Pre-diabetes comprises diverse subphenotypes linked to varying complications, type 2 diabetes, and mortality outcomes. This study aimed to explore these outcomes across different pre-diabetes subphenotypes.

The dataset included adults without type 2 diabetes with baseline HbA1c and fasting plasma glucose (FPG) measurements from Siriraj Hospital, Bangkok, Thailand. The participants were classified into six subphenotypes via the k-means clustering method on the basis of age, body mass index, FPG, HbA1c, high-density lipoprotein cholesterol and alanine aminotransferase levels. The incidences of type 2 diabetes, long-term vascular complications and mortality were compared among subphenotypes over a median follow-up of 8.8 years, employing Kaplan-Meier curves and Cox regression analysis adjusted for sex, statin use and hypertension status.

Among the 4915 participants (mean age 60.1±10.1 years; 54.6% female), six clusters emerged: cluster 1, low risk (n=650; 13.2%); cluster 2, mild dysglycemia elderly (n=791; 16.1%); cluster 3, severe dysglycemia obese (n=1127; 22.9%); cluster 4, mild dysglycemia obese (n=963; 19.7%); cluster 5, severe dysmetabolic obese (n=337; 6.9%); and cluster 6, severe dysglycemia elderly (n=1042; 21.2%). Clusters were classified into diabetes risk subgroups: low risk (clusters 1 and 4) and high risk (clusters 3 and 5). Cluster 6 exhibited the highest risk, with significantly increased incidences of macrovascular complications (adjusted HR 2.22, 1.51-3.27) and type 2 diabetes (1.73, 1.42-2.12). In contrast, cluster 4 demonstrated the lowest risk, with significantly decreased incidences of new chronic kidney disease (0.65, 0.44-0.96), microvascular complications (0.62, 0.43-0.89) and mortality (0.25, 0.10-0.63).

Our pre-diabetes phenotyping approach effectively provides valuable insights into the risk of type 2 diabetes, vascular complications and mortality in individuals with pre-diabetes. Those with high-risk phenotypes should be prioritized for type 2 diabetes and cardiovascular interventions to mitigate risks.

Diabetes mellitus (DM) is a growing public health concern globally, particularly in Saudi Arabia, where increasing prevalence is associated with significant morbidity. This study aimed to assess the prevalence of diabetes-related complications among patients in Riyadh and examine the impact of sociodemographic factors, comorbidities, and lifestyle habits on these complications. A cross-sectional study was conducted with 980 diabetic patients attending health centers in Riyadh from March to April 2023. Data were collected via a validated bilingual questionnaire that captured sociodemographic information, diabetes-related variables, comorbid conditions, lifestyle habits, and complications. Statistical analyses, including descriptive statistics, chi-square tests, and binary regression, were performed via SPSS to identify significant associations. A p-value less than 0.05 was considered significant for all comparisons. Among the participants (980), 38% (378) reported diabetes-related complications, primarily neuropathy (30%), retinopathy (25%), and cardiovascular diseases (20%). Complications were significantly associated with older age (p < 0.001) and longer diabetes duration (more than 5 years; p < 0.001). Individuals with hypertension, hyperlipidemia, heart disease, kidney disease, and obesity had significantly higher complication rates than those without these conditions (p < 0.05). The most pronounced association was observed in participants with heart disease (85% vs. 15%; RR = 1.506), highlighting the need for better management of these comorbidities. Consuming fruits and vegetables, milk, and regular exercise were inversely associated with the risk of complications (p < 0.05). Conversely, sugary drinks, white bread, sheesha/vaping, and inadequate sleep were linked to increased risk (p < 0.05), highlighting the protective role of healthy dietary and lifestyle habits. This study highlights the impact of sociodemographic factors and lifestyle choices-such as age, education, family history, comorbidities, and poor diet-on diabetes complications. While early detection and lifestyle interventions are vital, a cautious approach is needed when applying these findings to other regions, given differences in socioeconomic circumstances.

This study seeks to compare the effectiveness of Semaglutide compared to Liraglutide, Dulaglutide, or Tirzepatide. Additionally, it aims to investigate the implications of transitioning from Dulaglutide or Liraglutide to Semaglutide.

We searched PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science (ClinicalTrials.gov for unpublished records) from their inception to 5 February 2025, including observational cohort studies and randomized controlled trials. Analyses were conducted using Review Manager (RevMan) version 5.4.1 and STATA 17.

The meta-analysis comprised 16 studies and 5,997 patients. Semaglutide significantly reduced hemoglobin A1c (HbA1c) levels compared to Liraglutide (0.56; 95% CI: 0.19-0.94; p < 0.001). However, no significant differences were observed between Semaglutide and Liraglutide in terms of fasting blood sugar (FBS), body mass index (BMI), and weight change. In comparison to Dulaglutide, Semaglutide displayed superior efficacy in reducing HbA1c levels (3.72; 95% CI: 0.02-7.41; p = 0.05) and FBS (2.66; 95% CI: 0.26-5.07; p = 0.03). However, no significant differences were found in weight and BMI change. Tirzepatide exhibited a notable advantage over Semaglutide in reducing HbA1c levels (-0.45; 95% CI: -0.88 to -0.02; p = 0.04). However, no clear superiority was observed for weight and FBS change. Transitions from Liraglutide to Semaglutide did not significantly impact HbA1c levels. However, weight loss (2.48; 95% CI: 0.45-4.51; p = 0.02) and reduced FBS levels (10.76; 95% CI: 0.55-20; p = 0.04) were observed. Transitioning from Dulaglutide to Semaglutide did not significantly affect HbA1c levels and weight change.

While the precise source of heterogeneity remains elusive across most studies, analyses consistently demonstrate Semaglutide's superior efficacy compared to Liraglutide in reducing both HbA1c levels and weight. Moreover, it presents advantages over Dulaglutide, specifically in lowering FBS levels. However, Tirzepatide surpasses Semaglutide in its efficacy for reducing HbA1c levels.

We investigated the association between younger-onset type 2 diabetes, duration of diabetes, and cancer risk based on data from the Da Qing Diabetes Prevention Outcome Study (DQDPOS).

The analysis recruited 620 younger-onset (age≤50 years) and 649 older-onset (age>50 years) patients with type 2 diabetes, and 310 younger non-diabetes controls (age≤50 years). Multiple regression analysis was used to test the influence of younger-onset diabetes and duration of diabetes on the long-term risk of cancer.

The annual incidence of all cancer among the non-diabetes, younger-, and older-onset type 2 diabetes was significantly different (3.7, 5.5, and 4.0/1000 person-years, respectively). The standard Cox analysis revealed that the patients with younger-onset diabetes had a significantly higher risk of cancer than those with older-onset diabetes (hazard ratio [HR]:1.81; 95% confidence interval [CI]:1.20-2.73) and younger non-diabetic controls (HR:2.43; 95% CI:1.34-4.41) after adjustment for diabetes duration and other confounders. Stepwise general linear regression model analysis revealed that a longer diabetes-free time was associated with longer lifetime cancer-free years (partial R2 = 0.36, p < 0.001), in addition to the non-modifiable predictor duration of diabetes.

Younger-onset type 2 diabetes was significantly associated with an increased risk of cancer beyond the influence of diabetes duration.

The extensive use of smokeless tobacco and the worldwide occurrence of diabetes mellitus (DM) poses significant public health obstacles. A comprehensive review of the literature was undertaken to assess epidemiological research, clinical trials, and meta-analyses that examine the link between smokeless tobacco use and DM. The key results indicate that the biological constituents of smokeless tobacco may interfere with the process of glucose metabolism and lead to an increase in insulin resistance. An association between consumption levels and diabetes risk is evident, with higher levels of usage being positively correlated with an increased chance of developing diabetes. Smokeless tobacco usage is identified as a significant risk factor for DM. This highlights the need to implement focused public health initiatives and policies aimed at decreasing the usage of smokeless tobacco and its influence on the incidence of diabetes. Future research should prioritize elucidating the processes behind this correlation and developing efficacious preventative methods to mitigate the worldwide burden of diabetes.

Obesity is a chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes.

We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods.

At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified.

Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

We are at the start of an exciting new era of very effective pharmacotherapy for patients with obesity, with the latest generation of drugs approaching the efficacy of obesity surgery. Clinical trials of obesity drugs tend to emphasise the importance of participation in some form of structured lifestyle intervention for all trial participants. This usually consists of advice to reduce calorie intake and increase moderate to vigorous physical activity. There is strong evidence that structured lifestyle modification programmes improve health in patients with obesity and related disorders. However, there is no specific evidence that they improve the response to obesity medications. This is because of the way that drug trials for patients with obesity have traditionally been designed, with participants in the active drug treatment group being compared to participants on placebo drug treatment, but with both groups always receiving the same structured lifestyle intervention. While this approach is entirely reasonable, it makes it impossible to draw any inferences about the efficacy of structured lifestyle modification to augment the response to drug therapy. Given this genuine equipoise, a critical step in ensuring that our treatment of patients with obesity is robustly evidence-based is to determine whether "drug plus lifestyle" offer any advantage over "drug plus placebo" in large, well-designed and adequately powered clinical trials. We also need to determine the cost-effectiveness of these programmes.

Prediabetes is a highly prevalent and increasingly common condition affecting a significant proportion of the global population. The heterogeneous nature of prediabetes presents a challenge in identifying individuals who particularly benefit from lifestyle or other therapeutic interventions aiming at preventing type 2 diabetes (T2D) and associated comorbidities. The phenotypic characteristics of individuals at risk for diabetes are associated with both specific risk profiles for progression and a differential potential to facilitate prediabetes remission and reduce the risk of future T2D. This review examines the current definition and global prevalence of prediabetes and evaluates the potential of prediabetes remission to reduce the alarming increase in the global burden of T2D.

Inflammaging, a state of chronic, progressive low-grade inflammation during aging, is associated with several adverse clinical outcomes, including frailty, disability, and death. Chronic inflammation is a hallmark of aging and is linked to the pathogenesis of many aging-related diseases. Anti-inflammatory therapies are also increasingly being studied as potential anti-aging treatments, and clinical trials have shown benefits in selected aging-related diseases. Despite promising advances, significant gaps remain in defining, measuring, treating, and integrating inflammaging into clinical geroscience research. The Clin-STAR Inflammation Research Interest Group was formed by a group of transdisciplinary clinician-scientists with the goal of advancing inflammaging-related clinical research and improving patient-centered care for older adults. Here, we integrate insights from nine medical subspecialties to illustrate the widespread impact of inflammaging on diseases linked to aging, highlighting the extensive opportunities for targeted interventions. We then propose a transdisciplinary approach to enhance understanding and treatment of inflammaging that aims to improve comprehensive care for our aging patients.

Lifestyle scores have emerged as a practical tool to assess the risk of major non-communicable diseases (NCDs). However, most of them are primarily developed for single NCDs. Given the common risk factors for some of the major NCDs, we conducted a systematic review to evaluate the potential of existing lifestyle scores in predicting the risk of multiple NCD-related endpoints.

PubMed, Web of Science, the Cochrane Library, Embase, and Google Scholar were searched from inception to October 2024. We included observational studies assessing the association between lifestyle scores and the risk of morbidity or mortality of multiple NCDs, including type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer.

Of 16,138 unique records identified by the search, 56 eligible studies were included in the systematic review, consisting of 48 cohort studies, 5 case-control studies, 2 case-cohort studies, and 1 cross-sectional study from 16 countries. 15 lifestyle scores were identified to estimate the risk of 32 NCDs, with HLIBMI being the most reported score (14/56, 25.0%). Moderate to strong associations were found between the 15 lifestyle scores and the risk of developing and dying from multiple types of cancers, CVDs, and T2D. Healthy lifestyle scores including additional risk factors (i.e., blood pressure, blood glucose, and waist circumference) aside from major risk factors (i.e., Body Mass Index (BMI), smoking, and diet) seemed to have a stronger ability to estimate NCDs risk than scores including only major risk factors.

All 15 simple lifestyle scores were shown to estimate the risk of multiple NCDs endpoints, although some scores were originally developed to estimate the risk of single diseases only. Therefore, further research is required to identify which lifestyle score is most effective for assessing the risk of multiple NCD-related endpoints in a head-to-head comparison.

Previous studies have established that coronary artery calcification (CAC) is a robust predictor of adverse cardiovascular events.

To examine the association between levels of glycated hemoglobin (HbA1c), an indicator of long-term blood glucose levels, and CAC in middle-aged and elderly Chinese populations undergoing routine health screenings.

A cross-sectional study was conducted on 8,955 Chinese adults over 40 years of age who underwent physical examinations in the Department of Health Medicine at our hospital from January 2022 to July 2023. The odds ratios (ORs) of CAC in relation to HbA1c were determined using multiple logistic regression analysis, both as a continuous and categorical variable. Furthermore, dose-response relationships between HbA1c levels and CAC were visualized using restricted cubic spline models.

Compared to the group with HbA1c lower than 5.7%, individuals in the groups with HbA1c of 5.7% to 6.4% and ≥ 6.5% exhibited an elevated prevalence of CAC (P for trend < 0.0001). Multivariable logistic regression showed that each 1% increase in HbA1c was associated with a 24% increased risk of CAC (OR = 1.24, 95% CI: 1.03-1.48, P = 0.02). Compared with the group with HbA1c lower than 5.7%, the groups with HbA1c at 5.7% - 6.4% and HbA1c ≥ 6.5% were associated with a 28% (OR = 1.28, 95% CI: 1.07 - 1.52) and 116% (OR = 2.16, 95% CI: 1.48 - 3.16) (P for trend < 0.0001) increased risk of CAC, respectively. Restricted cubic spline analyses showed a non-linear association between HbA1c and CAC (P for nonlinearity < 0.0001). At higher levels of HbA1c exposure (> 5.7%), the exposure dose-response curves appeared upward-sloping. Subgroup analyses showed that the association between HbA1c and CAC was more pronounced in those aged less than 60 years, with normal weight and blood pressure less than 135/85 mmHg, although none of the interactions between HbA1c and subgroups were statistically significant.

This study indicated that higher HbA1c levels are associated with a greater likelihood of CAC in the middle-aged and elderly Chinese checkup population.

Life expectancy is reduced in people with obesity and is further reduced in those with concomitant type 2 diabetes. The aim of the study was to assess whether a 2-year delay in diabetes development influences life expectancy in people with obesity.

Participants from the Swedish Obese Subjects study without diabetes at baseline and known diabetes status at the 2-year follow-up were included: bariatric surgery (n = 1471) and usual obesity care (n = 1392). Median follow-up was 26.1 years (interquartile range: 22.7-28.7 years). The Swedish Cause of Death Register, case sheets and autopsy reports were assessed to determine the direct cause of death. Analyses were adjusted for preselected risk factors: inclusion year, sex, baseline age, body mass index (BMI) and smoking.

Across both study arms, 146 participants were newly diagnosed with type 2 diabetes at the 2-year examination, whereas 2717 remained diabetes-free. Most participants diagnosed with diabetes (n = 140) were from the usual care control group. During the follow-up, there were 18.3 deaths per 1000 person-years (95% confidence interval [CI]:14.1-23.9) in the group with diagnosed diabetes at the 2-year follow-up and 10.9 deaths per 1000 person-years (95% CI:10.2-11.8) in the group that remained diabetes-free (adjusted hazard ratio [HRadj] 1.60, 95% CI: 1.19-2.15, p = 0.002). The adjusted median life expectancy in the diabetes group was 3.7 years (95% CI: 1.4-6.0, p = 0.002) shorter than in the diabetes-free group. Specifically, cardiovascular mortality was higher in the group with diabetes (adj sub-hazard ratio [sub-HR] 1.74 [95% CI: 1.09-2.77], p = 0.021).

A 2-year delay in diabetes development may be linked to increased life expectancy, possibly due to a reduction in cardiovascular mortality. Future studies should confirm these findings.

The multicomponent Remission Evaluation of Medical Interventions in T2D (REMIT) program has shown reduction of hazard of diabetes relapse by 34-43%, but could benefit from improved ability to scale, spread, and sustain it. This study explored, at the conceptualization phase, patient and health coach perspectives on the acceptability, adoption, feasibility, and appropriateness of a digital REMIT adaptation (diabetes technology enabled coaching (DTEC)). Twelve semi-structured interviews were conducted with patients (n = 6) and health coaches (n = 6) to explore their experiences with the REMIT study, opportunities for virtualisation, and a cognitive walkthrough of solution concepts. Transcripts were analyzed both inductively and deductively to allow for organic themes to emerge and to position these themes around the constructs of acceptability, adoption, feasibility, and appropriateness while allowing new codes to emerge for discussion. Participants saw value in DTEC as: an opportunity to facilitate and extend REMIT support; a convenient, efficient, and scalable concept (acceptability); having potential to motivate through connecting behaviours to outcomes (adoption); an opportunity for lower-effort demands for sustained use (feasibility). Participants also highlighted important considerations to ensure DTEC could provide compassionate insights and support automated data entry (appropriateness). Several considerations regarding equitable access were raised and warrant further consideration including: provision of technology, training to support technology literacy, and the opportunity for DTEC to support and improve health literacy. As such, DTEC may act as a moderator that can enhance or diminish access which affects who can benefit. Provided equity considerations are addressed, DTEC has the potential to address previous shortcomings of the conventional REMIT program.

Whether improvements in cardiovascular health (CVH) in midlife mitigate cardiovascular disease (CVD) risk in patients with diabetes remains underexplored.

The aim of the study was to examine the relationships between changes in CVH during midlife and subsequent risks of CVD events and all-cause mortality among individuals with and without diabetes.

The study utilized data from the Atherosclerosis Risk in Communities Study. CVH data were collected during visits 1 and 3 and the median follow-up was 23 years. CVH was based on ideal Life's Simple 7 metrics and categorized as low (0-2 metrics), moderate (3 or 4 metrics), and favorable CVH (5-7 metrics). Cox proportional hazards regression models were used to determine the association between changes in CVH and CVD outcomes.

Among the final sample (N = 8,741), 806 had diabetes (9.2%). Of those with diabetes, 62.3% had low CVH at both visits, 12.0% maintained moderate CVH, 15.0% showed improvement, and 10.3% experienced a decline in CVH. Only 0.4% maintained favorable CVH. Those with improved CVH had lower CVD event risks (HR: 0.69; 95% CI: 0.50-0.93), as did those who maintained moderate CVH (HR: 0.68; 95% CI: 0.50-0.94) or shifted from moderate to low CVH (HR: 0.60; 95% CI: 0.41-0.88). Similar patterns were observed for all-cause mortality. In comparison to participants without diabetes who maintained a favorable CVH trajectory at midlife, those with diabetes consistently displayed higher risks of CVD events and mortality, regardless of their CVH trajectory.

For patients with diabetes, achieving or maintaining ideal CVH levels at midlife may help improve outcome; however, CVD risk is not completely mitigated by favorable CVH trajectories.

To explore the effects of lifestyle interventions on the prevention of type 2 diabetes (T2D) and reversion to normoglycemia by prediabetes phenotype.

We searched MEDLINE, Embase, and the Cochrane Library for randomized controlled trials (RCTs) that evaluated the effects of lifestyle interventions in adults with prediabetes for a minimum duration of one year. Two reviewers independently screened articles, extracted data, and performed quality assessment. The relative effects were analyzed using a random-effects model, subgroup analysis was employed to explore the potential effects among subpopulations.

A total of 31 RCTs involving 23684 participants were analyzed. Compared with usual care, lifestyle interventions reduced the incident T2D by 41 % (RR 0.59 [95 % CI 0.52-0.68]) and increased the probability of reverting to normoglycemia by 44 % (RR 1.44 [95 % CI 1.15-1.81]) in adults with prediabetes. No significant difference was observed between the impaired fasting glucose (IFG5.6)/impaired glucose tolerance (IGT) and IFG6.1/IGT (P = 0.752). IGT + IFG benefited more than isolated IGT in prevention of T2D (RRIGT + IFG 0.47 [95 % CI 0.41-0.55]; RRisolatedIGT 0.77 [95 % CI 0.64-0.93]), whereas no benefit was found in isolated IFG (RR 0.77 [95 % CI 0.51-1.16]) or elevated HbA1c (RR 0.89 [95 % CI 0.74-1.07]).

Lifestyle intervention could help prevent T2D and revert to normoglycemia in adults with prediabetes, with significant benefit in people with IGT but not in those with isolated IFG or elevated HbA1c.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

Sedentary behaviour (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific SB (CS-SB) are most detrimental for CMD risk, the lifestyle behaviours that cluster with CS-SBs and the socioecological predictors of CS-SB.

This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals. Two laboratory visits will occur, spaced 12 months apart, where a novel composite CMD risk score (eg, arterial stiffness, metabolic and inflammatory biomarkers, heart rate variability and body fat distribution) will be calculated, and questionnaires to measure lifestyle behaviours and levels of the socioecological model will be administered. After each laboratory visit, total SB (activPAL) and CS-SB (television, transportation, academic/occupational, leisure computer, 'other'; ecological momentary assessment) will be measured across 7 days.

This study has received full ethical approval, and participants provide written informed consent. Our hypothesis is that certain CS-SB will show stronger associations with CMD risk, compared with total sedentary behaviour (T-SB), even after accounting for coexisting lifestyle behaviours. We also expect a range of intra-individual, inter-individual and physical environmental socioecological factors will predict CS-SB. Findings addressing both the primary and any secondary research aims will be submitted for publication in a high-impact peer-reviewed journal.

Cardiorespiratory fitness (CRF) has been increasingly recognized in recent years as an important predictor of risk for adverse outcomes in numerous chronic conditions. In fact, a growing body of epidemiological and clinical evidence demonstrates that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, hyperlipidemia, and type 2 diabetes. Moreover, adding CRF to these traditional risk factors significantly improves the reclassification of risk for adverse outcomes. The utility of CRF now extends far beyond all-cause and cardiovascular mortality to include the prevention and treatment of numerous other chronic conditions; CRF has been demonstrated to have a mitigating influence in as many as 40 such conditions. Herein we discuss the impact of CRF in the prevention of chronic disease in both adults and children. This discussion includes recent data on interactions between CRF and aging, obesity, statin use, incidence of diabetes, and the impact of CRF and physical activity patterns in adolescents including mental health, scholastic achievement, and cardiometabolic health. Finally, we discuss how CRF, as an essential vital sign, can be implemented in clinical practice.

Unhealthy lifestyle behaviors such as poor diets and physical inactivity account for most of the cardiometabolic disease (CMD) burden, including type 2 diabetes and cardiovascular diseases. Much of this burden is mediated by the effects of unhealthy lifestyle behaviors on overweight and obesity, and disproportionally impacts certain population groups-including those from disadvantaged socioeconomic backgrounds. Combined lifestyle interventions (CLIs), which target multiple behaviors, have the potential to prevent CMD, but their implementation, reach and effectiveness in routine practice are often limited. Considering the increasing availability of effective but expensive pharmaceutical options for weight loss, we review the short-term and long-term benefits and cost-effectiveness of CLIs on overweight, obesity and associated CMDs, in controlled studies and in routine care. Against the backdrop of changing living environments, we discuss the effective components of CLIs and the many challenges associated with implementing them. Finally, we outline future directions for research and implications for policy and practice to improve lifestyle behaviors and cardiometabolic health at the population level.

The Finnish multidomain lifestyle intervention study to prevent cognitive impairment and disability (FINGER, N = 1259), a randomised controlled trial had beneficial effects on morbidity in older people, but to what extent such a lifestyle intervention may affect the use of health care services and their costs especially in long term are unknown.

This study investigated the effect of a two-year FINGER multidomain intervention on health care service use during the 8-year follow-up. The costs of service use were also evaluated.

Health care service use obtained from national health care registers (days of inpatient hospital stay and long-term care, number of visits to emergency services, hospital as outpatient, home care, primary care physician and primary care nurse) was analysed among participants of the FINGER. Trial targeted community-dwelling people aged 60-77 years at risk for cognitive impairment, who were randomly allocated to the multidomain intervention or control group. Costs were evaluated as the mean costs of services used.

There were no significant differences in total health care costs between the intervention and control groups. The participants in the intervention group, however, had a lower use of the hospital inpatient care (RR 0.73, 95% CI 0.54-1.00) and emergency services (RR 0.83, 95% CI 0.70-0.97) than those in the control group. Hospital inpatient care was lower especially among men. The use of other types of health care services did not differ between the groups. The costs of health care service use without including long-term care were lower in the intervention group (RR 0.81, 95% CI 0.68-0.99).

The FINGER intervention has a potential to reduce the need for the inpatient hospital care and emergency visits and associated costs, especially among men.

Type 2 diabetes (T2D) is a disease characterized by heterogeneously progressive loss of islet β cell insulin secretion usually occurring after the presence of insulin resistance (IR) and it is one component of metabolic syndrome (MS), and we named it metabolic dysfunction syndrome (MDS). The pathogenesis of T2D is not fully understood, with IR and β cell dysfunction playing central roles in its pathophysiology. Dyslipidemia, hyperglycemia, along with other metabolic disorders, results in IR and/or islet β cell dysfunction via some shared pathways, such as inflammation, endoplasmic reticulum stress (ERS), oxidative stress, and ectopic lipid deposition. There is currently no cure for T2D, but it can be prevented or in remission by lifestyle intervention and/or some medication. If prevention fails, holistic and personalized management should be taken as soon as possible through timely detection and diagnosis, considering target organ protection, comorbidities, treatment goals, and other factors in reality. T2D is often accompanied by other components of MDS, such as preobesity/obesity, metabolic dysfunction associated steatotic liver disease, dyslipidemia, which usually occurs before it, and they are considered as the upstream diseases of T2D. It is more appropriate to call "diabetic complications" as "MDS-related target organ damage (TOD)", since their development involves not only hyperglycemia but also other metabolic disorders of MDS, promoting an up-to-date management philosophy. In this review, we aim to summarize the underlying mechanism, screening, diagnosis, prevention, and treatment of T2D, especially regarding the personalized selection of hypoglycemic agents and holistic management based on the concept of "MDS-related TOD".

Diabetes mellitus (DM) is a prevalent chronic disease marked by significant metabolic dysfunctions. Understanding its molecular mechanisms is vital for early diagnosis and treatment strategies.

We used datasets GSE7014, GSE25724, and GSE156248 from the GEO database to build a diagnostic model for DM using Random Forest (RF) and LASSO regression models. GSE20966 served as a validation cohort. DM patients were classified into two subtypes for functional enrichment analysis. Expression levels of key diagnostic genes were validated using quantitative real-time PCR (qRT-PCR) on Peripheral Blood Mononuclear Cells (PBMCs) from DM patients and healthy controls, focusing on CXCL12 and PPP1R12B with GAPDH as the internal control.

After de-batching the datasets, we identified 131 differentially expressed genes (DEGs) between DM and control groups, with 70 up-regulated and 61 down-regulated. Enrichment analysis revealed significant down-regulation in the IL-12 signaling pathway, JAK signaling post-IL-12 stimulation, and the ferroptosis pathway in DM. Five genes (CXCL12, MXRA5, UCHL1, PPP1R12B, and C7) were identified as having diagnostic value. The diagnostic model showed high accuracy in both the training and validation cohorts. The gene set also enabled the subclassification of DM patients into groups with distinct functional traits. qRT-PCR results confirmed the bioinformatics findings, particularly the up-regulation of CXCL12 and PPP1R12B in DM patients.

Our study pinpointed seven energy metabolism-related genes differentially expressed in DM and controls, with five holding diagnostic value. Our model accurately diagnosed DM and facilitated patient subclassification, offering new insights into DM pathogenesis.

An updated definition was developed to better evaluate cardiovascular health (CVH). We aimed to investigate whether optimal or improvement of six CVH metrics defined by new Life's Essential 8 (LE8) may counteract the risk of subclinical atherosclerosis among patients with hyperglycemia.

We conducted a prospective analysis of 5225 participants without prior cardiovascular diseases, of whom 4768 had complete data on CVH change. Subjects with CVH scores of 0-49, 50-79, and 80-100 points were categorized as having low, moderate, or high CVH, respectively. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity, pulse pressure and albuminuria, both separately and in combination.

Of the 5225 participants, 1937 (37.1%) had normal glucose regulation, while 3288 (62.9%) had hyperglycemia. The multivariable-adjusted odds ratio (OR) for composite subclinical atherosclerosis was 2.34 (95% confidence interval [CI], 1.88-2.91), 1.43 (95% CI, 1.21-1.70), and 0.74 (95% CI, 0.46-1.18), for participants with hyperglycemia who had low, moderate, or high overall CVH scores, respectively, compared with participants with normal glucose regulation. In addition, compared with those with stable CVH and normal glucose regulation, participants who exhibited greater improvements in overall CVH from 2010 to 2014 had a reduced risk of composite subclinical atherosclerosis with an OR of 0.72 (95% CI, 0.53-0.98) for those with normal glucose regulation, and 1.13 (95% CI, 0.87-1.48) for those with hyperglycemia.

The novel defined CVH using six metrics was inversely associated with subsequent risk of subclinical atherosclerosis. Both the status of CVH and its changes modified the relationship between hyperglycemia and subclinical atherosclerosis.

Obesity is a chronic multi-system disease and major driver of type 2 diabetes and cardiometabolic disease. Nutritional interventions form the cornerstone of obesity and type 2 diabetes management. Some interventions such as Mediterranean diet can reduce incident cardiovascular disease, probably independently of weight loss. Weight loss of 5% or greater can improve many adiposity-related comorbidities. Although this can be achieved with lifestyle intervention, it is often difficult to sustain in the longer term due to adaptive endocrine changes. In recent years glucagon-like-peptide-1 receptor agonists (GLP-1RAs) have emerged as effective treatments for both type 2 diabetes and obesity. Newer GLP-1RAs can achieve average weight loss of 15% or greater and improve cardiometabolic health. There is heterogeneity in the weight loss response to GLP-1RAs, with a substantial number of patients unable to achieve 5% or greater weight. Weight loss, on average, is lower in older adults, male patients and people with type 2 diabetes. Mechanistic studies are needed to understand the aetiology of this variable response. Gastrointestinal side effects leading to medication discontinuation are a concern with GLP-1RA treatment, based on real-world data. With weight loss of 20% or higher with newer GLP-1RAs, nutritional deficiency and sarcopenia are also potential concerns. Lifestyle interventions that may potentially mitigate the side effects of GLP-1RA treatment and enhance weight loss are discussed here. The efficacy of such interventions awaits confirmation with well-designed randomized controlled trials.

Coronary atherosclerotic heart disease (CHD) is highly prevalent in Northwest China; however, effective preventive measures are limited. This study aimed to develop metabolic risk models tailored for the primary and secondary prevention of CHD in Northwest China.

This hospital-based cross-sectional study included 744 patients who underwent coronary angiography. Data on demographic characteristics, comorbidities, and serum biochemical indices of the participants were collected. Three machine learning algorithms-recursive feature elimination, random forest, and least absolute shrinkage and selection operator-were employed to construct risk models. Model validation was performed using receiver operating characteristic and calibration curves, and the optimal cutoff values for significant risk factors were determined.

The predictive model for CHD onset included sex, overweight/obesity, and hemoglobin A1c (HbA1c) levels. For CHD progression to multiple coronary artery disease, the model included age, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and HbA1c levels. The model predicting an increased coronary Gensini score included sex, overweight/obesity, TC, LDL-C, high-density lipoprotein cholesterol, lipoprotein(a), and HbA1c levels. Notably, the optimal cutoff values for HbA1c and lipoprotein(a) for determining CHD progression were 6 % and 298 mg/L, respectively.

Robust metabolic risk models were established, offering significant value for both the primary and secondary prevention of CHD in Northwest China. Weight loss, strict hyperglycemic control, and improvement in dyslipidemia may help prevent or delay the occurrence and progression of CHD in this region.

Despite extensive evidence related to the prevention and management of type 2 diabetes (T2D) and its complications, most people at risk for and people who have diabetes do not receive recommended guideline-based care. Clinical implementation of proven care strategies is of the utmost importance because without this, even the most impressive research findings will remain of purely academic interest. In this review, we discuss the promise and challenges of implementing effective approaches to diabetes prevention and care in the real-world setting. We describe successful implementation projects in three critical areas of diabetes care-diabetes prevention, glycemic control, and prevention of diabetes-related complications-which provide a basis for further clinical translation and an impetus to improve the prevention and control of T2D in the community. Advancing the clinical translation of evidence-based care must include recognition of and assessment of existing gaps in care, identification of barriers to the delivery of optimal care, and a locally appropriate plan to address and overcome these barriers. Care models that promote team-based approaches, rather than reliance on patient-provider interactions, will enhance the delivery of contemporary comprehensive diabetes care.

This study aimed to investigate the potential differences in the influence of impaired glucose tolerance (IGT) with and without metabolic syndrome (MetS) on cardiovascular (CV) events and mortality.

Participants having IGT with MetS (IGT_MetS), those having IGT without MetS (IGT_non_MetS), and those having normal glucose tolerance (NGT) without MetS (NGT_non_MetS) (N = 246, N = 294, and N = 471, respectively) were included in this study. Cox proportional hazards regression was used to examine the relationship among these three groups and CV events and mortality.

Over the 30-year follow-up period, 57 (12.1%) participants having NGT_non_MetS, 55 (18.71%) with IGT_non_MetS, and 74 (30.08%) with IGT_MetS experienced CV mortality. After adjusting for risk factors, the hazard ratios for CV mortality were 2 (95% confidence interval [CI], 1.38-2.91) for the IGT_non_MetS group and 2.96 (95% CI, 2.09-4.19) for the IGT_MetS group, compared with the NGT_non_MetS group. Similar patterns were observed for CV events, with hazard ratios of 1.49 (95% CI, 1.19-1.88) for the IGT_non_MetS group and 1.97 (95% CI, 1.58-2.47) for the IGT_MetS group. Sensitivity analysis revealed that the hazard ratios of the IGT_non_MetS and IGT_MetS groups indicated a higher risk of all-cause mortality, myocardial infarction events or myocardial infarction mortality, and stroke events or stroke mortality compared with that of the NGT_non_MetS group.

IGT_non_MetS increased the risk of CV mortality and events. Furthermore, when it occurred in conjunction with MetS, it further increased the risk of CV mortality and events. This suggested that active intervention is required.

The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified.

In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population.

In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.

Individuals at high risk for type 2 diabetes are also at an increased risk for developing cardiovascular disease (CVD). Although there are separate trials examining the effects of lifestyle interventions on absolute CVD risk among people at high risk for type 2 diabetes, a comprehensive evidence synthesis of these trials is lacking.

We will systematically synthesize the evidence on the effects of lifestyle interventions in reducing absolute CVD risk and CVD risk factors among people at high risk for type 2 diabetes.

We adhered to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) statement in reporting the details of this protocol. Randomized controlled trials of diabetes prevention that examined the effects of lifestyle interventions for at least 6 months on absolute CVD risk and CVD risk factors among individuals at high risk for type 2 diabetes will be eligible. We will systematically search the MEDLINE, Embase, PsycINFO, CENTRAL, and Scopus databases and ClinicalTrials.gov using a mix of Medical Subject Headings and text words. Two authors will independently screen the abstract and title of the articles retrieved from the search, followed by full-text reviews using the inclusion and exclusion criteria and data extraction from the eligible studies. Article screening and data extraction will be performed in the Covidence software. The primary outcome will be the changes in absolute 10-year CVD risk, as estimated by risk prediction models. The secondary outcomes are the changes in CVD risk factors, including behavioral, clinical, biochemical, and psychosocial risk factors, and incidence of type 2 diabetes.

An initial database search was conducted in July 2023. After screening 1935 articles identified through the database search, 42 articles were considered eligible for inclusion. It is anticipated that the study findings will be submitted for publication in a peer-reviewed journal by the end of 2024.

This study will provide up-to-date, systematically synthesized evidence on the effects of lifestyle interventions on absolute CVD risk and CVD risk factors among individuals at high risk for type 2 diabetes.

PROSPERO CRD42023429869; https://tinyurl.com/59ajy7rw.

DERR1-10.2196/53517.