ABSTRACTAims: To investigate the association between body mass index (BMI) and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and to determine any sex-specific differences in this association.Methods: We retrospectively enrolled patients with T2DM and investigated the annual death data for seven years starting from 2010. All-cause mortality was calculated using Life Tables analysis. Multivariate Cox proportional hazards analysis was performed to identify the association between BMI and mortality.Results: During a mean survey period of 7.33 ± 1.42 years (X± SD), 996 of the 17259 patients enrolled died, resulting in an all-cause mortality rate of 5.77%, with no significant difference between women and men (6.04% vs. 5.56%; x2 = 1.766, P = 0.184). The top three causes of death were ischemic heart disease, cerebrovascular disease, and chronic kidney failure. A total of 87, 266, 332, and 311 patients with a BMI of <18.5, 18.5–23.99, 24.0–27.99, and ≥28.0 kg/m2, respectively, died, with the corresponding mortality rate calculated at 15.45%, 3.30%, 5.80%, and 10.70%, respectively. The BMI value associated with the highest all-cause mortality was <18.5 kg/m2, but this association was only significant in women aged <50 years (HR: 3.12; 95% CI, 1.62–4.34; P < 0.001).Conclusions: In patients with T2DM, a low BMI in women aged <50 years predicted high all-cause mortality.

ABSTRACTBackground: Diabetes has recently been identified as a risk factor for a variety of cancers, possibly due to hyperinsulinemia or exogenous insulin use. Thyroid cancer is the most common endocrine malignancy, and its incidence has been exponentially increasing worldwide at an alarming rate. The aim of this study was to establish whether insulin use affects thyroid cancer development and progression, specifically cell proliferation and migration in vitro.Methods: In this study, we investigated the effects of the insulin agents most commonly used in the clinic, regular human insulin (HI) and insulin glargine (IG), on the proliferation and migration of thyroid cells.Results: Both HI and IG affected the thyroid cells in a dose-dependent manner and at high concentrations significantly promoted thyroid cell proliferation and tumor cell migration. The promoting effect might be elicited by activation of the insulin receptor and insulin-like growth factor-1 receptor and through the downstream Akt-signaling pathway, which inhibits the activity of the tumor-suppressor FoxO3a. In particular, MAPK-signaling cascades were activated in papillary thyroid carcinoma cell-1 cells but not in follicular rat thyroid-5 cells.Conclusion: The in vitro evidence demonstrated that HI and IG can promote thyroid cell proliferation and tumor cell migration at supraphysiological concentrations, but the effect was not significant at low concentrations. Whether high-dose insulins could affect diabetic patients with thyroid cancer or undetected (pre)cancerous lesions needs further in vivo study.Abbreviations: HI: human regular insulin; IG: insulin glargine; IR: insulin receptor; IGF-1R: insulin-like growth factor-1 receptor; Akt: protein kinase B (PKB); MAPK: mitogen-activated protein kinase; FoxO3a: the forkhead box-containing protein: class O 3a

ABSTRACTPurpose: We present a patient with adrenal Cushing’s syndrome causing steroid myopathy. The purpose of the case report is to illustrate the clinical usefulness of quantitative muscle ultrasonography for the assessment of glucocorticoid-induced changes in muscle mass (MM) and structure. Methods: Assessments of physical performance, muscle strength, MM (i.e., total body skeletal MM, appendicular skeletal MM, and thickness of lower limb muscles), and muscle structure (i.e., echo intensity of lower limb muscles) were performed in the patient both in the active phase of the disease (preoperatively) and 6 months after surgical intervention (postoperatively). Results: Muscle strength, physical performance, and MM were low both preoperatively and postoperatively. We also found preoperatively an increased echo intensity that normalized postoperatively. Conclusions: Clinical implications of these findings are double-fold. First, although the muscle structure can recover quickly in steroid myopathy patients, the recovery of MM may take months to years. Second, we show that muscle echo intensity can be useful to track the progression of steroid myopathy overtime and may help to indicate early response to therapeutic interventions. Further prospective studies are needed to confirm the value of muscle echo intensity in patients with endogenous or exogenous Cushing’s syndrome presenting with steroid myopathy.

ABSTRACTPurpose: Anemia has been reported to be associated with diabetes, but the association between new-onset diabetes after transplantation (NODAT) and anemia has not been reported.Methods: Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in this study. Hemoglobin levels and the prevalence of anemia (hemoglobin <12 g/dL in females and <13 g/dL in males) were evaluated at three time points (prior to transplantation, 6 months following transplantation or 1 month before the development of NODAT, 2 years following transplantation, or following the development of NODAT) and were compared between those who developed NODAT and those who did not. Variables associated with the development of anemia were compared between the two groups.Results: A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow-up. Hemoglobin and hematocrit levels and the prevalence of anemia were similar in those with and without NODAT at all three time points evaluated. Ferritin levels, prior to transplantation and mean corpuscular volume (MCV) posttransplantation post-NODAT development, were slightly but significantly lower in those with NODAT, although both were within the normal range.Conclusions: Pretransplantation ferritin levels and posttransplantation post-NODAT development MCV are inversely associated with the development of NODAT in kidney transplants.

ABSTRACTObjective: TSH-suppression is a therapy for thyroid cancer management, but it may lead to adverse effects, which should be balanced with its benefits. Previous studies evaluating the consequences of TSH suppression on insulin sensitivity have only been done with indirect techniques, and results were controversial. Therefore, we aimed to assess insulin sensitivity in patients with thyroid cancer and suppressed thyroid-stimulating hormone (TSH) with the most appropriate direct method (hyperinsulinemic-euglycemic clamp) in order to get a more conclusive response about the topic. Methods: A group of 20 non-obese and non-diabetic thyroid cancer patients with suppressed TSH underwent a hyperinsulinemic-euglycemic clamp to evaluate insulin sensitivity. Their results were compared to the results of a sex and body mass index (BMI) -paired control group composed of 20 healthy volunteers. Results: Patients were all female, aged 36.8 ± 10.2 years-old, with mean TSH 0.1 ± 0.1 μIU/mL and mean BMI 26.2 ± 3.3 kg/m2. Insulin sensitivity, determined by the insulin-stimulated glucose uptake (M-value), was lower in the patients group (4.2 ± 1.6 mg/min*kg versus 5.8 ± 1.7, age-adjusted p-value = 0.0205). Conclusion: This study shows for the first time that subclinical thyrotoxicosis in patients with thyroid cancer is associated with insulin resistance, as measured by hyperinsulinemic-euglycemic clamp technique. Such finding may be taken into consideration by clinicians when balancing risks and benefits of TSH-suppression therapy in thyroid cancer patients.

ABSTRACTPurpose: The effect of ultrasonography (US)-guided fine-needle aspiration (US-FNA) for the collapse of benign cystic thyroid nodules is still unclear. This study aimed to assess the positive response rate following US-FNA of the cystic component of thyroid cysts and of partially cystic thyroid nodules (PCTNs), and to evaluate the factors influencing the outcome. Methods: From June to December 2013, seven radiologists at seven institutions prospectively performed US-FNA on 320 cystic thyroid nodules in 320 patients. Among them, 179 underwent at least one follow-up US examination following US-FNA of the cystic component at each institution by the same radiologist. A variety of factors, including US features of cystic thyroid nodules, the characteristics of the aspirates, and the follow-up US findings, were analyzed. Results: Of 179 cystic thyroid nodules, there were 53 thyroid cysts and 126 PCTNs. Of 179 cystic thyroid nodules, no malignancies were detected. On follow-up US, the mean size reduction rate of the cystic component was 31.9%, and 102 out of 179 thyroid nodules (57.0%) were assigned to the response group. On univariate analysis, the degree of aspiration and time interval between US-FNA and the final follow-up US showed the significant differences between the response and no response groups. On multivariate analysis, the only factor that influenced the outcome was the nodule type. The cystic component’s positive response rate after simple aspiration was higher in the thyroid cysts than in the PCTNs. Conclusions: US-FNA may be effective at collapsing the cystic components of benign thyroid cysts and PCTNs.

ABSTRACTPurpose of the study: There was inconsistent evidence about the benefit of vitamin D plus evening primrose oil (EPO) supplement intake on lipid profiles and reduced oxidative stress among women with polycystic ovary syndrome (PCOS). The current study was performed to evaluate the effects of vitamin D plus EPO supplementation on lipid profiles and biomarkers of oxidative stress in vitamin D-deficient women with PCOS. Materials and methods: This randomized, double-blind, placebo-controlled trial was performed among 60 vitamin D-deficient women with PCOS. Participants were randomly assigned into two groups to receive either 1000 IU vitamin D3 plus 1000 mg EPO (n = 30) or placebo (n = 30) for 12 weeks. Metabolic profiles were quantified at baseline and after the 12-week intervention. Results: Compared with the placebo group, women in vitamin D and EPO co-supplementation group had significant increases in serum 25-hydroxyvitamin D (25(OH)D) (+10.7 ± 8.4 vs. −0.5 ± 1.6 ng/mL, p < 0.001) and plasma total glutathione (GSH) (+62.7 ± 58.0 vs. −0.7 ± 122.7 µmol/L, p = 0.01), while there were significant decreases in triglycerides (−7.3 ± 23.8 vs. +6.9 ± 26.3 mg/dL, p = 0.03), very low-density lipoprotein (VLDL) cholesterol levels (−1.5 ± 4.7 vs. +1.4 ± 5.3 mg/dL, p = 0.03), total/high-density lipoprotein cholesterol ratio (−0.3 ± 0.4 vs. −0.02 ± 0.4, p = 0.02), and malondialdehyde (MDA) concentration (−0.4 ± 0.4 vs. +0.5 ± 1.8 µmol/L, p = 0.008). Conclusion: Overall, vitamin D and EPO co-supplementation for 12 weeks among vitamin D-deficient women with PCOS significantly improved triglycerides, VLDL cholesterol, GSH, and MDA levels.

ABSTRACTPurpose: Differentiated thyroid cancer is the most common endocrine malignancy. Recurrences (5–20%) are the main reason for follow-up. Thyroglobulin (Tg) has proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab) may interfere with Tg measurement, leading to over or underestimation. It is proposed that the Tg-Ab trend can be used as a marker for disease recurrence, yet few studies define trend and have a long-term follow-up. The objective of our study was to investigate the value of a well-defined Tg-Ab trend as a surrogate marker for disease recurrence during long-term follow-up. Methods: We retrospectively studied patients treated at the Nuclear Department of the University Medical Center Utrecht from 1998 to 2010 and the Netherlands Cancer Institute from 2000 to 2009. All patients with Tg-Ab 12 months after treatment were included. The definition of a rise was >50% increase of the Tg-Ab value in a 2 year time period. A decline as >50% decrease of the Tg-Ab value. Results: Twenty-five patients were included. None of the patients with declining or stable Tg-Ab without a concomitant rise in Tg developed a recurrence. Four patients did suffer a recurrence. Three of these patients had a rising Tg-Ab trend, in two of these patients Tg was undetectable. Conclusions: Tg-Ab trend can be used as a crude surrogate marker for long-term follow-up of Tg-Ab patients. A rising trend in Tg-Ab warrants further investigation to detect recurrent disease. Stable or declining Tg-Ab levels do not seem to reflect a risk for recurrence.

ABSTRACTAim: Vitamin D acts through the binding to the vitamin D receptor (VDR). Several polymorphisms in VDR gene have been studied. Among these, the rs2228570 C>T (FokI) variant has been demonstrated to be functional, leading to a protein with a different size and activity. So far, genetic studies on the association between VDR gene rs2228570 single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) showed contradictory results. Thus, we performed an association study in a large cohort of adult Italian subjects with T2DM and in nondiabetic controls. Materials and methods: For this study, 1713 subjects, 883 T2DM patients and 830 controls, were genotyped for the polymorphism. All participants without a diagnosis of diabetes underwent oral glucose tolerance test (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance (Homeostatic model assessment of insulin resistance, insulin sensitivity index), secretion (homeostatic model assessment for beta-cell, corrected insulin response at 30 minutes) and disposition index were calculated. Results: Genotype distributions and allele frequencies did not show difference between T2DM subjects and controls. We did not find significant differences among the three genotypes regarding gender, age, BMI, waist, hip, waist-to-hip ratio, and blood pressure. There were also no significant differences in lipid parameters, aspartate aminotransferase, and alanine aminotransferase levels. We tested for association with OGTT-derived data and surrogate indices of insulin resistance and secretion. We did not find significant differences among the genotypes in any of above-mentioned parameters. Furthermore, vitamin D levels were measured in a subgroup of subjects. We did not find significant differences among the genotypes. Conclusions: Our study does not provide evidence for the association of the rs2228570 polymorphism with T2DM in a Caucasian population.