Thyroid Cancer Detection in a Routine Clinical Setting: Performance of ACR TI-RADS, FNAC, and Molecular Testing in Prospective Cohort Study.

The aim of our study was to address the potential for improvements in thyroid cancer detection in routine clinical settings using a clinical examination, the American College of Radiology Thyroid Imaging Reporting and Database System (ACR TI-RADS), and fine-needle aspiration cytology (FNAC) concurrently with molecular diagnostics. A prospective cohort study was performed on 178 patients. DNA from FNA samples was used for next-generation sequencing to identify mutations in the genes BRAF, HRAS, KRAS, NRAS, and TERT. RNA was used for real-time PCR to detect fusion genes. The strongest relevant positive predictors for malignancy were the presence of genetic mutations (p < 0.01), followed by FNAC (p < 0.01) and ACR TI-RADS (p < 0.01). Overall, FNAC, ACR TI-RADS, and genetic testing reached a sensitivity of up to 96.1% and a specificity of 88.3%, with a diagnostic odds ratio (DOR) of 183.6. Sensitivity, specificity, and DOR decreased to 75.0%, 88.9%, and 24.0, respectively, for indeterminate (Bethesda III, IV) FNAC results. FNA molecular testing has substantial potential for thyroid malignancy detection and could lead to improvements in our approaches to patients. However, clinical examination, ACR TI-RADS, and FNAC remained relevant factors.

Relations of prediabetes and type 2 diabetes to the thyroid cancer.

OBJECTIVE: Patients with type 2 diabetes (T2DM) generally experience a higher incidence of cancer. However, the association between T2DM and thyroid cancer is inconclusive. METHODS: Case-control prospective study, 722 patients were screened for T2DM and prediabetes (PDM) and underwent thyroid ultrasound and biochemical tests. The patients were assigned to groups of PDM (n=55), T2DM (n=79) or a non-diabetes group (NDM) (n=588). Fine needle aspiration biopsy was carried out in 263 patients. Histological examinations were done for 109 patients after surgery, with findings of 52 benign (BS) and 57 malignant tumors (MS). RESULTS: 33 % of patients with T2DM and especially PDM were newly diagnosed by our screening: 6.5 % with T2DM and 72 % with PDM, respectively. The percentage of thyroid cancers did not significantly differ between the groups (χ2 test=0.461; p=0.794). Relevant positive thyroid predictors for T2DM (t-statistic=25.87; p<0.01) and PDM (21.69; p<0.01) contrary to NDM (-26.9; p<0.01) were thyroid volume (4.79; p<0.01), thyroid nodule volume (3.25; p<0.01) and multinodular thyroid gland (4.83; p<0.01), while negative relevant predictors included the occurrence of autoimmune thyroid disease (AITD) (-2.01; p<0.05). CONCLUSION: In general, we did not observe an increased risk for thyroid cancer in the diabetic and prediabetic groups in comparison to controls, in spite of well-established increased risk for other malignancies. Structural and benign changes such as larger and multinodular thyroid glands, in comparison to autoimmune thyroid disease, are present more often in diabetics.

Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma.

BACKGROUND: Diabetes mellitus is unfavorably associated with cancer risk. The purpose of this multidisciplinary project was to evaluate a possible association of diabetes mellitus and other comorbidities and their treatment with progression of colorectal cancer. PATIENTS AND METHODS: We investigated the correlation between pathological characteristics and clinical course, including comorbidities in 1004 Czech patients diagnosed and surgically treated for colorectal adenocarcinoma (CRC) between 1999 and 2016. RESULTS: In our data set, CRC patients treated with metformin due to coexisting diabetes mellitus type 2 (T2DM) developed fewer distant metastases which clinically correlates with slower CRC progression. Survival in metformin subgroup was longer, particularly in men with CRC. Osteoporosis may be a negative factor of survival in CRC patients. CONCLUSIONS: Our findings also indicate that aging, higher tumor grade and TNM stage, coexistence of selected endocrine disorders, and metabolic abnormalities may change the tumor microenvironment and impact survival in colorectal cancer, although mechanism of these observations yet to be explained. Patients with diabetes mellitus type 2 treated with metformin may represent the altered microenvironment with specifically tuned metabolic molecular responses and with various epigenetic characteristics. More awareness and increased understanding of the mechanisms underlying the positive effect of metformin on patients' survival could offer insight into new treatment methods and permit more individualized treatment plans.

Insulin Sensitivity and Secretion in Obese Type 2 Diabetic Women after Various Bariatric Operations.

OBJECTIVE: To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). METHODS: A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. RESULTS: Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. CONCLUSION: We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity.

Validation of a deconvolution procedure (AutoDecon) for identification and characterization of fasting insulin secretory bursts.

BACKGROUND: Insulin secretion is pulsatile, and has been shown to be altered in both physiologic and pathophysiologic conditions. The identification and characterization of such pulses have been challenging, partially because of the low concentrations of insulin during fasting and its short half-life. Existing pulse detection algorithms used to identify insulin pulses either cannot separate hormone pulses into their secretory burst and clearance components, or have been limited by both the subjective nature of initial peak selection and a lack of statistical verification of bursts. METHODS: To address these concerns, we have developed AutoDecon, a novel deconvolution computer program. RESULTS: AutoDecon was applied to synthetic insulin concentration-time series modeled on data derived from normal fasting subjects and simulated to reflect several sampling frequencies, sampling durations, and assay replicates. The operating characteristics of AutoDecon were compared to those obtained with Cluster, a standard pulse detection algorithm. AutoDecon performed considerably better than Cluster with regard to sensitivity and secretory burst detection rates for true positives, false positives, and false negatives. As expected, given the short half-life of insulin, sampling at 30-second intervals is required for optimal analytical results. The choice of sampling duration is more flexible and relates to the number of replicates assayed. CONCLUSION: AutoDecon represents a viable alternative to standard pulse detection algorithms for the appraisal of fasting insulin pulsatility.

Beta cell function and insulin sensitivity in women with polycystic ovary syndrome: influence of the family history of type 2 diabetes mellitus.

AIM: To study the impact of family history (FH) of type 2 diabetes mellitus on beta-cell compensatory mechanism in women with polycystic ovary syndrome (PCOS). SUBJECTS AND METHODS: A total of 70 women with PCOS, 14 with first-degree relative with type 2 diabetes mellitus (T2DM) (FH+), 56 with negative FH of T2DM (FH-) and 72 age and BMI matched control healthy women (CNT) underwent oral glucose tolerance test (OGTT). Insulin resistance was evaluated as oral glucose index (OGIS); insulin and C-peptide secretion as the insulinogenic index in 30th min of OGTT. RESULTS: Fasting blood glucose levels were significantly higher in FH+ than in FH- (p < 0.05). Fasting insulin was higher in FH+ than in CNT (p < 0.05). Fasting C-peptide was significantly higher in both FH- and FH+ than in CNT (p < 0.05 and p < 0.01, respectively). OGIS was lower in FH+ than in FH- or in CNT (p < 0.05). Insulinogenic index calculated from C-peptide values (II-Cp) was lower in FH+ than in CNT (p < 0.05). Adaptation index calculated from the values of OGIS and insulinogenic index was significantly lower in FH+ than in CNT or in FH- (p < 0.0001 and p < 0.01, respectively). CONCLUSIONS: Insulin resistance and defective early-phase insulin secretion is present only in those PCOS-affected subjects who had positive FH of T2DM.

Incretin levels in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) has been linked to a high risk of type 2 diabetes mellitus. Disturbances in the secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) have been observed in states with impaired glucose regulation. This paper considers the secretion of GIP and GLP-1 after oral glucose load in a group of lean, glucose-tolerant PCOS women in comparison with age- and body mass index (BMI)-matched healthy women. DESIGN: Case control. METHODS: PCOS (n=21, 25.8+/-4.1 years, BMI 21.6+/-1.7 kg/m(2)) and control healthy women (CT, n=13, 28.5+/-7.2 years, BMI 20.3+/-2.5 kg/m(2)) underwent oral glucose tolerance test (OGTT) with blood sampling for glucose, insulin, C-peptide, total GIP, and active GLP-1. Insulin sensitivity was determined both at fasting and during the test. STATISTICS: Repeated measures ANOVA. RESULTS: Glucose levels and insulin sensitivity did not differ between PCOS and CT. PCOS had significantly higher levels of C-peptide (P<0.05) and tended to have higher insulin levels. The levels of total GIP were significantly higher in PCOS than in CT (P<0.001). Active GLP-1 levels exhibited a significantly different time-dependent pattern in PCOS (P<0.002 for PCOS versus time interaction). GLP-1 concentrations were similar in PCOS and CT in the early phase of OGTT and then reached significantly lower levels in PCOS than in CT at 180 min (P<0.05). CONCLUSIONS: Increased total GIP and lower late phase active GLP-1 concentrations during OGTT characterize PCOS women with higher C-peptide secretion in comparison with healthy controls, and may be the early markers of a pre-diabetic state.

Prevalence of insulin resistance and prediction of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome.

BACKGROUND: Diabetes mellitus type 2 (DM2) affects 10% of women with polycystic ovary syndrome (PCOS). We evaluated the sensitivity and specificity of clinical and fasting biochemical parameters in screening for impaired glucose tolerance (IGT) and DM2. METHODS: Women with PCOS [n=244, age 27.4+/-7.5 years, body mass index (BMI) 27.5+/-6.9 kg/m(2)] and healthy women (n=57, age 26.8+/-5.8 years, BMI 21.3+/-2.1 kg/m(2)) underwent basal blood sampling and an oral glucose tolerance test (oGTT). RESULTS: Insulin resistance was identified in 40.2% of PCOS women. Impaired fasting glucose (5.6-6.9 mmol/L) was found in 30 subjects (12.3%), but the oGTT revealed IGT in only six of these cases and DM2 in one subject. IGT was found in 23 (9.4%) and DM2 in four (1.6%) of the women with PCOS. The conventional upper limits for total cholesterol, triglycerides, systolic and diastolic blood pressure and fasting glucose revealed low sensitivity for the identification of impaired glucose metabolism. CONCLUSIONS: No single parameter nor any combination of them showed an accuracy sufficient for screening of IGT or DM2 in PCOS patients. All PCOS patients should be screened using an oGTT to identify disturbances in glucose metabolism.