High-normal TSH values in obesity: is it insulin resistance or adipose tissue's guilt?

Objective: Clinical evidences reported subclinical alterations of thyroid function in obesity, although the relationship between thyroid status and obesity remains unclear. We cross-sectionally investigated the influence of metabolic features on hypothalamic-pituitary-thyroid axis in obesity. Design and methods: We enrolled 60 euthyroid subjects with no history of type 2 diabetes mellitus and assessed the relationship of thyroid function with insulin resistance, measured using euglycemic clamp, and abdominal fat volume, quantified by computed tomography scan (CT scan). Thyroid stimulating hormone (TSH) correlated with BMI (r = 0.46; P = 0.02), both visceral (r = 0.58; P = 0.02) and subcutaneous adipose tissue volumes (r = 0.43; P = 0.03) and insulin resistance (inverse relationship with insulin sensitivity-glucose uptake: r = -0.40; P = 0.04). Results: After performing multivariate regression, visceral adipose tissue volume was found to be the most powerful predictor of TSH (β = 3.05; P = 0.01), whereas glucose uptake, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, subcutaneous adipose tissue volume, and triglycerides were not. To further confirm the hypothesis that high-normal TSH values could be dependent on adipose tissue, and not on insulin resistance, we restricted our analyses to moderately obese subjects' BMI ranging 30-35 kg/m(2). This subgroup was then divided as insulin resistant and insulin sensitive according to the glucose uptake (≤ or >5 mg · kg(-1) · min(-1), respectively). We did not find any statistical difference in TSH (insulin resistant: 1.62 ± 0.65 µU/ml vs. insulin sensitive: 1.46 ± 0.48; P = not significant) and BMI (insulin resistant: 32.2 ± 1.6 kg/m(2) vs. insulin sensitive: 32.4 ± 1.4; P = not significant), thus confirming absence of correlation between thyroid function and insulin sensitivity per se. Conclusion: Our study suggests that the increase in visceral adipose tissue is the best predictor of TSH concentration in obesity, independently from the eventual concurrent presence of insulin resistance

Metabolic syndrome in transplant patients: an academic or a health burden?

Metabolic syndrome is a cluster of risk factors that predispose to major cardiovascular diseases, liver steatosis and fibrosis, as well as reduced renal function. Metabolic syndrome and its early hepatic manifestation, non-alcoholic fatty liver disease, are prevalent both among the general population and in pre- and posttransplantation settings. Because indications for solid-organ transplantation are gradually increasing, attention should focus on the incidence of metabolic syndrome among transplanted patients, defined as posttransplant metabolic syndrome (PTMS). Subjects with worse metabolic profiles with two or more criteria of the syndrome show lower survival rates and greater co-morbidities. However, it is still unclear whether the pathophysiology of posttransplantation metabolic syndrome differ from that of the general population and may be determined by the primary disease affecting the liver or kidney, or amplified or altered by the immunosuppressive treatment, as it has already been established that corticosteroids and calcineurin inhibitors cause metabolic disarrangements. Although there is controversy regarding the definition and the impact of PTMS on overall survival rates following transplantation, these patients are at increased risk for cardiovascular morbidity and mortality. Early recognition, prevention, and treatment of these conditions may impact long-term survival after transplantation. Thus, even if metabolic syndrome in transplant patients remains an unclear definition, an insulin resistance is present in these patients. The treatment of this condition represents a health problem that requires intervention by clinicians before and after transplantation

Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes

We read with interest the article by Kayaniyil et al. that supplied elegant data suggesting that 25- hydroxyvitamin D [25(OH)D] is related to insulin resistance and _-cell function in a large population at high risk for type 2 diabetes and/or metabolic syndrome, thus concluding that 25(OH)D may be an independent risk factor for diabetes. We have, however, some concerns. First, the studied population was mainly composed of obese subjects (the mean BMI was 30.5 kg/m2). Clearly, within a population with such a high BMI, the major variable influencing insulin sensitivity is fat mass. An increased fat mass (within the same BMI) could determine both the reduced insulin sensitivity and 25(OH)D. The two variables therefore correlate, but are not causally related. In our recently published article, we approached this important question by comparing two groups of obese subjects matched by BMI but different in terms of insulin sensitivity: no differences in 25(OH)D concentrations could be found, suggesting that the adipose tissue is its reservoir. Kayaniyil et al. themselves reported a weaker correlation in their obese (BMI 30 kg/m2) subpopulation but, unfortunately, they did not provide data on body composition. Second, although the correlation within the high risk (for diabetes) population is intriguing, a control population is missing. In particular, it is not reported whether the studied population has lower 25(OH)D concentration than an hypothetical control cohort. If this was not the case, the working hypothesis fails. How could normal 25(OH)D determine insulin resistance? Third, if 25(OH)D is involved in the pathogenesis of type 2 diabetes, one would expect that a supplementation of calcitriol or its analogues would ameliorate the glucose metabolism. This was not the case either in insulin-resistant diabetic patients or in healthy subjects (4). As we and others reported, 25(OH)D concentration mainly reflects body fat mass; the reduction of fat mass, rather than vitamin D supplementation, is the main road for the prevention and treatment of insulin resistance and diabetes

Will vitamin D reduce insulin resistance? Still a long way to go

We read with interest the article by Alvarez et al, which aimed to investigate the relations of circulating 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentrations with direct measurements of insulin sensitivity, after robust measures of body composition and fat distribution were accounted for. We would like to express our opinion and a different interpretation of the data provided by authors, with the hope that other points for discussion are brought up. In a very recent publication, Alvarez et al provided novel findings suggesting that dietary vitamin D is independently associated with insulin sensitivity in African Americans (AAs) but not in European Americans (EAs). Interestingly, the 2 groups were identical for hepatic insulin sensitivity [homeostatic model assessment (HOMA)], whereas Si, a method for measuring insulin sensitivity that encompasses both hepatic and peripheral tissues, was lower in AAs, therefore suggesting a pivotal role for insulin resistance in skeletal muscle [especially in the presence of identical body mass index (BMI)] in correlation with 25(OH)D. In the present article, the authors suggest that 25(OH)D and PTH concentrations are independently associated with whole-body insulin sensitivity and suggest that these variables may influence insulin sensitivity through independent mechanisms. In fact, multiple linear regression analysis indicated that 25(OH)D and PTH concentrations were independently related to Si after adjustment for age, race, and intraabdominal adipose tissue. It is well known, however, that adipose tissue is the natural reservoir for lipo-soluble 25(OH)D. The higher BMI and the higher subcutaneous fat content found in AAs (although the latter difference was not statistically significant) could therefore explain the differences in 25(OH)D concentration, as well as in HOMA index, found by the authors. We examined the effect of 25(OH)D on insulin sensitivity in obese subjects and found a linear correlation between them, which is apparently in agreement with Alvarez et al. Obesity, however, is not invariably associated with insulin resistance, because normal insulin sensitivity can be present in some obese subjects. If 25(OH)D concentration influences insulin sensitivity independently of obesity, it should be found to be low in insulin-resistant obese subjects and high in insulin-sensitive obesity. We divided our obese population into 2 subgroups, according to their insulin sensitivity (low and high). The 2 groups were similar in BMI, age, and sex but did not show any difference in 25(OH)D concentration, thus confirming the hypothesis that 25(OH)D concentrations are not influenced by the degree of insulin resistance but mainly by the adipose tissue\u2019s reservoir, at least in our EA participants. Unfortunately, in the presentstudied population but not in the previous one, AAs had higher BMI (and HOMA) and the actual role of these variables in determining hypovitaminosis D was not ruled out. In conclusion, we are certain that 25(OH)D concentration mainly reflects body fatmass, either subcutaneous or visceral; the reduction of fat mass, rather than vitamin D supplementation, is the best route for the prevention and treatment of insulin resistance and diabetes

Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or a cause-effect in PCOS?

BACKGROUND & AIMS: Recent investigations have identified low vitamin D status as a hypothetical mechanism of insulin-resistance in Polycystic Ovary Syndrome (PCOS). Instead, some authors supported the hypothesis that low vitamin D levels and insulin-resistance are 2 unrelated features of body size in PCOS. Hence, we aimed to explore the association of 25-hydroxyvitamin D (25(OH)D) with anthropometric, metabolic and hormonal features in PCOS. METHODS: We assessed the association of low 25(OH)D levels with endocrine parameters, insulin-sensitivity evaluated by hyperinsulinemic euglycemic clamp (HEC) and body composition measured by DEXA in 38 women affected by PCOS. RESULTS: Low 25(OH)D (25(OH)D\ua0<\ua050\ua0nmo/L) was detected in 37% of the entire cohort of patients. Body Mass Index (BMI), in particular total fat mass (p\ua0<\ua00.001), resulted to be the most predictor factor of 25(OH)D levels whereas Sex Hormone Binding Globulin (SHBG), Free Androgen Index (FAI), glucose uptake and fat free mass were not. CONCLUSIONS: Our data demonstrated that in PCOS low 25(OH)D levels are significantly determined by the degree of adiposity

Removal of Duodenum Elicits GLP-1 Secretion

OBJECTIVETo evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects.RESEARCH DESIGN AND METHODSFor evaluation of hormonal secretion and insulin sensitivity, 10 overweight patients without type 2 diabetes (age 61 \ub1 19.3 years and BMI 27.9 \ub1 5.3 kg/m(2)) underwent a mixed-meal test and a hyperinsulinemic-euglycemic clamp before and after pylorus-preserving pancreatoduodenectomy for ampulloma.RESULTSAll patients experienced a reduction in insulin (P = 0.002), C-peptide (P = 0.0002), and gastric inhibitory peptide (GIP) secretion (P = 0.0004), while both fasting and postprandial glucose levels increased (P = 0.0001); GLP-1 and glucagon responses to the mixed meal increased significantly after surgery (P = 0.02 and 0.031). While changes in GIP levels did not correlate with insulin, glucagon, and glucose levels, the increase in GLP-1 secretion was inversely related to the postsurgery decrease in insulin secretion (R(2) = 0.56; P = 0.012) but not to the increased glucagon secretion, which correlated inversely with the reduction of insulin (R(2) = 0.46; P = 0.03) and C-peptide (R(2) = 0.37; P = 0.04). Given that the remaining pancreas presumably has preserved intraislet anatomy, insulin secretory capacity, and \u3b1- and \u3b2-cell interplay, our data suggest that the increased glucagon secretion is related to decreased systemic insulin.CONCLUSIONSPylorus-preserving pancreatoduodenectomy was associated with a decrease in GIP and a remarkable increase in GLP-1 levels, which was not translated into increased insulin secretion. Rather, the hypoinsulinemia may have caused an increase in glucagon secretion

METABOLIC SYNDROME IN TRANSPLANT PATIENTS: AN UPDATING POINT OF VIEW

Metabolic Syndrome is a cluster of risk factors that predispose individuals to major cardiovascular diseases and its complications, determining liver and kidney impairment. In the last decade, the indications to transplantation are increasing, with a linear incidence of the complications of the procedure. Metabolic syndrome represents one of the most common, being in turn the consequence of the underlying disease that required the transplantation, or the result of the medical treatment, as well as one of the most important factor influencing the morbidity and mortality of the transplanted patients. Due to the growing incidence of the metabolic syndrome in these patients, it is crucial to focus and clarify the leading causes determining the onset of the metabolic disarrangement, its outcome and the hypothetical mechanism through which the clinicians could reduce the impact of the disease. In fact, prevention, early recognition and treatment of the factor that could predict the onset or progression of the metabolic syndrome after the transplantation may impact long term survival of patients again, the scope of the same transplant. This review will update the different mechanisms of the pathogenesis of metabolic syndrome in this population, the clinical effects of the presence of the metabolic syndrome, observing the risk factors to be treated before and after the transplantation and suggesting the management of the follow-up

High-normal TSH values in obesity depends on adipose tissue rather than insulin resistance

Clinical evidences reported subclinical alterations of thyroid function in obesity, although the relationship between thyroid status and obesity remains unclear. We cross-sectionally investigated the influence of metabolic features on hypothalamic-pituitary- thyroid axis in obesity. We enrolled 60 euthyroid subjects with no history of type 2 diabetes mellitus and assessed the relationship of thyroid function with insulin-resistance, measured using euglycemic clamp, and abdominal fat volume, quantified by CT-Scan. TSH correlated with BMI (r=0.46;p=0.02), both visceral (r=0.58;p=0.02) and subcutaneous adipose tissue volumes (r=0.43;p=0.03) and insulin-resistance (inverse relationship with insulin-sensitivity - glucose uptake: r=-0.40 p=0.04). After performing multivariate regression, visceral adipose tissue volume was found to be the most powerful predictor of TSH (\u3b2=3.05;p=0.01), whereas glucose uptake, HDL cholesterol, LDL cholesterol, subcutaneous adipose tissue volume and triglycerides were not. To further confirm the hypothesis that high-normal TSH values could be dependent on adipose tissue, and not on insulin-resistance, we restricted our analyses to moderately obese subjects BMI ranging 30-35 kg/ m2. This subgroup was then divided in insulin-resistant and insulinsensitive according to the glucose uptake ( 64 or > 5 mg\ub7kg-1\ub7min-1, respectively). We did not find any statistical difference in TSH (insulin-resistant: 1.62\ub10.65 \u3bcU/mL vs. insulin-sensitive:1.46 \ub1 0.48;p=NS) and BMI (insulin-resistant: 32.2 \ub1 1.6 kg/m2 vs. insulin-sensitive:32.4 \ub1 1.4;p=NS), thus confirming absence of correlation between thyroid function and insulin-sensitivity per se. Our study suggests that the increase in visceral adipose tissue is the best predictor of subclinical thyroid dysfunction in obesity, independently from the eventual concurrent presence of insulin resistance

25-Hydroxyvitamin D concentration correlates with insulin-sensitivity and BMI in obesity

The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25-hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor for type 2 diabetes, although its relation with insulin-sensitivity is not well investigated. Thus, we aimed to investigate the relationship between 25(OH)D concentration and insulin-sensitivity, using the glucose clamp technique. In total, 39 subjects with no known history of diabetes mellitus were recruited. The association of 25(OH)D concentration with insulin-sensitivity was evaluated by hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50\ua0nmol/l) had higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol (P = 0.012), low-density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides (P = 0.048), and lower insulin-sensitivity as evaluated by clamp study (P = 0.047). There was significant correlation between 25(OH)D and BMI (r = -0.58; P = 0.01), PTH (r = -0.44; P < 0.01), insulin-sensitivity (r = 0.43; P < 0.01), total (r = -0.34; P = 0.030) and LDL (r = -0.40; P = 0.023) (but not high-density lipoprotein (HDL)) cholesterol, and triglycerides (r = 0.45; P = 0.01). Multivariate analysis using 25(OH)D concentration, BMI, insulin-sensitivity, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the cofactors was performed. BMI was found to be the most powerful predictor of 25(OH)D concentration (r = -0.52; P < 0.01), whereas insulin-sensitivity was not significant. Our study suggested that there is no cause-effect relationship between vitamin D and insulin-sensitivity. In obesity, both low 25(OH)D concentration and insulin-resistance appear to be dependent on the increased body size