Dragana Tomic-Naglic

Obesity and vitamin D deficiency: trends to promote a more proatherogenic cardiometabolic risk profile.

Vitamin D deficiency is associated with cardiometabolic risk factors (eg, hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We studied 50 obese patients (body mass index [BMI]: 43.5 ± 9.2 kg/m2) and 36 normal weight participants (BMI: 22.6 ± 1.9 kg/m2). The prevalence of vitamin D deficiency (25-hydroxyvitamin D, 25(OH)D < 50 nmol/L) was 88% among obese patients and 31% among nonobese individuals; 25(OH)D levels were lower in the obese group (27.3 ± 13.7 vs 64.6 ± 21.3 nmol/L; P < .001). There was a negative correlation between vitamin D level and anthropometric indicators of obesity: BMI (r = −0.64; P < .001), waist circumference (r = −0.59; P < .001), and body fat percentage (r = −0.64; P < .001) as well as with fasting plasma insulin (r = −0.35; P < .001) and homeostasis model assessment of insulin resistance (r = −0.35; P < .001). In conclusion, we observed a higher prevalence of vitamin D deficiency among obese participants and this was associated with a proatherogenic cardiometabolic risk profile.

Vitamin D and Dysfunctional Adipose Tissue in Obesity.

Vitamin D deficiency and dysfunctional adipose tissue are involved in the development of cardiometabolic disturbances (eg, hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We evaluated the relation between vitamin D and adipocytokines derived from adipose tissue. We studied 50 obese individuals who were classified into different subgroups according to medians of observed anthropometric parameters (body mass index, body fat percentage, waist circumference, and trunk fat mass). There was a negative correlation between vitamin D level and leptin and resistin (r = −.61, P < .01), while a positive association with adiponectin concentrations was found (r = .7, P < .001). Trend estimation showed that increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations (growth coefficient: 12.13). In conclusion, a positive trend was established between vitamin D and the protective adipocytokine adiponectin. The clinical relevance of this relationship needs to be investigated in larger studies.

Influence of glucoregulation quality on c-reactive protein, interleukin-6 and tumor necrosis factor-α level in patients with diabetes type 1

BACKGROUND/AIM Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs) which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-alpha) in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. METHODS The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-alpha) and glucoregulation parameters (fasting glucose HbA(1c)). RESULTS The values of CRP (p = 0.014), IL-6 (p = 0.020) and TNF-alpha (p = 0.037) were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004); the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001), smoking (p = 0.055), fasting glucose (p = 0.021) and triglycerides (p = 0.048) as well as between IL-6 and LDL-cholesterol (p = 0.009). No statistically significant correlations were found between glycosilated hemoglobin (HbA(1c)) and the inflammatory markers (CRP, IL-6 and TNF-alpha). CONCLUSION The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-alpha.

The Wnt/β-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity

BACKGROUND Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/β-catenin signalling pathway (WβcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WβcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results. The aim of this study is to test the value of CSL as a biomarker of subclinical carotid atherosclerosis (SCA) in obese persons. METHODS The cross-sectional study included 50 obese persons without previous history of diabetes and AD. Participants underwent adequate anthropometrical, ultrasound and laboratory examinations, including 2h 75 g oral glucose tolerance test (OGTT). RESULTS Only the presence of SCA significantly indirectly correlated with CSL (p<0.05). Based on the median value of CSL, we formed two groups: low CSL (CSL<7.9 pmol/l) and high CSL (CSL>7.9 pmol/l). There were no statistically significant differences in general (gender, age and current smoking) and anthropometrical characteristics (body mass index, waist circumference, systolic and diastolic blood pressure), inflammatory (total white blood cell count, erythrocyte sedimentation rate, fibrinogen, C-reactive protein and uric acid), glucose metabolism (fasting and 2h OGTT blood glucose, glycated hemoglobin and presence of dysglycemia) and lipid metabolism (low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B and lipoprotein (a)) parameters between low and high CSL groups. Low CSL group had significantly higher incidence of SCA (p<0.05). CONCLUSION CSL could serve as a useful biomarker of early atherosclerosis in obese persons without previous history of cardiometabolic disorders but the final conclusion requires further testing.

Relation between osteocalcin and the energy metabolism in obesity

Background/aims:Numerous findings have indicated the potential relation between the osteocalcin, the traditional parameter of bone turnover and the regulation of energy metabolism. The aim of this study was to identify the relationship between osteocalcin and calculated indexes, which evaluate insulin sensitivity, insulin resistance and/or secretory capacity of the pancreas, in non-diabetic, obese subjects. Methods:The study included 57 (11 men and 46 women) euglycemic, obese patients (BMI:41,03 ± 6,61kg/m2) and 48 healthy individuals, age and sex matched (BMI:23,15±2,04kg/m2). Plasma glucose and insulin levels during two hour oral glucose tolerance test (OGTT) were determined in order to calculate HOMA indexes (HOMA-IR, HOMA-B%), EISI (estimated insulin sensitivity index), EFP (estimated first phase) and ESP (estimated second phase). Osteocalcin was measured using Electrochemiluminescence (ECLIA) methodology. Results: Statistically lower osteocalcin was found in obese subjects (24.72±9.80 vs 33.31±10.89 ng/mL;p<0.01). Тhere was a statistically significant positive correlation between osteocalcin and EISI (r=0.340;p<0.01). The inverse correlations were found between the osteocalcin and HOMA-IR (r=-0.276;p<0.01), HOMA-B% (r=-0.337;p<0.01), EFP (r=-0.332;p<0.01) and ESP (r=-0.266;p<0.01). Multiple regression showed that, BMI and osteocalcin have a significant inverse prediction with EISI and HOMA-IR, but the level of prediction of BMI was is substantially higher. Conclusion: The effect of osteocalcin in the glyco-regulation is evident, but its contribution is significantly smaller in relation to primarily, obesity associated factors. Therefore, when assessing the position and the role in glycemic control, aways must bear in mind that osteocalcin represents only one of the many contributing factors, some of which exhibit dominant influence then osteocalcin itself.

The impact of currently used oral antihyperglycemic drugs on dysfunctional adipose tissue

Obesity is a disease with pandemic frequency, often accompanied by chronic metabolic and organic complications. Type 2 diabetes mellitus (T2DM) is among the most common metabolic complications of obesity. The first step in the treatment of T2DM is medical nutrition therapy combined with moderate physical activity and with advice to patients to reduce their body weight. Pharmacotherapy starts with metformin, and in the case of inadequate therapeutic response, another antihyperglycemic agent should be added. The most clinical experience exists with sulfonylurea agents, but their use is limited due to high incidence of hypoglycemia and increase in body weight. Based on the fact that dysfunction of adipose tissue can lead to the development of chronic degenerative complications, precise use of drugs with a favorable effect on the functionality of adipose tissue represents an imperative of modern T2DM treatment. Antihyperglycemic drugs of choice in obese individuals are those which cause maturation of adipocytes, improvement of secretion of protective adipokines, and redistribution of fat mass from visceral to subcutaneous depots. Oral antihyperglycemic agents that can affect the functionality of adipose tissue are metformin, SGLT-2 inhibitors, DPP-4 inhibitors, and thiazolidinediones.

1h Post-load Blood Glucose in the Identification of Proatherogenic Cardiometabolic Profile in Obesity

BACKGROUND AND AIM Current data show that 1h oral glucose tolerance test (OGTT) blood glucose (1h-BG) might identify persons at increased risk of developing type 2 diabetes and cardiovascular diseases more precisely than fasting blood glucose (FBG) and 2h OGTT blood glucose (2h-BG). The aim of study was to determine whether is justified to use 1h-BG over traditional blood glucose measurements, in cardiometabolic profiling of obese individuals. METHOD Cross-sectional study enrolled 60 obese individuals without previous history of diabetes and other cardiometabolic disorders. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS All three parameters significantly directly correlated with age, body mass index, waist circumference, erythrocyte sedimentation rate, C-reactive protein, triglycerides and glycated hemoglobin. FBG and 1h-BG significantly directly correlated with alanine transaminase, gammaglutamyltransferase and total cholesterol. FBG significantly directly correlated with fibrinogen and aspartate transaminase, 1h-BG with systolic blood pressure and 2h-BG with diastolic blood pressure. None of parameters significantly correlated with gender, total white blood cell count, uric acid, 25-hydroxyvitamin D, high density lipoprotein cholesterol, low density lipoprotein cholesterol, serum adiponectin and albuminuria. Differences in correlation coefficients were not statistically significant. Individuals with 1h-BG >8.6 mmol/l had much more proatherogenic cardiometabolic profile, as well as higher incidence of dysglycemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) than ones with 1h-BG <8.6 mmol/l, but all differences were driven by the average value of glycemia. There were no statistically significant differences in ability of predicting MetS, NAFLD and pathologically increased carotid artery intima media thickness among analyzed glucose metabolism parameters. CONCLUSION 1h-BG is not superior to FBG and 2h-BG in the identification of proatherogenic cardiometabolic profile in obesity.

Surrogates of Insulin Sensitivity and Indices of Cardiometabolic Profile in Obesity

BACKGROUND AND OBJECTIVES Obesity is often associated with insulin resistance (IR). We considered different IR indexes: the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, the two specimen (0 and 120 min) oral glucose tolerance test Matsuda Index (MI) and the Homeostasis Model Assessment-Adiponectin (HOMA-AD) index. These IR indexes were compared with indicators of the cardiometabolic profile. METHOD This cross-sectional study enrolled 60 obese individuals without previous history of diabetes. Anthropometrical, ultrasound and laboratory examinations were conducted. RESULTS All 3 indexes significantly correlated with indicators of central obesity, systolic and diastolic blood pressure, inflammation parameters, liver enzymes, HbA1c and some lipid parameters. The majority of correlation coefficients were the highest for HOMA-AD, but only the difference in correlation with waist circumference comparing with MI was statistically significant. HOMA-IR directly, and MI indirectly, significantly correlated with age, while HOMA-AD significantly directly correlated with the mean carotid artery intima media thickness (CAIMT). MI showed the best performances in predicting non-alcoholic fatty liver disease and pathologically increased CAIMT; HOMA-AD was the best in predicting metabolic syndrome, while HOMA-IR demonstrated the poorest performances in the prediction of all 3 conditions. There were no statistically significant differences in predicting performances of the analysed indexes. CONCLUSION The HOMA-AD and MI are not superior compared with the HOMA-IR, in the identification of obese individuals with a proatherogenic cardiometabolic profile.

Vitamin D and Dysfunctional Adipose Tissue in Obesity (Authors’ Reply)

Response to Editor to the Comment “Vitamin D Trials and Their Limitations” by Kucukseymen et al We thank Kucukseymen et al for their interest in our paper entitled “Vitamin D and Dysfunctional Adipose Tissue in Obesity.” We assessed vitamin D levels in obese individuals and evaluated the relationship between this vitamin and adipose tissue dysfunction. We showed that an increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations. Therefore, we suggested that vitamin D supplementation may have a beneficial effect on obesity via modulation of adipocytokine secretion. However, a recent meta-analysis did not demonstrate such a link. We mentioned that previous studies reported that intra-abdominal obesity has a direct impact on increased cardiovascular risk due to the increased action of pro-inflammatory and proatherogenic cytokines. Kucukseymen et al mentioned that in our study, there were no details about serum inflammation markers such as highsensitivity C-reactive protein (hsCRP), white blood cells, and neutrophil-to-lymphocyte ratio (NLR). Our unpublished data show that hsCRP was significantly increased (P < .001) in obese compared to nonobese, control participants (control: 0.82 + 1.28 mg/L, obese: 7.67 + 6.92 mg/L). We also measured plasma level of nitric oxide (NO) as an inflammatory marker, and our unpublished data show that the level of NO was significantly increased (P < .001) in obese compared to nonobese control participants (control: 5.67 + 4.52 mmol/L, obese: 13.75 + 9.06 mmol/L). However, we agree with the comment that even if we measure hsCRP, white blood cell, and NLR, this will not be enough because some intestinal diseases (eg, Crohn disease or celiac disease) impair dietary vitamin D absorption. Kucukseymen et al mention that it would be helpful to know during which season this study was carried out. The study was carried out from March to June (ie, spring). We do not have specific information about sunlight exposure and vitamin D obtained from food. Finally, Pereira-Santos et al reported a systematic review and meta-analysis of studies that examined the relationships between vitamin D deficiency and obesity. As is in our study, they pointed out the fact that the prevalence of vitamin D deficiency was higher in obese participants compared to normal-weight participants. In addition, they concluded that the vitamin D deficiency was associated with obesity irrespective of age, latitude, and cutoff values to define vitamin D deficiency and the Human Development Index of the study location.

Influence of some traditional risk factors for osteoporosis on bone metabolism during substitution therapy of primary hypothyroidism

INTRODUCTION The relation between thyroid hormones and bone metabolism markers in hyperthyroidism is well known. Earlier studies indicate the possibility of bone metabolism acceleration during the excessive replacement therapy with l-thyroxin in hypothyroid patients especially in one with other risk factors for bone metabolism impairment. This study evaluated the effect of physiological l-thyroxine treatment on bone metabolism in patient with primary hypothyroidism. MATERIAL AND METHODS In the study group of 30 hypothyroid patients individual thyroxine replacement was performed targeting euthyroid status. Bone and calcium metabolism parameters (osteocalcin-OC, alkaline phosphates-ALP, C-terminal cross-linking telopeptide type l-CL, parathormone-PTH, Ca, ionized Ca, P), thyroid hormone levels (T3, T4, TSH) were measured before treatment and when euthyroid status was achieved. RESULTS AND DISCUSSION A significant treatment effect was observed for bone formation and resorption parameters before and during the therapy; OC (p = 0.000024), CL (p = 0.002648). Ionized calcium levels also showed significantly higher values in euthyroid status confirming bone metabolism acceleration during the l-thyroxine therapy (p = 0.020). Thus, calcium metabolism hormone regulators were not significantly different before and after the therapy; PTH (p = 0.27). Thyroid hormone levels showed significant correlation with bone metabolism parameters before the therapy whereas this correlation was not found during therapy because of different individual l-thyroxine doses. CONCLUSION It can be concluded that physiological doses of l-thyroxine therapy accelerate bone metabolism in hypothyroid patients. Thus, the argument against bone loss during physiological substitution is highly specific mutual correlation between bone formation and resorption parameters. These assumptions require further investigations in long-term prospective studies in patients on replacement l-thyroxine therapy.