Effects of a community gardening intervention on diet, physical activity, and anthropometry outcomes in the USA (CAPS): an observer-blind, randomised controlled trial.

BACKGROUND: Unhealthy diet, physical inactivity, and social disconnection are important modifiable risk factors for non-communicable and other chronic diseases, which might be alleviated through nature-based community interventions. We tested whether a community gardening intervention could reduce these common health risks in an adult population that is diverse in terms of age, ethnicity, and socioeconomic status. METHODS: In this observer-blind, randomised, controlled trial, we recruited individuals who were on Denver Urban Garden waiting lists for community gardens in Denver and Aurora (CO, USA), aged 18 years or older, and had not gardened in the past 2 years. Participants were randomly assigned (1:1), using a randomised block design in block sizes of two, four, or six, to receive a community garden plot (intervention group) or remain on a waiting list and not garden (control group). Researchers were masked to group allocation. Primary outcomes were diet, physical activity, and anthropometry; secondary outcomes were perceived stress and anxiety. During spring (April to early June, before randomisation; timepoint 1 [T1]), autumn (late August to October; timepoint 2 [T2]), and winter (January to March, after the intervention; timepoint 3 [T3]), participants completed three diet recalls, 7-day accelerometry, surveys, and anthropometry. Analyses were done using the intention-to-treat principle (ie, including all participants randomly assigned to groups, and assessed as randomised). We used mixed models to test time-by-intervention hypotheses at an α level of 0·04, with T2 and T3 intervention effects at an α level of 0·005 (99·5% CI). Due to potential effects of the COVID-19 pandemic on outcomes, we excluded all participant data collected after Feb 1, 2020. This study is registered with ClinicalTrials.gov, NCT03089177, and data collection is now complete. FINDINGS: Between Jan 1, 2017, and June 15, 2019, 493 adults were screened and 291 completed baseline measures and were randomly assigned to the intervention (n=145) or control (n=146) groups. Mean age was 41·5 years (SD 13·5), 238 (82%) of 291 participants were female, 52 (18%) were male, 99 (34%) identified as Hispanic, and 191 (66%) identified as non-Hispanic. 237 (81%) completed measurements before the beginning of the COVID-19 pandemic. One (<1%) participant in the intervention group had an adverse allergic event in the garden. Significant time-by-intervention effects were observed for fibre intake (p=0·034), with mean between-group difference (intervention minus control) at T2 of 1·41 g per day (99·5% CI -2·09 to 4·92), and for moderate-to-vigorous physical activity (p=0·012), with mean between-group difference of 5·80 min per day (99·5% CI -4·44 to 16·05). We found no significant time-by-intervention interactions for combined fruit and vegetable intake, Healthy Eating Index (measured using Healthy Eating Index-2010), sedentary time, BMI, and waist circumference (all p>0·04). Difference score models showed greater reductions between T1 and T2 in perceived stress and anxiety among participants in the intervention group than among those in the control group. INTERPRETATION: Community gardening can provide a nature-based solution, accessible to a diverse population including new gardeners, to improve wellbeing and important behavioural risk factors for non-communicable and chronic diseases. FUNDING: American Cancer Society, University of Colorado Cancer Centre, University of Colorado Boulder, National Institutes of Health, US Department of Agriculture National Institute of Food and Agriculture, Michigan AgBioResearch Hatch projects.

Insulin sensitivity and arterial stiffness in youth with type 1 diabetes: the SEARCH CVD study.

AIMS: Decreased insulin sensitivity is a cardiovascular risk factor (CVRF) in youth with type 1 diabetes (T1D). Whether baseline insulin sensitivity is independently associated with changes in early arterial stiffness (pulse wave velocity (PWV)) over time in youth with T1D is not known. METHODS: Two hundred ninety-eight youth with T1D in the SEARCH CVD study had PWV measured~five years apart. Insulin sensitivity and other CVRFs were measured at baseline. The association between baseline insulin sensitivity with PWV over time was explored using linear mixed models. Models were adjusted for baseline age, sex and race, with subsequent adjustment for CVRFs. RESULTS: There was a significant interaction (p=0.0326) between baseline insulin sensitivity and time on PWV, independent of CVRFs, indicating that higher insulin sensitivity levels were associated with lower rate of change in PWV over time. Other significant predictors of PWV change were baseline age [ß=0.007 (p=0.03) increase in logPWV/year increase in age] and mean arterial blood pressure (MAP) [ß=0.005 (p<0.01) increase in logPWV/mmHg increase in MAP] and smoking status (current vs. never smoker). CONCLUSIONS: Lower insulin sensitivity at baseline appears to be an important risk factor for increased arterial stiffness over time in youth with T1D. This identifies a potentially modifiable therapeutic target.

Factors affecting the decline in incidence of diabetes in the Diabetes Prevention Program Outcomes Study (DPPOS).

During the first 7 years of the Diabetes Prevention Program Outcomes Study (DPPOS), diabetes incidence rates, when compared with the Diabetes Prevention Program (DPP), decreased in the placebo (-42%) and metformin (-25%), groups compared with the rates in the intensive lifestyle intervention (+31%) group. Participants in the placebo and metformin groups were offered group intensive lifestyle intervention prior to entering the DPPOS. The following two hypotheses were explored to explain the rate differences: "effective intervention" (changes in weight and other factors due to intensive lifestyle intervention) and "exhaustion of susceptible" (changes in mean genetic and diabetes risk scores). No combination of behavioral risk factors (weight, physical activity, diet, smoking, and antidepressant or statin use) explained the lower DPPOS rates of diabetes progression in the placebo and metformin groups, whereas weight gain was the factor associated with higher rates of progression in the intensive lifestyle intervention group. Different patterns in the average genetic risk score over time were consistent with exhaustion of susceptibles. Results were consistent with exhaustion of susceptibles for the change in incidence rates, but not the availability of intensive lifestyle intervention to all persons before the beginning of the DPPOS. Thus, effective intervention did not explain the lower diabetes rates in the DPPOS among subjects in the placebo and metformin groups compared with those in the DPP.

Use of administrative and electronic health record data for development of automated algorithms for childhood diabetes case ascertainment and type classification: the SEARCH for Diabetes in Youth Study.

BACKGROUND: The performance of automated algorithms for childhood diabetes case ascertainment and type classification may differ by demographic characteristics. OBJECTIVE: This study evaluated the potential of administrative and electronic health record (EHR) data from a large academic care delivery system to conduct diabetes case ascertainment in youth according to type, age, and race/ethnicity. SUBJECTS: Of 57 767 children aged <20 yr as of 31 December 2011 seen at University of North Carolina Health Care System in 2011 were included. METHODS: Using an initial algorithm including billing data, patient problem lists, laboratory test results, and diabetes related medications between 1 July 2008 and 31 December 2011, presumptive cases were identified and validated by chart review. More refined algorithms were evaluated by type (type 1 vs. type 2), age (<10 vs. ≥10 yr) and race/ethnicity (non-Hispanic White vs. 'other'). Sensitivity, specificity, and positive predictive value were calculated and compared. RESULTS: The best algorithm for ascertainment of overall diabetes cases was billing data. The best type 1 algorithm was the ratio of the number of type 1 billing codes to the sum of type 1 and type 2 billing codes ≥0.5. A useful algorithm to ascertain youth with type 2 diabetes with 'other' race/ethnicity was identified. Considerable age and racial/ethnic differences were present in type-non-specific and type 2 algorithms. CONCLUSIONS: Administrative and EHR data may be used to identify cases of childhood diabetes (any type), and to identify type 1 cases. The performance of type 2 case ascertainment algorithms differed substantially by race/ethnicity.

Smoking and arterial stiffness in youth with type 1 diabetes: the SEARCH Cardiovascular Disease Study.

OBJECTIVE: To evaluate the effects of smoking on early markers of cardiovascular disease (arterial stiffness) in adolescents with and without type 1 diabetes (T1D) in the SEARCH Cardiovascular Disease Study. STUDY DESIGN: Participants included 606 youth (18.9 ± 3.3 years, 83% non-Hispanic white; 50% male). Six groups were defined: (1) smokers with T1D (n = 80); (2) former smokers with T1D (n = 88); (3) nonsmokers with T1D (n = 232); (4) smokers without T1D (n = 40); (5) former smokers without T1D former (n = 51); and (6) nonsmokers without T1D (n = 115). Arterial stiffness measurements included pulse wave velocity (PWV), augmentation index, and brachial distensibility. Multivariate linear regression was used to assess the independent and joint effects of T1D and smoking on arterial stiffness. RESULTS: Nearly 20% of both youth with and without T1D and T1D were smokers. In youth without T1D, smokers had higher trunk and arm PWV. After adjustment for potential confounders, T1D, but not smoking, was an independent predictor of PWV (P < .05). Moreover, smoking status did not modify the association between T1D and increased arterial stiffness. CONCLUSIONS: We found a high prevalence of smoking among youth with and without T1D; however, smoking status was not independently associated with increased arterial stiffness in youth with T1D.

Reduced heart rate variability is associated with increased arterial stiffness in youth with type 1 diabetes: the SEARCH CVD study.

OBJECTIVE: Reduced heart rate variability (HRV) and increased arterial stiffness (AS) are both present in youth with type 1 diabetes. However, it is unclear whether they are associated and whether their association is independent of cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODS: The SEARCH Cardiovascular Disease (SEARCH CVD) study explored the cross-sectional relationships between HRV and several measures of AS in youth with (n = 344) and without (n = 171) type 1 diabetes. The SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure HRV using SD of normal R-R interval (SDNN), as well as AS, using pulse wave velocity in the carotid to femoral segment (PWV-trunk) and augmentation index adjusted to a heart rate of 75 bpm (AIx75). Brachial distensibility (BrachD), another index of AS, was measured with a DynaPulse instrument (Pulse Metric, San Diego, CA). Multiple linear regression analyses explored the associations between HRV and each of the three AS measures, after adjusting for demographic characteristics and traditional CVD risk factors (blood pressure, lipids, obesity, microalbuminuria, and smoking) separately, for youth with and without type 1 diabetes. RESULTS: Among youth with type 1 diabetes, lower SDNN was associated with peripheral AS (lower BrachD, P = 0.01; r(2) = 0.30) and central AS (higher PVW-trunk, P < 0.0001; r(2) = 0.37; and higher AIx75, P = 0.007; r(2) = 0.08). These associations were attenuated with adjustment for CVD risk factors, but remained statistically significant for BrachD and PWV-trunk. While a similar association between HRV and BrachD was present in control youth, lower HRV was not associated with increased central AS or with AIx75. CONCLUSIONS: Longitudinal studies are needed to understand the pathways responsible for these associations.

Inflammatory markers are increased in youth with type 1 diabetes: the SEARCH Case-Control study.

CONTEXT: Increased inflammation may contribute to type 1 diabetes (T1D) complications. OBJECTIVE: The objective of the study was to investigate the association of inflammation with obesity, hyperglycemia and dyslipidemia in youth with T1D. DESIGN: This was a cross-sectional study of youth with and without T1D. SETTING: The study was conducted in Colorado and South Carolina. PATIENTS: SEARCH Case-Control participants with T1D [n = 553, mean age 15 yr (range 10-22), median duration 2.7 yr] and without diabetes [n = 215, mean age 15 yr (range 10-22)]. INTERVENTION: This was an observational study. MAIN OUTCOME MEASURES: IL-6, high-sensitivity C-reactive protein (hsCRP), fibrinogen, and leptin were measured. RESULTS: Inflammatory markers were evaluated by diabetes status, quartiles of glycated hemoglobin, and obesity using multiple linear regression analyses, adjusted for age, sex, study site, race/ethnicity, T1D duration, body mass index, and pubertal status. Compared with controls, youth with T1D had higher IL-6 and fibrinogen levels at all levels of glycemia and obesity, and hsCRP levels were significantly higher in youth with T1D in the top three quartiles of glycated hemoglobin (> or = 7.2%) and among normal-weight subjects. Leptin was lower in youth with poor glycemic control. Higher hsCRP and fibrinogen were correlated with higher total and LDL cholesterol, and apolipoprotein B in youth with T1D, whereas higher fibrinogen was correlated with higher LDL and apolipoprotein B in controls. CONCLUSIONS: T1D is characterized by excess inflammation, independent of adiposity and glycemic control. Even T1D youth in good glycemic control had higher levels of IL-6 and fibrinogen than controls. Elevated inflammatory markers were associated with an atherogenic lipid profile, which may contribute to accelerated atherosclerosis in youth with T1D.

The impact of executive cognitive functioning on rates of smoking cessation in the San Luis Valley Health and Aging Study.

Cigarette smoking is one of the leading preventable causes of death. Previous research has shown that many common smoking cessation interventions are effective with older smokers; a few interventions have been tailored to this population. To our knowledge, however, no smoking cessation research or interventions targeted at older adults have addressed the influence of cognition on successful smoking cessation. We hypothesized that impairment of executive cognitive functioning (ECF), which is relatively prevalent among older adults, would negatively influence smoking cessation rates among older smokers. The relationship of ECF to smoking cessation was examined in a population-based sample of 1,338 community-dwelling older persons in Colorado's San Luis Valley, 204 of whom were current smokers. As predicted, current ECF did not predict early smoking behaviour, but was a significant predictor of successful smoking cessation. Older persons suffering from executive dysfunction were less likely to have quit smoking than were their cognitively intact counterparts (OR = 1.10, 95% CI 1.04-1.17, P < 0.01). Among those with normal ECF, 73.7% had quit smoking, compared with 65.1% of participants showing any level of ECF impairment. Limiting the sample to individuals who were active smokers at or after the age of 65, when executive impairment is relatively common, produced similar results. Individuals with better executive functioning were more likely to have quit smoking (OR = 1.12, 95% CI 1.02-1.23, P = 0.02).

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.

Adapting and implementing a long-term nutrition and physical activity curriculum to a rural, low-income, biethnic community.

This study adapted an urban-based school nutrition program for delivery in a rural community. Specific aims were to adapt the curriculum; expand it to include physical activity; determine effectiveness on students' attitudes, knowledge, and self-efficacy; and assess teachers' impressions. Three cohorts were established: 173 students taught by a resource teacher, 170 students taught by classroom teachers, and 187 students who did not receive the curriculum. Pre- and posttest surveys measured outcomes, and classroom teachers were observed and interviewed. The curriculum was shown to be effective in enhancing student outcomes for both the resource teacher and classroom teacher cohorts. Teachers reported that lessons needed to be simplified and that children enjoyed them. Findings support the transferability of an urban-based nutrition curriculum to a rural community and the need for students to receive health education annually.

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.

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.

Attendance and graduation patterns in a group-model health maintenance organization alternative cardiac rehabilitation program.

PURPOSE: Poor rates of participation in cardiac rehabilitation programs are well documented, especially among women and older patients. The Colorado Kaiser Permanente Cardiac Rehabilitation (KPCR) program is a home-based, case-managed, goal-oriented program with an active recruitment process and unlimited program length. This study evaluated the participation rates for the program and the predictors of attendance and graduation. METHODS: Patients hospitalized with acute myocardial infarction, coronary artery bypass graft, and percutaneous coronary intervention from June 1999 to May 2000 (n = 1030) were identified from the administrative database, and the proportion captured by the KPCR staff was determined. Subsequent attendance and graduation patterns were evaluated. RESULTS: Nearly 94% of patients with one of the three aforementioned conditions were identified by the rehabilitation staff, and 41% of all patients attended the KPCR program. More than 75% of the patients who participated went on to graduate from the program. Gender comparisons showed no difference in participation between men (66.8%) and women (59.7%) (P =.07). Participation rates were inversely associated with age, yet age was not associated with graduation from the program. Surgical interventions and two or more events experienced within the first 4 weeks of the index event were the strongest predictors of attendance and graduation from the KPCR program. CONCLUSIONS: Innovative approaches for the capture and retention of patients in cardiac rehabilitation programs are urgently needed. The alternative program evaluated in this study showed little difference in participation between men and women, yet participation among older patients remained poor. Overall, patients who underwent surgical interventions or multiple events were more likely to attend and graduate from the program.

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.

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.

Effect of type 1 diabetes on the gender difference in coronary artery calcification: a role for insulin resistance? The Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study.

The objective of this is study was to examine whether estimated insulin resistance and insulin resistance-related factors are associated with coronary artery calcification (CAC) in 1,420 asymptomatic participants in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. A total of 656 patients with type 1 diabetes and 764 control subjects aged 20-55 years were examined. CAC was assessed by electron-beam computed tomography. Insulin resistance was computed with linear regression based on an equation previously validated in clamp studies on type 1 diabetic adults. Insulin resistance was associated with CAC (OR 1.6 in type 1 diabetes and 1.4 in control subjects, P < 0.001), independent of coronary artery disease risk factors. There was a male excess of CAC in control subjects (OR 2.7, adjusted for age, smoking, and LDL and HDL cholesterol levels) and in type 1 diabetic patients (OR 2.2, adjusted for the same factors and diabetes duration). After adjusting for insulin resistance, the CAC male excess in diabetic patients decreased from OR 2.2 (P < 0.001) to 1.8 (P = 0.04). After adjustment for waist-to-hip ratio, waist circumference, or visceral fat, the gender difference in CAC was not significant in diabetic subjects. In conclusion, gender differences in insulin resistance-associated fat distribution may explain why type 1 diabetes increases coronary calcification in women relatively more than in men.

Variation in the FABP2 promoter alters transcriptional activity and is associated with body composition and plasma lipid levels.

The fatty acid-binding proteins (FABPs) are cytoplasmic proteins involved in intracellular fatty acid transport and metabolism. FABP2, the intestinal-type FABP, is expressed exclusively in enterocytes in the small intestine. In previous studies of an Ala54Thr substitution in FABP2, the Thr-allele showed association with increased lipid oxidation, elevated plasma lipids, and impaired insulin sensitivity. We screened roughly 1 kb 5' of the FABP2 initiation codon and identified three insertion/deletion polymorphisms and four single nucleotide polymorphisms (SNPs). Three of the SNPs were in complete linkage disequilibrium with the three insertion/deletion polymorphisms, defining exactly two haplotypes (FABP2p-ID). We tested the hypothesis that this variation alters gene expression by transfecting Caco-2 cells with pGL3-Basic constructs containing opposite FABP2p-ID haplotypes. Luciferase assays showed a statistically significant two-fold increase in gene expression of the pGL3-insertion construct over the pGL3-deletion construct (P<0.001; n=5). We also tested for association between three FABP2 variants and measurements of body composition, plasma lipids, and insulin sensitivity in non-diabetic control subjects from the San Luis Valley Diabetes Study (n=714). The only informative variant, FABP2p-ID, was statistically significantly associated with body mass index (P=0.042) and marginally associated with fat mass (P=0.084), cholesterol (P=0.066), and HOMA IR (a derived measure of insulin resistance; P=0.062) in the entire cohort. Similar associations were seen only in non-Hispanics when the analysis was stratified by ethnicity. Within the non-Hispanic subgroup, the effects of FABP2p-ID on plasma lipids were sex-specific. These results suggest that genetic variation in the 5' region of FABP2 affects transcriptional activity, presumably leading to alterations in body composition and lipid processing.

Modifiable risks of incident functional dependence in Hispanic and non-Hispanic white elders: the San Luis Valley Health and Aging Study.

PURPOSE: This study identified modifiable risks associated with incident functional dependence, compared their effects, and estimated the percent risk attributable to each factor, by ethnicity. DESIGN AND METHODS: The prospective study cohort comprised 751 rural Hispanic and non-Hispanic White elders from southern Colorado who reported no dependence in basic and instrumental activities of daily living (ADLs and IADLs) at baseline. Logistic regression modeled the effects of physical inactivity, nutritional risk, smoking, and falls on incident disability 22 months later, with and without adjustment for baseline ADL and IADL difficulty. Population attributable risk percentages assessed these modifiable risks by ethnicity. RESULTS: Each risk factor multiplied the likelihood of incident dependence by 1.4 or more, adjusted for covariates. Attributable risk percentages ranged from 8% to 32% depending on risk factor, ethnicity, and baseline ADL and IADL difficulty status. Attributable risk was generally greater among Hispanic elders, the result of higher prevalence of most of the risk factors. IMPLICATIONS: Interventions targeted at inadequate nutrition, inactivity, smoking, and preventable falls offer opportunities to reduce incident functional disability, especially among Hispanic elders.

Serum selenium and the risk of cervical cancer among women in the United States.

OBJECTIVE: To explore the relationship between serum selenium and cervical cancer. METHODS: We conducted a case-control study of cervical cancer in five areas around Birmingham, AL; Chicago, IL; Denver, CO; Miami, FL; and Philadelphia, PA. Community controls were selected by random-digit dialing and were matched to invasive cervical cancer cases by age, race/ethnicity, and telephone exchange. Serum selenium was determined by neutron activation analysis. Logistic regression analysis controlling for known risk factors of cervical cancer, including human papillomavirus (HPV) type-16 measured serologically, was performed on 227 invasive cases, 127 in-situ cases, and 526 controls. RESULTS: Values of serum selenium ranged from 67.5 to 185.0 ng/ml. Adjusted odds ratios for invasive cervical cancer by quintile were: 1.0 (highest selenium), 1.1, 1.0, 0.8, and 1.0 (lowest selenium), p for trend = 0.82. Similar patterns were observed for Stage I invasive, and Stages II-IV invasive cases, suggesting severity of disease did not influence the null results. Although no associations were seen among current or never smokers, a protective effect of selenium was suggested among former smokers. Effect modification was not evident for other variables examined. CONCLUSIONS: This study does not support a relationship between serum selenium and invasive cervical cancer at typical serum selenium levels in the US.

Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer.

OBJECTIVES: To evaluate whether the risk of bladder cancer is greater in individuals with spinal cord injury (SCI) than in the general population and whether indwelling catheter (IDC) use is a significant independent risk factor for bladder cancer. DESIGN: Historical cohort study in which subjects with SCI were stratified according to bladder management method and followed for the development of bladder cancer. SETTING: A large rehabilitation hospital in the Spinal Cord Injury Model Systems. PARTICIPANTS: A total of 3670 patients with SCI who were evaluated for bladder cancer on at least 1 occasion by cystoscopy over a period of 1 to 47 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Bladder cancer occurring after SCI determined by diagnosis at our facility, by subject report, or by report of next of kin. RESULTS: Twenty-one cases of bladder cancer were found in the 3670 study participants. The risk of bladder cancer for subjects with SCI using IDC is 77 per 100,000 person-years, corresponding to an age- and gender-adjusted standardized morbidity ratio (SMR) of 25.4 (95% confidence interval [CI], 14.0--41.9) when compared with the general population. After controlling for age at injury, gender, level and completeness of SCI, history of bladder calculi, and smoking, those using solely IDC had a significantly greater risk of bladder cancer (relative risk [RR] = 4.9; 95% CI, 1.3--13.8) than those using nonindwelling methods. Mortality caused by bladder cancer in individuals with SCI was significantly greater than that of the US population (SMR = 70.6; 95% CI, 36.9--123.3). CONCLUSIONS: Bladder cancer risk and mortality are heightened in SCI compared with the general population. IDC is a significant independent risk factor for the increased risk of and mortality caused by bladder cancer in the SCI population.