The Relationship between Insulin Resistance and Thyroid Volume in Georgia.

Patients with insulin resistance (IR) have a higher thyroid volume therefore the aim of our study is to examine the correlation between IR and thyroid volume in the residents of Georgia. METHODS: 413 patients with a mean age of 37.3 ± and 11.4 years were included in this study. Out of those, 120 were males, and 293 were females who were studied retrospectively. They had hyperinsulinemia and were referred to the clinic from 2017 to 2019. The factors studied were age, sex, body mass index (BMI), clinical signs, thyroid ultrasound, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipids, fasting insulin, fasting glucose, thyroid stimulating hormone (TSH), Free thyroxine (FT4), and Zinc (Zn). RESULTS: IR was detected in 252 individuals. The frequency of men with insulin resistance was significantly higher than in the control group - 72.50%, and 56.31%, respectively (F = 9.55, p= 0.0021). Mean thyroid volume in the patients with IR was significantly higher compared to the controls 20.52 + 6.39 cm3 and 15.25 + 6.55 cm3, respectively (p < 0.001). Hyperinsulinemia had a significant positive correlation with Goiter r = 0.445, p < 0.0001. The associated factors for hyperinsulinemia are: Goiter (1) - OR = 5.12 (95% CI:3.02-8.69); Cholesterol - OR = OR = 3.31 (95% CI: 1.54-7.14); Triglycerides - OR = 3.23 (95% CI:1.02-10.28); Obesity (1)- OR = 3.94 (95% CI: 2.23-6.98); Thyroid structural changes (1) - OR = 2.01 (95% CI: 1.12-3.60); ALT/AST-OR = 4.53 (95% CI: 2.33-8.80); Zn decreased Odds Ratio hyperinsulinemia - OR = 0.95 (95% CI: 0.94-0.97). CONCLUSION: Hyperinsulinemia is the most common cause of diffuse goiter and the heterogeneous structure of the thyroid. The volume of the thyroid gland shows a significant positive association with the characteristics of metabolic syndrome and increased thyroid volume predictors of metabolic syndrome.

Correlation Between Vitamin B12 Deficiency and Autoimmune Thyroid Diseases.

BACKGROUND: Autoimmune thyroid diseases (AITD) are the most prevalent organ-specific autoimmune disorders. Vitamin B12 plays an important role in the proper functioning of the immune system. The aim of this study was therefore to investigate the correlation between vitamin B12 deficiency and AITD. MATERIALS AND METHODS: A total of 306 patients (aged 18-65 years, mean - 37.6 ± 11.3 years and comprising 87 males and 219 females) were studied retrospectively (observational study). Patients were divided into groups: with and without vitamin B12 deficiency, and with and without AITD. Differences between groups were evaluated by Fisher's exact test for qualitative variables and by Student's t-test for quantitative variables. Correlations for quantitative factors were determined by the Pearson correlation coefficient and for qualitative factors by Spearman correlation analysis. The sensitivity and specificity of vitamin B12 deficiency for AITD were calculated by ROC analysis. RESULTS: The vitamin B12 level was significantly lower in patients with AITD (and 200.70 + 108.84) compared to controls (393.41+150.78 p<0.0001). Patients with vitamin B12 deficiency were characterized by significantly higher mean values of anti-TPO (236.60+455.74) compared to controls (39.51+165.57 p<0.0001). Vitamin B12 levels were inversely correlated to anti-TPO levels (r=- 0.233, p<0.001). Roc analysis of vitamin B12 as a diagnostic test for AITD gave the area under curve as 0.881 (95% CI: 0.839-0.924), a sensitivity of - 0.947, a specificity of - 0.768, and a cutoff value of - 178.9. CONCLUSION: The vitamin B12 level correlates significantly to AITD. The concentration of vitamin B12 should therefore be determined in patients with autoimmune thyroiditis as a diagnostic test with high sensitivity and good specificity.

Comprehensive study of the rheological status and intensity of oxidative stress during the progression of type 2 diabetes mellitus to prevent its complications.

BACKGROUND: Prevention of Type 2 diabetes mellitus (T2DM) requires a modifying effect on the pathological processes inducing the ß-cell dysfunction. OBJECTIVES: the comprehensive study of the violation of rheological parameters in patients with different stages of diabetes and identification of possible links between these alterations with the intensity of the oxidative stress in the patient's body. METHODS: 60 patients with IR, prediabetes, T2DM and healthy volunteers were included. Full range of the rheological parameters of the patients' blood - the indicators of erythrocytes aggregation index (EAI), the relative deformability of the erythrocytes membranes (ERDI), blood plasma viscosity (BPV), and oxidative stress intensity (OSI) were examined. RESULTS: In patients with insulin resistance (IR), prediabetes, and T2DM the ERDI was statistically significantly lower and BPV - higher compared to control; a significant increase in EAI was detected in the patient group with prediabetes and T2DM compared to the control. CONCLUSION: The level of rheological disorders in patients increases with the increase of the level of carbohydrate metabolism disorders and intensity of oxidative stress and reaches a maximum during manifested diabetes. Diagnosis of hemorheological disorders and OSI in T2DM can serve as an early marker of target organ damage possibility.

The Impact of Obesity Assessed by Different Criteria on the Metabolic Parameters in Children and Adolescents in Georgia.

The aim of our study was comparative analysis of anthropometric characteristics in children and adolescents significantly correlated with the parameters of metabolic syndrome. The study group is consisted of 113 children and adolescents (study group) with excessive body weight and obesity (group 1-BMI percentile; group 2-waist circumference; group 3-waist to height ratio). The control group consisted of 113 children and adolescents without. Comparative analysis of obtained data have been carried out by multiple regression analysis. BMI percentile is more an indicator of a generalized obesity; WC and WHR percentiles better describe visceral obesity and metabolic disorders-insulin resistance, hypertension and dyslipidemia. However, the WHR Percentile may be a more useful tool. To assess obesity in children and adolescents, it is necessary to evaluate together BMI, WC, and WHR percentiles. It can be also concluded that these findings indicate the need to continue research in this direction.

"Vitamin D Deficiency Is More Common in Women with Autoimmune Thyroiditis: A Retrospective Study".

BACKGROUND: Vitamin D is a hormone that is mainly produced in the skin upon ultraviolet B radiation exposure and has important influence on various organs. In recent years, data have been collected that vitamin D deficiency plays an important role in the development of various nonskeletal diseases, including autoimmune diseases. Chronic autoimmune thyroiditis (Hashimoto's thyroiditis) is one of the most common organ-specific autoimmune endocrine diseases. It is characterized by increased level of antithyroid peroxidase and/or antithyroglobulin antibodies in blood, which often leads to thyroid dysfunction and structural changes of the gland. There is an opinion that vitamin D deficiency may be considered as an important risk factor for development of chronic autoimmune thyroiditis, but data of various small studies are controversial. Despite the fact that Georgia is a sunny country, vitamin D deficiency is a widespread problem here. Thyroid diseases, including the chronic autoimmune thyroiditis, are also very common in Georgia. The aim of our research was to compare the level of vitamin D between the patients with chronic autoimmune thyroiditis and the healthy subjects. METHODS: This retrospective study enrolled subjects, who were 18-70 years old and visited the clinics "Cortex" and "National Institute of Endocrinology" in 2018 or in 2019 from mid-spring to mid-summer. Data of thyroid-stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, antithyroglobulin antibodies, thyroid ultrasonography, and 25(OH) vitamin D were retrospectively analysed based on medical history. In total, data of 1295 patients were collected. The statistical processing of data was performed through the SPSS 20 program. RESULTS: The negative association between thyroid-stimulating hormone, antithyroid peroxidase antibodies, antithyroglobulin antibodies, heterogeneous parenchyma of thyroid gland, and vitamin D was found in women. Statistically significant association was not detected in men. CONCLUSIONS: Serum vitamin D is lower in women with autoimmune thyroiditis and primary hypothyroidism. Further studies are needed to evaluate the influence of vitamin D supplementation on thyroid autoantibody positivity or primary hypothyroidism.

Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial.

CONTEXT: For children with growth hormone deficiency (GHD), treatment burden with daily somatropin injections [human growth hormone (hGH)] is high, which may lead to poor adherence and suboptimal overall treatment outcomes. Lonapegsomatropin (TransCon hGH) is an investigational long-acting, once-weekly prodrug for the treatment of GHD. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of once-weekly lonapegsomatropin vs daily somatropin. DESIGN: The heiGHt trial was a randomized, open-label, active-controlled, 52-week Phase 3 trial (NCT02781727). SETTING: This trial took place at 73 sites across 15 countries. PATIENTS: This trial enrolled and dosed 161 treatment-naïve, prepubertal patients with GHD. INTERVENTIONS: Patients were randomized 2:1 to receive lonapegsomatropin 0.24 mg hGH/kg/week or an equivalent weekly dose of somatropin delivered daily. MAIN OUTCOME MEASURE: The primary end point was annualized height velocity (AHV) at week 52. Secondary efficacy end points included change from baseline in height SD scores (SDS). RESULTS: Least squares (LS) mean (SE) AHV at 52 weeks was 11.2 (0.2) cm/year for lonapegsomatropin vs 10.3 (0.3) cm/year for daily somatropin (P = 0.009), with lonapegsomatropin demonstrating both noninferiority and superiority over daily somatropin. LS mean (SE) height SDS increased from baseline to week 52 by 1.10 (0.04) vs 0.96 (0.05) in the weekly lonapegsomatropin vs daily somatropin groups (P = 0.01). Bone age/chronological age ratio, adverse events, tolerability, and immunogenicity were similar between groups. CONCLUSIONS: The trial met its primary objective of noninferiority in AHV and further showed superiority of lonapegsomatropin compared to daily somatropin, with similar safety, in treatment-naïve children with GHD.

The Frequency of Langerhans Islets ß-Cells Autoantibodies (Anti-GAD) in Georgian Children and Adolescents with Chronic Autoimmune Thyroiditis.

Aim. Chronic autoimmune thyroiditis and type 1 diabetes mellitus are organ-specific autoimmune diseases. There is large evidence that autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus is increased, but little is known about anti-islet cell autoimmune status in patients with chronic autoimmune thyroiditis. We evaluated the concentration of antibodies against glutamic acid decarboxylase (GAD) which are widely used as a diagnostic and predictive tool for type 1 diabetes mellitus, in school-aged Georgian children with chronic autoimmune thyroiditis. Methods. The frequency of anti-GAD antibodies was measured in Georgian school-aged children with chronic autoimmune thyroiditis and compared to healthy age and sex matched controls. Results. Of the 41 patients with chronic autoimmune thyroiditis 4 (9.8%) were positive for GAD antibodies. The frequency of GAD positivity in the chronic autoimmune thyroiditis group was significantly higher than in the control subjects (P = 0.036). Conclusion. In the study we found that the frequency of GAD antibody positivity in autoimmune thyroiditis patients was significantly higher (9.8%, P = 0.036) than in the control group. Our findings support the concept that patients with autoimmune thyroid disease may develop type 1 diabetes mellitus in future life.

Influence of testosterone replacement therapy on metabolic disorders in male patients with type 2 diabetes mellitus and androgen deficiency.

BACKGROUND: Multiple epidemiological studies have shown that low testosterone levels are associated with and predict the future development of type 2 diabetes mellitus and the metabolic syndrome. The aim of our study was to show the influence of testosterone replacement therapy on obesity, HbA1c level, hypertension and dyslipidemia in patients with diabetes mellitus and androgen deficiency. METHODS: One hundred and twenty-five male patients with diabetes mellitus were screened; 85 subjects aged 41 to 65 years, with BMI from 27.0 to 48.0 kg/m(2), were randomized in a placebo-controlled study. They also underwent a routine physical examination and selected by free testosterone examination. We divided patients into two groups: 1) treatment group, where we used diet, physical activity, patient's antidiabetic therapy and testosterone replacement therapy; 2) placebo group, where we used diet, physical activity, patient's antidiabetic therapy and placebo. RESULTS: After 6 months of treatment we repeated the diagnostic assessments: lipid profile was improved in both groups but in first group it was clinically significant. Free testosterone level increased in all groups, but in group I was clinically significant. HbA1c decreased in both groups, but in group I we obtained the best result. Leptin level after treatment was approximately the same in both groups. Also, blood pressure was reduced in both groups but results were similar. CONCLUSIONS: Our study demonstrated that it is possible to break this metabolic vicious circle by raising testosterone levels in diabetic men with androgen deficiency. Re-instituting physiological levels of testosterone, as the study has shown, has an important role in reducing the prevalence of diabetic complications.

Association of the apolipoprotein b/apolipoprotein a-I ratio, metabolic syndrome components, total cholesterol, and low-density lipoprotein cholesterol with insulin resistance in the population of georgia.

The study was designed to assess the association between insulin resistance (IR) and apolipoprotein B/apolipoprotein A-I ratio (ApoB/ApoA-I ratio), metabolic syndrome (MetS) components, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in the nondiabetic population of Georgia. The subjects were 1522 Georgians of Caucasian origin (mean age = 45 years, 653 women) without diabetes who had visited the clinics for a related health checkup between 2012 and 2013. IR was calculated using the computer homeostasis model assessment (HOMA2-IR) and was defined as the upper quartile. MetS was diagnosed using the updated ATP-III definition of the metabolic syndrome. Logistic and multiple regression models were used to estimate the association between IR and other components. IR was positively correlated with age, ApoB, ApoB/ApoA-I ratio, MetS components (excluding high-density lipoprotein cholesterol-HDL-C), LDL-C, fasting insulin, and TC and negatively correlated with HDL-C and ApoA-I in both sexes (all P < 0.001). In the logistic regression models, gender, age, ApoB/ApoA-I ratio, diastolic pressure, HDL-C, LDL-C, fasting glucose, and triglycerides were the covariates significantly associated with IR (OR: 8.64, 1.03, 17.95, 1.06, 0.13, 1.17, 3.75, and 2.29, resp.; all P < 0.05). Multiple regression models demonstrated that these components (except for HDL-C) made an independent contribution to the prediction of HOMA2 (all P < 0.05).