Adiponectin Ratio Research Articles

Associations of epigenetic age acceleration at birth and age 12 years with adolescent cardiometabolic risk: the HOME study

BackgroundCardiometabolic risk factors among youth are rising. Epigenetic age acceleration, a biomarker for aging and disease-risk, has been associated with adiposity in children, but its association with other cardiometabolic risk markers remains understudied. We employed data from the Health Outcomes and Measures of the Environment (HOME) study, a prospective pregnancy and birth cohort in the greater Cincinnati metropolitan area, to examine whether accelerated epigenetic age at birth as well as accelerated epigenetic age and faster pace of biological aging at age 12 years were associated with higher cardiometabolic risk in adolescents.ResultsAfter adjusting for potential confounders, including estimated cell type proportions, epigenetic gestational age acceleration at birth, derived from the Bohlin, Knight, and Haftorn clocks using cord blood DNA methylation data, was not associated with cardiometabolic risk z-scores or individual cardiometabolic risk score components (visceral fat, leptin to adiponectin ratio, HOMA-IR, triglycerides to HDL-C ratio, HbA1c, or systolic blood pressure) at age 12 years. We also did not observe any associations of epigenetic age acceleration, calculated with Horvath’s skin and blood, Hannum’s, and Wu’s epigenetic clocks using peripheral blood at age 12 years, with these same cardiometabolic risk markers. In contrast, faster pace of biological aging was associated with higher cardiometabolic risk [βs (95% CIs)] cardiometabolic risk score 0.25 (0.07, 0.42); visceral fat 0.21 (0.05, 0.38); and hemoglobin A1c 0.23 (0.05, 0.41) per standard deviation increase in pace of biological aging. Faster pace of biological aging was also positively associated with systolic blood pressure, triglycerides to HDL-C ratio, HOMA-IR, and leptin to adiponectin ratio, although these associations were not statistically significant.ConclusionsOur findings provide evidence that faster pace of biological aging was associated with higher cardiometabolic risk score, visceral fat, and HbA1c at age 12 years. Further research is needed to determine whether these associations persist from adolescence through adulthood.

SMIM1 absence is associated with reduced energy expenditure and excess weight

Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

The Association of Adiposity and RAAS with Incident Diabetes in African Americans: The Jackson Heart Study.

The renin-angiotensin-aldosterone system (RAAS) and adiposity measures are independently associated with the development of diabetes in African American (AA) adults. However, studies have not examined the combined interaction between RAAS and adiposity measures in relation to diabetes risk in AA adults. We examined the longitudinal association of combined RAAS and adiposity measures with incident diabetes among AAs in the Jackson Heart Study. AA adults were assessed at baseline (2000-2004) and over 12 years of follow-up. RAAS, anthropometric (waist circumference [WC], body mass index [BMI]) and adipokine (adiponectin, leptin, leptin: adiponectin ratio [LAR]) measures were collected at baseline. Aldosterone, WC, and LAR were chosen as the best predictor variables. The final model, adjusting for age, sex, education, occupation, systolic blood pressure, smoking, physical activity and RAAS altering medications, incorporated these variables and their interactions (WC*Aldosterone + LAR*Aldosterone) to explore their impact on incident diabetes. Among 3,220 participants without diabetes at baseline, there were 554 incident cases over a median follow-up of 7.5 years. Aldosterone, WC, and LAR were positively associated with incident diabetes (all p < 0.05). A significant interaction was found between WC and aldosterone with a greater association among individuals with lower WC. This interaction was significant in participants with prediabetes but not in those with normoglycemia. No significant interaction was found between log-LAR and aldosterone with risk of incident diabetes. Higher aldosterone in participants is associated with greater risk of diabetes, particularly among individuals with prediabetes and lower WC.

The impact of the obesity onset on the inflammatory and glycemic profile of women with severe obesity

BackgroundThe stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk. ObjectivesThis study aimed to evaluate the relationship between the obesity onset and the inflammatory profile in women with severe obesity. SettingPublic hospital, Brazil. MethodsForty-eight women with severe obesity (20–59 yr old) were evaluated according to weight, height, neck circumference (NC), waist circumference (WC), and hip circumference, as well blood metabolic and inflammatory parameters. The participants were grouped according to obesity onset stage of life (early group: ≤19 yr; late group: >19 yr). ResultsThe demographic means of the participants were: age of 39.7 years, weight of 122.7 kg and body mass index (BMI) of 48.4 kg/m2. The late group presented significantly higher values of leptin (lep)/adiponectin (adipo) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) than the early group. The late group also had a lower adipo/lep ratio. Moreover, the late group showed correlations between the lep/adipo ratio and BMI (r = .460, P = .021), NC (r = .478, P = .016), and WC (r = .535, P = .006). Adipo was also correlated with NC (r = −.418, P = .038), WC (r = −.437, P = .029), and glycated hemoglobin (HbA1C) (r = −.485, P = .019). By contrast, in the early group, the lep/adipo ratio showed correlations with insulin (r = .647, P = .004) and HOMA-B (r = .564, P = .015). ConclusionsThe inflammatory profile is correlated with anthropometric values in women with late-onset obesity. Inflammatory markers seemed to correlate with the glycemic profile in women with early-onset obesity. Furthermore, inflammation was higher in women with late-onset obesity compared to those with early-onset obesity.

The multidirectional assessment of moderate caloric restriction and metformin treatment in obese patients.

Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.

The Prevalence, Risk Factors and Cardiometabolic Complications of Obesity in Childhood Survivors of Acute Lymphoblastic Leukemia.

Prevalence, risk factors and metabolic complications of overweight/obesity (OW/OB) are not well described in the childhood survivors of acute lymphoblastic leukemia (ALL). Longitudinal changes in body mass index-z score (BMIz) from diagnosis to the last follow-up visit after the end of treatment were evaluated in 73 children at first complete remission. Of them, 40 were tested for adipokine profiles at visit. The mean BMIz increased gradually from diagnosis (0.07 ± 1.68) to the end of dexamethasone containing reinduction therapy (0.70 ± 1.48, P:0.007), followed by a fall at the end of treatment (0.15 ± 1.24) and a rise again at visit (0.40 ± 1.23, P:0.007). OW/OB percentage of 15% at diagnosis, increased to 35% at visit (p < 0.05). Post-treatment OW/OB in survivors was related with being OW/OB at diagnosis (OR 5.4, 95% CI [0.94-31.7]; P = 0.02) and after dexamethasone containing reinduction therapy (OR 5.1, 95% CI [1.1-21.4]; P = 0.05), but not with age at diagnosis, gender, treatment intensity and cranial irradiation. Metabolic syndrome (MetS) was more prevalent in survivors (13%) than in Turkish children (2%). As compared with controls, survivors had higher leptin level (8.1 ± 8.6 vs 3.2 ± 2.2ng/ml, P = 0.01) and leptin/adiponectin ratio (2.1 ± 3.5 vs 0.6 ± 0.5, P = 0.03). Leptin/adiponectin ratio was correlated with HOMA-IR (r: 0.57, P = 0.001). The prevalence of OW/OB and MetS are elevated in the childhood survivors of ALL. Post-treatment OW/OB in survivors is related with OW/OB at diagnosis and dexamethasone containing therapy. Elevated leptin level and leptin: adiponectin ratio may serve as an early sign of metabolic derangement increasing the risk for early cardiovascular disease.

Circulating Sex-Specific Markers of Plaque Instability in Women and Men With Severe Carotid Atherosclerosis.

Sex-specific differences in plaque composition and instability underscore the need to explore circulating markers for better prediction of high-risk plaques. This cross-sectional study aims to (1) investigate differences in lipid, immune, and adipokine circulating profiles between men and women with stable versus unstable plaques and (2) identify circulating markers that can better classify men and women according to plaque instability. Preoperative blood samples and plaque specimens were collected from consecutive men and women with carotid artery stenosis ≥50% and who underwent a carotid endarterectomy between 2009 and 2018. Adipokine, lipid, and immune profiling was conducted. Plaque stability was determined by gold-standard histological classifications. Statistical analyses, including χ2, ANOVA, Kruskal-Wallis, and logistic regression, assessed differences in plaque features and blood parameters between men and women with stable and unstable plaques. Of 470 recruited patients (aged 70.8±9.2 years), the final study analyses included 317 men and 143 women (aged 71.0±9.0 years). Men exhibited more unstable plaques (P<0.001), characterized by increased plaque hemorrhage, larger lipid core, and inflammation (P<0.001), along with less favorable circulating profiles. Antagonistic interactions between sex and white blood cell (WBC) counts, basophil-to-WBC ratio, and platelet counts influenced plaque instability. In men, low WBC counts, high monocyte-to-WBC ratio, low basophil-to-WBC ratio, and high LDL-C (low-density lipoprotein cholesterol) levels were associated with greater plaque instability (odds ratio, 0.827 [95% CI, 0.713-0.926], 1.158 [95% CI, 1.027-1.305], 0.495 [95% CI, 0.281-0.871], and 1.564 [95% CI, 1.001-2.443], respectively) and more unstable features (ie, inflammation, foam cells, and neovascularization). In women, a high basophil-to-WBC ratio was associated with greater plaque instability (3.142 [95% CI, 1.220-8.093]), hemorrhage, and thrombosis, while a high molecular weight-to-total adiponectin ratio was associated with decreased instability (0.014 [95% CI, 0.000-0.646]) and inflammation. Our findings demonstrated sex-specific differences, with women displaying more stable plaque phenotypes and favorable circulating profiles compared with men. This proof-of-concept study was also designed as the key first step in exploring novel sex-specific associations between circulating lipid, immune, and adipokine profiles and carotid plaque instability.

Interplay of adiponectin and resistin in type 2 diabetes: Implications for insulin resistance and atherosclerosis

Aim: The study aims to investigate the association between type 2 diabetes and adipokines, particularly resistin and adiponectin, in insulin resistance. It also explores the potential of the resistin to adiponectin ratio as an indicator for these conditions Methods: This research involved 198 participants, including 100 patients with type 2 diabetes and 98 controls. It focused on measuring various biochemical parameters like HbA1c, fasting plasma glucose, lipid profiles (low-density lipoprotein, oxidized low-density lipoprotein, triglyceride, total cholesterol), and adipokines (resistin and adiponectin). The study utilized the Homeostasis Model Assessment of Insulin Resistance and Triglyceride-Glucose index to evaluate insulin resistance. Results: Type 2 diabetic patients exhibited higher levels of HbA1c, fasting plasma glucose, lipid profiles, and resistin, but lower adiponectin levels compared to controls. Adiponectin showed a negative correlation with insulin resistance, while resistin demonstrated a positive correlation. Both adipokines significantly related to atherogenic markers, with adiponectin offering protection against atherosclerosis and resistin augmenting it. Conclusion: The findings underscore the complex roles of resistin and adiponectin in the pathophysiology of type 2 diabetes, insulin resistance. The resistin to adiponectin ratio could be a useful biomarker for insulin resistance. These insights suggest potential therapeutic strategies for treating diabetes and preventing its complications.

Changes in Leptin to Adiponectin Ratio After Antiretroviral Therapy: A Pilot Observational Study.

Weight gain with the use of dolutegravir, bictegravir, and tenofovir alafenamide for antiretroviral therapy has been reported. However, studies on changes in body composition and the leptin/adiponectin ratio after antiretroviral therapy initiation are limited. These factors are important because they can be used as indicators of metabolic syndrome and cardiovascular disease risk. This study aimed to investigate the changes in waist circumference, body composition, and adipokine levels after the initiation of antiretroviral therapy consisting of dolutegravir, bictegravir, and tenofovir alafenamide and evaluate the relationships between these parameters in Japanese patients living with human immunodeficiency virus. This is a single-center, prospective, observational study. Waist circumference, body composition, and adipokine levels were measured at baseline and 12 months after antiretroviral therapy initiation in antiretroviral therapy-naive Japanese patients living with human immunodeficiency virus. Body composition was determined by bioelectrical impedance analysis. We included 11 patients (10 bictegravir/TAF/emtricitabine, 1 dolutegravir/lamivudine) in this study. The results showed no significant changes in waist circumference and body composition among the patients. The leptin/adiponectin ratio and serum leptin levels significantly increased after antiretroviral therapy initiation. Changes in waist circumference, fat mass, and visceral fat area showed a strong positive correlation. The leptin/adiponectin ratio increased following antiretroviral therapy initiation. The waist circumference measurement can be a simple, inexpensive, and useful method to identify changes in fat mass and visceral fat area after initiation of antiretroviral therapy.

Abdominal Obesity in Women with Polycystic Ovary Syndrome and Its Relationship with Diet, Physical Activity and Insulin Resistance: A Pilot Study.

Abdominal obesity is a common feature of women with polycystic ovary syndrome (PCOS), and it is known to exacerbate insulin resistance (IR). Improper dietary and physical activity patterns are crucial environmental factors involved in the development of obesity, and they can significantly influence the central deposition of adipose tissue. Therefore, in this cross-sectional study, we aimed to evaluate the relationship between abdominal adiposity (measured by VAT (visceral adipose tissue), SAT (subcutaneous adipose tissue), VAT/SAT ratio (visceral to subcutaneous fat ratio), and WHR (waist-to-hip ratio)) and the prevalence and odds ratios of IR (measured by the homeostatic model assessment of insulin resistance (HOMA-IR), the homeostatic model assessment-adiponectin (HOMA-AD) and leptin to adiponectin ratio (L/A ratio)) in 56 PCOS women. Furthermore, we investigated the relationship between these abdominal obesity indices and diet and physical activity. An original food frequency questionnaire and Actigraph GT3X-BT were used to assess adherence to the diet recommended in IR and the level of physical activity, respectively. We observed a higher prevalence of IR among women with higher VAT, VAT/SAT, and WHR values compared to women with normal values of those abdominal obesity indices. Moreover, VAT/SAT seemed to be the best predictor of IR measured by HOMA-IR and HOMA-AD. However, VAT appeared to be the best and strongest predictor of IR measured by the L/A ratio. We also observed that higher adherence to the diet recommended in IR and higher levels of vigorous physical activity were associated with lower values of central fat accumulation indices and a greater chance of their normal values. Our findings indicate that central obesity increases the odds of IR and supports the beneficial role of diet and physical activity in the management of abdominal obesity in PCOS women.

Correlation of Leptin - Adiponectin Ratio with HDL and hsCRP in Obese Postmenopausal Women: Implications for Metabolic Health

Correlation of Leptin - Adiponectin Ratio with HDL and hsCRP in Obese Postmenopausal Women: Implications for Metabolic Health

Correlations between modest weight loss and leptin to adiponectin ratio, insulin and leptin resensitization in a small cohort of Norwegian individuals with obesity

BackgroundWeight loss is important to reduce the risk of metabolic complications in obese individuals, in whom dysregulated adipokines play a central role. This study aims to investigate whether dysregulated adipokines and postprandial triglycerides (TG) improve with a modest weight loss. MethodsIndividuals with obesity (BMI ≥ 30 kg/m2) were recruited among patients at the University Hospital of North Norway and the Stamina Health weight loss rehabilitation program. We measured resting energy expenditure (REE), and calculated the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), leptin to adiponectin (L:A) ratio, indirect leptin sensitivity (REE:leptin ratio), postprandial TG clearance at 6 h, and TG response before and after weight loss. The goal of the weight loss intervention was a loss of ≥5 % of initial total body weight. Results28 participants completed the study, of which 13 lost ≥ 5 % body weight and 18 lost <5 % body weight. HOMA-IR (−23.1 %), REE:leptin ratio (+80.1 %) and L:A ratio (−45.7 %) significantly improved with weight loss, whereas there was no improvement of postprandial TG response or clearance. No significant changes were observed in the non-weight loss group. ConclusionThe data are consistent with the general concept that modest weight loss in obese patients may restore metabolic regulation by improving L:A ratio and insulin and leptin sensitivity.

Markers of adipokine metabolism and hormonal-metabolic disorders in workers exposed to electric and magnetic fields of industrial frequency

Introduction. With the growth of urbanization processes, the problem of professional exposure to electric and magnetic fields of industrial frequency is an increasingly relevant topic. Recently, the scientists paid a special attention to the long-term health consequences associated with prolonged exposure to harmful physical factors. The previously obtained data on the increase in the levels of lipid metabolism and hormonal and metabolic disorders in workers exposed to electric and magnetic fields of industrial frequency determine the relevance of studying adipokine metabolism and assessing genetic risk factors for predisposition to cardiovascular pathology in employees of the electric power industry.&#x0D; The study aims to research the relationship of biochemical and molecular genetic markers of adipokine metabolism with indicators of hormonal and metabolic disorders for a comprehensive assessment of cardiovascular risk in workers exposed to electric and magnetic fields of industrial frequency.&#x0D; Materials and methods. The researchers examined 144 employees of the main group engaged in the repair and operation of power grid facilities and 40 employees of the control group who are not exposed to electromagnetic fields of industrial frequency.The concentration of leptin and adiponectin was determined in blood serum samples. The authors have calculated the ratio of adiponectin to leptin. We have performed a molecular genetic study of single nucleotide polymorphisms of leptin (LEP) G2548A (rs7799039), leptin receptor (LEPR) A668G (rs1137101) and adiponectin type two receptor (ADIPOR2) G795A (rs16928751) genes.&#x0D; Results. The staff of the main group revealed a higher level of leptin (8.1 (3.7; 14.4) ng/ml) relative to the same indicator in the control group (6.0 (4.1; 11.1) ng/ml), p&lt;0.028. Levels of leptin and adiponectin moderately and weakly correlate with hormonal and metabolic parameters. In the group of employees with less than 10 years of experience, a higher level of adiponectin was established compared to the group with 11–20 years of experience (6.1 (4.6; 9.1) mcg/ml and 4.5 (3.6; 6.4) mcg/ml, respectively); with an increase in work experience of more than 20 years, a significant increase in the concentration of leptin was found (p&lt;0.05). Scientists have identified the significance of single-nucleotide polymorphisms of the LEPR, LEP, ADIPOR2 genes in the development of abdominal obesity, an increase in cholesterol levels and a decrease in the level of total testosterone in workers exposed to electric and magnetic fields of industrial frequency.&#x0D; Limitations. The study is limited to the number of surveyed (144 employees).&#x0D; Conclusion. The results of the study indicate the relationship of biochemical and molecular genetic markers of adipokine metabolism with indicators of hormonal and metabolic disorders in employees exposed to electric and magnetic fields of industrial frequency. When examining workers exposed to electric and magnetic fields of industrial frequency, the use of clinical and laboratory markers of adipokine metabolism (biochemical, molecular genetic) is informative in a comprehensive assessment of cardiovascular risk.&#x0D; Ethics. The work complies with ethical standards developed in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting Scientific medical research with human participation" as amended in 2000 and the "Rules of Clinical Practice in the Russian Federation" approved by Order of the Ministry of Health of the Russian Federation No. 200n dated 01.04.2016. Informed consent to participate in the study was received from each of the surveyed, approved in accordance with the established procedure by the local ethics committee of Izmerov Research Institute of Occupational Health (minutes of the meeting of the Ethics committee of Izmerov Research Institute of Occupational Health No. 4 dated 12/25/2013).

Abstract #1398611: A High Chemerin: Adiponectin Ratio is Associated with Dysglycemia in Patients with the Polycystic Ovarian Syndrome (PCOS)

PCOS is a multifactorial disease, which in turn increases the chance of progression to Type 2 diabetes (T2D) and metabolic syndrome. Since PCOS is now recognized as the ovarian manifestation of metabolic syndrome, identifying potential biomarkers predictive of glucose intolerance in a subset of PCOS could have important implications for the prevention of T2D in this young population. We observed impaired glucose tolerance (IGT) in PCOS to precede impaired fasting glucose (IFG), indicating impaired insulin-mediated peripheral glucose disposal. Two-hour post-glucose plasma glucose (2h-PGPG), the gold standard protocol to detect IGT, has its limitations, i.e., expensive, labor-intensive, and variability issues. Identifying a biomarker is therefore an unmet need for community studies. Chemerin and Adiponectin are two important organokines that are inversely associated with each other in people with metabolic syndrome (MetS). We looked at Chemerin: Adiponectin ratio as a possible biomarker for glucose intolerance in PCOS. Both fasting plasma glucose and 2h-PGPG were measured biochemically by the GOD-POD method. HbA1c level was measured by HPLC. Serum chemerin and adiponectin levels were measured by ELISA using commercial kits from Cusa-Bio. Serum c-peptide level was used to calculate HOMA2IR and HOMA2β, using ELISA kits from G-Biosciences. Subjects with PCOS with glucose intolerance (PCOS-IGT); median (interquartile range), 26.71 (10.19 - 45.09) [n = 44] showed higher serum chemerin: adiponectin ratio (CAR) compared to controls (PCOS-NGT); median (interquartile range), 6.977 (5.470 - 14.06). CAR correlated positively with 2h-PGPG (r = 0.5347, p < 0.01) and negatively with HOMA-2β (r = -0.5029, p < 0.05). A CAR cut-off value of 14.15 on the ROC curve provided the optimum trade-off between sensitivity and specificity (70.59% and 78.95% respectively). The same cut-off value showed sensitivity and specificity of 76.92%, with an AUC of 0.8964 and likelihood ratio of 3.333, in the case of comparison between PCOS-NGT and PCOS subjects having 2h-PGPG in the diabetic range (PCOS-T2D). With a power (1 – β) of 0.9258, CAR could identify 93% of the subjects having peak plasma glucose levels on OGTT ≥ 140 mg/dL. Moreover, CAR correlated strongly with TG: HDLc ratio (r = 0.62, p < 0.0001). These results suggest that CAR may be utilized as a biomarker for dysglycaemia in the study population. CAR could be a surrogate marker of dysglycaemia in PCOS. The strong correlation between CAR and TG: HDLc ratio is consistent with the premise that lipid abnormalities might precede glucose abnormalities in PCOS, like the situation in metabolic syndrome.

Novel Adiponectin-Resistin Indices and Ratios Predict Increased Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus.

Adiponectin and resistin are adipokines involved in insulin resistance, glucometabolic control and adiposity. There is evidence that hypoadiponectinemia and hyperresistinemia are associated with cardiovascular disease. Whether the ratio of Adiponectin-Resistin (AR) and Insulin Resistance Adiponectin-Resistin (IRAR) indices can be used as non-invasive biomarker of cardiovascular disease needs more attention. Therefore, the aim of this study was to assess the relationships of AR and IRAR indices with adiposity, glucometabolic control and cardiovascular risk incurred by high-sensitivity C-reactive protein (hsCRP) in healthy subjects and patients with Type 2 Diabetes Mellitus. This observational case control study was conducted in the Department of Physiology and Medicine, King Saud University, Riyadh. A total of 191 (control = 84 and diabetic = 107) subjects were recruited. Body composition was assessed by bioelectrical impendence analyzer (BIA). Fasting blood samples were analyzed for glucose, glycosylated hemoglobin (HbA1c), high-sensitivity C-reactive protein (hsCRP), lipid profile, adiponectin, and resistin levels. The AR and IRAR indices were determined by formulas. Serum adiponectin levels were significantly lower in diabetics compared to control (95.45 ± 39.27 ng/ml vs 146.64 ± 56.36 ng/ml, p < .001) while serum resistin was significantly higher in diabetic when compared to control (2.94 ± 1.30 ng/ml vs 2.40 ± 1.09 ng/ml, p = .003). Furthermore, AR and IRAR indices were significantly increased in diabetic subjects when compared to control (.82 ± .29 vs .48 ± .35, p < .001) and (.30 ± .10 vs .17 ± .12, p < .001) respectively. ROC analysis revealed that these indices predicted increased cardiovascular risk with area under the curve (AUC) for adiponectin = .717 ( p = .001), resistin = .635 ( p = .002), AR index = .740 ( p < .001), and IRAR index = .737 ( p < .001) respectively. AR index correlated positively with Triglycerides (r = .354, p < .01), hsCRP (r = .264, p < .01), HbA1c (r = .425, p < .01), fat mass (r = .164, p < .05), Waist/Hip Ratio (WHR) (r = .248, p < .01), and negatively with high density lipoprotein (r=-.327, p < .01). Furthermore, IRAR index more strongly correlated with Triglycerides (r = .409, p < .01), hsCRP (r = .268, p < .01), HbA1c (r = .508, p < .01), fat mass (r = .152, p < .05), WHR (r = .256, p < .01), and negatively with high density lipoprotein (r = -.340, p < .01). AR and IRAR indices correlate significantly with adiposity, glucometabolic control and cardiovascular risk in type 2 diabetic patients and non-diabetic individuals. They may prove to be useful integrated biomarkers to predict metabolic dysregulation and cardiovascular risk.

Growth differentiation factor-15/adiponectin ratio as a potential biomarker for metabolic syndrome in Han Chinese.

Growth differentiation factor-15 (GDF-15) and adiponectin are adipokines that regulate metabolism. This study aimed to evaluate the roles of GDF-15, adiponectin, and GDF-15/adiponectin ratio (G/A ratio) as biomarkers for detecting metabolic syndrome (MS). This cross-sectional study included 676 participants aged 20-70 years in Jurong, China. The participants were divided into four groups based on sex and age (<40 and ≥40 years). MS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Receiver operating characteristic curves were used to evaluate the performance of GDF-15, adiponectin, and the G/A ratio in predicting MS. The prevalence of MS was 22.0% (149/676). Logistic regression analysis indicated that the G/A ratio and adiponectin levels, but not GDF-15 levels, were correlated with MS [odds ratio; 95% CI 1.010 (1.006-1.013) and 0.798 (0.735-0.865), respectively] after adjusting for confounding factors. The G/A ratio displayed a significant relationship with MS in each subgroup and with each MS component in both men and women; however, adiponectin concentrations were significantly associated with MS and all its components only in men (all P <0.05). The area under the curve (AUC) of the G/A ratio and the adiponectin level for MS was 0.758 and 0.748, respectively. The highest AUC was 0.757 for the adiponectin level in men and 0.724 for the G/A ratio in women. This study suggests that the G/A ratio and adiponectin are potential biomarkers for detecting MS in women and men, respectively.

Adiposity, aldosterone and plasma renin activity among African Americans: The Jackson Heart Study

ObjectiveTo analyze associations between adiposity and the renin-angiotensin-aldosterone system (RAAS) in a large African American (AA) cohort. MethodsCross-sectional associations of adiposity (body mass index [BMI], waist circumference [WC], waist:height ratio, waist:hip ratio, leptin, adiponectin, leptin:adiponectin ratio [LAR], subcutaneous [SAT] and visceral adipose tissue [VAT], and liver attenuation [LA]) with aldosterone, plasma renin activity (renin), and aldosterone:renin ratio (ARR) were assessed in the Jackson Heart Study using adjusted linear regression models. ResultsA 1-SD higher BMI was associated with a 4.8 % higher aldosterone, 9.4 % higher renin, and 5.0 % lower ARR (all p < 0.05). Log-leptin had the largest magnitude of association with renin (30.2 % higher) and ARR (9.6 % lower), while the strongest association of aldosterone existed for log-LAR (15.3 % higher) (all 1-SD, p < 0.05). SAT was only associated with renin. VAT was associated with higher aldosterone, renin, and ARR. Liver fat was associated with aldosterone and renin, but not ARR. Associations of WC, BMI, and SAT with aldosterone were greater in men while the association with VAT was greater in women (p-interactions < 0.05). ConclusionMultiple measures of adiposity are associated with the RAAS in AAs. Further studies should examine the role of RAAS in obesity-driven cardiometabolic diseases.

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6–7 Years: A Follow-Up of a Randomized Controlled Trial

BackgroundDeficiencies of vitamin B12 and folate are associated with elevated concentrations of metabolic markers related to CVDs. ObjectivesWe investigated the effect of supplementation of vitamin B12 with or without folic acid for 6 mo in early childhood on cardiometabolic risk markers after 6–7 y. MethodsThis is a follow-up study of a 2 × 2 factorial, double-blind, randomized controlled trial of vitamin B12 and/or folic acid supplementation in 6–30-mo-old children. The supplement contained 1.8 μg of vitamin B12, 150 μg of folic acid, or both, constituting >1 AI or recommended daily allowances for a period of 6 mo. Enrolled children were contacted again after 6 y (September 2016–November 2017), and plasma concentrations of tHcy, leptin, high molecular weight adiponectin, and total adiponectin were measured (N = 791). ResultsAt baseline, 32% of children had a deficiency of either vitamin B12 (<200 pmol/L) or folate (<7.5 nmol/L). Combined supplementation of vitamin B12 and folic acid resulted in 1.19 μmol/L (95% CI: 0.09; 2.30 μmol/L) lower tHcy concentration 6 y later compared to placebo. We also found that vitamin B12 supplementation was associated with a lower leptin–adiponectin ratio in subgroups based on their nutritional status. ConclusionsSupplementation with vitamin B12 and folic acid in early childhood was associated with a decrease in plasma tHcy concentrations after 6 y. The results of our study provide some evidence of persistent beneficial metabolic effects of vitamin B12 and folic acid supplementation in impoverished populations.The original trial was registered at www.clinicaltrials.gov as NCT00717730, and the follow-up study at www.ctri.nic.in as CTRI/2016/11/007494.

Abstract P4-03-31: Lifestyle factors are associated with breast cancer risk in women biopsied for benign breast diseases in China: 10-year results of a multi-center, hospital-based, case-control study

Abstract Objective: Benign breast disease (BBD), especially benign proliferative breast disease (BPBD), is related to increased breast cancer risk. However, few studies have examined whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD. The aim of this study was to evaluate the associations of lifestyle factors with risk of breast cancer among women biopsied for BBD within a multi-center, hospital-based, case-control study in China, in order to provide scientific basis of health guidance for BBD patients and lay the foundation for primary prevention of breast cancer. Methods: A multi-center, hospital-based, case-control study was conducted. Patients with BPBD (n=608) and patients with non-proliferative breast disease (NPBD) (n=366) were collected from 23 hospitals in 11 provinces during April 2012 to April 2013. A face-to-face survey, baseline data and fasting blood was collected with all study subjects. Serum adiponectin levels were assayed using ELISA. After 10 years, the cumulative incidence rate of breast cancer in the two groups was counted through follow-up. Logistic regression analysis was used to obtain the association between specific factors and risk of breast cancer. Results: After 10 years’ follow-up, 388 BPBD and 240 NPBD cases were included in the final analysis (Table 1), of which 16 (4.12%) and 3 (1.25%) developed breast cancer, respectively. The cumulative incidence of breast cancer between the two groups was significant difference (P=0.041). Compared with women in the NPBD group, BPBD group were more likely to be central obesity (with higher waist-to-hip ratio (WHR)) (OR 24.98, 95% CI 1.845-336.203, P=0.015) and less likely to have physical activity (OR 0.626, 95% CI 0.416-0.943, P=0.025) and less often to eat carrots (OR 0.616, 95% CI 0.398-0.953, P=0.030) (Table 2). Subgroup analyze indicated that, physical activity, eat carrots and ham sausage, body weight, BMI, waist circumference and WHR were statistical differences in premenopausal BPBD patients, while only physical activity (OR 0.423, 95% CI 0.269-0.665 P &amp;lt; 0.001) was the independent risk factors. Meanwhile, among the factors of Tea consumption, Glycemia, Body weight, BMI, Waist circumference, WHR and HMW/total adiponectin ratio in postmenopausal group, only HMW/total adiponectin ratio (OR 0.041, 95% CI 0.002-0.820 P=0.037) was statistically significant factor. These stratified multivariate logistic regression analysis results are shown in Table 3. Conclusion: In patients with BBD, physical activity may be the protect factor for breast cancer carcinogenesis in premenopausal women while lower HMW/total adiponectin ratio is a risk factor for postmenopausal women, which can provide direction for primary prevention of breast cancer. Table 1. Pathological types of all subjects. Table 2. The results of multivariate Logistic regression analysis. Table 3. Stratified multivariate Logistic regression analysis by menopause status. Citation Format: Chao Zheng, Dandan Ma, Linfeng Zhao, Maolin Guo, Shude Cui, Fuguo Tian, Zhimin Fan, Cuizhi Geng, Xuchen Cao, Zhenlin Yang, Xiang Wang, Hong Liang, Shu Wang, Hongchuan Jiang, Xuening Duan, Haibo Wang, Guolou Li, Qitang Wang, Jianguo Zhang, Feng Jin, Jinhai Tang, Liang Li, Shi-Guang Zhu, Wenshu Zuo, Fei Wang, Lixiang Yu, Fei Zhou, Yujuan Xiang, Mingming Guo, Yongjiu Wang, Wenzhong Zhou, Shuya Huang, Zhaohui Li, Yajie Zhou, Lijuan Hou, Xinyi Yang, Xuan Zhang, Liyuan Liu, Zhigang Yu. Lifestyle factors are associated with breast cancer risk in women biopsied for benign breast diseases in China: 10-year results of a multi-center, hospital-based, case-control study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-31.

Pre- and postnatal exposure to secondhand tobacco smoke and cardiometabolic risk at 12 years: Periods of susceptibility

BackgroundTo identify periods of heightened susceptibility to the association of secondhand tobacco smoke (SHS) exposure with cardiometabolic (CM) risk at age 12 years. MethodsWe used data from 212 adolescents from the HOME Study, a prospective pregnancy and birth cohort in Cincinnati, OH. Using multiple informant models, we estimated associations of maternal serum cotinine (mean of concentrations at 16 and 26 weeks of pregnancy) and children's serum cotinine concentrations (mean of concentrations at ages 1, 2, 3, and 4 years) with a CM risk summary score constructed of five risk components measured at age 12 years. We determined if these associations differed for pre- and postnatal exposure periods, and adolescent's sex. ResultsWe found some evidence that the cotinine-outcome associations differed by exposure period and sex. Postnatal, but not prenatal, cotinine was associated with higher CM risk scores and individual CM risk component values (interaction p-values = 0.04 to 0.35). Each 10-fold increase in postnatal cotinine was associated with 0.57 (95% CI: 0.32, 1.45), 0.09 (95% CI: 0.13, 0.31), 0.14 (−0.08, 0.35), 0.07 (95% CI: 0.34, 0.48), and 0.11 (95% CI: 0.04, 0.27) higher CM risk, HOMA-IR, TG to HDL-C ratio, leptin to adiponectin ratio, and visceral fat area. Postnatal cotinine was associated with higher visceral fat area among females but not males (sex × period × cotinine interaction p-value = 0.01). ConclusionsSerum cotinine concentrations during the postnatal period had greater influence on adolescent's CM risk compared to the prenatal period, and these associations may be sex-specific. This study reinforces the need for ongoing public health interventions to minimize children's exposure to SHS.