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P H Bennett

Publications and source records attributed to P H Bennett.

At least 19 recordsLinked to original sources
PubMed2000

Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies.

The metabolic characteristics of type 2 diabetes, insulin resistance, and diminished insulin secretion are costly to measure directly. To evaluate the utility of several simple indices derived from insulin and glucose measurements, the indices were examined from 1982 to 1997 with respect to correlation with more sophisticated measures of insulin sensitivity and secretion in Pima Indians in the Gila River Indian Community of Arizona. Ability to predict the incidence of diabetes in 1,731 persons was also examined. Indices were calculated from fasting and 2-hour glucose (G0, G120) and insulin (I0, I120) concentrations obtained during an oral glucose tolerance test. Fasting serum insulin concentration and the insulin sensitivity index (10(4)/(I0 x G0)) each showed a moderate correlation with the estimate of insulin sensitivity derived from the hyperinsulinemic-euglycemic clamp (absolute value r approximately 0.60). They also strongly predicted the incidence of diabetes (incidence rate ratio comparing the most and least insulin-resistant tertile groups approximately 3.0). Corrected insulin response (I120/(G120 x (G120 - 70))) was modestly correlated with insulin secretion as measured by an intravenous glucose tolerance test (r = 0.35). Impaired insulin secretion assessed by this index predicted incidence of diabetes, particularly after control for insulin sensitivity index (incidence rate ratio = 1.6). Thus, simple indices of insulin sensitivity and secretion may be reasonable surrogates for more sophisticated measures in epidemiologic studies.

Adult↗
PubMed2000

Daily energy expenditure in Mexican and USA Pima indians: low physical activity as a possible cause of obesity.

BACKGROUND: Obesity is caused by an imbalance between energy intake and energy expenditure. However, it is unknown whether increased physical activity protects susceptible populations against the development of obesity and type 2 diabetes. OBJECTIVE: To investigate the potential protective role of environment and physical activity against obesity by measuring total energy expenditure in Mexican and USA Pima Indians. METHODS: We compared the physical activity level of 40 (17 female and 23 male; 37+/-11 y, 66+/-13 kg) Mexican Pima Indians from a remote, mountainous area of Northwest Mexico, with 40 age-and-sex matched (17 female and 23 male; 37+/-12 y, 93+/-22 kg) Pima Indians from the Gila River Indian Community in Arizona, USA. We measured total energy expenditure (TEE) by doubly labeled water and calculated physical activity by different methods: physical activity level (PAL) as the ratio of TEE on resting metabolic rate (RMR), TEE adjusted for RMR by linear regression, activity energy expenditure adjusted for body weight (AEE), and activity questionnaire. RESULTS: Physical activity was higher in Mexican Pima Indians when compared with USA Pima Indians as assessed by PAL (1.97+/-0.34 vs 1.57+/-0.16, P<0.0001), TEE adjusted for RMR (3289+/-454 vs 2671+/-454 kcal/day, P<0.0001) and AEE adjusted for body weight (1243+/-415 vs 711+/-415 kcal/day, P<0. 0001). Questionnaires revealed more time spent on occupational activities among Mexican Pima compared with USA Pima (23.9+/-13.3 vs 12.6+/-13.9 h/week, P<0.001). CONCLUSION: These data support a significant role for physical activity in the prevention of obesity in genetically susceptible populations. International Journal of Obesity (2000)24, 55-59

Adult↗
PubMed2000

Evolution of incipient nephropathy in type 2 diabetes mellitus.

BACKGROUND: We examined the course of glomerular injury in 12 Pima Indians with long-standing (>8 years) type 2 diabetes mellitus, normal serum creatinine, and microalbuminuria. They were compared with a group of 10 Pima Indians in Arizona with new-onset (<5 years) type 2 diabetes, normal renal function, and normoalbuminuria (<30 mg albumin/g creatinine on random urine specimens). METHODS: A combination of physiological and morphological techniques was used to evaluate glomerular function and structure serially on two occasions separated by a 48-month interval. Clearances of iothalamate and p-aminohippuric acid were used to determine glomerular filtration rate (GFR) and renal plasma flow, respectively. Afferent oncotic pressure was determined by membrane osmometry. The single nephron ultrafiltration coefficient (Kf) was determined by morphometric analysis of glomeruli and mathematical modeling. RESULTS: The urinary albumin-to-creatinine ratio (median + range) increased from 84 (28 to 415) to 260 (31 to 2232) mg/g between the two examinations (P = 0.01), and 6 of 12 patients advanced from incipient (ratio = 30 to 299 mg/g) to overt nephropathy (>/=300 mg/g). A 17% decline in GFR between the two examinations from 186 +/- 41 to 155 +/- 50 mL/min (mean +/- SD; P = 0.06) was accompanied by a 17% decline in renal plasma flow (P = 0.003) and a 6% increase in plasma oncotic pressure (P = 0.02). Computed glomerular hydraulic permeability was depressed by 13% below control values at both examinations, a result of a widened basement membrane and a reduction in frequency of epithelial filtration slits. The filtration surface area declined significantly, however, from 6.96 +/- 2.53 to 5.51 +/- 1.62 x 105 mm2 (P = 0.01), a change that was accompanied by a significant decline in the number of mesangial cells (P = 0.001), endothelial cells (P = 0.038), and podocytes (P = 0.0005). These changes lowered single nephron Kf by 20% from 16.5 +/- 6.0 to 13.2 +/- 3.6 nL/(minutes + mm Hg) between the two examinations (P = 0.02). Multiple linear regression analysis revealed that among the determinants of GFR, only the change in single nephron Kf was related to the corresponding change in GFR. CONCLUSION: We conclude that a reduction in Kf is the major determinant of a decline in GFR from an elevated toward a normal range as nephropathy in type 2 diabetes advances from an incipient to an overt stage.

Adult↗
PubMed2000

A locus influencing total serum cholesterol on chromosome 19p: results from an autosomal genomic scan of serum lipid concentrations in Pima Indians.

A genome-wide linkage study was analyzed to identify loci that influence serum lipid concentrations in Pima Indians. Linkage analyses were conducted for total cholesterol measured in 998 siblings from 292 nuclear families, for total triglycerides in 547 siblings from 188 families, and for high density lipoprotein (HDL) cholesterol in 590 siblings from 201 families. Genotypes were generated for 516 autosomal microsatellite markers. Multipoint variance components methods were used to assess linkage. The strongest evidence for linkage with total cholesterol was on chromosome 19p (lod score 3.89), in the vicinity of the marker D19S1034, which is near the low density lipoprotein receptor gene. The strongest evidence for linkage with HDL cholesterol was on chromosome 3q (lod score 2.64) near D3S3053. For triglycerides, the strongest evidence for linkage was on chromosome 2p near D2S1788 (lod score 1.70) and on chromosome 3p near D3S2406 (lod score 1.77). This genomic scan provides evidence for a locus influencing total cholesterol concentration on chromosome 19p. It also suggests a locus influencing HDL cholesterol on chromosome 3q.

Adult↗
PubMed2000

Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships.

Intrauterine exposure to diabetes is associated with an excess of diabetes and obesity in the offspring, but the effects of intrauterine exposure are confounded by genetic factors. To determine the role of the intrauterine diabetic environment per se, the prevalence of diabetes and the mean BMI were compared in siblings born before and after their mother was recognized as having diabetes. Nuclear families in which at least one sibling was born before and one after the mother was diagnosed with type 2 diabetes were selected. Consequently, the siblings born before and after differed in their exposure to diabetes in utero. A total of 58 siblings from 19 families in which at least one sibling had diabetes were examined at similar ages (within 3 years). The risk of diabetes was significantly higher in siblings born after the mother developed diabetes than in those born before the mother's diagnosis of diabetes (odds ratio 3.7, P = 0.02). In 52 families, among 183 siblings without diabetes, the mean BMI was 2.6 kg/m2 higher in offspring of diabetic than in offspring of nondiabetic pregnancies (P = 0.003). In contrast, there were no significant differences in risk of diabetes or BMI between offspring born before and after the father was diagnosed with diabetes. Intrauterine exposure to diabetes per se conveys a high risk for the development of diabetes and obesity in offspring in excess of risk attributable to genetic factors alone.

Adult↗
PubMed2000

Type 2 diabetes and low birth weight: the role of paternal inheritance in the association of low birth weight and diabetes.

Lower birth weight is associated with an increased occurrence of type 2 diabetes in later life. Whether this relationship is explained by environmental or genetic factors is unknown. We have examined the potential for genetic influences by determining whether parental diabetes is associated with lower birth weight in 1,608 children of known birth weight and gestational age born between 1941 and 1993 in the Gila River Indian Community in Arizona. The previously described relationships of maternal diabetes to increased birth weight and offspring diabetes were observed. In contrast to this we have determined novel relationships between low birth weight and paternal diabetes. The offspring of diabetic fathers were, on average, 78 g lighter than the offspring of nondiabetic fathers. For fathers, lower birth weight in their offspring was associated with an increased risk of later diabetes, i.e., fathers of offspring in the lowest quintile of birth weight, who were not diabetic at the time of birth of their child, had a 1.8-fold increased risk of developing diabetes later in life (95% CI 1.2-2.7; P = 0.004). For children, lower birth weight predicted diabetes in the offspring if paternal but not maternal diabetes was present, but it was not associated with higher plasma glucose if neither parent had diabetes. We conclude that the risk of diabetes associated with low birth weight is strongly related to the development of paternal diabetes, suggesting a genetic link between lower birth weight and later diabetes.

Adult↗
PubMed2000

Segregation analysis of diabetic nephropathy in Pima Indians.

Familial aggregation of diabetic nephropathy suggests the existence of genes determining susceptibility to nephropathy in addition to those leading to diabetes. In the present study, complex segregation analysis was performed in diabetic members of Pima Indian families to determine whether familial aggregation of nephropathy in this population could reflect the action of a single major gene. Nephropathy, defined by a urinary protein-to-creatinine ratio (PCR) > or = 500 mg/g, was analyzed as a discrete trait in a class C regressive logistic model. Individuals with PCR <500 mg/g were considered unaffected. Segregation analysis was performed both for nephropathy at the last examination (prevalent cases) and for duration of diabetes at the onset of nephropathy (incident cases). The REGD program was used for the analysis of the prevalent cases and the REGTL program for the incident cases, both from the Statistical Analysis for Genetic Epidemiology package (Case Western University, Cleveland, OH). The analysis of prevalent cases included 2,107 Pima Indians from 715 nuclear families. A subset of 504 of these families containing 1,403 individuals was used in the analysis of incident cases. Analysis of prevalent cases supported the existence of a gene with a major role, in that hypotheses of no major effect and of no transmission of a major effect were rejected (P = 0.00001; P = 0.003), whereas Mendelian transmission was not rejected (P = 0.85). A dominant model provided the best fit, but a recessive model could not be rejected. The analysis of incident cases, however, did not support a major gene effect on duration of diabetes at the onset of nephropathy, and analyses of lifetime occurrence of nephropathy were inconclusive. The analysis of prevalent cases supports the hypothesis of a major genetic effect on susceptibility to diabetic nephropathy in Pima Indians, but the analysis of incident cases does not support a genetic effect on duration of diabetes at the onset of nephropathy. The discrepancy may reflect the difficulty in precisely dating onset of nephropathy. The parameters of the model derived from segregation analysis of prevalent cases may be useful in linkage studies to detect nephropathy susceptibility loci.

Adult↗
PubMed2000

The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes.

OBJECTIVE: The 1997 American Diabetes Association (ADA) and the 1985 and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia differ. The appropriateness of these diagnostic criteria in terms of individuals identified as abnormal and their prognosis has been debated. The purpose of this study is to compare the classifications of people by these criteria and to compare fasting and postload plasma glucose concentrations in the prediction of diabetes. RESEARCH DESIGN AND METHODS: The frequencies of diabetes by the 3 sets of criteria were compared in 5,023 adult Pima Indians not taking hypoglycemic drugs. Among nondiabetic subjects, fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) concentrations and categories of impaired glucose regulation or diabetes were evaluated as predictors of diabetes defined by 1999 WHO criteria. RESULTS: The frequency of diabetes was 12.5% by 1997 ADA criteria, 14.6% by 1985 WHO criteria, and 15.3% by 1999 WHO criteria. The incidence of diabetes was strongly related to higher FPG and 2-h PG, each of which had very similar predictive powers. Impaired glucose tolerance (IGT) was more common than impaired fasting glucose (IFG) (15 vs. 5%), but the 5-year incidence of diabetes was higher in IFG than IGT (37 vs. 24%). CONCLUSIONS: The prevalence and incidence of diabetes are somewhat lower with the ADA criteria than with the 1985 or 1999 WHO criteria. The intermediate categories of glycemia differ substantially IFG defines a smaller number of people who are at higher risk of developing diabetes than those with IGT. More people at high risk of diabetes could be identified by using either IFG or IGT, as recommended by the 1999 WHO criteria, or by using the FPG concentration alone, but with a lower cutoff value.

Adult↗
PubMed2000

Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes.

OBJECTIVE: The 1997 American Diabetes Association (ADA) and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia were evaluated and compared with respect to prediction of microvascular and macrovascular disease and mortality RESEARCH DESIGN AND METHODS: The prevalence of retinopathy and nephropathy at baseline and during the subsequent 10 years and mortality rates were examined in relation to baseline fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) among 5,023 Pima Indian adults and in relation to the cut points defined by the ADA and WHO criteria. RESULTS: The frequencies of retinopathy and nephropathy were directly related to baseline FPG and 2-h PG with approximate thresholds near or below the current diagnostic criteria for diabetes (FPG > or =7.0 and 2-h PG > or = 11.1 mmol/l). The rates of retinopathy were 4.7% in impaired fasting glucose (IFG) and 20.9% in diabetes by ADA criteria; 1.6% for impaired glucose tolerance (IGT) and 19.7% for diabetes by 1985 WHO criteria; and 1.2% for IGT and 19.2% for diabetes by the 1999 WHO criteria. Mortality rates from cardiovascular-renal-related diseases were higher in diabetic individuals (FPG > or =7.0 or 2-h PG > 11.1 mmol/l) than in those with normal FPG and 2-h PG but were not elevated in those with IFG or IGT. CONCLUSIONS: Retinopathy and nephropathy were directly related to higher FPG or 2-h PG. FPG, which identifies those at high risk of microvascular disease and mortality, can be used to predict these outcomes and to diagnose diabetes when oral glucose tolerance testing is not practical.

Adult↗
PubMed2000

Diabetes duration and cause-specific mortality in the Verona Diabetes Study.

OBJECTIVE: To examine the 10-year mortality and effect of diabetes duration on overall and cause-specific mortality in diabetic subjects in the Verona Diabetes Study (VDS). RESEARCH DESIGN AND METHODS: Records from diabetes clinics, family physicians, and a drug consumption database were used to identify 5,818 subjects > or =45 years of age with type 2 diabetes who were alive and residing in Verona, Italy on 31 December 1986. Vital status of each subject was ascertained on 31 December 1996. Underlying causes of death were determined from death certificates. Death rates and death rate ratios (DRRs) were computed and standardized to the population of Verona in 1991. RESULTS: During the study, 2,328 subjects died; 974 deaths were attributable to cardiovascular disease, 517 to neoplasms, 324 to diabetes-related diseases, 134 to digestive diseases, 250 to other natural causes, and 48 to external causes. There were 81 subjects who died of unknown causes. Death rates from natural causes were higher in men than in women (DRR 1.4, 95% CI 1.2-1.5) and rose in both sexes with increasing duration of diabetes (P = 0.001). Among the natural causes of death, those for diabetes-related diseases were strongly related to diabetes duration (P = 0.001). a modest relationship with duration was also found for ischemic heart disease in men (P = 0.07). CONCLUSIONS: Cardiovascular disease was the principal cause of death among people with type 2 diabetes in the VDS. Rates for natural causes of death rose with increasing duration of diabetes. Deaths from diabetes-related diseases in both sexes and from ischemic heart disease in men were largely responsible for this increase.

Adolescent↗
PubMed2000

Secular trends in birth weight, BMI, and diabetes in the offspring of diabetic mothers.

OBJECTIVE: The offspring of mothers who had diabetes during pregnancy experience increased risk later of diabetes and obesity later. We hypothesized that, in light of the historical improvements in the management of diabetes during pregnancy, these late consequences of the early environment might be diminishing with time. RESEARCH DESIGN AND METHODS: Birth weight and information on BMI and glucose tolerance have been collected as part of the epidemiological survey of the Gila River Indian Community in Arizona. We examined birth weight, BMI, and diabetes in offspring of mothers with type 2 diabetes during pregnancy born in four 10-year time intervals since 1955 compared with offspring whose mothers either had not developed diabetes or were prediabetic (i.e., developed diabetes after the index pregnancy). RESULTS: Offspring of diabetic mothers (ODM) were heavier at birth, had a higher BMI at all ages throughout childhood, and had an increased incidence rate of diabetes in childhood and early adulthood (7- to 20-fold, offspring of nondiabetic mothers [ONDM]; 3- to 5-fold, offspring of prediabetic mothers [OPDM]). Relative differences in birth weight and BMI between ODM and ONDM were greatest for those born before 1965. In those born after 1965, despite secular trends to higher BMI and diabetes incidence in the ONDM, differences in BMI and birth weight of ODM versus ONDM and OPDM appeared to have been maintained. CONCLUSIONS: With the possible exception of individuals born before 1965, the increased risk of diabetes and obesity experienced by ODM does not seem to be diminishing with time.

Age of Onset↗
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

Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria.

AIMS/HYPOTHESIS: The predictive value of glomerular structure on progression of renal disease was examined in patients with Type II (non-insulin-dependent) diabetes and microalbuminuria (urinary albumin-to-creatinine ratio = 30-299 mg/g). METHODS: Kidney biopsy specimens were obtained from 16 diabetic Pima Indians (6 men, 10 women). Progression of renal disease was assessed by measuring urinary albumin excretion 4 years after the biopsy (UAE(4 years)) and by computing the change in urinary albumin excretion during the study (Delta UAE). RESULTS: At baseline, the duration of diabetes averaged 13.3 years (range = 4.0-23.8 years) and the mean glomerular filtration rate was 159 ml x min(-1) x 1.73 m(-2) (range = 98 - 239 ml x min(-1) x 1.73 m(-2)). Median urinary albumin excretion was 67 mg/g (range = 25-136 mg/g) and it increased to 625 mg/g (range = 9-13471 mg/g) after 4 years; 10 subjects (63 %; 4 men, 6 women) developed macroalbuminuria (urinary albumin-to-creatinine ratio >/= 300 mg/g). Neither mean arterial pressure nor HbA(1 c) changed substantially during follow-up. Among the glomerular morphologic characteristics, the number of visceral epithelial cells, or podocytes, per glomerulus was the strongest predictor of renal disease progression (UAE(4 years), r = -0.49, p = 0.05; DeltaUAE, r = -0.57, p = 0.02), with fewer cells predicting more rapid progression. Glomerular basement membrane thickness did not predict progression (UAE(4 years), r = 0.11, p = 0.67; DeltaUAE, r = 0.09, p = 0.73) and mesangial volume fraction had only a modest effect (UAE(4 years,) r = 0.42, p = 0.11; DeltaUAE, r = 0.48, p = 0.06). CONCLUSION/INTERPRETATION: Whether lower epithelial cell number per glomerulus among those that progressed was due to cellular destruction, a reduced complement of epithelial cells, or both is uncertain. Nevertheless, these findings suggest that podocytes play an important part in the development and progression of diabetic renal disease. [Diabetologia (1999) 42: 1341-1344]

Adult↗
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↗