Adipocytokine dysregulation, abnormal glucose metabolism, and lipodystrophy in HIV-infected adolescents receiving protease inhibitors.

BACKGROUND: Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types. METHODS: A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type). RESULTS: Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (ß = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (ß = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05). CONCLUSIONS: Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.

Relationships of apelin concentration and APLN T-1860C polymorphism with obesity in Thai children.

BACKGROUND: Childhood obesity represents a serious global health crisis. Apelin and its receptor system are widely distributed throughout the central nervous system and have been demonstrated to serve a role modulating feeding behaviour and energy homeostasis. The purposes of this study were to examine apelin concentrations and anthropometric-cardiometabolic parameters in obese and non-obese children and to identify associations of APLN T-1860C and APLNR G212A polymorphisms with apelin levels and obesity among Thai children. METHODS: This case-control study included an analysis of 325 Thai children: 198 children with obesity and 127 healthy non-obese children. Anthropometric-cardiometabolic variables and apelin concentration were measured. Genotyping of APLN T-1860C and APLNR G212A was performed using the polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The obese group had significantly lower apelin and HDL-C levels but significantly higher triglycerides and glucose (TyG) index values, TG/HDL-C ratio and TC/HDL-C ratio than the non-obese group (p < 0.01). Apelin level was negatively correlated with body size phenotypes and cardiometabolic parameters (p < 0.05). The APLN T-1860C polymorphism (OR = 4.39, 95% CI = 1.25-15.28) and apelin concentration (OR = 0.45, 95% CI = 0.23-0.92) were significantly associated with obesity among female children (p < 0.05) only, after adjusting for potential covariates. However, the APLNR G212A polymorphism showed no significant relationship with apelin concentration or obesity. CONCLUSION: These findings in Thai children suggest that apelin concentrations are related to obesity and cardiometabolic parameters. Furthermore, the APLN T-1860C polymorphism may influence susceptibility to obesity among female children.

Associations among serum folate, waist-to-hip ratio, lipid profile, and eating habits with homocysteine in an elderly Thai population.

A lower serum folate level is common in older populations and is associated with increased serum homocysteine concentration. In turn, an elevated homocysteine level is associated with increased risk of cardiovascular disease and age-related diseases. Contemporary studies of folate and dietary risk factors for cardiovascular disease among the elderly population in Thailand are lacking. This cross-sectional study aimed to investigate the relationships among serum folate, homocysteine level, and nutritional status in the elderly Thai. Three hundred individuals, aged 60 years and over, underwent anthropometric and physiological measurements, and biochemical parameters, and eating habits were also determined. Folate insufficiency was found in approximately 35% of subjects. Folate and homocysteine showed a significant inverse correlation. Serum homocysteine levels rose with increasing age. Folate deficiency and high waist-to-hip ratio were associated with 7-fold and 2.5-fold increased risk for hyperhomocysteinemia, respectively. There were positive correlations between homocysteine and waist-to-hip ratio and systolic blood pressure, but a negative correlation between homocysteine and high-density lipoprotein (r = -0.239, p < 0.01), which are markers for cardiovascular disease risk. Folate negatively correlated with body mass index, waist-to-hip ratio, and diastolic blood pressure, but positively with high-density lipoprotein (r = 0.162, p < 0.01). Investigation of eating habits showed that low consumption of green leafy vegetables and high consumption of sugary foods were associated with high homocysteine levels. Given associations between nutritional status and cardiovascular disease confirmed in this study, nutrition education, holistic health promotion, and appropriate behavioral modification of eating habits represent important measures for preventing premature cardiovascular disease in the elderly Thai population.

Maoberry (Antidesma bunius) ameliorates oxidative stress and inflammation in cardiac tissues of rats fed a high-fat diet.

BACKGOUND: Chronic fat-rich diets consumption is increased risk associated with cardiovascular diseases (CVD). Prevention or reduction the progression of cardiac tissue deterioration could benefit in CVD. This study aimed to examine the effects of maoberry (Antidesma bunius), a antioxidant-rich tropical fruit, supplementation on oxidative stress and inflammation in cardiac tissues of rats fed a high-fat diet (HFD). METHODS: The male rats orally received HFD with maoberry extract doses of 0.38, 0.76 or 1.52 g/kg or simvastatin (10 mg/kg) for 12 weeks. At the end of the experimental period, the rats were fasted, euthanized and harvested for the hearts. RESULTS: Significantly reduced oxidative stress (malondialdehyde levels) and enhanced antioxidant capacity (ferric-reducing activities) in cardiac tissues of the rats were found. Maoberry extract remarkably ameliorated the expressions of genes involved with pro-inflammatory such as the tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and endothelial nitric oxide synthase (eNOS). CONCLUSIONS: Our findings suggest that maoberry extract has remarkable effects on preventing progression of cardiac tissue deterioration at least through lowering oxidative stress and inflammation.

Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women.

BACKGROUND: Osteoporosis, characterized by low bone mineral density (BMD) and high bone fracture risk, is prevalent in Thai menopausal women. Genetic factors are known to play a key role in BMD. Low density lipoprotein receptor-related protein 5 (LRP5), a co-receptor in the Wnt/beta-catenin pathway, is involved in many aspects of bone biology. As coding single nucleotide polymorphisms (cSNPs) of LRP5, including A1330V (rs3736228), and Asian-related Q89R (rs41494349) and N740N (rs2306862), are associated with lowered BMD, this study aimed to determine the relationship between these LRP5 polymorphisms and BMD in 277 Thai menopausal women. RESULTS: Only rs3736228 deviated from the Hardy-Weinberg equilibrium of allele frequency (p = 0.022). The median, range and p value for the BMD related to each SNP parameter were compared (Mann-Whitney U test). Significant differences were observed between wild-type and risk alleles for both rs3736228 (total radial, p = 0.011; and radial 33, p = 0.001) and rs2306862 (radial 33: p = 0.015) SNPs, with no significant difference for rs41494349 SNP. Linkage disequilibrium was strong for both rs3736228 and rs2306862 SNPs. Haplotype analysis identified high CC frequency in both normal and osteopenia/osteoporosis groups, with a significant odds ratio for carrying the TT haplotype; however, this was non-significant after adjusting for age. Multivariate binary logistic regression analysis performed for rs3736228 showed that individuals with a body mass index <25 kg/m(2) had an increased risk of osteoporosis for each decade, but the polymorphism had no effect. CONCLUSIONS: This study did not identify LRP5 polymorphisms as a risk factor for osteoporosis in Thai menopausal women. Further studies with larger sample sizes are needed to further clarify the role of LRP5 as a genetic determinant of osteoporosis.

Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action.

Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ω-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ω-oxidation of fatty acids.

ADIPOQ POLYMORPHISMS AMONG THAIS WITH PRE-DIABETES.

Studies have shown that polymorphisms of adiponectin gene (ADIPOQ) are associated with risk of developing type 2 diabetes mellitus (T2DM). However, no studies have investigated the association between genetic variants of ADIPOQ and pre-diabetes, a group at higher risk for developing T2DM. A total of 75 pre-diabetes and 130 normal subjects were recruited from volunteers in Bangkok, Thailand. Individuals with pre-diabetes were selected based on American Diabetes Association diagnostic criteria. Six ADIPOQ polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique. ADIPOQ polymorphism rs266729 C>G is significantly associated with pre-diabetes (p = 0.006). CG/GG genotypes were found among 60% and 40% of pre-diabetes and normal subjects, respectively. SNP rs266729 C>G was associated with increased pre-diabetes risk (OR = 2.64; 95% CI: 1.18-5.89, p = 0.018). No significant differences were found between pre-diabetes and normal subjects for other ADIPOQ polymorphisms. However, haplotype analysis revealed that haplotype GGTAAT is significantly associated with pre-diabetes when compared with GCGAAC reference haplotype (OR = 22.31; 95% CI: 1.37-361.93, p = 0.03). Our data indicate that ADIPOQ rs266729 C>G polymorphism may contribute to the genetic risk of pre-diabetes and provide preliminary data useful in genetic screening for pre-diabetes among Thais.

Prevalence of plasma small dense LDL is increased in obesity in a Thai population.

BACKGROUND: Plasma low density lipoprotein (LDL) particles vary in size, density, electrical charge and chemical composition. An increased presence of small dense LDL (sdLDL), along with raised triglyceride concentrations and decreased high density lipoprotein (HDL) cholesterol concentrations is commonly known as the atherogenic triad and has been observed in some cases of obesity, principally in Europe and America. This study examines the prevalence of sdLDL in the plasma of an obese (BMI≥25 kg/m2) Thai population. METHODS: Plasma from fasted obese (n=48) and non-obese (n=16) Thai participants was subjected to density gradient ultracentrifugation in iodixanol to separate lipoproteins. Gradients were unloaded top-to-bottom into 20 fractions which were assayed for cholesterol, triglyceride, apo B and apo A-1 to identify lipoprotein types and subtypes. RESULTS: LDL cholesterol was subfractionated into LDL I+II (fractions 3-6, ρ=1.021-1.033 g/ml) which was considered to represent large buoyant LDL (lbLDL), LDL III (fractions 7-9, ρ=1.036-1.039 g/ml) which was considered to represent sdLDL, and, LDL IV (fractions 10-12, ρ=1.044-1.051 g/ml) which was considered to represent very sdLDL. Concentrations of LDL III and IV were increased by 15-20% in obese participants whilst that of LDL I+II was concomitantly decreased by 10%. This was accompanied by a 50% increase in plasma triglyceride concentrations and 15% decrease in HDL cholesterol concentrations. Only 3/16 (19%) non-obese participants had a pattern B LDL cholesterol profile (peak density of >1.033 g/ml), whilst 28/48 (58%) obese participants were pattern B. When expressed as a fraction of the LDL concentration, total sdLDL (i.e. LDL III+IV) showed highly significant correlations to plasma triglyceride concentrations and the triglyceride/HDL cholesterol ratio. CONCLUSIONS: The prevalence of sdLDL is increased in obesity in a Thai population such that they demonstrate a similar atherogenic triad to that previously observed in European and American populations.

Adiponectin mediated APPL1-AMPK signaling induces cell migration, MMP activation, and collagen remodeling in cardiac fibroblasts.

Defects in adiponectin action have been implicated in the development of cardiac dysfunction in obesity and diabetes. Cardiac fibroblasts play an important role in regulating extracellular matrix remodeling yet little is known regarding the direct effects of adiponectin on cardiac fibroblasts. In this study, we first demonstrated temporal relocalization of cellular APPL1 in response to adiponectin in primary cardiac fibroblasts and that siRNA-mediated knockdown of APPL1 attenuated stimulation of AMPK by adiponectin. The cell surface content of MT1-MMP and activation of MMP2 were induced by adiponectin and these responses were dependent on AMPK signaling. Enhanced MMP activity facilitated increased fibroblast migration in response to adiponectin which was also prevented by inhibition of AMPK, with no change in cell proliferation observed. Collagen and elastin immunofluorescence demonstrated reorganization of the extracellular matrix in accordance with increased MMP activity, whereas quantitative mRNA analysis, (3) H-proline incorporation and picrosirius red assays showed no change in intracellular or extracellular total collagen levels in response to adiponectin. In summary, these data are the first to report the adiponectin stimulated APPL1-AMPK signaling axis in cardiac fibroblasts and characterize MT1-MMP translocation, MMP2 activity and cell migration as functional outcomes. These effects may be of significance in heart failure associated with obesity and diabetes.

Homocysteine but not serum amyloid A, vitamin A and E related to increased risk of metabolic syndrome in post-menopausal Thai women.

This study aims to investigate serum amyloid A, homocysteine, and biochemical-anthropometric measurements in post-menopausal women with and without metabolic syndrome (MS), and determine whether serum amyloid A and homocysteine are linked to MS among this group. This study was performed with 405 post-menopausal Thai volunteers with a mean age of 57.95±5.90 years (135 subjects with MS and 270 subjects without MS). The levels of serum amyloid A, homocysteine, vitamins, glucose, and lipids were measured. Homocysteine levels were significantly higher in the group with MS than in that without MS (p<0.001), whereas for serum amyloid A, vitamin A, vitamin E and vitamin B12, there were no significant differences. There were significant differences between the groups in folate, HDL-C, and anthropometric measurements (p<0.001). Thirty seven percent of the group with MS and 14.1% of the group without MS were classified as having hyperhomocysteinemia (p<0.001). Furthermore, logistic regression analysis revealed that hyperhomocysteinemia (odds ratio (OR): 2.67, 95% confidence interval (95%CI): 1.57-4.58), low folate (OR: 1.79, 95%CI: 1.11-2.89), and BMI (OR: 1.25, 95%CI: 1.16-1.33) were significantly related to MS. These findings suggest that increased homocysteine levels and decreased folate concentrations may influence susceptibility to MS and this effect may be an early event in the development of cardiovascular diseases among post-menopausal women. Therefore, there is a need to evaluate homocysteine levels, especially among post-menopausal Thai women.

Effects of PCSK1 genetic variants on obesity among Thai children and their family members: in relation to health risk, and biochemical and anthropometric parameters.

Single nucleotide polymorphisms (SNPs) in PCSK1, namely, rs6234, rs6235, and rs271939 have been linked to obesity in European population; and rs3811951 has also been connected to type 2 diabetes and obesity parameters in Chinese population. In this family-based case-control study, we analyzed links between PCSK1 genetic variants and obesity in Thai children and their families. Eleven obese children with a percent weight for height > or = 140 who had family history of obesity and 69 family members were recruited. SNPs rs6234, rs6235, rs3811951, and rs271939 of PCSK1 were analyzed using PCR and gene sequencing methods. DNA of 200 normal weight subjects was used as control. Participants with variant genotypes in the rs6234-6235 pair are at significantly more risk of being obese [OR = 2.44 (1.35-4.43), p = 0.003], and also at increased risk of being severely obese (obese class III) [OR = 3.03 (1.20-7.66), p = 0.015]. Variant rs3811951 showed no association with being obese, but is significantly linked to an increased risk of being severely obese [OR = 3.59 (1.42-9.08) p = 0.005]. Moreover, high density lipoprotein (HDL)-C levels between normal and variant rs3811951 group differed considerably, with patients with variant genotype having a lower HDL-C level (p = 0.037). Thus, Thais carrying SNPs rs6234-5 are at increased risk of being obese, and the risk of severe obesity increases when carrying both rs6234-5 and rs3811951, but not with rs271939. Furthermore, patients with genetic variations at rs3811951 are at risk of having low HDL-C levels.

ID4 gene polymorphism and osteoporosis in Thai menopausal women.

BACKGROUND: The inhibitor of DNA binding 4 (ID4) protein regulates osteogenic and adipogenic cell fate and lack of lD4 gene expression decreased osteoblast differentiation. Variant in the ID4 gene polymorphism has not been reported with osteoporosis. OBJECTIVE: To identify whether ID4 can be a marker gene for osteoporosis in Thai menopausal women. MATERIAL AND METHOD: The 3 'UTR of lD4 (rs3798339) single nucleotide polymorphism was examined bypolymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), together with lumbar spine bone mineral density (BAMD) in 160 Thai menopausal women. RESULTS: Lumbar spine 3 (L3) had a significantly lower BMD score in women with the TT genotype, compared with the CT+CC genotypes (p = 0.037). This disappeared after the adjustment of various factors. CONCLUSION: The polymorphism at 3'UTR of lD4 gene can alter ID4 mRNA stability, and may be linked to the function of proteins. However, this needs confirmation in larger populations. The present study is useful as an initial investigation into ID4 gene polymorphism in osteoporosis.

Association of MTHFR C677T polymorphism with bone mineral density of osteoporosis in postmenopausal Thai women.

BACKGROUND: Osteoporosis and osteopenia is rising with the increase in numbers of postmenopausal women. Methylenetetrahydrofolate reductase (MTHFR), a homocysteine catabolizing enzyme, is involved in the regulation of bone mineral density (BMD). The association between MTHFR C677T polymorphism with osteoporosis in postmenopausal Thai women is hitherto unclear. OBJECTIVE: To investigate the association between MTHFR C677T and BMD in postmenopausal Thai women. MATERIAL AND METHOD: The study subjects consisted of 346 postmenopausal Thai women volunteers. Standard dual-energy X-ray absorptiometry (DXA) was used for measurement of BMD T-score. Restriction fragment length polymorphism (RFLP) analysis was used for measurement of MTHFR C677T polymorphism. RESULTS: In the evaluation of 346 postmenopausal Thai women heterozygous (CT) genotype had a risk of osteopenia than normal control (odds ratio (OR) = 5.66, p < 0.001). BMD T-scores at each bone position revealed that heterozygous (CT) genotype had increased risk of osteopenic bones than normal controls at lumbar spines 1, 2, and 4 (OR = 2.48, p < 0.001, OR = 1.98, p = 0.008 and OR = 1.83, p = 0.016 respectively), ward's triangle (OR = 2.08, p = 0.008), and head of radius (OR = 2.95, p = 0.008). CONCLUSION: These results indicate the possibility of using MTHFR C677T polymorphism to identify postmenopausal Thai women at high risk of osteopenia.

Decreased retinol transport proteins in Thai post-menopausal women with osteoporosis.

High vitamin A ingestion or high serum retinol have been postulated to increase the risk of fractures and osteoporosis by reduced bone mineral density (BMD). Retinol is carried and transported to the tissues bound to retinol binding protein 4 (RBP4) and transthyretin (TTR). The relationships between retinol, retinol transport protein, retinol binding protein 4 (RBP4) and transthyretin (TTR) and BMD and osteoporosis are unclear. To examine the association between retinol and RBP4 and TTR and osteoporosis, 73 osteoporotic and 71 normal Thai postmenopausal women were studied. RBP4 and retinol levels did not differ between the groups. Serum TTR was significantly higher in control than osteoporotic subjects (89.47 and 144.53 microg/ml, respectively, p = 0.003, Mann-Whitney U test). TTR was positively correlated with BMD at several sites, such as the total radius bone (r = 0.172, p = 0.008, Spearman rank test). Osteoporosis risk was analyzed with binary logistic regression. Lean elderly Thais with lower TTR levels had a higher risk of osteoporosis. RBP4 and retinol levels had no relationship with disease status among Thai post-menopausal women. These results suggest calcium, minerals, vitamins and the retinol transport protein, transthyretin may be involved in the pathogenesis of osteoporosis.

Association between retinol-binding protein and renal function among Asian subjects with type 2 diabetes mellitus: a cross-sectional study.

Retinol-binding protein 4 (RBP4) has been suggested as new adipokine, possibly linking obesity to type 2 diabetes mellitus (T2DM). Since the kidneys are the main site of RBP4 degradation and since renal failure is a frequent co-morbid condition with diabetes mellitus, we evaluated the association among RBP4, renal function and T2DM in an Asian population. RBP4 serum levels were analyzed in 110 subjects (50 with T2DM) using an enzyme-linked immunosorbent assay (ELISA). Based on a cut-off estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m2 (calculated according the abbreviated MDRD formula which uses serum creatinine level, age and gender) and on the T2DM status, subjects were assigned to four subgroups: Group A- controls with an eGFR > 60 ml/min per 1.73 m2, Group B - controls with an eGFR < 60 ml/min per 1.73 m2, Group C- T2DM subjects with an eGFR > 60 ml/min per 1.73 m2, and Group D - T2DM subjects with an eGFR < 60 ml/ min per 1.73 m2. In both the T2DM and control groups, RBP4 levels were higher in subjects with an eGFR < 60 ml/min per 1.73 m2 than in subjects with an eGFR > 60 ml/min per 1.73 m2. However, the difference was only significant between the control groups (p < 0.05). After adjusting for age, gender, BMI, eGFR and the presence of T2DM, eGFR, not T2DM, was associated with plasma RBP4 levels (p < 0.05). These results suggest among Asians the eGFR, but not the presence of T2DM, is a major determinant of RBP4 serum levels. The eGFR should be taken into account when evaluating the role of RBP4 in the pathogenesis of insulin resistance and T2DM.

Alterations in malondialdehyde levels and laboratory parameters among methamphetamine abusers.

OBJECTIVE: To determine the concentrations of malondialdehyde, biochemical, and hematological parameters among methamphetamine abusers compared with a healthy control group and to evaluate the association between malondialdehyde and biochemical-hematological parameters. MATERIAL AND METHOD: The concentrations of malondialdehyde, lipids, liver enzymes, albumin, blood urea nitrogen, creatinine, and hematological measurements were determined in 60 methamphetamine abusers and 60 controls. RESULTS: Significantly higher levels of malondialdehyde were found in the methamphetamine abusers than the controls [2.45 (2.12-2.81) vs. 1.41 (1.15-2.08)]. The levels ofalanine aminotransferase and alkaline phosphatase and white blood cell and platelet counts of the methamphetamine abusers were significantly elevated (p-value < 0.05) compared with the controls. Meanwhile, the levels of hemoglobin, hematocrit, albumin and body mass index were significantly lower among the methamphetamine-abusing group than the control group (p-value < 0.05). It was found that higher numbers of methamphetamine tablets per day were associated with higher malondialdehyde concentrations in methamphetamine abusers, and that malondialdehyde concentration inversely correlated with albumin level (r = -0.458, p-value < 0.05). Stepwise multiple regression analysis revealed that number of methamphetamine tablets per day, white blood cell count and albumin level were independent predictors of malondialdehyde level (p-value < 0.05). CONCLUSION: Methamphetamine abuse is related to increased lipid peroxidation, changes in inflammatory marker level, increase in liver enzymes, and decrease in hemoglobin and hematocrit concentrations. These effects may be early signs of the development of diseases associated with methamphetamine abuse.

The -11377C > G adiponectin gene polymorphism alters the adiponectin concentration and the susceptibility to type 2 diabetes in Thais.

The aims of this study were first to detect the levels of adiponectin, insulin, albumin, glucose, alanine aminotransferase (ALT), lipids, homeostasis model assessment for insulin resistance (HOMA-IR), and anthropometric variables in type 2 diabetes mellitus (T2DM) as well as healthy control groups, and to determine whether two adiponectin gene polymorphisms, at the position -11377C > G as well as +45T > G, are associated with serum levels of adiponectin and other variables; then to search for the association between these two single nucleotide polymorphisms (SNPs) of the adiponectin gene and T2DM. We investigated 93 T2DM patients and 90 healthy volunteers. Compared with the healthy control group, the T2DM group had significantly lower adiponectin levels. Waist circumference, total cholesterol, ALT, glucose, insulin, and HOMA-IR scores were significantly higher in the T2DM group than in the control group. The polymorphism of the adiponectin gene at position -11377C > G among type 2 diabetes subjects showed that the adiponectin concentration was significantly lower in CG/GG genotypes (6.2 µg/mL) than the CC genotype (7.8 µg/mL), whereas SNP +45T > G was not associated with adiponectin levels. Adiponectin gene polymorphisms at position -11377C > G and +45T > G were significantly more frequent in type 2 diabetes patients than in the control group (p = 0.022; p = 0.045, respectively). However, multivariate logistic regression analysis showed that the strong impact on T2DM was found for -11377C > G gene polymorphism (p = 0.023) and waist circumference (p < 0.001). Therefore, the single nucleotide polymorphism of -11377C > G in adiponectin promoter region has impact on the lower adiponectin concentrations, and may influence susceptibility to T2DM in Thais.

Serum leptin levels and body composition in obese Thai children.

This study aimed to investigate the relationship between serum leptin concentrations and body composition among a sample of obese Thai children. A cross-sectional study was conducted in 158 schoolchildren, of whom 107 were obese and 51 normal weight; their mean age was 8.2 years. Body weight, height, waist circumference (WC), and subcutaneous skinfold thickness at 4 sites (triceps, biceps, subscapular, and supra-iliac) were measured. Total body fat (TBF) was determined by bioelectrical impedance analysis. Fasting blood samples were obtained to determine serum lipid profiles. The food intake of the children was estimated from interviews with the children and their mothers to elicit 24-hour food recall over 2 days. The results reveal subcutaneous fat skinfold, total body fat and waist circumference were significantly higher in obese than normal weight children (p < 0.001). Serum leptin levels and lipid profile results, ie serum triglycerides (TG), serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and energy intake, were also significantly higher in the obese children than their normal-weight peers. Stepwise multiple regression analysis indicates that among boys, WC (p < 0.001) and serum TG (p = 0.019), and among girls, WC (p < 0.001) and TBF (p = 0.030), were significantly associated with leptin concentrations. No associations were found between leptin and energy intake in these children. A prospective study should investigate the influence of leptin levels on weight gain and subcutaneous adiposity, and the interrelationship between food intake and circulating leptin levels in children.

Identification of leptin gene variants in school children with early onset obesity.

OBJECTIVE: To investigate leptin gene variations in Thai primary school children. MATERIAL AND METHOD: Direct DNA sequencing was performed following polymerase chain reaction (PCR) amplification of the leptin gene in 30 obese children aged 10-12 years old. RESULTS: A heterozygous variant 19 (G > A), located in the non-coding region of exon 1 was detected in 13 subjects (43.3%, A: 0.22). Only 2 subjects (6.7%, G: 0.03) harbored a heterozygous (CAA > CAG) polymorphism in codon 25 of exon 2. CONCLUSION: The 25 (CAA > CAG) polymorphism appeared to be a new leptin gene variant in Thai people. This study provides basic information concerning the prevalence of leptin gene polymorphisms in Thai children with early onset obesity. It might be useful as genetic marker for screening for obesity potential in large populations.