 and acute insulin response (P = 0.04), but no linkage was observed with NIDDM. The coding region of the GLUT2 gene was screened for mutations using polymerase chain reaction-single-strand conformation polymorphism analysis. A single base change was identified in exon 3 in approximately 5% of the study population, and it constitutes the first reported mutation in the human GLUT2 gene. This base change resulted in an amino acid substitution (Thr110-->Ile110) in the second membrane-spanning region of the GLUT2 protein. No significant association was noted between AIR and the presence or absence of the mutation. Thus, this mutation in GLUT2 is unlikely the cause of a low AIR in Pima Indians.

Amino Acid Sequence↗
PubMed1994

The correct usage of the new radiation oncology codes. 77395--3-dimensional simulation; 77419--conformal weekly radiation therapy treatment management; 77432--stereotactic treatment management.

In summary, radiation oncology now has three new related codes describing the 3-dimensional simulation and treatment of relatively small tumor volumes. These codes, when properly used and completely documented, are reimbursable at rates higher than the conventional simulation and treatment delivery codes that they replace. The physician should be cautioned however, that the indiscriminate use of these codes without accurate documentation of the medical necessity could result in penalties and/or pay back in the event of an audit. As with all new codes, we may rest assured that the insurance carrier will be looking very carefully at the documentation of these new and expensive procedures.

Computer Simulation↗
PubMed1994

Glycemic response to stress is altered in euglycemic Pima Indians.

The aim of this work was to study the effects of a computer-driven mental arithmetic task on blood glucose in a group of four male and four female euglycemic Caucasians and a group of seven male and six female euglycemic Pima Indians. Approximately 60% of euglycemic Pima Indian Native Americans eventually develop type 2 diabetes, while only 5% of Caucasians develop the disease. All subjects had normal glucose tolerance. Subjects were given a standard breakfast; 2 h later, they were given a computerized mental arithmetic stress test for 10 min. Before, during and after the test, several variables were analyzed, including serum concentrations of glucose, insulin, glucagon and plasma cortisol and catecholamines. Heart rate, systolic and diastolic blood pressure and all the stress hormones increased during stress and decreased during recovery in all subjects. Blood glucose consistently declined one hour after the meal in all subjects. However, while it continued to decline following stress in seven out of eight Caucasian subjects, it consistently increased during and following stress in 10 out of 13 Pima Indians. Fasting serum glucose in Pima Indians and Caucasians was respectively 5.07 + 0.08 mM and 5.04 + 0.09 mM. Two-hour post-prandial values were 5.63 + 0.22 mM and 5.48 + 0.19 mM respectively, whereas post-stress values were 6.15 + 0.19 mM for Pima Indians and 5.22 + 0.20 mM for Caucasians. Both serum glucose means following stress (t = 3.1, P < 0.005) and the direction of change in serum glucose in response to mental arithmetic (chi 2 = 8.2, P < 0.01) clearly differentiated Pimas from Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians.

BACKGROUND: The relative roles of obesity, insulin resistance, insulin secretory dysfunction, and excess hepatic glucose production in the development of non-insulin-dependent diabetes mellitus (NIDDM) are controversial. We conducted a prospective study to determine which of these factors predicted the development of the disease in a group of Pima Indians. METHODS: A body-composition assessment, oral and intravenous glucose-tolerance tests, and a hyperinsulinemic--euglycemic clamp study were performed in 200 non-diabetic Pima Indians (87 women and 113 men; mean [+/- SD] age, 26 +/- 6 years). The subjects were followed yearly thereafter for an average of 5.3 years. RESULTS: Diabetes developed in 38 subjects during follow-up. Obesity, insulin resistance (independent of obesity), and low acute plasma insulin response to intravenous glucose (with the degree of obesity and insulin resistance taken into account) were predictors of NIDDM: The six-year cumulative incidence of NIDDM was 39 percent in persons with values below the median for both insulin action and acute insulin response, 27 percent in those with values below the median for insulin action but above that for acute insulin response, 13 percent in those with values above the median for insulin action and below that for acute insulin response, and 0 in those with values originally above the median for both characteristics. CONCLUSIONS: Insulin resistance is a major risk factor for the development of NIDDM: A low acute insulin response to glucose is an additional but weaker risk factor.

Adult↗
PubMed1993

Serum androgens in hyperinsulinemic Pima Indian and obese Caucasian women and their response to short-term insulin infusion.

Insulin resistance and its attendant hyperinsulinemia has been linked with hyperandrogenism. Insulin resistance is characteristic of the Pima Indians of the Gila River Indian community in central Arizona. Serum androgens, testosterone and dehydroepiandrosterone sulfate (DHEA-S) were quantitated at baseline and in response to low- and high-dose insulin infusion in 11 obese, hyperinsulinemic Pima Indian and 10 obese, hyperinsulinemic Caucasian women and were compared with baseline androgens in 16 nonobese Caucasian women. While there was no significant testosterone or DHEA-S response to short-term insulin infusion in either Pimas or obese Caucasians, both these groups had higher baseline testosterone concentrations (67 +/- 6.5 ng/dl in the Pimas, 55 +/- 5.9 ng/dl in the obese Caucasians) as compared with the nonobese Caucasians (28 +/- 2 ng/dl; p < 0.001). Baseline DHEA-S concentrations were not significantly different in the three groups. Given the hyperinsulinemic status of both the Pimas and the obese Caucasians, the finding of higher testosterone concentrations in these subjects as compared with nonobese Caucasians supports a role for insulin in ovarian androgen production and demonstrates that hormonal interactions that may be operating in obese hyperinsulinemic Caucasian subjects also operate in obese, hyperinsulinemic Pima Indians.

Adipose Tissue↗
PubMed1993

Norepinephrine turnover and energy expenditure in Pima Indian and white men.

There is growing evidence of the involvement of sympathetic nervous system (SNS) activity in determining metabolic rate. Whole-body plasma norepinephrine turnover and its relationship to resting metabolic rate (RMR) and 24-hour energy expenditure (24EE) were compared in 14 Pima Indian men (25 +/- 4 years, 96 +/- 33 kg, 25% +/- 9% fat) and nine white men (25 +/- 3 years, 88 +/- 43 kg, 17% +/- 13% fat). Plasma norepinephrine turnover rate correlated strongly with body surface area (r = .76 and .54 for clearance and appearance, respectively) and fat-free mass (r = .74 and .52, respectively). However, independent of body size, there was no difference in either norepinephrine clearance or appearance rates between Pima Indian and white men. Norepinephrine appearance rate correlated positively with absolute values of 24EE and RMR, but not when adjusted for differences in body surface area or fat-free mass. However, norepinephrine appearance rate adjusted for differences in body size correlated with spontaneous physical activity. The results indicate that Pima Indian and white men have similar plasma norepinephrine appearance rates, but Pima Indians tend to be more resistant to beta-adrenergic stimulation. Although energy expenditure and SNS activity were not directly related, a higher SNS tone may either promote or reflect elevated levels of spontaneous physical activity and therefore influence both energy balance and body composition.

Adult↗
PubMed1993

Linkage of chromosomal markers on 4q with a putative gene determining maximal insulin action in Pima Indians.

Insulin action in vivo varies widely in nondiabetic Pima Indians. Not all of this variance is attributable to individual differences in obesity, physical fitness, sex, or age, and after correcting for these co-variates, measures of insulin action aggregate in families. Insulin action at maximally stimulating insulin concentrations has a trimodal frequency distribution, particularly among obese individuals. This is consistent with the hypothesis that a codominantly inherited autosomal gene, unrelated to obesity, determines MaxM in the population. Preliminary sib-pair linkage analyses indicated the possibility of linkage between MaxM and the GYPA/B locus (encoding the MNSs red cell surface antigens) on chromosome 4q. To confirm and extend these findings, 10 additional loci on 4q were typed in 123 siblings and many of their parents from 46 nuclear families. The results indicate significant (P < 0.001) linkage of the FABP2 and ANX5 loci on 4q with MaxM, and of FABP2 with fasting insulin concentration. No linkage was found between the 4q markers and obesity. Our findings indicate that a gene on 4q, near the FABP2 and ANX5 loci, contributes to in vivo insulin action in Pima Indians.

Adult↗
PubMed1993

Insulin resistance in the pathogenesis of NIDDM in Pima Indians.

NIDDM in Pima Indians is characterized by obesity, abnormal insulin secretion, insulin resistance, and excess hepatic glucose output. Cross-sectional studies, and, as yet incomplete longitudinal studies of nondiabetic and diabetic Pima Indians suggest that the natural history of the disease begins with insulin resistance and, subsequently, when insulin secretion fails, increasing hepatic glucose output occurs, resulting in increasing fasting hyperglycemia. The insulin resistance that precedes the development of fasting hyperglycemia is not due solely to obesity. Insulin resistance aggregates in families and the trimodel frequency distribution of insulin action in vivo suggests it may have genetic determinants.

Arizona↗
PubMed1992

Pima Indians as a model to study the genetics of NIDDM.

More than half the Pima Indians over 35 years of age have non-insulin dependent diabetes mellitus (NIDDM). They have been the focus of prospective epidemiologic and metabolic studies for over two decades and the data collected during these studies are now proving invaluable in efforts to find genetic markers for NIDDM in humans. The Pima Indian model of this disease affords two major advantages. The population is genetically homogeneous compared to Caucasian populations, and therefore the causes of NIDDM are less heterogeneous, simplifying genetic linkage studies. Equally important, based on results from metabolic studies, two pre-diabetic phenotypes have been identified in the Pimas: insulin resistance and a low metabolic rate. Use of these phenotypes in genetic linkage analyses should greatly improve chances of finding genetic markers for NIDDM since these phenotypes may be more closely related to the putative abnormal gene products, and actual disease genes, than is the hyperglycemia of the fully developed phenotype of NIDDM.

Adult↗
PubMed1992

A brief overview of human energy metabolism and its relationship to essential obesity.

Twenty-four hour energy expenditure (24EE) can be measured in a respiratory chamber. 24EE is comprised of the basal metabolic rate, the thermic effect of food, and the energy cost of physical activity. The major determinant of 24EE, fat-free mass, accounts for approximately 80% of the variance observed between individuals. Genetic factors seem to be the cause of the familial aggregation of 24EE in man. The variability of 24EE for a given body size and composition is of importance because a low metabolic rate is a major risk factor for weight gain in man. There is increasing evidence that obesity, often an inherited disorder, cannot always be attributed to gluttony and sloth. Similar to the need to treat essential hypertension, there is a need to treat a disorder perhaps best called essential obesity.

Basal Metabolism↗
PubMed1992

Spontaneous physical activity and obesity: cross-sectional and longitudinal studies in Pima Indians.

Healthy, nondiabetic Pima Indians [103 males, 77 females; 27 +/- 6 (SD) yr, 97 +/- 25 kg, 33 +/- 9% body fat] were studied in a respiratory chamber in which spontaneous physical activity (SPA) was measured by two microwave sensors. SPA, defined as the percentage of time the subjects were active, varied widely from 4.4 to 17.5%. It was higher in males (9.3 +/- 2.0%) than in females (8.6 +/- 2.3%; P less than 0.05) and was not related to body fatness in either sex. However, SPA accounted for a significant portion of the daily energy expenditure (24-h EE) in males (1,389 +/- 423 kJ/day) and females (1,163 +/- 351 kJ/day) and correlated positively with 24-h EE adjusted for differences in fat-free mass, fat mass, age, and sex (r = 0.42, P less than 0.0001). In 88 siblings, family membership accounted for 57% of the variance in SPA (r(i) = 0.57, P less than 0.02). Body composition was reassessed in a subgroup of 123 subjects (65 males, 58 females) 33 +/- 14 mo later. In males only, SPA correlated inversely to the rate of subsequent body weight change (r = -0.25, P less than 0.05) and the rate of fat-mass change (r = -0.35, P less than 0.005). We conclude that spontaneous physical activity is a familial trait that may play a role in the pathogenesis of obesity.

Adult↗
PubMed1992

Concomitant interindividual variation in body temperature and metabolic rate.

There is significant variation in metabolic rate in humans, independent of differences in body size, body composition, age, and gender. Although it has been generally held that the normal human "set-point" body temperature is 37 degrees C, these interindividual variations in metabolic rate also suggest possible variations in body temperature. To examine the possibility of correlations between metabolic rate and body temperature, triplicate measurements of oral temperatures were made before and after measurement of 24-h energy expenditure in a respiratory chamber in 23 Pima Indian men. Fasting oral temperatures varied more between individuals than can be attributed to methodological errors or intraindividual variation. Oral temperatures correlated with sleeping (r = 0.80, P < 0.0001), and 24-h (r = 0.48, P < 0.02) metabolic rates adjusted for differences in body size, body composition, and age. Similarly, in the 32 Caucasian men of the Minnesota Semi-Starvation Study, oral temperature correlated with adjusted metabolic rate, and the interindividual differences in body temperature were maintained throughout semistarvation and refeeding. These results suggest that a low body temperature and a low metabolic rate might be two signs of an obesity-prone syndrome in humans.

Adult↗