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Biomedical subjects

R L Hanson

Publications and source records attributed to R L Hanson.

At least 55 records · Page 3Linked to original sources
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

Enzymatic synthesis of L-6-hydroxynorleucine.

L-6-Hydroxynorleucine, a key chiral intermediate used for synthesis of a vasopeptidase inhibitor, was prepared in 89% yield and > 99% optical purity by reductive amination of 2-keto-6-hydroxyhexanoic acid using glutamate dehydrogenase from beef liver. In an alternate process, racemic 6-hydroxynorleucine produced by hydrolysis of 5-(4-hydroxybutyl)hydantoin was treated with D-amino acid oxidase to prepare a mixture containing 2-keto-6-hydroxyhexanoic acid and L-6-hydroxynorleucine followed by the reductive amination procedure to convert the mixture entirely to L-6-hydroxynorleucine, with yields of 91 to 97% and optical purities of > 99%.

Animals↗
PubMed1999

HDL cholesterol subfractions and risk of developing type 2 diabetes among Pima Indians.

OBJECTIVE: To examine the relationships between HDL cholesterol subfractions and the incidence of type 2 diabetes and to evaluate potential sex differences in these relationships. RESEARCH DESIGN AND METHODS: Proportional hazards analyses were performed to examine the relationships between HDL subfractions and the development of type 2 diabetes in Pima Indian women and men. Results were controlled for age, BMI, systolic blood pressure, and 2-h glucose. RESULTS: Some 54 of 123 women and 25 of 50 men developed type 2 diabetes during a mean follow-up of 10 (2-19) years. For women, in separate models, high levels of total HDL, HDL2a, and HDL3 were negatively associated with incidence of type 2 diabetes; results were unchanged in models further controlled for fasting insulin level or alcohol consumption. For men, the results were inconsistent and associated with wide confidence intervals; high total HDL and HDL3 were positively associated with incidence of type 2 diabetes in models further controlled for fasting insulin level, but the risk estimates were attenuated in models further controlled for alcohol consumption. CONCLUSIONS: High levels of total HDL, HDL2a, and HDL3 were potential protective factors against type 2 diabetes in women after accounting for alcohol consumption and insulin resistance. High levels of total HDL and HDL3 were predictive of type 2 diabetes in men; the relationship in men appeared to be due to an association with alcohol consumption. The sex differences in the effects of HDL cholesterol may be related to the effects of sex hormones or lipoproteins.

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

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

Analytic strategies to detect linkage to a common disorder with genetically determined age of onset: diabetes mellitus in Pima Indians.

Segregation analysis suggests that the high prevalence of non-insulin-dependent diabetes mellitus in Pima Indians may be partially due to a single locus with a major effect on age of onset. A simulation study was conducted to evaluate the power of various age-adjustment strategies in linkage analysis to detect this putative gene in 1,862 sib-pairs from 264 potentially informative nuclear families. Simulations were performed at a recombination fraction (theta) of 0.05 for values of polymorphism information content (PIC) ranging from 0.38 to 1.00. Under the codominant age-of-onset model supported by segregation analysis, power to detect linkage (at P < 0.0001) at PIC = 1.00 was 75% for the Haseman-Elston (HE) sib-pair test and 63% for the affected sib-pair test (ASP) with no age adjustment. Substantial improvements in power were possible for the HE test by defining the trait as a survival analysis "residual" (power = 91%) and for the ASP test by use of an age-of-onset threshold above which individuals are not included in the analysis (power = 90%, for age of onset < 45 yrs). The parametric method of linkage analysis was most powerful, as long as both the analysis model and the simulation model involved a genetic effect on age of onset, regardless of whether dominance at the trait locus was misspecified. Methods of age adjustment based on the probability of eventually becoming affected only improved power when the genetic effect was on susceptibility rather than age of onset. The method of age adjustment in linkage analysis may depend on whether one anticipates a genetic effect primarily on age of onset or on ultimate susceptibility.

Adolescent↗
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

Dietary calcium and blood pressure in a Native American population.

OBJECTIVE: To assess the relationship between dietary calcium and blood pressure. METHODS: Cross-sectional study of 404 adult Pima Indians of Arizona. Dietary variables were assessed by the 24-hour recall. Hypertension (HTN) was defined as systolic blood pressure (SBP) > or = mmHg or diastolic blood pressure (DBP) > or = 90 mmHg or drug treatment. RESULTS: Controlled for age and sex, dietary calcium intake was higher in subjects with HTN than in those without (p < 0.01), and higher dietary calcium was associated with a higher prevalence of HTN (odds ratio comparing highest with lowest tertile group of calcium = 2.6, 95% CI 1.4-4.8). Age-sex-adjusted men DBP in low, middle and high tertiles of calcium was 74, 76, and 79 mmHg, respectively (p < 0.001). SBP was not significantly different in the three tertiles (p = 0.07). Multiple regression analyses that controlled for age, sex, body mass index, sodium, potassium and alcohol also suggested a positive association between DBP and dietary calcium (p < 0.01), an association which was stronger at higher glucose concentrations (p < 0.01 for the calcium-glucose interaction). CONCLUSION: In Pima Indians, a population with a high incidence of diabetes, the inverse association between dietary calcium and blood pressure reported in other populations was not found.

Adolescent↗
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

Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima indians.

The UCP2-UCP3 gene cluster maps to chromosome 11q13 in humans, and polymorphisms in these genes may contribute to obesity through effects on energy metabolism. DNA sequencing of UCP2 and UCP3 revealed three polymorphisms informative for association studies: an Ala-->Val substitution in exon 4 of UCP2, a 45 bp insertion/deletion in the 3'-untranslated region of exon 8 of UCP2 and a C-->T silent polymorphism in exon 3 of UCP3. Initially, 82 young (mean age = 30 +/- 7 years), unrelated, full-blooded, non-diabetic Pima Indians were typed for these polymorphisms by direct sequencing. The three sites were in linkage disequilibrium ( P < 0.00001). The UCP2 variants were associated with metabolic rate during sleep (exon 4, P = 0.007; exon 8, P = 0.016) and over 24 h (exon 8, P = 0.038). Heterozygotes for UCP2 variants had higher metabolic rates than homozygotes. The UCP3 variant was not significantly associated with metabolic rate or obesity. In a further 790 full-blooded Pima Indians, there was no significant association between the insertion/deletion polymorphism and body mass index (BMI). However, when only individuals >45 years of age were considered, heterozygotes (subjects with the highest sleeping metabolic rate) had the lowest BMI (P = 0.04). The location of the insertion/deletion polymorphism suggested a role in mRNA stability; however, it appeared to have no effect on skeletal muscle UCP2 mRNA levels in a subset of 23 randomly chosen Pima Indians. In conclusion, these results suggest a contribution from UCP2 (or UCP3) to variation in metabolic rate in young Pima Indians which may contribute to overall body fat content later in life.

Adolescent↗
PubMed1998

Variations in the vitamin D-binding protein (Gc locus) are associated with oral glucose tolerance in nondiabetic Pima Indians.

Electrophoretic variants of the vitamin D-binding protein (DBP) have been associated with type 2 diabetes as well as with metabolic characteristics that predispose to type 2 diabetes in several populations. The Gc gene that encodes DBP maps to chromosome 4q12, a region that has recently been found to be potentially linked to plasma glucose and insulin concentrations in Pima Indians. Therefore, the gene that encodes DBP was analyzed as a candidate gene for our linkage findings in the Pima Indians. Sequence analysis of the coding exons identified two previously described missense polymorphisms at codons 416 and 420, which are the genetic basis for the three common electrophoretic variants of DBP (Gc1f, Gc1s, and Gc2). These variants in DBP were associated with differences in oral glucose tolerance in nondiabetic Pima Indians.

Adult↗
PubMed1998

Sib-pair linkage analysis for susceptibility genes for microvascular complications among Pima Indians with type 2 diabetes. Pima Diabetes Genes Group.

The aim of this study was to identify loci influencing susceptibility to microvascular complications (nephropathy and retinopathy) in Pima Indians with type 2 diabetes. Affected sib-pair linkage analyses were performed on 98 diabetic sibling pairs with nephropathy in both members and on 103 sibling pairs with retinopathy in both members. Four chromosomal regions with some evidence of linkage (P < 0.01; logarithm of odds [LOD] >1.18) with nephropathy were identified. The strongest evidence for linkage with nephropathy was on chromosome 7, where two adjacent markers, D7S500 and D7S1804, were linked both by two-point analysis (LOD = 2.73 and LOD = 2.28; respectively) and by multipoint analysis (LOD = 2.04). Additional loci potentially linked to nephropathy were found on chromosome 3, near D3S3053 (multipoint LOD = 1.48); on chromosome 9, near D9S910 (multipoint LOD = 1.12) and D9S302 (two-point LOD = 1.28); and on chromosome 20, near D20S115 (multipoint LOD = 1.83) and GATA65E01 (two-point LOD = 1.89). Multipoint analyses showed two regions with some evidence for linkage to retinopathy: chromosome 3 between D3S3053 and D3S2427 (LOD = 1.36), and chromosome 9 between D9S1120 and D9S910 (LOD = 1.46). These linkage analyses suggest that a genetic element on chromosome 7 and possibly one on chromosome 20 influence susceptibility to diabetic nephropathy but not retinopathy. Genetic elements on chromosome 3 and 9 may determine susceptibility to both these complications. These loci could presumably influence susceptibility to the complications by influencing the microvasculature directly, by influencing the severity of hyperglycemia, or by other unknown mechanisms.

Arizona↗
PubMed1998

The relationship of menstrual irregularity to type 2 diabetes in Pima Indian women.

OBJECTIVE: Menstrual irregularity is associated with hyperinsulinemia and hyperandrogenemia in nondiabetic Pima Indian women of child-bearing age. In this population-based study, we determined the relationship of menstrual irregularity to type 2 diabetes in Pima Indian women. RESEARCH DESIGN AND METHODS: Participants for this cross-sectional analysis were 695 nonpregnant Pima Indian women, aged 18-44 years, involved in an ongoing epidemiologic study of diabetes among residents of the Gila River Indian Community of Arizona. Clinical data were collected by questionnaire and an examination that included a 75-g oral glucose tolerance test; diabetes was diagnosed by World Health Organization criteria. Menstrual irregularity was defined as an interval of 3 months or more between menses, when not pregnant, since age 18 years. RESULTS: History of menstrual irregularity was significantly associated with a high prevalence of diabetes (37 vs. 13%; odds ratio = 4.2, 95% CI = 1.6-10.8) in the least obese women (BMI < 30 kg/m2), adjusted for the effects of age and overall obesity. This association was, in part, because of greater central obesity in women with irregular menses. In more obese women, there was little association with menstrual irregularity, and diabetes was frequent regardless of menstrual history. CONCLUSIONS: Prevalence of type 2 diabetes is higher among Pima indian women with a history of menstrual irregularity. The difference is most pronounced among the least obese group of women. This association may be because of insulin resistance and hyperinsulinemia, which predict type 2 diabetes, also causing hyperandrogenism and menstrual irregularity. The findings reinforce the need to evaluate women with menstrual irregularity for hyperglycemia.

Adult↗
PubMed1997

Serum cholesterol and mortality rates in a Native American population with low cholesterol concentrations: a U-shaped association.

BACKGROUND: Low serum cholesterol concentrations are associated with high death rates from cancer, trauma, and infectious diseases, but the meaning of these associations remains controversial. The present report evaluates whether low cholesterol is likely to be a causal factor for mortality from all causes or from specific causes. METHODS AND RESULTS: Among 4553 Pima Indians > or =20 years old, a population with low serum cholesterol (median, 4.50 mmol/L), 1077 deaths occurred during a mean follow-up of 12.8 years. Trauma was the most common cause. The relationship between serum cholesterol measured at 2-year intervals and age- and sex-standardized mortality rates was U-shaped. Cholesterol was related positively to mortality from cardiovascular diseases and diabetes (including nephropathy) and negatively to mortality from cancer and alcohol-related diseases. The relationship was U-shaped for mortality from infectious diseases, and cholesterol was not related to mortality from trauma. Change in cholesterol from one examination to the next was positively related to mortality from diabetes. In proportional-hazards models adjusted for potential confounders, the relationship between baseline cholesterol and mortality was U-shaped for all causes and diabetes and positive for cardiovascular diseases. Other relationships were nonsignificant. Among 3358 subjects followed > or =5 years, the relationship was significant and positive only for mortality from cardiovascular diseases. CONCLUSIONS: Despite a high exposure risk for Pima Indians, if low cholesterol level is a causal factor, the relationships between low serum cholesterol and high mortality rates probably result from diseases lowering cholesterol rather than from a low cholesterol causing the diseases.

Adult↗