The syndromic triad of COVID-19, type 2 diabetes, and malnutrition.

The coronavirus disease 2019 (COVID-19) pandemic challenges our collective understanding of transmission, prevention, complications, and clinical management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Risk factors for severe infection, morbidity, and mortality are associated with age, environment, socioeconomic status, comorbidities, and interventional timing. Clinical investigations report an intriguing association of COVID-19 with diabetes mellitus and malnutrition but incompletely describe the triphasic relationship, its mechanistic pathways, and potential therapeutic approaches to address each malady and their underlying metabolic disorders. This narrative review highlights common chronic disease states that interact epidemiologically and mechanistically with the COVID-19 to create a syndromic phenotype-the COVID-Related Cardiometabolic Syndrome-linking cardiometabolic-based chronic disease drivers with pre-, acute, and chronic/post-COVID-19 disease stages. Since the association of nutritional disorders with COVID-19 and cardiometabolic risk factors is well established, a syndromic triad of COVID-19, type 2 diabetes, and malnutrition is hypothesized that can direct, inform, and optimize care. In this review, each of the three edges of this network is uniquely summarized, nutritional therapies discussed, and a structure for early preventive care proposed. Concerted efforts to identify malnutrition in patients with COVID-19 and elevated metabolic risks are needed and can be followed by improved dietary management while simultaneously addressing dysglycemia-based chronic disease and malnutrition-based chronic disease.

Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial.

We evaluated the effect of diets low in energy density (1 kcal/g) and high in either potatoes (Potato) or pulses (Bean) on blood glucose control in participants with insulin resistance. We hypothesized that the Potato and Bean diets would have equivalent effects. This was an 8-week randomized, parallel design, controlled feeding study comparing Potato and Bean diets (50-55% carbohydrate, 30-35% fat, 15-20% protein). Equivalence was prespecified as the mean change in the blood glucose concentration for Potato that was within ±20% of the Bean diet. Thirty-six participants (age: 18-60 years, body mass index: 25-40 kg/m2) with insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] >2) were enrolled. Body weight was measured, and subjects underwent a mixed meal tolerance test at baseline and after 8 weeks. Intent-to-treat (ITT) and completer analyses were conducted. Equivalence between the two diets in the area under the curve for serum glucose was attained within ±10%, but the reduction from baseline was not statistically significant. For the Bean diet, insulin (area under the response curve: -2136.3 ± 955.5 mg/[dL∙min], P = .03) and HOMA-IR (-1.4 ± 0.6, P = .02) were lower compared with baseline. ITT and completer analyses were similar, except that HOMA-IR was also reduced by the Potato diet (-1.3 ± 0.6, P < .05). Compliance with the diets was 87-88%, and body weight was reduced in both diets (Potato: -5.6% ± 0.6%; Bean: -4.1% ± 0.6%, P < .001) with no significant difference between the two diets. Potato and Bean diets low in energy density were equally effective in reducing insulin resistance and promoting weight loss in individuals with impaired blood glucose control. Clinical Trial: The trial was registered with ClinicalTrials.gov Identifier: NCT04203238.

Insulin resistance persists despite a metabolically healthy obesity phenotype.

OBJECTIVE: Metabolically healthy obesity (MHO) is often defined as the absence of metabolic syndrome in the presence of obesity. However, phenotypic features of MHO are unclear. Insulin sensitivity in MHO was cross-sectionally compared with metabolically unhealthy obesity (MUO) and a reference group of young healthy participants without obesity. METHODS: Sedentary adults (n = 96) undergoing anthropometric, blood chemistries, maximal aerobic capacity, and euglycemic-hyperinsulinemic clamp measurements were classified by BMI (<25 and ≥30 kg/m2 ). MUO was defined as having obesity with metabolic syndrome (≥2 additional risk factors). Data were analyzed using a linear mixed models approach. RESULTS: Body weight was similar between MHO and MUO. Body fat (percentage) and high-density lipoprotein cholesterol were higher (p < 0.001), and systolic blood pressure, triglycerides, glucose, and insulin were lower in MHO versus MUO (p < 0.03, all). The MHO group also had lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol, diastolic blood pressure, and insulin compared with the reference. Both the MHO and MUO groups displayed impaired insulin sensitivity compared with the reference control (p < 0.001). CONCLUSIONS: Participants with MHO had distinct clinical measures related to hypertension, lipid metabolism, and glycemic control compared with a healthy reference group. Peripheral insulin resistance in obesity independent of metabolic status portends increased risk for type 2 diabetes in the MHO patient population.

Resting Energy Expenditure Is Elevated in Asthma.

Background: Asthma physiology affects respiratory function and inflammation, factors that may contribute to elevated resting energy expenditure (REE) and altered body composition. Objective: We hypothesized that asthma would present with elevated REE compared to weight-matched healthy controls. Methods: Adults with asthma (n = 41) and healthy controls (n = 20) underwent indirect calorimetry to measure REE, dual-energy X-ray absorptiometry (DEXA) to measure body composition, and 3-day diet records. Clinical assessments included spirometry, fractional exhaled nitric oxide (FENO), and a complete blood count. Results: Asthmatics had greater REE than controls amounting to an increase of ~100 kcals/day, even though body mass index (BMI) and body composition were similar between groups. Inclusion of asthma status and FENO in validated REE prediction equations led to improved estimates. Further, asthmatics had higher white blood cell (control vs. asthma (mean ± SD): 4.7 ± 1.1 vs. 5.9 ± 1.6, p < 0.01) and neutrophil (2.8 ± 0.9 vs. 3.6 ± 1.4, p = 0.02) counts that correlated with REE (both p < 0.01). Interestingly, despite higher REE, asthmatics reported consuming fewer calories (25.1 ± 7.5 vs. 20.3 ± 6.0 kcals/kg/day, p < 0.01) and carbohydrates than controls. Conclusion: REE is elevated in adults with mild asthma, suggesting there is an association between REE and the pathophysiology of asthma.

Sleep Extension: A Potential Target for Obesity Treatment.

PURPOSE OF REVIEW: Sleep and obesity share a bidirectional relationship, and weight loss has been shown to enhance sleep. Aiming to extend sleep on its own or as part of a lifestyle intervention may attenuate health consequences of short sleep. This review highlights several sleep extension approaches, discusses feasibility of each, and summarizes findings relevant to obesity. RECENT FINDINGS: Sleep extension in response to experimental sleep restriction demonstrates partial rescue of cardiometabolic dysfunction in some but not all studies. Adequate sleep on a nightly basis may be necessary for optimal health. While initial sleep extension interventions in habitually short sleepers have been met with obstacles, preliminary findings suggest that sleep extension or sleep hygiene interventions may improve glycemic control, decrease blood pressure, and enhance weight loss. Sleep extension has the potential to attenuate obesity risk and cardiometabolic dysfunction. There is tremendous opportunity for future research that establishes a minimum threshold for sleep extension effectiveness and addresses logistical barriers identified in seminal studies.

Intermittent Fasting and Metabolic Health: From Religious Fast to Time-Restricted Feeding.

Over the past 10 to 15 years, intermittent fasting has emerged as an unconventional approach to reduce body weight and improve metabolic health beyond simple calorie restriction. In this review, we summarize findings related to Ramadan and Sunnah fasting. We then discuss the role of caloric restriction not only as an intervention for weight control, but importantly, as a strategy for healthy aging and longevity. Finally, we review the four most common intermittent fasting (IF) strategies used to date for weight management and to improve cardiometabolic health. Weight loss is common after IF but does not appear to be different than daily caloric restriction when compared directly. IF may also provide additional cardiometabolic benefit, such as insulin sensitization, that is independent from weight loss. While no specific fasting regimen stands out as superior at this time, there is indeed heterogeneity in responses to these different IF diets. This suggests that one dietary regimen may not be ideally suited for every individual. Future studies should consider strategies for tailoring dietary prescriptions, including IF, based on advanced phenotyping and genotyping prior to diet initiation.

Weight loss efficacy of alternate day fasting versus daily calorie restriction in subjects with subclinical hypothyroidism: a secondary analysis.

This study compared the weight loss efficacy of alternate-day fasting (ADF) versus daily calorie restriction (CR) in adults with subclinical hypothyroidism. After 6 months, body weight decreased (P < 0.001) similarly by ADF (-7% ± 1%) and CR (-8% ± 2%). Insulin resistance decreased (P < 0.05) more by ADF versus CR. Free thyroxin and thyroid-stimulating hormone remained unchanged. Thus, ADF and CR produce similar weight loss in this population, without affecting thyroid hormone levels. Novelty Intermittent fasting and daily restriction produce similar reductions in body weight in subjects with subclinical hypothyroidism.

Differential Effects of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance.

OBJECTIVE: This study compared the effects of alternate-day fasting (ADF) with those of daily calorie restriction (CR) on body weight and glucoregulatory factors in adults with overweight or obesity and insulin resistance. METHODS: This secondary analysis examined the data of insulin-resistant individuals (n = 43) who participated in a 12-month study that compared ADF (25% energy needs on "fast days"; 125% energy needs on alternating "feast days") with CR (75% energy needs every day) and a control group regimen. RESULTS: In insulin-resistant participants, weight loss was not different between ADF (-8% ± 2%) and CR (-6% ± 1%) by month 12, relative to controls (P < 0.0001). Fat mass and BMI decreased (P < 0.05) similarly from ADF and CR. ADF produced greater decreases (P < 0.05) in fasting insulin (-52% ± 9%) and insulin resistance (-53% ± 9%) compared with CR (-14% ± 9%; -17% ± 11%) and the control regimen by month 12. Lean mass, visceral fat mass, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, blood pressure, C-reactive protein, tumor necrosis factor α, and interleukin 6 values remained unchanged. CONCLUSIONS: These findings suggest that ADF may produce greater reductions in fasting insulin and insulin resistance compared with CR in insulin-resistant participants despite similar decreases in body weight.

Effect of 8-h time-restricted feeding on sleep quality and duration in adults with obesity.

This study examined the effects of time-restricted feeding (TRF; 8-h feeding window/16-h fasting window daily) on sleep. Obese adults (n = 23) followed 8-h TRF for 12 weeks. Pittsburgh Sleep Quality Index (PSQI) total score was below 5 at week 1 (4.7 ± 0.5) and week 12 (4.8 ± 0.7), indicating good sleep quality throughout the trial. Subjective measures of wake time, bedtime, and sleep duration remained unchanged. Findings from this secondary analysis indicate that TRF does not alter sleep quality or duration in subjects with obesity. Novelty This study is the first to show that TRF (8-h feeding window/16-h fasting window daily) does not alter sleep quality or duration in subjects with obesity.

Safety of 8-h time restricted feeding in adults with obesity.

This study examines the safety of time restricted feeding (TRF; 8-h feeding window/16-h fasting window daily) in obese adults. Twenty-three subjects participated in an 8-h TRF intervention for 12 weeks. Self-reported adverse events, body image perception, complete blood count, and disordered eating patterns did not change from baseline to week 12. These findings suggest that consuming food within an 8-h window can safely facilitate weight loss in subjects with obesity.

Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: A pilot study.

BACKGROUND: Time restricted feeding decreases energy intake without calorie counting and may be a viable option for weight loss. However, the effect of this diet on body weight in obese subjects has never been examined. OBJECTIVE: This study investigated the effects of 8-h time restricted feeding on body weight and metabolic disease risk factors in obese adults. DESIGN: Obese subjects (n = 23) participated in an 8-h time restricted feeding intervention (ad libitum feeding between 10:00 to 18:00 h, water fasting between 18:00 to 10:00 h) for 12 weeks. Weight loss and other outcomes were compared to a matched historical control group (n = 23). RESULTS: Body weight and energy intake decreased in the time restricted group (-2.6% ± 0.5; -341 ± 53 kcal/d) relative to controls over 12 weeks (P < 0.05). Systolic blood pressure decreased in the time restricted feeding group (-7 ± 2 mm Hg) versus controls (P < 0.05). Fat mass, lean mass, visceral fat mass, diastolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, fasting glucose, fasting insulin, HOMA-IR, and homocysteine were not significantly different from controls after 12 weeks (no group×time interaction). CONCLUSION: These findings suggest that 8-h time restricted feeding produces mild caloric restriction and weight loss, without calorie counting. It may also offer clinical benefits by reducing blood pressure.

Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: Secondary analysis of a randomized controlled trial.

BACKGROUND & AIMS: Indirect comparisons suggest that alternate-day fasting (ADF) may produce greater improvements in body composition, fat distribution, and/or the adipokine profile compared to daily calorie restriction (CR), but this has not been tested directly. In a pre-planned secondary analysis of a randomized controlled trial, we compared changes in the VAT:SAT ratio, FFM:total mass ratio, and the adipokine profile between ADF and CR. METHODS: Overweight and obese participants (n = 100) were randomized to 1) ADF (alternating every 24-h between consuming 25% or 125% of energy needs); 2) CR (consuming 75% of needs every day); or 3) control (consuming 100% of needs every day) for 24 wk. RESULTS: The VAT:SAT ratio did not change in any group. The FFM:total mass ratio increased in both ADF (0.03 ± 0.00) and CR (0.03 ± 0.01) compared to the control group (P < 0.01), with no differences between the intervention groups. Circulating leptin decreased in both the ADF group (-18 ± 6%) and CR group (-31 ± 10%) relative to the control group (P < 0.05), with no differences between the intervention groups. Circulating levels of adiponectin, resistin, IL-6, and TNF-α did not change in either intervention group relative to the control group. CONCLUSION: ADF and CR similarly improve the FFM:total mass ratio and reduce leptin after a 24-wk intervention. TRIAL REGISTRATION: Clinicaltrials.gov, number NCT00960505.

Effect of alternate day fasting on markers of bone metabolism: An exploratory analysis of a 6-month randomized controlled trial.

BACKGROUND: Alternate day fasting (ADF) is a novel diet therapy that reduces body weight, but its effect on bone health remains unknown. OBJECTIVE: This study examined the impact of ADF versus traditional daily calorie restriction (CR) on markers of bone metabolism in a 6-month randomized controlled trial. METHODS: Overweight and obese subjects (n = 100) were randomized to 1 of 3 groups for 6 months: 1) ADF (25% energy intake fast day, alternated with 125% intake feast day; 2) CR (75% intake every day); or 3) control (usual intake every day). RESULTS: Body weight decreased similarly (P < 0.001) by ADF (-7.8±1.2%) and CR (-8.8±1.5%), relative to controls by month 6. Lean mass, total body bone mineral content and total body bone mineral density remained unchanged in all groups. Circulating osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide type I collagen (CTX) did not change in any group. IGF-1 increased (P < 0.01) in the CR group, with no change in the ADF or control group. When the data were sub-analyzed according to menopausal status, there were no differences between premenopausal or postmenopausal women for any marker of bone metabolism. CONCLUSION: These findings suggest that 6 months of ADF does not have any deleterious impact on markers of bone metabolism in obese adults with moderate weight loss.

Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial.

Importance: Alternate-day fasting has become increasingly popular, yet, to date, no long-term randomized clinical trials have evaluated its efficacy. Objective: To compare the effects of alternate-day fasting vs daily calorie restriction on weight loss, weight maintenance, and risk indicators for cardiovascular disease. Design, Setting, and Participants: A single-center randomized clinical trial of obese adults (18 to 64 years of age; mean body mass index, 34) was conducted between October 1, 2011, and January 15, 2015, at an academic institution in Chicago, Illinois. Interventions: Participants were randomized to 1 of 3 groups for 1 year: alternate-day fasting (25% of energy needs on fast days; 125% of energy needs on alternating "feast days"), calorie restriction (75% of energy needs every day), or a no-intervention control. The trial involved a 6-month weight-loss phase followed by a 6-month weight-maintenance phase. Main Outcomes and Measures: The primary outcome was change in body weight. Secondary outcomes were adherence to the dietary intervention and risk indicators for cardiovascular disease. Results: Among the 100 participants (86 women and 14 men; mean [SD] age, 44 [11] years), the dropout rate was highest in the alternate-day fasting group (13 of 34 [38%]), vs the daily calorie restriction group (10 of 35 [29%]) and control group (8 of 31 [26%]). Mean weight loss was similar for participants in the alternate-day fasting group and those in the daily calorie restriction group at month 6 (-6.8% [95% CI, -9.1% to -4.5%] vs -6.8% [95% CI, -9.1% to -4.6%]) and month 12 (-6.0% [95% CI, -8.5% to -3.6%] vs -5.3% [95% CI, -7.6% to -3.0%]) relative to those in the control group. Participants in the alternate-day fasting group ate more than prescribed on fast days, and less than prescribed on feast days, while those in the daily calorie restriction group generally met their prescribed energy goals. There were no significant differences between the intervention groups in blood pressure, heart rate, triglycerides, fasting glucose, fasting insulin, insulin resistance, C-reactive protein, or homocysteine concentrations at month 6 or 12. Mean high-density lipoprotein cholesterol levels at month 6 significantly increased among the participants in the alternate-day fasting group (6.2 mg/dL [95% CI, 0.1-12.4 mg/dL]), but not at month 12 (1.0 mg/dL [95% CI, -5.9 to 7.8 mg/dL]), relative to those in the daily calorie restriction group. Mean low-density lipoprotein cholesterol levels were significantly elevated by month 12 among the participants in the alternate-day fasting group (11.5 mg/dL [95% CI, 1.9-21.1 mg/dL]) compared with those in the daily calorie restriction group. Conclusions and Relevance: Alternate-day fasting did not produce superior adherence, weight loss, weight maintenance, or cardioprotection vs daily calorie restriction. Trial Registration: clinicaltrials.gov Identifier: NCT00960505.

Effects of different degrees of insulin resistance on endothelial function in obese adults undergoing alternate day fasting.

BACKGROUND: Obesity can have deleterious effects on insulin sensitivity leading to endothelial dysfunction. Whether alternate day fasting (ADF) can ameliorate insulin sensitivity in a way that improves endothelial function remains unknown. OBJECTIVE: This study examined the impact of ADF on endothelium dependent flow mediated dilation (FMD) in obese subjects with different degrees of insulin resistance. METHODS: Obese non-diabetic adults (n = 54) participated in an 8-week ADF protocol (25% energy intake "fast day", alternated with ad libitum intake "feast day"). Subjects were divided into tertiles according to degree of insulin resistance based on HOMA-IR (Homeostatic model assessment-Insulin resistance): tertile 1 (0.8-2.4), tertile 2 (2.5-3.6), tertile 3 (3.7-12.4). RESULTS: Body weight decreased (P < 0.001) by 4% in each tertile. Fat mass, lean mass, and visceral fat mass also decreased (P < 0.001) similarly in each tertile. After 8 weeks of ADF, FMD and adiponectin differed (P < 0.05) between tertile 1 (3±0%; 26±23%) versus tertile 3 (-3±0%; -13±10%). Changes in leptin did not differ between tertiles (tertile 1: -23±7%; tertile 2: -20±7%; tertile 3: -9±7%). Fasting glucose did not change in any tertile. Fasting insulin and HOMA-IR differed (P < 0.05) between tertile 1 (10±11%; 11±11%) versus tertile 3 (-27±8%; -30±9%). Plasma lipids, blood pressure and heart rate did not change in any tertile. CONCLUSION: Our data suggest that ADF may be effective for decreasing insulin resistance in insulin resistant subjects, but these changes have no effect on endothelial function.

Changes in hunger and fullness in relation to gut peptides before and after 8 weeks of alternate day fasting.

BACKGROUND & AIMS: Alternate day fasting (ADF; 25% energy intake "fast day", alternated with an ad libitum intake "feed day") is effective for weight loss. Whether or not ADF modulates hunger, fullness and gut peptides in a way that enhances dietary compliance and weight loss, remains unknown. Accordingly, this study examined the effect of ADF on postprandial appetite ratings and gut peptides. METHODS: Obese subjects (n = 59) participated in an 8-week ADF protocol where food was provided on the fast day. RESULTS: Body weight decreased (P < 0.0001) by 3.9 ± 0.6 kg after 8 weeks of diet. Reductions (P < 0.05) in fat mass (-2.2 ± 0.2 kg), fat free mass (-1.4 ± 0.2 kg), visceral fat mass (-0.1 ± 0.1 kg), and resting metabolic rate (RMR; -104 ± 28 kcal/day) were also observed. Fasting leptin and insulin decreased (P < 0.05), while AUC ghrelin levels increased (P < 0.05). Despite these metabolic changes, there was no increase in subjective hunger by the end of the study. Furthermore, fullness and PYY increased (P < 0.05). Fat free mass and RMR were not related to hunger or ghrelin at any time point. CONCLUSION: These findings suggest that the absence of a compensatory increase in hunger in conjunction with an increase in sensations of fullness may contribute to the weight loss efficacy of an 8-week ADF regimen.

Determinants of weight loss success with alternate day fasting.

This study examined what characteristics predict weight loss success with alternate day fasting (ADF). Four 8-week trials of ADF (n=121) were included in the analysis. Subjects aged 50-59 y achieved greater (P=0.01) weight loss than other age groups. Males and females achieved similar weight loss. Caucasian subjects achieved greater (P=0.03) weight loss than other races. Baseline body weight and baseline BMI did not predict degree of weight loss achieved with the diet. These findings may help clinicians to decide which population groups may benefit most from an ADF approach.

Safety of alternate day fasting and effect on disordered eating behaviors.

BACKGROUND: Alternate day fasting (ADF; ad libitum intake "feed day" alternated with 75% restriction "fast day"), is effective for weight loss, but the safety of the diet has been questioned. Accordingly, this study examined occurrences of adverse events and eating disorder symptoms during ADF. FINDINGS: Obese subjects (n = 59) participated in an 8-week ADF protocol where food was provided on the fast day. Body weight decreased (P < 0.0001) by 4.2 ± 0.3%. Some subjects reported constipation (17%), water retention (2%), dizziness (<20%), and general weakness (<15%). Bad breath doubled from baseline (14%) to post-treatment (29%), though not significantly. Depression and binge eating decreased (P < 0.01) with ADF. Purgative behavior and fear of fatness remained unchanged. ADF helped subjects increase (P < 0.01) restrictive eating and improve (P < 0.01) body image perception. CONCLUSIONS: Therefore, ADF produces minimal adverse outcomes, and has either benign or beneficial effects on eating disorder symptoms.

Meal timing during alternate day fasting: Impact on body weight and cardiovascular disease risk in obese adults.

OBJECTIVE: Alternate day fasting (ADF; 24-h feeding/24-h 25% energy intake at lunchtime), is effective for weight loss, but diet tolerability is questionable. Moving the fast day meal to dinnertime, or dividing it into smaller meals, may improve tolerability. Accordingly, this study compared the effects of ADF with three meal times on body weight and heart disease risk. METHODS: Obese subjects (n = 74) were randomized to 1 of 3 groups for 8 weeks: 1) ADF-L: lunch, 2) ADF-D: dinner, or 3) ADF-SM: small meals. RESULTS: Body weight decreased similarly (P < 0.001) in all groups (ADF-L: 3.5 ± 0.4 kg, ADF-D 4.1 ± 0.5 kg, ADF-SM 4.0 ± 0.5 kg). Reductions (P < 0.001) in fat mass and visceral fat were also comparable. Plasma lipids remained unchanged, and low density lipoprotein (LDL) particle size increased (P < 0.05) in all groups (1.3 ± 0.5 Å). Systolic blood pressure decreased (P < 0.05) by ADF-SM only. Fasting glucose, insulin, and HOMA-IR remained unchanged. CONCLUSIONS: Thus, allowing individuals to consume the fast day meal at dinner or small meals produces similar weight loss and cardio-protection as consuming the meal at lunch. This flexibility in meal timing may increase tolerability and long-term adherence to ADF protocols.

Impact of weight regain on metabolic disease risk: a review of human trials.

Dietary restriction interventions are effective for weight loss and reduction of chronic disease risk. Unfortunately, most people tend to regain much of this lost weight within one year after intervention. While some studies suggest that minor degrees of weight regain have no effect on metabolic disease risk parameters, other studies demonstrate a complete reversal in metabolic benefits. In light of these conflicting findings, it is of interest to determine how complete weight maintenance versus mild weight regain affects key risk parameters. These findings would have important clinical implications, as they could help identify a weight regain threshold that could preserve the metabolic benefits of weight loss. Accordingly, this review examined the impact of no weight regain versus mild regain on various metabolic disease risk parameters, including plasma lipids, blood pressure, glucose, and insulin concentrations, in adult subjects.