Hypoadiponectinemia in obesity: association with insulin resistance.

Obesity is risk factor for insulin resistance, diabetes, and other chronic diseases. Adiponectin, an adipose-specific protein with antiatherogenic and antiinflammatory effects, were found to be associated with obesity, type 2 diabetes, and insulin resistance. Our aim to identify possible relationships between circulating adiponectin and obesity as well as obesity related phenotypes. A total of 642, obese and non-obese individuals were included in this cross-sectional study. Hormone and glucose levels were estimated using standard protocols. The adiponectin levels showed a significant decrease with increasing quartiles of insulin resistance index. Subjects in lowest quartile of adiponectin level had a significantly higher risk than those in the highest quartile, with higher body mass index, waist circumference, blood pressure, percentage body fat, fat mass, fasting insulin, insulin resistance index, total cholesterol (p < 0.001), low density lipoprotein-cholesterol (p = 0.001), very low density lipoprotein-cholesterol (p = 0.002), and Triglyceride (p = 0.002). The present study indicates that adiponectin is significantly associated with obesity, insulin resistance and other obesity related phenotypes.

Sensorineural deafness in patients of type 2 diabetes mellitus in uttar pradesh: a pilot study.

B/L symmetrical sensorineural hearing loss has long been associated with diabetes Mellitus. Microangiopathy associated with thickening of the basement membrane of small vessels has been implicated as a major source. This study was done to observe the predominant site of lesion whether cochlear or retrocochlear in patients of diabetic sensorineural hearing loss. This was a random study. Forty two patients with diabetic B/L symmetrical sensorineural hearing loss were selected in a tertiary referral centre. All the patients selected were of diabetic B/L symmetrical sensorineural hearing loss. The study was designed to show the predominant site of lesion whether cochlear or retrocochlear in patients of diabetes with or without noise exposure. The parameter for inferring blood sugar control was level of glycosylated haemoglobin (Hb1AC). The incidence of the classical symptoms of diabetes mellitus namely polyurea, polydypsia and polyphagia were seen in (40.8%) of patients. The present study was designed to show that even early diabetic patients without symptoms of hearing loss had mild bilaterally symmetrical purely sensorineural hearing loss (32.65%) signifying the diabetic hypoacusis is present significantly even in early aural symptomless diabetics. On follow up it was revealed that the hearing loss of these patients was irreversible. The predominant site of lesion was found to be cochlear by performing Chi Square test P < .05 and so this is applicable to the general population of Uttar Pradesh.

Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women.

BACKGROUND: Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels. METHODS: The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91±6.05) and 272 healthy females without metabolic syndrome (age 30.96±7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion. RESULTS: Homozygous mutant genotype (AA) (p=<0.001: OR=3.24: 95% CI=2.15-4.89) and mutant allele (A) (p=<0.001: OR=3.04: 95% CI=2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors. CONCLUSIONS: Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.

Association of FTO rs17817449 SNP with obesity and associated physiological parameters in a north Indian population.

BACKGROUND: Obesity is a very common disorder directly linked with various diseases such as type-2 diabetes, hypertension and atherosclerosis. Variants in the FTO gene have been associated with Body Mass Index in Western European and North American populations. AIM: This study analysed the association between the FTO gene variant rs17817449 (G>T) and obesity and obesity-related phenotypes in a north Indian population. SUBJECTS AND METHODS: A total of 642 subjects, 309 obese and 333 non-obese individuals, were included in this case-control study. Genotyping of FTO gene (rs17817449) polymorphism for all subjects was performed by the PCR-RFLP method. RESULTS: Significant associations were found for FTO rs17817449 SNP with obesity and obesity-related phenotypes. The strongest associations were observed between the rs17817449 and fasting blood glucose, insulin, homeostasis model of assessment--insulin resistance (HOMA-IR) and fat mass under a recessive model. CONCLUSIONS: This study replicated the genetic association of SNP of FTO (rs17817449) with obesity in a north Indian population and, to the authors' knowledge; this is the first such association study in a north Indian population. This study also established that SNP in intron 1 of FTO (rs17817449) are strongly associated with several measures of adiposity and are also associated with plasma insulin, insulin resistance, percentage body fat and fat mass.

Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1, rs41423247) on Blood Pressure, Glucose in Northern Indians.

Glucocorticoids and its receptor are known to be involved in the dysregulation of hormone and lipid levels. Therefore, we evaluated the association of Bcl1 gene polymorphism of glucocorticoids receptor (GCR) gene variant with hormone and lipid levels in Northern Indians obese. A total of 435 obese and non-obese age matched subjects were included in the case-control study. Lipid and hormonal levels were estimated using standard protocols. Analysis of +646 C>G NR3C1 gene polymorphism was done using PCR-RFLP. The frequencies of GR Bcl1, C>G genotypes and alleles did not differ significantly (P > 0.05) between obese and non-obese. The +646 G allele carriers had higher waist to hip ratio, blood pressure, insulin and glucose levels than non-carriers in obese subjects while diastolic blood pressure and glucose in non-obese. The NR3C1, +646 C>G polymorphism did not associate with obesity. However, the GG genotype may modulate blood pressure, blood glucose and hormonal levels in northern Indians.

A common polymorphism in the promoter of UCP2 is associated with obesity and hyperinsulenemia in northern Indians.

A polymorphism in the promoter region of uncoupling protein 2 gene -866 G/A has been associated with its expression levels, the risk of obesity, and metabolic abnormalities. We aimed to investigate the associations of uncoupling protein (UCP)2 gene variants with obesity and related traits. A total of 440 subjects, 200 obese, and 240 non-obese individuals were included in this case-control study. Hormone and glucose levels were estimated using standard protocols. Genotyping of UCP-2 gene polymorphism for all subjects was performed by the PCR-RFLP polymerase chain reaction (PCR) method. Higher Systolic blood pressure, Diastolic blood pressure, Waist to hip ratio, Leptin, Insulin, and blood glucose levels were observed in obese than non-obese (P < 0.05). The distributions of genotype (0.001) and allele (0.003) were significantly different between the non-obese and the obese groups. In the obese group, subjects with the A allele showed significant high insulin levels (<0.001) in comparison with A allele non-carriers. In conclusion, our results suggest that the -866 AA genotype and A allele of the UCP2 gene is associated with obesity and A allele associated with hyperinsulinemia in obese subjects.

Bilateral sudden sensorineural deafness with vertigo as the sole presenting symptoms of diabetes mellitus - a case report.

This Paper reports a late uncontrolled diabetic presenting to an otolaryngologist with sudden severe sensorineural hearing loss of immediate origin with vertigo and tinnitus as the symptoms. Appropriate investigative and treatment measure resulted in deterioration of hearing in the right ear and mild improvement of hearing in the left ear, with no recovery of imbalance.

Association of cholesteryl ester transfer protein (TaqIB) and apolipoprotein E (HhaI) gene variants with obesity.

Background The pathophysiology of obesity is known to be influenced by alterations in lipid levels. We aimed to evaluate association of cholesteryl ester transfer protein (CETP) and apolipoprotein (APO) E gene variants with asymptomatic obesity. Methods A total of 437 subjects, 159 asymptomatic obese (BMI = 29.29 +/- 3.76) and 278 non-obese (BMI = 23.38 +/- 1.71) individuals, were included in this case-control study. Lipid levels were estimated using standard protocols. Analysis of CETP (TaqIB) and APOE (HhaI) gene polymorphisms was done using PCR-RFLP. Results We found significant difference in blood pressure (systolic, P < 0.0001 and diastolic, P < 0.0001), total cholesterol (P < 0.0001), LDL-cholesterol (P < 0.0001), and HDL-cholesterol (P < 0.0001) in obese as compared to non-obese group. Homozygous APO E4E4 genotype was only observed in 5.7% of obese individuals and none in non-obese group. APO E4 allele carriers were also susceptible for obesity (P = 0.016, OR = 1.73; 95% CI = 1.12-2.68) than non-carriers. Higher blood pressure (Systolic, P = 0.001 and Diastolic, P = 0.004) and triglyceride levels (P = 0.029) were observed in obese subjects with APO E4 allele than individuals without APO E4. However, CETP B1 variant allele carriers did not show alteration in blood pressure and lipid profile in asymptomatic obese subjects. Conclusions APO E4 genotype and allele were found to be associated with asymptomatic obesity, whereas CETP Taq1B polymorphism showed no such association in North Indian subjects.

Association of beta2-adrenergic receptor and insulin receptor substrate-1 polymorphisms with obesity in a Northern Indian population.

BACKGROUND: Imbalance in hormonal levels, regulated by host genetic factors, are known to be a major cause of obesity. Therefore, we aimed to evaluate association of genetic polymorphisms of beta(2)-adrenergic receptor (beta(2)-AR) and insulin receptor substrate-1 (IRS-1) with hormonal levels in northern Indian obese. METHODS: A total of 111 obese and 89 age matched non-obese subjects were studied after taking detailed clinical profile. Hormonal assays in serum/plasma for different hormones were done using IRMA and RIA kits. Genetic analysis of beta(2)-AR (-47 and -20, T to C) and IRS-1 (Arg972Gly) was done using PCR-RFLP. STATISTICAL ANALYSIS: Statistical analysis was performed by SPSS (version 11.5) software. All continuous variables were expressed as mean +/- SD and tested by ANOVA test. Comparisons of categorical variables were assessed using X(2) tests or Fisher's exact test. P-value <0.05 was considered as significant. RESULTS: Analysis showed that obese subjects had significantly higher value of blood pressure (systolic), WHR, leptin insulin and glucagon and lower value of GH. In beta(2)-AR (-47) T/C and IRS-1 Gly972Arg gene polymorphisms we did not found significant differences in genotype or allele frequencies. Moreover, none of the studied hormonal or metabolic parameters showed any association with the gene polymorphisms. CONCLUSIONS: Study reveals no significant association of beta(2)-AR (-47 and -20, T to C) and IRS-1 Gly 972 Arg polymorphisms with obesity in northern Indians.

"Effect of short-term cigarette smoking on insulin resistance and lipid profile in asymptomatic adults".

Present study examined the effect of short-term cigarette smoking on insulin resistance and lipid profile in asymptomatic healthy adults. This case control study comprised of 44 healthy male subjects in the age group of 18-40 yrs having BMI 25+3 and WHR < 1.0. Of these 22 smokers were included in the study group and 22 non-smokers in the control group. Subject selection was done such that one smoker and one non-smoker sibling or first degree male relative were selected from the same family. We compared fasting plasma glucose, insulin, lipid profile, and homeostatic model assessment index (HOMA Index) as a measure of insulin resistance between both the groups. Our observation showed that significantly higher values of serum glucose (133.36 +/- 23.45 mg/dl; P < 0.001), serum insulin (32.04 +/- 6.0 2 microU/ml; P < 0.001) and HOMA index (3.62 +/- 0.21; P < 0.001) were found in smokers as compared to non-smokers (serum glucose 86.95 +/- 19.32 mg/dl, insulin 20.09 +/- 4.8 microU/ml, HOMA index 3.29 +/- 0.30). No significant difference was observed for number of subjects having insulin resistance (HI > 3.8) and lipid profile in both the groups. Thus it appears that smokers are prone to develop hyperinsulenemia, hyperglycemia and the metabolic syndrome.

Acth and the dexamethasone suppression test in depression.

Hypercortisolemia, as measured by baseline serum Cortisol levels (Carroll and Mendels, 1976) and abnormal response to dexamethasone suppression test (DST) (Carroll et at., 1981) is thought to characterize abnormal hypothalamic-pituitory- adrenal (HPA) axis functions in patients of depression. Whether adrenocorticotrophic hormone (ACTH) shows similar abnormalities is a matter of controversy. Whereas Nasretal. (1983) and Roy et al. (1986) reported higher plasme ACTH levels in depressed patients as compared to controls. Fang et al. (1981) and Yerevanian and Woolf (1933) did not find such difference.

Frequency and severity of depressive symptoms among diabetic patients.

One hundred patients of Diabetes Mellitus (30 insulin dependent and 70 non-insulin dependent) were studied for frequency and severity of depressive symptoms. The subjects were evaluated on Schedule for Standardised Assessment of Affective Disorder (SADD) and Hamilton Rating Scale for Depression (HRSD).Result show that symptoms such as depressed mood-decreased work and activities and loss of weight were present in more than 60% of patients belonging to insulin and non-insulin dependent diabetics. Severity of depressive symptoms as rated on HRSD were significantly higher (P < .001) in insulin dependent patients as compared to non-insulin dependent diabetics.

Retrospective glycemic status of diabetic patients: glycosylation of blood proteins in diabetes and chronic renal failure.

In vivo and in vitro studies were carried out to evaluate the clinical application of glycosylated hemoglobin and plasma proteins in the diagnosis and management of diabetes mellitus. Glycosylated hemoglobin registered an almost 80% fall in diabetic patients following controlled glycemia for two months while glycosylated plasma protein level registered an 80% fall in the patients after fifteen days of blood glucose homeostasis. Human serum proteins were glycosylated in vitro and glycosylation was linearly proportional to the glucose concentration and incubation time. Polyacrylamide gel electrophoresis of glycosylated serum proteins revealed that albumin and transferrin are the major proteins that are significantly glycosylated. Glycosylated hemoglobin and plasma protein levels were also increased in chronic renal failure patients without any history of diabetes.

Changes in insulin receptor functions of the erythrocyte by treatment of non-insulin-dependent diabetes mellitus (NIDDM) patients with glibenclamide and diet control.

The insulin binding of erythrocytes from: (i) fifteen age-matched normal subjects, (ii) ten untreated NIDDM patients and (iii) fifteen treated (glibenclamide + hypocaloric diet) NIDDM patients (all males) has been studied. A significant decrease in specific insulin binding was observed in group (ii) which improved in cases controlled after treatment (group iii). Scatchard analysis of the results suggested that changes in insulin binding were due to alteration in the number of insulin receptors on erythrocytes. The number of insulin receptors/cell was 471 in normals, 160 in diabetics and 282 in treated diabetic subjects. No significant change in the binding affinity was observed in the three groups (1.0 X 10(8), 1.2 X 10(8) and 1.1 X 10(8) M-1 in normal subjects, untreated diabetics and treated diabetics, respectively).