Expression of leptin mRNA as non-invasive biomarker in type 2 diabetes mellitus.

CONTEXT: Leptin, an adipocyte-derived signalling molecule that plays important role in the regulation of energy balance, body weight and glucose metabolism. OBJECTIVE: To evaluate leptin mRNA expression as a predictive biomarker in type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: To detect the expression patterns of leptin mRNA, a quantitative real-time polymerase chain reaction was performed on samples collected from 71 T2DM patients and 32 non-diabetic controls. The receiver operating characteristic curve (ROC) was utilised to assess the discriminatory power of leptin mRNA. RESULTS: Leptin mRNA levels were reduced significantly in diabetic patients compared with non-diabetic controls (P ≤ .0001). The ROC curve analysis showed a significant association between leptin mRNA levels and T2DM (P ≤ .0001), with a high area under the ROC curve (AUC) of 0.95 (95% CI: 0.89-0.98). The analysis also showed that fasting blood glucose and glycosylated haemoglobin had high AUC values of 0.88 and 0.97 with (95% CI: 0.80-0.93 and 0.92-0.99), respectively. CONCLUSION: This study shows that the reduced leptin mRNA expression level is significantly associated with T2DM and could be used as a predictive and diagnostic biomarker for T2DM.

Ghrelin intronic lncRNAs, lnc-GHRL-3:2 and lnc-GHRL-3:3, as novel biomarkers in type 2 diabetes mellitus.

BACKGROUND: We aim to identify circulating lncRNAs located in the region of the ghrelin (GHRL) gene that play a role in the development of T2DM. METHODS: Bioinformatic tool was used to identify candidates GHRL-lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to compare the expression levels of selected lncRNAs on diabetic patients and non-diabetic controls.Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory power of selected GHRL-lncRNAs. RESULTS: The bioinformatic analysis predicted three antisense and eight sense-intronic GHRL- lncRNAs. Two differentially expressed GHRL-lncRNAs were detected in diabetic patients. The expression levels of lnc-GHRL-3:2, lnc-GHRL-3:3, and the GHRL mRNA were significantly (p ≤ .0001) lower in the diabetic patients. ROC analysis showed that the area under the curve (AUC) value was 0.93 for lnc-GHRL-3:2 and 0.90 for lnc-GHRL-3:3. CONCLUSION: lnc-GHRL-3:2 and lnc-GHRL-3:3 are novel biomarkers and might play a regulatory role in T2DM pathogenesis.

Intergenic lnc-LEP-2:6 and lnc-LEP-2:7 as novel biomarkers associated with type 2 diabetes mellitus.

CONTEXT: Type 2 diabetes mellitus (T2DM) has undeniably become a significant threat to public health in the modern world. OBJECTIVE: To identify molecules involved in the development of T2DM, the expression patterns of cis-lincRNAs-LEP were investigated in T2DM patients. MATERIALS AND METHODS: The expression levels of 11 lncRNAs-LEP and LEP mRNA in 71 diabetic patients and 32 controls were determined using qRT-PCR. The association between lncRNAs-LEP and T2DM was performed using ROC curve analysis. RESULTS: The expression analysis of lnc-LEP-2:6 and lnc-LEP-2:7 was significantly different (p≤ .0001) in diabetic patients compared to the controls. The ROC curve data showed that lnc-LEP-2:6 and lnc-LEP-2:7 have a high AUC, with 0.940 (95% CI: 0.875-0.977) and 0.958 (95% CI: 0.899-0.988), respectively. CONCLUSIONS: Our results revealed two novel biomarkers associated with the T2DM and suggest that the circulating intergenic, lnc-LEP-2:6 and lnc-LEP-2:7, might have a regulatory role in the disease pathogenesis.

Visfatin and global histone H3K9me levels in colon cancer.

BACKGROUND: Visfatin is considered to be a biomarker in various types of cancers, including colon cancer. Moreover, evidence for epigenetic mechanism must be reported for an association between visfatin level and colon cancer. Therefore, this study was designed to investigate the status of visfatin expression and the global histone three modifications in colon cancerous tissue. METHODS: Colon cancerous tissue and paired adjacent non-cancerous tissue from 30 patients were used to determine the global histone three modifications using Western blot. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess visfatin's expression level in tissues. RESULTS: The visfatin and the global H3K9me expression levels were significantly higher in colon cancerous tissue than in the paired adjacent non-cancerous tissue. CONCLUSION: The present study makes a crucial noteworthy contribution to visfatin effect on colon cancer development via H3K9me.

Correlation of leptin and sex hormones with endocrine changes in healthy Saudi women of different body weights.

BACKGROUND: A relationship between estrogen and leptin has been described during the follicular phase of both spontaneous menstrual cycles and cycles stimulated with exogenous follicle-stimulating hormone (FSH), which suggest that leptin has either a direct effect on or is regulated by gonadal steroids in the human ovary. To examine the changes in plasma leptin levels during the menstrual cycle, we studied the association between plasma leptin and reproductive hormones in young, healthy Saudi women. SUBJECTS AND METHODS: Sixty-five young women between 19 to 39 years of age, with a normal menstrual cycle, were grouped into 33 overweight and obese females of BMI >25 kg/m2, and 32 lean females of BMI <25 kg/m2. Anthropometrics measurements were made at the time of the collection. Samples were analyzed for leptin, progesterone, estradiol (E2), FSH, luteinizing hormone (LH), cortisol, and testosterone concentrations. RESULTS: Overweight and obese women, compared with lean, tended to have a significantly higher plasma leptin levels (11.38 +/- 4.06 vs. 6.22 +/- 2.87 ng/mL; P=0.05). In overweight and obese subjects, circulating leptin concentrations showed a directcorrelation with BMI (r=0.53; P=0.002), hip circumference (r=0.32; P=0.005), waist-hip ratio (r=0.37; P=0.042), weight (r=0.41; P=0.021), and E2 on day 3 (r=0.35; P=0.048). In all correlation analyses, leptin levels did not correlate with cortisol or testosterone. In lean subjects, a bivariate correlation analysis showed that plasma leptin concentrations were directly correlated to hip circumference (r=0.43; P=0.012). Moreover, a direct correlation was found with progesterone on day 10 (r=0.43; P=0.014) and E2 on day 24 (r=0.47; P=0.007). CONCLUSION: There is a link between plasma leptin and progesterone concentrations during the menstrual cycle, and the variation in circulating estradiol concentrations may have an influence on circulating leptin in female subjects.

Serum resistin, adiposity and insulin resistance in Saudi women with type 2 diabetes mellitus.

BACKGROUND: The role of adipocyte hormones in modulating insulin sensitivity and glucose tolerance are of increasing interest and importance in studies of type 2 diabetes mellitus. Recently a unique signaling molecule, resistin, has been proposed as playing a role in the pathogenesis of obesity-related insulin resistance, but its relevance to human diabetes remains uncertain. Therefore, we assessed the relationship between serum resistin concentrations and insulin resistance in lean, overweight and obese (OW/OB) non-diabetic and diabetic Saudi women. SUBJECTS AND METHODS: We measured fasting serum resistin levels in 44 diabetic women with a mean body mass index (BMI) of 31.82 +/- 4.35 kg/m2, 21 OW/OB non-diabetic women with a mean BMI 30.71 +/- 3.42 kg/m2 and in 24 lean women with a mean BMI of 23.33 +/- 1.24 kg/m2. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance formula derived from fasting insulin and glucose levels. RESULTS: The concentrations of fasting serum resistin showed significant differences among the three groups (P<0.001). Mean serum resistin concentrations increased from lean (11.59 +/- 2.08) to OW/OB non-diabetic (16.29 +/- 2.29) to diabetic (19.42 +/- 3.60 ng/mL) women. Significantly higher levels of glucose (P<0.001) and values for the homeostasis model assessment ratio (HOMA-R) (P<0.01) occurred in the diabetic compared to the lean and OW/OB non-diabetic subjects. Furthermore, resistin correlated significantly and positively with hip circumferences (r=0.39, P=0.039), weight (r=0.51, P=0.005), insulin (r=0.40, P=0.033), HOMA-R (r=0.49, P=0.007) and glucose (r=0.39, P=0.038) in diabetic women. In OW/OB non-diabetic subjects, resistin correlated with insulin (r=0.59, P=0.015) and HOMA-R (r=0.616, P=0.011). No correlation was observed with glucose, height, hip, waist, weight, and waist-hip ratio (WHR) in the lean and OW/OB non-diabetic groups. CONCLUSION: Resistin concentrations are elevated in patients with type 2 diabetes and are associated with obesity and insulin resistance. These data indicate that resistin might be involved in the development of diabetes in humans.

Relationship of leptin concentration to gender, body mass index and age in Saudi adults.

OBJECTIVE: Leptin concentrations are highly correlated with body fat storage and exhibit sexual dimorphism, with women having higher concentrations at every level of relative or absolute adiposity. To test whether or not this relation is consistent across the Saudi population. This study aims to investigate the effect of gender, obesity related parameters, and age on leptin levels from representative samples of Saudi women and men. METHODS: This study was carried out at King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia during the year 2003. Fasting leptin concentrations were determined after an overnight fast in 122 healthy subjects (57 women, 65 men; age 20-75 years; body mass index [BMI] 16-56 kg/m2). The subjects were separated into female and male groups. To clarify the age and BMI-related changes in leptin levels, each gender was divided into 3 BMI groups (lean 15-24, overweight 25-30 and obese >30 kg/m2), and 3 age groups (younger 20-34, middle-aged 35-49 and older 50-75 years); and they were treated separately. Anthropometrics measurements (weight, height, waist, and hip circumferences), blood pressure, and fasting glucose levels were taken at the time of the collection. RESULTS: In the whole group, leptin levels were between 0.16-21.72 ng/ml, and females had higher leptin concentration (6.04 +/- 4.71 ng/ml versus 1.72 +/- 0.95 ng/ml, p<0.0001) than males. Gender differences remained clear when leptin concentrations were divided by BMI or age. In comparing the pattern of changes between the 2 genders, leptin levels were low in lean individuals and rose with increased BMI in both genders. Age-related change in leptin levels showed a tendency toward a non-significant reduction in older women and a significant (p=0.05) rise in older men. Correlation analysis between leptin and BMI were highly significant in female (r=0.64; p=0.0001) and male (r=0.49; p=0.0001) groups independent of age and sex. The findings were further explored using stepwise multiple linear regression analysis with leptin concentrations as the dependent variable and age, BMI, waist hip ratio (WHR), waist, and hip measurements as independent variables. The analysis demonstrated that the determinants of leptin concentrations were BMI and age (r=0.69; p=0.015) in women and BMI, age and WHR (r=0.61; p=0.01) in men. CONCLUSION: The present study demonstrates that there are gender-specific and age-dependent gender-specific differences in leptin concentrations in healthy Saudi individuals. However, this study indicates that there may be unknown variables that may also influence leptin levels in Saudi women and men.

The adiponectin gene, ADIPOQ, and genetic susceptibility to colon cancer.

In order to evaluate the contribution of polymorphisms of the adiponectin gene, ADIPOQ, to the risk of colon cancer, we conducted a case-control study of 60 colon cancer patients and 60 age, gender and ethnicity-matched controls in the Saudi population. We tested the hypothesis by analyzing the genotypes for two single nucleotide polymorphisms (SNPs), rs1501299 (G276T) and rs2241766 (T45G), in the ADIPOQ gene. In addition, the study was also designed to assess whether the two SNPs contribute to circulating adiponectin levels. We observed an increased risk of colon cancer associated with the 276T allele. The odds ratio (OR) was 2.64 [95% confidence interval (CI), 0.49-14.6]. The G allele at the T45G polymorphism was associated with a lower risk of colon cancer (OR=0.41; 95% CI, 0.19-0.86). Our results suggest that the risk of developing colon cancer may be partially explained by genetic polymorphisms in the ADIPOQ gene.

Resistin in human colon cancer. Increased expression independently of resistin promoter C-180G genotype.

OBJECTIVE: To determine the relationship between resistin gene RETN C-180G variant and circulating resistin concentration in Saudi colon cancer patients. METHODS: This case-control study was conducted in the Biochemistry Department, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia from April 2009 to December 2009. The serum concentration had been measured with enzyme-linked immunosorbent assay in 60 colon cancer patients and in 60 controls matched in gender and age. The single nucleotide polymorphism SNP C-180G was genotyped using polymerase chain reaction PCR and restriction fragment length polymorphism RFLP techniques. RESULTS: We observed a significantly higher serum resistin level in colon cancer group compared with control group 19.44 +/- 8.46 versus 5.45 +/- 2.73 ng/ml; p=0.0001, with significant p=0.03 higher levels showed in women than in men in patients and controls. In patients, the heterozygous CG and homozygous GG genotype carriers showed higher p=0.08 levels of serum resistin compared to CC homozygous. This difference was not observed p=0.78 among SNP C-180G genotypes in control group. CONCLUSION: Our result showed no association between the C-180G SNP and the serum resistin concentrations and suggests that the high resistin level in colon cancer patients may play an important role in colon cancer development.