What about TSH and Anti-Thyroid Antibodies in Patients with Autoimmune Thyroiditis and Celiac Disease Using a Gluten-Free Diet? A Systematic Review.

The prevalence of celiac disease (CD) in patients with chronic autoimmune thyroiditis (CAIT) is estimated to be between 2 and 7.8%. A gluten-free diet (GFD) in patients with CD is suggested to have a beneficial effect on CAIT. Thus, the present systematic review was undertaken to achieve more robust evidence about the change in thyroid stimulating hormone (TSH) and thyroid-specific antibodies (T-Ab) levels obtained in CD patients following a GFD. A specific search strategy was planned. The last search was performed on March 2022. The following data were mainly searched for in order to be extracted: sample size, mean and/or median with standard deviation (SD), and error (SE), individually, of thyroid hormones and T-Ab at baseline and after GFD, and the duration of the study. The initial search retrieved 297 records and 6 articles met the inclusion criteria. In total, 50 patients with both CD and CAIT and 45 controls were reported. The effects of a GFD on the thyroid hormonal and immunological profile could be extracted only in a part of the studies. Two studies were case reports. A low risk of bias was observed. These findings advise further studies, ideally randomized, in order to better investigate the potential relationship between GFD and thyroid homeostasis. The level of evidence is not still sufficient to recommend GFD to patients with CAIT.

The impact of the metabolic phenotype on thyroid function in obesity.

BACKGROUND: Obesity is known to promote mild hyperthyrotropinaemia by unknown metabolic mechanisms. This investigation aimed to explore the association between thyroid function and metabolic phenotype in euthyroid obese individuals. Retrospective, cross-sectional study. Tertiary care center. METHODS: 952 euthyroid obese individuals referred to our Institution for obesity. Serum levels of TSH, FT4, glucose, insulin and HbA1c levels, lipid profile, liver function and proinflammatory indices were measured. Resting energy expenditure was assessed by indirect calorimetry and body composition by bioimpedance analysis. RESULTS: On admission, 306 patients had previously diagnosed diabetes mellitus on treatment with metformin, while 113 patients were diagnosed with incident diabetes mellitus. Serum TSH levels were similar between metformin-treated diabetic subjects and metformin-untreated subjects, while FT4 was slightly but significantly higher in the former. Analysis stratified by TSH categories found no effect of metformin-treated diabetes mellitus on TSH levels. Interestingly, obese patients with incident diabetes showed lower TSH levels than normoglycaemic ones. In correlation studies on the whole dataset, an association related TSH to BMI and total cholesterol levels, which was lost upon adjustment for individual confounders. FT4 levels were found to be inversely related to BMI, insulin resistance and triglycerides, while being directly associated with HDL-cholesterol levels. These correlations remained unaltered after controlling for individual confounders. In multivariate linear regression analysis, TSH was associated with FT4, total cholesterol and BMI values. Significant predictors of FT4 were constituted by previously diagnosed diabetes mellitus, BMI, TSH and age. CONCLUSIONS: In euthyroid obese subjects, FT4 seems more closely related than TSH levels to parameters of cardiometabolic risk. TSH levels did not differ between metformin-treated and untreated subjects, while they were lower in patients with incident diabetes mellitus compared to normoglycaemic ones.

Inherent insulin sensitivity is a major determinant of multimeric adiponectin responsiveness to short-term weight loss in extreme obesity.

High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77 kg/m(2)), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese patients, short-term weight loss did not change total adiponectin levels and insulin resistance, while the distribution pattern of adiponectin oligomers changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A (p < 0.05). By multivariate analysis, final HMW-A levels were significantly related to baseline ISIOGTT and final body weight (adjusted R(2) = 0.41). Our data suggest that HMW adiponectin may reflect baseline insulin sensitivity appropriately in the context of extreme obesity. Especially, we documented that HMW-A is promptly responsive to short-term weight loss prior to changes in insulin resistance, by a magnitude that is proportioned to whole body insulin sensitivity. This may suggest an insulin sensitivity-dependent control operated by HMW-A on metabolic dynamics of patients with extreme obesity.

Altered glucose metabolism rather than naive type 2 diabetes mellitus (T2DM) is related to vitamin D status in severe obesity.

CONTEXT: The last decades have provided insights into vitamin D physiology linked to glucose homeostasis. Uncertainties remain in obesity due to its intrinsic effects on vitamin D and glucose tolerance. OBJECTIVES: To assess the relationship between vitamin D and glucose abnormalities in severely obese individuals previously unknown to suffer from abnormal glucose metabolism. SETTING: Tertiary care centre. PATIENTS: 524 obese patients (50.3 ± 14.9 yrs; BMI, 47.7 ± 7.3 kg/m2) screened by OGTT, HbA1c and the lipid profile. Vitamin D status was assessed by 25(OH)D3, PTH and electrolyte levels. 25(OH)D3 deficiency/insufficiency were set at 20 and 30 ng/ml, respectively. All comparative and regression analyses were controlled for age, BMI and gender. RESULTS: The prevalence of vitamin D deficiency/insufficiency and secondary hyperparathyroidism were 95% and 50.8%, respectively. Normal glucose tolerance (NGT), impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) were found in 37.8%, 40.5% and 21.7% of cases, respectively. Large variations in metabolic parameters were seen across categories of vitamin D status, but the only significant differences were found for C-peptide, tryglicerides, LDL- and HDL-cholesterol levels (p < 0.05 for all). The prevalence of vitamin D deficiency was documented to be slightly but significantly more frequent in glucose-intolerant patients (IFG + IGT + T2DM) compared to the -normotolerant counterpart (87% vs. 80%, p < 0.05). In partial correlation analyses, there was no association between vitamin D levels and glucose-related markers but for HbA1c (r = -0.091, p < 0.05), and both basal and OGTT-stimulated insulin levels (r = 0.097 and r = 0.099; p < 0.05 for all). Vitamin D levels were also correlated to HDL-cholesterol (r = 0.13, p = 0.002). Multivariate regression analysis inclusive of vitamin D, age, BMI, gender and fat mass as independent variables, showed that vitamin D was capable of predicting HbA1c levels (ß = -0.101, p < 0.05). CONCLUSIONS: Given the inherent effect of obesity on vitamin D and glucose homeostasis, current data suggest a potential independent role for vitamin D in the regulation of glucose metabolism in a setting of obese patients previously unknown to harbour glucose metabolism abnormalities.

Cocaine abuse and sleep apnea in severe obesity.

Obesity is a cause of sleep breathing disorders that result in excessive daytime sleepiness. We describe the adaptive strategy used by an obese person who started to snort cocaine to remedy incoercible drowsiness affecting his working financial skills. Clinical workup documented severe sleep apnea, which was treated by noninvasive ventilation and resulted in withdrawing cocaine abuse. Undiagnosed sleep disorders may trigger surreptitious psychostimulant abuse in vulnerable individuals.

Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants.

OBJECTIVES: Obesity can alter the thyroid hormone status as a result of a dysregulated endocrine loop between the hypothalamo-pituitary unit and adipose tissue. The adipocytokine leptin has been shown to promote autoimmunity; hence, we aimed to clarify whether leptin excess of obesity could increase the susceptibility to develop autoimmune thyroid disease (AITD). STUDY DESIGN: This cross-sectional study was performed in a tertiary care center. METHODS: Free thyroid hormones, TSH, thyroglobulin, and antithyroid antibodies levels were tested in 165 obese and 118 lean subjects. Results were plotted against variables related to body composition, leptin levels, glucose homeostasis, energy expenditure, and pattern of weight accrual. RESULTS: Compared with controls, obese patients had lower free T3 levels and free T4 levels (P<0.01), greater prevalence of hypothyroidism (P<0.05), and higher commonness of antithyroid antibodies (P<0.05). As a marker of AITD, thyroid peroxidase antibodies were more frequent in the obese group (P<0.01). Correlation analysis showed that leptin levels were associated with AITD (P<0.01) independent of bioanthropometric variables. Multiple logistic regression analysis in pooled groups identified female sex and leptin as significant predictors of AITD. CONCLUSIONS: Obesity increases the susceptibility to harbor AITD with an emerging role for leptin as a peripheral determinant, which needs to be confirmed in future investigations.

Subcutaneous abdominal adipose tissue subcompartments: potential role in rosiglitazone effects.

Abdominal visceral tissue (VAT) and subcutaneous adipose tissue (SAT), comprised of superficial-SAT (sSAT) and deep-SAT (dSAT), are metabolically distinct. The antidiabetic agents thiazolidinediones (TZDs), in addition to their insulin-sensitizing effects, redistribute SAT suggesting that TZD action involves adipose tissue depot-specific regulation. We investigated the expression of proteins key to adipocyte metabolism on differentiated first passage (P1) preadipocytes treated with rosiglitazone, to establish a role for the diverse depots of abdominal adipose tissue in the insulin-sensitizing effects of TZDs. Adipocytes and preadipocytes were isolated from sSAT, dSAT, and VAT samples obtained from eight normal subjects. Preadipocytes (P1) left untreated (U) or treated with a classic differentiation cocktail (DI) including rosiglitazone (DIR) for 9 days were evaluated for strata-specific differences in differentiation including peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and lipoprotein lipase (LPL) expression, insulin sensitivity via adiponectin and glucose transport-4 (GLUT4), glucocorticoid metabolism with 11 beta-hydroxysteroid dehydrogenase type-1 (11 beta HSD1), and alterations in the adipokine leptin. While depot-specific differences were absent with the classic differentiation cocktail, with rosiglitazone sSAT had the most potent response followed by dSAT, whereas VAT was resistant to differentiation. With rosiglitazone, universal strata effects were observed for PPAR-gamma, LPL, and leptin, with VAT in all cases expressing significantly lower basal expression levels. Clear dSAT-specific changes were observed with decreased intracellular GLUT4. Specific sSAT alterations included decreased 11 beta HSD1 whereas secreted adiponectin was potently upregulated in sSAT with respect to dSAT and VAT. Overall, the subcompartments of SAT, sSAT, and dSAT, appear to participate in the metabolic changes that arise with rosiglitazone administration.

The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure.

Ghrelin is a gastric hormone that exerts a stimulatory effect on appetite and fat accumulation. Ser(3) octanoylation is regarded as a prerequisite for ghrelin biological activity, although des-octanoylated forms may retain biological functions in vitro. Circulating ghrelin levels are usually low in obesity and in states of positive energy balance. Hence, the aim of our study was to analyze plasma active and serum total ghrelin levels in 20 obese (ages, 22-42 yr; body mass index, 41.3 +/- 1.1 kg/m(2)) and 20 lean subjects (ages, 22-43 yr; body mass index, 22.4 +/- 0.6 kg/m(2)) as well as their relationship to measures of glucose homeostasis, body fat, and resting energy expenditure (REE). The measured/predicted REE percentage ratio was calculated to subdivide groups into those with positive (> or = 100% ) and negative (<100%) ratio values. In obese patients, plasma active (180 +/- 18 vs. 411 +/- 57 pg/ml; P < 0.001) and serum total ghrelin levels (3650 +/- 408 vs. 5263 +/- 643 pg/ml; P < 0.05) were significantly lower when compared with lean subjects. Hence, ghrelin activity, defined as the proportion of active over total ghrelin levels, was similarly reduced in the obese state (6.1 +/- 0.9% vs. 8.4 +/- 1%; P < 0.05). There was a significant correlation between active and total ghrelin (r = 0.62; P < 0.001), and between total ghrelin and insulin (r = -0.53; P < 0.001) or insulin resistance using the homeostatis model of assessment-insulin resistance (r = -0.49; P < 0.001) approach. Significantly higher active ghrelin levels (214 +/- 22 vs. 159 +/- 30 pg/ml; P < 0.05) and ghrelin activity (8 +/- 1.7% vs. 4.9 +/- 0.9%; P < 0.05) were observed in patients with positive compared with negative measured/predicted REE ratio values. Our study shows that obesity is associated with an impairment of the entire ghrelin system. The observation that ghrelin is further decreased in cases of abnormal energy profit adds new evidence to the relationship between ghrelin activity and energy balance in obesity.

Prevalence and concomitants of glucose intolerance in European obese children and adolescents.

OBJECTIVE: The worldwide increase in the prevalence of childhood obesity is reaching epidemic proportions and is associated with a dramatic rise in cases of type 2 diabetes. The prevalence of glucose intolerance and its determinants and the relation of cardiovascular risk factors with levels of glycemia and degree of obesity were studied in grossly obese children of European origin. RESEARCH DESIGN AND METHODS: A total of 710 grossly obese Italian children (SD score [SDS] of BMI 3.8 +/- 0.7) aged 6-18 years, including 345 male subjects, underwent an oral glucose tolerance test. Insulin resistance and insulin secretion were estimated using the homeostasis model assessment for insulin resistance and the insulinogenic index, respectively. Fibrinogen, C-reactive protein, lipids, and uric acid were measured. The 2-h postload glucose and degree of obesity, calculated as the SDS of weight/height(2), were used as dependent variables. RESULTS: The prevalence of glucose intolerance was 4.5%. Insulin resistance (P < 0.0001), impaired insulin secretion (P < 0.0001), and diastolic blood pressure (BP) (P < 0.05) were significantly and independently related to 2-h postload glucose values. The degree of obesity did not relate to insulin resistance but was independently correlated with inflammatory proteins, uric acid, and systolic BP, variables that were often abnormal in this population. CONCLUSIONS: In these grossly obese children, both insulin resistance and impaired insulin secretion contribute to the elevation of glycemia, and the degree of obesity is related to cardiovascular risk factors independently of insulin resistance.

Comparison between beta-cell function and insulin resistance indexes in prepubertal and pubertal obese children.

Several methods have been developed to assess insulin resistance (IR), insulin secretion, and sensitivity: some of them, such as the homeostasis model assessment (HOMA) for IR (HOMA IR) and for insulin secretion (HOMA beta cell) and the quantitative insulin sensitivity check index (QUICKI) are based on fasting levels of glucose (fasting G) and insulin (fasting I); others, such as the pancreatic insulin response to glucose (IRG) and the insulin sensitivity index (ISI) are derived from the glycemic and insulinemic responses to the oral glucose tolerance test (OGTT). The aim of the study was to compare these indexes in a large group of prepubertal and pubertal obese subjects and verify whether the data from fasting samples were enough for evaluating IR and insulin secretion or if OGTT was mandatory. A total of 405 obese subjects (221 boys and 184 girls) was studied. Ninty-three were prepubertal (Tanner stage I), 98 early pubertal (stage II to III) and 214 late pubertal (stage IV to V). In each subject, a 120-minute OGTT was performed, and the glycemic (mean blood glucose [MBG]) and insulinemic (mean serum insulin [MSI]) responses, expressed as AUC/120, as well as IRG and ISI were calculated. The fasting I/fasting G ratio (FIGR), HOMA IR, HOMA beta cell, and QUICKI were then measured. FIGR and HOMA IR increased in both sexes during puberty, but in girls, the increase was already evident from stage I to stage II to III, while in boys, it was evident only from stage II to III to stage IV to V. QUICKI decreased in girls at the onset of puberty and was lower than in boys in stage II to III; on the other hand, HOMA beta cell did not show any variation. IRG increased throughout puberty, although it was higher in boys than in girls in stages II to III and IV to V, while ISI decreased at the onset of puberty in boys; HOMA IR correlated with MSI and IRG, and HOMA beta cell with MSI in pubertal subjects only. In conclusion, the indexes deriving from fasting samples, such as FIGR and HOMA IR, proved to be enough for evaluating IR in prepubertal and pubertal obese subjects, as did QUICKI for insulin sensitivity, However, OGTT is still useful for assessing insulin secretion, because IRG is more sensitive in depicting the pubertal variations of IR than HOMA beta cell.