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Biomedical subjects

R F Hamman

Publications and source records attributed to R F Hamman.

At least 91 records · Page 5Linked to original sources

The roles of insulin, obesity, and fat distribution in the elevation of cardiovascular risk factors in impaired glucose tolerance. The San Luis Valley Diabetes Study.

The objective of this study was to determine whether a less favorable risk factor pattern for cardiovascular disease among persons with impaired glucose tolerance could be explained by fasting insulin, obesity, and/or a central distribution of body fat. Between 1984 and 1988, cardiovascular risk factors were examined cross-sectionally in Hispanic and non-Hispanic white participants in the San Luis Valley Diabetes Study who had either impaired (n = 173) or normal (n = 1,107) glucose tolerance. Sex-specific analysis of covariance models were constructed to adjust risk factor levels for age, age and insulin, and age, insulin, body mass index, and centrality index. Both males and females with impaired glucose tolerance had higher age-adjusted mean diastolic blood pressures, heart rates, uric acid levels, and triglyceride levels and lower levels of high density lipoprotein (HDL) cholesterol and HDL3 cholesterol than normal subjects; differences were significant for all risk factors except HDL cholesterol and HDL3 cholesterol in males. Differences in diastolic blood pressure in males, and differences in heart rate and triglyceride in both sexes, remained significant after adjustment for all covariates. However, differences in uric acid in males and differences in diastolic blood pressure and HDL3 cholesterol in females were attenuated to borderline significance levels. Differences in uric acid and HDL cholesterol in females were diminished to nonsignificant levels, especially after adjustment for obesity-related measures. With few exceptions, fasting insulin did not appear to play a major role in accounting for differences in these risk factors. With adjustment, ethnic differences (Hispanic vs. non-Hispanic white) were smaller and were statistically significant less often than differences observed between impaired and normal glucose tolerant groups. The authors concluded that hyperinsulinemia, obesity, and a central body fat distribution accounted for some, but usually not all, of the less favorable cardiovascular risk factor pattern found in subjects with impaired glucose tolerance.

Adult↗

Prevalence of coronary heart disease in subjects with normal and impaired glucose tolerance and non-insulin-dependent diabetes mellitus in a biethnic Colorado population. The San Luis Valley Diabetes Study.

The prevalence of coronary heart disease was studied in 1984-1988 in 1,092 individuals with normal glucose tolerance, 173 individuals with impaired glucose tolerance, and 429 individuals with non-insulin-dependent diabetes mellitus, who were age 25-74 years and were from a biethnic community in the San Luis Valley, Colorado. Glucose tolerance was classified using the World Health Organization criteria, and coronary heart disease prevalence was assessed using the Rose Questionnaire and a resting electrocardiogram. Compared with normal glucose tolerance, coronary heart disease was significantly more prevalent in diabetic non-Hispanic white women (odds ratio (OR) for all end points combined = 3.2, 95% confidence interval (Cl) 1.8-5.5) and men (OR = 1.9, 95% Cl 1.1-3.3) and in diabetic Hispanic women (OR = 1.7, 95% Cl 1.1-2.5), but not men (OR = 1.0, 95% Cl 0.6-1.7). Among diabetic men, the prevalence of possible myocardial infarction was lower in Hispanics than in non-Hispanic whites (OR = 0.4, 95% Cl 0.2-0.7). Similar patterns of coronary heart disease were observed in individuals with impaired glucose tolerance. The paradoxically low prevalence of coronary heart disease in Hispanics with non-insulin-dependent diabetes mellitus, especially men, may be due to unknown protective factors, increased case fatality, or competing mortality in this group.

Adult↗

Two common polymorphisms in the APO A-IV coding gene: their evolution and linkage disequilibrium.

Human apolipoprotein A-IV (APO A-IV) exhibits a common protein polymorphism detectable by isoelectric focusing (IEF) due to a single base substitution at codon 360 which replaces the frequently occurring glutamine residue (allele 1) with histidine (allele 2). Recently, sequence analysis of the APO A-IV coding region has revealed another common nucleotide substitution at codon 347 which converts the commonly present threonine residue (allele A) into serine (allele T). In order to investigate the extent of genetic variation at codon 347, we screened DNA samples from 192 unrelated individuals using a polymerase chain reaction based assay. The frequencies of the two alleles, A-IV*A and A-IV*T, were 0.81 and 0.19, respectively, with average heterozygosity 0.31. Genetic screening of the corresponding 192 plasma samples by IEF gave frequencies of 0.922 and 0.078 for the A-IV*1 and A-IV*2 alleles, respectively, at codon 360 with average heterozygosity 0.14. Genotype data at the two polymorphic sites were used to assign unequivocal haplotypes to all the 384 chromosomes. Of the expected four haplotypes (A1, T1, A2, and T2) only three were observed and their frequencies were 0.732 for A1, 0.190 for T1 and 0.078 for A2, with average heterozygosity 0.42. Although our data indicate significant linkage disequilibrium between the two sites (chi 21 = 7.65, P < 0.006, standardized disequilibrium constant phi = -0.14) the degree of nonrandom association varied between alleles at the two sites. Based upon allele frequency data and variable linkage disequilibrium between alleles, we propose that the A2 and T1 haplotypes may have evolved from the parental A1 haplotype by two independent mutations.

Apolipoproteins A↗

Determinants of total high density lipoprotein cholesterol and high density lipoprotein subfraction levels among Hispanic and non-Hispanic white persons with normal glucose tolerance: the San Luis Valley Diabetes Study.

Determinants of total high-density lipoprotein cholesterol (HDL-C) and HDL subfractions were assessed in Hispanic and non-Hispanic white persons (n = 932), aged 20-74 years, in the San Luis Valley, Colorado. Using multiple regression, BMI was negatively associated with HDL-C, HDL2-C, and HDL3-C in men and HDL-C and HDL3-C in women. Among females, current smokers had lower HDL-C and subfractions. Women on beta-blockers had lower HDL3-C levels. For both sexes, a positive association was observed between age and HDL-C and subfractions and physical activity with HDL-C and HDL3-C. Drinking alcohol (> or = 50 g/week) was associated with higher HDL-C and HDL3-C in both sexes and HDL2-C in women. The positive association of age and negative associations of the subscapular/triceps ratio and fasting insulin had consistent relationships with HDL-C, HDL2-C, and HDL3-C in men and women. Ethnicity was not significantly associated with HDL-C or subfractions after controlling for body fat distribution or fasting insulin.

Adrenergic beta-Antagonists↗

Incidence of insulin-dependent diabetes mellitus in Colorado.

We examined the incidence of insulin-dependent diabetes mellitus in children 0-17 years of age in Colorado from 1978 to 1988. Cases were ascertained from a statewide registry based on physician surveillance. A total of 1,376 children were diagnosed during this interval in a population averaging 860,000 children. The degree of ascertainment was estimated to be 93.3%. The age-adjusted incidence rate of insulin-dependent diabetes mellitus was 14.8/100,000 person-years. The rate was lower in individuals of Spanish origin (Hispanics) (8.7/100,000 person-years) compared with non-Hispanic individuals (15.5/100,000 person-years) (incidence rate ratio = 0.6, 95% confidence interval = 0.4-0.8). Incidence rates were higher in winter and lower in summer for children 5-17 years old. Children diagnosed before the age of 5 years showed no significant seasonal pattern, although peak incidences were observed in autumn and spring. No temporal trend in diabetes incidence was observed overall or by ethnic group. The increasing insulin-dependent diabetes incidence reported by registries in Europe during this time period was not observed in Colorado.

Adolescent↗

Outpatient management vs in-hospital management of children with new-onset diabetes.

The long-term results of outpatient management of subjects with newly diagnosed insulin-dependent diabetes mellitus (IDDM) are unknown. The longest follow-up described to date is for only one year, a time when most children with IDDM still make endogenous insulin. In this study, 41 young subjects with IDDM, treated and educated in the outpatient setting (1980 to 1984), were compared to a group of 80 similar subjects who received their initial education as hospital inpatients. Long-term glycemic control, as measured by longitudinal glycohemoglobin (HbA1) values was not different in the two groups (p greater than .05). We conclude that outpatient education and management of newly diagnosed subjects with IDDM is as safe and effective as inpatient treatment.

Adolescent↗

Accuracy of a filter paper method for measuring glycosylated hemoglobin.

OBJECTIVE: To compare glycosylated hemoglobin (GH) results obtained by filter paper fingerstick collection and mailed for assay by affinity chromatography with results from a venous sample assayed by ion-exchange chromatography (HbA1) in a local laboratory. RESEARCH DESIGN AND METHODS: Fifty-eight volunteer subjects with insulin-dependent diabetes mellitus (IDDM), aged 5-24 yr, included patients at a referral-based IDDM clinic and subjects in an ongoing research study. We obtained two blood samples from each subject. One was collected by fingerstick onto filter paper, the other by venipuncture into a vacutainer. We sent filter paper samples to the Diabetes Research Laboratory (Univ. of Missouri, Columbia, MO) for analysis. Vacutainer samples were sent to the Clinical Chemistry Department of the Clinical Laboratory, University of Colorado Health Sciences Center. RESULTS: Results were highly correlated (r = 0.89, P = 0.0001). Fifty-nine percent were classified identically when results were normalized to SD units and grouped to suggest levels of clinical concern. CONCLUSIONS: The filter paper method is a convenient, accurate measure of glycosylated hemoglobin in young people with IDDM. It should be considered a credible alternative research and clinical tool.

Adolescent↗

Increasing trend of outpatient management of children with newly diagnosed IDDM. Colorado IDDM Registry, 1978-1988.

OBJECTIVE: To examine the management of newly diagnosed insulin-dependent diabetes mellitus (IDDM) in Colorado over time and to determine the prevalence of outpatient care at IDDM diagnosis on a statewide basis. RESEARCH DESIGN AND METHODS: The Colorado IDDM Registry was used to assess medical care at the diagnosis of IDDM in 1182 patients less than 18 yr of age between 1978 and 1988. RESULTS: Twenty-three percent of children with IDDM in Colorado reported never being hospitalized during the diagnosis period. Treatment of IDDM at diagnosis (outpatient vs. inpatient) did not differ by age, sex, or ethnicity/race. Patients living in rural counties were less likely to have been treated as outpatients at diagnosis than those living in urban counties. Physicians at specialized diabetes clinics (e.g., The Barbara Davis Center for Childhood Diabetes and The Childrens Hospital) were more likely to treat newly diagnosed children in an outpatient setting than physicians not affiliated with these clinics. The proportion of patients receiving only outpatient care at IDDM diagnosis increased from 6% in 1978 to 35% in 1988. This increase can be attributed to three factors: 1) an increase in the number of Colorado children diagnosed at The Barbara Davis Center, where outpatient care is strongly advocated; 2) a change in treatment practices at The Childrens Hospital away from routine hospitalization at onset; and 3) a steady increase in outpatient care for newly diagnosed diabetic children by physicians who were not affiliated with the aforementioned specialized diabetes clinics. CONCLUSIONS: The relatively new practice of outpatient care at diagnosis of IDDM increased between 1978 and 1988 in Colorado, in both specialized diabetes clinics and physicians' practices not affiliated with specialized clinics.

Adolescent↗

Clinical characteristics of IDDM in Hispanics and non-Hispanic whites. Little evidence of heterogeneity by ethnicity.

OBJECTIVE: To compare the clinical characteristics of IDDM in HD and NHWD subjects in order to evaluate potential heterogeneity of IDDM by ethnicity. RESEARCH DESIGN AND METHODS: HD subjects (n = 73) and NHWD subjects (n = 97) were recruited from the Colorado IDDM Registry. The registry included individuals who were Colorado residents, less than 18 yr old at diagnosis, placed on insulin within 2 wk of diagnosis, and had diabetes not secondary to other conditions. Residual beta-cell function was measured as the 1-h C-peptide response to a Sustacal challenge. RESULTS: HD subjects were similar to NHWD subjects in insulin dose, HbA1, HLA-DR antigens, ICAs, and family history of IDDM. HD subjects were more likely to have a family history of NIDDM than NHWD subjects (11 vs. 3%, P = 0.03). HD girls had higher C-peptide levels (0.27 vs. 0.11 nm/L [0.83 vs. 0.33 ng/ml], P = 0.01), BMI (22.7 vs. 20.9 kg/m2 P = 0.04), subscapular skinfold thickness (18.9 vs. 15.0 mm, P = 0.04), and WHR (0.81 vs. 0.77, P = 0.03) than NHWD females. After controlling for diabetes duration, BMI, sex, and family history of NIDDM, residual beta-cell function was associated significantly with Hispanic ethnicity, although the term accounted for just 3% of the overall variability in C-peptide levels. CONCLUSIONS: Little evidence of heterogeneity by ethnicity of IDDM patients in the Colorado IDDM Registry was found. Ethnic differences in C-peptide levels may be related to differences in body fat distribution in females rather than heterogeneity of the disease.

Adolescent↗

Nitrate levels in community drinking waters and risk of IDDM. An ecological analysis.

OBJECTIVE: To investigate whether higher IDDM incidence rates occurred in areas with high nitrate levels in their potable water supplies. RESEARCH DESIGN AND METHODS: Incidence rates for the 63 counties in Colorado were calculated using the Colorado IDDM Registry of children diagnosed < 18 yr of age between 1978 and 1988 (n = 1280). A weighted average of the nitrate levels from each water district within each county was calculated using data collected by the Colorado Department of Health between 1984 and 1988. RESULTS: The rs between nitrate levels and IDDM incidence was 0.26 (P = 0.03). After controlling for differences in ethnicity, counties with water nitrate levels in the third tertile (0.77-8.2 mg/L) had a significantly increased risk of IDDM compared with those in the first tertile (0.0-0.084 mg/L) (rp = 0.29, P = 0.02). CONCLUSIONS: This ecological analysis suggests that low-level nitrate exposure through drinking water may play a role in the etiology of IDDM, perhaps as a promoter through the generation of free radicals.

Adolescent↗

Smokers with IDDM experience excess morbidity. The Colorado IDDM Registry.

OBJECTIVE--To determine whether there is an association between smoking and the self-reported morbidity of people with IDDM and to evaluate the nature of a possible interaction between smoking and IDDM in increasing the risk of morbidity among smokers with IDDM. RESEARCH DESIGN AND METHODS--Subjects were non-Hispanic whites aged 18-28 yr who participated in the Colorado IDDM Registry Follow-up Survey (case subjects, n = 24) or the 1985 NHIS (control subjects, n = 5876). Assessments of self-reported morbidity included any hospitalization in the past year; bed days, sick days, and limited-activity days in the past 2 wk; and ratings of poor health. The criteria outlined by Saracci were used to determine whether smoking was associated with greater morbidity among IDDM case compared to control subjects (smoking by IDDM interaction). RESULTS--Age- and sex-adjusted ORs, estimated from logistic regression, showed that people with IDDM reported excess morbidity compared with control subjects, regardless of smoking status. Smokers with IDDM reported morbidity 3-10 times as often as nonsmoking control subjects and were 2-3 times more likely to report morbidity than nonsmokers with IDDM. The smoking by IDDM interaction was more than multiplicative for all morbidity measures. Fifty to 75% of excess morbidity in young smokers with IDDM over simple additive effects was related to the interaction between smoking and IDDM. CONCLUSIONS--There was excess reported morbidity among people with IDDM who smoked, greater than that expected from the combined effects of smoking and IDDM. Smoking cessation in young people with IDDM may alleviate some of this excess, but more study is needed to determine whether smoking serves as an indicator of poor IDDM care practices or has a physiological impact that compounds the morbidity experienced by people with IDDM.

Adult↗

Apolipoprotein A-IV genetic polymorphism and its impact on quantitative traits in normoglycemic and non-insulin-dependent diabetic Hispanics from the San Luis Valley, Colorado.

Apolipoprotein A-IV exhibits a common two-allele polymorphism in several human populations studied to date. Using isoelectric focusing and immunoblotting, we have analyzed plasmas from 188 non-insulin-dependent diabetic and 238 normoglycemic Hispanic individuals from the San Luis Valley, Colorado, to determine APOA4 genotype frequencies and to estimate the impact of the genotypes on quantitative traits. The frequencies of the two common alleles, APOA4*1 and APOA4*2, were 0.929 and 0.069, respectively, in normal subjects and 0.901 and 0.096, respectively, in diabetics. The third rare allele, APOA4*3, was detected sporadically in both groups. We studied the impact of APOA4 polymorphism on the levels of total plasma cholesterol, HDL cholesterol and its subfractions (HDL3 and HDL2), LDL cholesterol, triglycerides, glucose, and insulin. We observed no significant effect of the APOA4 polymorphism on any trait in diabetics. However, we did note a significant sex-specific effect in normoglycemic females on the level of total HDL cholesterol (p = 0.001) and its subfractions HDL2 (p = 0.043) and HDL3 (p = 0.001). The effect of the APOA4*2 allele in normal Hispanic females was to lower the total HDL, HDL2, and HDL3 cholesterol by 8.75 mg/dl, 2.37 mg/dl, and 5.36 mg/dl, respectively, compared to the common APOA4*1 allele.

Adult↗

High-fat, low-carbohydrate diet and the etiology of non-insulin-dependent diabetes mellitus: the San Luis Valley Diabetes Study.

Diet has long been believed to be an important risk factor for non-insulin-dependent diabetes. Animal studies generally support a relation between high-fat diets and development of insulin resistance. However, conclusive epidemiologic evidence is lacking. To further investigate the role of dietary fat and carbohydrate as potential risk factors for the onset of non-insulin-dependent diabetes mellitus, current diet was assessed among a geographically based group of 1,317 subjects without a prior diagnosis of diabetes who were seen in the period from 1984 to 1988 in two countries in southern Colorado. In this study, 24-hour diet recalls were reported prior to an oral glucose tolerance test. Persons with previously undiagnosed diabetes (n = 70) and impaired glucose tolerance (n = 171) were each compared with confirmed normal controls (n = 1,076). The adjusted odds ratios relating a 40-g/day increase in fat intake to non-insulin-dependent diabetes mellitus and impaired glucose tolerance were 1.51 (95% confidence interval 0.85-2.67) and 1.62 (95% confidence interval 1.09-2.41), respectively. Restricting cases to diabetic persons with fasting glucose greater than 140 mg/dl and persons with impaired glucose tolerance confirmed on follow-up, the odds ratios increased to 3.03 (95% confidence interval 1.07-8.62) and 2.67 (95% confidence interval 1.33-5.36), respectively. The findings support the hypothesis that high-fat, low-carbohydrate diets are associated with the onset of non-insulin-dependent diabetes mellitus in humans.

Adult↗

Diet and the risk of in situ cervical cancer among white women in the United States.

A case-control study of women with incident in situ and invasive cervical cancer was conducted during 1982-83 in five US areas reporting to the Comprehensive Cancer Patient Data System: Birmingham, AL; Chicago, IL; Denver, CO; Miami, FL; and Philadelphia, PA. Controls were selected by random-digit dialing and matched to invasive cases on age, race, and telephone exchange. Of the white non-Hispanic in situ cases and controls identified, 229 (78 percent) and 502 (74 percent) were successfully interviewed. Diet was assessed by asking about the usual adult frequency of consumption of 75 food items and the use of vitamin supplements. Included were the major sources of the four micronutrients postulated to reduce the risk of cervical cancer: carotenoids, vitamin A, vitamin C, and folate. Weak inverse associations between risk of in situ disease and intake of carotenoids, vitamin C, folate, fruit, and vegetables/fruits were noted but, with further analysis, these seemed attributable to residual confounding by the multiple lifestyle-related risk factors for this disease and possibly to selection bias. Vitamin A and vegetable intake were unrelated to risk. Dark yellow-orange vegetable consumption and duration of multivitamin use were each strongly related to reduced risk of in situ disease (P for trend = 0.02 and 0.002, respectively) and need to be evaluated in other studies. The absence of persuasive protective effects for the four micronutrients and the similar findings from our analysis of invasive cervical cancer do not concur with other epidemiologic studies and suggest that the role of diet and nutrition in the etiology of cervical cancer is not yet resolved.

Adult↗

Apolipoprotein A-IV polymorphism, and its role in determining variation in lipoprotein-lipid, glucose and insulin levels in normal and non-insulin-dependent diabetic individuals.

Apolipoprotein A-IV (apo A-IV) is a major component of several lipoprotein particles and may, therefore, play an important role in lipid metabolism. Genetic polymorphism of apo A-IV has been reported in humans and several other animal species. The presence of two common alleles, apo A-IV * 1 and apo A-IV * 2 has been documented in several human populations. In this investigation, we have determined apo A-IV polymorphism by isoelectric focusing-immunoblotting in 82 non-insulin-dependent diabetic and 204 control non-Hispanic Whites from the San Luis Valley, Colorado. We have also estimated the impact of apo A-IV polymorphism on eight quantitative traits: total cholesterol, HDL-cholesterol, HDL3 and HDL2-cholesterol, LDL-cholesterol, triglycerides, fasting glucose and fasting insulin. No statistically significant difference was seen in apo A-IV allele frequencies between the control and diabetics, and these frequencies were comparable with those reported for U.S. White and European populations. Among controls, the impact of the apo A-IV polymorphism was significant on LDL-cholesterol (P = 0.04) in females and on fasting insulin levels (P = 0.06) in males. In diabetics, the effect was significant on insulin (P = 0.03) levels in males only. Furthermore, our data suggest that when making comparison of lipid profiles between the controls and diabetics the presence or absence of common apo A-IV phenotypes should be taken into account as these appear to effect these comparisons.

Adult↗

Physical-activity-assessment measures compared in a biethnic rural population: the San Luis Valley Diabetes Study.

We evaluated the consistency of three questionnaire methods of assessing work and leisure activity in the rural biethnic population of the San Luis Valley Diabetes Study. A 7-d physical activity recall (PAR), a ranking of usual activity, and a history of usual participation in vigorous activity were used. Energy expenditure (kJ.kg-1.wk-1) (EE) was estimated from PAR. Subjects were 503 adults [49% non-Hispanic white (NHW), 51% Hispanic]. Physical activity at work rather than leisure-time activity largely determined total energy expenditure. Average EE at work increased with work rank for all subjects combined [mean EE (SEE) for rank 1 (low) = 324.2 (24.4), rank 4 (high) = 874.0 (102.1)] and within sex, ethnic, and occupational subgroups. Leisure EE increased with leisure rank only for NHW men and employed women. Similar patterns were observed in comparisons of PAR data with history of vigorous activity. Further development and validation of instruments appropriate for use across population subgroups are needed.

Adult↗

Invasive cervical cancer and intrauterine device use.

Although the hypothesis that intrauterine device (IUD) use might promote cervical cancer has been considered since the introduction of IUDs in the early 1900s, previous studies are inconclusive. Data collected in interviews with 481 invasive cervical cancer cases and 801 general population controls from Birmingham, Chicago, Denver, Miami and Philadelphia were used to address this issue. These data were analysed to determine the relationship between IUD use and the risk of cervical cancer, with consideration of the type of IUD (copper and inert) and duration of use. A non-significant reduced risk of cervical cancer was associated with copper IUD use, indicated by an adjusted odds ratio (OR) of 0.6 (95% Cl: 0.3-1.2), but virtually no effect was found for inert IUD use (OR = 1.1, 95% Cl: 0.9-1.7). Decreased risk with increased duration of copper IUD use supports a possible protective effect of copper IUD use on the development of invasive cervical cancer.

Adult↗