Do menopausal status and APOE4 genotype alter the long-term effects of intensive lifestyle intervention on cognitive function in women with type 2 diabetes mellitus?
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SUBMITTER: Yassine HN
PROVIDER: S-EPMC7269875 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The GEMINAL Study- Gene Expression Modulation by Intervention with Nutrition and Lifestyle We conducted a pilot study to examine changes in gene expression in men diagnosed with low risk prostate cancer who participated in an intensive nutrition and lifestyle intervention. We profiled gene expression in morphologically normal tissues from prostate biopsies of all 30 participants before and after the intervention. Keywords: Differential gene expression analysis
2008-03-01 | GSE10306 | GEO
Project description:The GEMINAL Study- Gene Expression Modulation by Intervention with Nutrition and Lifestyle We conducted a pilot study to examine changes in gene expression in men diagnosed with low risk prostate cancer who participated in an intensive nutrition and lifestyle intervention. We profiled gene expression in morphologically normal tissues from prostate biopsies of all 30 participants before and after the intervention. Keywords: Differential gene expression analysis Pre-intervention versus Post-Intervention
2010-05-26 | E-GEOD-10306 | biostudies-arrayexpress
Project description:ObjectiveTo assess whether an average of 10 years of lifestyle intervention designed to reduce weight and increase physical activity lowers the prevalence of cognitive impairment among adults at increased risk due to type 2 diabetes and obesity or overweight.MethodsCentral adjudication of mild cognitive impairment and probable dementia was based on standardized cognitive test battery scores administered to 3,802 individuals who had been randomly assigned, with equal probability, to either the lifestyle intervention or the diabetes support and education control. When scores fell below a prespecified threshold, functional information was obtained through proxy interview.ResultsCompared with control, the intensive lifestyle intervention induced and maintained marked differences in weight loss and self-reported physical activity throughout follow-up. At an average (range) of 11.4 (9.5-13.5) years after enrollment, when participants' mean age was 69.6 (54.9-87.2) years, the prevalence of mild cognitive impairment and probable dementia was 6.4% and 1.8%, respectively, in the intervention group, compared with 6.6% and 1.8%, respectively, in the control group (p = 0.93). The lack of an intervention effect on the prevalence of cognitive impairment was consistent among individuals grouped by cardiovascular disease history, diabetes duration, sex, and APOE ε4 allele status (all p ≥ 0.50). However, there was evidence (p = 0.03) that the intervention effect ranged from benefit to harm across participants ordered from lowest to highest baseline BMI.ConclusionsTen years of behavioral weight loss intervention did not result in an overall difference in the prevalence of cognitive impairment among overweight or obese adults with type 2 diabetes.Clinicaltrialsgov identifierNCT00017953 (Action for Health in Diabetes).Level of evidenceThis study provides Class II evidence that for overweight adults with type 2 diabetes, a lifestyle intervention designed to reduce weight and increase physical activity does not lower the risk of cognitive impairment.
| S-EPMC5440245 | biostudies-literature
Project description:ObjectivesTo assess whether randomization to 10 years of lifestyle intervention to induce and maintain weight loss improves cognitive function.DesignRandomized controlled clinical trial.SettingData obtained as part of the Action for Health in Diabetes (Look AHEAD) trial (NCT00017953) and Look AHEAD Continuation study (U01 DK057136-15).ParticipantsOverweight and obese individuals with type 2 diabetes mellitus aged 45 to 76 (N = 3,751).InterventionIntensive lifestyle intervention (ILI) for weight loss through reduced caloric intake and increased physical activity compared with a control condition of diabetes support and education (DSE).MeasurementsCertified examiners who were masked to intervention assignment administered a standard battery of cognitive function tests (Modified Mini-Mental State Examination, Rey Auditory Verbal Learning Test, Digit Symbol Coding, Trail-Making Test, Modified Stroop Color-Word Test) to participants 10 to 13 years after enrollment.ResultsAssignment to lifestyle intervention was not associated with significantly different overall (P = .10) or domain-specific (all P > .10) cognitive function than assignment to diabetes support and education. Results were fairly consistent across prespecified groups, but there was some evidence of trends for differential intervention effects showing modest harm in ILI in participants with greater body mass index and in individuals with a history of cardiovascular disease. Cognitive function was not associated with changes in weight or fitness (all P > .05).ConclusionA long-term behavioral weight loss intervention for overweight and obese adults with diabetes mellitus was not associated with cognitive benefit. Trial Registration clinicaltrials.gov Identifier: NCT00017953.
| S-EPMC5435531 | biostudies-literature
Project description:BackgroundWeight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients.MethodsIn 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.ResultsThe trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51).ConclusionsAn intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).
| S-EPMC3791615 | biostudies-literature
Project description:This prospective longitudinal study of breast cancer survivors (n = 167) examined the association of apolipoprotein ε4 (APOE ε4) genotype with cognition and interactions with chemotherapy or endocrine therapy up to 6 years after treatment. In general, we found no effects of ε4 across timepoints and treatment exposures; post hoc analysis at 3-6 years suggested a trend towards worse cognition in the domains of attention and learning among ε4 carriers exposed to endocrine therapy. Further study is needed.
| S-EPMC8417038 | biostudies-literature
Project description:ObjectivesTo determine whether long-term behavioral intervention targeting weight loss through increased physical activity and reduced caloric intake would alter cerebral blood flow (CBF) in individuals with type 2 diabetes mellitus.DesignPostrandomization assessment of CBF.SettingAction for Health in Diabetes multicenter randomized controlled clinical trial.ParticipantsIndividuals with type 2 diabetes mellitus who were overweight or obese and aged 45 to 76 (N = 310).InterventionsA multidomain intensive lifestyle intervention (ILI) to induce weight loss and increase physical activity for 8 to 11 years or diabetes support and education (DSE), a control condition.MeasurementsParticipants underwent cognitive assessment and standardized brain magnetic resonance imaging (MRI) (3.0 Tesla) to assess CBF an average of 10.4 years after randomization.ResultsWeight changes from baseline to time of MRI averaged -6.2% for ILI and -2.8% for DSE (P < .001), and increases in self-reported moderate or intense physical activity averaged 444.3 kcal/wk for ILI and 114.8 kcal/wk for DSE (P = .03). Overall mean CBF was 6% greater for ILI than DSE (P = .04), with the largest mean differences between ILI and DSE in the limbic region (3.39 mL/100 g per minute, 95% confidence interval (CI) = 0.07-6.70 mL/100 g per minute) and occipital lobes (3.52 mL/100 g per minute, 95% CI = 0.20-6.84 mL/100 g per minute). In ILI, greater CBF was associated with greater decreases in weight and greater increases in physical activity. The relationship between CBF and scores on a composite measure of cognitive function varied between intervention groups (P = .02).ConclusionsLong-term weight loss intervention in overweight and obese adults with type 2 diabetes mellitus is associated with greater CBF.
| S-EPMC5777883 | biostudies-literature
Project description:Some cancer survivors experience marked cognitive impairment, referred to as cancer-related cognitive impairment (CRCI). CRCI has been linked to the genetic factor APOE4, the strongest genetic risk factor for Alzheimer's disease (AD). We used APOE knock-in mice to test whether the relationship between APOE4 and CRCI can be demonstrated in a mouse model, to identify associations of chemotherapy with behavioural and structural correlates of cognition, and to test whether chemotherapy affects markers of AD. Twelve-month old C57BL/6 J female APOE3 (n = 30) and APOE4 (n = 31) knock-in mice were randomized to treatment with either doxorubicin (10 mg/kg) or saline. Behavioural assays at 2-21 weeks-post exposure included open field maze, elevated zero maze, pre-pulse inhibition, Barnes maze, and fear conditioning. Ex-vivo magnetic resonance imaging was used to determine regional volume differences at 31-35 weeks-post exposure, and tissue sections were analyzed for markers of AD pathogenesis. Minimal toxicities were observed in the aged mice after doxorubicin exposure. In the Barnes maze assay, APOE3 mice did not exhibit impairment in spatial learning after doxorubicin treatment, but APOE4 mice demonstrated significant impairments in both the initial identification of the escape hole and the latency to full escape at 6 weeks post-exposure. Both APOE3 and APOE4 mice treated with doxorubicin showed impairment of spatial memory. Grey matter volume in the frontal cortex decreased in APOE4 mice treated with doxorubicin vs. APOE3 mice. This study demonstrates cognitive impairments in aged APOE4 knock-in mice after doxorubicin treatment and establishes this system as a novel and powerful model of CRCI.
| S-EPMC7082850 | biostudies-literature
Project description:The frequency of remission of type 2 diabetes achievable with lifestyle intervention is unclear.To examine the association of a long-term intensive weight-loss intervention with the frequency of remission from type 2 diabetes to prediabetes or normoglycemia.Ancillary observational analysis of a 4-year randomized controlled trial (baseline visit, August 2001-April 2004; last follow-up, April 2008) comparing an intensive lifestyle intervention (ILI) with a diabetes support and education control condition (DSE) among 4503 US adults with body mass index of 25 or higher and type 2 diabetes.Participants were randomly assigned to receive the ILI, which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 (n=2241) or the DSE, which was an offer of 3 group sessions per year on diet, physical activity, and social support (n=2262).Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose <126 mg/dL and hemoglobin A1c <6.5% with no antihyperglycemic medication). RESULTS Intensive lifestyle intervention participants lost significantly more weight than DSE participants at year 1 (net difference, -7.9%; 95% CI, -8.3% to -7.6%) and at year 4 (-3.9%; 95% CI, -4.4% to -3.5%) and had greater fitness increases at year 1 (net difference, 15.4%; 95% CI, 13.7%-17.0%) and at year 4 (6.4%; 95% CI, 4.7%-8.1%) (P < .001 for each). The ILI group was significantly more likely to experience any remission (partial or complete), with prevalences of 11.5% (95% CI, 10.1%-12.8%) during the first year and 7.3% (95% CI, 6.2%-8.4%) at year 4, compared with 2.0% for the DSE group at both time points (95% CIs, 1.4%-2.6% at year 1 and 1.5%-2.7% at year 4) (P < .001 for each). Among ILI participants, 9.2% (95% CI, 7.9%-10.4%), 6.4% (95% CI, 5.3%-7.4%), and 3.5% (95% CI, 2.7%-4.3%) had continuous, sustained remission for at least 2, at least 3, and 4 years, respectively, compared with less than 2% of DSE participants (1.7% [95% CI, 1.2%-2.3%] for at least 2 years; 1.3% [95% CI, 0.8%-1.7%] for at least 3 years; and 0.5% [95% CI, 0.2%-0.8%] for 4 years).In these exploratory analyses of overweight adults, an intensive lifestyle intervention was associated with a greater likelihood of partial remission of type 2 diabetes compared with diabetes support and education. However, the absolute remission rates were modest. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00017953.
| S-EPMC4771522 | biostudies-literature
Project description:BackgroundAgeing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons.MethodsA total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured.ResultsThe sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05).ConclusionsHigh levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.
| S-EPMC6596393 | biostudies-literature