Intensive Lifestyle Modification Research Articles

Achieving Remission in the Era of Clinical Inertia: What Is Preventing Us from Treating Type 2 Diabetes?

Despite evolution in treatment options and improved understanding of pathophysiology, the treatment of type 2 diabetes remains unsatisfactory. Current management guidelines complicated by clinical inertia have resulted in over half of patients failing to meet glycemic targets. Expert consensus has defined a state of diabetes remission whereby treatment can induce sustained normalization of glucose levels. Evidence suggests that metabolic surgery, intensive lifestyle modification, and pharmacologic approaches are each viable options for achieving remission when implemented early in the disease course. The authors review each of these strategies and include practical considerations to aid in the pursuit of remission.

Perceived benefits and barriers to implementing precision preventive care: Results of a national physician survey.

Polygenic risk scores (PRS) may improve risk-stratification in preventive care. Their clinical implementation will depend on primary care physicians' (PCPs) uptake. We surveyed PCPs in a national physician database about the perceived clinical utility, benefits, and barriers to the use of PRS in preventive care. Among 367 respondents (participation rate 96.3%), mean (SD) age was 54.9 (12.9) years, 137 (37.3%) were female, and mean (SD) time since medical school graduation was 27.2 (13.3) years. Respondents reported greater perceived utility for more clinical action (e.g., earlier or more intensive screening, preventive medications, or lifestyle modification) for patients with high-risk PRS than for delayed or discontinued prevention actions for low-risk patients (p < 0.001). Respondents most often chose out-of-pocket costs (48%), lack of clinical guidelines (24%), and insurance discrimination concerns (22%) as extreme barriers. Latent class analysis identified 3 subclasses of respondents. Skeptics (n = 83, 22.6%) endorsed less agreement with individual clinical utilities, saw patient anxiety and insurance discrimination as significant barriers, and agreed less often that PRS could help patients make better health decisions. Learners (n = 134, 36.5%) and enthusiasts (n = 150, 40.9%) expressed similar levels of agreement that PRS had utility for preventive actions and that PRS could be useful for patient decision-making. Compared with enthusiasts, however, learners perceived greater barriers to the clinical use of PRS. Overall results suggest that PCPs generally endorse using PRS to guide medical decision-making about preventive care, and barriers identified suggest interventions to address their needs and concerns.

Opioid Use After Gastric Bypass, Sleeve Gastrectomy or Intensive Lifestyle Intervention.

To compare opioid use in patients with obesity treated with bariatric surgery versus adults with obesity who underwent intensive lifestyle modification. Previous studies of opioid use after bariatric surgery have been limited by small sample sizes, short follow-up, and lack of control groups. Nationwide matched cohort study including individuals from the Scandinavian Obesity Surgery Registry and the Itrim health database with individuals undergoing structured intensive lifestyle modification, between August 1, 2007 and September 30, 2015. Participants were matched on Body Mass Index, age, sex, education, previous opioid use, diabetes, cardiovascular disease, and psychiatric status (n = 30,359:21,356). Dispensed opioids were retrieved from the Swedish Prescribed Drug Register from 2 years before to up to 8 years after intervention. During the 2-year period before treatment, prevalence of individuals receiving ≥1 opioid prescription was identical in the surgery and lifestyle group. At 3 years, the prevalence of opioid prescriptions was 14.7% versus 8.9% in the surgery and lifestyle groups (mean difference 5.9%, 95% confidence interval 5.3-6.4) and at 8 years 16.9% versus 9.0% (7.9%, 6.8-9.0). The difference in mean daily dose also increased over time and was 3.55 mg in the surgery group versus 1.17 mg in the lifestyle group at 8 years (mean difference [adjusted for baseline dose] 2.30 mg, 95% confidence interval 1.61-2.98). Bariatric surgery was associated with a higher proportion of opioid users and larger total opioid dose, compared to actively treated obese individuals. These trends were especially evident in patients who received additional surgery during follow-up.

The 18-month efficacy of an Intensive LifeStyle Modification Program (ILSM) to reduce type 2 diabetes risk among rural women: a cluster randomized controlled trial

BackgroundMany lifestyle interventions have demonstrated efficacy up to one-year follow-up, yet maintaining improvements at longer-term follow-up is a well-recognized worldwide challenge, especially in underserved areas. The purpose of this study is to compare the 18-month efficacy of an Intensive LifeStyle Modification Program to usual care in reducing the risk for type 2 diabetes (T2D) among women with a history of gestational diabetes mellitus (GDM).MethodsWe conducted a two-arm, cluster randomized controlled trial among women with a history of GDM in China. A total of 16 towns (clusters) in two distinct rural areas in south-central China were randomly selected (8 towns per area) and assigned (1:1) to the intervention (Intensive LifeStyle Modification Program) or control (usual care) group with stratification in the two rural areas. The strategies for maintaining intervention effects were used (including setting recursive goals and providing a supportive environment, etc.) under the guidance of social cognitive theory. The primary outcome was a change in T2D risk; secondary outcomes included glycemic, weight-related, behavioral, and psychological variables. All outcomes were collected at baseline, 6, and 18 months. All participants entered the intention-to-treat analysis. Data were analyzed via generalized estimation equation models (accounting for clusters) at the individual level, with subgroup analysis included in the model.ResultsThe sample included 320 women from 16 clusters (20 women per cluster). At 18 months, the intervention group demonstrated a significant improvement in T2D risk score, fasting blood glucose, body mass index (BMI), waist circumference, intention to eat low glycemic index food, perceived stress, quality of life in psychological and environmental domains, and social support over time (p < 0.05) based on the intention-to-treat analysis set. Subgroup analysis showed a significant interaction effect on T2D risk score in subgroups of different BMI, waist circumference, and blood glucose (p < 0.05).ConclusionsOver 18 months, the Intensive LifeStyle Modification Program reduced T2D risk among rural women with a history of GDM in China. Women who were overweight, had high abdominal adiposity, or had blood glucose intolerance benefited more from this intervention. This program serves as a potential diabetes prevention model for women with a history of GDM in low-resource settings worldwide.Trial registrationRegistered on Chinese Clinical Trial Registry (ChiCTR1800015023) on 1st March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25569

Changes in Plasma Metabolomic Profile Following Bariatric Surgery, Lifestyle Intervention or Diet Restriction-Insights from Human and Rat Studies.

Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans, translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled Würzburg Adipositas Study (WAS) and from RYGB-treated rats (n = 6) as well as body-weight-matched controls (n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI -34.3% (OP) vs. -1.2% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss.

Association of Metformin With the Development of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD. To investigate the association between metformin use and age-related macular degeneration (AMD). The Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for developing diabetes. Participants with retinal imaging at a follow-up visit 16 years posttrial (2017-2019) were included. Analysis took place between October 2019 and May 2022. Participants were randomly distributed between 3 interventional arms: lifestyle, metformin, and placebo. Prevalence of AMD in the treatment arms. Of 1592 participants, 514 (32.3%) were in the lifestyle arm, 549 (34.5%) were in the metformin arm, and 529 (33.2%) were in the placebo arm. All 3 arms were balanced for baseline characteristics including age (mean [SD] age at randomization, 49 [9] years), sex (1128 [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level. AMD was identified in 479 participants (30.1%); 229 (14.4%) had early AMD, 218 (13.7%) had intermediate AMD, and 32 (2.0%) had advanced AMD. There was no significant difference in the presence of AMD between the 3 groups: 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo arm. There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups. Mean duration of metformin use was similar for those with and without AMD (mean [SD], 8.0 [9.3] vs 8.5 [9.3] years; P = .69). In the multivariate models, history of smoking was associated with increased risks of AMD (odds ratio, 1.30; 95% CI, 1.05-1.61; P = .02). These data suggest neither metformin nor lifestyle changes initiated for diabetes prevention were associated with the risk of any AMD, with similar results for AMD severity. Duration of metformin use was also not associated with AMD. This analysis does not address the association of metformin with incidence or progression of AMD.

The therapeutic aspects of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world. NAFLD is encompasses a spectrum of liver manifestations ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. NASH is an aggressive form of NAFLD, associated with an increased risk of liver and non-liver-related mortality. Liver-biopsy remains the gold standard for diagnosis, but the majority of patients liver damage can be diagnosed accurately by noninvasive methods.&#x0D; Early identification and management of patients with intensive dietary and lifestyle modification are essential to prevent the development of advanced liver disease and its complications. Pharmacological therapy should be administered to patients with NASH purposed on the fibrosis inhibition, especially in case of the established predictors of high risk of disease progression (age ˃ 50 years, metabolic syndrome, type 2 diabetes mellitus, or ALT increase), as well as to the patients with active NASH with high inflammatory activity

Adherence to Dietary Recommendation and Its Associated Factors among People with Type 2 Diabetes: A Cross-Sectional Study in Nepal.

Introduction Intensive lifestyle modification including a healthy diet changes the diagnostic status of patient from prediabetes to nondiabetes. In type 2 diabetes, improper eating habits increase insulin resistance. This study is aimed at assessing adherence to the dietary recommendation and its associated factors among people with type 2 diabetes. Methods A cross-sectional descriptive study was conducted among systematically sampled type 2 diabetic patients using interview on Gandaki Medical College Teaching Hospital and Diabetes, Thyroid, and Endocrinology Care Center, Pokhara. The Perceived Dietary Adherence Questionnaire was used to assess dietary adherence. Data was entered in EpiData version 3.1 and analyzed on SPSS version 20. Logistic regression with adjusted odds ratio and the corresponding 95% confidence intervals were used to find out significance of association. Results Among 204 participants, only 15.7% of the participants had good dietary adherence. The mean age and standard deviation were 53.03 ± 11.90 years. Factors such as participants living in single family (AOR 2.7, 95% CI 1.0-7.4), participants who could afford recommended diet (AOR 2.9, 95% CI 1.0-8.3), participants having self-control on food (AOR 4.1, 95% CI 1.2-14.1), participants who were engaged in moderate to heavy physical activities (AOR 3.3, 95% CI 1.2-9.2), and participants who had adherence to medication (AOR 3.5, 95% CI 1.2-10.1) were significantly associated with adherence to dietary recommendation. Conclusions Adherence to dietary recommendation among people with type 2 diabetes was low. Factors such as family type, affordability of recommended diet, self-control on food, physical activity, and medication adherence were significantly associated with adherence to dietary recommendations among people with type 2 diabetes. These factors should be considered by nutrition counselors and clinical decision-makers in patient counseling regarding dietary adherence.

S1329 Nonalcoholic Fatty Liver Disease in Overweight Primary Care Patients: Comparison of Clinical Diagnosis vs Fibrosis-4 and Hepatic Steatosis Index Scores

Introduction: More than two-thirds of US adults are overweight or have obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD). NAFLD is asymptomatic until late in the disease. Therefore, the aim of this study was to assess whether early evidence of NAFLD is being appropriately diagnosed in a primary care patient population. Methods: A retrospective data analysis was performed of overweight (BMI ≥ 23 for Asians or ≥ 25 for other races) patients (age ≥ 18) who had established primary care (defined as ≥ 2 visits in primary care) in a large healthcare system in Minneapolis between 2010 to 2019. Patients with a diagnosis of alcoholic liver disease, and hepatitis B and C virus infections were excluded. The clinical diagnosis of NAFLD was based on ICD-9 and -10 codes (571.8, K75.81, K76.0). Fibrosis 4 (FIB-4) score ≥ 3.25 and hepatic steatosis index (HSI) score ≥ 36 were calculated as markers of hepatic fibrosis and fatty liver disease, respectively. ICD codes were compared to FIB-4 and HSI scores. Results: 373,917 patients met study criteria; 52% were female, 86% white, average BMI at first primary care visit was 31.1 (SD 6.0) and average age was 46.4 (SD 17.3). At the end of the follow-up period in 2019, 6.6% of patients met criteria for hepatic fibrosis by FIB-4 score and 90.4% met criteria for fatty liver disease by HSI score. Among patients who met criteria for hepatic fibrosis by FIB-4 score, only 10.7% had been diagnosed as having NAFLD/NASH by ICD code; among those who met criteria for fatty liver disease by HSI criteria, only 6% had been diagnosed by ICD code (Table). A formal diagnosis of NAFLD/fatty liver/NASH by ICD code had been made in 4.1% of patients. Out of these patients, 97.7% had fatty liver by HSI score and 11.9% had hepatic fibrosis by FIB-4 score. Limitations: For 110,994 patients, a FIB-4 or HSI score could not be calculated. Duration of follow up was maximally nine years. Treatment information was not analyzed. Conclusion: Hepatic fibrosis and fatty liver disease are underdiagnosed in this healthcare system based on abnormal FIB-4 and HSI scores. These results are likely generalizable to other healthcare systems in the US. Given the frequency and reversibility of early NAFLD, primary care providers should have a low threshold to screen using simple labs tests (AST, ALT, platelet count) for fatty liver disease and hepatic fibrosis. Those with abnormal results should pursue intensive lifestyle modification and weight loss treatment. Table 1. - *Data Missing: Data to calculate FIB-4 or HSI score not available Yes Percentage No Data Missing Total (N) FIB-4 score ≥ 3.25 15,696 6.6 221,093 137,128 373,917 Patients with abnormal FIB-4 score who are diagnosed by ICD code 1,686 10.7 14,010 0 15,696 HSI score ≥ 36 241,357 90.4 25,543 107,017 373,917 Patients with abnormal HSI score who are diagnosed by ICD code 14,470 6.0 226,887 0 241,357 NAFLD/Fatty Liver/NASH diagnosis by ICD code 15,324 4.1 358,593 0 373,917 FIB-4 score ≥ 3.25 among patients who are diagnosed with NAFLD/fatty liver/NASH by ICD code 1,686 11.9 12,468 1,170 15,324 HSI score ≥ 36 among patients who are diagnosed with NAFLD/fatty liver/NASH by ICD code 14,470 97.7 346 508 15,324

Combination anti-obesity medications to effectively treat bariatric surgery weight regain at an academic obesity center.

Combination anti-obesity medications (AOMs) to treat postoperative bariatric surgery weight regain have limited data on their use in the clinical setting. Understanding the optimal treatment protocol in this cohort will maximize weight loss outcomes. A retrospective review of bariatric surgery patients (N=44) presenting with weight regain at a single academic multidisciplinary obesity center who were prescribed AOM(s) plus intensive lifestyle modification for 12months. Age: 28-76years old, 93% female, mean weight 110.2±20.3kg, BMI 39.7±7.4kg/m2, presenting 5.2±1.6years post-bariatric surgery [27 (61.4%), 14 (31.8%), and 3 (6.8%) laparoscopic Roux-en-Y gastric bypass (RYGB), laparoscopic vertical sleeve gastrectomy (VSG), and open RYGB, respectively], with 15.1±11.1kg mean weight gain from nadir. Mean weight loss after medical intervention at 3-, 6-, and 12-month time points was 4.4±4.6kg, 7.3±7.0kg, and 10.7±9.2kg, respectively. At 12months, individuals prescribed 3 or more AOMs lost more weight than those prescribed one (-14.5±9.0kg vs. -4.9±5.7kg, p<0.05) irrespective of age, gender, number of comorbidities, initial weight or BMI, type of surgery, or GLP1 use. RYGB patients lost less weight overall (7.4% vs. 14.8% VSG respectively; p<0.05). Combination AOMs may be needed to achieve optimal weight loss results to treat post-operative weight regain.

The role of age on the risk relationship between prediabetes and major morbidities and mortality: analysis of the Hong Kong diabetes surveillance database of 2 million Chinese adults

Intensive lifestyle modification showed variable success in the prevention of major clinical events and mortality among people with prediabetes. We propose that age may partly explain the heterogeneity and that health hazards related to prediabetes are age-specific. We conducted a retrospective analysis of a territory-wide diabetes surveillance dataset from the Hong Kong Hospital Authority between 2000 and 2019. Prediabetes was defined according to the American Diabetes Association criteria. Proportional Cox regression was performed, stratified by baseline age categories (20-39, 40-59, 60-79 and ≥80 years). 1,630,942 individuals were included in the analysis. Compared with normoglycaemia, prediabetes was associated with greater hazards for cardiovascular disease (CVD) and all-cause mortality in most age groups but the effect size attenuated with ascending age (p value for trend <0·05). In the youngest and in the oldest age categories, the respective hazard ratios (95% confidence interval) of prediabetes vs normoglycaemia were 1·79 (1·59, 2·01) and 1·00 (0·95, 1·05) for CVD, and 1·36 (1·20, 1·55) and 0·99 (0·97, 1·02) for all-cause mortality. Similar associations were found for chronic kidney disease, end-stage kidney disease, all-site cancer, all-site infection, subtypes of CVD, and cause-specific mortality. The associations became attenuated but remained after excluding people who later developed diabetes and adjusting for metabolic factors. Similar associations were observed in prediabetes defined by impaired fasting glucose, but not HbA1c. Prediabetes is associated with higher risk of major clinical events, even excluding subsequent development of diabetes and adjusting for metabolic factors. The risk relationships are stronger in young than older people. This study did not receive any specific funding.

The use of metformin for type 2 diabetes prevention: Observational multicenter study from Saudi Arabia.

BackgroundPatients with prediabetes are at higher risk of developing type 2 diabetes. While intensive lifestyle modification is the primary approach to delaying diabetes, metformin has been shown to be effective, especially among patients younger than 60 years and obese (body mass index (BMI) > 35 kg/m2), patients with fasting blood glucose ≥ 6.1 mmol/L or HbA1c ≥ 6%, and women with history of gestational diabetes. Thus, metformin is now recommended as an option for diabetes prevention by the American Diabetes Association (ADA). The use of metformin among patients with prediabetes in Saudi Arabia and their adherence to the guideline's recommendation for the prevention of type 2 diabetes is unknown. This study aimed to identify the prevalence of metformin use among prediabetes patients overall and patients who are more likely to benefit from metformin use per the ADA guidelines.MethodsA retrospective cohort study was conducted encompassing data from three tertiary care hospitals between January 2015 and June 2019. All patients aged 20 to 70 years with prediabetes (HbA1c of 5.7–6.4%) were included, while patients with an established diagnosis of diabetes, creatinine clearance <45 ml/min, using antihyperglycemic medications other than metformin, or on metformin for other indications were excluded. Prediabetes patients who are most likely to benefit from metformin for type 2 diabetes prevention are those younger than 60 years with a BMI ≥ 35 kg/m2, patients with fasting blood glucose ≥ 6.1 mmol/L or HbA1c ≥ 6%, and women with history of gestational diabetes. This study examined the prevalence of metformin use among all patients with prediabetes, as well as patients who would be more likely to benefit from metformin use per the ADA guidelines.ResultsA total of 251 patients were included in this study; 52.2% were female, with a mean age of 47.0 (11.9) years and BMI of 32.3 (6.5) kg/m2, and the median HbA1c at baseline was 5.8% (5.7–6.0). Among the overall sample, 18 patients (7.2%) received metformin for the prevention of type 2 diabetes, 14 of those were from the groups that are more likely to benefit from metformin use per the ADA guidelines (9.9%).ConclusionsAmong individuals with prediabetes in Saudi Arabia, metformin use was very low despite the evidence supporting its safety, convenience, and efficacy. Healthcare providers seemed hesitant to medicalize prediabetes; furthermore, the low use of metformin suggests the existence of several barriers that need to be identified and resolved. Increasing providers' knowledge and awareness regarding screening and management of prediabetes is highly encouraged.

The iHealth-T2D study: a cluster randomised trial for the prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes—a statistical analysis plan

BackgroundSouth Asians are at high risk of type 2 diabetes (T2D). Lifestyle modification is effective at preventing T2D amongst South Asians, but the approaches to screening and intervention are limited by high costs, poor scalability and thus low impact on T2D burden. An intensive family-based lifestyle modification programme for the prevention of T2D was developed. The aim of the iHealth-T2D trial is to compare the effectiveness of this programme with usual care.MethodsThe iHealth-T2D trial is designed as a cluster randomised controlled trial (RCT) conducted at 120 sites across India, Pakistan, Sri Lanka and the UK. A total of 3682 South Asian men and women with age between 40 and 70 years without T2D but at elevated risk for T2D [defined by central obesity (waist circumference ≥ 95 cm in Sri Lanka or ≥ 100 cm in India, Pakistan and the UK) and/or prediabetes (HbA1c ≥ 6.0%)] were included in the trial. Here, we describe in detail the statistical analysis plan (SAP), which was finalised before outcomes were available to the investigators. The primary outcome will be evaluated after 3 years of follow-up after enrolment to the study and is defined as T2D incidence in the intervention arm compared to usual care. Secondary outcomes are evaluated both after 1 and 3 years of follow-up and include biochemical measurements, anthropometric measurements, behavioural components and treatment compliance.DiscussionThe iHealth-T2D trial will provide evidence of whether an intensive family-based lifestyle modification programme for South Asians who are at high risk for T2D is effective in the prevention of T2D. The data from the trial will be analysed according to this pre-specified SAP.Ethics and disseminationThe trial was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations.Trial registrationEudraCT 2016–001,350-18. Registered on 14 April 2016. ClinicalTrials.gov NCT02949739. Registered on 31 October 2016.

Comparison of Sleeve Gastrectomy vs Intensive Lifestyle Modification in Patients With a BMI of 30 to Less Than 35

There is a lack of studies evaluating sleeve gastrectomy compared with intensive lifestyle treatment in patients with class 1 obesity (body mass index [BMI] 30 to <35 [calculated as weight in kilograms divided by height in meters squared]). To compare outcomes and safety of sleeve gastrectomy compared with intensive nonoperative obesity treatment in patients with class 1 obesity. This matched, nationwide cohort study included patients with class 1 obesity who underwent a sleeve gastrectomy or intensive lifestyle treatment between January 1, 2012, and December 31, 2017, and who were registered in the Scandinavian Obesity Surgery Registry or the Itrim health database. Participants with class 1 obesity were matched 1:2 using a propensity score including age, sex, BMI, treatment year, education level, income, cardiovascular disease, and use of antibiotic drugs, antidepressants, and anxiolytics. Sleeve gastrectomy or intensive lifestyle treatment. Outcomes included weight loss after intervention, changes in metabolic comorbidities, substance use disorders, self-harm, and major cardiovascular events retrieved from the National Patient Register, Prescribed Drug Register, and Cause of Death Register as well as the Scandinavian Obesity Surgery Registry and the Itrim health database. Data were analyzed from December 1, 2021 until May 31, 2022. The study included 1216 surgery patients and 2432 lifestyle participants with similar mean (SD) BMI (32.8 [1.4] vs 32.9 [1.4]), mean (SD) age (42.4 [9.7] vs 42.6 [12.7] years), and sex (1091 [89.7%] vs 2191 [90.1%] women). Surgery patients had greater 1-year weight loss compared with controls (22.9 kg vs 11.9 kg; mean difference, 10.7 kg; 95% CI, 10.0-11.5 kg; P < .001). Over a median follow-up of 5.1 years (IQR, 3.9-6.2 years), surgery patients had a lower risk of incident use of diabetes drugs (59.7 vs 100.4 events per 10 000 person-years; hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02) and greater 2-year diabetes drug remission (48.4% vs 22.0%; risk difference 26.4%; 95% CI, 11.7%-41.0%; P < .001), but higher risk for substance use disorder (94 vs 50 events per 10 000 person-years; HR, 1.86; 95% CI, 1.30-2.67; P < .001) and self-harm (45 vs 25 events per 10 000 person-years; HR, 1.81; 95% CI, 1.09-3.01; P = .02). No between-group difference in occurrence of major cardiovascular events was observed (23.4 vs 24.8 events per 10 000 person-years; HR, 0.96; 95% CI, 0.49-1.91; P = .92). In this cohort study, compared with intensive nonoperative obesity treatment, sleeve gastrectomy in patients with class 1 obesity was associated with greater weight loss, diabetes prevention, and diabetes remission but a higher incidence of substance use disorder and self-harm.

Disease Burden, Risk Factors, and Trends of Leukaemia: A Global Analysis.

Leukaemia accounted for approximately 2.5% of all new cancer incidence and 3.1% of cancer-related mortality. The investigation of its risk factors and epidemiologic trends could help describe the geographical distribution and identify high-risk population groups. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of leukaemia by sex, age, and country. We extracted incidence and mortality of leukaemia from GLOBOCAN, CI5, WHO mortality database, NORDCAN, and SEER. We searched the WHO Global Health Observatory data repository for the age-standardised prevalence of lifestyle and metabolic risk factors. We tested the trends by calculating Average Annual Percentage Change (AAPC) from Joinpoint regression. The age-standardized rate of incidence and mortality were 5.4 and 3.3 per 100,000 globally. The incidence and mortality of leukaemia were associated with Human Development Index, Gross Domestics Products per capita, prevalence of smoking, physical activity, overweight, obesity, and hypercholesterolaemia at the country level. Overall, more countries were showing decreasing trends than increasing trends in incidence and mortality. However, an increasing trend of leukaemia incidence was found in Germany, Korea, Japan, Canada and the United Kingdom (AAPC, 2.32-0.98) while its mortality increased in the Philippines, Ecuador, Belarus, and Thailand (AAPC, 2.49-1.23). There was a decreasing trend of leukaemia for the past decade while an increase in incidence and mortality was observed in some populations. More intensive lifestyle modifications should be implemented to control the increasing trends of leukaemia in regions with these trends. Future studies may explore the reasons behind these epidemiological transitions.

Global prevalence of prediabetes in children and adolescents: A systematic review and meta-analysis.

BackgroundPrediabetes is a pivotal risk factor for developing diabetes. This meta‐analysis was performed to assess the global prevalence of childhood prediabetes.MethodsA systematic search was conducted for studies of prediabetes prevalence in the general pediatric population from inception until December 2021. Random‐effects meta‐analysis was used to combine the data. Variations in the prevalence estimates in different subgroups (age group, sex, setting, investigation period, body mass index [BMI] group, family history of diabetes, diagnosis criteria, World Health Organization [WHO] and World Bank [WB] regions) were examined by subgroup meta‐analysis.ResultsA total of 48 studies were included in the meta‐analysis. The pooled prevalence was 8.84% (95% CI, 6.74%‐10.95%) for prediabetes in childhood. Subgroup meta‐analyses showed that the prevalence was higher in males than females (8.98% vs 8.74%, P < .01), in older compared to younger children (7.56% vs. 2.51%, p < 0.01), in urban compared to rural areas (6.78% vs. 2.47, p < 0.01), and higher in children with a family history of diabetes than in those without such a history (7.59% vs. 6.80%, p < 0.01). We observed an upward trend in prediabetes prevalence from 0.93% to 10.66% over past decades (p < 0.01). The pooled prevalence increased from 7.64% to 14.27% with increased BMI (p < 0.01). Pooled prevalence was the lowest for criterion A among different diagnosis criteria (p < 0.01). For WHO and WB regions, the European Region and high‐income countries yielded the lowest pooled prevalence (p < 0.01).ConclusionsElevated prediabetes prevalence in childhood reaches an alarming level. Intensive lifestyle modification is needed to improve the prediabetes epidemic.

The 6-Month Efficacy of an Intensive Lifestyle Modification Program on Type 2 Diabetes Risk Among Rural Women with Prior Gestational Diabetes Mellitus: a Cluster Randomized Controlled Trial

This study aimed to evaluate the efficacy of an intensive lifestyle modification program tailored to rural Chinese women with prior gestational diabetes mellitus compared with usual care. In a cluster randomized controlled trial, 16 towns (clusters) in two distinct rural areas in China were randomly selected (8 towns per district); and 320 women with prior gestational diabetes mellitus were recruited from these towns. With stratification for the two study districts, eight towns (160 women) were randomly assigned to the intervention group of a tailored intensive lifestyle modification program and 8 towns (160 women) to the control group. Process measures were collected on attendance, engagement, fidelity, and satisfaction. Primary efficacy outcomes included glycemic and weight-related outcomes, while secondary efficacy outcomes were behavioral outcomes and type 2 diabetes risk score, which were collected at baseline, 3-month, and 6-month follow-up. Generalized estimation equations were used to analyze the data. High attendance (72% of sessions), engagement (67% of interactive activities and group discussions), fidelity (98%), and satisfaction (92%) with the tailored intensive lifestyle modification program were achieved. There were significant reductions in fasting blood glucose, oral glucose tolerance test 2 h, waist circumference, and type 2 diabetes risk score of participants in the intervention group compared to the control group (p < .05). There was no significant intervention effect on body mass index or behavioral outcomes (p > .05). In this study, we demonstrate the successful efficacy of an Intensive Lifestyle Modification Program in reducing type 2 diabetes risk among younger women with prior gestational diabetes mellitus. This tailored program delivered by local healthcare providers is a promising approach for diabetes prevention in rural China, reducing health disparities in rural communities about diabetes prevention. Registered in the Chinese Clinical Trial Registry (ChiCTR2000037956) on 3rd Jan 2018.

Metabolically healthy obesity: Inflammatory biomarkers and adipokines in elderly population.

Obesity is linked to elevated levels of inflammatory serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa). Adiponectin and resistin are adipokines related to obesity. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of fat cells as well as systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, by following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers and adipokine profile in a Metabolically Healthy Obese (MHO) elderly population from Malaga (Andalusia, Spain). Subjects aged ≥65 years (65 to 87 years old) with obesity (BMI ≥30 kg/m2) were included in this study if they met ≤1 of the following criteria: systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥ 85 mmHg; triglycerides ≥150 mg/dL; HDL-C <40mg/dL in men and <50mg/dL women; and fasting blood glucose ≥100mg/dL. Selected subjects underwent a personalized intensive lifestyle modification. Anthropometric measurements, PA, MedDiet adherence, analytical parameters, and inflammatory biomarkers were analyzed after 12 months of intervention. 166 MHO elderly subjects, 40 (24.1%) male and 126 (75.9%) female (p < 0.0001), aged 71.7±5.2 years old (65 to 87 years old) were included in the study. After 12 months of intervention, only the waist circumference was significantly reduced in all the population (-2.5 cm, p<0.0001), although weight and BMI were maintained. MedDiet adherence increased significantly (p<0.001), but all intensity levels of PA decreased significantly (p<0.001). Concerning inflammatory biomarkers, only TNFa serum increased their levels after the intervention (p<0.001). Regarding the adipokine profile, adiponectin concentrations experienced a significant increment (p<0.001); besides, resistin concentrations decreased significantly (p<0.001). In this sense, only TNFa, adiponectin, and resistin correlated with PA. Adiponectin also correlates with insulin, triglycerides and HDL-c in baseline conditions and after 12 months of intervention; CRP, IL-6, TNFa, adiponectin, and resistin concentrations correlated with anthropometric parameters and some intensities of PA. In addition, adiponectin levels correlates with insulin, triglycerides and HDL-c. In baseline conditions, resistin levels correlated positively with TNFa (p = 0.01) and CRP (p<0.0001) levels. TNFa and IL-6 correlated positively with CRP (p = 0.03 and p<0.0001, respectively). After 12 months of intervention, only IL-6 correlated positively with CRP (p = 0.006). In addition, adipokines levels correlated positively during the process of lifestyle modification. However, during this process, only IL-6 correlated positively with itself (p<0.0001) and with CRP (p = 0.03). Healthy aging is a multifactorial biological process in which lifestyle is essential. The presence of obesity in elderly metabolically healthy population is not a problem necessarily. Elderly MHO population who eat a MedDiet and practice regularly PA are capable to modulate their production of inflammatory cytokines (CRP, IL-6, TNFa) and adipokines profile (adiponectin, resistin), preventing other metabolic disorders.

Type 2 Diabetes Remission with Significant Weight Loss: Definition and Evidence-Based Interventions.

Type 2 diabetes (T2D) has long been regarded as an incurable and chronic disease according to conventional management methods. Clinical and pathophysiological studies on the natural course of T2D have shown that blood glucose control worsens with an increase in the number of required anti-hyperglycemic agents, as β-cell function progressively declines over time. However, recent studies have shown remission of T2D after metabolic surgery, intensive lifestyle modification, or medications, raising the possibility that β-cell function may be preserved or the decline in β-cell function may even be reversible. The World Health Organization as well as the American Diabetes Association and the European Association for the Study of Diabetes recognize remission as an appropriate management aim. In the light of the state of evidence for T2D reversal, physicians need to be educated on treatment options to achieve T2D remission so that they can actively play a part in counseling patients who may wish to explore these approaches to their disease. This review will introduce each of these approaches, summarizing their beneficial effects, supporting evidence, degree of sustainability, and challenges to be addressed in the future.

Worldwide Burden, Risk Factors, and Temporal Trends of Ovarian Cancer: A Global Study.

Simple SummaryOvarian cancer was the third most common gynecological cancer globally in 2020. Ovarian carcinoma is the most common type of ovarian cancer, comprising over 90% of all ovarian cancer cases. The risk of ovarian cancer increases in females with age, along with having a family history, having a family cancer syndrome, and breast cancer susceptibility gene (BRCA) mutations. Investigation of the latest disease burden, risk factors, and temporal trends of ovarian cancer is important for the reduction of its associated mortality globally. The global incidence and mortality rates of ovarian cancer for 185 countries in 2020 were retrieved from the Global Cancer Observatory (GLOBOCAN) database established by the International Agency for Research on Cancer (IARC, WHO, Lyon, France). The incidence of ovarian cancer has been increasing substantially among younger females, probably caused by the increasing prevalence of obesity, metabolic syndrome, estrogen exposure and nulliparity.This study aimed to investigate the most updated worldwide incidence and mortality, risk factors, and epidemiologic trend of ovarian cancer in different countries, regions, and age groups. The Global Cancer Observatory database was used for incidence and mortality rates of ovarian cancer in 2020. Data from Cancer Incidence in Five Continents and the WHO mortality database was accessed for trend analysis. Age-standardized rates (ASRs, per 100,000 persons) were calculated for incidence and mortality. The 10-year annual average percent change (AAPC) was estimated by Joinpoint regression analysis. There was an overall decreasing trend of ovarian cancer, yet its burden has been increasing in lower-income countries and among younger females in some countries. Intensive lifestyle modifications are warranted, especially for the populations at high risk for ovarian cancer, including smoking cessation, alcohol use reduction, physical activity, weight control, and treatment of metabolic diseases.