Cardiometabolic Morbidity Research Articles

Is Breastfeeding an Effective Approach to Reduce Metabolic Risk After GDM in Mothers and Infants?

Gestational diabetes mellitus (GDM) leads to increased lifelong cardiometabolic risk in both mothers and their offspring. The identification of effective strategies to contain the future risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is of utmost importance to reduce the burden of the disease. Breastfeeding (BF) is effective in reducing short- and long-term child morbidity. In recent years, BF has emerged as a candidate low-cost intervention to prevent future cardiometabolic complications both in mothers and infants exposed to GDM. The aim of this review is to provide an overview of the evidence about the possible metabolic benefits of BF for both mothers with a history of GDM and their offspring. Increasing evidence supports the positive effects of exclusive BF over formula feeding (FF) or mixed feeding on glucose homeostasis and the lipid profile in women with previous GDM in the early postpartum period. Studies with a longer observation suggest clear benefits of intensive and longer BF on the risk of diabetes and prediabetes in mothers after adjustment for confounders. In regards to infants, in most studies, the intensity and duration of BF are positively associated with slower infant growth curves compared with FF, indicating that the positive effect of BF on growth trends might contrast the increased risk of obesity and metabolic diseases observed in infants exposed to GDM. Considering these findings, a global effort should be made to support BF practice to possibly reduce cardiometabolic morbidity after GDM.

The Molecular Basis of Polycystic Ovary Syndrome and Its Cardiometabolic Correlates: Exploring the Intersection and Its Clinical Implications-A Narrative Review.

Recent studies have highlighted the association between polycystic ovary syndrome (PCOS) and cardiometabolic diseases, leading to an improved understanding of the underlying mechanistic factors. PCOS significantly increases cardiovascular risk by predisposing individuals to various subclinical and clinical conditions, including atherosclerosis and type 2 diabetes mellitus. Additionally, it interacts synergistically with other traditional cardiovascular risk factors, such as obesity, hyperlipidemia, and insulin resistance. Several molecular mechanisms involving genetics, epigenetics, adipokine secretion, hyperandrogenemia, and hyperinsulinemia play a role in the relationship between PCOS and these comorbidities. For instance, androgen excess has been implicated in the development of hypertension, type 2 diabetes mellitus, endothelial dysfunction, and ultimately, broader cardiovascular disease. A deeper understanding of these underlying mechanisms facilitates the development of diagnostic, preventative, and therapeutic strategies directed at reducing cardiometabolic morbidity. This narrative review summarizes the current evidence, explores the potential clinical implications of these findings, and discusses emerging therapies to reduce cardiometabolic morbidity in women with PCOS.

Increased Waist Circumference Is Associated With Severe Postoperative Medical Complications Following Total Knee Arthroplasty: Understanding Waist Circumference and Relation to Body Mass Index.

Increased Waist Circumference Is Associated With Severe Postoperative Medical Complications Following Total Knee Arthroplasty: Understanding Waist Circumference and Relation to Body Mass Index.

Effects of MyBFF@school, a multifaceted obesity intervention program, on anthropometry and body composition of overweight and obese primary schoolchildren

BackgroundRecently, there has been an increase in the prevalence of childhood obesity in Malaysia, raising concerns about increased cardiometabolic morbidity. MyBFF@school is a multifaceted program comprising physical activity, nutritional education, and psychological empowerment introduced to combat childhood obesity in Malaysia. The efficacy of a six-month intervention on the body composition of overweight and obese primary schoolchildren was evaluated.MethodsThis is a school-based, cluster randomized controlled trial involving selected primary schools in Kuala Lumpur, Selangor, and Negeri Sembilan. A total of 1,397 primary-school students aged 9–11 with a body mass index (BMI)z-score (corrected for age) greater than + 1 standard deviation based on the World Health Organization 2007 Growth Reference were assigned to intervention (n=647) and control (n=750) groups. BMI z-score, waist circumference (WC), percentage body fat (PBF), and skeletal muscle mass (SMM) were assessed at baseline and after three and six months of the study. Analyses of all outcomes except for the baseline characteristics were conducted according to the intention-to-treat principle.ResultsAfter three months, there was no significant difference in the BMI z-score or PBF between the control and intervention groups, but SMM and WC were significantly higher in the intervention group versus the control group with mean difference of 0.15 kg; 95% confidence interval [CI]: 0.07–0.22, p < 0.001 and mean difference of 1.53 cm; 95% confidence interval [CI]: 1.21- 1.85, p < 0.001 for SMM and WC respectively. After six months, the intervention group demonstrated a significantly greater reduction in PBF compared to the controls (% mean difference: 0.43%, 95% CI: − 0.73 to − 0.12, p < 0.001) as well as a greater increase in SMM (mean difference: 0.28 kg, 95% CI: 0.18–0.37, p < 0.001). There was no difference in the BMI z-score or WC between the intervention and control groups at six months.ConclusionsThe multicomponent MyBFF@school intervention significantly improved body composition among obese primary schoolchildren in terms of percentage body fat and skeletal muscle mass compared to the control after six months. However, BMI z-score and waist circumference measures did not reflect the benefits of this program.Trial registrationClinical trial number: NCT04155255, November 7, 2019 (Retrospective registered). National Medical Research Register: NMRR-13–439-16,563. Registered July 23, 2013. The intervention program was approved by the Medical Research and Ethics Committee (MREC), Ministry of Health Malaysia and the Educational Planning and Research Division (EPRD), Ministry of Education Malaysia. It was funded by the Ministry of Health Malaysia.

Effects of early, late and self-selected time-restricted eating on visceral adipose tissue and cardiometabolic health in participants with overweight or obesity: a randomized controlled trial.

The optimal eating window for time-restricted eating (TRE) remains unclear, particularly its impact on visceral adipose tissue (VAT), which is associated with cardiometabolic morbidity and mortality. We investigated the effects of three TRE schedules (8 h windows in the early day, late day and participant-chosen times) combined with usual care (UC, based on education about the Mediterranean diet) versus UC alone over 12 weeks in adults with overweight or obesity. The primary outcome was VAT changes measured by magnetic resonance imaging. A total of 197 participants were randomized to UC (n = 49), early TRE (n = 49), late TRE (n = 52) or self-selected TRE (n = 47). No significant differences were found in VAT changes between early TRE (mean difference (MD): -4%; 95% confidence interval (CI), -12 to 4; P = 0.87), late TRE (MD: -6%; 95% CI, -13 to 2; P = 0.31) and self-selected TRE (MD: -3%; 95% CI, -11 to 5; P ≥ 0.99) compared with UC, nor among the TRE groups (all P ≥ 0.99). No serious adverse events occurred; five participants reported mild adverse events. Adherence was high (85-88%) across TRE groups. These findings suggest that adding TRE, irrespective of eating window timing, offers no additional benefit over a Mediterranean diet alone in reducing VAT. TRE appears to be a safe, well-tolerated and feasible dietary approach for adults with overweight or obesity. ClinicalTrials.gov registration: NCT05310721 .

Increased risk of type 2 diabetes after traumatic amputation: a nationwide retrospective cohort study.

Amputation confers disabilities upon patients and is linked to cardiometabolic morbidity and mortality. We aimed to compare the incidence of type 2 diabetes (T2DM) between individuals following amputation with those of the general population. We performed a population-based retrospective cohort study using the Nationwide Health Insurance Service database. A total of 21,343 individuals with amputation during 2010-2018 and their 1:3 age- and sex-matched controls was included. We conducted Cox proportional hazard analysis to calculate the risk of T2DM among individuals with amputation. During the 4.2 ± 2.5 year mean follow-up period, there were 912 incident T2DM cases (10.7 per 1,000 person-years) among individuals with amputation. Individuals with amputation had a higher risk for T2DM (adjusted hazard ratio [aHR] 1.11, 95% confidence interval [CI] 1.03-1.20) compared with matched controls. The risks were increased further when accompanied with disability; those with severe disability had a higher risk of T2DM (aHR 1.77, 95% CI 1.20-2.60) than matched controls. Individuals with proximal upper limb amputation (aHR 1.10, 95% CI 1.02-1.18) and proximal lower limb amputation (aHR 3.60, 95% CI 1.50-8.64) had a higher risk of T2DM compared with matched controls. Individuals with amputation were at significantly greater risk for T2DM than the general population, particularly those with severe disability and proximal amputation. Innovative strategies that improve and support the long-term T2DM risk for severely injured individuals with proximal amputation are warranted.

Association of Serum Ferritin with Total and Regional Fat Measured by Dual-Energy X-Ray Absorptiometry in a Nationally Representative Survey

Introduction: Fat distribution is a stronger predictor for cardiometabolic morbidity and mortality. We aimed to investigate the association of elevated iron stores, measured as serum ferritin levels, with total and regional body fat. Methods: Data from 2,646 adults from the National Health and Nutrition Examination Survey 2017–2018 were analyzed. Dual-energy X-ray absorptiometry was used to measure overall and regional body fat. The fat mass index (FMI) was calculated by dividing the fat mass (kg) by the square of body height (m2). The leg fat mass to trunk fat mass ratio (LTR) was used to assess the relative distribution of leg fat compared to trunk fat. Results: Medians (IQR) of serum ferritin levels were 0.168 μg/mL (0.104–0.269) for men and 0.053 μg/mL (0.026–0.102) for women. After adjusting for sociodemographic, lifestyle, and metabolic factors, serum ferritin showed a significant positive association with total FMI (β = 2.662) and trunk FMI (β = 0.983), and a negative association with leg FMI (β = −0.324) and LTR (β = −0.160) in men. In women, serum ferritin showed a significant positive association with total FMI (β = 4.658), trunk FMI (β = 2.085), and negative association with LTR (β = −0.312). Significant positive trends were observed for serum ferritin with total and trunk FMI in men and women, using the lowest serum ferritin quartile as the reference group. Additionally, significant negative trends were observed for serum ferritin with leg FMI and LTR in men. The mediation analysis revealed that C-reactive protein mediated 16.4% and 22.6% of the potential effects of serum ferritin on trunk FMI in men and women, respectively. Conclusion: Higher ferritin levels were associated with greater total and trunk fat but lower leg fat. Further prospective and mechanistic studies are warranted to confirm the study results.

Cardio-metabolic risk and morbidity of a cohort in a rural community of Bangladesh

Background and objectives: Of the ever-increasing non-communicable diseases (NCDs), cardiometabolic morbidity and mortality constitute the major health burden world-wide. Several cross-sectional studies revealed the increasing prevalence of NCDs irrespective of cast, culture, ethnicity, socio-economic growth and geopolitical environment. Recent cross-sectional studies revealed South Asians are the most susceptible to cardiovascular diseases (CVD). Few cohort studies addressed cardiometabolic morbidity and related risks, particularly in the rural population.This study was carried out to find out the prevalence of metabolic syndrome (MetSyn) and its changes overtime in a rural cohort of Bangladesh. Methods: The study used baseline data of a study conducted in 2011- 2013 on prevalence of coronary artery disease among a cohort living in 16 villages. During 2021-2023, the baseline data collected in 2011-2013 were retrieved and the participants were searched and categorized into a) physically present, b) died and c) missing. Those who were present were requested to volunteer for re-investigations. Briefly the investigations included interviewing on social, family, personal and clinical history, anthropometry, blood pressure measurement, blood biochemistry and electrocardiography (ECG). Results: A total of 3928 people participated in baseline study of 2011- 2013. Of them, 1075 could be tracked by village and household. Of them, 953 were found alive. Of the 953 available participants, 651 (254 men and 397 women) volunteered to participate in 2021-2023 study. Compared to 2011-2013 baseline, the prevalence of MetSyn and type 2 diabetes mellitus (T2DM) increased to 31.6% and 5.2% from 7.5% and 0.8% respectively in 2021-2023. Similarly, compared to baseline, the prevalence of obesity and hypertension also showed significant increase overtime. Estimated incidence of MetSyn was 260.8 per 1000 population, which was more profound in women than men (W: M= 300.3:200.8). Conclusions: The study revealed a significant increase of obesity, hypertension, diabetes and metabolic syndrome within a decade indicating an emerging health burden among the rural people of Bangladesh. January 2025; Vol. 19(1):003. DOI:https://doi.org/10.55010/imcjms.19.003 *Correspondence: MA Sayeed, Department of Community Medicine, Ibrahim Medical College, 1/A Ibrahim Sarani, Segunbagicha, Dhaka 1000, Bangladesh. Email: sayeed950@gmail.com; © 2025 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License(CC BY 4.0).

Relationship quality and educational attainment links to development of cardiometabolic morbidity and multimorbidity across middle adulthood.

The prevalence of cardiometabolic morbidity (e.g., high blood pressure, heart attack, stroke, type 2 diabetes) and multimorbidity development (2 or more cardiometabolic morbidities) are rapidly growing in the US. Cardiometabolic morbidity and multimorbidity are linked to poor well-being outcomes, high healthcare costs, and mortality. There is little known about cardiometabolic multimorbidity health disparities, particularly regarding mutable factors that might be targeted in future health interventions. In the present study, using a biopsychosocial framework (Biobehavioral Family Model), we examine whether cardiometabolic morbidity and multimorbidity development are linked to premorbid family and marital relationships and if it differs depending on socioeconomic status (i.e., educational attainment) using three waves of Midlife in the US (N = 4951). We assessed cardiometabolic development with three conceptualizations: number of cardiometabolic morbidities (i.e., count variable), individual cardiometabolic morbidities (i.e., diabetes, high blood pressure, stroke, heart attack), and severity of cardiometabolic multimorbidity (e.g., 3+ vs. zero morbidities). Family strain increased the number of cardiometabolic morbidities (OR = 1.17) and the severity of multimorbidity (e.g., 3+ morbidities: OR = 1.38). People with a high school education experienced family support as a buffer to the negative health impact of education level. Generally, marital quality appeared less impactful on cardiometabolic morbidity and multimorbidity development compared to family strain. Positive and negative family characteristics appear to function differently across educational attainment. These findings indicate that adults' non-intimate family relationships predict important outcomes such as diabetes, heart attack, stroke, and cardiometabolic multimorbidity and should be considered targets for preventative health interventions.

Cardiometabolic Morbidity (Obesity and Hypertension) in PTSD: A Preliminary Investigation of the Validity of Two Structures of the Impact of Event Scale-Revised.

Background: Posttraumatic stress disorder (PTSD) and/or specific PTSD symptoms may evoke maladaptive behaviors (e.g., compulsive buying, disordered eating, and an unhealthy lifestyle), resulting in adverse cardiometabolic events (e.g., hypertension and obesity), which may implicate the treatment of this complex condition. The diagnostic criteria for PTSD have lately expanded beyond the three common symptoms (intrusion, avoidance, and hyperarousal). Including additional symptoms such as emotional numbing, sleep disturbance, and irritability strengthens the representation of the Impact of Event Scale-Revised (IES-R), suggesting that models with four, five, or six dimensions better capture its structure compared to the original three-dimensional model. Methods: Using a convenience sample of 58 Russian dental healthcare workers (HCWs: mean age = 44.1 ± 12.2 years, 82.8% females), this instrumental study examined the convergent, concurrent, and criterion validity of two IES-R structures: IES-R3 and IES-R6. Results: Exploratory factor analysis uncovered five factors, which explained 76.0% of the variance in the IES-R. Subscales of the IES-R3 and the IES-R6 expressed good internal consistency (coefficient alpha range = 0.69-0.88), high convergent validity (item total correlations r range = 0.39-0.81, and correlations with the IES-R's total score r range = 0.62-0.92), excellent concurrent validity through strong correlations with the PTSD Symptom Scale-Self Report (PSS-SR: r range = 0.42-0.69), while their criterion validity was indicated by moderate-to-low correlations with high body mass index (BMI: r range = 0.12-0.39) and the diagnosis of hypertension (r range = 0.12-0.30). In the receiver-operating characteristic (ROC) curve analysis, all IES-R models were perfectly associated with the PSS-SR (all areas under the curve (AUCs) > 0.9, p values < 0.001). The IES-R, both hyperarousal subscales, and the IES-R3 intrusion subscale were significantly associated with high BMI. Both avoidance subscales and the IES-R3 intrusion subscale, not the IES-R, were significantly associated with hypertension. In the two-step cluster analysis, five sets of all trauma variables (IES-R3/IES-R6, PSS-SR) classified the participants into two clusters according to their BMI (normal weight/low BMI vs. overweight/obese). Meanwhile, only the IES-R, PSS-SR, and IES-R3 dimensions successfully classified participants as having either normal blood pressure or hypertension. Participants in the overweight/obese and hypertensive clusters displayed considerably higher levels of most trauma symptoms. Input variables with the highest predictor importance in the cluster analysis were those variables expressing significant associations in correlations and ROC analyses. However, neither IES-R3 nor IES-R6 contributed to BMI or hypertension either directly or indirectly in the path analysis. Meanwhile, age significantly predicted both health conditions and current smoking. Irritability and numbing were the only IES-R dimensions that significantly contributed to current smoking. Conclusions: The findings emphasize the need for assessing the way through which various PTSD symptoms may implicate cardiometabolic dysfunctions and their risk factors (e.g., smoking and the intake of unhealthy foods) as well as the application of targeted dietary and exercise interventions to lower physical morbidity in PTSD patients. However, the internal and external validity of our tests may be questionable due to the low power of our sample size. Replicating the study in larger samples, which comprise different physical and mental conditions from heterogenous cultural contexts, is pivotal to validate the results (e.g., in specific groups, such as those with confirmed traumatic exposure and comorbid mood dysfunction).

MON-436 Age and Smoking Status Affect Cardiometabolic Risk Trends Over Time in People with Serious Mental Illness on Psychotropic Medications - A Call for Personalized Screening

Abstract H. Chin: None. L. Wang: None. S.H. Lopa: None. T. Pauly: None. S.U. Miedlich: None. People with serious mental illness (SMI) have high cardiometabolic morbidity and mortality. Psychotropic medications, socioeconomic deprivation, adverse health behaviors, poor access to and quality of healthcare mediate unfavorable health outcomes in people with SMI. Per prospective screening by oral glucose tolerance test and hemoglobin A1c (HbA1c), we previously showed that the majority of adult patients with SMI on second-generation antipsychotic medications (SGA), seen at a large primary care clinic for people with SMI at the University of Rochester, have prediabetes or diabetes mellitus1. In this study, we explored cardiometabolic risk profiles in the above patients over time with respect to psychotropic medication use, age, and smoking status. Data were obtained per review of electronic health records, entered into REDCap, and analyzed using R. The following data were collected between 2014-2021: weight, systolic and diastolic blood pressure, pulse rate (average of last 3 observations/year), annual HbA1c and lipid profiles, as well as use of psychotropic medications. Smoking rates are high in our patient cohort (37.5%). More than 90% of patients were on at least one SGA at any given year, and 10-25% of patients were on more than one SGA, 46-65% of patients were also on antidepressant medications (ADM), 12-28% of patients were on mood stabilizers. Overall, weight trends correlated tightly with HbA1c trends (+0.5kg/year, +0.06%/year, p&amp;lt;0.0001). Smokers gained less weight (-0.8kg/year, p=0.02) and had lower HbA1c levels over time (-0.1%/year, p=0.02) with a trend of lower triglyceride as well as higher HDL levels. Conversely, younger patients (&amp;lt;50 years) gained more weight (+1kg/year, p=0.003) and had larger HbA1c increases (+0.23%/year, p&amp;lt;0.0001) than patients aged 50 years or older. Cardiometabolic trends did not differ between patients on various SGA and/or additional psychotropic medications except for cholesterol profiles. Both, total cholesterol and LDL levels were higher in patients on ADM compared to patients not on ADM (p=0.03). In conclusion, patients with SMI on SGA, and more specifically non-smokers and younger patients, are at risk for ongoing weight gain and concomitant HbA1c increases over time, stressing the importance of regular diabetes screening, particularly in non-smokers and younger patients with SMI. Notably, young adult patients with SMI are less likely to be screened for diabetes mellitus despite their metabolic risk2. Conversely, smokers will likely benefit more from a focus on smoking cessation counseling and therapy. Altogether, our data stress the need for personalized cardiometabolic health screening in people with SMI. Differences in lipid profiles in patients off/on ADM need further investigation.

Preconception HbA1c Levels in Adolescents and Young Adults and Adverse Birth Outcomes

Subclinical hyperglycemia before pregnancy may be associated with the likelihood of maternal morbidity but is understudied among young people. To explore the association of preconception hemoglobin A1c (HbA1c) levels among adolescents and young adults with risk of gestational diabetes at first live birth. This retrospective cohort study used linked 2009 to 2017 birth registry, hospital discharge, and New York City Department of Health A1C Registry data for birthing individuals aged 10 to 24 years with no history of diabetes and at least 1 preconception HbA1c test in New York, New York. Statistical analysis was performed from August to November 2022. Preconception HbA1c values categorized as no diabetes (HbA1c <5.7%) or prediabetes (HbA1c ≥5.7% to <6.5%). The primary outcome was gestational diabetes at first birth. Secondary outcomes included hypertensive disorders of pregnancy, preterm birth, cesarean delivery, and macrosomia. Log binomial regression was used to estimate the relative risk (RR) of gestational diabetes at first birth by preconception HbA1c level, adjusting for prepregnancy characteristics. The optimal HbA1c threshold for gestational diabetes was examined using receiver operating curve regression. A total of 14 302 individuals (mean [SD] age, 22.10 [1.55] years) met study eligibility criteria. Of these, 5896 (41.0%) were Hispanic, 4149 (29.0%) were Black, 2583 (18.1%) were White, 1516 (10.6%) were Asian, and 185 (1.3%) had other or unknown race and ethnicity. Most (11 407 individuals [79.7%]) had normoglycemia before pregnancy, and 2895 individuals (20.2%) had prediabetes. Adjusting for prepregnancy characteristics, those with preconception prediabetes had more than twice the risk of gestational diabetes vs those with normoglycemia (adjusted RR [aRR], 2.21; 95% CI, 1.91-2.56). Preconception prediabetes was associated with small increases in the likelihood of a hypertensive disorder of pregnancy (aRR, 1.18; 95% CI, 1.03-1.35) and preterm delivery (aRR, 1.18; 95% CI, 1.02-1.37). The aRRs for cesarean delivery (aRR, 1.09; 95% CI, 0.99-1.20) and macrosomia (aRR, 1.13; 95% CI, 0.93-1.37) were increased but not statistically significant. The optimal HbA1c threshold to identify gestational diabetes among adolescents and young adults was 5.6%. The threshold did not vary by obesity status but was slightly lower among Hispanic individuals (HbA1c of 5.5%). In this study of adolescents and young adults with at least 1 preconception HbA1c test, prediabetes was associated with increased likelihood of maternal cardiometabolic morbidity at first birth. Efforts to optimize cardiometabolic health before pregnancy may avert excess maternal risk.

Obstructive sleep apnea comorbid with insomnia symptoms and objective short sleep duration is associated with clinical and preclinical cardiometabolic risk factors: Clinical implications

Obstructive sleep apnea comorbid with insomnia symptoms and objective short sleep duration is associated with clinical and preclinical cardiometabolic risk factors: Clinical implications

Tissue-Level Effect of Andrographis and Ashwagandha Metabolites on Metabolic and Inflammatory Gene Expression in Skeletal Muscle and Adipose Tissue: An Ex Vivo/In Vitro Investigation.

Adipose tissue and skeletal muscle dysfunction play a central role in cardiometabolic morbidity. Ashwagandha and Andrographis are purported to have anti-inflammatory and antioxidant activity, but this is based on exposure of cells to the parent compounds ignoring phytochemical absorption and metabolism. We explored the anti-inflammatory/antioxidant effects of ashwagandha and Andrographis in ex vivo human models of skeletal muscle and adipose tissue. Healthy participants supplemented with 2000 mg/day Andrographis (n = 10) or 1100 mg/day ashwagandha (n = 10) for 28 days. Sera collected pre (D0) and post (D28) supplementation were pooled by timepoint and added to adipose explant (AT) and primary human myotube (SKMC) culture media (15% v/v) for treatment. A Taqman panel of 56 genes was used to quantify these. In AT, treatment with ashwagandha sera decreased the expression of genes involved in antioxidant defence and inflammatory response (CCL5, CD36, IL6, IL10, ADIPOQ, NFEL2, UCP2, GPX3, GPX4; geometric 95% CI for fold change > 1) and altered the expression of genes involved in fatty acid metabolism. In SKMC, ashwagandha sera altered FOXO1 and SREBF1 expression. Andrographis sera decreased IL18 and SERPINEA3 expression in AT. This physiologically relevant in vitro screening characterises the effects of ashwagandha in AT to guide future clinical trials.

Metformin use correlated with lower risk of cardiometabolic diseases and related mortality among US cancer survivors: evidence from a nationally representative cohort study

BackgroundIn the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce.MethodsA prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants’ levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin.ResultsAmong 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47–0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44–0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28–0.59), stroke (OR, 0.44; 95% CI, 0.26–0.74), hypertension (OR, 0.27; 95% CI, 0.14–0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21–0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress.ConclusionsIn this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.

Paternal Use of Metformin During the Sperm Development Period Preceding Conception and Risk for Major Congenital Malformations in Newborns.

Metformin is the most used oral antidiabetic medication. Despite its established safety profile, it has known antiandrogenic and epigenetic modifying effects. This raised concerns about possible adverse developmental effects caused by genomic alterations related to paternal use of metformin during the spermatogenesis period preceding conception. To assess the potential adverse intergenerational effect of metformin by examining the association between paternal metformin use during spermatogenesis and major congenital malformations (MCMs) in newborns. Nationally representative cohort study. A large Israeli health fund. 383 851 live births linked to fathers and mothers that occurred in 1999 to 2020. MCMs and parental cardiometabolic conditions were ascertained using clinical diagnoses, medication dispensing information, and laboratory test results. The effect of metformin use on MCMs was estimated using general estimating equations, accounting for concurrent use of other antidiabetic medications and parental cardiometabolic morbidity. Compared with unexposed fathers, the prevalence of cardiometabolic morbidity was substantially higher among fathers who used metformin during spermatogenesis, and their spouses. Whereas the crude odds ratio (OR) for paternal metformin exposure in all formulations and MCMs was 1.28 (95% CI, 1.01 to 1.64), the adjusted OR was 1.00 (CI, 0.76 to 1.31). Within specific treatment regimens, the adjusted OR was 0.86 (CI, 0.60 to 1.23) for metformin in monotherapy and 1.36 (CI, 1.00 to 1.85) for metformin in polytherapy, a treatment that was more common in patients with more poorly controlled diabetes. Laboratory test results for hemoglobin A1c to assess underlying diabetes severity were available only for a subset of the cohort. Paternal use of metformin in monotherapy does not increase the risk for MCMs. Association for metformin in polytherapy could potentially be explained by worse underlying parental cardiometabolic risk profile. None.

Required elements for an educational programme for lay exercise instructors in charge of community-based exercise targeting young adults with schizophrenia spectrum disorders – A stakeholder focus group study

BackgroundExercise plays a crucial role in addressing the increased cardiometabolic morbidity and premature mortality in people with schizophrenia spectrum disorders. When delivered in community-based settings, exercise may also reduce loneliness, while promoting overall physical activity behaviours. Skilled instructors are essential to deliver effective community-based exercise; however, knowledge about their roles and required training is lacking. We aim to explore various stakeholders’ perspectives regarding lay exercise instructors’ roles, and the required elements in an educational programme supporting the delivery of community-based exercise for young adults with SSD.MethodsWe used semi-structured homogeneous focus groups with representatives from different stakeholder groups (i.e., including representatives of clinical staff within mental health, physiotherapists, exercise instructors, young adults with schizophrenia spectrum disorders, and relatives of individuals with schizophrenia spectrum disorders) targeted or affected by a community-based exercise intervention. Data were analysed using qualitative content analysis.ResultsWe conducted six focus groups comprising a total of 30 individuals representing five different stakeholder groups The analysis identified three categories: (i) awareness and understanding of mental illness, i.e., providing basic knowledge to dispel common myths and stigma regarding mental illness (ii) protecting youth identity, i.e., supporting the feeling of being more than just a patient, and (iii) promoting exercise as a shared activity, i.e., a communal pursuit, fostering personal growth among participants, their peers and the instructors.ConclusionsAn educational programme for lay exercise instructors delivering community-based exercise targeting young adults with SSD should empower the instructors to assume the role of guardians of an inclusive exercise culture. Educational elements identified were adapted and integrated into an educational programme implemented and evaluated as a part of the Vega trial. Our results may be transferable to the education of lay workers in mental health care where the aim is to facilitate sustainable, recreational, community-based activities.

The longitudinal association of adipose-to-lean ratio with incident cardiometabolic morbidity: The CARDIA study

The longitudinal association of adipose-to-lean ratio with incident cardiometabolic morbidity: The CARDIA study

Cardio-Metabolic Health of Offspring Exposed in Utero to Human Immuno-Deficiency Virus and Anti-Retroviral Treatment: A Systematic Review.

Antiretroviral treatment (ART) use during pregnancy continues to rise as it is known to decrease the likelihood of HIV transmission from mother to child. However, it is still unknown whether foetal exposure to (ART) may affect the foetal environment, predisposing the offspring to cardiometabolic risk. Therefore, the aim of this study was to systematically review the cardio-metabolic effects of in utero exposure to HIV/ART on offspring. We carried out a systematic review and obtained literature from the Google scholar, PubMed, ProQuest, Web of Science, and Scopus databases. Two independent reviewers evaluated the titles, abstracts, and full-length English contents. Data from the eligible studies were included. The search yielded 7596 records. After assessing all of these records, 35 of the full-length articles were included in this systematic review. Several studies showed that low birth weight, small head circumference, and altered mitochondrial content were more common among HIV-exposed uninfected (HEU) children compared to HIV-unexposed uninfected children (HUU). A few studies demonstrated elevated triglyceride levels, lower levels of insulin, and increased blood pressure, oxidative stress, vascular dysfunction, cardiac damage, and myocardial dysfunction among HEU children compared with HUU children. Most findings showed that there were cardio-metabolic health risk factors among HEU children, indicating that maternal exposure to HIV and ART may negatively affect foetal health, which may lead to cardio-metabolic morbidity later in life.

Low-Carbohydrate and Ketogenic Dietary Patterns for Type 2 Diabetes Management.

Type 2 diabetes mellitus (T2DM) has been traditionally considered a chronic, progressive disease. Since 2017, guidelines from the US Department of Veterans Affairs and US Department of Defense have included low-carbohydrate (LC) dietary patterns in managing T2DM. Recently, carbohydrate reduction, including ketogenic diets, has gained renewed interest in the management and remission of T2DM. This narrative review examines the evidence behind carbohydrate reduction in T2DM and a practical guide for clinicians starting patients on therapeutic LC diets. We present an illustrative case and provide practical approaches to prescribing a very LC ketogenic (< 50 g), LC (50-100 g), or a moderate LC (101-150 g) dietary plan and discuss adverse effects and management of LC diets. We provide a medication management and deprescription approach and discuss strategies to consider in conjunction with LC diets. As patients adopt LC diets, glycemia improves, and medications are deprescribed, hemoglobin A1c levels and fasting glucose may drop below the diagnostic threshold for T2DM. Remission of T2DM may occur with LC diets (hemoglobin A1c < 6.5% for ≥ 3 months without T2DM medications). Finally, we describe barriers and limitations to applying therapeutic carbohydrate reduction in a federal health care system. The effective use of LC diets with close and intensive lifestyle counseling and a safe approach to medication management and deprescribing can improve glycemic control, reduce the overall need for insulin and medication and provide sustained weight loss. The efficacy and continuation of therapeutic carbohydrate reduction for patients with T2DM appears promising. Further research on LC diets, emerging strategies, and long-term effects on cardiometabolic risk factors, morbidity, and mortality will continue to inform practice.