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P H Bennett

Publications and source records attributed to P H Bennett.

At least 73 records · Page 4Linked to original sources
PubMed1997

Diagnosing diabetes mellitus--do we need new criteria?

The current classification and diagnostic criteria for diabetes mellitus were introduced by the United States National Data Group in 1979 and endorsed by the World Health Organization in 1980, with modifications in 1985 and 1994. The criteria, chosen to reflect the risk of complications, were the synthesis of considerable thought and expertise and represented a consensus which, it was hoped, would prove helpful to all those involved with diabetes-practising clinician, research scientist and epidemiologist alike. The inconvenience, variability and non-physiological nature of the oral glucose tolerance test (OGTT) are well-recognised. In spite of these limitations the 2-h post-load plasma glucose has remained the standard against which all other tests have been evaluated. This article reviews the original justification for the OGTT, and in the light of more recent epidemiological research seeks to place the current diagnostic criteria for diabetes into a pathophysiological, diagnostic and prognostic perspective.

Blood Glucose↗
PubMed1997

Relatively low plasma leptin concentrations precede weight gain in Pima Indians.

Leptin, the product of the ob gene, is a hormone, produced by adipose cells, that inhibits food intake and increases energy expenditure in rodents. In humans, plasma leptin concentrations correlate closely with the size of the adipose tissue depot; however, there is considerable variation in plasma leptin concentrations at any given degree of fatness. To investigate whether individuals prone to weight gain are hypoleptinemic, we measured fasting plasma leptin concentrations in two groups of weight-matched nondiabetic Pima Indians followed for approximately 3 years, 19 of whom subsequently gained weight and 17 of whom maintained their weight. After we adjusted for initial percent body fat, mean plasma leptin concentration was lower in those who gained weight than in those whose weight was stable. These data indicate that relatively low plasma leptin concentrations may play a role in the development of obesity in Pima Indians, a population prone to obesity.

Adult↗
PubMed1997

Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians.

The cloning of human and mouse cDNAs from brain that encode high affinity leptin receptors was recently reported. We have physically localized the human leptin receptor gene (LEPR) to a region at 1p31, between the anonymous microsatellite markers D1S515 and D1S198. The genomic structure of the human leptin receptor gene, corresponding to the published human brain cDNA sequence, spans over 70 kb and includes 20 exons. Since the leptin receptor gene is a candidate gene for obesity, and because of its proximity to D1S198, a marker previously linked to insulin secretion, the LEPR gene was sequenced in 20 non-diabetic Pima Indians chosen for extremes in percent body fat and in their acute insulin response to intravenous glucose. Seven polymorphic sites were identified. Two of these polymorphisms, Lys109Arg and Gln223Arg, are amino acid substitutions in the extracellular domain of the leptin receptor, one polymorphism is a silent substitution, and four occur in non-coding regions of the leptin receptor. Four of these sites are in linkage disequilibrium with one another. Nucleotides at three noncoding polymorphic sites were found exclusively in obese Pima Indians. This demonstrates an association between variation at the leptin receptor gene and obesity in humans.

Adipose Tissue↗
PubMed1997

Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.

OBJECTIVE: Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. RESEARCH DESIGN AND METHODS: In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. RESULTS: The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8-75.2) in the control group compared with 43.8% (95% CI, 35.5-52.3) in the diet group, 41.1% (95% CI, 33.4-49.4) in the exercise group, and 46.0% (95% CI, 37.3-54.7) in the diet-plus-exercise group (P < 0.05). When analyzed by clinic, each of the active intervention groups differed significantly from the control clinics (P < 0.05). The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight (BMI < or > or = 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively. CONCLUSIONS: Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.

Adult↗
PubMed1997

Genomewide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome 11q21-q22. Pima Diabetes Gene Group.

On the basis of accumulating evidence that obesity has a substantial genetic component, a genomewide search for linkages of DNA markers to percent body fat is ongoing in Pima Indians, a population with a very high prevalence of obesity. An initial screen of the genome (>600 markers in 874 individuals) has been completed using highly polymorphic markers (mean heterozygosity = .67). Reported here are the sib-pair linkage results for percent body fat (277 siblings), the best available indicator of overall obesity. Single-marker linkages to percent body fat were evaluated by sib-pair analysis for quantitative traits. From these analyses, the best evidence of genes influencing body fat came from markers at chromosome 11q21-q22 and 3p24.2-p22 (P = .001; LOD = 2.0). Regions flanking these markers were further investigated by multipoint linkage. The evidence for linkage at 11q21-q22 increased to P = .0002 (LOD = 2.8), peaking between markers D11S2000 and D11S2366. Evidence for linkage at 3p24.2-p22 did not change. No association was detected for any marker in the region. Although several genes are known in the 11q21-q22 region, none have been implicated as candidate genes for obesity.

Adipose Tissue↗
PubMed1997

Clinical and pathological course of renal disease in non-insulin-dependent diabetes mellitus: the Pima Indian experience.

Non-insulin-dependent diabetes mellitus (NIDDM) and the renal disease attributable to it have been characterized extensively in the Pima Indians, a group of American Indians who form the Gila River Indian Community in Arizona. Both of these diseases are common in this community, and their onset and duration are known with greater certainty than in other populations because research examinations, which include oral glucose tolerance tests and measures of urinary protein excretion, have been performed frequently on most members of the population for the past 30 years. Studies of glomerular structure and hemodynamic function in diabetic Pima Indians indicate that glomerular hyperfiltration often develops at the onset of NIDDM and remains elevated until after overt nephropathy appears. Structurally, the glomeruli in subjects with microalbuminuria are not clearly distinguishable from those in subjects with normoalbuminuria, but macroalbuminuria is characterized by extensive glomerular sclerosis, mesangial expansion, and widening of epithelial cell foot processes that together lead to a rapid decline in the glomerular filtration rate. The decline in glomerular function in subjects with macroalbuminuria is due both to a loss of ultrafiltration surface area and to reduction in glomerular hydraulic permeability.

Albuminuria↗
PubMed1997

Enlarged acetabular labra in the Pima Indians.

OBJECTIVE: To report the descriptive epidemiology of acetabular labral enlargement and analyze associations of other variables with this variant. METHODS: Pelvis radiographs from 761 Pima Indians aged > or = 45 years enrolled in a population based study were read by Kellgren-Lawrence global and individual radiographic features grading scales for osteoarthritis (OA) at separate settings. In total, 722 radiographs remained eligible for this study after excluding 12 unreadable radiographs and 27 cases of radiographic hip OA (Kellgren-Lawrence grade > or = 2). Enlarged acetabular labra were recorded during readings of individual radiographic features. RESULTS: Enlarged acetabular labra were present in 16% of study participants without OA and were significantly associated with female sex, but not with the variables age, body mass index, clinical hip joint involvement, diabetes, or serum insulin concentrations. CONCLUSION: Acetabular labral enlargement is common in the Pima Indians, and although not in excess of other reported acetabular margin anomalies, it differs in appearance and is not associated with age. Recognition of this structural variant is important because it can mimic fractures or osteophytes.

Acetabulum↗
PubMed1997

Course of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus.

The course of renal disease attributable to non-insulin-dependent diabetes mellitus (NIDDM) has been characterized extensively in the Pima Indians of Arizona. Studies in this population indicate that the glomerular filtration rate often increases at the onset of NIDDM and remains elevated as long as normal urinary albumin excretion (< 30 mg albumin/g creatinine) or microalbuminuria (30-299 mg albumin/g creatinine) persist. After the development of macroalbuminuria (> or = 300 mg albumin/g creatinine), the glomerular filtration rate declines at least as rapidly as reported in subjects with insulin-dependent diabetes. Morphologic examination of kidney tissue reveals extensive glomerular sclerosis, mesangial expansion, and widening of epithelial cell foot processes and the glomerular basement membrane in the subjects with macroalbuminuria, but not in those with normo- or microalbuminuria. These findings suggest that substantial structural damage to the kidney occurs at or about the time that macroalbuminuria develops, and the decline in glomerular function in those with macroalbuminuria is due to a loss of ultrafiltration surface area and a reduction in glomerular hydraulic permeability.

Albuminuria↗
PubMed1997

[Non-insulin-dependent diabetes in populations at risk: the Pima Indians].

Pima Indians have the highest prevalence of non-insulin-dependent diabetes mellitus reported in the world, reaching 70% in the 55-64 year age-group. Although obesity is also quite prevalent in this population, it cannot in itself be held responsible for the high frequency of the disease. Profound changes in the way of life of the Pima Indians during the past century have been associated with the emergence of diabetes. A genetic susceptibility in this population probably explains why diabetes became an "epidemic". Compared to Caucasians with similar degrees of obesity and glucose tolerance, Pima Indians are insulin-resistant. This characteristic, which is a strong predictor of diabetes, seems to be genetically determined in this population, and an active search for the gene(s) involved has started. Surprisingly, for an insulin-resistant population, cardiovascular mortality is low in Pima Indians. An understanding of the similarities and differences between diabetic Caucasians and Pima Indians is one means of advancing our knowledge of non-insulin-dependent diabetes mellitus and insulin resistance.

Diabetes Mellitus↗
PubMed1996

Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. Diabetic Renal Disease Study Group.

BACKGROUND: Non-insulin-dependent diabetes mellitus (NIDDM) is a major cause of end-stage renal disease. However, the course and determinants of renal failure in this type of diabetes have not been clearly defined. METHODS: We studied glomerular function at intervals of 6 to 12 months for 4 years in 194 Pima Indians selected to represent different stages in the development and progression of diabetic renal disease. Initially, 31 subjects had normal glucose tolerance, 29 had impaired glucose tolerance, 30 had newly diagnosed diabetes, and 104 had had diabetes for five years or more; of these 104, 20 had normal albumin excretion, 50 had microalbuminuria, and 34 had macroalbuminuria. The glomerular filtration rate, renal plasma flow, urinary albumin excretion, and blood pressure were measured at each examination. RESULTS: Initially, the mean (+/-SE) glomerular filtration rate was 143+/-7 ml per minute in subjects with newly diagnosed diabetes, 155+/-7 ml per minute in those with microalbuminuria, and 124+/-7 ml per minute in those with macroalbuminuria; these values were 16 percent, 26 percent, and 1 percent higher, respectively, than in the subjects with normal glucose tolerance (123+/-4 ml per minute). During four years of follow-up, the glomerular filtration rate increased by 18 percent in the subjects who initially had newly diagnosed diabetes (P=0.008); the rate declined by 3 percent in those with microalbuminuria at base line (P=0.29) and by 35 percent in those with macroalbuminuria (P<0.001). Higher base-line blood pressure predicted increasing urinary albumin excretion (P=0.006), and higher base-line urinary albumin excretion predicted a decline in the glomerular filtration rate (P<0.001). The initial glomerular filtration rate did not predict worsening albuminuria. CONCLUSIONS: The glomerular filtration rate is elevated at the onset of NIDDM and remains so while normal albumin excretion or microalbuminuria persists. It declines progressively after the development of macroalbuminuria.

Adolescent↗
PubMed1996

Parental hypertension and proteinuria in Pima Indians with NIDDM.

To determine if parental hypertension is associated with proteinuria in offspring with non-insulin-dependent diabetes mellitus (NIDDM), 438 diabetic Pima Indians (172 men, 266 women) aged 20 years or more and both of their parents were examined. Hypertension was defined as a systolic blood pressure 140 mm Hg or more, diastolic blood pressure 90 mm Hg or more, or treatment with antihypertensive medicine. Sixty-three percent of the fathers and 80% of the mothers had diabetes at the time their blood pressure was measured. Families in which either parent had proteinuria, defined as a urine protein-to-creatinine ratio > or = 0.5 g/g were excluded; 73 (16.7%) of the offspring had proteinuria. The prevalence rates of proteinuria in the offspring were similar if neither parent or only one parent had hypertension (8.9 and 9.4%, respectively), but was significantly higher if both parents had hypertension (18.8%), after adjustment for age, sex, duration of diabetes, and 2-h post-load plasma glucose concentration in the offspring and diabetes in the parents by logistic regression. The odds for proteinuria being present in the offspring if both parents had hypertension was 2.2 times (95% confidence interval, 1.2 to 4.2) that if only one parent had hypertension. When mean arterial pressure and blood pressure treatment in the offspring were added to the model the relationship remained (odds ratio = 2.2; 95% confidence interval, 1.1 to 4.3). Hypertension in both parents is associated with the development of proteinuria in offspring with NIDDM. This relationship was present even when controlled for the effects of blood pressure and its treatment in the offspring.

Adult↗
PubMed1996

Survey of the diet of Pima Indians using quantitative food frequency assessment and 24-hour recall. Diabetic Renal Disease Study.

OBJECTIVE: A dietary survey was conducted in the Gila River Indian Community in Arizona using two methods of dietary assessment--24-hour recall and quantitative food frequency (QFF) assessment--to determine the usual intake of the population. DESIGN: Interviews were conducted by Pima women who were trained and monitored by a research dietitian. Energy and nutrient intake were calculated using a computerized dietary database that included specific Pima foods. SUBJECTS: An age- and sex-stratified sample of 575 Pima Indians (273 men, 302 women) aged 18 to 74 years participated in the study. STATISTICAL ANALYSES: Spearman correlations were used to compare the results of the two survey methods for energy and each nutrient. Intraclass correlations were used to measure reproducibility. RESULTS: According to the 24-hour recall, mean reported energy intakes within decades of age were 95% to 112% of those in the US population for Pima women, and 76% to 94% of those in the US population for Pima men. Total energy intake assessed using QFF was 30% higher in men and 33% higher in women than the intake assessed using the 24-hour recall method. CONCLUSIONS: A large dietary survey conducted using lay interviewers in a Native-American community was as reproducible as studies conducted in the general US population. The Pima diet was distributed among the major nutrients in a proportion similar to the US diet.

Adolescent↗
PubMed1996

Survival during renal replacement therapy for diabetic end-stage renal disease in Pima Indians.

OBJECTIVE: To examine survival in Pima Indians receiving renal replacement therapy for end-stage renal disease attributed to NIDDM. RESEARCH DESIGN AND METHODS: Vital status through 1994 was determined for 136 diabetic Pima Indians from the Gila River Indian Community who began renal replacement therapy between 1973 and 1990. RESULTS: Median survival from the onset of renal replacement therapy was 39 months (95% Ci, 31-54), 31 months (95% Ci, 11-48) in those who began treatment between 1973 and 1981, and 44 months (95% Ci, 32-56) in those who began treatment between 1982 and 1990 (P = 0.020). During these periods, mean age at onset of treatment increased from 53.3 to 56.1 years (P = 0.166), and mean duration of diabetes at the onset of treatment increased from 16.5 to 20.2 years (P = 0.003). After adjustment for sex, duration of diabetes, initial dialysis type, and kidney transplantation by an age-stratified proportional-hazards analysis, the death rate after starting renal replacement therapy in the second half of the study was 0.54 times (95% CI, 0.33-0.88) that in the first half. If this analysis was restricted to those who survived at least 90 days of therapy, the difference between the time periods was diminished (death rate ratio = 0.76; 95% CI, 0.43-1.32). CONCLUSIONS: Survival in Pima Indians receiving renal replacement therapy improved significantly over the study despite an increase in the average age and diabetes duration of those beginning dialysis. Much of the improvement in survival is attributable to a reduction in the number of deaths within the first 90 days of therapy. The median survival of 47 months in Pima Indians < 65 years old at the initiation of therapy is substantially longer than the 30 months reported in blacks and 16 months reported in whites of similar age with NIDDM.

Adult↗
PubMed1996

Sequential trends in overall and cause-specific mortality in diabetic and nondiabetic Pima Indians.

OBJECTIVE: To compare sequential trends in overall and cause-specific death rates for diabetic and nondiabetic Pima Indians. RESEARCH DESIGN AND METHODS: Underlying causes of death in Pimas aged > or = 15 years old were determined for the years 1975-1989 from review of death certificates and medical records. Overall and cause-specific death rates were compared for consecutive intervals. RESULTS: The all-causes death rate, age- and sex-adjusted, did not change significantly between the first and second halves of the study for diabetic (death rate ratio [DRR] = 0.99, 95% CI 0.70-1.4) or nondiabetic Pimas (DRR = 0.92, 95% CI 0.74-1.1). Among diabetic Pimas, however, the death rate for diabetic nephropathy declined from 2.7 to 1.5/1,000 person-years (DRR = 0.55, 95% CI 0.33-0.93), with ischemic heart disease (IHD) replacing diabetic nephropathy as the leading cause in the second half (DRR = 1.5, 95% CI 0.91-2.6). For diabetic and nondiabetic Pimas combined, the death rate in three consecutive 5-year periods declined progressively for alcoholic liver disease (P = 0.024) and external causes of death (P = 0.016), the largest component of which was automobile accidents. CONCLUSIONS: The decrease in death rate for diabetic nephropathy may be a result of greater access to and improvements in renal replacement therapy. Because of shared risk factors, however, the IHD death rate increased and largely offset the decrease in diabetic nephropathy deaths. The decline in deaths from alcoholic liver disease and from automobile accidents parallels the national trend.

Adolescent↗
PubMed1996

Familial aggregation of medial arterial calcification in Pima Indians with and without diabetes.

OBJECTIVE: Little is known about medial arterial calcification (MAC) other than its association with age, sex, diabetes, and diabetes complications. Familial aggregation of this disorder was studied to determine the importance of potential genetic factors and to assess whether such familial aggregation was independent of that of diabetes. RESEARCH DESIGN AND METHODS: Members of 1,256 Pima Indian nuclear families with 3,339 offspring were examined radiologically for MAC of the feet. Multiple logistic regression analyses were used to compare the presence of the disorder in a parent with the presence of MAC in an offspring and to determine whether familial aggregation of MAC was independent of parental diabetes. RESULTS: Controlled for age, sex, diabetes, serum cholesterol, and blood pressure, offspring of one parent with MAC had 3.3 (95% CI 1.5-7.6) times the odds of MAC as did offspring of parents without MAC, and offspring with both parents affected had an even higher risk (odds ratio, 8.1; 95% CI 3.4-18.8). Controlled for offspring age and sex and for parental age and diabetes, parental MAC was associated with the disorder in offspring (P < 0.001), but the effect of parental diabetes on MAC in the offspring was not significant when controlled for parental MAC (P = 0.36). Furthermore, offspring of nondiabetic parents with MAC, controlled for age, sex, diabetes, and diabetes duration, had 1.7 (95% CI 0.9-3.1) times the odds of MAC than did offspring of diabetic parents with MAC. CONCLUSIONS: Independent of parental age and diabetes and offspring age, sex, diabetes, and diabetes complications, parental MAC confers an increased risk of MAC in offspring. These findings suggest that the factors responsible for the familial clustering of MAC may be different from those for diabetes.

Adult↗
PubMed1996

A two-step strategy for identification of high-risk subjects for a clinical trial of prevention of NIDDM.

OBJECTIVE: To evaluate 2-h plasma glucose (2HPG), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1), a combination of FPG and HbA1 (FPG-HbA1), and other factors as screening tests for identifying high-risk subjects for a clinical trial of prevention of NIDDM and to identify strategies to minimize the total number of oral glucose tolerance tests (OGTTs) required to recruit eligible subjects to the trial. RESEARCH DESIGN AND METHODS: One thousand, one hundred and eight nondiabetic Pima Indians aged 25-64 years were followed for up to 5 years, and factors predicting NIDDM, defined by World Health Organization criteria (2HPG > or = 11.1 mmol/l), were assessed using Cox's proportional hazards analysis. Various threshold values of FPG, HbA1, and FPG-HbA1 were determined, which, when combined with an OGTT, identified subjects with impaired glucose tolerance (IGT) (2HPG > or = 7.8 and < 11.1 mmol/l) at a number of specified risks for developing NIDDM in 5 years. The value of each of the three tests was then assessed by calculating (for each threshold) the numbers to be screened, the numbers requiring an OGTT, and the sample size of IGT subjects needed to detect a 33% reduction in NIDDM by an experimental intervention at a power of 80%. RESULTS: During a median of 4.3 years of follow-up, 91 (8.2%) of the 1.108 nondiabetic subjects developed NIDDM. The estimated 5-year cumulative incidence rate was 13.5%. Each of the variables, 2HPG, FPG, HbA1, FPG-HbA1, BMI, IGT, and systolic (sBP), diastolic (dBP), and mean (MBP) blood pressures, predicted NIDDM (P < 0.05 for each) when controlled for age and sex. In a stepwise proportional hazards analysis model, 2HPG and FPG-HbA1 (P < 0.001 for each) were selected as the best set of predictors of NIDDM and of fasting hyperglycemia (FPG > or = 7.8 mmol/l). CONCLUSIONS: A two-step strategy, in which high-risk individuals are first identified by FPG or FPG-HbA1 and then the OGTT is used to select subjects with IGT, requires fewer OGTTs than when using 2HPG as the initial screening test without substantially increasing the numbers that would need to be screened. Such a strategy also offers the advantage of reducing the necessary sample size and is therefore an effective, efficient, and convenient method of identifying eligible subjects for a clinical trial of prevention of NIDDM.

Adult↗
PubMed1996

Weight fluctuation, mortality and vascular disease in Pima Indians.

OBJECTIVE: To examine the relationship of weight fluctuation to mortality rates and incidence of vascular disease. SUBJECTS: A cohort of Pima Indians, 572 of whom had non-insulin-dependent diabetes mellitus and 766 without diabetes. DESIGN: Individuals were invited biennially to research examinations. The root mean square error (RMSE) of the linear trend of weight with time for the first four examinations after age 20 years was used as an index of weight fluctuation. Subjects were followed from the fourth examination until death or until 31 December 1991. The mortality rate ratio (MRR) and its 95% confidence interval (CI) for those with a high weight fluctuation index relative to those with a lower value were determined. The median duration of follow up was 9.3 (range 0.1-22.6) years. MEASUREMENTS: All cause mortality (n = 356); incidence of diabetic retinopathy (n = 145), diabetic nephropathy (n = 132) and electrocardiographic abnormalities (n = 82). RESULTS: There was no significant relationship between weight fluctuation and mortality for diabetic subjects (MRR = 1.0, 95% CI 0.8-1.3, p = 0.91). Nondiabetic subjects with a high weight fluctuation index had a higher mortality rate than those with a lower index (MRR = 1.5, 95% CI 1.0-2.1, p = 0.03); the association was stronger among men than among women. The excess mortality in the high weight fluctuation group was not due to cardiovascular diseases, but to noncardiovascular causes and the risk for alcohol-related death was particularly increased. Weight fluctuation was not associated with the incidence of diabetic retinopathy, nephropathy or electrocardiographic abnormalities. CONCLUSIONS: A high weight fluctuation index was associated with higher mortality rates in nondiabetic, but not in diabetic, Pima Indians. The excess mortality is largely due to noncardiovascular causes of death and may reflect lifestyle factors associated with weight fluctuation, rather than its metabolic effects.

Adult↗