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Margit Kovács

Publications and source records attributed to Margit Kovács.

16 recordsLinked to original sources
PubMed2006

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients.

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.

Adolescent↗
PubMed2006

Decreased frequency of the TNF2 allele of TNF-alpha -308 promoter polymorphism is associated with lacunar infarction.

BACKGROUND AND PURPOSE: Enhanced release of proinflammatory cytokines may contribute to the pathogenesis of stroke. It was examined whether G to A promoter polymorphism in the tumor necrosis factor-alpha gene at position -308 affects the risk of stroke. METHODS: We genotyped 336 patients with ischemic stroke and 333 healthy controls for this polymorphism. Patients were divided into different groups based on the Oxfordshire Community Stroke Project (OCSP) or a modified TOAST classification. Distribution of the alleles at -308 G>A promoter polymorphism was determined by PCR-RLFP method. RESULTS: Patients with ischemic stroke had a significantly (p<0.001) decreased (0.115) frequency of the -308 A (TNF2) allele compared to the healthy controls (0.196). When patients were categorized according to the OCSP classification, it turned out that significant (p=0.002) decrease in TNF2 allele frequency (0.065) was restricted to the patients with lacunar infarct (LACI) whereas the frequency of the TNF2 alleles in patients with the other three subtypes (TACI, PACI, and POCI) did not significantly differ from that in healthy controls. Similar results were obtained when the patients were divided according to the modified TOAST classification: the frequencies of the TNF2 allele were 0.068 and 0.140 (p=0.010) in the patients with small-vessel and non-small vessel (large vessel infarction or ischemic stroke of other origin) infarction, respectively. The age-adjusted odds ratio of the patients carrying the TNF2 allele to develop lacunar infarct was 0.33 (0.16-0.68) (p=0.002) compared to the non-carriers. This difference was also restricted to the male patients. CONCLUSIONS: Our results suggest that male carriers of TNF2 allele are less susceptible for the development of lacunar subtype of ischemic stroke than the non-carriers.

Aged↗
PubMed2006

Distinction of tris(diimine)ruthenium(II) enantiomers chiral by virtue of helical chirality: temperature-dependent deuterium NMR spectroscopy in partially oriented phases.

2H NMR spectra of perdeuterated tris(diimine)ruthenium(II) complexes have been recorded in lyotropic liquid crystalline phase formed by the chiral polypeptide, poly-gamma-benzyl-L-glutamate (PBLG) and co-solvents. It is demonstrated that the left- and right-rotation isomers of these octahedral metal complexes with D3 symmetry can be distinguished. The effects of temperature and ligand size on spectral resolution were also studied. Although in the case of free bipyridine ligands excellent optical resolution could be obtained at room temperature in the complexes studied, the increase in ligand size has a detrimental effect on the resolution. This can be compensated to some extent by elevating the sample temperature and decreasing the deuterium relaxation rates, but the available temperature range and therefore the applicability of the technique are limited.

Journal Article↗
PubMed2006

Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma.

Claudins (CLDNs), a family of transmembrane proteins, are major constituents of tight junctions (TJs). They have been shown to be differentially regulated in malignant tumors and play a role in carcinogenesis and progression. We aimed to explain the molecular mechanism underlying the main epithelial components of hepatoblastomas (HBs) based on the composition of TJs. Fourteen formalin-fixed, paraffin-embedded surgical resection specimens were analyzed by immunohistochemistry for CLDN-1, -2, -3, -4, -7; proliferating cell nuclear antigen (PCNA); Ki-67; beta-catenin; cytokeratin-7 (CK-7); and hepatocyte-specific antigen; messenger RNA was isolated for real-time reverse transcriptase polymerase chain reaction analysis of the CLDNs from dissected fetal and embryonal cell types. Significantly increased protein and messenger RNA expression of CLDN-1 and -2 was detected in the fetal compared with the embryonal component. Both cell types displayed negative or weak immunostainings for CLDN-3, -4, and -7. Hepatocyte-specific antigen was dominantly expressed in the fetal component. PCNA and Ki-67 labeling indices were significantly higher in embryonal compared with fetal cells. beta-catenin cytoplasmic/nuclear immunoreaction was frequent, although not showing significant differences between fetal and embryonal cells. Mutational analysis of beta-catenin detected mutation in two cases. Our results suggest that increased expression of CLDN-1 and -2 characterizes the more differentiated fetal component in HBs and is a reliable marker for differentiating fetal and embryonal cell types in HBs. The results proved that the embryonal and fetal components of HBs differ in such important feature as the protein composition of TJs. The expression of CLDN-1 and -2 is inversely correlated with cell proliferation. The more aggressive, rapidly proliferating embryonal phenotype is associated with the decrease/loss of CLDN-1 and -2. However, there are no data indicating association with the nuclear translocation of beta-catenin.

Biomarkers, Tumor↗
PubMed2005

Metal-metal bond or isolated metal centers? Interaction of Hg(CN)2 with square planar transition metal cyanides.

Three adducts have been prepared from Hg(CN)(2) and square planar M(II)(CN)(4)(2)(-) transition metal cyanides (M = Pt, Pd, or Ni, with d(8) electron shell) as solids. The structure of the compounds K(2)PtHg(CN)(6).2H(2)O (1), Na(2)PdHg(CN)(6).2H(2)O (2), and K(2)NiHg(CN)(6).2H(2)O (3) have been studied by single-crystal X-ray diffraction, XPS, Raman spectroscopy, and luminescence spectroscopy in the solid state. The structure of K(2)PtHg(CN)(6).2H(2)O consists of one-dimensional wires. No CN(-) bridges occur between the heterometallic centers. The wires are strictly linear, and the Pt(II) and Hg(II) centers alternate. The distance d(Hg)(-)(Pt) is relatively short, 3.460 A. Time-resolved luminescence spectra indicate that Hg(CN)(2) units incorporated into the structure act as electron traps and shorten the lifetime of both the short-lived and longer-lived exited states in 1 compared to K(2)[Pt(CN)(4)].2H(2)O. The structures of Na(2)PdHg(CN)(6).2H(2)O and K(2)NiHg(CN)(6).2H(2)O can be considered as double salts; the lack of heterometallophilic interaction between the remote Hg(II) and Pd(II) atoms, d(Hg)(-)(Pd) = 4.92 A, and Hg(II) and Ni(II) atoms, d(Hg)(-)(Ni) = 4.61 A, is apparent. Electron binding energy values of the metallic centers measured by XPS show that there is no electron transfer between the metal ions in the three adducts. In solution, experimental findings clearly indicate the lack of metal-metal bond formation in all studied Hg(II)-CN(-)-M(II)(CN)(4)(2)(-) systems (M = Pt, Pd, or Ni).

Journal Article↗
PubMed2005

[Pancreas pseudocyst or metastasis?].

The authors review a case of a 24-year-old male patient hospitalised for repeated acute abdominal symptoms. His medical history included no diseases worth of mentioning. By imaging techniques (abdominal US and CT scan) a cystic lesion, measuring 40 x 35 x 30 mm in diameter was found, and was diagnosed as pseudocyst in the region of the tail of the pancreas. Jejunal feeding was introduced. The lesion did not improve and the second CT scan suggested a suspicion of pancreatic cystadenoma. Three months after first presentation the surgical resection was performed. The tumour, however, was found independent of the pancreas (90 x 80 x 50 mm). Both histologically and immunohistochemically the lesion proved to be the metastasis of a germ cell (yolk-sac) tumour. Following the morphological diagnosis, detailed urological and medical check up was performed. A previously nonpalpable small tumour was found in the left testis which was radically resected. The testicular tumour measuring 9 x 9 x 5 mm in diameter was diagnosed as embryonal carcinoma. Later on the patient underwent chemotherapy. He has been undergoing close oncological followup. Clinically, he is disease free. Authors emphasize the importance of imaging techniques and fine needle aspiration cytology in the case of retroperitoneal masses in young males. The possibility of a metastasis, especially of germ cell origin, should be excluded (not only by physical examination, but by ultrasound of testis also) in case of retroperitoneal cystic tumours even with unusual morphology.

Adult↗
PubMed2005

Association between interleukin-6 polymorphism and age-at-onset of type 1 diabetes. Epistatic influences of the tumor necrosis factor-alpha and interleukin-1beta polymorphisms.

Multiple immune mediators have been mentioned as playing a role in the pathomechanism of type1 DM. Interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha play a central role in the autoimmune destruction of pancreatic beta-cells, whereas IL-6 inhibits TNF-alpha secretion, and may have some protecting effects. In our study, we aimed to investigate the association between these three cytokines' single nucleotide polymorphisms (IL-6 gene G(-174)C, TNF-alpha gene G(-308)A and IL-1beta gene C(3954)T polymorphisms) and age-at-onset of type 1 diabetes mellitus (T1DM) in 165 diabetic children (median age: 17 years). Polymorphisms were determined using the PCR-RFLP method. We found that the age-at-onset of T1DM was significantly different in patients with a different IL-6 genotype (median age-at-onset of T1DM was: 8, 6 and 4.5 years in children with the (-174)GG, GC and CC genotypes, respectively; p < 0.01). Adjusted for TNF-alpha and IL-1beta polymorphisms, patients with a IL-6 (-174)CC genotype have a 3.0-fold (95% CI: 1.2-7.1) increased risk of developing diabetes before the age of 6 years than (-174)G allele carrier patients. However, we found this association to be present only in patients who carried the TNF-alpha (-308)A or IL-1beta (3954)T allele, i.e. in patients with high TNF-alpha and high IL-1beta producer genotypes. We suppose that in the case of high TNF-alpha and IL-1beta producer genotypes, elevated proinflammatory cytokine levels result in a higher production of IL-6 in (-174)G allele carrier patients. This elevated IL-6 level may have a protective effect against the development of T1DM and may delay the destruction of pancreatic beta-cells.

Age of Onset↗
PubMed2004

Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior.

The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.

Adult↗
PubMed2004

[Malignant rhabdoid tumour in the liver].

The authors describe the case of a 6-months-old child with liver tumour. The newborn was healthy until 6 months of age. Prior to hospitalization meteorism and remarkably enlarged liver were observed. A tumour occupying the right lobe of the liver was found with ultrasound and computer tomography, which proved to be inoperable. Intraoperative liver biopsy and few days later the autopsy histology showed a malignant rhabdoid tumour. Authors describe the clinical and morphological features of a rare case of primary hepatic rhabdoid tumour.

Autopsy↗
PubMed2003

Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index.

Among the genes and proteins of the human immune system, complement component C4 is extraordinary in its frequent germline variation in the size and number of genes. Definitive genotypic and phenotypic analyses were performed on a central European population to determine the C4 polygenic and gene size variations and their relationships with serum C4A and C4B protein concentrations and hemolytic activities. In a study population of 128 healthy subjects, the number of C4 genes present in a diploid genome varied between two to five, and 77.4% of the C4 genes belonged to the long form that contains the endogenous retrovirus HERV-K(C4). Intriguingly, higher C4 serum protein levels and higher C4 hemolytic activities were often detected in subjects with short C4 genes than those with long genes only, suggesting a negative epistatic effect of HERV-K(C4) on the expression of C4 proteins. Also, the body mass index appeared to affect the C4 serum levels, particularly in the individuals with medium or high C4 gene dosages, a phenomenon that was dissimilar in several aspects from the established correlation between body mass index and serum C3. As expected, there were strong, positive correlations between total C4 gene dosage and serum C4 protein concentrations, and between serum C4 protein concentrations and C4 hemolytic activities. There were also good correlations between the number of long genes with serum levels of C4A, and the number of short genes with serum levels of C4B. Thus, the polygenic and gene size variations of C4A and C4B contribute to the quantitative traits of C4 with a wide range of serum protein levels and hemolytic activities, and consequently the power of the innate defense system.

Adult↗
PubMed2003

Relationship between complement components C4A and C4B diversities and two TNFA promoter polymorphisms in two healthy Caucasian populations.

The RP-C4-CYP21-TNX (RCCX) modules and the tumor necrosis factor (TNF) gene cluster are probably the most polymorphic genomic regions in the human central major histocompatibility complex (MHC). Using definitive methods for genotypic and phenotypic analyses of complement components C4A and C4B, determination of the RCCX length variants, and SSP-PCR/RFLP analyses of TNFA promoter polymorphisms at positions -308 and -238, we studied the complex relationships between the C4 and TNFA polymorphisms in two normal Caucasian populations. The patterns of the RCCX modular structures and the allelic frequency of -308A TNFA (TNF2) were similar between the Budapest (n = 125) and the Ohio (n = 80) Caucasians. However, the frequency of the -238A allele was significantly higher in the Ohio (11.3%) than in the Budapest (1.6%) study population (p < 0.0001). Marked features were found in the RCCX length variants in the TNF2 carriers and noncarriers. Strong associations were found between the C4AQ0 B1 haplotype from the monomodular short (mono-S) RCCX structure and the TNF2 allele, and between the C4A6 B1 haplotype from the bimodular long-short (LS) structure of the RCCX and the TNFA -238A allele. However, 36%-46% of the TNF2 carriers did not associate with a mono-S in both study cohorts, and 57.1% of the TNFA -238A carriers in Ohio did not associate with C4A6, which has a defective complement C5 convertase activity. The carriers of TNF2 allele had significantly lower C4A serum concentration (0.17 +/- 0.08 g/l) than noncarriers (0.23 +/- 0.09 g/l) (p < 0.001). The lowest C4A serum levels were found in TNF2 carriers with mono-S structures (0.14 +/- 0.06 g/l). In essence, our results demonstrated the heterogeneities of the TNFA promoter polymorphisms, and the linkage disequilibrium of TNFA -308A and -238A alleles with complement C4A deficiency and impaired C4A protein function, respectively.

Blotting, Southern↗
PubMed2003

Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C-peptide level.

OBJECTIVE: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume, serum TNF-alpha, soluble TNF-receptor-2 (sTNFR-2) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons. DESIGN: A cross-sectional case-control study was used. PATIENTS: Twenty-eight overweight/obese probands with normal glucose tolerance (BMI>27 kg/m(2)) and 15 lean people (BMI<25 kg/m(2)), all of them undergoing planned surgical operation, participated in the study. METHODS: Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein. Serum TNF-alpha, sTNFR-2 (ELISA) and fasting C-peptide (RIA) were measured. RESULTS: TNF-alpha protein was expressed in adipocytes of both depots. The expression was evaluated visually and found to be greater in the obese patients. Significantly higher serum TNF-alpha (5.58+/-0.87 pg/ml vs 4.21+/-0.55, mean+/-s.d., P<0.01, Mann-Whitney) and sTNFR-2 levels (7.84+/-3.56 ng/ml vs 4.59+/-1.35, P=0.005) were found in the obese subgroup in correlation with the fasting C-peptide level (r=0.49, P=0.003; and r=0.74, P=0.001) and the C-peptide/ blood glucose ratio (r=0.47, Spearman, P=0.005; and r=0.70, P=0.001). The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients (subcutaneous: r=0.52, P=0.0003; r=0.69, P<0.0001; visceral: r=0.65, P<0.0001; r=0.63, P<0.0001) and in both subgroups. CONCLUSIONS: Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha, sTNFR-2 production and obesity-linked insulin resistance.

Adipocytes↗
PubMed2003

Influence of leptin and the TNF system on insulin resistance in pregnancy and their effect on anthropometric parameters of newborns.

BACKGROUND: We studied the contribution of the tumor necrosis factor system and leptin to insulin resistance during the course of normal pregnancy. METHODS: Forty-five healthy pregnant women (15 in the 1st, 15 in the 2nd2 and 15 in the 3rd3 trimester) and 25 age-matched healthy nonpregnant women as controls. Twenty-three newborns delivered by women followed in the 2nd and 3rd trimesters were also investigated. Fasting serum immunoreactive tumor necrosis factor-alpha, soluble tumor necrosis factor receptor-1, soluble tumor necrosis factor receptor-2, leptin (by enzyme-linked immunoassay) and C-peptide (by radioimmunoassay) concentrations in the patients and controls were measured. Body weight, length and head circumference of the newborns were analyzed in connection with the measured maternal parameters. RESULTS: Significantly elevated tumor necrosis factor-alpha, tumor necrosis factor receptor-1 and -2, leptin, and C-peptide levels were found in the 3rd3 trimester as compared with the 1st1 and 2nd2 trimesters and with the nonpregnant controls. Tumor necrosis factor-alpha, tumor necrosis factor receptor-2, C-peptide, leptin concentrations and body mass index were found to be in a significant positive linear correlation with each other. Significant negative linear correlations were calculated among maternal serum C-peptide, tumor necrosis factor-alpha and leptin concentrations and the head circumference of the newborns. CONCLUSIONS: In conclusion, increased tumor necrosis factor-alpha and leptin levels may contribute to insulin resistance in late pregnancy. Tumor necrosis factor-alpha and leptin may be regulators of intrauterine bone development of newborns.

Adult↗
PubMed2002

Tumor necrosis factor system in insulin resistance in gestational diabetes.

OBJECTIVE: The aim of the study was to investigate the pathophysiological role of the tumor necrosis factor (TNF) system in insulin resistance in patients with gestational diabetes (GDM) and during the course of normal pregnancy. PATIENTS AND METHODS: Thirty women with GDM (16-39 gestational weeks), 35 healthy pregnant women (15 first, nine second and 11 third trimester) and 25 healthy age-matched non-pregnant women were studied. Serum TNF-alpha, and its soluble receptors 1 and 2 (sTNFR-1 and -2) were measured. RESULTS: In non-diabetic pregnant women in the third trimester all measures were significantly higher (P<0.05 or less) than in the first trimester and in non-pregnant women (BMI 27.6 +/- 4.1 (+/- S.D.), 24.1 +/- 2.6, 22.4 +/- 2.4 kg/m(2)), serum TNF-alpha (4.6 +/- 0.6, 4.1 +/- 0.4, 4.1 +/- 0.4 ng/l), sTNFR-1 (2.7 +/- 0.9, 2.0 +/- 0.5, 2.0 +/- 0.1 microg/l), sTNFR-2 (5.6 +/- 2.6, 4.6 +/- 2.1, 3.3 +/- 0.2 microg/l), C-peptide (3.1 +/- 1.7, 1.1 +/- 0.7, 1.1 +/- 0.8 microg/l), and C-peptide:blood glucose ratio (0.6 +/- 0.2, 0.2 +/- 0.1, 0.2 +/- 0.1 microg/mmol). In GDM these measures were even higher than in any subgroup of healthy pregnant women (BMI) (33.4 +/- 6.4 kg/m(2), TNF-alpha) (6.3 +/- 0.6 microg/l), sTNFR-1 (3.0 +/- 0.5 microg/l), sTNFR-2 (10.0 +/- 6.9 microg/l, C-peptide 6.0 +/- 2.7 microg/l, C-peptide:blood glucose ratio: 1.2 +/- 0.5 microg/mmol, P<0.01). Significant (P<0.01) positive linear correlations were found in gestational diabetic and non-diabetic women between serum TNF-alpha, C-peptide levels, and BMI. In gestational diabetic women, in multivariate analysis studying the dependency of C-peptide only BMI remained significant (r(2)=0.67, P=0.01). CONCLUSIONS: Our observation emphasizes the obesity-related component of insulin resistance driven by adipocytokines, such as TNF-alpha and its receptors during the course of normal pregnancy and GDM.

Antigens, CD↗
PubMed2002

Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes.

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

Blood Glucose↗