High Molecular Weight Adiponectin Concentrations Research Articles

Serum levels of adiponectin differentiate generalized lipodystrophies from anorexia nervosa.

The differential diagnosis of lipodystrophy involves other disorders characterized by severe fat loss and may be sometimes challenging. Owing to the rarity of lipodystrophy, it is relevant to search for tools and assays that differentiate it from other diseases that may mimic it. We conducted a study on leptin and high molecular weight (HMW) adiponectin serum concentrations in a series of patients diagnosed with lipodystrophy and compared them with those found in anorexia nervosa, one of the illnesses that may be cause of a missed diagnosis of lipodystrophy. Leptin and HMW adiponectin serum concentrations were measured in six patients diagnosed with generalized lipodystrophy (GL), six with progeroid syndromes (PS), 13 with familial partial lipodystrophy type 1 (FPLD1, Kobberling syndrome), 10 with familial partial lipodystrophy type 2 (FPLD2, Dunnigan syndrome), 18 with acquired partial lipodystrophy (APL) and 12 affected by anorexia nervosa (AN). Measurements were compared to those obtained in 12 normal weight healthy subjects. Serum leptin concentrations were reduced to a similar degree in GL, PS and AN, proportionally to the extent of fat loss. Serum concentrations of HMW adiponectin were found extremely low in patients with GL and PS, while comparable to normal weight subjects in patients with AN. Serum HMW adiponectin can be regarded as a useful tool to discriminate between generalized lipodystrophy syndromes (including PS) and AN.

Docosahexaenoic acid supplementation in gestational diabetes mellitus and neonatal metabolic health biomarkers.

Gestational diabetes mellitus (GDM) "programs" an elevated risk of metabolic dysfunctional disorders in the offspring, and has been associated with elevated leptin and decreased adiponectin levels in cord blood. We sought to assess whether docosahexaenoic acid (DHA) supplementation in GDM affects neonatal metabolic health biomarkers especially leptin and adiponectin. In a randomized controlled trial, singleton pregnant women with de novo diagnosis of GDM at 24-28 weeks of gestation were randomized to dietary supplementation of 500 mg DHA per day (intervention, n = 30) until delivery or standard care (control, n = 38). The primary outcomes were cord blood leptin and total adiponectin concentrations. Secondary outcomes included high-molecular-weight (HMW) adiponectin and insulin-like growth factor-1 (IGF-1) concentrations in cord blood, maternal glycemic control post-intervention and birth weight (z score). In parallel, 38 euglycemic pregnant women were recruited for comparisons of cord blood biomarkers. There were no significant differences in cord serum leptin, total and HMW adiponectin and IGF-1 concentrations between DHA supplementation and control groups (all p > 0.05). Maternal fasting and 2-h postprandial blood glucose levels at 12-16 weeks post-intervention were similar between the two groups. The newborns in the DHA group had higher birth weight z scores (p = 0.02). Cord blood total and HMW adiponectin concentrations were significantly lower in GDM vs. euglycemic pregnancies. Docosahexaenoic acid supplementation at 500 mg/day in GDM women did not affect neonatal metabolic biomarkers including leptin, adiponectin and IGF-1. The results are reassuring in light of the absence of influence on neonatal adipokines (leptin and adiponectin), and potential benefits to fetal growth and development. Clinicaltrials.gov, NCT03569501.

Adherence to healthy eating patterns is associated with higher circulating total and high-molecular-weight adiponectin and lower resistin concentrations in women from the Nurses' Health Study

Background:Adherence to a healthy dietary pattern, such as the Alternate Healthy Eating Index (AHEI), is associated with a lower risk of diabetes and atherosclerosis. Objective:We aimed to determine whether adherence to the AHEI is associated with higher plasma total and high-molecular-weight (HMW) adiponectin concentrations and lower concentrations of resistin, as well as biomarkers of inflammation, endothelial dysfunction, and insulin resistance. Design:The study evaluated 1922 women from the Nurses' Health Study (62% of whom were overweight) who had no history of diabetes or cardiovascular disease. Their plasma biomarker concentrations were measured in 1990, and data on dietary intake from semiquantitative food-frequency questionnaires administered in 1984, 1986, and 1990 were averaged to account for long-term dietary exposure and to reduce within-subject variability. Results:After adjustment for age and energy intake, women with the highest adherence to the AHEI had 24% higher median total adiponectin and 32% higher median HMW adiponectin concentrations, as well as 16% lower resistin, 41% lower CRP, 19% lower sE-selectin, and 24% lower ferritin concentrations (P < 0.01 for all) than did women with the lowest adherence to the AHEI. These associations remained significant after adjustment for potential confounders. Inverse associations between the AHEI and soluble tumor necrosis factor-α receptor II, interleukin-6, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, C-peptide, insulin, and glycated hemoglobin were evident, but they were not significant after adjustment for body mass index. Conclusion:The preventive effects of healthier dietary patterns on risk for diabetes and atherosclerosis may be mediated by improvements in plasma concentrations of adipokines or other biomarkers of risk for diabetes and cardiovascular disease.

Divergent metabolic phenotypes in two genetic syndromes of low insulin secretion

AimsWe examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS). MethodsAdults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP). ResultsBoth syndromic cohorts displayed DIS during OGTT. LS subjects had higher serum concentrations of total and HMW adiponectin, and lower levels of IGF-I, IGF-II, and IGF-Binding Protein-3 than individuals in other study groups. Furthermore, they displayed normal glycemic responses during OGTT with the lowest IAPP secretion. In contrast, individuals with GRS had higher levels of protein glycation, deficient glucose control during OGTT, and increased secretion of IAPP. ConclusionsA distinct metabolic phenotype depending on GH counter-regulatory status, associates with diabetes development and excess glucose-induced IAPP secretion.

'Energy-Dense, High-SFA and Low-Fiber' Dietary Pattern Lowered Adiponectin but Not Leptin Concentration of Breast Cancer Survivors.

Dietary pattern (DP) and its relationship with disease biomarkers have received recognition in nutritional epidemiology investigations. However, DP relationships with adipokines (i.e., adiponectin and leptin) among breast cancer survivors remain unclear. Therefore, we assessed relationships between DP and high-molecular weight (HMW) adiponectin and leptin concentration among breast cancer survivors. This cross-sectional study involved 128 breast cancer survivors who attended the oncology outpatient clinic at two main government hospitals in the East Coast of Peninsular Malaysia. The serum concentration of HMW adiponectin and leptin were measured using enzyme-linked immunosorbent assay (ELISA) kits. A reduced rank regression method was used to analyze DP. Relationships between DP with HMW adiponectin and leptin were examined using regression models. The findings show that with every 1-unit increase in the ‘energy-dense, high-SFA, low-fiber’ DP z-score, there was a reduction by 0.41 μg/mL in HMW adiponectin which was independent of age, BMI, education level, occupation status, cancer stage, and duration since diagnosis. A similar relationship with leptin concentration was not observed. In conclusion, the ‘energy-dense, high-saturated fat and low-fiber’ DP, which is characterized by high intake levels of sugar-sweetened drinks and fat-based spreads but low intake of fruits and vegetables, is an unhealthy dietary pattern and unfavorable for HMW adiponectin concentration, but not for leptin. These findings could serve as a basis in developing specific preventive strategies that are tailored to the growing population of breast cancer survivors.

Large-for-Gestational-Age, Leptin, and Adiponectin in Infancy.

Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health. This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants. In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years. LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only. This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

Associations Between Antioxidant Vitamin Status, Dietary Intake, and Retinol-binding Protein 4 Levels in Prepubertal Obese Children After 3-month Weight Loss Therapy

Objective:Adiposity is associated with increased oxidative stress, leading to changed fat-soluble vitamin concentrations. The aim of this study was to determine whether weight loss alters fat-soluble vitamin status and whether these alterations are associated with dietary intake, anthropometric parameters and adipokines in obese children.Methods:Vitamin A and E concentrations were measured using high-pressure liquid chromatography in 60 obese children before and after weight loss therapy. Retinol-binding protein 4 (RBP4), leptin, soluble leptin receptor (sOB-R), and high molecular weight adiponectin concentrations were determined by immunoenzymatic assays.Results:The intake of vitamin E was lower in obese children with weight loss after therapy (p=0.038). In this group, an increase was found in the vitamin A/lipids (p=0.022) and the vitamin E/lipids (p=0.008) ratios but due to the reduction in triglyceride levels. In the obese group, changes in vitamin E level were positively correlated with changes in dietary vitamin E (p=0.017) and the leptin/sOB-R ratio (p=0.046). Changes in vitamin A level were positively correlated with changes in dietary vitamin A (p=0.001) and RBP4 concentration (p=0.023). Associations between changes in RBP4 level with the changes in body mass index (BMI) (p=0.011) and total cholesterol concentration (p=0.023) but not with changes in vitamin A concentration were found in the obese after therapy.Conclusion:An increased risk of vitamin E deficiency may occur in children losing weight during lifestyle intervention. Changes in BMI value may influence changes in RBP4 concentrations and consequently the vitamin A status in obese children after therapy.

Cord Blood IGF-I, Proinsulin, Leptin, HMW Adiponectin, and Ghrelin in Short or Skinny Small-for-Gestational-Age Infants.

Small-for-gestational-age (SGA) is an indicator of poor fetal growth "programming" an elevated risk of type 2 diabetes in adulthood. Little is known about early-life endocrine characteristics in SGA subtypes. Stunting (short) and wasting (skinny) are considered distinct SGA phenotypes in neonatal prognosis. This work aimed to assess whether SGA infants with stunting or wasting have similar alterations in neonatal endocrine metabolic health biomarkers. This was a nested case-control study based on the 3D (Design, Develop, and Discover) birth cohort in Canada. The study subjects were 146 SGA (birth weight < 10th percentile) and 155 optimal-for-gestational age (OGA, 25th-75th percentiles) infants. Stunting was defined as birth length less than the 10th percentile, and wasting as body mass index less than the 10th percentile for sex and gestational age, respectively. Main outcome measures included cord plasma concentrations of insulin-like growth factor I (IGF-I), proinsulin, leptin, high-molecular-weight (HMW) adiponectin, and ghrelin. Comparing to OGA infants adjusted for maternal and neonatal characteristics, SGA infants with either stunting only or wasting only had lower cord plasma IGF-I and leptin concentrations. HMW adiponectin concentrations were lower in SGA infants with wasting only (P = .004), but similar in SGA infants with stunting only (P = .816). Only SGA infants with both stunting and wasting had substantially lower proinsulin (P < .001) and higher ghrelin concentrations (P < .001) than OGA infants. This study is the first to demonstrate that SGA infants with wasting only are characterized by low HMW adiponectin concentrations, whereas those with stunting only are not. SGA with both stunting and wasting are characterized by low proinsulin and high ghrelin concentrations.

Sex dimorphism in the associations of gestational diabetes with cord blood adiponectin and retinol-binding protein 4

IntroductionGestational diabetes (GD) is associated with impaired insulin sensitivity in newborns. Adiponectin and retinol-binding protein 4 (RBP-4) are involved in regulating insulin sensitivity. Females are more likely to develop diabetes...

Linoleic Acid-Rich Oil Supplementation Increases Total and High-Molecular-Weight Adiponectin and Alters Plasma Oxylipins in Postmenopausal Women with Metabolic Syndrome.

ABSTRACTBackgroundThe onset of menopause increases the risk of metabolic syndrome (MetS). Adiponectin is an adipokine associated with insulin sensitivity that is lower in people with MetS. Supplementing diets with linoleic acid (LA)-rich oil increased adiponectin concentrations and improved glucose control in women with type 2 diabetes. The effect of LA on adipokines, especially total and the bioactive form of adiponectin, high-molecular-weight (HMW) adiponectin, in women with MetS is unknown.ObjectivesThe aim of this study was to explore the effect of supplementation of the diet with an oil rich in LA on adipokines in women with MetS. The effect of the LA-rich oil (LA-oil) on oxylipins, key metabolites that may influence inflammation and metabolism, was also explored.MethodsIn this open-label single-arm pilot study, 18 postmenopausal nondiabetic women with MetS enrolled in a 2-phase study were instructed to consume LA-rich vegetable oil (10 mL/d) as part of their habitual diets. Women consumed an oleic acid–rich oil (OA-oil) for 4 wk followed by an LA-oil for 16 wk. Fasting concentrations of adipokines, fatty acids, oxylipins, and markers of glycemia and inflammation were measured.ResultsAfter 4 wk of OA-oil consumption, fasting glucose and total adiponectin concentrations decreased whereas fasting C-reactive protein increased. After 16 wk of LA-oil supplementation total and HMW adiponectin and plasma oxylipins increased. Markers of inflammation and glycemia were unchanged after LA-oil consumption.ConclusionsSupplementation with LA-oil increased total and HMW adiponectin concentrations and altered plasma oxylipin profiles. Larger studies are needed to elucidate the links between these changes and MetS.This trial was registered at clinicaltrials.gov as NCT02063165.

Long-term retrospective observation study to evaluate effects of adiponectin on skeletal muscle in renal transplant recipients

Although it has been reported that chronic kidney disease exacerbates sarcopenia progression, the mechanisms of the process remain unclear. Fifty-one patients who underwent renal transplantation at our hospital since 1998 (31 males and 20 females; aged 29–52 years at the time of transplantation) were retrospectively examined for the relationships among the psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), serum adiponectin fractions (high-/low-molecular-weight) and new-onset diabetes after transplantation (NODAT). Before transplantation, age at kidney transplantation negatively correlated with PMI and positively correlated with IMAC (rS = − 0.427, p < 0.01; rS = 0.464, p < 0.01, respectively). Both at 1 and 5 years after transplantation, PMI was higher than before transplantation (p < 0.01). IMAC transiently decreased to − 0.39 at 1 year after kidney transplantation but subsequently increased to − 0.36 at 5 years after kidney transplantation. Multivariate analyses revealed that the mean increase in high-molecular weight adiponectin concentrations was an exacerbating factor for the mean change in PMI (p = 0.003). Moreover, the mean increases in IMAC were exacerbating factors for NODAT. In conclusion, the increase in the PMI is associated with high–molecular weight adiponectin levels after renal transplantation.

Plasma leptin, but not adiponectin, is associated with cognitive impairment in older adults

BackgroundLeptin and adiponectin are adipose-tissue derived hormones primarily involved in glucose, lipid, and energy metabolism, inflammation, and atherosclerosis. Both adipokines may cross the blood-brain barrier but evidence on their roles in cognitive impairment is limited and conflicting. Here, we determined associations of plasma adipokine concentration with cognitive impairment in older adults. MethodsCross-sectional analysis of baseline data from 669 participants aged ≥65 years of the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study were recruited 2014–2017 at study sites in Berlin, Germany and Utrecht, the Netherlands. Cognitive impairment was defined as the lowest tertile of a cognitive summary score derived from six neuropsychological tests. ResultsAfter adjustment for age, sex, fasting, BMI, diabetes, hypertension, cerebrovascular disease, and coronary heart disease, higher leptin concentrations and a higher leptin/adiponectin ratio (LAR) were associated with a higher odds of cognitive impairment (OR per 1 SD higher leptin concentration, 1.33; 95 % CI 1.05, 1.69; p = 0.02; OR per 1 SD higher LAR, 1.26; 95 % CI 1.01, 1.57; p = 0.04). Sensitivity analyses determined that these findings were driven by the non-obese group (BMI < 30 kg/m2), whereas leptin and LAR were not associated with cognitive impairment in the obese group (BMI ≥ 30 kg/m2). Soluble leptin receptor, leptin/soluble leptin receptor ratio, total adiponectin and high-molecular weight adiponectin concentrations were each not associated with impairment. ConclusionsWith leptin as a known promoter of atherosclerosis and inflammation, our findings point to a pathogenic role of leptin in age-related cognitive impairment that may be limited to non-obese individuals and warrants further investigation.

Association of Total and High Molecular Weight Adiponectin with Components of Metabolic Syndrome in Mexican Children

Objective:Childhood obesity linked to metabolic alterations, tend to appear simultaneously with altered adipocytokines, suggesting a role in pathogenetic development. Low circulating level of total and high molecular weight (HMW) adiponectin have been associated with components of the metabolic syndrome (MetS) and could represent an independent risk factor with potential use as a biomarker. To examine the prevalence of MetS in Mexican school children and to investigate the association of total and HMW adiponectin levels with biochemical parameters related to MetS.Methods:The study included a population of boys and girls, from 8 to 11 years old. Anthropometric and biochemical parameters were evaluated according to weight and MetS status. A correlation analysis was fitted to establish an association between adiponectin concentrations and metabolic indicators.Results:One-hundred and fifty five children participated (59.4% females) from 8-11 years of age. The prevalence of MetS was of 10.3%. Impaired biochemical parameters, including total and HMW adiponectin, were associated with obesity. The adiponectin level was significantly lower in MetS than in non-MetS subjects (4.5 vs. 5.4 μg/mL). Total- but not HMW adiponectin concentration was negatively correlated with blood pressure, fasting insulin, fasting blood sugar and Homeostatic Model Assessment for Insulin Resistance.Conclusion:In young children, the total adiponectin level is associated with impaired biochemical parameters of carbohydrate metabolism and could be an excellent early predictor of metabolic complications.

Варианты гена адипонектина () rs2441766 и rs266729: ассоциация с концентрацией общего и высокомолекулярного адипонектина сыворотки крови у женщин с абдоминальным ожирением и метаболическим синдромом

Актуальность. Адипонектин (АН) - протективный адипоцитокин, продуцируемый жировой тканью и циркулирующий в крови в виде различных изомеров. При абдоминальном ожирении (АО) сниженная концентрация АН ассоциируется с развитием метаболи- ческого синдрома (МС), его отдельных компонентов и различных сердечно-сосудистых заболеваний. АН кодируется геном ADIPOQ . Показано, что генетические варианты ADIPOQ ассоциированы с изменением концентрации АН сыворотки крови.Цель исследования. Выявить ассоциации полиморфных вариантов T(+45)G rs2441766 и С(-11377)G rs 266729 гена ADIPOQ с кон- центрацией АН сыворотки крови, АО и МС у женщин.Результаты. Обследованы 302 женщины с АО в возрасте от 30 до 55 лет. Группу сравнения составила 161 практически здоровая женщина без АО. У 185 обследованных с АО был диагностирован МС в соответствии с критериями Международной федерации диа- бета (IDF, 2005). Частоты генотипов и аллелей вариантов T(+45)G и С(-11377)G гена ADIPOQ у женщин с АО и без АО не различались (р&gt;0,05). Среди женщин с АО и МС реже встречались носители аллеля G варианта T(+45)G гена ADIPOQ , чем среди женщин с АО без МС (р&lt;0,05). Частоты генотипов и аллелей варианта С(-11377)G гена ADIPOQ у женщин с АО и МС и у пациенток с АО без МС не разли- чались (р&gt;0,05). У женщин с АО - носителей аллеля G варианта T(+45)G гена ADIPOQ концентрация высокомолекулярного АН (ВМАН) была выше, чем у носителей генотипа TТ этого гена. При анализе частот гаплотипов вариантов T(+45)G и С(-11377)G гена ADIPOQ в обследованных группах достоверных различий не выявлено (р&gt;0,05). Концентрации общего АН в сыворотке крови у женщин с АО и МС - носителей различных генотипов и гаплотипов вариантов T(+45)G и С(-11377)G гена ADIPOQ не различались (р&gt;0,05). Концен- трация ВМАН у женщин с АО - носителей гаплотипа TGC(X) (Х - аллель С или G варианта С(-11377)G ) была выше, чем у женщин с АО - носителей других гаплотипов гена ADIPOQ (р&lt;0,05).Выводы. Носительство аллеля G варианта T(+45)G гена ADIPOQ является протективным в отношении МС у женщин с АО. У женщин с АО - носителей аллеля G концентрация ВМАН выше, чем у женщин с АО - носителей TT генотипа варианта T(+45)G гена ADIPOQ . Background. Adiponectin (AN) - a protective adipocytokine, produced by fat tissue and circulating in the form of various isomers in the blood. With obesity, a decreased level of AN is associated with the development of metabolic syndrome (MS) and various cardiovascular diseases. Regulation of its level can be caused by genetic factors, including single nucleotide polymorphism T(+45)G and C(-11377)G of the ADIPOQ gene. Allelic variants of the ADIPOQ gene was associated with AN concentrarion in blood.Objective. To identify the association of genetic variants of ADIPOQ with adiponectin level, AO and MS in women.Results. A total of 302 women with abdominal obesity (AO) aged 30-55 years were examined. The comparison group consisted of 161 practically healthy women without AO. 185 patients with AO had MS according to the criteria of the International Diabetes Federation (IDF, 2005). The frequencies of genotypes and alleles of variants T (+45) G and C (-11377) G of the ADIPOQ gene among women with and without AO did not differ (p&gt; 0,05). Among women with AO and MS, carriers of G allele variant T (+45) G of the ADIPOQ gene were less common than among women with AO without MS (р&lt;0,05). The frequencies of genotypes and alleles of variant C (-11377) G of the ADIPOQ gene did not differ in women with AO and MS and in patients with AO without MS (p&gt; 0.05). In women with AO - carriers of the G allele variant T (+45) G of the ADIPOQ gene, the concentration of high molecular weight AN (HMWA) was higher than that of the TT carriers of the genotype of this gene The haplotypes of the T (+45) G and C (-11377) G variants of the ADIPOQ gene did not differ in the studied groups (p&gt; 0,05). The con- centration of total AN in the serum of women with AO and MS - carriers of different genotypes and haplotypes of variants T (+45) G and C (-11377) G of the ADIPOQ gene did not differ (p&gt; 0,05). The concentration of HMWA in women with AO - carriers of the TGC(X) haplotype (X - allele C or G variant C (-11377) G) was higher than in women with AO - carriers of other haplotypes of the ADIPOQ gene (p &lt;0,05). Coclusions. G allele of the T(+45)G variant the ADIPOQ gene is protective against MS in women with AO. In women with AO - carriers of the G allele, the concentration of HMWA is higher than in women with AO - carriers of the TT genotype of variant T(+45)G of the ADIPOQ gene.

Investigation of the Effects of a Dietary Supplement on Insulin and Adipokine Concentrations in Equine Metabolic Syndrome/Insulin Dysregulation

High insulin concentrations are a common clinical feature of equine metabolic syndrome (EMS) and insulin dysregulation. Hyperinsulinemia can induce laminitis, so reduction of insulin concentrations in response to an oral challenge should decrease risk. In human studies, diets containing a polyphenol (resveratrol) led to improvements in insulin sensitivity. In rodents, the addition of leucine to a resveratrol supplement caused a decrease in the amount of resveratrol needed to achieve a clinical effect. We hypothesize a supplementation with a low dose of a synergistic polyphenol and amino acid blend including leucine (SPB+L) would improve metabolic health in EMS/insulin dysregulated horses. Fifteen EMS/ID horses received a high or low dose of SPB+ L daily for 6 weeks. Insulin during an oral sugar test (OST), body condition score, weight, baseline high-molecular-weight (HMW) adiponectin, triglycerides, nonesterified fatty acids, and tumor necrosis factor alpha were assessed before supplementation (PRE) and after supplementation (POST) via paired Student’s t-tests and a repeated-measures mixed-model analysis of variance (significant at P < .05). There were no differences between doses. Horses in the POST group weighed significantly less, had significantly higher baseline HMW adiponectin concentrations, and had significantly lower insulin concentrations at 60- and 75-minute time points (P < .05). Insulin concentrations of the horsesin the POST group, but not in the PRE group, were lower and similar to results from the study conducted three years before the present study (PRIOR) for 0- and 60-minute time points (P < .002). An increased HMW adiponectin level supports increasing insulin sensitivity after supplementation. These results suggest that SPB + L supplementation at either dose leads to improvements in the clinical manifestations of EMS/insulin dysregulation, potentially reducing laminitis risk.

Pharmacodynamic Effects of Pioglitazone on High Molecular Weight Adiponectin Concentrations and Insulin Response After Oral Sugar in Equids

Chronic insulin dysregulation is challenging to manage with pharmaceuticals in horses. Pioglitazone improves insulin sensitivity in humans, and the pharmacokinetics of pioglitazone have been evaluated in horses. The objectives of this study were to assess the pharmacodynamic effects of oral pioglitazone on morphometric parameters, hepatic enzyme activity and function, adipokines, and enteroinsular response to oral sugar. A prospective pilot study was performed using fifteen adult equids (8 ponies, 7 horses) to evaluate the effects of short-term pioglitazone administration (2 mg/kg PO q 24 hours, 28 days). Oral sugar tests (OST) were performed before and after treatment. Adipokines were measured at day 0, 14, and 28 of administration. Plasma drug concentrations were measured at day 14 and 28 of administration. The subjects were grouped into horses, ponies, and insulin dysregulated (ID) animals. Baseline values for all parameters were compared with values obtained at day 14 and 28 using one-way or two-way analysis of variance. Mild changes were noted in morphometric parameters and hepatic enzymes. No differences were found in leptin concentrations or the blood glucose response to the OST. Significant decreases were found in the insulin response to OST at 90 and 120 minutes time points and the area under the curve after pioglitazone treatment in the pony and ID groups. High-molecular-weight (HMW) adiponectin concentrations were significantly increased in all groups after pioglitazone treatment. Decreased insulin concentrations in response to oral sugar and increased HMW adiponectin concentrations indicate positive effects of pioglitazone for treatment of metabolic derangements in equine metabolic syndrome, which warrant future clinical study.

Glucagon-like peptide-1, insulin-like growth factor-1, and adiponectin in insulin-dysregulated ponies: effects of feeding a high nonstructural carbohydrate diet and association with prospective laminitis

Endocrinopathic laminitis, related to equine metabolic syndrome and insulin dysregulation, causes marked pain and suffering in horses and represents a substantial cost to the horse industry. This study investigated the effect of feeding a diet high in nonstructural carbohydrates on concentrations of active glucagon-like peptide-1 (aGLP-1), total insulin-like growth factor-1 (IGF-1), and high-molecular-weight (HMW) adiponectin, in insulin-dysregulated ponies. Thirty-seven ponies were challenged with this diet for up to 18 d to induce hyperinsulinemia. Hormone concentrations were measured in selected samples on day 2 of the diet challenge period, over 4 h after feeding. Fourteen of the ponies developed mild laminitis induced by the diet challenge. Insulin and glucose responses to the diet have been reported previously. Feeding increased the concentrations of aGLP-1 (P < 0.05) and HMW adiponectin (P < 0.001), but there was no difference between the laminitic and nonlaminitic groups for either hormone. Concentrations of IGF-1 and insulin were inversely related, with IGF-1 being 32% lower in hyperinsulinemic/laminitic ponies compared with nonlaminitic ponies (P = < 0.05). These results indicate that unlike insulin and possibly IGF-1, concentrations of aGLP-1 and HMW adiponectin do not have a strong association with, or play a major role in, the pathogenesis of equine laminitis.

Low dietary magnesium intake alters vitamin D—parathyroid hormone relationship in adults who are overweight or obese

Vitamin D metabolism is dependent on magnesium (Mg) as a cofactor; therefore, poor Mg status may alter the relationship between vitamin D metabolite serum 25-hydroxyvitamin D (s25OHD) and serum parathyroid hormone (sPTH). We hypothesized that low dietary Mg intake may alter sPTH response to s25OHD in a population with excess body weight, thereby leading to a worsening of cardiometabolic health. To explore this hypothesis, we conducted a cross-sectional study on adults who were either overweight or obese (owt/ob). Dietary Mg intake was measured using a Mg food frequency questionnaire (MgFFQ). Body composition information was measured using Dual Energy X-ray Absorptiometry (DXA). Blood samples were obtained for all biochemical analyses. A total of 57 participants, 22 to 65 years of age, with a body mass index between 25 to 45 kg/m2 were divided into 3 groups, according to dietary Mg intake percentiles (Low Mg Group = <33 percentile, Medium Mg Group = 33 to 66 percentile, High Mg Group = >66 percentile). Higher s25OHD was negatively associated with lower sPTH in the High Mg Intake group (r = −0.472, P = .041), but not in other groups. A positive relationship between s25OHD and serum high-molecular weight adiponectin concentrations was observed in the High Mg Group (r = 0.532, r = 0.022), but not in other groups. Serum Interleukin-6 concentrations were negatively associated with s25OHD (r = −0.316, P = .017) for the entire study group. Based on these results, our study demonstrated that a low dietary Mg intake may alter PTH response to 25OHD.

Relationship between insulin dysregulation and morphometric neck measurements in the non-obese stock-type horse

Endocrinopathic laminitis, related to equine metabolic syndrome and insulin dysregulation, causes marked pain and suffering in horses and represents a substantial cost to the horse industry. This study investigated the effect of feeding a diet high in nonstructural carbohydrates on concentrations of active glucagon-like peptide-1 (aGLP-1), total insulin-like growth factor-1 (IGF-1), and high-molecular-weight (HMW) adiponectin, in insulin-dysregulated ponies. Thirty-seven ponies were challenged with this diet for up to 18 d to induce hyperinsulinemia. Hormone concentrations were measured in selected samples on day 2 of the diet challenge period, over 4 h after feeding. Fourteen of the ponies developed mild laminitis induced by the diet challenge. Insulin and glucose responses to the diet have been reported previously. Feeding increased the concentrations of aGLP-1 (P < 0.05) and HMW adiponectin (P < 0.001), but there was no difference between the laminitic and nonlaminitic groups for either hormone. Concentrations of IGF-1 and insulin were inversely related, with IGF-1 being 32% lower in hyperinsulinemic/laminitic ponies compared with nonlaminitic ponies (P = < 0.05). These results indicate that unlike insulin and possibly IGF-1, concentrations of aGLP-1 and HMW adiponectin do not have a strong association with, or play a major role in, the pathogenesis of equine laminitis.

Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals

Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses' Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (-8.7%), IGFBP-3 (-2.2%), estrone (-6.4%), total estradiol (-5.7%), free estradiol (-8.1%), leptin (-6.4%), CRP (-16.6%), IL-6 (-8.1%), and sTNFR-2 (-5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.