Genetic polymorphism of Pro12Ala in type 2 diabetes mellitus: Role in inflammation linked to Insulin resistance.

Peroxisome Proliferator-Activated Receptor gamma 2 (PPARγ2) belongs to nuclear receptor superfamily and plays a role in adipocyte differentiation and inflammation. Evidences suggest that inflammatory processes hold key to insulin resistance and PPARγ2 has also been implicated. PPARγ2 exhibits gene polymorphism. The Ala allele of Pro12Ala polymorphism (rs1801282) is associated with a reduced risk for insulin resistance. We attempted the study in overweight and obese males to generate evidences linking insulin resistance, inflammatory mediators, and gene polymorphism of PPARγ2 in overweight and obese males. The conventional biochemical parameters were estimated using established methods. Adiponectin and Haptoglobin were quantitated by ELISA, whereas Ferritin and hs-CRP were by chemi-luminescence. Indices of insulin sensitivity /Insulin resistance were computed based on established formulae. Gene analysis was based on PCR and RFLP. Appropriate statistical analysis was enabled to project gene polymorphism.The heterozygous variant (CG) was around 8 and 38 percent respectively in overweight and obese males. The G Allele was 3.89% and 18.82%. The wild type and heterozygous variant of PPARγ2 depicted significance with haptoglobin, whereas adiponectin showed significance in the wild type. Chi-square test was performed to assess the relation between polymorphic genotypes and ferritin emerged significant. Indices of insulin resistance showed different characteristics with wild type and heterozygous variant ofPPARγ2 gene polymorphism. The inflammatory mediators (hs-CRP, Ferritin, Haptoglobin and adiponectin) exhibited variegated characteristics with the wild type and heterozygous variant of PPARγ2, thus pointing to the nexus among insulin resistance, inflammation, and adipocyte differentiation.

Impact of an Integrated Yoga Therapy Protocol on Insulin Resistance and Glycemic Control in Patients with Type 2 Diabetes Mellitus.

OBJECTIVE: Diabetes mellitus (DM), characterized by chronic hyperglycemia, is attributed to relative insulin deficiency or resistance, or both. Studies have shown that yoga can modulate parameters of insulin resistance. The present study explored the possible beneficial effects of integrated yoga therapy with reference to glycemic control and insulin resistance (IR) in individuals with diabetes maintained on standard oral medical care with yoga therapy, compared to those on standard oral medical care alone. METHODS: In this study, the subjects on yoga intervention comprised 35 type 2 diabetics, and an equal number of volunteers constituted the control group. Subjects ranged in age from 30 to 70 years, with hemoglobin A1c (HbA1c) test more than 7%, and were maintained on diabetic diet and oral hypoglycemic agents. Blood samples were drawn prior to and after 120 days of integrated yoga therapy intervention. Fasting blood glucose (FBG), post-prandial blood glucose (PPBG), HbA1c, insulin, and lipid profile were assessed in both the intervention and control groups. RESULTS: The intervention group revealed significant improvements in body mass index (BMI) (0.7 kg/m2 median decrease; P=0.001), FBG (20 mg/dL median decrease; P<0.001), PPBG (33 mg/dL median decrease; P<0.001), HbA1c (0.4% median decrease; P<0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (1.2 median decrease; P<0.001), cholesterol (13 mg/dL median decrease, P=0.006), triacylglycerol (22 mg/dL median decrease; P=0.027), low-density lipoprotein (6 mg/dL median decrease; P=0.004), and very-low-density lipoprotein levels (4 mg/dL median decrease; P=0.032). Increases in high-density lipoprotein after 120 days were not significant (6 mg/dL median increase; P=0.15). However, when compared to changes observed in patients in the control group, all these improvements proved to be significant. CONCLUSION: Administration of integrated yoga therapy to individuals with diabetes leads to a significant improvement in glycemic control, insulin resistance, and key biochemical parameters.

Linking inflammatory mediators and indicators of insulin resistance in anthropometry specified type 2 diabetic males.

Inflammation associated with insulin resistance is a risk factor in the development of complications in Type 2 diabetes mellitus (T2DM). The study was conducted to assess the relationship between inflammatory mediators and insulin resistance, independent of lipid profile in anthropometry specified male Type 2 diabetics. 180 males having T2DM for more than 5yrs and on diabetic medication were chosen for the study and categorized into obese and overweight. Patients with thyroid or other endocrine disorders, kidney, muscle, liver, systemic, and inflammatory diseases were excluded from the study. Blood glucose, glycated hemoglobin, plasma insulin, and the inflammatory biomarkers namely hs-CRP, ferritin, haptoglobin, and adiponectin were evaluated. HOMA-IR and QUICKI were computed to assess insulin resistance. The study demonstrated significant changes in adiponectin and hsCRP in obese and overweight T2DM. However, Ferritin and Haptoglobin were insignificant. The entire biochemical study was carried out to demonstrate lipid profile independent associations. The significant insulin resistance associated with a substantial increase in hs-CRP levels and a pronounced decrease in the adiponectin levels suggests impending diabetic complications in anthropometry specified male T2DM. This could promote the use of personalised medicine to regulate levels of hs-CRP or to improve the secretion of adiponectin thereby countering insulin resistance in T2DM, independent of the lipid profile which is the novelty of our study.

Association of Triglyceride-Glucose Index (TyG index) with HbA1c and Insulin Resistance in Type 2 Diabetes Mellitus.

Background: The aim of this study was to assess the association of triglyceride-glucose (TyG) index with glycated haemoglobin (HbA1c) and insulin resistance in type 2 diabetes mellitus (T2DM). Methods:A total of 140 patients with T2DM were included in this cross-sectional study and divided into two groups according to their HbA1c levels: participants with HbA1c <7.0% (n=75) and those with HbA1c >7.0% (n=65) were defined as having a good glycemic control (group I) and a poor glycaemic control (group II) in T2DM. Anthropometric and biochemical parameters were measured, while the values of triglyceride (TG) to high density lipoprotein cholesterol (HDL-C) (TG/HDL-C) ratio and TyG index were calculated using formula. Results: Body mass index (BMI), fasting blood glucose (FBS), HbA1c and homeostatic model assessment for insulin resistance (HOMA-IR) were significantly higher in diabetic patients with poor glycemic control. TyG index was significantly correlated with HbA1c, HOMA-IR, TyG-BMI and TyG-WC. The receiver operating characteristic (ROC) analysis showed that TyG had a maximum area under the curve of 0.806, with a cut off value of 15.5 for identifying glycemic control in diabetic patients. Conclusion:TyG index is a useful tool for assessing glycemic control in T2DM patients and positively correlated with HbA1c and HOMA-IR. Hence, TyG can be used as a simple and inexpensive alternative to assess glycemic control in patients with diabetes.

Biochemical isthmus [nexus] between type 2 diabetes mellitus and thyroid status-an update.

Both Type 1 [T1DM] and Type 2 diabetes mellitus [T2DM] share a nexus with altered thyroid status. In recent times, evidences point to the link between thyroid hormones andT2DM in particular. Several lines of evidences suggest an array of biochemical and molecular events. Gene polymorphism, disturbances in gene expression and regulation, enhanced and bizarre absorption of dietary glucose from intestine, decreased utilization of glucose by tissues and aberrations in hepatic handling of glucose with the onus on Gluconeogenesis are some of the projected mechanisms. Insulin resistance, a progressive condition is the hallmark in T2DM. Hypothyroidism as well as hyperthyroidism have been associated with insulin resistance which are synonymous with impaired glucose metabolism in T2DM. A multitude of basic, clinical and molecular studies provide an insight into thyroid comorbidity in T2DM, though there are a few instances to suggest equivocal link denoting cause-effect relationship. In biochemical pharmacology, as fortified by pharmacogenomics, modalities have now been proposed, through drug trials, to underline the utility of specifically designed thyroid hormone analogues in addressing metabolic syndrome, DM and associated cardiovascular pathology. A thorough understanding of the physiological, biochemical and molecular mechanisms would certainly open newer vistas in the perspectives of T2DM with special reference to alterations in thyroid status.

Clinical sensitivity and specificity of serum total bilirubin - A study on thyroid status in clinically euthyroid non-obese, overweight, and obese type 2 diabetics.

OBJECTIVE: The objective of this study was to evaluate the sensitivity and specificity of total bilirubin (serum) in determining thyroid status in clinically euthyroid non-obese, overweight, and obese type 2 diabetics. SUBJECTS AND METHODS: Three anthropometry specific groups of clinically euthyroid type 2 diabetics were enabled, following enrolment: 153 non-obese (body mass index [BMI] = 18.5-24.99), 291 overweight (BMI = 25-29.99), and 126 obese type 2 diabetes mellitus (BMI ≥30). Total bilirubin (serum), glycemic status, insulin resistance (IR), and thyroid hormones, besides routine biochemistry, were estimated, as per International Federation of Clinical Chemistry approved procedures. RESULTS: Receiver operating characteristic curves for non-obese, overweight, and obese were plotted to assess the role of total bilirubin (serum) in determining thyroid status in clinically euthyroid type 2 diabetics. In overweight, the area under curve (AUC) for FT3 and postprandial sugar showed 0.621 and 0.531 with cutoff values of 2.02 pg/ml and 147.5 mg/dl, respectively, whereas for aspartate aminotransferase/alanine aminotransferase (De Ritis ratio), the AUC was 0.583. As regards, obese diabetics and the AUC for insulin and homeostatic model assessment IR were 0.657 and 0.709, respectively, with cutoff values of 16.06 mIU/L and 7.274, respectively, and for postprandial sugar 0.727, in the same group (obese) with cutoff value of 208.5 mg/dl. CONCLUSION: Total bilirubin could predict thyroid status and IR in anthropometry specific clinically euthyroid type 2 diabetics.

"Sex hormone independent associations between insulin resistance and thyroid status -a gender based biochemical study on clinically euthyroid non-obese, overweight and obese type 2 diabetics''.

AIM: Studies indicate that type 2 diabetes mellitus (T2DM) might contribute to the development of thyroid disorders (TD). However, few gender based reports are available describing therelationship between T2DM and TD in clinically euthyroid, anthropometry specified groups of type 2 diabetics. The aim of this study was to relategender based biochemical changes in anthropometry specified, clinically euthyroid type 2 diabetics. METHODOLOGY: The study was carried out on clinically euthyroid type 2 diabetics (male n = 269; female n = 301) at a tertiary health care unit in Pondicherry, South India. Three groups were segregatedbased on Body mass Index: 153 non-obese type 2 diabetics (BMI = 18.5-24.99), 291 overweight type 2 diabetics (BMI = 25-29.99) and 126 obese type 2 diabetics (BMI ≥ 30). Biochemical parameters included glycated hemoglobin, insulin resistance, Cortisol and Thyroid profile. RESULTS: The study had included clinically euthyroid type 2 diabetics (52.8% females and 47.2% males). Statistically significant associationsweredifferently observed between insulin resistance (dependent variable) andother independent variables, irrespective of sex hormone status. Total protein was negatively related in non -obese male type 2 diabetics (R = 0.780); Triiodothyronine was inversely associated in overweight males, whereas cortisol and the divalent cations (Zinc and Magnesium) depicted positive association (R = 0.555) in the same group (overweight), butcortisol in non -obese female type 2 diabeticswas negative (R = 0.742); Glycated hemoglobin and calcium exhibited positive relationshipin obese type 2 female diabetics (R = 0.771).. CONCLUSION: Our study has revealed distinctive relationship between T2DM and TD in the anthropometry specified, clinically euthyroid and gender based type 2 diabetics, independent of the sex hormones.

Thyroid status in premenopausal and postmenopausal women - A biochemical study on insulin resistance in non obese, overweight and obese type 2 diabetics.

BACKGROUND: Insulin resistance with altered thyroid status in women is observed in type 2 diabetics and varies with advancing age and estrogen profile. We compared thyroid status between premenopausal and postmenopausal women in obese, non obese and overweight type 2 diabetes. METHODOLOGY: We included 301type 2 diabetics who were segregated into premenopausal (n = 100) 33.2% and postmenopausal (n = 201) 66.8% among three sub groups (Non obese, overweight and Obese).Anthropometry, fasting blood glucose, lipid profile, glycated hemoglobin, homeostasis model assessment of insulin resistance, liver function tests, Free T4, T3, TSH, Zn2+and Mg2+ were enabled. RESULTS: Non obese type 2 diabetics were segregated into two groups n = 21 (29.2%)- premenopausal with mean age of 41.48 ±â€¯4.30 and n = 51 (70.8%) - post menopausal with mean age of 58.49 ±â€¯7.32 There were significant differences in WHR, HbA1c, HDL with p < 0.05 and ALP with p < 0.01; Overweight type 2 diabetics n = 55 (37.9%) -premenopausal with mean age of 41.96 ±â€¯3.80 and n = 90 (62.1%)- post menopausal with mean age of 57.80 ±â€¯7.20. There were significant differences in Urea, Zinc, Total protein, Albumin with p < 0.05 and T4, TSH with p < 0.01. Obese Type 2 diabetics n = 24 (28.6%) -premenopausal with mean age of 42.00 ±â€¯4.30 and n = 60 (71.4%) -post menopausal with mean age of 57.80 ±â€¯7.20. There were significant differences in Urea, Magnesium, Triacylglycerols, and VLDL with p < 0.05, Insulin and HOMA-IR with p < 0.01. CONCLUSION: Anthropometry specified classification of type 2 diabetics in pre and postmenopausal women reflects thyroid status.

Association of divalent cations and insulin resistance with thyroid hormones in patients with type 2 diabetes mellitus.

AIM: The study was primarily aimed at investigating the association of Magnesium and Zinc levels in the serum of adult Non- obese and Obese type 2 diabetic patients, with particular reference to thyroid comorbidity. METHODS: 108 patients with T2DM of both genders (24 Non obese and 84 Obese) were enrolled from a tertiary health care unit in Puducherry. The cardio-metabolic risk factors were assessed through body mass index, Waist hip ratio, blood pressure, fasting blood glucose, lipid profile and glycated haemoglobin. Zinc and Magnesium were quantitated. Insulin resistance was by Homeostasis model assessment. Serum free T4, T3 and TSH were also measured. RESULTS: In non-obese type 2 diabetic group, Glycated haemoglobin had a strong positive correlation with free T4(r=0.784; p=0.003).TSH also depicted a positive association with HOMA-IR (r=0.924; p<0.001); whereas,T3 and Insulin had negative correlation with Magnesium (r=-0.599* and r=-0.620*; p 0.04 and 0.031). The levels of Zinc and Magnesium in the serum of obese diabetic patients had a positive correlation among them (r=0.565#; p<0.001). TAG/HDL ratio a measure of small dense LDL is positively correlated with LDL in both groups (r=0.881 and 0.912) with p value<0.001 for both. CONCLUSION: Correlation among Glycemic control, Insulin resistance, Thyroid hormones, divalent cations and dyslipidemia depict differential characteristics in obese and non-obese type2 diabetes with Thyroid comorbidity.

Associations among Insulin Resistance, Triacylglycerol/High Density Lipoprotein (TAG/HDL ratio) and Thyroid hormone levels-A study on Type 2 diabetes mellitus in obese and overweight subjects.

AIM: Triacylglycerol/High density lipoprotein (TAG/HDL) ratio, a surrogate marker of LDL particle size (small dense) was included in our study to observe the link with insulin resistance and thyroid co-morbidity. METHODS: Ninety three patients with T2DM of both genders were enrolled from a tertiary health care unit in Puducherry, during the latter half of 2015. The cardio-metabolic risk factors were assessed through body mass index (BMI), blood pressure, fasting blood glucose and lipid profile, glycated haemoglobin and homeostasis model assessment of insulin resistance (HOMA-IR). Serum free T4, T3 and TSH were also measured to evaluate the thyroid co-morbidity as a function of insulin resistance. RESULTS: In addition to insulin resistance, results of our study were focussed on thyroid comorbidity. In overweight diabetic patients, the ROC curve analyses demonstrated that the best marker for insulin resistance was Triacylglycerol/High density lipoprotein (TAG/HDL), with the area under the ROC curve being 0.902. Thyroxine (T4) was less significant when compared to TAG/HDL with area under the ROC curve of 0.583. Triiodothyronine (T3) and T4 were more significant in obese group with areas under the curve being 0.842 and 0.816 respectively when compared against insulin resistance (cut-off value for HOMA-IR 2.69). The optimal cut-off points for overweight were: TAG≥101mg/dl; T4≥1.16ng/dl; TAG/HDL≥2.26 whereas for obese: TC≥163.5mg/dl; TAG≥141.5mg/dl; T3≥2.42pg/ml; T4≥0.96ng/ml. CONCLUSIONS: In overweight type 2 diabetics, TAG/HDL ratio could be used as a reliable marker for insulin resistance with thyroid co-morbidity and T3, T4 were better objective markers in obese type 2 diabetics.