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Biomedical subjects

P H Bennett

Publications and source records attributed to P H Bennett.

At least 19 recordsLinked to original sources
PubMed1999

Effect of hypertension on mortality in Pima Indians.

BACKGROUND: The effect of hypertension on mortality was examined in 5284 Pima Indians, 1698 of whom had type 2 diabetes at baseline or developed it during follow-up. METHODS AND RESULTS: During a median follow-up of 12.2 years (range, 0.01 to 24.8 years), 470 nondiabetic subjects and 488 diabetic subjects died. In the nondiabetic subjects, 45 of the deaths were due to cardiovascular disease, 208 to other natural causes, and 217 to external causes; in the diabetic subjects, 106 of the deaths were due to cardiovascular disease, 85 to diabetic nephropathy, 226 to other natural causes, and 71 to external causes. In the nondiabetic subjects, after adjusting for age, sex, body mass index, and serum cholesterol concentration in a proportional hazards model, hypertension predicted death from cardiovascular disease (death rate ratio [DRR]=2.8; 95% CI, 1.4 to 5. 6; P=0.003). In the diabetic subjects, after additional adjustment for duration of diabetes, plasma glucose concentration, and proteinuria, hypertension strongly predicted deaths from diabetic nephropathy (DRR=3.5; 95% CI, 1.7 to 7.2; P<0.001), but it had little effect on deaths from cardiovascular disease (DRR=1.4; 95% CI, 0.88 to 2.3; P=0.15). CONCLUSIONS: We propose that the weak relationship between hypertension and cardiovascular disease in diabetic Pima Indians is not because of a diminished effect of hypertension on cardiovascular disease in diabetes, but because of a relatively greater effect of hypertension on the progression of diabetic nephropathy. Factors that may account for this finding in Pima Indians include a younger age at onset of type 2 diabetes, a low frequency of heavy smoking, favorable lipoprotein profiles and, possibly, enhanced susceptibility to renal disease.

Adolescent↗
PubMed1999

Changing glomerular filtration with progression from impaired glucose tolerance to Type II diabetes mellitus.

Glomerular filtration rate (iothalamate clearance) was measured serially for 48 months in 26 Pima Indians with impaired glucose tolerance and 27 with normal glucose tolerance. At baseline, the mean glomerular filtration rate (SEM) was 133+/-8 ml/min in subjects with impaired glucose tolerance and 123+/-5 ml/min in those with normal glucose tolerance (p = 0.12). In the 12 subjects with impaired glucose tolerance who progressed to Type II (non-insulin-dependent) diabetes during follow-up, mean glomerular filtration rate increased by 30% (p = 0.011). Among the remaining 14 subjects with impaired glucose tolerance, 12 reverted to normoglycaemia. The glomerular filtration rate both at baseline and after 48 months in this subgroup exceeded the values of subjects with normal glucose tolerance by 20 % (p = 0.008) and 14% (p=0.013), respectively. A pronounced rise in the glomerular filtration rate occurs at the onset of Type II diabetes but a trend to hyperfiltration is also present in those with impaired glucose tolerance.

Analysis of Variance↗
PubMed1999

Effect of glycemia on mortality in Pima Indians with type 2 diabetes.

The effect of plasma glucose concentration on overall and cause-specific mortality was examined in 1,745 Pima Indians (725 men, 1,020 women) > or = 15 years old with type 2 diabetes. During a median follow-up of 10.6 years (range 0.1-24.8), 533 subjects (275 men, 258 women) died; 113 of the deaths were attributable to cardiovascular disease, 96 to diabetes-related diseases (diabetic nephropathy for 92 of these), 249 to other natural causes, and 75 to external causes. After adjusting for age, sex, duration of diabetes, and BMI in a generalized additive proportional hazards model, higher baseline 2-h postload plasma glucose concentration predicted deaths from cardiovascular disease (P = 0.007) and diabetes-related diseases (P = 0.003), but not from other natural causes (P = 0.73). An increment of 5.6 mmol/l (100 mg/dl) in the 2-h plasma glucose concentration was associated with 1.2 times (95% CI 1.1-1.4) the death rate from cardiovascular disease, 1.3 times (95% CI 1.1-1.5) the death rate from diabetes-related diseases, and almost no change in the death rate from other natural causes (rate ratio = 1.0; 95% CI 0.94-1.1). In Pima Indians with type 2 diabetes, higher plasma glucose concentration predicts deaths from cardiovascular and diabetes-related diseases but has little or no effect on deaths from other natural or external causes.

Adolescent↗
PubMed1999

Plasma leptin concentrations in Pima Indians living in drastically different environments.

OBJECTIVE: Plasma leptin, an important signal for the regulation of energy stores, is known to be influenced by many hormonal factors, but may also be affected by behavioral and environmental factors. The purpose of this study was to investigate the impact of lifestyle (diet composition, level of physical activity) on plasma leptin concentrations among Pima Indians living in drastically different environments. RESEARCH DESIGN AND METHODS: We studied 224 Mexican Pima Indians (115 women, 109 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 418 U.S. Pima Indians (281 women, 137 men) living a North American lifestyle on the Gila River Indian Reservation in Arizona. We hypothesized that the absolute value of leptin would be lower in Mexican Pima Indians because of their lower percent body fat, but could be further influenced by their lifestyle, independent of body composition. RESULTS: Leptin concentration (enzyme-linked immunosorbent assay [ELISA]) was strongly correlated with percent fat (bioimpedance) in Mexican Pima Indians (r = 0.83, P < 0.0001) and U.S. Pima Indians (r = 0.86, P < 0.0001). Among U.S. Pima Indians, independent of percent fat, subjects with type 2 diabetes had lower leptin than nondiabetic subjects (difference = 6.9 +/- 1.0 ng/ml, P < 0.002). Among nondiabetic subjects, Mexican Pima Indians had lower absolute leptin concentrations than U.S. Pima Indians, but higher after adjustment for percent body fat, waist circumference, age, and sex. In a subset of 70 pairs of subjects matched for sex and percent body fat, leptin concentration was 4.4 +/- 1.0 ng/ml (P < 0.0001) higher in Mexican Pima Indians versus U.S. Pima Indians. CONCLUSIONS: These results suggest that independent of body composition, leptin concentration may be increased by environmental factors, such as a high-carbohydrate diet and a high level of physical activity.

Adult↗
PubMed1999

Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults.

OBJECTIVE: To investigate the mechanisms underlying the association between birth weight and type 2 diabetes in a population-based study of 3,061 Pima Indians aged 5-29 years. RESEARCH DESIGN AND METHODS: Glucose and insulin concentrations were measured during a 75-g oral glucose tolerance test, and insulin resistance was estimated according to the homeostatic model (homeostasis model assessment-insulin resistance [HOMA-IR]). Relationships between birth weight, height, weight, fasting and postload concentrations of glucose and insulin, and HOMA-IR were examined with multiple regression analyses. RESULTS: Birth weight was positively related to current weight and height (P < 0.0001, controlled for age and sex, in each age-group). The 2-h glucose concentrations showed a U-shaped relationship with birth weight in subjects > 10 years of age, and this relation was independent of current body size. In 2,272 nondiabetic subjects, after adjustment for weight and height, fasting and 2-h insulin concentrations and HOMA-IR were negatively correlated with birth weight. CONCLUSIONS: Low-birth-weight Pimas are thinner at ages 5-29 years, yet they are more insulin resistant relative to their body size than those of normal birth weight. By contrast, those with high birth weight are more obese but less insulin resistant relative to their body size. The insulin resistance of low-birth-weight Pima Indians may explain their increased risk for type 2 diabetes.

Adolescent↗
PubMed1998

Birth weight and renal disease in Pima Indians with type 2 diabetes mellitus.

Congenital retardation of renal development may increase the risk of renal disease, and this risk may be enhanced by diseases, such as diabetes, that damage the kidney. In this study, the prevalence of urinary albumin excretion, determined in 308 Pima Indians with type 2 diabetes, was 63% in subjects with low birth weight (<2,500 g), 41% in those with normal birth weight (2,500-4,499 g), and 64% in those with high birth weight (> or =4,500 g). When examined as a continuous variable by generalized additive logistic regression, birth weight had a U-shaped association with the prevalence of elevated urinary albuminuria (p = 0.04) after adjustment for age, sex, duration of diabetes, glycosylated hemoglobin, and blood pressure. The odds of elevated albuminuria in subjects of low birth weight was 2.3 times (95% confidence interval 0.72-7.2) that in subjects of normal birth weight, and the odds in subjects of high birth weight was 3.2 times (95% confidence interval 0.75-13.4) as high. Sixty-four percent of the subjects with high birth weight and none of those with low birth weight were offspring of diabetic mothers. After maternal diabetes during pregnancy was controlled for, the odds of elevated albuminuria in subjects of high birth weight was no longer higher (odds ratio = 1.0, 95% confidence interval 0.22-4.9). The higher prevalence of elevated albuminuria in diabetic Pima Indians with high birth weight may be due to intrauterine diabetes exposure, whereas the higher prevalence in those with low birth weight may be due to the effects of intrauterine growth retardation.

Adolescent↗
PubMed1998

Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population.

To identify specific genes affecting vulnerability or resistance, we performed a whole-autosomal genome scan for genetic linkage to alcohol dependence in a Southwestern American Indian tribe. Genotypes at 517 autosomal microsatellite loci and clinical evaluations were available for 152 subjects belonging to extended pedigrees and forming 172 sib-pairs. Highly suggestive evidence for linkage emerged for two genomic regions using two- and multipoint sib-pair regression methods; both regions harbored neurogenetic candidate genes. The best evidence is seen with D11S1984 (nominal P = 0.00007, lod approximately equal to 3.1) on chromosome 11p, in close proximity to the DRD4 dopamine receptor and tyrosine hydroxylase (TH) genes. Good evidence is seen with D4S3242 (nominal P = 0.0002, lod approximately equal to 2.8) on chromosome 4p, near the beta1 GABA receptor gene. Interestingly, three loci in the alcohol dehydrogenase gene cluster on chromosome 4q showed evidence for linkage with two-point analyses, but not multipoint analysis.

Adult↗
PubMed1998

An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians.

Type 2 diabetes mellitus is a common chronic disease that is thought to have a substantial genetic basis. Identification of the genes responsible has been hampered by the complex nature of the syndrome. Abnormalities in insulin secretion and insulin action predict the development of type 2 diabetes and are, themselves, highly heritable traits. Since fewer genes may contribute to these precursors of type 2 diabetes than to the overall syndrome, such genes may be easier to identify. We, therefore, undertook an autosomal genomic scan to identify loci linked to prediabetic traits in Pima Indians, a population with a high prevalence of type 2 diabetes. 363 nondiabetic Pima Indians were genotyped at 516 polymorphic microsatellite markers on all 22 autosomes. Linkage analyses were performed using three methods (single-marker, nonparametric multipoint [MAPMAKER/SIBS], and variance components multipoint). These analyses provided evidence for linkage at several chromosomal regions, including 3q21-24 linked to fasting plasma insulin concentration and in vivo insulin action, 4p15-q12 linked to fasting plasma insulin concentration, 9q21 linked to 2-h insulin concentration during oral glucose tolerance testing, and 22q12-13 linked to fasting plasma glucose concentration. These results suggest loci that may harbor genes contributing to type 2 diabetes in Pima Indians. None of the linkages exceeded a LOD score of 3.6 (a 5% probability of occurring in a genome-wide scan). These findings must, therefore, be considered tentative until extended in this population or replicated in others.

Adult↗
PubMed1998

Randomized clinical trial of lifestyle interventions in Pima Indians: a pilot study.

A pilot trial was conducted to test adherence to specific lifestyle interventions among Pima Indians of Arizona, and to compare them for changes in risk factors for diabetes mellitus. Ninety-five obese, normoglycaemic men and women, aged 25-54 years, were randomized to treatments named 'Pima Action' (Action) and 'Pima Pride' (Pride), which were tested for 12 months. Action involved structured activity and nutrition interventions, and Pride included unstructured activities emphasizing Pima history and culture. Adherence to interventions, changes in self-reported activity and diet, and changes in weight, glucose concentrations, and other risk factors were assessed regularly. Thirty-five eligible subjects who had declined randomization were also followed as an 'observational' group and 22 members of this group were examined once at a median of 25 months for changes in weight and glucose concentration. After 12 months of intervention, members of both intervention groups reported increased levels of physical activity (median: Action 7.3 h month(-1), Pride 6.3 h month(-1), p < 0.001 for each), and Pride members reported decreased starch intake (28 g, p = 0.008). Body mass index, systolic and diastolic blood pressures, weight, 2-h glucose and 2-h insulin had all increased in Action members (p < 0.003 for each), and waist circumference had decreased in Pride members (p = 0.05). Action members gained more weight than Pride members (2.5 kg vs 0.8 kg, p = 0.06), and had a greater increase in 2-h glucose than Pride members (1.33 mM vs 0.03 mM, p = 0.007). Members of the observational group gained an average of 1.9 kg year(-1) in weight and had an increase of 0.36 mM year(-1) in 2-h glucose. Sustaining adherence in behavioural interventions over a long term was challenging. Pimas may find a less direct, less structured, and more participative intervention more acceptable than a direct and highly structured approach.

Adult↗
PubMed1998

Hip osteoarthritis prevalence estimates by three radiographic scoring systems.

OBJECTIVE: To estimate and compare the age- and sex-specific prevalence of radiographic hip osteoarthritis (RHOA) in a population-based study of the Pima Indians, using 3 atlas-based methods for assessing features of RHOA. METHODS: Pelvic radiographs from 755 Pima Indians age > or = 45 years enrolled in a population-based study were read using the Kellgren/Lawrence (K/L) grading scale (grade 0-4) and 2 validated individual-radiographic-features (IRF) scales (grades 0-3 for narrowing and osteophytes). RESULTS: The age- and sex-specific prevalence of RHOA among Pima Indians assessed using the K/L scale was < 10% in all age and sex groups. The prevalence of grade > or = 2 osteophytes assessed using the 2 IRF scales were similar to each other in all age and sex groups. However, differences between the 2 IRF scoring systems were found for the prevalence of grade > or = 2 joint space narrowing. CONCLUSION: Pima Indians have an age- and sex-specific prevalence of RHOA similar to that found in the US population. Our finding of different joint space narrowing prevalence by the 2 IRF grading scales supports the use of the same atlas-based case definitions for determining disease prevalence for comparative studies.

Age Distribution↗
PubMed1998

Rheumatoid arthritis in the Pima Indians: the intersection of epidemiologic, demographic, and genealogic data.

OBJECTIVE: To describe the clinical features and familial distribution of rheumatoid arthritis (RA) in the Pima Indians. METHODS: From 1965 through 1990, all cases of RA as defined by the American College of Rheumatology (formerly, the American Rheumatism Association) 1987 criteria or all cases of seropositive, erosive disease as defined by the Rome criteria were identified in individuals who were age 20 years and older and were of 50% or more Pima/Tohono-O'odham heritage. Radiographs were reviewed by 2 musculoskeletal radiologists who were blinded to case status. Kinship coefficients were used to evaluate familial aggregation. RESULTS: Eighty-eight RA cases were identified from this population-based sample. Over 66% of the cases had seropositive disease, over 60% had erosive disease, and over 40% had subcutaneous nodules. Of the 88 RA cases, 40 were members of families with more than 1 RA case. The remainder were simplex cases. CONCLUSION: In this population, clinical markers of severe RA were present in a majority of cases. The presence of familial aggregation for RA in the Pima Indians suggests underlying genetic factors in disease pathogenesis.

Adult↗
PubMed1998

Increasing prevalence of Type II diabetes in American Indian children.

Until recently, Type II diabetes was considered rare in children. The disease is, however, increasing among children in populations with high rates of Type II diabetes in adults. The prevalence of Type II diabetes was determined in 5274 Pima Indian children between 1967 and 1996 in three 10-year time periods, for age groups 5-9, 10-14 and 15-19 years. Diabetes was diagnosed using World Health Organisation criteria, based on an oral glucose tolerance test. The prevalence of diabetes increased over time in children aged 10 years and over: in boys from 0 % in 1967-1976 to 1.4% in 1987-1996 in the 10-14 year old age group, and from 2.43% to 3.78% for age group 15-19 and in girls from 0.72 % in 1967-1976 to 2.88 % in 1987-1996 in the 10-14 year old age group, and from 2.73 % to 5.31 % for age group 15-19 years. Along with the increase in the prevalence of Type II diabetes (p < 0.0001), there was an increase in weight (calculated as percentage of relative weight, p < 0.0001), and in frequency of exposure to diabetes in utero (p < 0.0001). The increasing weight and increasing frequency of exposure to diabetes in utero accounted for most of the increase in diabetes prevalence in Pima Indian children over the past 30 years. Type II diabetes is now a common disease in American Indian children aged 10 or more years and has increased dramatically over time, along with increasing weight. A vicious cycle related to an increase in the frequency of exposure to diabetes in utero appears to be an important feature of this epidemic.

Adolescent↗
PubMed1998

An epidemic of proteinuria in Pima Indians with type 2 diabetes mellitus.

BACKGROUND: The risk of proteinuria in Type 1 diabetes declined > or = 30% over the past 50 years, and improvements in metabolic control are believed to be largely responsible. Little is known about secular changes in the risk of proteinuria in Type 2 diabetes. METHODS: We examined trends in the incidence rate of proteinuria in Pima Indians > or = 20 years of age with diabetes diagnosed between January 1, 1955 and December 31, 1994. RESULTS: Among 1305 initially non-proteinuric diabetic subjects, 433 developed proteinuria during a median follow-up of 8.0 years (range 0.8 to 30.2 years). With subjects with diabetes diagnosed between 1955 and 1964 serving as the reference group, the rate of proteinuria was similar (rate ratio 1.0; 95% confidence interval, 0.79 to 1.3) in the cohort diagnosed between 1965 and 1974, 1.5 times as high (95% confidence interval, 1.1 to 2.0) in the cohort diagnosed between 1975 and 1984, and 1.9 times as high (95% confidence interval, 1.1 to 3.0) in the cohort diagnosed between 1985 and 1994, after adjusting for potential confounders in a generalized additive proportional hazards model. Between the first and last cohorts, plasma glucose concentration declined, on average, by 17% (P = 0.0001) and the mean arterial pressure declined by 11% (P = 0.0001). CONCLUSIONS: The incidence rate of proteinuria in Pima Indians with Type 2 diabetes increased nearly twofold in the last 40 years, despite improvements in plasma glucose and blood pressure. Rapidly changing environmental or behavioral factors must play an important role in the pathogenesis of diabetic renal disease in this population.

Adult↗
PubMed1998

Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians.

An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesity. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumference). Energy metabolism was measured in a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotient (24RQ), an indicator of the ratio of carbohydrate oxidation to fat oxidation. Five hundred sixteen microsatellite markers with a median spacing of 6.4 cM were analyzed, in 362 siblings who had measurements of body composition and in 220 siblings who had measurements of energy metabolism. These comprised 451 sib pairs in 127 nuclear families, for linkage analysis to obesity, and 236 sib pairs in 82 nuclear families, for linkage analysis to energy metabolism. Pointwise and multipoint methods for regression of sib-pair differences in identity by descent, as well as a sibling-based variance-components method, were used to detect linkage. LOD scores >=2 were found at 11q21-q22, for percent body fat (LOD=2.1; P=.001), at 11q23-q24, for 24-h energy expenditure (LOD=2.0; P=.001), and at 1p31-p21 (LOD=2.0) and 20q11.2 (LOD=3.0; P=.0001), for 24RQ, by pointwise and multipoint analyses. With the variance-components method, the highest LOD score (LOD=2.3 P=.0006) was found at 18q21, for percent body fat, and at 1p31-p21 (LOD=2.8; P=.0003), for 24RQ. Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signaling protein), at 20q11.2.

Chromosome Mapping↗
PubMed1998

An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians.

Genetic factors influence the development of type II diabetes mellitus, but genetic loci for the most common forms of diabetes have not been identified. A genomic scan was conducted to identify loci linked to diabetes and body-mass index (BMI) in Pima Indians, a Native American population with a high prevalence of type II diabetes. Among 264 nuclear families containing 966 siblings, 516 autosomal markers with a median distance between adjacent markers of 6.4 cM were genotyped. Variance-components methods were used to test for linkage with an age-adjusted diabetes score and with BMI. In multipoint analyses, the strongest evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome 11q, in the region that was also linked most strongly with BMI (LOD = 3.6). Bivariate linkage analyses strongly rejected both the null hypothesis of no linkage with either trait and the null hypothesis of no contribution of the locus to the covariation among the two traits. Sib-pair analyses suggest additional potential diabetes-susceptibility loci on chromosomes 1q and 7q.

Analysis of Variance↗
PubMed1998

Is a low leptin concentration, a low resting metabolic rate, or both the expression of the "thrifty genotype"? Results from Mexican Pima Indians.

BACKGROUND: The high prevalence of obesity and type 2 diabetes in some populations is believed to be the expression of a "thrifty genotype," which conferred survival advantages during periods of harsh environmental conditions, but has become a liability in industrialized environments of abundance. Low plasma leptin concentrations and a low metabolic rate may be the phenotypic expression of this genotype. OBJECTIVE: We hypothesized that plasma leptin concentrations and resting metabolic rate would be lower in Mexican Pima Indians not yet exposed to an affluent lifestyle than in non-Pima Mexicans living in the same environment. DESIGN: We studied 208 nondiabetic Pima Indians (105 women and 103 men) living a traditional lifestyle in a remote, mountainous area of northwest Mexico and 183 nondiabetic non-Pima Mexicans (90 women and 93 men) living in the same environment. A subset of 40 (17 women and 23 men) Pima Indians and 40 (19 women and 21 men) non-Pima Mexicans was selected for studies of energy metabolism with a ventilated-hood system. RESULTS: Leptin concentrations were strongly correlated with percentage body fat in both groups (r = 0.83, P < 0.0001). There was no significant difference in plasma leptin concentration between groups in absolute value (P = 0.90) or after adjustment for percentage body fat, waist circumference, age, and sex (P = 0.40). Similarly, there was no significant difference in resting metabolic rate between groups in absolute value (P = 0.27) or after adjustment for fat-free mass (P = 0.32). CONCLUSIONS: These results do not support the hypothesis that hypoleptinemia, a relatively low resting metabolic rate, or both are expressions of the thrifty genotype.

Adult↗