Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study.

AIMS/HYPOTHESIS: We examined the association of attainment of diabetes remission in the context of a 12 year intensive lifestyle intervention with subsequent incidence of chronic kidney disease (CKD) and CVD. METHODS: The Look AHEAD study was a multi-centre RCT comparing the effect of a 12 year intensive lifestyle intervention with that of diabetes support and education on CVD and other long-term health conditions. We compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on achievement and duration of diabetes remission. Participants were 58% female, and had a mean age of 59 years, a duration of diabetes of 6 year and BMI of 35.8 kg/m2. We applied an epidemiological definition of remission: taking no diabetes medications and having HbA1c <48 mmol/mol (6.5%) at a single point in time. We defined high-risk or very high-risk CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, and CVD incidence as any occurrence of non-fatal acute myocardial infarction, stroke, admission for angina or CVD death. RESULTS: Participants with evidence of any remission during follow-up had a 33% lower rate of CKD (HR 0.67; 95% CI 0.52, 0.87) and a 40% lower rate of the composite CVD measure (HR 0.60; 95% CI 0.47, 0.79) in multivariate analyses adjusting for HbA1c, BP, lipid levels, CVD history, diabetes duration and intervention arm, compared with participants without remission. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission. CONCLUSIONS/INTERPRETATION: Participants with type 2 diabetes with evidence of remission had a substantially lower incidence of CKD and CVD, respectively, compared with participants who did not achieve remission. This association may be affected by post-baseline improvements in weight, fitness, HbA1c and LDL-cholesterol. TRIAL REGISTRATION: ClinicalTrials.gov NCT00017953 DATA AVAILABILITY: https://repository.niddk.nih.gov/studies/look-ahead/.

Technical report: an online international weight control registry to inform precision approaches to healthy weight management.

BACKGROUND: Personalizing approaches to prevention and treatment of obesity will be a crucial aspect of precision health initiatives. However, in considering individual susceptibility to obesity, much remains to be learned about how to support healthy weight management in different population subgroups, environments and geographical locations. SUBJECTS/METHODS: The International Weight Control Registry (IWCR) has been launched to facilitate a deeper and broader understanding of the spectrum of factors contributing to success and challenges in weight loss and weight loss maintenance in individuals and across population groups. The IWCR registry aims to recruit, enroll and follow a diverse cohort of adults with varying rates of success in weight management. Data collection methods include questionnaires of demographic variables, weight history, and behavioral, cultural, economic, psychological, and environmental domains. A subset of participants will provide objective measures of physical activity, weight, and body composition along with detailed reports of dietary intake. Lastly, participants will be able to provide qualitative information in an unstructured format on additional topics they feel are relevant, and environmental data will be obtained from public sources based on participant zip code. CONCLUSIONS: The IWCR will be a resource for researchers to inform improvements in interventions for weight loss and weight loss maintenance in different countries, and to examine environmental and policy-level factors that affect weight management in different population groups. This large scale, multi-level approach aims to inform efforts to reduce the prevalence of obesity worldwide and its associated comorbidities and economic impacts. TRIAL REGISTRATION: NCT04907396 (clinicaltrials.gov) sponsor SB Roberts; Tufts University IRB #13075.

Relationship of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to the remainder of the lipid profile: The Very Large Database of Lipids-4 (VLDL-4) study.

BACKGROUND: High levels of the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio are associated with obesity, metabolic syndrome, and insulin resistance. OBJECTIVES: We evaluated variability in the remaining lipid profile, especially remnant lipoprotein particle cholesterol (RLP-C) and its components (very low-density lipoprotein cholesterol subfraction 3 and intermediate-density lipoprotein cholesterol), with variability in the TG/HDL-C ratio in a very large study cohort representative of the general U.S. METHODS: We examined data from 1,350,908 US individuals who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL) from 2009 to 2011. Demographic information other than age and sex was not available. Changes to the remaining lipid profile across percentiles of the TG/HDL-C ratio were quantified, as well as by three TG/HDL-C cut-off points previously proposed in the literature: 2.5 (male) and 2 (female), 3.75 (male) and 3 (female), and 3.5 (male and female). RESULTS: The mean age of our study population was 58.7 years, and 48% were men. The median TG/HDL-C ratio was 2.2. Across increasing TG/HDL-C ratios, we found steadily increasing levels of RLP-C, non-HDL-C and LDL density. Among the lipid parameters studied, RLP-C and LDL density had the highest relative increase when comparing individuals with elevated TG/HDL-C levels to those with lower TG/HDL-C levels using established cut-off points. Approximately 47% of TG/HDL-C ratio variance was attributable to RLP-C. CONCLUSIONS: In the present analysis, a higher TG/HDL-C ratio was associated with an increasingly atherogenic lipid phenotype, characterized by higher RLP-C along with higher non-HDL-C and LDL density.

Statins, mood, sleep, and physical function: a systematic review.

PURPOSE: We aimed to evaluate the effects of statins on mood, sleep, and physical function. METHODS: We performed a systematic computer-aided search of MEDLINE/PubMed, EMBASE, and the Cochrane Central Register and augmented this search by scrutinizing reference lists and making inquiries among colleagues and experts in the field. All patient populations and study types were considered. We selected studies of statin therapy compared with no statin or placebo. Outcome measures included mood, sleep, and physical function. RESULTS: Thirty-four studies were included in qualitative synthesis. Seven of eight (88 %) observational studies, 4/6 (66 %) randomized trials with mood as a primary endpoint (487 total participants; exposure 4 weeks to 1 year), and 3/3 (100 %) randomized trials with mood as a secondary endpoint (2,851 total participants; exposure 1-4 years) were not compatible with a negative mood effect of statins. Comparatively, fewer studies examined statin effects on sleep and physical function. Studies reporting negative effects contained potential sources of bias, including multiple testing or lack of adjustment for confounders in observational studies, and failure to prespecify outcomes or report blinding in trials. CONCLUSIONS: A limited body of available evidence is most compatible with no adverse effect of statins on quality of life measures, namely, mood, sleep, and physical function. Studies suggesting such effects suffer from an increased risk of bias. High-quality, prospective, and adequately powered studies are needed, especially in the domains of sleep and physical function, with careful attention to patients who may be most vulnerable to adverse effects.

Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects.

OBJECTIVE: To evaluate the effect of statins on short-term cognitive function and the long-term incidence of dementia. PATIENTS AND METHODS: A systematic search was performed of MEDLINE, EMBASE, and the Cochrane Central Register from their inception to April 25, 2013. Adults with no history of cognitive dysfunction treated with statins were included from high-quality randomized controlled trials and prospective cohort studies after formal bias assessment. RESULTS: Sixteen studies were included in qualitative synthesis and 11 in quantitative synthesis. Short-term trials did not show a consistent effect of statin therapy on cognitive end points. Digit Symbol Substitution Testing (a well-validated measure of cognitive function) was the most common short-term end point, with no significant differences in the mean change from baseline to follow-up between the statin and placebo groups (mean change, 1.65; 95% CI, -0.03 to 3.32; 296 total exposures in 3 trials). Long-term cognition studies included 23,443 patients with a mean exposure duration of 3 to 24.9 years. Three studies found no association between statin use and incident dementia, and 5 found a favorable effect. Pooled results revealed a 29% reduction in incident dementia in statin-treated patients (hazard ratio, 0.71; 95% CI, 0.61-0.82). CONCLUSION: In patients without baseline cognitive dysfunction, short-term data are most compatible with no adverse effect of statins on cognition, and long-term data may support a beneficial role for statins in the prevention of dementia.