Distinguishing benign and malignant thyroid nodules using plasma trimethylamine N-oxide, carnitine, choline and betaine.

PURPOSE: Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, and its precursors (carnitine, choline, betaine) have not been fully examined in relation to thyroid cancer (TC) risk. The aim of this study was to assess the value of TMAO and its precursors in diagnosis of benign and malignant thyroid nodules. METHODS: In this study, high-performance liquid chromatography-tandem mass spectrometry was utilized to measure the levels of plasma TMAO and its precursors (choline, carnitine, and betaine) in 215 TC patients, 63 benign thyroid nodules (BTN) patients and 148 healthy controls (HC). The distribution of levels of TMAO and its precursors among the three groups were compared by the Kruskal-Wallis test. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the sensitivity, specificity, and the predictive accuracy of single and combined biomarkers. RESULTS: In comparison to HC, TC showed higher levels of TMAO and lower levels of its precursors (carnitine, choline, and betaine) (all P < 0.001). Plasma choline (P < 0.01) and betaine (P < 0.05) were declined in BTN than HC. The levels of carnitine (P < 0.001) and choline (P < 0.05) were significantly higher in BTN than that in TC group. Plasma TMAO showed lower levels in TC with lymph node metastasis (101.5 (73.1-144.5) ng/ml) than those without lymph node metastasis (131 (84.8-201) ng/ml, P < 0.05). Combinations of these four metabolites achieved good performance in the differential diagnosis, with the area under the ROC curve of 0.703, 0.741, 0.793 when discriminating between TC and BTN, BTN and HC, TC and HC, respectively. CONCLUSION: Plasma TMAO, along with its precursors could serve as new biomarkers for the diagnosis of benign and malignant thyroid nodules.

Fasting Glucose of 6.1 mmol/L as a Possible Optimal Target for Type 2 Diabetic Patients with Insulin Glargine: A Randomized Clinical Trial.

To observe whether different insulin glargine titration algorithms based on fasting blood glucose (FBG) levels lead to different glycaemic variations (GVs) in type 2 diabetes (T2D) patients, a prospective, randomized, single-centre, comparative, three-arm parallel-group, open-label, treat-to-target, 24-week study was performed. A total of 71 uncontrolled T2D patients were recruited and randomized 1 : 3 : 3 into Groups 1, 2, and 3 (insulin titration goals of FBG ≤ 5.6, ≤6.1, and ≤7.0) for this study. The initiated insulin glargine dose was recommended at 0.2 U/kg/day and was then titrated following the FBG target. Patients were subjected to two 3-day continuous glucose monitoring (CGM) at baseline and the endpoint, wherein the CGM data were analysed, and the study's primary endpoint was the difference in 24 hrs mean amplitude of glycaemic excursion (MAGE) among the three groups. We observed that patients in the three groups had similar MAGE levels at the endpoint; however, Group 2 achieved a significant decrease in the MAGE level from baseline to the endpoint as compared to Groups 1 and 3 (all p < 0.05). We also observed that these patients had significant glycated haemoglobin A1c (HbA1c) value improvements as compared to the other two groups (all p < 0.05). Therefore, choosing an FBG level of 6.1 mmol/L as an insulin titration target provided significant GVs and HbA1c value improvements in T2D patients. Moreover, our data indicated that an FBG of 6.1 mmol/L could possibly be an insulin glargine titration target in T2D patients.

The plasma levels of atrial natriuretic peptide and brain natriuretic peptide in type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor.

PURPOSE: The aim of this study was to determine the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) after treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitor or dipeptidyl peptidase-4 (DPP4) inhibitor in patients with type-2 diabetes inadequately controlled by insulin, and to determine whether variation in ANP levels can explain favorable cardiovascular outcome. METHODS: We enrolled 56 patients, aged 18-80years, with type-2 diabetes inadequately controlled by insulin: i.e., HbA1c level 7.5-10.5% despite at least 8weeks' injectable insulin at a stable mean dose of 20-150IU daily, with or without no more than two oral antidiabetic agents. FINDINGS: The 56 patients were randomized between 3 treatment groups: SGLT2 inhibitor (n=18), DPP4 inhibitor (n=19) and placebo (n=19). Patients who received SGLT2 inhibitor or DPP4 inhibitor treatment all showed significantly lower HbA1c levels, fasting blood glucose (FBG) levels and systolic blood pressure at 24weeks than controls. SGLT2 inhibitor treatment decreased ANP levels, BNP levels, systolic blood pressure and weight compared with placebo. Compared to those receiving DPP4 inhibitor, patients receiving SGLT2 inhibitor showed lower HbA1c levels (7.01 vs. 7.58%; P=0.03), ANP levels (28.41 vs. 43.03 pg/mL; P=0.00) and weight (66.14 vs. 71.76 kg; P=0.04) at 24weeks after adjusting for baseline values. The SGLT2 inhibitor group showed higher sodium concentrations than the placebo and DPP4 inhibitor groups (145.89 vs. 143.89 and 144.79 mmol/L, respectively; P=0.00 and P=0.04) at 24 weeks. ANP and BNP levels did not significantly correlate with HbA1c and blood glucose levels. IMPLICATIONS: These results indicated that SGLT2 inhibitors may be superior to DPP4 inhibitors in reducing risk of cardiovascular disease in diabetic patients. The major study limitation was the small number of patients per group, which should be enlarged in further research.

Association between Free Thyroxine Levels and Diabetic Retinopathy in Euthyroid Patients with Type 2 Diabetes Mellitus.

Background: This study aimed to evaluate the association between thyroid parameters and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Materials and Methods: In this cross-sectional study, a total of 911 euthyroid patients with T2DM (539 men and 372 women; mean age, 60.81 ± 12.93 years) were enrolled. Clinical factors were assessed and free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were measured. DR was diagnosed using fundus fluorescein angiography.Results: Compared with patients without DR (n = 718), patients with DR (n = 193) exhibited lower FT3 (4.40 ± 0.58 vs. 4.50 ± 0.51 pmol/L; P = .019) and FT4 (14.86 ± 2.09 vs. 15.91 ± 2.18 pmol/L; P < .001) and higher TSH (1.86 [1.22, 2.66] vs. 1.58 [1.14, 2.34] µIU/mL; P = .015) levels. After adjustment for potential DR risk factors, patients in the highest tertile of plasma FT4 levels had a 0.332-fold likelihood of developing DR compared with those in the lowest tertile of plasma FT4 levels (Ptrend < 0.001). The prevalence of DR showed a significantly decreasing trend across the three tertiles based on FT4 levels (31.35%, 19.08% and 13.16%; Ptrend < 0.001). Similar results were obtained for the presence of proliferative DR.Conclusion: These findings suggest that low-normal FT4 levels are associated with the prevalence of DR in euthyroid patients with T2DM.

Association between thyroid function and diabetic nephropathy in euthyroid subjects with type 2 diabetes mellitus: a cross-sectional study in China.

Previous studies have suggested that even in euthyroid subjects, thyroid function may affect the risk factors of diabetic nephropathy (DN). Thus, we investigated the association between thyroid parameters and DN in euthyroid subjects with type 2 diabetes mellitus (T2DM). This was a cross-sectional study of 1,071 euthyroid subjects with T2DM (mean age of 61.90 ± 12.74 years; 622 men). Clinical factors, including levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid autoantibodies, albumin excretion rate were measured. DN was present in 400 (37.35%) individuals. Patients with DN exhibited higher serum TSH and lower serum FT3 and FT4 levels than those without DN (P<0.05). After adjusting traditional risk factors of DN, the levels of both FT3 (per-SD increase, odds ratio [OR] 0.606 [95% confidence interval (CI), 0.481-0.762], P<0.001) and FT4 (per-SD increase, OR 0.944 [0.894-0.998], P = 0.040) were inversely correlated with DN. Meanwhile, we found that serum TSH levels were positively correlated with DN (per-SD increase, OR1.179 [1.033-1.346], P = 0.015). Low-to-normal thyroid hormones (THs) were also associated with the presence of macroalbuminuria. In conclusion, the relatively low levels of THs were significantly associated with DN in euthyroid subjects with T2DM.

Glycemic variation in uncontrolled Graves' disease patients with normal glucose metabolism: Assessment by continuous glucose monitoring.

PURPOSE: To observe the glycemic variation (GV) in uncontrolled Graves' disease (GD) patients with normal glucose metabolism measured by continuous glucose monitoring (CGM). METHODS: This was a single-center, open-label, observational study. From January 2017 to October 2017, 20 GD patients with normal glucose metabolism and 24 healthy control subjects were recruited. Serum samples were obtained at 0, 30, and 120 min after oral glucose loading for glucose, insulin, and C-peptide level measurements. Fasting plasma fasting free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone concentrations were also detected. All participants were subjected to a 3-day CGM after baseline data were collected. The primary endpoint was the difference in the mean amplitude of the glycemic excursions between the two groups. RESULTS: Compared with the healthy subjects, the GD patients had higher mean amplitude of glycemic excursions (MAGE) (P < 0.01). Multiple linear stepwise regression analysis showed that FT4 level was an independent factor for the MAGE. Interestingly, the GD patients had a significant prolongation in the time to peak glucose, especially after breakfast (P < 0.01), and the elevation in the incremental area under the curve of glucose after breakfast till 4 hours later. CONCLUSIONS: Uncontrolled GD patients with normal glucose metabolism had a greater GV, and the FT4 level may contributed to the increased GV.

Glucose metabolism before and after radioiodine therapy of a patient with Graves' disease: Assessment by continuous glucose monitoring.

Hyperthyroidism causes impaired glucose tolerance, insulin resistance (IR) and insulin secretion. However, the glucose variability affected by thyroid dysfunction remains unclear. Glucose variability was assessed by continuous glucose monitoring (CGM) in a non-diabetic patient with Graves' disease (GD), to the best of our knowledge, for the first time. A 28-year-old man with GD, who had been taking methimazole for 4 years, was treated with radioiodine on August 17th 2016. Although the patient exhibited normal glycated hemoglobin (HbA1c; 5.3%) and blood glucose values during the oral glucose tolerance test (OGTT; fasting and 120 min blood glucose were 5.38 and 6.39 mmol/l, respectively) before radioiodine therapy, CGM exhibited high 24 h mean glucose and nocturnal hyperglycemia. An increased fasting insulin level, suppressed levels of blood glucagon and high homeostatic model assessment of IR were also observed. The disordered glucose metabolism improved as soon as the patient's thyroid function turned to hypothyroidism 4 months after radioiodine therapy. The glucose intolerance in patients with hyperthyroidism, missed by the OGTT and HbA1c tests, may be more common than anticipated.

Influence of Dapagliflozin on Glycemic Variations in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

Objectives. To observe changes in blood glycemic variations and oxidative stress level before and after dapagliflozin treatment in patients with newly diagnosed T2DM. Methods. This was a randomized, double-blind, placebo-controlled, phase 3 trial. A total of 28 patients with newly diagnosed T2DM with HbA1c levels of 7.5-10.5% were randomly selected to receive dapagliflozin or placebo treatment for 24 weeks. After baseline data were collected, we analyzed glycemic variations and plasma 8-iso PGF2α level at baseline and at the endpoint. Primary outcome was the changes of mean amplitude glycemic excursion (MAGE) within groups. Results. After 24-week dapagliflozin therapy, our data showed the significant improvement of MAGE with dapagliflozin therapy (P = 0.010). Compared with control group, patients in dapagliflozin group exhibited reduction in 24-hour MBG (P = 0.026) and lower mean plasma glucose concentrations, especially during periods from 2400 to 0200 and 1300 to 1800 (P < 0.05, resp.). In addition, plasma 8-iso PGF2α level was notably decreased in the treatment group compared to the control group (P = 0.034). Conclusions. In conclusion, this study shows the ability of dapagliflozin to improve glycemic variations and associate with reduction of oxidative stress in patients with T2DM, which may benefit the cardiovascular system.

Effect of exenatide on inflammatory and oxidative stress markers in patients with type 2 diabetes mellitus.

AIM: This study was designed to determine the effect of exenatide on inflammatory and oxidative stress markers in type 2 diabetes mellitus (T2DM) patients who were suboptimally controlled with metformin and/or sulfonylurea. SUBJECTS AND METHODS: Twenty-three patients with T2DM with inadequate glucose control were randomly divided into two groups: exenatide group (E group) (12 patients, 5 µg b.d. × 4 weeks followed by 10 µg b.d. × 12 weeks) and placebo group (P group) (11 patients). Glycosylated hemoglobin (HbA1c), the seven-point glucose profile, daily mean glucose, and glycemic excursion were determined. The effects of exenatide on 8-iso-prostaglandin F2α (PGF2α), monocyte chemoattractant protein-1 (MCP-1), and high-sensitivity C-reactive protein (hs-CRP) were investigated. RESULTS: Exenatide treatment reduced body weight and body mass index (BMI) and improved HbA1c, the seven-point glucose profile, and daily mean glucose compared with placebo (P < 0.05). Limited glycemic excursion was found in the E group compared with the P group (P < 0.05), including a smaller SD and postprandial glucose excursion. In addition, the oxidative stress maker PGF2α was significantly reduced by exenatide treatment (P < 0.05). The inflammatory markers hs-CRP and MCP-1 were also significantly reduced in the E group compared with the P group (P < 0.05). PGF2α was significantly correlated with glycemic excursion (P < 0.05), whereas MCP-1 was significantly correlated with body weight, BMI, glycemic excursion, and HbA1c (P < 0.05 for all). CONCLUSIONS: Exenatide treatment reduced patient body weight and BMI, improved HbA1c and the seven-point glucose profile, reduced daily mean glucose, limited glycemic excursion, and reduced oxidative stress and inflammatory markers in patients of T2DM having inadequate glucose control.

Use of plastic valve in cholangiojunostomy / 中国普通外科杂志

Reflux cholangitis is a common complicatian follawing cholangio-jejunostomy,During a period between July 1981 and June 1994 the authors have performed plastic valve in 116 cases undergo- ing Cholangrojunostomy adding a plastic valve to each of three forms of cholang iojejunostomy that was Y-shape,loop-shape,and interposition-shape in Order tO prevent reflux.There was no inhospital mor- tality and fistula,and symptoms related to biliary tract disappeared in 92 cases(79.3%)during fouow- up.