Newly proposed insulin resistance indexes called TyG-NC and TyG-NHtR show efficacy in diagnosing the metabolic syndrome.

PURPOSE: Obesity and insulin resistance are considered cardinal to the pathophysiology of metabolic syndrome. Several simple indexes of insulin resistance calculated from biochemical or anthropometric variables have been proposed. The study aimed to assess the diagnostic accuracy of indirect insulin resistance indicators in detecting metabolic syndrome in non-diabetic patients, including TG/HDLc, METS-IR, TyG, TyG-BMI, TyG-WC, TyG-WHtR, and new indicators TyG-NC (TyG-neck circumference) and TyG-NHtR (Tyg-neck circumference to height ratio). METHODS: The diagnostic accuracy of eight insulin resistance indexes was assessed using the receiver operating characteristic curves (ROC curves) in 665 adult non-diabetic patients. Then, the analysis was performed after the division into groups with proper body mass index, overweight and obese. RESULTS: All indexes achieved significant diagnostic accuracy, with the highest AUC (area under the curve) for TyG (0.888) and Tg/HDLc (0.874). The highest diagnostic performance in group with the proper body mass index was shown for TyG (0.909) and TyG-BMI (0.879). The highest accuracy in the group of overweight individuals was presented by TyG (0.884) and TG/HDLc (0.855). TG/HDLc and TyG showed the highest AUC (0.880 and 0.877, respectively) in the group with obesity. Both TyG-NC and TyG-NHtR reached significant areas under the curve, which makes them useful diagnostic tests in metabolic syndrome. CONCLUSIONS: Indirect indices of insulin resistance, including proposed TyG-NC and TyG-NHtR, show an essential diagnostic value in diagnosing metabolic syndrome. TyG and TG/HDLc seem to be the most useful in the Caucasian population.

Climacteric symptoms are related to thyroid status in euthyroid menopausal women.

BACKGROUND: Climacteric symptoms are a variety of disturbing complaints occurring during menopausal transition, many of which may be influenced by hormonal abnormalities other than related to sex steroids. AIM OF THE STUDY: In this study, we investigated the association between the intensity of climacteric symptoms measured with the Kupperman index and a thyroid status. MATERIAL AND METHODS: We evaluated by measuring serum thyrotropin (TSH), and free thyroxine (fT4) 202 euthyroid women admitted to the Department of Gynecological Endocrinology, Poznan University of Medical Sciences because of climacteric symptoms. Patients were both in perimenopause (n = 74) and postmenopause (n = 128), with no history of thyroid disorders. RESULTS: Results presented as the mean value and standard deviation were as follows: age 54.2 ± 4.9 years, BMI 26.8 ± 4.6 kg/m2, Kupperman index 26 ± 13.1 points, TSH 2.4 ± 2.6 mU/l, fT4 1.2 ± 0.37 ng/dl. We observed a negative correlation between fT4 and the time since the last menses (R = - 0.38; p = 0.02) as well as between serum TSH concentration and sweating (R = - 0.18; p = 0.03), general weakness (R = - 0.17; p = 0.03), and palpitation (R = - 0.18; p = 0.02) and a positive correlation between fT4 and nervousness (R = 0.34; p = 0.007) and palpitations (R = 0.25; p = 0.04). In the perimenopausal subgroup, there was a positive correlation between fT4 and general weakness (R = 0.42; p = 0.03), palpitations (R = 0.50; p = 0.009), and paresthesia (R = 0.46; p = 0.01). In the postmenopausal subgroup, there was a negative correlation between TSH and sweating (R = - 0.21; p = 0.03). CONCLUSIONS: Menopausal symptoms are related to thyroid status in euthyroid menopausal women.

Pulsatility index in carotid arteries is increased in levothyroxine-treated Hashimoto disease.

The aim of this case-control study was to evaluate carotid hemodynamic variables and traditional cardiovascular risk factors in women with Hashimoto thyroiditis (HT). The study group consisted of 31 females with HT on levothyroxine (L-T4) and 26 euthyroid women with HT without L-T4 matched for age and body mass index (BMI) as controls. Carotid intima-media thickness (CIMT), carotid extra-media thickness (CEMT), and pulsatility indexes in common carotid artery (PI CCA) and in internal carotid artery (PI ICA) were measured. BMI, waist circumference, lipid profile, fasting glucose and insulin levels, and parameters of thyroid function [TSH, free thyroxine (FT4) and antithyroperoxidase antibodies (TPOAbs)] were assessed. The study and the control groups did not differ in age, BMI, waist circumference, lipid profile, fasting glucose, and insulin levels. Results are expressed as median (IQR). Treated HT group had higher FT4 levels than nontreated [17.13 (5.11) pmol/l vs. 14.7 (2.27) pmol/l; p=0.0011] and similar TSH [1.64 (2.08) IU/ml vs. 2.07 (3.14) IU/ml; p=0.5915]. PI CCA and PI ICA were higher in the study group than in controls (p=0.0224 and p=0.0477, respectively). The difference remained statistically significant for PI ICA and PI CCA after adjustment for other variables (coefficient=0.09487; standard error=0.04438; p=0.037 and coefficient=0.1786; standard error=0.0870; p=0.0449, respectively). CIMT and CEMT were similar in both groups (p=0.8746 and p=0.0712, respectively). Women with HT on L-T4 replacement therapy have increased PI in common and internal carotid arteries than nontreated euthyroid HT patients. Therefore, it seems that hypothyroidism, but not autoimmune thyroiditis per se, influences arterial stiffness.

Substantia nigra hyperechogenicity in Polish patients with Parkinson's disease.

BACKGROUND: Hyperechogenicity of the substantia nigra (SN) measured by transcranial sonography (TCS) is a characteristic feature observed in patients with Parkinson's disease (PD). To our knowledge, no SN hyperechogenicity data are available for Polish population. Moreover most of studies come from few centres, which used the one type of ultrasound device. The main aim of the study was to investigate the association between PD and SN hyperechogenicity measured by sonographic machine, not assessed so far. MATERIALS AND METHODS: In this study cross-sectional study SN hyperechogenicity was evaluated in 102 PD patients and 95 control subjects. Midbrain was visualised by Aloka Prosound 7 ultrasound device. SN area measurement, the relation to the clinical features of PD, inter- and intra-observer reliability were evaluated. RESULTS: We confirmed that SN echogenicity is significantly increased in PD patients compared to control subjects (p < 0.001). The area under curve for PD patients vs. controls was 0.93. Receiver operating characteristic analysis indicated a cut-offs for SN echogenicity at 0.19 cm² with accuracy equal to 90%, specificity - 86% and sensitivity - 93.7%. The SN hyperechogenicity was not related to PD clinical findings. Reliability was good if an experienced sonographer performed the SN measurements. CONCLUSIONS: This study shows that the SN abnormality observed by TCS isa specific feature, which can be helpful in the process of PD diagnosing.

Leptin, soluble leptin receptors, free leptin index, and their relationship with insulin resistance and BMI: high normal BMI is the threshold for serum leptin increase in humans.

Leptin binds to the soluble form of its receptor (sOB-R). Leptin and sOB-R balance (free leptin index, FLI) reflect leptin activity. Leptin correlates with obesity and insulin resistance, but it remains uncertain whether sOB-R and FLI also do the same. Therefore, the aim of this study was to measure serum leptin, sOB-R, and FLI, and evaluate their associations with BMI and insulin resistance. We studied 145 obese and 49 nonobese humans. Obesity was defined according to WHO (BMI >30 kg/m (2)). Results are given as: median and interquartile range, obese vs. nonobese, respectively. Leptin (ng/ml): 30.83, 37.27 vs. 8.31, 10.04; sOB-R (ng/ml): 17.62, 17.05 vs. 27.25, 11.30; FLI: 231.2, 310.0 vs. 30.85, 27.77; HOMA: 5.99, 6.64 vs. 3.92, 4.52; p<0.001 for all. Serum leptin, sOB-R, and FLI did not correlate with insulin resistance separately in obese and nonobese humans. Leptin and FLI, but not sOB-R, were associated with insulin resistance in obese and nonobese subjects examined together. Leptin, sOB-R and FLI differed between obese and nonobese humans, and, except sOB-R, correlated with BMI. In piecewise linear regression, BMI threshold where leptin increased was 24.6 (r=0.5969, p=0.00016 and <0.00001). Leptin and its free index, but not sOB-R, correlate with BMI only in a mixed obese and nonobese human cohort, and not in isolated obese or nonobese groups. Moreover, BMI threshold where leptin starts to increase is 24.6 kg/m (2), which is lower than the cutoff for overweight. Under the conditions, metabolic abnormalities may occur in parallel to much lower BMI levels as expected so far.

Serum adiponectin concentrations are not related to glycosylated hemoglobin levels (HbA1c) in obese diabetic and non-diabetic caucasians.

UNLABELLED: Although circulating adiponectin has been inversely correlated with obesity, type 2 diabetes and serum glycosylated hemoglobin (HbA1c) in humans, contradictory reports on that subject exist. In this study, serum concentrations of adiponectin in obese non-diabetic and diabetic humans were measured to examine whether they were associated with levels of HbA1c. The WHO definitions of obesity and diabetes were used. One hundred and five obese euglycemic subjects and 49 obese diabetics (aged 51+/-6.9, and 52+/-6.7 years, respectively) were studied. Their BMI, HbA1c and % of body fat were measured. Adiponectin was determined by an enzyme-linked immunosorbent assay. Although the serum adiponectin concentrations differed between diabetics and non-diabetics ( P<0.01), they were not correlated with HbA1c (r=-0.0814; P=0.5823, and r=-0.1861; P=0.1099, for diabetics and non-diabetics, respectively). Both diabetics and non-diabetics were segregated into tertiles according to their HbA1c levels. Plasma adiponectin did not differ significantly between the high (H), intermediate (I), and low (L) HbA1c tertiles. CONCLUSION: Concentrations of adiponectin were not correlated with levels of glycosylated hemoglobin in the diabetic and non-diabetic subjects examined.

Circadian rhythms of melatonin and cortisol in manifest Huntington's disease and in acute cortical ischemic stroke.

Recent studies indicate disruptions to the circadian system in brain injury and neurodegeneration. The results, however, are often not consistent and limited by measurement of only one circadian marker and by infrequent sampling rates. In this study, we examined diurnal rhythmicity in different stages of Huntington (HD) disease and in patients with acute moderate ischemic stroke (AIS) outside the retinohypothalamic pathway by evaluating serum concentrations of melatonin and cortisol at twelve timepoints. All study participants were subjected to the same study protocol of 12-hour light/dark cycle and controlled room conditions. Using cosinor analysis of data and comparing the results with the controls we found melatonin phase delay with lowered amplitude and mesor in stage III HD patients. These changes coexisted with phase advanced rhythm and elevated values of mesor and amplitude for cortisol. Early and mid-stages of HD showed only a phase advance in cortisol secretion. In AIS the circadian rhythm of serum melatonin was sustained without any phase shift and exhibited more flattened profile (lowered mesor and amplitude values), while advanced rhythm with higher mesor for cortisol was present. In conclusion, 1) abnormal pattern of melatonin release in the late stages of HD and in moderate AIS occurs in conjunction with phase-advanced rhythm of cortisol; 2) changes observed in late stages of HD are similar to those that occur with ageing; 3) brain regions other than the presumptive retinopineal neural pathway may play an important role in the pineal production of melatonin in humans; 4) lesion in extrahypothalamic region is related to the strong adrenal stimulation in response to AIS.

Serum resistin concentrations are higher in human obesity but independent from insulin resistance.

UNLABELLED: Although obesity may be linked to resistin, the role of resistin in humans is still controversial. Conflicting results of the associations between resistin and BMI and measures of insulin resistance were reported. In view of the yet unexplained role of resistin in human obesity, the aim of this study was to examine correlations between serum resistin concentrations and the degree of human obesity and insulin sensitivity. For this purpose, we investigated 2 homogenous groups of obese and non obese humans, in whom the presence of obesity was the solely differentiating factor. The WHO definition of obesity was used. Study group consisted of 136 obese subjects (75 women and 61 men) and 48 non-obese controls (31 women, 17 men) aged 48.0 ± 10.1, and 48.8 ± 13.4 yrs, respectively. RESULTS: Obese subjects showed higher resistin concentrations than non obese controls (24.89 ± 9.73 ng/mL, median 26.61 vs. 15.34 ± 4.68 ng/mL, median 14.76, P < 0.0001). Resistin concentrations correlated with BMI in the whole cohort (r = 0.4296, P < 0.0001), but not in obese and non-obese subjects separately (r = 0.1418, P = 0.0997; r = 0.2712, P = 0.0623, respectively). Moreover, serum resistin was not influenced by insulin resistance in either group examined. CONCLUSION: Although concentrations of resistin differ between obese and non-obese humans, no relationship between resistin concentration and insulin resistance has been found. Correlations between resistin and BMI are present only in a mixed population but disappear in non obese and obese subjects when analyzed separately.

Circulating serum adiponectin concentrations do not differ between obese and non-obese caucasians and are unrelated to insulin sensitivity.

Reduced serum levels of adiponectin in obesity and insulin resistance seem paradoxical, since adipose tissue is the only source of adiponectin, and reports on that subject are contradictory. The aim of this study was to investigate the concentrations of adiponectin in non-obese and obese normoglycemic humans, and to determine the correlation between adiponectin and HOMA index of insulin sensitivity. Based on the WHO definition of obesity, 145 obese subjects and 49 non-obese controls (aged 20-55 years) were studied. The serum adiponectin concentrations did not differ between subjects and controls (p=0.6398) and were not correlated with HOMA index (r=-0.0211; p=0.8048, and r=-0.0523; p=0.4757, for subjects and controls, respectively). Adiponectin was not correlated with HOMA index in females (r=-0.0521; p=0.6546, and r=-0.0825; p=0.3981, for female subjects and controls, respectively) as well as in males (r=0.0033; p=0.9791, and r=0.0123; p=0.9131, for male subjects and controls, respectively). These results lead to the conclusion that neither the concentrations of adiponectin differ between obese and non-obese humans, nor does any relationship between adiponectin concentration and insulin sensitivity exist.

The Y111 H (T415C) polymorphism in exon 3 of the gene encoding adiponectin is uncommon in Polish obese patients.

The genetic background of obesity is under research. Obesity-related phenotype candidate genes include the gene encoding adiponectin (AdipoQ). In this study, exon 3 of the adiponectin gene was screened for the Y111 H (Tyr111His, or T415C, rs17366743) polymorphism, and adiponectin serum concentrations were measured in 206 obese subjects (110 women and 96 men, aged 50.5+/-16.9 years). Their BMI, % of body fat, plasma glucose, insulin, and glycosylated hemoglobin were measured. Adiponectin was determined by enzyme-linked immunosorbent assay. Genomic DNA was extracted from peripheral blood leukocytes. A fragment of exon 3 of the adiponectin gene was amplified in PCR and screened for the Y111 H polymorphism in SSCP analysis. Genetic screening revealed a different SSCP pattern in 2 subjects. Subsequent genotyping disclosed the TC genotype in both subjects, resulting in Y111 H heterozygote variant frequency of 0.01 in the whole cohort. Other results for SNP (single nucleotide polymorphism) positive and negative subjects were as follows, respectively: BMI (kg/m (2)) 39.95+/-9.83 vs. 38.12+/-8.56; waist circumference (cm) 122+/-18.4 vs.115+/-16; glucose (mmol/l) 7.51+/-1.86 vs. 5.56+/-0.74; HbA1c (%) 7.55+/-1.86 vs. 6.58+/-1.36; body fat (%) 51+/-2 vs. 44+/-10; plasma insulin (mU/l) 28.92+/-16.50 vs. 37.59+/-47.34; adiponectin (ng/ml) 1301+/-15.8 vs. 5682+/-4156. Due to a proportion of 2 vs. 204, statistical calculations were not possible. The Y111 H adiponectin gene variant is uncommon in Polish obese subjects. Although we observed low adiponectin concentrations in Y111 H SNP heterozygote carriers, this finding was not confirmed by statistics.

What are subcutaneous adipocytes really good for?

Our acute awareness of the cosmetic, psychosocial and sexual importance of subcutaneous adipose tissue contrasts dramatically with how poorly we have understood the biology of this massive, enigmatic, often ignored and much-abused skin compartment. Therefore, it is timely to recall the exciting, steadily growing, yet underappreciated body of evidence that subcutaneous adipocytes are so much more than just 'fat guys', hanging around passively to conspire, at most, against your desperate attempts to maintain ideal weight. Although the subcutis, quantitatively, tends to represent the dominant architectural component of human skin, conventional wisdom confines its biological key functions to those of energy storage, physical buffer, thermoregulation and thermoinsulation. However, already the distribution of human superficial adipose tissue, by itself, questions how justified the popular belief is that 'skin fat' (which actually may be more diverse than often assumed) serves primarily thermoinsulatory purposes. And although the metabolic complications of obesity are well appreciated, our understanding of how exactly subcutaneous adipocytes contribute to extracutaneous disease - and even influence important immune and brain functions! - is far from complete. The increasing insights recently won into subcutaneous adipose tissue as a cytokine depot that regulates innate immunity and cell growth exemplarily serve to illustrate the vast open research expanses that remain to be fully explored in the subcutis. The following public debate carries you from the evolutionary origins and the key functional purposes of adipose tissue, via adipose-derived stem cells and adipokines straight to the neuroendocrine, immunomodulatory and central nervous effects of signals that originate in the subcutis - perhaps, the most underestimated tissue of the human body. The editors are confident that, at the end, you shall agree: No basic scientist and no doctor with a serious interest in skin, and hardly anyone else in the life sciences, can afford to ignore the subcutaneous adipocyte - beyond its ample impact on beauty, benessence and body mass.

Hypothyroidism has no impact on insulin sensitivity assessed with HOMA-IR in totally thyroidectomized patients.

UNLABELLED: The influence of thyroid hormones on insulin and glucose metabolism is controversial. We examined the impact of hypothyroidism on insulin sensitivity in 22 hypothyroid patients (15 females and 7 males, mean age 51.0 +/- 12.36 yrs). All subjects had a history of total thyroidectomy and radioiodine ablation for differentiated thyroid cancer. Each subject ceased levothyroxine treatment six weeks prior to admission. The controls were 17 healthy individuals, 6 women and 11 men, mean age 55.12 +/- 14.17 years. TSH, free thyroxine, and the HOMA index of insulin sensitivity, as well as HOMA B (%) and HOMA S (%) were assessed. Insulin sensitivity was compared between the groups, and the correlation between FT4 and TSH and insulin sensitivity was calculated. RESULTS: The mean FT4 was 4.6 +/- 4.64 pmol/L in the examined group vs. 16.2 +/- 1.8 pmol/L in controls, p<005; TSH 72.11 +/- 36.73 pmol/L vs. 1.24 +/- 1.07 pmol/L, p<0.005; plasma glucose 4.68 +/- 0.47 mmol/L vs. 5.04 +/- 0.62mmol/L, p=0.0436; plasma insulin 8.07 +/- 9.39 microU/mL vs. 7.24 +/- 4.06 microU/mL, p=0.7877; HOMA index 1.79 +/- 2.53 vs. 1.69 +/- 1.09, p=0.5148; HOMA B (%) 102.46 +/- 41.59 vs. 85.95 +/- 26.87, p=0.1926, and HOMA S (%) 150.46 +/- 95.90 vs. 153.80 +/- 108.85, p= 0.6710, in subjects and controls, respectively. The levels of insulin sensitivity did not differ significantly between the two groups. FT4 and TSH did not influence the insulin sensitivity in either group, the correlation was insignificant, respectively p=0.5426 and p=0.8175 in the examined group, and p=0.172 and p=0.4509 in the controls. CONCLUSION: Hypothyroidism has no impact on insulin sensitivity in the examined group.

Prolonged ventricular repolarization measured by corrected QT interval (QTc) in subclinical hyperthyroidism.

UNLABELLED: Overt hyperthyroidism and hypothyroidism exert a major effect on cardiac function and on ECG. The influence of subclinical hyperthyroidism on the circulatory system is still under debate. Few studies examined the effect of thyroid hormones on ventricular repolarization measured by corrected QT interval (QTc). Longer QTc is associated with increased risk of arrhythmia and cardiac mortality. The aim of this study was to examine the influence of subclinical hyperthyroidism on ventricular repolarization measured by corrected QTc in a standard 12-lead electrocardiogram. The examined group consisted of thirty-two patients with subclinical hyperthyroidism; the controls were thirty-nine healthy individuals. In the group with subclinical hyperthyroidism, we observed a significant increase in heart rate (80.3 +/- 10.59 vs. 73.7 +/- 11.37 bpm, p < 0.05). The mean corrected QTc was 0.434 +/- 0.0207 seconds and 0.414 +/- 0.0208 in the examined groups and in controls, respectively (p < 0.001). QTc did not correlate with free thyroxin concentrations (p = 0.5084). CONCLUSION: Corrected QT intervals were significantly longer in patients with subclinical hyperthyroidism.