Serum levels of undercarboxylated osteocalcin are related to cardiovascular risk factors in patients with type 2 diabetes mellitus and healthy subjects (original) (raw)

Association between Osteocalcin, Metabolic Syndrome, and Cardiovascular Risk Factors: Role of Total and Undercarboxylated Osteocalcin in Patients with Type 2 Diabetes

International Journal of Endocrinology, 2013

Studies have demonstrated that total osteocalcin (TOC) is associated with metabolic syndrome (MetS) and therefore might influence the risk of cardiovascular disease in humans. Undercarboxylated osteocalcin (uOC) regulates insulin secretion and sensitivity in mice, but its relation to MetS in humans is unclear. We aimed to determine whether uOC is related to MetS and/or its individual components and other cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM), and whether TOC and uOC have utility in predicting the cardiovascular risk. We studied 203 T2DM patients with and without MetS. MetS was defined based on the NCEP-ATP III criteria. A correlation analysis was performed between the three outcome variables: (i) TOC, (ii) uOC, and (iii) carboxylated osteocalcin (cOC) and MetS components and other cardiovascular risk factors. Both TOC and uOC were significantly lower in patients with MetS compared to those without MetS, independent of body mass index. In patients with MetS, uOC was significantly and positively correlated with HDL cholesterol, while TOC was significantly and negatively correlated with serum triglycerides. We report for the first time that uOC is related to lipid indices in patients with T2DM. Further studies are necessary to determine whether uOC can be utilized for cardiovascular risk assessments in these patients. of Hindawi Publishing Corporation

Circulating Undercarboxylated Osteocalcin as Estimator of Cardiovascular and Type 2 Diabetes Risk in Metabolic Syndrome Patients

Scientific Reports

Undercarboxylated osteocalcin (ucOC) could be a biomarker of glucose disturbances and cardiovascular risk. Our study aimed to determine the association between serum levels of ucOC and cardiovascular risk in metabolic syndrome (MetS) patients and to analyse its potential role as estimator of type 2 diabetes (T2D) risk in this population. This cross-sectional study included 235 patients with MetS, 53.2% women, aged 55–75 years. Circulating ucOC levels were measured by ELISA. Cardiovascular risk was determined as Z-score of the diagnostic criteria for MetS (CV-ZS). Linear regression model was performed to analyse the association between circulating ucOC and CV-ZS. A receiver operating curve (ROC) was performed to analyse the usefulness of ucOC as T2D risk estimator. Patients above the CV-ZS median showed significant lower ucOC levels. We found an inverse association between ucOC levels and CV-ZS in MetS patients without T2D. Patients with ucOC levels below the 25th percentile showed w...

Relationship between serum osteocalcin/undercarboxylated osteocalcin and type 2 diabetes: a systematic review/meta-analysis study protocol

BMJ Open, 2019

IntroductionThe global burden of type 2 diabetes (T2DM) is steadily increasing. Experimental studies have demonstrated that a novel hormone secreted by bone cells, osteocalcin (OC), can stimulate beta-cell proliferation and improve insulin sensitivity in mice. Observational studies in humans have investigated the relationship between OC and metabolic parameters, and T2DM. Importantly, few studies have reported on the undercarboxylated form of OC (ucOC), which is the putative active form of OC suggested to affect glucose metabolism.ObjectivesWe will conduct a systematic review and meta-analysis to: (1) compare the levels of serum OC and ucOC between T2DM and normal glucose-tolerant controls (NGC); (2) investigate the risk ratios between serum OC and ucOC, and T2DM; (3) determine the correlation coefficient between OC and ucOC and fasting insulin levels, homeostatic model assessment-insulin resistance, haemoglobin A1c and fasting glucose levels and (4) explore potential sources of bet...

Undercarboxylated osteocalcin in patients with newly diagnosed type 2 diabetes after blood glucose regulation

Polish Archives of Internal Medicine

RESEARCH LETTER Undercarboxylated osteocalcin and newly diagnosed type 2 diabetestion studies are required to clarify the effects of improved glycemic control on this marker. The present study aimed to investigate the association and changes of serum ucOC levels and glycated hemoglobin A 1c (HbA 1c) in patients with type 2 diabetes over 3 months of lifestyle improvement. Patients and methods This study included 57 consecutive male and female patients with type 2 diabetes (according to the World Health Organization criteria), aged between 19 and 79 years. The exclusion criteria were as follows: malignant diseases, kidney or liver diseases, metabolic bone disorders, glucocorticoid treatment, hormonal contraception, hormone replacement therapy, and androgen treatment. Participants were outpatients or inpatients at the Department of Internal Medicine, Zagreb Clinical Hospital Centre. All patients were examined by the same specialist throughout the study. Clinical assessment included the measurement of height, weight, body mass index (BMI), as well as calculation of the homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (HOMA_%S). The values were calculated from fasting BG (FBG) and fasting insulin using the HOMA calculator (https://www. dtu.ox.ac.uk/homacalculator/). Blood was collected at baseline and at 3-month follow-up after overnight fasting. Six biochemical parameters were measured: ucOC (Takara Bio Inc., Kusatsu, Shiga, Japan), TOC, FBG, fasting insulin, HbA 1c , and bone turnover marker (crosslaps telopeptide), measured using Roche instruments and reagents (

Total and undercarboxylated osteocalcin predict changes in insulin sensitivity and cell function in elderly men at high cardiovascular risk

American Journal of Clinical Nutrition, 2012

BSTRACT Background: Osteocalcin has been related to insulin secretion in experimental models. Few prospective studies have evaluated the association between circulating osteocalcin concentrations and insulin secretion and sensitivity in humans. Objective: The objective was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin and insulin secretion and sensitivity in elderly men at high cardiovascular risk. Design: We examined cross-sectional and longitudinal associations between serum measurements of total osteocalcin and undercarboxylated osteocalcin (ucOC) with fasting glucose, fasting insulin, HOMA-IR, and HOMA b cell function (HOMA-BCF) in 79 elderly men. We also examined the association between 2-y changes in osteocalcin and changes in fasting glucose, insulin, HOMA-IR, and HOMA-BCF. Results: In an adjusted multivariable linear regression analysis, increases in serum osteocalcin were significantly associated with an increase in HOMA-BCF (b coefficient: 2.87; 95% CI: 0.23, 5.52; P = 0.033), and changes in ucOC were linked to a decrease in HOMA-IR (b coefficient: 20.31; 95% CI: 20.60, 0.03; P = 0.032). Moreover, in subjects not taking oral antidiabetic drugs, baseline osteocalcin concentrations were positively associated with higher fasting insulin concentrations and HOMA-BCF even after adjustment for BMI, physical activity, intervention group, presence of type 2 diabetes mellitus, and baseline values of each dependent variable. Conclusions: Changes in serum osteocalcin and ucOC are associated with an improvement in insulin secretion and sensitivity, which suggests a possible role of bone in the development of type 2 diabetes. This trial is registered at clinicaltrials.gov as ISRCTN35739639.

Undercarboxylated osteocalcin does not correlate with insulin resistance as assessed by euglycemic hyperinsulinemic clamp technique in patients with type 2 diabetes mellitus

Diabetology & Metabolic Syndrome, 2012

Background: Recent in vitro and in vivo studies have suggested a critical role of osteocalcin (OC), especially the undercarboxylated form (ucOC), in insulin secretion and insulin sensitivity. The objective of this study was to investigate the association between serum ucOC levels and insulin resistance in humans with type 2 diabetes mellitus. Findings: We measured serum ucOC levels in 129 patients with type 2 diabetes. Insulin resistance was assessed using the euglycemic hyperinsulinemic clamp technique. The insulin resistance indices used were the M value, which is the total body glucose disposal rate, and the M/I value, which is the M value adjusted for the steady state plasma insulin level. ucOC levels were not correlated with the M value (ρ = −0.013, p = 0.886) or the M/I value (ρ = 0.001, p = 0.995). Conclusions: We found no association between ucOC levels and insulin resistance in patients with type 2 diabetes mellitus.

Assessment of Uncarboxylated Osteocalcin Levels in Type 2 Diabetes Mellitus

Cureus, 2023

Osteocalcin is one of the main organic components of the bone matrix and consists of 49 amino acids excreted from osteoblastic cells in carboxylated and uncarboxylated forms. Carboxylated Osteocalcin belongs to the bone matrix, whereas uncarboxylated osteocalcin (ucOC) is an important enzyme of osteocalcin in the circulatory system. It is an essential protein for balancing the minerals in bones, binding with calcium, and regulating body glucose levels. In this review, we point out the assessment of ucOC levels in type 2 diabetes mellitus. The experimental results that show ucOC controls glucose metabolism are significant because they relate to the current obesity, diabetes, and cardiovascular disease. To confirm that, low serum levels of ucOC were a risk factor for poor glucose metabolism, and further clinical studies are required.

Undercarboxylated Osteocalcin: A Promising Target for Early Diagnosis of Cardiovascular and Glycemic Disorders in Patients with Metabolic Syndrome: A Pilot Study

Nutrients

Lifestyle changes are causing an exponential increase in the prevalence of obesity and metabolic syndrome (MetS) worldwide. The most frequent complications of these are the development of diabetes (T2D) and cardiovascular disease (CVD). Accurate tools are needed to classify the cardiovascular risk (CVR) in the MetS population. In recent years, numerous biomarkers of bone metabolism have been associated with CVR. The aim of this study was to determine the levels of undercarboxylated osteocalcin (ucOC) in a cohort of patients with MetS and to analyse its association with MetS parameters and CVR as well as with T2D prevalence. A longitudinal study was conducted in which a MetS population was followed for one year. Weight change, adherence to the Mediterranean diet (MedDiet), ucOC levels, MetS parameters and CVR were analysed and CVR was calculated using different scores. Our results showed a decrease of CVR associated with a better adherence to the MetDiet resulting in higher HDL-C and...

Levels of carboxylated and undercarboxylated osteocalcin in patients with type 2 diabetes

Scripta Scientifica Medica, 2020

INTRODUCTION: Osteocalcin (OC) is a bone-derived protein that undergoes vitamin K-dependent carboxylation. The undercarboxylated form of the protein (ucOC) is released in the circulation during the process of bone resorption. Experimental studies on mice and rats have revealed that ucOC is involved in the regulation of energy homeostasis, linking in this way the bone, pancreas, and adipose tissue metabolism. Experimental studies suggest no hormonal role for the carboxylated form (cOC) of the protein. AIM: In the current study we aimed to examine the levels of OC in its carboxylated and undercarboxylated form in patients with type 2 diabetes and control subjects, and to compare the vitamin K status between the two groups. MATERIALS AND METHODS: The present cross-sectional study involved a sample of 46 adults type 2 diabetes patients and a control group of 19 individuals. The carboxylated and undercarboxylated forms of OC were measured in serum by using highly sensitive sandwich-type enzyme immunoassay kits. Vitamin K status was evaluated by the ratio ucOC/cOC. Student's two-tailed unpaired t-test was used to compare the groups. RESULTS: UcOC and cOC serum levels were significantly lower in patients with type 2 diabetes compared to controls. We found no difference in the vitamin K status between the groups. CONCLUSION: Our results show that OC might be involved in the regulation of carbohydrate metabolism. In humans, it appears that the carboxylation state might not be essential for the hormonal role of the protein as in mice and rats.