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.