The Association of Total Knee Arthroplasty With Weight Loss in the Look AHEAD (Action for Health in Diabetes) Clinical Trial.

BACKGROUND: Patients who have obesity seldom lose weight after total knee arthroplasty (TKA). The Look AHEAD (Action for Health in Diabetes) trial randomized patients with type 2 diabetes who were overweight or had obesity to a 10-year intensive lifestyle intervention (ILI) or diabetes support and education (DSE). METHODS: Of the total 5,145 participants enrolled who had a median 14-year follow-up, a subset of 4,624 met inclusion criteria. The ILI aimed at achieving and maintaining a 7% weight loss and included weekly counseling the first 6 months, with decreasing frequency thereafter. This secondary analysis was undertaken to determine what effects a TKA had on patients participating in a known successful weight loss program and specifically if there was a negative impact on weight loss or their Physical Component Score. RESULTS: The analysis suggests that the ILI remained effective for maintaining or losing weight after TKA. Participants in ILI had significantly greater percent weight loss than those in DSE both before and after TKA (ILI-DSE before TKA: -3.6% (-5.0, -2.3); after TKA: -3.7% (-4.1, -3.3); both P < .0001). When comparing percent weight loss before to after TKA, there was no significant difference within either the DSE or ILI group (least square means ± standard error ILI: -0.36% ± 0.3, P = .21; DSE: -0.41% ± 0.29, P = .16). Physical Component Scores improved after TKA (P < .001), but no difference was found between TKA ILI and DSE groups before or after surgery. CONCLUSION: Participants who had a TKA did not have an altered ability to adhere to intervention goals to maintain weight loss or obtain further weight loss. The data suggest patients who have obesity can lose weight after TKA on a weight loss program.

End-of-Trial Health Outcomes in Look AHEAD Participants who Elected to have Bariatric Surgery.

OBJECTIVE: This study examined end-of-trial health outcomes in participants in the Action for Health in Diabetes (Look AHEAD) trial who had bariatric surgery during the approximately 10-year randomized intervention. METHODS: Data were obtained from the Look AHEAD public access database of 4,901 individuals with type 2 diabetes and overweight/obesity who were assigned to intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) control group. Changes in outcomes in participants who had bariatric surgery were compared with those in participants with BMI ≥ 30 kg/m2 who remained in the ILI and DSE groups. RESULTS: A total of 99 DSE and 97 ILI participants had bariatric surgery. At randomization, these 196 participants were significantly younger and more likely to be female and to have higher BMI than the remaining ILI (N = 1,972) and DSE (N = 2,009) participants. At trial's end, surgically treated participants lost 19.3% of baseline weight, compared with 5.8% and 3.3% for the ILI and DSE groups, respectively, and were more likely to achieve partial or full remission of their diabetes. CONCLUSIONS: The large, sustained improvements in weight and diabetes observed in this self-selected sample of surgically treated participants are consistent with results of multiple randomized trials.

A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup.

Recent advances indicate that biological aging is a potentially modifiable driver of late-life function and chronic disease and have led to the development of geroscience-guided therapeutic trials such as TAME (Targeting Aging with MEtformin). TAME is a proposed randomized clinical trial using metformin to affect molecular aging pathways to slow the incidence of age-related multi-morbidity and functional decline. In trials focusing on clinical end-points (e.g., disease diagnosis or death), biomarkers help show that the intervention is affecting the underlying aging biology before sufficient clinical events have accumulated to test the study hypothesis. Since there is no standard set of biomarkers of aging for clinical trials, an expert panel was convened and comprehensive literature reviews conducted to identify 258 initial candidate biomarkers of aging and age-related disease. Next selection criteria were derived and applied to refine this set emphasizing: (1) measurement reliability and feasibility; (2) relevance to aging; (3) robust and consistent ability to predict all-cause mortality, clinical and functional outcomes; and (4) responsiveness to intervention. Application of these selection criteria to the current literature resulted in a short list of blood-based biomarkers proposed for TAME: IL-6, TNFα-receptor I or II, CRP, GDF15, insulin, IGF1, cystatin C, NT-proBNP, and hemoglobin A1c. The present report provides a conceptual framework for the selection of blood-based biomarkers for use in geroscience-guided clinical trials. This work also revealed the scarcity of well-vetted biomarkers for human studies that reflect underlying biologic aging hallmarks, and the need to leverage proposed trials for future biomarker discovery and validation.

Ethnic comparison of weight loss in the Trial of Nonpharmacologic Interventions in the Elderly.

OBJECTIVE: To compare weight loss in blacks and whites in the Trial of Nonpharmacologic Interventions in the Elderly (TONE). RESEARCH METHODS AND PROCEDURES: TONE enrolled 421 overweight white and 164 overweight black adults, 60 to 79 years old, with blood pressure well-controlled on a single, antihypertensive drug. Drug therapy withdrawal was attempted 3 months after randomization to counseling for weight loss, sodium reduction, both weight loss and sodium reduction, or to usual care, with follow-up for 15 to 36 months after enrollment. Statistical procedures included repeated measures analysis of covariance and logistic and proportional hazards regression. RESULTS: In the weight-loss condition, net weight change (in kilograms) was -2.7 in blacks and -5.9 in whites (p < 0.001; ethnic difference, p = 0.0002) at 6 months and -2.0 (p < 0.05) in blacks and -4.9 (p < 0.001) in whites at the end of follow-up (ethnic difference, p = 0.007). In weight/sodium, net weight change was -2.1 (p < 0.01) in blacks and -2.8 (p < 0.001) in whites at 6 months, and -1.9 in blacks and -1.7 in whites at the end of follow-up (p < 0.05; ethnic difference, p > 0.5). Exploratory analyses suggested a more favorable pattern of weight change in blacks than in whites from 6 months onward. There was no ethnic difference in blood pressure outcomes. DISCUSSION: Whites lost more weight than blacks without, but not with, a concurrent focus on sodium reduction.