Leptin-adiponectin Ratio Research Articles

6613 Liver and Spleen Linked in Hepatic Steatosis during Weight Reduction in Type 2 Diabetes

Abstract Disclosure: K. Han: None. K. Min: None. Splenectomy increased serum lipids, except triglyceride (TG) and high-density lipoprotein (HDL), significantly accelerating hepatic steatosis in animal study. Recently, the concept of a liver-spleen axis has been proposed in nonalcoholic fatty liver disease. The purpose of this study was to investigate change of the liver Hounsfield Units (HU), reflecting the hepatic steatosis, and its relation to spleen HU, central, or peripheral and ectopic adipose tissue during weight reduction in type 2 diabetes. Total 187 women with type 2 diabetes were educated on lifestyle modification. We assessed liver Hounsfield Units(HU) and spleen HU with total abdominal fat(ATAF) , visceral adipose tissue (AVAT), subcutaneous adipose tissue(ASAT) at mid-abdomen level, and total adipose tissue (TTAT)and intramuscular adipose tissue(TIMAT) at midthigh level using nonenhanced computed tomography, at baseline and 12 weeks. We investigated whether changes in liver HD were related to fat in other regions, serum triglycerides, free fatty acids, and adiponectin-leptin ratio (ALR). The participants’ age was 55.2±7.3 years, BMI was 27.3±2.7 kg/m2, Body Weight (BW) 66.8±6.9kg). Baseline liver HU was 54.7±11.5, and spleen HU was 48.5±8.5. At 12 weeks, BW lost 2.4±2.2kg. Liver HU changed with spleen HU (r=0.357, p<0.001, ATAT(r=-0.343, p<0.0001), AVAT (r=0.220, p=.011), ASAT(r=-0.339, p<0.001) and adiponectin-leptin ratio (ALR) (r=-0.174, p=0.047), but no significant relations with TTAT, TIMAT, triglyceride, and free fatty acid. Linear regression analysis showed the best model for change of liver HU (Model R2=0.209, p<0.001) was as follows: Change of Liver HU=0.534 +0.038* change of spleen HU - 0.290* change of ATAF. Higher spleen HU (p<0.001) and lower abdominal fat (p<0.001) predicted higher liver HU (less steatosis). These results suggested that the liver might be metabolically linked to the spleen in hepatic steatosis of type 2 Diabetes. Presentation: 6/2/2024

The association between macrosomia and glucose, lipids and hormones levels in maternal and cord serum: a case-control study

BackgroundThe formation of macrosomia is associated with excessive nutrition and/or unable to regulate effectively. This case-control study aims to explore the relationship between macrosomia and glucose, lipids and hormones levels in maternal and cord serum.MethodsIn the case-control study, 78 pairs of mothers and newborns were recruited who received care at one hospital of Hebei, China between 2016 and 2019. According to the birth weight (BW) of newborns, participants were divided into macrosomia group (BW ≥ 4000 g, n = 39) and control group (BW between 2500 g and 3999 g, n = 39). Maternal vein blood and cord vein blood were collected and assayed. All data were compared between the two groups. Unconditional logistics regression analysis was used to test the relationship between macrosomia and glucose, lipids and hormones in maternal and cord serum.ResultsIn maternal and cord serum, the levels of leptin, leptin/adiponectin ratio (LAR), glucose and triglyceride (TG) in macrosomia group were higher than those in control group, and the levels of high-density lipoprotein cholesterol (HDL-C) were lower. The percentage of maternal glucose and lipids transfer to cord blood did not differ between the two groups. High levels of TG in maternal serum were positively correlated with macrosomia, and high levels of LAR, TG and glucose in cord serum were positively correlated with macrosomia.ConclusionIn conclusion, the results of the current study, suggest that the nutrients and metabolism-related hormones in maternal and umbilical cord are closely related to macrosomia. During pregnancy, the nutritional status of pregnant women should be paid attention to and to obtain a good birth outcome.

Associations of sedentary behavior and screen time with biomarkers of inflammation and insulin resistance.

Sedentary behavior (SB) has been linked to risk factors of cardiometabolic disease, with inconsistent findings reported in the literature. We aimed to assess the associations of SB with multiple biomarkers of inflammation and insulin resistance in adults. Domain-specific SB, sitting time and moderate-to-vigorous physical activity (MVPA) were measured in 78 adults (mean ± SD 52.0 ± 10.8 y). Body fat percentage (BF%) was assessed using multi-frequency bioelectrical impedance. A blood draw assessed glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, and adiponectin. Adiponectin-leptin ratio (ALR), homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) were calculated. Multivariable linear regression analyses, controlling for age, sex, MVPA, and BF%, were used to assess associations. After adjustment for age, sex and MVPA, total SB (7.5 ± 2.5h/day) was positively associated with leptin, insulin, HOMA-IR, HOMA-β (Standardized Beta (β) range 0.21-0.32) and negatively associated with ALR (β = -0.24, p < 0.05 for all). Similarly, total sitting time (7.2 ± 2.9h/day) was associated with TNF-α (β = 0.22) and ALR (β = -0.26). These associations were attenuated to non-significance after adjustment for BF%. Leisure screen time was detrimentally associated with IL-6 (β = 0.24), leptin (β = 0.21), insulin (β = 0.37), HOMA-IR (β = 0.37), and HOMA-β (β = 0.34), independent of age, sex and MVPA (p < 0.05 for all). Only the associations with insulin (β = 0.26), HOMA-IR (β = 0.26), and HOMA-β (β = 0.23) remained significant after further controlling BF% (p < 0.05). Self-reported SB is associated with biomarkers of inflammation and insulin resistance, independent of MVPA, and in some cases BF%.

Surrogate indices of insulin resistance using the Matsuda index as reference in adult men-a computational approach.

Overweight and obesity, high blood pressure, hyperglycemia, hyperlipidemia, and insulin resistance (IR) are strongly associated with non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular disease, stroke, and cancer. Different surrogate indices of IR are derived and validated with the euglycemic-hyperinsulinemic clamp (EHC) test. Thus, using a computational approach to predict IR with Matsuda index as reference, this study aimed to determine the optimal cutoff value and diagnosis accuracy for surrogate indices in non-diabetic young adult men. A cross-sectional descriptive study was carried out with 93 young men (ages 18-31). Serum levels of glucose and insulin were analyzed in the fasting state and during an oral glucose tolerance test (OGTT). Additionally, clinical, biochemical, hormonal, and anthropometric characteristics and body composition (DEXA) were determined. The computational approach to evaluate the IR diagnostic accuracy and cutoff value using difference parameters was examined, as well as other statistical tools to make the output robust. The highest sensitivity and specificity at the optimal cutoff value, respectively, were established for the Homeostasis model assessment of insulin resistance index (HOMA-IR) (0.91; 0.98; 3.40), the Quantitative insulin sensitivity check index (QUICKI) (0.98; 0.96; 0.33), the triglyceride-glucose (TyG)-waist circumference index (TyG-WC) (1.00; 1.00; 427.77), the TyG-body mass index (TyG-BMI) (1.00; 1.00; 132.44), TyG-waist-to-height ratio (TyG-WHtR) (0.98; 1.00; 2.48), waist-to-height ratio (WHtR) (1.00; 1.00; 0.53), waist circumference (WC) (1.00; 1.00; 92.63), body mass index (BMI) (1.00; 1.00; 28.69), total body fat percentage (TFM) (%) (1.00; 1.00; 31.07), android fat (AF) (%) (1.00; 0.98; 40.33), lipid accumulation product (LAP) (0.84; 1.00; 45.49), leptin (0.91; 1.00; 16.08), leptin/adiponectin ratio (LAR) (0.84; 1.00; 1.17), and fasting insulin (0.91; 0.98; 16.01). The computational approach was used to determine the diagnosis accuracy and the optimal cutoff value for IR to be used in preventive healthcare.

Gestational Diabetes Mellitus and Colostral Appetite-Regulating Adipokines.

Gestational diabetes mellitus (GDM) is a complex metabolic disorder that has short- and long-term effects on maternal and offspring health. This study aimed to assess the impact of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment) on colostral appetite-regulating molecules. Colostrum samples were collected from hyperglycemic (N = 30) and normoglycemic (N = 21) mothers, and the concentrations of milk hormones were determined by immunoenzymatic assay. A difference was found for milk ghrelin, but not for molecules such as adiponectin, leptin, resistin, or IGF-I levels, in relation to maternal hyperglycemia. The colostral ghrelin in the GDM-G1 cohort (0.21 ng/mL) was significantly lower than for GDM-G2 (0.38 ng/mL) and non-GDM groups (0.36 ng/mL). However, colostral resistin was higher, but not significantly, for GDM-G1 (13.33 ng/mL) and GDM-G2 (12.81 ng/mL) cohorts than for normoglycemic mothers (7.89 ng/mL). The lack of difference in relation to hyperglycemia for milk leptin, adiponectin, leptin-adiponectin ratio, resistin, and IGF-I levels might be the outcome of effective treatment of GDM during pregnancy. The shift between ghrelin and other appetite-regulating hormones might translate into altered ability to regulate energy balance, affecting offspring's metabolic homeostasis.

To Study the Evidence of Linking Adipokines (Adiponectin, Leptin) with Metabolic Syndrome: A Systematic Review

Background: A growing body of world health has shown that there is a correlation between derangement of adipokines section and metabolic syndrome, but a small number of studies also refused the data. Considering these aspects, this study is intense in pursuing precise knowledge regarding the same and the conclusion. Aim and Objective: This study investigates the connection between markers of metabolic syndrome and adipokines, particularly leptin and adiponectin. Methods: PubMed, Scopus, and Web of Science databases were used for a thorough literature review. From 2013 to 2023, the terms “adipokines and metabolic syndrome”, “adiponectin and metabolic syndrome”, and “leptin and metabolic syndrome” were searched. This review made use of the preferred reporting items for systematic review and meta. Results: About 3448 previous studies were searched, of which 85 studies fulfilled the inclusion and exclusion criteria. A total of 85 papers comprised this systematic review, and we examined 60 of them. An overvalue of most studies showed that decreased adiponectin levels are linked with a higher risk of metabolic syndrome. However, patients with metabolic syndrome had higher risk levels of both leptin and the leptin-adiponectin ratio. Conclusions: Obesity affects the generation of adipokines, which regulates the many factors of the metabolic syndrome, through unique and linked pathways. Therefore, we conclude that obesity resulting from a high-fat, high-sugar, high-lipid diet may affect various organs, increasing the risk of metabolic diseases and the underlying causes of insulin resistance and triggering an inflammatory response.

Association between plasma leptin/adiponectin ratio and insulin resistance indexes in prepubertal children.

To assess the association between leptin/adiponectin ratio (LAR) and insulin resistance surrogates in prepubertal children. Study based on data from the Growth and Obesity Chilean Cohort Study (GOCS) involving 968 Chilean prepubertal children. Plasma insulin, leptin, and adiponectin were determined by immunoassays. Several common insulin resistance surrogates were calculated, including the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride/HDL cholesterol index, triglyceride-glucose (TyG) index, and the TyG index corrected for body mass index (BMI; TyG-BMI) and waist circumference (WC; TyG-WC). Associations among variables were assessed using multiple linear and logistic regression analysis. There was a significant direct association between plasma leptin and LAR with BMI z-score but no association between plasma adiponectin and adiposity. After adjustments for sex and age, LAR was significantly associated with all insulin resistance surrogates (which were categorized using the 75th percentile as the cutoff point), with the TyG-WC index emerging as the surrogate with the highest magnitude of association (odds ratio [OR] 2.44, 95% confidence interval [CI] 2.05-2.9). After additional adjustment for BMI z-score, only the association between LAR and TyG-WC remained significant (OR 1.64, 95% CI 1.27-2.12). Plasma leptin and LAR were strongly associated with several common insulin resistance surrogates in prepubertal children, most notably with the TyG-WC index. Associations between LAR and insulin resistance indexes were mainly driven by the effect of plasma leptin, which is also directly associated with increased adiposity.

Alternative dosing regimen of exemestane in a randomized presurgical trial: the role of obesity in biomarker modulation

In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4–6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)< or ≥30 kg/m2. Post-treatment median exemestane and 17-OH exemestane levels were 5–6 times higher in the QD arm compared to the TIW arm. For obese women, TIW maintained comparable reductions to QD in systemic estradiol levels, although the reduction in estrone was less with the TIW regimen. There was less suppression of SHBG with the TIW versus the QD dose schedule in obese women which should result in less systemic bioavailable estrogens. Metabolically, the effect of the TIW regimen was similar to the QD regimen for obese women in terms of leptin suppression and increase in the adiponectin-leptin ratio. Reduction in tissue Ki-67 was less for obese women on the TIW regimen than QD, although changes were similar for non-obese women. Our findings suggest that TIW exemestane should be explored further for primary cancer prevention in both normal weight and obese cohorts.

Serum Adipokines as Biomarkers for Surveillance of Metabolic Syndrome in Childhood Acute Lymphoblastic Leukemia Survivors in Low Middle-Income Countries

Background Serum adipokines (leptin and adiponectin) are dysregulated before the onset of metabolic syndrome and hence may be useful biomarkers for screening of cardiometabolic late effects in childhood Acute Lymphoblastic Leukemia (cALL) survivors. Methods We compared serum adipokine levels between 40 cALL survivors (aged 10–18 years, >2 years from treatment completion) with similar controls. A multivariable logistic regression analysis was then done to assess the association of metabolic syndrome in cALL survivors with variables including adipokines and other metabolic parameters, demographic and treatment details, and Dual-energy X-ray absorptiometry scan-derived variables. Results Compared to controls, cALL survivors had a higher prevalence of metabolic syndrome (8/40 vs. 2/40, P = .044) and central obesity (11/40 vs. 4/40, P = 0.042). Median Serum Leptin (7.39 vs. 4.23 ng/ml, P = 0.207) levels and derived Leptin-Adiponectin Ratio (1.44 vs. 0.80, P = 0.598), were higher but not statistically different in our survivors compared to controls; Adiponectin levels were similar (6.07 vs. 5.01 µg/ml, P = 0.283). In the cALL survivors, overweight/obesity (odds ratio [OR] 21.9, P = 0.020) or higher Leptin levels (OR 1.11, P = 0.047), were independently associated with metabolic syndrome. Conclusions Serum Leptin, independently predictive of metabolic syndrome in our cALL survivors, may be tested in larger studies to assess its utility in surveillance and initiation of early preventive measures.

Serum Leptin-adiponectin Ratio in Patients With and Without Metabolic Syndrome: A Cross-sectional Study

Introduction: Metabolic Syndrome (MetS) is one of the most significant global public health concerns. Leptin, adiponectin, and the Leptin-adiponectin (LA) ratio have been shown to be informative biomarkers for obesity, Type 2 Diabetes Mellitus (T2DM), and Cardiovascular Diseases (CVD). Many contributing factors, such as Insulin Resistance (IR), adipose tissue dysfunction, chronic inflammation, and genetic factors, are proposed to be the aetiological factors of MetS. Leptin and adiponectin have opposite effects on IR, so the combined use of these adipokines may serve as a better biomarker in MetS. Aim: To determine serum leptin levels, adiponectin levels, and the LA ratio in patients with and without MetS. Materials and Methods: This cross-sectional study was conducted in the Department of Biochemistry and Medicine at the Regional Institute of Medical Sciences (RIMS), Imphal, Manipur, India, from January 2021 to October 2022. The study included 50 diagnosed cases of MetS and 50 individuals without MetS. Leptin, adiponectin, and parameters of MetS {Body Mass Index (BMI), weight, Waist Circumference (WC), skinfold thickness, High-density Lipoprotein (HDL), Triglycerides (TG), and Blood Pressure (BP)} were assessed in the study. The data were statistically analysed using Independent Sample t-test and Pearson’s correlation test. Results: There were 23 males and 27 females in the study group. The mean age was found to be 61.10±12.52 years in cases and 57.08±10.67 years in controls. Leptin levels were significantly higher in cases (26.58±14.6 ng/mL) compared to controls (12.99±8.59 ng/mL). However, adiponectin levels were significantly decreased in cases (7.16±4.19 μg/mL) compared to controls (12.18±9.4 μg/mL). The LA ratio was found to be higher in cases (5.38±4.71 ng/μg) than in the controls (1.84±1.99 ng/ μg). Multiple linear regression analysis demonstrated that the LA ratio was strongly associated with MetS among Leptin, Adiponectin, and the LA ratio (p&lt;0.05). Conclusion: Metabolic syndrome was strongly associated with an increased LA ratio, leptin, and decreased adiponectin levels. The LA ratio can better discriminate the risk of MetS than leptin and adiponectin alone and may be used as a sensitive clinical surrogate biomarker of MetS.

Insulin resistance is associated with incident chronic kidney disease in population with normal renal function.

Insulin resistance is prevalent in chronic kidney disease and may accelerate the progression of chronic kidney disease. This study aimed to investigate whether insulin resistance is associated with the development of incident chronic kidney disease in a population with normal renal function. A total of 3,331 participants from a community-based cohort with normal renal function were prospectively analyzed. We determined the relationship of insulin resistance indices with the incident chronic kidney disease using the Cox proportional hazard model and Kaplan-Meier survival analysis. During a mean follow-up of 11.03 ± 4.22 years, incident chronic kidney disease occurred in 414 participants (12.4%). The high homeostasis model assessment-insulin resistance level group had an increased risk of incident chronic kidney disease (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.13-1.74; p = 0.002) compared to the normal group after adjustment for age, sex, history of hypertension, body mass index, total cholesterol, alcohol drinking status, smoking status, and baseline estimated glomerular filtration rate. The risk of incident chronic kidney disease also increased with the lower quantitative insulin sensitivity check index level (HR, 0.62; 95% CI, 0.41-0.92; p = 0.02) and higher leptin-adiponectin ratio level (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006). Higher insulin resistance indices are associated with the incidence of chronic kidney disease. Our data suggest that increased insulin resistance may be involved in the development of incident chronic kidney disease in a population with normal renal function.

A Whole Foods Plant-Based Weight Loss Intervention Improves Quality of Life, Metabolic, Microbiome and Immune Profile in MGUS/SMM As Well As Progression Trajectory in a Subset - the Nutrivention Trial

Introduction Obesity, low adiponectin, high leptin, high insulin, and diets lacking plant-based foods are risk factors for plasma cell disorders (PCDs). Patients (pts) with monoclonal gammopathy (MGUS) and smoldering myeloma (SMM) and an elevated body mass index (BMI) are twice as likely to progress to myeloma (MM). There is evidence of microbiome dysbiosis in pts with PCDs and dietary changes can induce large microbial shifts. Therefore, there is a rationale to study a whole food plant-based dietary (WFPBD) intervention to improve modifiable biomarkers and disease trajectory. Methods This was a pilot, single-arm trial of WFPBD (self-selected prepared frozen lunch/dinner provided by Plantable with breakfast/snack guidance and no calorie restriction) for 12-weeks (w) and health coaching for 24w (by Plantable coach and a research dietitian) in pts with MGUS/SMM and BMI ≥25 (NCT04920084). The primary endpoint was feasibility (mean BMI reduction ≥5% and mean dietary adherence [kcal % unprocessed plant food intake] ≥70%) at 12w; secondary endpoints included quality of life (QoL) (EORTC QLQ C30 survey using a linear-mixed effect model), metabolic markers (plasma insulin, adiponectin leptin (AL) ratio via ELISA), gut microbiome (inverse Simpson index α-diversity and relative abundance of butyrate producers (RABP) via stool 16S sequencing), peripheral blood immune profile (leukocyte subsets via 36 color flow cytometry), secreted biomarkers (plasma via Olink inflammation panel) and change in monoclonal (M)-spike concentrations. Rate of change of M-spike/year (y) measured by slope with 95% CI was calculated for up to 20 months (m) pre-intervention and 20m post intervention start (baseline (BL)). A p-value for difference in M-spike rates was calculated. Results The study enrolled 23 pts of which 20 completed the 12w intervention and 16 completed 1y. The median age was 62y with 43% male, 43% non-White, 52% MGUS, 74% obese, and 26% prediabetic/diabetic. The study met feasibility endpoints with 90% mean and 92% median adherence during 12w intervention and 77% median at 24w. There was an 8.3% mean and 6.6% median BMI reduction at 12w and 8.6% median at 24w. There was an improvement in global health status/QoL (median increase 16.7 points, p=0.03), a reduction in dyspnea (median decrease -33.3 points, p=0.001), fatigue (median decrease -11.1 points, p=0.06), and insulin (median decrease 0.791 mU/L; p=0.01), and an increase in AL ratio (median increase 0.09; p=0.0002), α-diversity (median increase 6.18 to 8.42; p= 0.03) and RABP (median increase 0.03 to 0.08; p=0.042) at 12w. Prelim results at 12w suggest a measurable, albeit not significant change in immune subsets such as an increase in monocytes, regulatory T cells, and a decrease in dendritic cells, trends previously associated with anti-inflammatory diets, as well as increase in butyrate. A decrease in proinflammatory cytokines IL8 (p=0.065), IL12B (p=0.068), and TNFB (p=0.082) and an increase in FGF21 (p=0.043) (promoter of insulin sensitivity) was also observed. Butyrate is known to reduces pro-inflammatory cytokines and increase anti-inflammatory proteins, including FGF21. Further immune and microbiome analysis is ongoing. Of 16 pts followed for 1y, 2 with significant BMI reduction had significant improvement in M-spike trajectory: Case 1: Mayo Int Risk IgGκ/IgGλ MGUS achieved a 1y BMI reduction of 19%. Pre-intervention M-spike changed +0.28g/dL/y (6 M-spike values), and during intervention M-spike changed +0.03g/dL/y (11 M-spike values); p=0.008. BL M-spike 1.2g/dL and bone marrow plasma cells (BM PC) &amp;lt;5%; 1.5y BM PC 5-9%. Case 2: IMWG Int Risk IgGκ SMM achieved a 1y BMI reduction of 13%. Pre-intervention M-spike changed +0.11g/dL/y (8 M-spike values), and during intervention M-spike changed -0.05g/dL/y (8 M-spike values); p=0.04. BL M-spike 1.2g/dL and BM PC 20-30%; 1y BM PC 10-15%. Two pts without significant BMI reduction (-4% and -1% at 1y) had rising M-spikes. The remaining 12 pts had median 7.5% BMI reduction at 1y with stable M-spike. Conclusions This is the first dietary intervention trial in PCDs with insights into the mechanisms by which a WFPBD may delay progression. The intervention improves QoL, metabolic (BMI, insulin resistance), microbiome (α-diversity and butyrate producers) as well as immune (reduced inflammation) profile with potentially slowing progression trajectory in a subset. A larger trial is underway (NCT05640843).

#3781 INSULIN RESISTANCE IS ASSOCIATED WITH INCIDENT CHRONIC KIDNEY DISEASE IN POPULATION WITH NORMAL RENAL FUNCTION

Abstract Background and Aims Insulin resistance is prevalent in chronic kidney disease (CKD) and may accelerate its progression. This study aimed to investigate whether insulin resistance was associated with the development of incident CKD in a population with normal renal function. Method A total of 3,331 individuals with normal renal function from a community-based cohort formed the study population. We determined the relationship between insulin resistance indices and incident CKD using Cox proportional hazard model and Kaplan-Meier survival analysis. Results During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 414 (12.4%) participants. The high homeostasis model assessment-insulin resistance (HOMA-IR) level group had an increased risk of incident CKD (HR, 1.40; 95% CI, 1.13-1.74; p = 0.002) compared to the normal group after adjusting for confounding factors The risk of incident CKD also increased with lower quantitative insulin sensitivity check index (QUICKI) levels (HR, 0.62; 95% CI, 0.41-0.92; p = 0.018) and higher leptin-adiponectin ratio (LAR) levels (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006). Conclusion Higher insulin resistance indices were associated with the incidence of CKD. Our data suggests that increased insulin resistance may be involved in the development of incident CKD in individuals with normal renal function.

Adiponectin-leptin ratio as a marker of cardio-metabolic risk in Indian children and youth with type 1 diabetes.

Adiponectin/leptin ratio (ALR) is a promising novel marker of cardio-metabolic risk in patients with metabolic syndrome. Our aim was to study theassociation of adiponectin-leptin ratio with markers of obesity and adiposity and also to assess its usefulness as a marker of increased cardiometabolic risk (CMR) in Indian children and youth with type 1 diabetes mellitus. This observational study included 79 children and youth with type 1 diabetes (T1DM) (10-21 years) having disease duration>6months. Demographic data and laboratory findings were obtained from patients' records. Patients with ALR<1 were categorised as having increased CMR and those with ALR>1 were categorised as having no CMR. ALR showed a significant negative correlation with body mass index (BMI), waist and hip circumference and body fat percentage (p<0.05). Body fat percentage was the single most important predictor of ALR. Children and youth with increased CMR had higher weight, BMI, waist and hip circumferences and body fat percentage as compared to those with no CMR (p<0.05). In T1DM children with dyslipidemia, ALR was significantly lower as compared to those without dyslipidemia (p<0.05). ALR may be a useful marker for adiposity and increased cardiometabolic risk in Indian children and youth with type 1 diabetes mellitus.

Impact of the Remission of Type 2 Diabetes on Cardiovascular Structure and Function, Exercise Capacity and Risk Profile: A Propensity Matched Analysis.

Type 2 diabetes (T2D) confers a high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The impact of the remission of T2D, beyond weight loss and glycaemia, on cardiovascular structure and function and exercise capacity is described. Adults with T2D without cardiovascular disease underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing and cardiometabolic profiling. T2D remission cases (Glycated hemoglobin (HbA1c) < 6.5% without glucose-lowering therapy, ≥3 months) were propensity score matched 1:4 based on age, sex, ethnicity and time of exposure to those with active T2D (n = 100) with the nearest-neighbour method and 1:1 with non-T2D controls (n = 25). T2D remission was associated with a lower leptin-adiponectin ratio, hepatic steatosis and triglycerides, a trend towards greater exercise capacity and significantly lower minute ventilation/carbon dioxide production (VE/VCO2 slope) vs. active T2D (27.74 ± 3.95 vs. 30.52 ± 5.46, p < 0.0025). Evidence of concentric remodeling remained in T2D remission vs. controls (left ventricular mass/volume ratio 0.88 ± 0.10 vs. 0.80 ± 0.10, p < 0.025). T2D remission is associated with an improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population.

Leptin/adiponectin ratio as a prognostic factor for increased weight gain in girls with central precocious puberty.

To determine if the leptin, adiponectin, and leptin/adiponectin ratio (LAR) can predict weight gain at the end of GnRH analogs (GnRHa) treatment in girls with central precocious puberty (CPP). Study design: prospective cohort. Serum levels of leptin and adiponectin were determined at diagnosis of CPP. Anthropometry was performed at diagnosis of CPP and every six-months, until treatment with GnRHa was discontinued and they presented menarche. Patients were divided according to BMI<94 and BMI>95 percentile at diagnosis of CPP. The outcome was the increased in weight gain (e.g., from normal weight to overweight) at the end of follow-up. Statistical analysis: repeated measures ANOVA test and Student's t-test were used to compare groups. Logistic regression analysis was used to evaluate the association of leptin and adiponectin levels, as well as LAR values with increased weight gain. Fifty-six CPP patients were studied, 18 had BMI >95 percentile and 38 BMI <94 percentile. Of the 18 patients who initially had BMI >95th, two patients went from obesity to overweight, while among the 38 patients who started with BMI <94th, 21 (55.2%) increased their weight gain at the end of follow-up. This last group had higher leptin levels (8.99 ± 0.6 vs 6.14 ± 0.8, p=0.005) and higher LAR values compared to those who remained in the same weight (1.3 ± 0.5 vs 0.96 ± 0.56, p=0.01). In the logistic regression analysis, it was found that higher leptin levels and higher LAR values were associated with increased weight gain (RR 1.31, 95%CI 1.03-1.66, RR 4.86, 95%CI 1.10-21.51, respectively), regardless of birth weight, pubertal stage, age, and bone/chronological age ratio. In patients with CPP, leptin levels and higher LAR values appear to be associated with significantly greater weight gain during GhRHa treatment, particularly in girls starting with BMI < 94 percentile.

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.

Adiponectin–leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance

Background Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin–leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance. Materials and methods A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD. Results The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12–0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82–0.88), 0.83 (95% CI 0.78–0.87) and 0.86 (95% CI 081–0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001). Conclusions The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. [AQ3] Key messages The prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early. Adiponectin–leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio. Our study found that adiponectin–leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin–leptin ratio was 0.28(95%CI: 0.12–0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82–0.88). Further rigorous investigation is necessary and should be promptly performed.

Association of Adiponectin-Leptin Ratio and HOMA-IR in Obese Patients with and without Type 2 Diabetes Mellitus: A Cross-sectional Study

Introduction: Obesity is one of the leading causes of morbidity and mortality due to associated risk factors, including Type 2 Diabetes Mellitus (T2DM). Obese and diabetic patients have lower amounts of adiponectin. Leptin, a hormone released by adipocytes that controls hunger, is crucial in the emergence of obesity. Furthermore, it has been claimed that the Adiponectin/ Leptin Ratio (ALR) correlates with Insulin Resistance (IR) better than adiponectin or leptin alone. Aim: To evaluate adiponectin, leptin, and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) in obese subjects with and without T2DM and compare the variations, if any, from the normal subjects. Materials and Methods: This hospital-based, cross-sectional study was carried out at Sri Guru Ram Das (SGRD) University of Health Sciences, Amritsar, and Punjab Institute of Medical Sciences (PIMS), Jalandhar from January 2020 to December 2022. A total of 125 subjects of either gender aged above 18 years, visiting the medicine Outpatient Department (OPD) of PIMS, Jalandhar, were included in the study. Among them, 25 healthy volunteers served as controls. Serum levels of Adiponectin, Leptin, and Insulin were estimated using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The data obtained were statistically analysed using one-way Analysis of Variance (ANOVA) test (with Bonferroni post-hoc). Results: A total of 125 participants were analysed in the present study, with 50 being obese with T2DM (mean age: 50.22±8.6 years), 50 being obese without T2DM (mean age: 46.9±9.8 years), and 25 being non obese non diabetic individuals (controls) (mean age: 42.8±9.09 years). A higher number of females 78 (62.4%) reported to the OPD compared to males 47 (37.6%). Although no statistical significance was found, there was a considerable decrease in adiponectin levels in obese and obese with T2DM subjects. Moreover, the leptin levels and HOMA-IR were increased in obese and obese with T2DM subjects compared to the control subjects. Conclusion: ALR may be used as a clinical marker for assessing the morbidity due to obesity and in T2DM subjects. Moreover, lifestyle modifications can be targeted to prevent IR.

A Pilot Plant Based Dietary Intervention in MGUS and SMM Patients with Elevated BMI Is Feasible and Associated with Improvements in Metabolic and Microbiome Biomarkers of Progression

Introduction Obesity, low adiponectin, high leptin, high insulin, high IGF-1, and diets lacking plant-based foods or high in insulinemic foods are all risk factors for plasma cell disorders (PCDs). Patients (pts) with monoclonal gammopathy (MGUS) and an elevated body mass index (BMI) are twice as likely to progress from MGUS to multiple myeloma (MM). Additionally, there is gut dysbiosis in pts with PCDs, and whole food plant-based diets (WFPBDs) increase stool butyrate concentrations. Butyrate has anti-cancer (HDAC and NFkB inhibition) and anti-inflammatory (proinflammatory cytokine inhibition) properties. Prior studies show that increased relative abundance of stool butyrate producers are associated with improved outcomes in PCDs. Therefore, there is a rationale to study a dietary intervention in MGUS/smoldering MM (SMM), given the standard of care is observation despite the risk of progression. Methods Therefore, we initiated a pilot dietary intervention study (NUTRIVENTION) of a WFPBD in MGUS/SMM pts with BMI ≥25 (NCT04920084) with the primary objective of determining feasibility, as measured by weight loss (>5%) and adherence (>70%) at 12 weeks (wks). Here, we present interim results on feasibility, metabolic markers (insulin, adiponectin leptin ratio, IGF-1), microbiome (relative abundance of butyrate producers, short chain fatty acids) and secreted inflammatory biomarkers (CRP, Olink proteomics) for pts analyzed to date. The intervention, consisting of fully prepared WFPBD meals and behavioral coaching was provided by Plantable. Patients received self-selected WFPBD meals (lunch/dinner) for 12 wks, along with guidance for snacks and breakfast. Behavioral counseling was provided by health coaches and a research dietitian for 24 wks. Adherence was calculated as the percentage of kcal that were whole unprocessed plant foods out of total kcal consumed. Plasma total adiponectin, leptin, IGF-1 and insulin were measured via ELISA immunoassays. Stool samples were analyzed with 16S sequencing and gas chromatography mass spectrometry for short chain fatty acids and plasma was analyzed with the Olink Target 96 inflammation panel. We calculated the median at baseline and the median change % (median change/median at baseline) at 4 and 12 wks. Results The study has completed enrollment of 22 pts (2 dropped out within 12 wks for pt preference and were replaced), with 14 having completed the 12-wk intervention. The baseline demographics for 22 pts include median age 62 years (range 40-79), 45% male, 45% minorities (black, Hispanic, or other), 50% MGUS, 77% obese, and 27% prediabetic/diabetic. Preliminary results for clinical and correlative endpoints are provided in table 1. The study met both feasibility endpoints with 7% median BMI reduction and 90% median adherence at 12 wks as described in table 1. Metabolic markers indicate an improvement in LDL cholesterol, HgbA1c, insulin and adiponectin leptin (AL) ratio. The AL ratio is a marker of insulin resistance and higher levels imply improved insulin sensitivity, reduced BMI, and inflammation. Increased insulin, leptin, IGF-1 as well as decreased adiponectin are associated with the development of MM. Microbiome shows an improvement in the relative abundance of butyrate producers at 4 wks and stool butyrate concentrations at 12 wks. Additionally, a decrease in the branched chain fatty acids are seen. There is a decrease in the proinflammatory cytokines IL8, IL12B and TNFB, a decrease in DNER, a NOTCH1 activator and an increase in the protein FGF21 that is known to promote insulin sensitivity and downregulate hepatic IGF-1 production. Butyrate is known to inhibit the formation of proinflammatory cytokines and increase FGF21 via HDAC inhibition and inhibit NOTCH signaling. Conclusions This is the first interventional study in PCDs with mechanistic insights into risk reduction through modifiable risk factors with the potential to empower pts. Preliminary results show that a WFPBD is feasible given the BMI reduction and adherence in pts with PCDs. Our data suggests that a WFPBD improves metabolic profile (BMI, insulin resistance, AL ratio and FGF21) as well as increases stool butyrate producers and butyrate levels which in turn leads to a reduction in proinflammatory cytokines. Positive changes in metabolic, microbiome and inflammation markers are potential mechanisms by which diet may alter disease trajectory. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal