Hba1C Control And Cost-Effectiveness in Patients With Type 2 Diabetes Mellitus Initiated On Canagliflozin or A Glucagon-Like Peptide 1 Receptor Agonist in A Real-World Setting

Objective: To compare glycated hemoglobin (HbA1c) control and medication costs between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a glucagon-like peptide 1 receptor agonist (GLP-1 RA) in a real-world setting.Methods: Adults with T2DM newly initiated on CANA or a GLP-1 RA (index date) were identified from IQVIA™ Real-World Data Electronic Medical Records U.S. database (March 29, 2012–April 30, 2016). Inverse probability of treatment weighting accounted for differences in baseline characteristics. HbA1c levels at 3-month intervals were compared using generalized estimating equations. Medication costs used wholesale acquisition costs.Results: For both cohorts (CANA: n = 11,435; GLP-1 RA: n = 11,582), HbA1c levels decreased at 3 months postindex and remained lower through 30 months. Absolute changes in mean HbA1c from index to 3 months postindex for CANA and GLP-1 RA were -1.16% and -1.21% (patients with baseline HbA1c ≥7% [53 mmol/mol]); -1.54% and -1.51% (patients with baseline HbA1c ≥8% [64 mmol/mol]); and -2.13% and -1.99% (patients with baseline HbA1c ≥9% [75 mmol/mol]), respectively. Postindex, CANA patients with baseline HbA1c ≥7% had similar HbA1c levels at each interval versus GLP-1 RA patients, except 9 months (mean HbA1c, 7.75% [61 mmol/mol] vs. 7.86% [62 mmol/mol]; P = .0305). CANA patients with baseline HbA1c ≥8% and ≥9% had consistently lower HbA1c numerically versus GLP-1 RA patients and statistically lower HbA1c at 9 (baseline HbA1c ≥8% or ≥9%), 27, and 30 months (baseline HbA1c ≥9%). Continuous 12-month medication cost $3,326 less for CANA versus GLP-1 RA.Conclusion: This retrospective study demonstrated a similar evolution of HbA1c levels among CANA and GLP-1 RA patients in a real-world setting. Lower medication costs suggest CANA is economically dominant over GLP-1 RA (similar effectiveness, lower cost).Abbreviations:AHA = antihyperglycemic agentBMI = body mass indexCANA = canagliflozin 300 mgDCSI = diabetes complications severity indexeGFR = estimated glomerular filtration rateEMR = electronic medical recordGLP-1 RA = glucagon-like peptide 1 receptor agonistHbA1c = glycated hemoglobinICD-9-CM = International Classification of Diseases–Ninth Revision–Clinical ModificationICD-10-CM = International Classification of Diseases–Tenth Revision–Clinical ModificationIPTW = inverse probability of treatment weightingITT = intent-to-treatMPR = medication possession ratioPDC = proportion of days coveredPS = propensity scorePSM = propensity score matchingQuan-CCI = Quan-Charlson comorbidity indexSGLT2 = sodium-glucose cotransporter 2T2DM = type 2 diabetes mellitusWAC = wholesale acquisition cost     

Predictors Of Biochemical Remission And Recurrence After Surgical And Radiation Treatments Of Cushing Disease: A Systematic Review And Meta-Analysis

Objective: We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease.Methods: We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs).Results: First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive–adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence.Conclusion: First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.Abbreviations:ACTH = adrenocorticotropic hormoneMRI = magnetic resonance imagingRS = radiosurgeryRT = radiotherapySC = serum cortisolTSS = transsphenoidal surgeryUFC = urinary free cortisol     

The Effects of Perioperative Dexamethasone on Glycemic Control and Postoperative Outcomes

Objective: Perioperative glucocorticoids are commonly given to reduce pain and nausea in patients undergoing surgery. However, the glycemic effects of steroids and the potential effects on morbidity and mortality have not been systematically evaluated. This study investigated the association between perioperative dexamethasone and postoperative blood glucose, hospital length of stay (LOS), readmission rates, and 90-day survival.Methods: Data from 4,800 consecutive orthopedic surgery patients who underwent surgery between 2000 and 2016 within a single health system were analyzed retrospectively.Results: Patients with and without diabetes mellitus (DM) who were given a single dose of dexamethasone had higher rates of hyperglycemia during the first 24 hours after surgery as compared to those who did not receive dexamethasone (hazard ratio [HR] was 1.81, and 95% confidence interval [CI] was [1.46, 2.24] for the DM cohort; HR 2.34, 95% CI [1.66, 3.29] for the nonDM cohort). LOS was nearly 1 day shorter in patients who received dexamethasone (geometric mean ratio [GMR] 0.79, 95% CI [0.75, 0.83] for patients with DM; GMR 0.75, 95% CI [0.72, 0.79] for patients without DM), and there was no difference in 90-day readmission rates. In patients without DM, dexamethasone was associated with a higher 90-day overall survival (99.07% versus 96.90%; P = .004).Conclusion: In patients with and without DM who undergo orthopedic surgery, perioperative dexamethasone was associated with a transiently higher risk of hyperglycemia. However, dexamethasone treatment was associated with a shorter LOS in patients with and without DM, and a higher overall 90-day survival rate in patients without DM, compared to patients who did not receive dexamethasone.Abbreviations: BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; DM = diabetes mellitus; GMR = geometric mean ratio; HR = hazard ratio; IV = intravenous; LOS = length of stay; POD = postoperative day     

Pituitary Imaging By Mri and its Correlation with Biochemical Parameters in the Evaluation of Men with Hypogonadotropic Hypogonadism

Objective: A significant ambiguity still remains about which patient deserves a magnetic resonance imaging (MRI) scan of the pituitary during evaluation of hypogonadotropic hypogonadism (HH) in men.Methods: Retrospective case series of 175 men with HH referred over 6 years.Results: A total of 49.7% of men had total testosterone (TT) levels lower than the Endocrine Society threshold of 5.2 nmol/L. One-hundred forty-two patients (81.2%) had normal appearance of pituitary MRI, whereas others had different spectrum of abnormalities (empty sella &lsqb;n = 16], macroadenoma &lsqb;n = 8], microadenoma &lsqb;n = 8], and pituitary cyst &lsqb;n = 1]). In men with TT in the lowest quartile, MRI pituitary findings were not significantly different from men in the remaining quartiles (P = .50). Patients with raised prolactin had higher number of abnormal MRI findings (38.9% vs. 13.7%; P = .0014) and adenomatous lesions (macro and micro) (27.8% vs. 4.3%; P = .01) in comparison to men with normal prolactin. The prolactin levels (median &lsqb;interquartile range]) were highest in men with macroadenomas in both groups (9,950 &lsqb;915]; P = .007 and 300 &lsqb;68.0] mU/L; P = .02, respectively), with concomitant lower levels of other pituitary hormones. Multivariate logistic regression showed an association of abnormal pituitary MRI with insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) (odds ratio &lsqb;OR], 1.78 &lsqb;95% confidence interval (CI), 1.15 to 2.77]; P = .009) and prolactin (OR, 1.00 &lsqb;95% CI, 1.00 to 1.03]; P = .01).Conclusion: MRI of the pituitary is not warranted in all patients with HH, as the yield of identifiable abnormalities is quite low. Anatomic lesions are likely to be present only when low levels of TT (<5.2 nmol/L) are found concomitantly with high levels of prolactin and/or low IGF-1 SDS.Abbreviations: CI = confidence interval; FT4 = free thyroxine; GH = growth hormone; HH = hypogonadotropic hypogonadism; IGF-1 = insulin-like growth factor; LH = luteinizing hormone; MRI = magnetic resonance imaging; OR = odds ratio; SDS = standard deviation score; TSH = thyroid-stimulating hormone; TT = total testosterone     

Efficacy and Safety of Ideglira in Older Patients with Type 2 Diabetes

Objective: The efficacy and safety of insulin degludec/liraglutide (IDegLira) in older patients has not yet been reported. This analysis aimed to evaluate the efficacy and safety of IDegLira in patients aged ≥65 years.Methods: A post hoc analysis compared results of patients aged ≥65 versus <65 years from DUAL II, III, and V. These were 26-week, phase 3, randomized, twoarm parallel, treat-to-target trials in patients already taking injectable glucose-lowering agents. We evaluated 311 patients aged <65 and 87 patients aged ≥65 years from DUAL II, 326 patients <65 years and 112 patients ≥65 years from DUAL III, and 412 patients <65 years and 145 patients ≥65 years from DUAL V. Patients were randomized to IDegLira or insulin degludec (DUAL II), IDegLira or unchanged glucagon-like peptide 1–receptor agonist (GLP-1RA) (DUAL III), or IDegLira or IGlar U100 (DUAL V).Results: In patients ≥65 years, hemoglobin A1C decreased to a greater extent with IDegLira than with comparators (estimated treatment differences, -1.0% &lsqb;-1.5; -0.6]_{95% confidence interval &lsqb;CI]}, -0.8% &lsqb;-1.0; -0.5]_{95% CI}, and -0.9% &lsqb;-1.3; -0.6]95%CI) for DUAL II, V, and III, respectively; all P<.001). These mirrored results of patients <65 years of age. Hypoglycemia rates were lower with IDegLira versus basal insulin and higher versus unchanged GLP-1RA (estimated rate ratios, 0.5 &lsqb;0.2; 1.6]_{95% CI} &lsqb;P = .242]; 0.3 &lsqb;0.1; 0.5]_{95% CI} &lsqb;P<.001], and 11.8 &lsqb;3.3; 42.8]_{95% CI} &lsqb;P<.001] for DUAL II, V, and III, respectively).Conclusion: Patients aged ≥65 years on basal insulin or GLP-1RA can improve glycemic control with IDegLira, and it is well tolerated overall.Abbreviations: A1C = hemoglobin A1C; AE = adverse event; CI = confidence interval; Degludec = insulin degludec; EOT = end of trial; ETD = estimated treatment difference; FPG = fasting plasma glucose; GLP-1RA = glucagon-like peptide 1 receptor agonist; IDegLira = insulin degludec/liraglutide; IGlar U100 = insulin glargine 100 U/mL; SU = sulfonylurea; T2D = type 2 diabetes     

Risk of Malignancy in Thyroid Cytology: The Impact of The Reclassification of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)

Objective: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We aimed to compare the risk of malignancy (ROM) of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) on fine-needle aspiration cytology (FNAC), before and after the reclassification, in a large cohort of patients.Methods: We analyzed 5,625 consecutive FNAC samples performed in 2012–2014 and selected category III (atypia of undetermined significance &lsqb;AUS]/follicular lesion of undetermined significance &lsqb;FLUS]), IV (follicular neoplasm &lsqb;FN]/suspicious for a follicular neoplasm &lsqb;SFN]), V (suspicious for malignancy &lsqb;SFM]), and VI (malignant) of the BSRTC. We reviewed the histology of operated patients and compared ROM before and after the introduction of the NIFTP category.Results: A total of 772 patients were identified and 45% underwent surgery (n = 348). There were 180 cases of AUS/FLUS (10 NIFTP), 114 cases of FN/SFN (2 NIFTP), 29 cases of SFM (3 NIFTP), and 25 cases of BSRTC VI (no NIFTP). Exclusion of NIFTP from malignant lesions resulted in a relative and absolute decrease in the ROM in AUS/FLUS (15.2% and 5.5%, respectively), FN/SFN (7.6% and 1.8%, respectively) and SFM (14.2% and 10.3%, respectively) categories. Among the NIFTP patients, 93% underwent total thyroidectomy and 20% received radioiodine.Conclusion: Reclassification of noninvasive EFVPTC as NIFTP resulted in a decrease in overall ROM, and the BSRTC categories most affected were III and V.Abbreviations: AUS = atypia of undetermined significance; BSRTC = Bethesda System for Reporting Thyroid Cytopathology; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FLUS = follicular lesion of undetermined significance; FN = follicular neoplasm; FNAC = fine-needle aspiration cytology; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma; ROM = risk of malignancy; SFM = suspicious for malignancy; SFN = suspicious for a follicular neoplasm     

Bone Mineral Density In Patients With Addison Disease On Replacement Therapy With Prednisolone

Objective: In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement.Methods: Forty-one consecutive patients (31 males, age &lsqb;mean ± SD] 50.9 ± 13.0 years), receiving prednisolone (hydrocortisone equivalent &lsqb;HCE] 13.0 ± 3.0 mg/m²) for 104 ± 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677).Results: Among males, BMD Z-scores (mean &lsqb;95% confidence interval {CI}]) at lumbar spine (-0.42 &lsqb;-0.80, -0.04]), femoral neck (-0.50 &lsqb;-0.95, -0.06]) and total hip (-0.58 &lsqb;-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score ≤-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD.Conclusions: Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites.Abbreviations:ACTH = adrenocorticotropic hormoneBAP = bone-specific alkaline phosphataseBMD = bone mineral densityBMI = body mass indexCI = confidence intervalHCE = hydrocortisone equivalent25 (OH) D3 = 25-hydroxyvitamin D3PAI = primary adrenal insufficiency     

Total Body Adiposity,Triglycerides, and Leg Fat are Independent Risk Factors for Diabetic Peripheral Neuropathy in Chinese Patients with type 2 Diabetes Mellitus

Objective: To evaluate the risk factors associated with diabetic peripheral neuropathy (DPN) in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: Between January 2014 and December 2017, 107 participants who had obesity with T2DM and 349 participants who had normal weight with T2DM, matched for age, sex, and duration of diabetes, were recruited. The clinical and biochemical parameters were measured in each patient. DPN was diagnosed based on neuropathy symptom score and neuropathy deficit score. Motor and sensory nerve conduction velocities were measured by electromyography. Body fat mass was estimated by dual-energy X-ray absorptiometry, while hepatic steatosis was evaluated by ultrasonography.Results: The group with obesity had a significant higher prevalence of DPN (66.62%) than that (46.99%) of the group with normal weight. Compared to the patients with normal weight, the sural sensory nerve in the right lower limbs of the patients with obesity was more susceptible to damage. Hypertriglyceridemia in the patients with obesity was a significant independent risk factor for DPN (odds ratio &lsqb;OR], 3.90 &lsqb;95% confidence interval (CI), 1.01 to 15.02]; P = .04), while the duration of diabetes (OR, 1.33 &lsqb;95% CI, 1.07 to 1.65]; P<.01) and leg subcutaneous fat mass (OR, 0.72 &lsqb;95% CI, 0.57 to 0.90]; P<.01) in the patients with normal weight were independent risk factors for DPN. The presence of obesity alone in patients with T2DM could predict high DPN risk (OR, 3.09 &lsqb;95% CI, 1.11 to 8.65]; P = .04).Conclusion: Reducing total body adiposity and triglyceride levels, as well as avoiding leg subcutaneous fat atrophy, could be new prevention strategies for DPN in Chinese patients with T2DM.Abbreviations: ALB = albumin; ALT = alanine transaminase; AST = aspartate transaminase; AUC = area under the curve; AUCc-p/AUCglu = AUC of C-peptide/AUC of glucose; BMI = body mass index; BP = blood pressure; CI = confidence interval; Cr = creatinine; DBP = diastolic blood pressure; DPN = diabetic peripheral neuropathy; FC-P = fasting C-peptide; FPG = fasting plasma glucose; FFA = free fatty acid; γ-GGT = γ-glutamyl transferase; HbA1c = glycated hemoglobin A1c; HDL-C = high-density-lipoprotein cholesterol; ISI = insulin sensitivity index; ISSI-2 = insulin secretion-sensitivity index-2; LDL-C = low-density-lipoprotein cholesterol; MNCS = motor nerve conduction velocity; OGTT = oral glucose tolerance test; PG = plasma glucose; SAT = subcutaneous adipose tissue; SBP = systolic blood pressure; SNCS = sensory nerve conduction velocity; T2DM = type 2 diabetes mellitus; TC = total cholesterol; TG = triglyceride; UA = uric acid; VAT = visceral adipose tissue; WC = waist circumference     

Side Effects of PTU and MMI in the Treatment of Hyperthyroidism: A Systematic Review and Meta-Analysis

Objective: The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism.Methods: Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared.Results: Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio &lsqb;OR], 2.40; 95% confidence interval &lsqb;CI], 1.16 to 4.96; P = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; P<.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; P = .003).Conclusion: The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy.Abbreviations: ALT = alanine aminotransferase; ATD = antithyroid drug; CI = confidence interval; CMZ = carbimazole; GD = Graves disease; MMI = methimazole; MTU = methylthiouracil; NOS = Newcastle-Ottawa Scale; OR = odds ratio; PTU = propylthiouracil; RAI = radioactive iodine     

Timing of Radioactive Iodine Therapy does not Impact Overall Survival in High-Risk Papillary Thyroid Carcinoma

Objective: Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC.Methods: The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed.Results: There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98–1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75–1.58, P = .662).Conclusion: The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC.Abbreviations:CI = confidence intervalCLNM = cervical lymph node metastasisFVPTC = follicular variant papillary thyroid carcinomaHR = hazard ratioKM = Kaplan-MeierNCDB = National Cancer Data BaseOS = overall survivalPTC = papillary thyroid carcinomaRAI = radioactive iodine     

Association of Thyroid Function with Posttraumatic Stress Disorder: a Systematic Review and Meta-Analysis

Objective: To conduct a systematic review and meta-analysis describing the association of thyroid function with posttraumatic stress disorder (PTSD) in adults.Methods: The authors conducted a comprehensive search from databases’ inception to July 20, 2018. The meta-analysis included studies that reported mean values and standard deviation (SD) of thyroid hormone levels (thyroid-stimulating hormone &lsqb;TSH], free thyroxine &lsqb;FT4], free triiodothyronine &lsqb;FT3], total T4 &lsqb;TT4], and total T3 &lsqb;TT3]) in patients with PTSD compared with controls. Five reviewers worked independently, in duplicate, to determine study inclusion, extract data, and assess risk of bias. The mean value and SD of the thyroid function tests were used to calculate the mean difference for each variable. Random-effects models for meta-analyses were applied.Results: The meta-analysis included 10 observational studies at low-to-moderate risk of bias. Studies included 674 adults (373 PTSD, 301 controls). The meta-analytic estimates showed higher levels of FT3 (+0.28 pg/mL; P = .001) and TT3 (+18.90 ng/dL; P = .005) in patients with PTSD compared to controls. There were no differences in TSH, FT4, or TT4 levels between groups. In the subgroup analysis, patients with combat-related PTSD still had higher FT3 (+0.36 pg/mL; P = .0004) and higher TT3 (+31.62 ng/dL; P<.00001) compared with controls. Conversely, patients with non–combat-related PTSD did not have differences in FT3 or TT3 levels compared with controls.Conclusion: There is scarce evidence regarding the association of thyroid disorders with PTSD. These findings add to the growing literature suggesting that thyroid function changes may be associated with PTSD.     

Adding Rapid-Acting Insulin or Glp-1 Receptor Agonist to Basal Insulin: Outcomes in A Community Setting

ObjectiveTo evaluate real-world outcomes in patients with type 2 diabetes mellitus (T2DM) receiving basal insulin who initiate add-on therapy with a rapid-acting insulin (RAI) or a glucagon-like peptide 1 (GLP-1) receptor agonist.MethodsData were extracted retrospectively from a U.S. health claims database. Adults with T2DM on basal insulin who added an RAI (basal + RAI) or GLP-1 receptor agonist (basal + GLP-1) were included. Propensity score matching (with a 1 up to 3 ratio) was used to control for differences in baseline demographics, clinical characteristics, and health resource utilization. Endpoints included prevalence of hypoglycemia, pancreatic events, all-cause and diabetes-related resource utilization, and costs at 1-year follow-up.ResultsOverall, 6,718 matched patients were included: 5,013 basal + RAI and 1,705 basal + GLP1. Patients in both groups experienced a similar proportion of any hypoglycemic event (P = .4079). Hypoglycemic events leading to hospitalization were higher in the basal + RAI cohort (2.7% vs. 1.8%; P = .0444). The basal + GLP-1 cohort experienced fewer all-cause (13.55% vs. 18.61%; P < .0001) and diabetes-related hospitalizations (11.79% vs. 15.68%; P < .0001). The basal + GLP-1 cohort had lower total all-cause health care costs ($18,413 vs. $20,821; P = .0002) but similar diabetes-related costs ($9,134 vs. $8,985; P < .0001) compared with the basal + RAI cohort.ConclusionsAdd-on therapy with a GLP-1 receptor agonist in T2DM patients receiving basal insulin was associated with fewer hospitalizations and lower total all-cause costs compared with add-on therapy using an RAI and could be considered as an alternative to an RAI in certain patients with T2DM who do not achieve effective glycemic control with basal insulin. (Endocr Pract. 2015; 21:68-76)     

Clinical Recognition and Management of Patients with Prediabetes

Objective: Early identification and management of prediabetes is critical to prevent progression to diabetes. We aimed to assess whether prediabetes is appropriately recognized and managed among patients with impaired fasting glucose (IFG).Methods: We carried out an observational study of Olmsted County residents evaluated at the Mayo Clinic between 1999–2017. We randomly selected 108 subjects with biochemical criteria of IFG and 105 normoglycemic subjects. We reviewed their health records at baseline (1999–2004) and during follow up (2005–2017) collecting demographic and clinical data including vitals, diagnoses, laboratory, and medications associated with cardiovascular comorbidities. The main outcome was documentation of any recognition of prediabetes and management recommendations (lifestyle changes and/or medications).Results: At baseline (1999–2004), 26.85% (29/108) of subjects with IFG were recognized as having prediabetes, and of these 75.86% (22/29) received management recommendations with 6.9% (2/29) getting metformin. During follow-up (2005–2017), 26.67% (28/105) of initial cohort of normoglycemic subjects developed incident IFG and of these, 85.71% (24/28) were recognized as having prediabetes, and 58.33% (14/24) received management recommendations. During the entire study period, 62.50% (85/136) were recognized as having prediabetes of which 75.29% (64/85) had documented management recommendations. High body mass index (BMI) (≥35) was associated with increased recognition (odds ratio &lsqb;OR] 3.66; confidence interval &lsqb;CI] 1.065, 12.500; P = .0395), and normal BMI (<25) was associated with a lack of recognition (OR 0.146; CI 0.189, 0.966; P = .0413).Conclusion: Despite evidence supporting the efficacy of lifestyle changes and medications in managing prediabetes, this condition is not fully recognized in routine clinical practice. Increased awareness of diagnostic criteria and appropriate management are essential to enhance diabetes prevention.Abbreviations: BMI = body mass index; CI = confidence interval; EHR = electronic health records; FBG = fasting blood glucose; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; OR = odds ratio     

High Ratio of Early Postoperative Calcitonin to Preoperative Calcitonin Could be a Novel Indicator of Poor Prognosis in Patients with Biochemical Incomplete Responses in Sporadic Medullary Thyroid Cancer

Objective: In a cohort of medullary thyroid cancer (MTC) patients with biochemical incomplete responses, 37 to 48% developed structural persistent disease; however, few indictors were available to distinguish those patients who were more likely to develop structural disease. We hypothesized that the relationship between preoperative calcitonin (Ctn) and postoperative Ctn (within 3 days after surgery) could be used to predict early prognosis of these patients.Methods: A total of 92 sporadic MTC patients were enrolled in this study. Our team proposed a novel indicator of structural persistent MTC called the calcitonin ratio (CR; CR = postoperative Ctn/preoperative Ctn). Cox regression models and the Kaplan-Meier method were used to evaluate the prognostic capability of CR. The area under the time-dependent receiver-operating characteristic curves (AUC) and the Harrell concordance index (C-index) were used for analysis.Results: The cutoff CR value used to determine MTC prognosis was 0.15. Multivariate Cox analysis revealed that CR (hazard ratio &lsqb;HR]: 22.974, 95% confidence interval &lsqb;CI]: 3.259 to 161.959, P = .002), tumor-node-metastasis (HR: 3.968, 95% CI: 1.360 to 21.857; P = .031), and multifocality (HR: 8.466, 95% CI: 1.286 to 55.716; P = .026) independently correlated with MTC prognosis. Kaplan-Meier survival curves demonstrated a lower proportion with structural persistent disease in patients with CR <0.15 (P<.001). The 3, 5, and 10-year AUC values were 0.798, 0.752, and 0.743, respectively. The C-index of CR was 0.788 (95% CI: 0.763 to 0.813).Conclusion: In this study, CR was identified as a sensitive and specific risk stratification marker for patients with biochemical incomplete responses in sporadic MTC.Abbreviations: ATA = American Thyroid Association; AUC = area under curve; CEA = carcinoembryonic antigen; CR = calcitonin ratio; Ctn = calcitonin; HR = hazard ratio; MTC = medullary thyroid cancer; ROC = receiver operating characteristic; TNM = tumor-node-metastasis     

The Influence of Surgical Extent and Parafibromin Staining on The Outcome of Parathyroid Carcinoma: 20-Year Experience From a Single Institute

Objective: Parathyroid carcinoma (PC) is a rare endocrine malignancy with a poor prognosis. The optimal surgical procedure and prognostic factors for PC remain controversial.Methods: Clinical information and parafibromin staining results from 53 patients with PC were reviewed retrospectively from 1997 to 2018. Immunohistochemical staining for parafibromin was performed on formalin-fixed, paraffin-embedded tissue samples. The influence of clinical parameters, surgical procedure, and parafibromin staining of tumor tissues on prognosis were evaluated.Results: A total of 53 patients with PC were enrolled in this study. The male to female ratio was 1.94:1. En bloc resection was performed as initial surgery for 18 patients (34.0%), and 35 patients (66.0%) underwent local resection. Parafibromin staining was negative in the tumor tissues of 24 PC patients (45.3%). Thirty-three patients suffered from local recurrence or distant metastasis, and overall mortality was 16/53 at a median follow-up time of 80 months (range, 7 to 282 months). Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio &lsqb;HR], 4.13; 95% confidence interval &lsqb;CI], 1.73 to 9.87; P = .001) was related to recurrence or metastasis and that age >50 years (HR, 5.66; 95% CI, 1.58 to 20.31; P = .008) was related to mortality. The extent of resection was not related to recurrence or overall survival.Conclusion: The majority of PC patients have a relatively long survival with multiple recurrences. Absence of parafibromin staining was a factor that influenced PC recurrence. The main factor influencing PC outcomes may be the biological characteristics rather than surgical extent.Abbreviations: CI = confidence interval; DFS = disease-free survival; HR = hazard ratio; OS = overall survival; PC = parathyroid carcinoma; WHO = World Health Organization     

Case Finding for Hypothyroidism Should Include Type 2 Diabetes and Metabolic Syndrome Patients: A Latin American Thyroid Society (LATS) Position Statement

Objective: Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients.Methods: A search was made in PubMed using the following terms: “hypothyroidism” AND “diabetes” OR “metabolic syndrome.” The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected.Results: The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio &lsqb;OR], 3.45; 95% confidence interval &lsqb;CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60).Conclusion: Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients.Abbreviations: CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Dysregulation Of The Hypothalamic-Pituitary-Adrenal Axis Increases Central Body Fat Accumulation In Males Affected By Diabetes Mellitus And Late-Onset Hypogonadism

Objective: Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation on body composition in men affected by DM-associated late-onset hypogonadism (LOH).Methods: Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered.Results: The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 ± 0.27 ng/mL versus 2.31 ± 0.26 ng/mL; P = .003) and free (39.5 ± 6.44 pg/mL versus 46.8 ± 7.23 pg/mL; P = .005) (median, 38.7 &lsqb;interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 &lsqb;interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH-LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized β = 10.988 &lsqb;P<.001]; β = 1.156 &lsqb;P<.001]; β = -7.675 &lsqb;P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH.Conclusion: Dysregulation of the HPA axis in LOH-associated DM seems to be involved in abdominal fat accumulation.Abbreviations:ACTH = adrenocorticotropic hormoneAUC = area under the curveCRH = corticotropin-releasing hormoneCT = computed tomographyDEXA = dual-energy X-ray absorptiometryDM = diabetes mellitusFH = functional hypercortisolismFH-LOH = subjects affected by functional hypercortisolismFSH = follicle-stimulating hormoneHPA = hypothalamic-pituitary-adrenalLH = luteinizing hormoneLOH = late-onset hypogonadismN-LOH = subjects not affected by functional hypercortisolismOST = overnight low-dose dexamethasone suppression testSHBG = sex hormone–binding globulinUFC = urinary free cortisol     

Associations Between Vitamin D and Microvascular Complications in Middle-Aged And Elderly Diabetic Patients

Objective: The objective of this cross-sectional study was to investigate the association of serum 25-hydroxyvitamin D (25&lsqb;OH]D) levels with estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and the prevalence of diabetic retinopathy (DR) in Chinese diabetic adults.Methods: A total of 4,767 diabetic participants were enrolled from seven communities in Shanghai, China, in 2018. Participants underwent several examinations, which included the measurement of anthropometric parameters, blood pressure, glucose, lipid profiles, 25(OH)D, and ACR. DR was detected based on high-quality fundus photographs and remotely read by ophthalmologists.Results: Compared with the first 25(OH)D quartile, participants in the fourth quartile had a lower prevalence of high ACR (odds ratio &lsqb;OR], 0.77; 95% confidence interval &lsqb;CI], 0.61 to 0.96) (P for trend <.01). No association was found between 25(OH)D levels and eGFR. For DR, the OR (95% CI) for DR ranging from 0 to 4 in ordinal logistic regression associated with 25(OH)D was 0.62 (0.47 to 0.82) for the fourth 25(OH)D quartile (P for trend <.01) compared with the first quartile. These associations were all fully adjusted for confounding factors.Conclusion: Lower serum 25(OH)D concentration is significantly associated with increased ACR and higher prevalence of DR in middle-aged and elderly diabetic adults. However, the possibility of a causal relationship between 25(OH)D deficiency and diabetic microvascular complications remains to be demonstrated.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; ACR = albumin/creatinine ratio; BMI = body mass index; CI = confidence interval; DKD = diabetic kidney disease; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; OR = odds ratio; T2DM = type 2 diabetes mellitus     

Delayed 131-I First Treatment After Surgery has No Impact on the Median Term Outcome of Patients with Intermediate Risk Differentiated Thyroid Cancer

Objective: In intermediate risk (IR) differentiated thyroid cancer (DTC) patients, selective use of radioiodine (131-I) for remnant ablation and/or as adjuvant therapy (RRA) is advocated. The recently suggested postoperative evaluation could delay the use of RRA. The aim of this study was to evaluate if a delayed RRA can worsen the clinical outcome of IR-DTC patients.Methods: Four hundred and fourteen consecutive IR-DTC patients were divided according to the time elapsed from surgery to RRA, <6 months (group A, 186/414 &lsqb;44.9%]), or ≥6 months (group B, 228/414 &lsqb;55.1%]). Clinical and biochemical data were collected, and clinical outcome was analyzed at the first evaluation (EV) after RRA (first-EV) and after a median of 6 years of follow-up (last-EV).Results: No difference in the clinical outcome of group A and B was found. Since a different activity of 131-I could have an impact on the outcome, we separately analyzed the groups according to the 131-I activity (low-activity group: 1,110 MBq/30 mCi &lsqb;n = 320], and high-activity group: 3,700 MBq/100 mCi &lsqb;n = 94]), further subdivided according to the time elapsed from surgery to RRA. No major differences were found in both the low- and high-activity groups when comparing the features of their subgroups A and B, as far as in their clinical outcome.Conclusion: The time elapsed between surgery and the first 131-I treatment does not influence the clinical outcome of IR-DTC patients. This finding allows a more relaxed attitude in the decision making process whether to perform the RRA in IR-DTC cases in which a selective use of 131-I is recommended.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; EV = evaluation; HR = high risk; 131-I = radioiodine; IR = intermediate risk; LR = low risk; rhTSH = recombinant human thyroid-stimulating hormone; RRA = radioiodine for remnant ablation; Tg = thyroglobulin; TgAb = thyroglobulin autoantibody; US = ultrasound     

Greater Low-Density Lipoprotein Cholesterol Variability Increases the Risk of Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

Objective: Variability in lipid levels has been associated with poor cardiovascular outcomes in patients with coronary artery disease. The aim of this study was to investigate whether low-density lipoprotein cholesterol (LDLC) variability can be used to predict cardiovascular events in patients with type 2 diabetes mellitus (DM).Methods: A total of 5,354 patients with type 2 DM were enrolled in this study. Cardiovascular events including peripheral arterial disease, coronary artery disease, stroke, and cardiovascular death were defined as the study endpoints, and standard deviations of lipid levels were used to define intra-individual lipid variability.Results: Univariate Cox proportional hazards analysis showed that LDL-C standard deviation (hazard ratio &lsqb;HR] = 1.016; 95% confidence interval &lsqb;CI] = 1.006 to 1.022; P<.001) was associated with a higher risk of cardiovascular events. Multivariate Cox proportional hazards analysis showed that an increase in LDL-C standard deviation significantly increased the risk of cardiovascular events (HR = 1.063; 95% CI = 1.025 to 1.102; P = .01). Kaplan-Meier analysis of cardiovascular event-free survival showed that the patients in tertiles 2 and 3 of the standard deviation of LDL-C had worse cardiovascular event-free survival compared to those in tertile 1.Conclusion: Variability in LDL-C could predict cardiovascular events in the patients with type 2 DM in this study.Abbreviations: CAD = coronary artery disease; CI = confidence interval; CVD = cardiovascular disease; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; HbA1c = glycosylated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; KMUHRD = Kaohsiung Medical University Hospital Research Database; LDL-C = low-density lipoprotein cholesterol; SD = standard deviation; UACR = urine albumin to creatinine ratio