PubMed Health⌕ Search

Biomedical subjects

Richard F Hamman

Publications and source records attributed to Richard F Hamman.

At least 19 recordsLinked to original sources
PubMed2007

Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression to diabetes and response to troglitazone.

CONTEXT: The common P12A polymorphism in PPARG (a target for thiazolidinedione medications) has been consistently associated with type 2 diabetes. OBJECTIVE: We examined whether PPARG P12A affects progression from impaired glucose tolerance to diabetes, or responses to preventive interventions (lifestyle, metformin, or troglitazone vs. placebo). PATIENTS: This study included 3548 Diabetes Prevention Program participants. DESIGN: We performed Cox regression analysis using genotype at PPARG P12A, intervention, and their interactions as predictors of diabetes incidence. We also genotyped five other PPARG variants implicated in the response to troglitazone and assessed their effect on insulin sensitivity at 1 yr. RESULTS: Consistent with prior cross-sectional studies, P/P homozygotes at PPARG P12A appeared more likely to develop diabetes than alanine carriers (hazard ratio, 1.24; 95% confidence interval, 0.99-1.57; P=0.07) with no interaction of genotype with intervention. There was a significant interaction of genotype with body mass index and waist circumference (P=0.03 and 0.002, respectively) with the alanine allele conferring less protection in more obese individuals. Neither PPARG P12A nor five other variants significantly affected the impact of troglitazone on insulin sensitivity in 340 participants at 1 yr. CONCLUSIONS: The proline allele at PPARG P12A increases risk for diabetes in persons with impaired glucose tolerance, an effect modified by body mass index. In addition, PPARG P12A has little or no effect on the beneficial response to troglitazone.

Amino Acid Substitution↗
PubMed2006

The impact of diabetes on one-year health status outcomes following acute coronary syndromes.

BACKGROUND: Diabetes is an important predictor of mortality patients with ACS. However, little is known about the association between diabetes and health status after ACS. The objective of this study was to examine the association between diabetes and patients' health status outcomes one year after an acute coronary syndrome (ACS). METHODS: This was a prospective cohort study of patients hospitalized with ACS. Patients were evaluated at baseline and one year with the Seattle Angina Questionnaire (SAQ). Socio-demographic and clinical characteristics were ascertained during index ACS hospitalization. One year SAQ Angina Frequency, Physical Limitation, and Health-Related Quality of Life (HRQoL) scales were the primary outcomes of the study. RESULTS: Of 1199 patients, 326 (37%) had diabetes. Patients with diabetes were more likely to present with unstable angina (52% vs. 40%; p < 0.001), less likely to present with STEMI (20% vs. 31%; p < 0.001), and less likely to undergo coronary angiography (68% vs. 82%; p < 0.001). In multivariable analyses, the presence of diabetes was associated with significantly more angina (OR 1.36; 95% CI 1.01-1.38), cardiac-related physical limitation (OR 1.94; 95% CI 1.57-3.24) and HRQoL deficits (OR 1.43; 95% CI 1.01-2.04) at one year. CONCLUSION: Diabetes is associated with more angina, worse physical limitation, and worse HRQoL one year after an ACS. Future studies should assess whether health status outcomes of patients with diabetes could be improved through more aggressive ACS treatment or post-discharge surveillance and angina management.

Acute Disease↗
PubMed2006

Association between higher cumulative doses of recombinant erythropoietin and risk for retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity is a complication of premature birth that varies in its severity. The incidence and severity of retinopathy of prematurity at our perinatal center in a regional referral hospital changed substantially during 1995 to 1998 and presented us with an opportunity to examine whether there was a protective effect on risk of retinopathy associated with exposure to recombinant erythropoietin. METHODS: We undertook a retrospective cohort study. From January 1995 through December 1998, charts of infants weighing<1500 g, who were 30 weeks' gestation or less, and who were admitted and survived to the first eye examination at 6 weeks were reviewed. Primary and secondary risk factors were recorded from the first 6 weeks of life. Of the eligible infants, 327 of 390 (84%) had complete records and retinal examinations. The probability for progression of retinopathy was estimated by logistic regression multivariate analysis using the continuation-ratio model. RESULTS: The overall incidence of retinopathy of prematurity was 36%. Recombinant erythropoietin exposure, as total 6-week dose, was independently associated with an increased risk for progression of retinopathy, OR=1.27 per 500 units/kg (95%CI=1.04, 1.55, P=0.02). Postnatal day of recombinant erythropoietin initiation also was associated with retinopathy risk but did not reach conventional statistical significance, OR=1.07 (CI=1.00, 1.14, P=0.07). CONCLUSIONS: These findings identify an association between cumulative recombinant erythropoietin exposure, used to reduce blood transfusions in premature infants, and an increased risk for retinopathy of prematurity. The nonhematopoietic properties of erythropoietin may account for the above findings, however further evaluation with confirmation is required.

Disease Progression↗
PubMed2006

Lipid abnormalities are prevalent in youth with type 1 and type 2 diabetes: the SEARCH for Diabetes in Youth Study.

OBJECTIVE: Assessment of the prevalence of serum lipid abnormalities in US youth with type 1 or type 2 diabetes. STUDY DESIGN: The SEARCH for Diabetes in Youth Study was a cross-sectional, population-based study, conducted in six centers. Subjects were 2448 youth with diabetes who had a study examination. Outcome measures were fasting measures of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and non-HDL-C. Analysis was descriptive. RESULTS: The overall prevalence of high TC concentration (>240 mg/dL) was 5%; the overall prevalence of high LDL-C (>160 mg/dL) was 3%, and the overall prevalence of high triglyceride (>400 mg/dL) was 2%. About half of the participants (48%) had an LDL-C concentration above the optimal level of 100 mg/dL. Among youth ages 10+, the prevalence of abnormal lipids was higher in type 2 (n = 283) than in type 1 diabetes (n = 1963): 33% versus 19% had TC concentration >200 mg/dL; 24% versus 15% had LDL-C concentration >130 mg/dL; 29% versus 10% had triglyceride concentration >150 mg/dL; 44% versus 12% had HDL-C concentration <40 mg/dL. Only 1% of youth were receiving pharmacologic therapy for dyslipidemia. CONCLUSIONS: A substantial proportion of young patients with diabetes have abnormal serum lipids.

Adolescent↗
PubMed2006

Physical activity in individuals at risk for diabetes: Diabetes Prevention Program.

PURPOSE AND METHODS: Leisure physical activity was assessed using questionnaires with different time frames in the Diabetes Prevention Program (DPP) cohort of 3234 overweight individuals aged > 25 yr with impaired glucose tolerance (IGT) from 27 centers across the United States. The three questionnaires were the Modifiable Activity Questionnaire (MAQ; past year), the Low-Level Physical Activity Recall (LOPAR; past 7 d), and the Third National Health and Nutrition Examination Survey (NHANES III; past month). This provided the opportunity to examine the relationship between the three activity measures and to compare activity levels of the DPP sample with that of a national sample with IGT. RESULTS: Leisure activity determined by the three questionnaires significantly correlated with each other, although the correlations between MAQ and NHANES III were stronger (men: rho = 0.52; women: rho = 0.49; P < 0.01) than between LOPAR and either measure (men: rho = 0.20 for MAQ, 0.24 for NHANES; women: rho = 0.10 for MAQ, 0.13 for NHANES). In the DPP, measures of obesity and glucose tolerance were significantly correlated with activity levels determined by MAQ and NHANES, but not LOPAR. Activity levels in DPP participants determined by the NHANES III questionnaire were generally higher than those reported by individuals meeting DPP eligibility criteria who were part of the NHANES cohort for similar age, body mass index, and race or ethnicity. CONCLUSION: If the DPP participants were more active than a national sample of individuals with IGT, this would have implications for translation when using the DPP lifestyle intervention in less active or less motivated populations. Finally, the weak relationship between activity levels obtained with MAQ and LOPAR may result from the fact that they encompass different time frames and different components of leisure activity.

Adult↗
PubMed2006

The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study.

OBJECTIVE: Our goal was to estimate the prevalence of diabetes mellitus in youth <20 years of age in 2001 in the United States, according to age, gender, race/ethnicity, and diabetes type. METHODS: The SEARCH for Diabetes in Youth Study is a 6-center observational study conducting population-based ascertainment of physician-diagnosed diabetes in youth. Census-based denominators for 4 geographically based centers and enrollment data for 2 health plan-based centers were used to calculate prevalence. Age-, gender-, and racial/ethnic group-specific prevalence rates were multiplied by US population counts to estimate the total number of US youth with diabetes. RESULTS: We identified 6379 US youth with diabetes in 2001, in a population of approximately 3.5 million. Crude prevalence was estimated as 1.82 cases per 1000 youth, being much lower for youth 0 to 9 years of age (0.79 cases per 1000 youth) than for those 10 to 19 years of age (2.80 cases per 1000 youth). Non-Hispanic white youth had the highest prevalence (1.06 cases per 1000 youth) in the younger group. Among 10- to 19-year-old youth, black youth (3.22 cases per 1000 youth) and non-Hispanic white youth (3.18 cases per 1000 youth) had the highest rates, followed by American Indian youth (2.28 cases per 1000 youth), Hispanic youth (2.18 cases per 1000 youth), and Asian/Pacific Islander youth (1.34 cases per 1000 youth). Among younger children, type 1 diabetes accounted for > or = 80% of diabetes; among older youth, the proportion of type 2 diabetes ranged from 6% (0.19 cases per 1000 youth for non-Hispanic white youth) to 76% (1.74 cases per 1000 youth for American Indian youth). We estimated that 154,369 youth had physician-diagnosed diabetes in 2001 in the United States. CONCLUSIONS: The overall prevalence estimate for diabetes in children and adolescents was approximately 0.18%. Type 2 diabetes was found in all racial/ethnic groups but generally was less common than type 1, except in American Indian youth.

Adolescent↗
PubMed2006

Effect of weight loss with lifestyle intervention on risk of diabetes.

OBJECTIVE: Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants. RESEARCH DESIGN AND METHODS: For this study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up. RESULTS: A total of 1,079 participants were aged 25-84 years (mean 50.6 years, BMI 33.9 kg/m(2)). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35-0.51]; P < 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence. CONCLUSIONS: Interventions to reduce diabetes risk should primarily target weight reduction.

Adult↗
PubMed2006

Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1 (autoimmune) diabetes.

OBJECTIVE: The "accelerator hypothesis" predicts that fatness is associated with an earlier age at onset of type 1 diabetes. We tested the hypothesis using data from the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS: Subjects were 449 youth aged <20 years at diagnosis who had positive results for diabetes antibodies measured 3-12 months after diagnosis (mean 7.6 months). The relationships between age at diagnosis and fatness were examined using BMI as measured at the SEARCH visit and reported birth weight, both expressed as SD scores (SDSs). RESULTS: Univariately, BMI SDS was not related to age at diagnosis. In multiple linear regression, adjusted for potential confounders, a significant interaction was found between BMI SDS and fasting C-peptide (FCP) on onset age (P < 0.0001). This interaction remained unchanged after additionally controlling for number and titers of diabetes antibodies. An inverse association between BMI and age at diagnosis was present only among subjects with FCP levels below the median (<0.5 ng/ml) (regression coefficient -7.9, P = 0.003). A decrease of 1 SDS in birth weight (639 g) was also associated with an approximately 5-month earlier age at diagnosis (P = 0.008), independent of sex, race/ethnicity, current BMI, FCP, and number of diabetes antibodies. CONCLUSIONS: Increasing BMI is associated with younger age at diagnosis of type 1 diabetes only among those U.S. youth with reduced beta-cell function. The intrauterine environment may also be an important determinant of age at onset of type 1 diabetes.

Adolescent↗
PubMed2005

The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance.

BACKGROUND: The Diabetes Prevention Program (DPP) demonstrated that interventions can delay or prevent the development of type 2 diabetes. OBJECTIVE: To estimate the lifetime cost-utility of the DPP interventions. DESIGN: Markov simulation model to estimate progression of disease, costs, and quality of life. DATA SOURCES: The DPP and published reports. TARGET POPULATION: Members of the DPP cohort 25 years of age or older with impaired glucose tolerance. TIME HORIZON: Lifetime. PERSPECTIVES: Health system and societal. INTERVENTIONS: Intensive lifestyle, metformin, and placebo interventions as implemented in the DPP. OUTCOME MEASURES: Cumulative incidence of diabetes, microvascular and neuropathic complications, cardiovascular complications, survival, direct medical and direct nonmedical costs, quality-adjusted life-years (QALYs), and cost per QALY. RESULTS OF BASE-CASE ANALYSIS: Compared with the placebo intervention, the lifestyle and metformin interventions were estimated to delay the development of type 2 diabetes by 11 and 3 years, respectively, and to reduce the absolute incidence of diabetes by 20% and 8%, respectively. The cumulative incidence of microvascular, neuropathic, and cardiovascular complications were reduced and survival was improved by 0.5 and 0.2 years. Compared with the placebo intervention, the cost per QALY was approximately 1100 dollars for the lifestyle intervention and $31 300 for the metformin intervention. From a societal perspective, the interventions cost approximately 8800 dollars and 29,900 dollars per QALY, respectively. From both perspectives, the lifestyle intervention dominated the metformin intervention. RESULTS OF SENSITIVITY ANALYSIS: Cost-effectiveness improved when the interventions were implemented as they might be in routine clinical practice. The lifestyle intervention was cost-effective in all age groups. The metformin intervention did not represent good use of resources for persons older than 65 years of age. LIMITATIONS: Simulation results depend on the accuracy of the underlying assumptions, including participant adherence. CONCLUSIONS: Health policy should promote diabetes prevention in high-risk individuals.

Adult↗
PubMed2005

Assessing motor and cognitive regulation in AD, MCI, and controls using the Behavioral Dyscontrol Scale.

The objective of this study was to evaluate the utility of the Behavioral Dyscontrol Scale (BDS) as a measure of behavioral regulation in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Two patients groups (n=40 MCI and 40 AD) recruited from a memory clinic and an elderly control (EC) group (n=40) recruited from the community were administered a battery of neuropsychological tests including the BDS and a measure of functioning of activities of daily living (ADLs). Results of ROC analyses revealed that performance on the BDS discriminated between the AD group and the MCI and EC groups but did not discriminate between the MCI and EC groups. Performance on the BDS was an independent predictor of ADLs in patient groups after controlling for the effects of performance on a memory measure.

Activities of Daily Living↗
PubMed2005

The C161-->T polymorphism in peroxisome proliferator-activated receptor gamma, but not P12A, is associated with insulin resistance in Hispanic and non-Hispanic white women: evidence for another functional variant in peroxisome proliferator-activated receptor gamma.

The P12A variant in the peroxisome proliferator-activated receptor gamma (PPARgamma) gene has been intensely studied for association with obesity-related or type-2 diabetes-related traits; however, the results have been somewhat inconsistent in different populations. We genotyped a large cohort of Hispanic and non-Hispanic white individuals from the San Luis Valley Diabetes Study for P12A and another common variant, C161-->T, in the PPARgamma gene to determine if these sites were associated with fasting glucose, insulin, free fatty acid levels, insulin sensitivity, or body fat. There were no statistically significant frequency differences at these two sites between Hispanic and non-Hispanic individuals. No significant association with the metabolic phenotypes was observed for either of the polymorphisms in men; however, in women, significant associations were shown between the C161-->T variant and fasting insulin (P=.008) and the homeostasis model assessment of insulin resistance (HOMA IR; P=.007). After adjusting for age, smoking, fat mass, and skin reflectance, linear regression showed that C161-->T explained 1.5% of the variation in both fasting insulin (P=.031) and HOMA IR (P=.028) whereas P12A contributed only 0.04% (fasting insulin, P=.268) and 0.02% (HOMA IR, P=.418) to the total trait variation. In the San Luis Valley Diabetes Study female patients, C161-->T appears to be a better predictor of fasting insulin levels and insulin resistance than P12A although the effect of this variant is small. These results support the hypothesis that C161-->T is in linkage disequilibrium with unidentified functional variation in PPARgamma or in a linked gene. This could explain some of the inconsistencies in the P12A association studies as the allele frequency and level of linkage disequilibrium of another functional polymorphism in the region could vary in different populations.

Colorado↗
PubMed2005

Childhood femur fractures, associated injuries, and sociodemographic risk factors: a population-based study.

OBJECTIVE: The objectives of this study were to determine the incidence of femur fractures in Colorado children, to assess underlying causes, to determine the prevalence and predictors of associated injuries, and to identify potentially modifiable risk factors. METHODS: The study population included all Colorado residents who were aged 0 to 17 years at the time of injury between January 1, 1998, and December 31, 2001. Cases of femur fracture were ascertained using the population-based Colorado Trauma Registry and International Classification of Diseases, Ninth Revision, Clinical Modification codes 820.0 to 821.39. Associated injuries with an Abbreviated Injury Scale of 2 or higher were classified into 5 categories. Poisson regression, small area analysis, and multivariate logistic regression were used to identify predictors of femur fractures and associated injuries, respectively. RESULTS: During the study period, 1139 Colorado children (795 boys, 344 girls) sustained femur fractures, resulting in the incidence of 26.0 per 100000 person-years. Rates were higher in boys than in girls in all age groups (overall risk ratio: 2.19; 95% confidence interval: 1.92-2.47) but did not differ by race/ethnicity. Femur fractures that were caused by nonaccidental trauma showed more distal and combined shaft + distal pattern; their incidence did not differ by gender or race but was higher in census tracts with more single mothers and less crowded households. Associated injuries were present in 28.6% of the cases, more often in older children. Fatalities occurred only among children with associated injuries. Children who were involved in nonaccidental trauma, motor vehicle crashes, or auto-pedestrian accidents were 16 to 20 times more likely to have associated injuries than those with femur fractures as a result of a fall. In small-area analysis, the incidence of femur fractures in infants and toddlers was higher in census tracts characterized by higher proportion of Hispanics, single mothers, and more crowded households. Among children 4 to 12 years of age, the incidence was higher in census tracts with fewer single-family houses and more crowded households. Finally, the incidence of femur fractures among teenagers was higher in rural tracts and those with a higher proportion of Hispanics. CONCLUSIONS: Femur fractures and associated injuries remain a major cause of morbidity in children. Predictors of femur fractures change with age; however, the risk is generally higher among children who live in the areas with lower socioeconomic indicators.

Abbreviated Injury Scale↗
PubMed2005

Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program.

The Diabetes Prevention Program (DPP) was a randomized clinical trial of prevention of type 2 diabetes in high-risk people. Troglitazone, an insulin-sensitizing agent, was used initially but was discontinued during the trial. Troglitazone therapy was compared with other DPP interventions, considering both the short-term "in-trial" results and the longer-term results after troglitazone were discontinued. From 1996 to 1998, participants were randomly assigned to treatment with metformin (n = 587), troglitazone (n = 585), double placebo (n = 582), or intensive lifestyle intervention (ILS) (n = 589). Because of concern regarding its liver toxicity, the troglitazone arm was discontinued in June 1998, after which follow-up of all participants continued. During the mean 0.9 year (range 0.5-1.5 years) of troglitazone treatment, the diabetes incidence rate was 3.0 cases/100 person-years, compared with 12.0, 6.7, and 5.1 cases/100 person-years in the placebo, metformin, and ILS participants (P < 0.001, troglitazone vs. placebo; P = 0.02, troglitazone vs. metformin; P = 0.18, troglitazone vs. ILS). This effect of troglitazone was in part due to improved insulin sensitivity with maintenance of insulin secretion. During the 3 years after troglitazone withdrawal, the diabetes incidence rate was almost identical to that of the placebo group. Troglitazone, therefore, markedly reduced the incidence of diabetes during its limited period of use, but this action did not persist. Whether other thiazolidinedione drugs used for longer periods can safely prevent diabetes remains to be determined.

Chromans↗
PubMed2005

Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program.

OBJECTIVE: The prevalence of gestational diabetes mellitus (GDM) varies in direct proportion with the prevalence of type 2 diabetes in a given population or ethnic group. Given that the number of people with diabetes worldwide is expected to increase at record levels through 2030, we examined temporal trends in GDM among diverse ethnic groups. RESEARCH DESIGN AND METHODS: Kaiser Permanente of Colorado (KPCO) has used a standard protocol to universally screen for GDM since 1994. This report is based on 36,403 KPCO singleton pregnancies occurring between 1994 and 2002 and examines trends in GDM prevalence among women with diverse ethnic backgrounds. RESULTS: The prevalence of GDM among KPCO members doubled from 1994 to 2002 (2.1-4.1%, P < 0.001), with significant increases in all racial/ethnic groups. In logistic regression, year of diagnosis (odds ratio [OR] and 95% CI per 1 year = 1.12 [1.09-1.14]), mother's age (OR per 5 years = 1.7 [1.6-1.8]) and ethnicity other than non-Hispanic white (OR = 2.1 [1.9-2.4]) were all significantly associated with GDM. Birth year remained significant (OR = 1.06, P = 0.006), even after adjusting for prior GDM history. CONCLUSIONS: This study shows that the prevalence of GDM is increasing in a universally screened multiethnic population. The increasing GDM prevalence suggests that the vicious cycle of diabetes in pregnancy initially described among Pima Indians may also be occurring among other U.S. ethnic groups.

Adult↗
PubMed2004

The prevalence of diabetic retinopathy among adults in the United States.

OBJECTIVE: To determine the prevalence of diabetic retinopathy among adults 40 years and older in the United States. METHODS: Pooled analysis of data from 8 population-based eye surveys was used to estimate the prevalence, among persons with diabetes mellitus (DM), of retinopathy and of vision-threatening retinopathy-defined as proliferative or severe nonproliferative retinopathy and/or macular edema. Within strata of age, race/ethnicity, and gender, US prevalence rates were estimated by multiplying these values by the prevalence of DM reported in the 1999 National Health Interview Survey and the 2000 US Census population. RESULTS: Among an estimated 10.2 million US adults 40 years and older known to have DM, the estimated crude prevalence rates for retinopathy and vision-threatening retinopathy were 40.3% and 8.2%, respectively. The estimated US general population prevalence rates for retinopathy and vision-threatening retinopathy were 3.4% (4.1 million persons) and 0.75% (899 000 persons). Future projections suggest that diabetic retinopathy will increase as a public health problem, both with aging of the US population and increasing age-specific prevalence of DM over time. CONCLUSION: Approximately 4.1 million US adults 40 years and older have diabetic retinopathy; 1 of every 12 persons with DM in this age group has advanced, vision-threatening retinopathy.

Adult↗
PubMed2004

Genetic variation in fatty acid-binding protein-4 and peroxisome proliferator-activated receptor gamma interactively influence insulin sensitivity and body composition in males.

Obesity and type 2 diabetes are closely related, multifactorial metabolic conditions characterized by alterations in energy metabolism and glucose homeostasis, respectively. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor that regulates genes involved in lipid and glucose homeostasis, including the adipocyte-specific fatty acid-binding protein (FABP4). In turn, FABP4 binds fatty acids and transports them to the nucleus where the FABP4/fatty acid complex activates PPARgamma in a positive feedback loop. In this study, we tested the hypothesis that the polymorphisms, FABP4-376 and PPARgamma Pro12Ala, interactively influence insulin sensitivity and body composition in nondiabetic, Hispanic and non-Hispanic white males (n = 314) participating in the San Luis Valley Diabetes Study (SLVDS). Although the individual sites were not statistically significantly associated with any of the outcomes, we found statistically significant interaction terms in 2-way analysis of covariance (ANCOVA) models for homeostasis model assessment of insulin resistance (HOMA-IR) (P =.014) and lean mass (P =.019). While the PPARgamma Pro12Ala site was the only statistically significant predictor of fat mass in the 2-way model (P =.012), the FABP4 and PPARgamma main effect terms individually became stronger when considered in one model compared with the analysis of each polymorphism separately. These findings provide evidence that FABP4 and PPARgamma work together to influence a biologic pathway affecting insulin sensitivity and body composition, illustrating the importance of investigating the joint effect of genes in determining susceptibility for complex disease.

Adult↗
PubMed2004

Genetic variation in uncoupling protein 3 is associated with dietary intake and body composition in females.

The uncoupling proteins (UCPs) are a family of mitochondrial transport proteins that promote proton leakage across the inner mitochondrial membrane, uncoupling oxidative phosphorylation from adenosine triphosphate (ATP) production and releasing energy as heat. Variation in these genes may disrupt biochemical pathways influencing thermogenesis, energy metabolism, and fuel substrate partitioning and oxidation, which may in turn predispose to obesity. We genotyped polymorphisms in UCP2 and UCP3 in a sample of nondiabetic participants (n = 722) of the San Luis Valley Diabetes Study (SLVDS) and found female-specific associations between UCP3 polymorphisms and measures of dietary intake and body composition. The UCP3-5 variant was statistically significantly associated with total caloric intake (P =.012), fat intake (P =.011), fat mass (P =.004), and lean mass (P =.013), with the C allele corresponding to higher dietary intake and lower fat mass and lean mass. The UCP3p-55 and the UCP3-3 polymorphisms, which were in high linkage disequilibrium (D' = 0.9776), showed similar patterns of association with total caloric intake (P =.031 and P =.042, respectively) and lean mass (P =.035 and P =.059, respectively), with the rare alleles corresponding to higher total intake and lean mass. No statistically significant associations were detected between the outcome variables and polymorphisms in UCP2. Two-way analysis of covariance (ANCOVA), used to evaluate the multi-locus effects and interactions between UCP3-5 and UCP3p-55, showed association with the main effect terms, but no evidence for statistically significant interaction between UCP3-5 and UCP3p-55 in regard to dietary intake. The UCP3-5 polymorphism was the only statistically significant genetic predictor of fat mass. The lean mass model showed no statistically significant association with either UCP3 variant. These results support a role for UCP3 in fuel substrate management and energy metabolism, which may influence body weight regulation.

Alleles↗