Impact of Sustained Weight Loss on Cardiometabolic Outcomes

Abstract

•Sustained weight loss significantly lowers incidence of cardiometabolic outcomes.•Sustained weight loss significantly delays onset of cardiometabolic outcomes.•Greater weight loss significantly delays onset of cardiometabolic outcomes. Obesity increases the risk of developing type 2 diabetes, hypertension, and hyperlipidemia. We sought to determine the impact of obesity maintenance, weight regain, weight loss maintenance, and magnitudes of weight loss on future risk and time to developing these cardiometabolic conditions. This was a retrospective cohort study of adults receiving primary care at Geisinger Health System between 2001 and 2017. Using electronic health records, patients with ≥3-weight measurements over a 2-year index period were identified and categorized. Obesity maintainers (OM) had obesity (body mass index ≥30 kg/m²) and maintained their weight within ±3% from baseline (reference group). Both weight loss rebounders (WLR) and weight loss maintainers (WLM) had obesity at baseline and lost >5% body weight in year 1; WLR regained ≥20% of weight loss by end of year 2 and WLM maintained ≥80% of weight loss. Incident type 2 diabetes, hypertension, and hyperlipidemia, and time-to-outcome were determined for each study group and by weight loss category for WLM. Of the 63,567 patients included, 67% were OM, 19% were WLR, and 14% were WLM. The mean duration of follow-up was 6.6 years (SD, 3.9). Time until the development of electronic health record-documented type 2 diabetes, hypertension, and hyperlipidemia was longest for WLM and shortest for OM (log-rank test p <0.0001). WLM had the lowest incident type 2 diabetes (adjusted hazard ratio [HR] 0.676 [95% confidence interval [CI] 0.617 to 0.740]; p <0.0001), hypertension (adjusted HR 0.723 [95% CI 0.655 to 0.799]; p <0.0001), and hyperlipidemia (adjusted HR 0.864 [95% CI 0.803 to 0.929]; p <0.0001). WLM with the greatest weight loss (>15%) had a longer time to develop any of the outcomes compared with those with the least amount of weight loss (<7%) (p <0.0001). In an integrated delivery network population, sustained weight loss was associated with a delayed onset of cardiometabolic diseases, particularly with a greater magnitude of weight loss. Obesity increases the risk of developing type 2 diabetes, hypertension, and hyperlipidemia. We sought to determine the impact of obesity maintenance, weight regain, weight loss maintenance, and magnitudes of weight loss on future risk and time to developing these cardiometabolic conditions. This was a retrospective cohort study of adults receiving primary care at Geisinger Health System between 2001 and 2017. Using electronic health records, patients with ≥3-weight measurements over a 2-year index period were identified and categorized. Obesity maintainers (OM) had obesity (body mass index ≥30 kg/m²) and maintained their weight within ±3% from baseline (reference group). Both weight loss rebounders (WLR) and weight loss maintainers (WLM) had obesity at baseline and lost >5% body weight in year 1; WLR regained ≥20% of weight loss by end of year 2 and WLM maintained ≥80% of weight loss. Incident type 2 diabetes, hypertension, and hyperlipidemia, and time-to-outcome were determined for each study group and by weight loss category for WLM. Of the 63,567 patients included, 67% were OM, 19% were WLR, and 14% were WLM. The mean duration of follow-up was 6.6 years (SD, 3.9). Time until the development of electronic health record-documented type 2 diabetes, hypertension, and hyperlipidemia was longest for WLM and shortest for OM (log-rank test p <0.0001). WLM had the lowest incident type 2 diabetes (adjusted hazard ratio [HR] 0.676 [95% confidence interval [CI] 0.617 to 0.740]; p <0.0001), hypertension (adjusted HR 0.723 [95% CI 0.655 to 0.799]; p <0.0001), and hyperlipidemia (adjusted HR 0.864 [95% CI 0.803 to 0.929]; p <0.0001). WLM with the greatest weight loss (>15%) had a longer time to develop any of the outcomes compared with those with the least amount of weight loss (<7%) (p <0.0001). In an integrated delivery network population, sustained weight loss was associated with a delayed onset of cardiometabolic diseases, particularly with a greater magnitude of weight loss. The prevalence of obesity has risen dramatically in the United States; per the 2017 to 2018 National Health and Nutrition Examination Survey, 42.4% of US adults have obesity.1Hales CM Carroll MD Fryar CD Ogden CL. Prevalence of obesity and severe obesity among adults: United States, 2017–2018.NCHS Data Brief. 2020; : 1-8Google Scholar Managing obesity is a lifelong endeavor as there are many biological, social, psychological, and environmental factors contributing to weight gain and loss.2Bray GA Kim KK Wilding JPH World Obesity FederationObesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation.Obes Rev. 2017; 18: 715-723Crossref PubMed Scopus (514) Google Scholar,3Garip G Yardley L A synthesis of qualitative research on overweight and obese people's views and experiences of weight management.Clin Obes. 2011; 1: 110-126Crossref PubMed Google Scholar Modest weight loss of at least 5% is clinically beneficial4Magkos F Fraterrigo G Yoshino J Luecking C Kirbach K Kelly SC de Las Fuentes L He S Okunade AL Patterson BW Klein S. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity.Cell Metab. 2016; 23: 591-601Abstract Full Text Full Text PDF PubMed Scopus (421) Google Scholar and recommended by clinical treatment guidelines,5Jensen MD Ryan DH Apovian CM Ard JD Comuzzie AG Donato KA Hu FB Hubbard VS Jakicic JM Kushner RF Loria CM Millen BE Nonas CA Pi-Sunyer FX Stevens J Stevens VJ Wadden TA Wolfe BM Yanovski SZ American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Obesity Society, 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.J Am Coll Cardiol. 2014; 63: 2985-3023Crossref PubMed Scopus (1339) Google Scholar which can be achieved with various clinical and behavioral treatment options. However, long-term weight loss maintenance remains challenging owing to the biology of obesity, hence weight regain is common;6Elfhag K Rössner S. Who succeeds in maintaining weight loss? A conceptual review of factors associated with weight loss maintenance and weight regain.Obes Rev. 2005; 6: 67-85Crossref PubMed Scopus (850) Google Scholar,7Wing RR Phelan S. Long-term weight loss maintenance.Am J Clin Nutr. 2005; 82: 222s-225sCrossref PubMed Google Scholar about 80% of the weight loss is regained within 5 years.8Hall KD Kahan S. Maintenance of lost weight and long-term management of obesity.Med Clin North Am. 2018; 102: 183-197Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar Clinical outcomes of lifestyle, behavioral, and clinical treatment interventions have been examined,9Ma C Avenell A Bolland M Hudson J Stewart F Robertson C Sharma P Fraser C MacLennan G. Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis.BMJ. 2017; 359: j4849Crossref PubMed Scopus (224) Google Scholar but limitations include the relatively short duration of follow-up observations; additionally, there is scant literature describing clinical outcomes of sustained weight loss in real-world settings. This study aims to evaluate the long-term impact of obesity, weight loss with regain, and weight loss maintenance, with the latter explored across varying weight loss thresholds. This research seeks to understand the relation between long-term weight maintenance and clinical relevance to 3 cardiometabolic outcomes: type 2 diabetes, hypertension, and hyperlipidemia in a large integrated delivery network setting. This is a retrospective observational study of patients receiving primary care between 2001 and 2017 at Geisinger Health System, a Pennsylvania-based integrated delivery network that includes a health plan, acute care hospitals, specialty hospitals, ambulatory surgery centers, and clinical services such as the Center for Nutrition and Weight Management.10Paulus RA Davis K Steele GD. Continuous innovation in health care: implications of the Geisinger experience.Health Aff (Millwood). 2008; 27: 1235-1245Crossref PubMed Scopus (229) Google Scholar,11Geisinger research units. Available at: https://www.geisinger.edu/research/departments-and-centers/obesity-institute. Accessed September 21, 2020.Google Scholar Geisinger Health System is 1 of the largest healthcare organizations in the United States and serves over 3 million residents including employees, individuals/families, and adults aged 65 and older. The Geisinger Institutional Review Board reviewed the study and determined that the research does not involve human subjects, thus deeming it exempt from Institutional Board oversight (IRB #: 2019-0138). Data were extracted from the Epic electronic health record (EHR) system in several stages to efficiently capture eligible subjects and define and analyze study outcomes. The study population was limited to adult patients (age ≥18 years) with 3 or more EHR-documented weight measurements within 2 years, denoted as the index period; these measurements included a baseline weight, a 1-year weight (within 6 to 18 months), and a 2-year weight (within 12 to 24 months). The index period was set at 2 years to allow adequate time to discern clinically relevant weight change patterns. Patients who underwent bariatric surgery before or during the index period and patients with prevalent cancer or a history of cancer during the same time window were excluded from the study; for pregnant women, the weight measurements within 6 months of the pregnancy indicators were also excluded. The study sample was separated into 3 groups based on weight trends during each year of the index period: (1) obesity maintainers (OM), patients with a history of obesity who maintained weight within ±3% margin from baseline; (2) weight loss rebounders (WLRs), patients with a history of obesity who lost >5% weight via nonsurgical methods (i.e., pharmacotherapy and/or lifestyle intervention) and regained weight from baseline (defined as regaining ≥20% of 1-year weight loss12King WC Hinerman AS Belle SH Wahed AS Courcoulas AP. Comparison of the performance of common measures of weight regain after bariatric surgery for association with clinical outcomes.JAMA. 2018; 320: 1560-1569Crossref PubMed Scopus (111) Google Scholar); and (3) weight loss maintainers (WLMs), patients with obesity at baseline who lost >5% weight via non-surgical methods and maintained weight loss from baseline (defined as maintaining ≥80% of 1-year weight loss). The WLM group was stratified by the amount of initial weight loss. Patients who did not meet the definition of the 3 groups were excluded from the analysis. Outcomes analyzed include type 2 diabetes mellitus, hypertension, and hyperlipidemia. The status of these conditions was defined by EHR documentation of International Classification of Diseases 10th edition (ICD-10) codes (or at least 2 outpatient visits) or treatment for the condition; for diabetes, the presence of a hemoglobin A1c level of >6.5% with diabetes medication treatment was also included to identify the relatively few patients who had a strong indication of diabetes despite the lack of a diagnosis code (Online Appendix 1). Diabetes, hypertension, and hyperlipidemia were classified as prevalent or incident based on the timing of meeting the diagnostic criteria—before or during the index period was considered prevalent, and after the index period was considered incident (Online Appendix 1). Additionally, A1c and systolic blood pressure (SBP) were also examined as outcomes related to diabetes and hypertension, respectively. EHR data on weight measurements, socio-demographics, vital signs, laboratory tests, encounters, procedures, diagnostic codes, orders (pharmacological, nutrition consults, diet, etc.) were extracted. The median height of a patient was calculated and used for all body mass index (BMI) measures (Online Appendix 1). Timing of weight measurements was determined to identify periods when patients had 3 EHR-recorded weight measurements over a 2 to 3-year period. All weight measurements during the first 15 months of participation in Geisinger primary care for each patient were excluded to provide a lead-in period to establish A baseline weight in a ≥30 was used to define the of the index period time A weight 12 months after baseline (within 6 to 18 and a at least 12 months after the (within 12 to 24 months of A follow-up at least 6 months after the weight The median follow-up period between the baseline and 1-year weight from to across the 3 study duration between baseline and 2-year weight was also for the 3 from a median of to and of weight loss and weight maintenance on each clinical type 2 diabetes, hypertension, and hyperlipidemia, with and by The the association of each clinical for the study groups WLR, and for outcomes (i.e., each clinical time-to-outcome was calculated as the of between the initial baseline weight until the of patients who did not develop the of the time was at the follow-up for hazard for the of in the short and We used a with a were the were for patient and these the of weight loss on the clinical outcomes the OM group as the The were for diabetes, hypertension hyperlipidemia disease, and the The is a into a P A of in development and Full Text PDF PubMed Scopus Google Scholar in research were based on EHR diagnosis codes, for with greater were for A1c among patients with prevalent diabetes and A1c and for among those with prevalent hypertension and were not for owing to limited of laboratory test The incidence of each was by the and over years of follow-up for each In were used to time until within the WLM group by the amount of weight loss at the end of year 2 of the index period to to and weight loss as the A weight loss of was examined based on research the of weight loss of at least on or the development of type 2 WC RF CA follow-up of diabetes incidence and weight loss in the Outcomes Full Text Full Text PDF PubMed Scopus Google WC RF JM in the incidence of type 2 diabetes with lifestyle or J PubMed Scopus Google Scholar The were North Of the study sample of 63,567 the were classified as OM (reference group). The sample was between WLR and WLM The mean follow-up was 6.6 years 3.9). and patients were significantly more and to weight at 1 year (p for and disease status for the study population are in weight loss from baseline to the 2-year weight was for the WLR group and for the WLM of study 2 diabetes for for cardiovascular for disease conditions for which were were body mass OM obesity WLM weight loss WLR weight loss in a conditions for which were were body mass OM obesity WLM weight loss WLR weight loss a of patients had any of interventions including with a weight loss with a or obesity medication treatment (i.e., or Patients who lost weight and were more to have any of the 3 of WLR and of WLM had any weight loss treatment during the index compared with of OM (p <0.0001). A of patients were included in OM, WLR, and follow-up time for the 3 groups is in Patients with diabetes 1 and type before baseline or during the index period were excluded from the OM, WLR, and WLM patients had the longest time until EHR-documented type 2 diabetes and OM patients had the shortest time (log-rank test p 1). 5 years, the incidence of type 2 diabetes in the study population was for the OM for WLR, and for with a at years of for the OM for WLR, and for WLM. in the WLM group had a risk of future incident type 2 diabetes compared with those in the OM group (adjusted hazard ratio [HR] confidence interval [CI] to p the between OM and WLR was not the patients with prevalent diabetes and A1c in measures for within patients that have data to provide and from 1 study group to the WLR and WLM groups had a A1c level during follow-up as compared with the OM WLR had a mean A1c OM and WLM had a mean A1c p A sample of patients was included in the OM, WLR, and follow-up time for the 3 groups is in Patients with hypertension or who hypertension treatment before baseline or during the index period were excluded from the OM, WLR, and Time to EHR-recorded hypertension was greatest for WLM and shortest for OM (log-rank test p 1). 5 years of the incidence of hypertension was for OM, for WLR, and for WLM. years, the incidence was and for OM, WLR, and respectively. The WLM group had a risk of developing hypertension compared with OM (adjusted HR CI to p <0.0001). The between OM and WLR was not In the patients with prevalent hypertension (defined as treatment with a hypertension and in measures the WLR and WLM groups had during follow-up as compared with the OM The WLR group had a mean (p and the WLM group had a mean p Additionally, between WLR and WLM were (p A of patients in the study population were analyzed for hyperlipidemia OM, WLR, and follow-up time for the 3 groups is in Patients with hyperlipidemia or who treatment with a medication before baseline or during the index period were excluded from the OM, WLR, and WLM the longest time until treatment for hyperlipidemia and OM had the shortest time to treatment (log-rank test p 1). 5 years of the incidence of hyperlipidemia was for the OM for WLR, and for with the the the incidence was for the OM for WLR, and for WLM. with OM, the WLM group had a 14% risk of developing hyperlipidemia (adjusted HR CI to p <0.0001). was between OM and Patients in the WLM group with the greatest weight loss (>15%) had a longer time developing any of the 3 cardiometabolic outcomes compared with those who had the least amount of weight loss (<7%) (p the for the risk of developing each are in The risk of developing type 2 diabetes was for all loss compared with those with weight loss. 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