Relationship between plasma copeptin levels and complications of community-acquired pneumonia in preschool children

High plasma copeptin level has been associated with clinical outcomes after acute illness. The present study was undertaken to investigate the plasma copeptin concentrations in preschool children with community-acquired pneumonia (CAP) and to analyze the correlations of copeptin with CAP-related complications and pleural effusion. Plasma copeptin concentrations of 100 healthy children and 165 preschool children with CAP were measured. 35 children (21.2%) presented with complicated CAP and 28 children (17.0%) presented with pleural effusion. The admission copeptin levels were significantly increased in all patients (49.7 ± 21.4 pmol/L), children with complicated CAP (73.0 ± 16.9 pmol/L), those with uncomplicated CAP (43.4 ± 17.8 pmol/L), those with pleural effusion (70.9 ± 17.4 pmol/L) and those without pleural effusion (45.3 ± 19.5 pmol/L) compared with healthy control individuals (9.0 ± 2.7 pmol/L, all P < 0.001). Multivariate logistic regression analysis showed that plasma copeptin levels were independently related to CAP-related complications (odds ratio 1.214, 95% confidence interval 1.104–1.872, P < 0.001) and pleural effusion (odds ratio 1.226, 95% confidence interval 1.109–1.917, P < 0.001). A receiver operating characteristic curve analysis showed plasma copeptin level better predicted CAP-related complications (area under curve 0.876, 95% confidence interval 0.815–0.922) and pleural effusion (area under curve 0.831, 95% confidence interval 0.765–0.885). Thus, plasma copeptin level may represent a novel biomarker for predicting CAP-related complications in preschool children.     

Eating and Glycemic Control Among Critically Ill Patients Receiving Continuous Intravenous Insulin

Objective: Consensus guidelines recommend that intensive care unit (ICU) patients with blood glucose (BG) levels >180 mg/dL receive continuous intravenous insulin (CII). The effectiveness of CII at controlling BG levels among patients who are eating relative to those who are eating nothing by mouth (nil per os; NPO) has not been described.Methods: We conducted a retrospective cohort study of 260 adult patients (156 eating, 104 NPO) admitted to an ICU between January 1, 2014, and December 31, 2014, who received CII. Patients were excluded for a diagnosis of diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic syndrome, admission to an obstetrics service, or receiving continuous enteral or parenteral nutrition.Results: Among 22 baseline characteristics, the proportion of patients receiving glucocorticoid treatment (GCTx) (17.3% eating, 37.5% NPO; P<.001) and APACHE II score (15.0 ± 7.5 eating, 17.9 ± 7.9 NPO; P = .004) were significantly different between eating and NPO patients. There was no significant difference in the primary outcome of patient-day weighted mean BG overall (153 ± 8 mg/dL eating, 156 ± 7 mg/dL NPO; P = .73), or day-by-day BG (P = .37) adjusted for GCTx and APACHE score. Surprisingly, there was a significant difference in the distribution of BG values, with eating patients having a higher percentage of BG readings in the recommended range of 140 to 180 mg/dL. However, eating patients showed greater glucose variability (coefficient of variation 23.1 ± 1.0 eating, 21.2 ± 1.0 NPO; P = .034).Conclusion: Eating may not adversely affect BG levels of ICU patients receiving CII. Whether or not prandial insulin improves glycemic control in this setting should be studied.Abbreviations: BG = blood glucose; CII = continuous insulin infusion; CV = coefficient of variation; HbA1c = hemoglobin A1c; ICU = intensive care unit; NPO = nil per os; PDWMBG = patient day weighted mean blood glucose     

Postoperative plasma copeptin levels independently predict delirium and cognitive dysfunction after coronary artery bypass graft surgery

Copeptin can reflect individual's stress state and are correlated with poor outcome of critical illness. The occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD) is associated with worse outcome after coronary artery bypass graft (CABG) surgery. The present study aimed to investigate the ability of postoperative plasma copeptin level to predict POD and POCD in patients undergoing CABG surgery. Postoperative plasma copeptin levels of 108 patients were measured by an enzyme-linked immunosorbent assay. It was demonstrated that plasma copeptin levels were substantially higher in patients with POD than without POD (1.8 ± 0.6 ng/mL vs. 1.1 ± 0.3 ng/mL; P < 0.001) and in patients with POCD than without POCD (1.9 ± 0.6 ng/mL vs. 1.1 ± 0.4 ng/mL; P < 0.001). Plasma copeptin level and age were identified as independent predictors for POD [odds ratio (OR), 67.386; 95% confidence interval (CI), 12.031–377.426; P < 0.001 and OR, 1.202; 95% CI, 1.075–1.345; P = 0.001] and POCD (OR, 28.814; 95% CI, 7.131–116.425; P < 0.001 and OR, 1.151; 95% CI, 1.030–1.285; P = 0.003) using a multivariate analysis. For prediction of POD, the area under receiver operating characteristic curve (AUC) of the copeptin concentration (AUC, 0.883; 95% CI, 0.807–0.937) was markedly higher than that of age (AUC, 0.746; 95% CI, 0.653–0.825; P = 0.020). For prediction of POCD, the AUC of the copeptin concentration (AUC, 0.870; 95% CI, 0.792–0.927) was markedly higher than that of age (AUC, 0.735; 95% CI, 0.641–0.815; P = 0.043). Thus, postoperative plasma copeptin level may be a useful, complementary tool to predict POD and POCD in patients undergoing CABG surgery.     

Retinopathy is a Strong Determinant of Atherosclerosis in Type 2 Diabetes: Correlation with Carotid Intima Media Thickness

ObjectiveWe investigated the correlation between the severity of diabetic retinopathy (DR) and carotid intima media thickness (IMT) as a marker of atherosclerosis in patients with type 2 diabetes.MethodsThe study group consisted of 140 normo-tensive Egyptian patients (68 males and 72 females) with type 2 diabetes and DR. Carotid IMT was evaluated using high-resolution B-mode ultrasonography. DR was assessed and graded using colored fundus photography and fundus fluorescein angiography, as either nonproliferative DR (NPDR) or proliferative DR (PDR).ResultsCarotid IMT was greater in patients with PDR compared to those with NPDR (1.094 ± 0.142 mm vs. 0.842 ± 0.134 mm; P < .001). Carotid IMT showed positive correlation with diabetes duration (P < .01), systolic blood pressure (P < .001), diastolic blood pressure (P < .01), fasting blood glucose (P < .01), postprandial blood glucose (PPBG) (P < .001), glycated hemoglobin (P < .01), total cholesterol (P < .01), triglycerides (TGs) (P < .001), and DR (P < .0001). No significant difference was found between males and females in any of the studied parameters. Multiple regression analysis revealed that the determinants of carotid IMT in the studied group were age (P < .01), PPBG (P < .01), TGs (P < .001), and DR (P < .0001).ConclusionOur study proves that both NPDR and PDR are strong determinants of carotid IMT and atherosclerosis in patients with type 2 diabetes. (Endocr Pract. 2015;21:226-230)     

Plasma copeptin concentration and outcome after pediatric traumatic brain injury

Higher plasma copeptin level has been associated with poor outcomes of critical illness. The present study was undertaken to investigate the plasma copeptin concentrations in children with traumatic brain injury (TBI) and to analyze the correlation of copeptin with disease outcome. Plasma copeptin concentrations of 126 healthy children and 126 children with acute severe TBI were measured by enzyme-linked immunosorbent assay. Twenty-one patients (16.7%) died and 38 patients (30.2%) had an unfavorable outcome (Glasgow Outcome Scale score of 1–3) at 6 months. Plasma copeptin level was obviously higher in patients than in healthy children (46.2 ± 20.8 pmol/L vs. 9.6 ± 3.0 pmol/L, P < 0.001). Plasma copeptin level was identified as an independent predictor for 6-month mortality [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112–1.538, P = 0.005] and unfavorable outcome (OR 1.313, 95% CI 1.146–1.659, P = 0.003). The predictive value of copeptin was similar to that of Glasgow Coma Scale (GCS) score for 6-month mortality [area under curve (AUC) 0.832, 95% CI 0.755–0.892 vs. AUC 0.873, 95% CI 0.802–0.926, P = 0.412] and unfavorable outcome (AUC 0.863, 95% CI 0.790–0.918 vs. AUC 0.885, 95% CI 0.816–0.935, P = 0.596). Copeptin improved the AUC of GCS score for 6-month unfavorable outcome (AUC 0.929, 95% CI 0.869–0.967, P = 0.013), but not for 6-month mortality (AUC 0.887, 95% CI 0.818–0.936, P = 0.600). Thus, plasma copeptin level represents a novel biomarker for predicting 6-month clinical outcome in children with TBI.     

Vitamin D-Binding Protein in Healthy Pre- and Postmenopausal Women: Relationship with Estradiol Concentrations

Objective: To examine the relationship between endogenous serum estradiol and vitamin D–binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women.Methods: In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels.Results: Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in prethan postmenopausal women (P<.05). Serum estradiol correlated with DBP (r = 0.22; P<.01) and total 25OHD (r = 0.27; P<.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P<.05).Conclusion: Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration.Abbreviations: 25OHD = 25-hydroxyvitamin D BMI = body mass index CV = coefficient of variation DBP = vitamin D–binding protein PTH = parathyroid hormone SHBG = sex hormone–binding globulin     

Levothyroxine Replacement In Obese Hypothyroid Females After Total Thyroidectomy

Objective: Levothyroxine (LT4) replacement in hypothyroid obese patients is poorly understood. We assessed whether the LT4 regimen required to achieve euthyroidism differs between nonobese and obese hypothyroid females.Methods: We retrospectively identified nonobese and obese females who received LT4 starting with a standard dose of 1.6 μg/kg after total thyroidectomy for preoperative diagnosis of benign goiter. We examined the association between LT4 dosage required to achieve euthyroid state (thyroid-stimulating hormone [TSH] 0.4–2.5 mIU/L) and patient characteristics using linear regression models with and without adjustment for age, ethnicity, medication use, and postoperative hypoparathyroidism.Results: We identified 32 females (15 nonobese/17 obese) who achieved euthyroid state. Obese patients weighed more (104.1 ± 22.5 vs. 64.9 ± 10.0 kg, P<.0001) and required a higher final LT4 than nonobese (146 ± 38 vs. 102 ± 12 μg, P = .0002) but LT4 requirements per kg total body weight (TBW) were similar (1.60 ± 0.29 vs. 1.42 ± 0.38 μg/kg, P = .15). LT4 dose per kg ideal body weight (IBW) was higher in obese than in nonobese females (2.62 ± 0.67 vs. 1.88 ± 0.28 μg/kg, P = .0004) and this difference persisted after adjustments (P<.05). During LT4 titration, 47% and 20% of obese and nonobese patients had subnormal TSH episodes, respectively (P = .11). After taking LT4 compliance, malabsorption, and competing medication use into consideration, we found marked LT4 dose variability in obese patients. Patients who needed a mean daily LT4 dose ≤150 mg (124 ± 16 μg/day) compared with >150 μg (198 ± 4 μg/day) demonstrated lower LT4 per TBW (1.25 ± 0.18 vs. 1.84 ± 0.43 μg/kg, P = .03) and IBW (2.28 ± 0.47 vs. 3.44 ± 0.18 μg/kg, P<.0001), respectively.Conclusion: The standard approach to LT4 replacement in obese and nonobese females after thyroidectomy is imprecise. Mean daily LT4 doses in obese and nonobese patients were similar if expressed per kg TBW, though there was variability in the final LT4 among obese patients. We suggest initiating LT4 at a dose lower than that routinely recommended in obese females.Abbreviations:AACE = American Association of Clinical EndocrinologistsATA = American Thyroid AssociationBMI = body mass indexIBW = ideal body weightLT4 = levothyroxineTBW = total body weightTSH = thyroid-stimulating hormone     

High-Dose Glucocorticoid Treatment Does Not Induce Severe Hyperglycemia in Young Patients with Autoimmune Diseases by Cgms

Objective: High-dose glucocorticoids (HDG) are used in the treatment of autoimmune diseases. Glucocorticoids-induced hyperglycemia (GIH) is often described in elderly patients. In young patients with autoimmune diseases, however, the risk for GIH has not been well characterized.Methods: We recruited 24 inpatients (median age, 32 years; interquartile range, 25–42) with exacerbations of autoimmune diseases, receiving 1 to 2 mg/kg/day prednisone or equivalent methylprednisone. Fourteen subjects were naïve to glucocorticoids (group 1) and 10 subjects were on glucocorticoid maintenance (≤15 mg/day prednisone at least 3 months) (group 2) prior to HDG. All subjects were monitored by continuous glucose monitoring system (CGMS) for 3 days.Results: GIH developed in 21 (91%) subjects, 11/13 in group 1 and 10/10 in group 2. The main peak of glucose excursion (128.7 ± 6.4 mg/dL, group 1; 143.9 ± 10.0 mg/dL, group 2) occurred at 2 to 3 pm. Another peak occurred before sleep. Two-hour mean postprandial glucose levels were normal in both groups: breakfast, 105.0 ± 28.4 versus 125.6 ± 24.4 mg/dL, P = .065; lunch, 115.7 ± 21.1 versus 135.9 ± 29.0 mg/dL, P = .082; dinner, 122.8 ± 18.5 versus 137.8 ± 26.4 mg/dL, P = .144 in groups 1 and 2, respectively. There was a positive association between pretreatment hemoglobin A1C and peak glucose levels (P<.0001). Notably, 35% of our subjects experienced early morning hypoglycemia (65.2 ± 2.8 mg/dL).Conclusion: In hospitalized young patients with auto-immune diseases, CGMS data revealed that short-term consistent HDG treatment induced mild hyperglycemia, peaking in the early afternoon and before sleep. Early morning hypoglycemia was found in 35%.Abbreviations: A1C = hemoglobin A1C; AUC = the area under the curve; BG = blood glucose; BMI = body mass index; CGMS = continuous glucose monitoring system; DM = diabetes mellitus; FBG = fasting blood glucose; GA = glycated albumin; GCs = glucocorticoids; GIH = glucocorticoids-induced hyperglycemia; HDG = high-dose glucocorticoids; HOMA-IR = Homeostasis Model Assessment-Insulin Resistance; IG = interstitial glucose; IQR = interquartile range; PUMCH = Peking Union Medical College Hospital; SLE = systemic lupus erythematosus     

Improvement in Pancreatic β-Cell Function with Vitamin D and Calcium Supplementation in Vitamin D-Deficient Nondiabetic Subjects

ObjectiveThere are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency.MethodsNondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented.ResultsThirty-seven patients with 25-OHD deficiency participated in the study. The baseline and postvitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (− 0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (− 20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (− 4.88 ± 10.65 mg/dL); and homeostasis model assessment-2–percent β-cell function C-peptide secretion (HOMA-2–%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, − 3.751; P < .0001), 25-OHD (Z, − 4.9; P < .0001), intact PTH (Z, − 4.04; P < .0001), fasting plasma glucose (Z, − 2.7; P < .007), and HOMA-2–%B C-PEP (Z, − 1.923; P < .05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged.ConclusionOptimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and β-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis. (Endocr Pract. 2014;20:129-138)     

Health-Related Quality of Life After Percutaneous Radiofrequency Ablation of Cold,Solid, Benign Thyroid Nodules: A 2-Year Follow-Up Study in 40 Patients

Objective: We studied the impact of radiofrequency ablation (RFA) on health-related quality of life (HRQL) in patients with benign thyroid nodules (TN) in a 2-year follow-up.Methods: Forty patients (35 women and 5 men; age, 54.9 ± 14.3 years) with cold thyroid solitary nodules or a dominant nodule within a normofunctioning multi-nodular goiter (volume range, 6.5 to 90.0 mL) underwent RFA of thyroid nodular tissue under ultrasound real-time assistance.Results: Data are mean and standard deviation. Energy delivered was 37,154 ± 18,092 joules, with an output power of 37.4 ± 8.8 watts. Two years after RFA, nodule volume decreased from 30.0 ± 18.2 mL to 7.9 ± 9.8 mL (-80.1 ± 16.1% of initial volume; P<.0001). Thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels remained stable. Symptom score measured on a 0- to 10-cm visual analogue scale (VAS) declined from 5.6 ± 3.1 cm to 1.9 ± 1.3 cm (P<.0001). Cosmetic score (VAS 0–10 cm) declined from 5.7 ± 3.2 cm to 1.9 ± 1.5 cm (P<.0001). Two patients became anti-thyroglobulin antibody–positive. Physical Component Summary (PCS)-12 improved from 50.4 ± 8.9 to 54.5 ± 5.3, and the Mental Component Summary (MCS)-12 improved from 36.0 ± 13.3 to 50.3 ± 6.3 (P<.0001 for both score changes).Conclusion: Our 2-year follow-up study confirms that RFA of benign TNs is effective in reducing nodular volume and compressive and cosmetic symptoms, without causing thyroid dysfunction or life-threatening complications. Our data indicate that the achievement of these secondary endpoints is associated with HRQL improvement, measured both as PCS and MCS.Abbreviations: fT₃ = free triiodothyronine fT₄ = free thyroxine HRQL = health-related quality of life MCS-12 = Mental Component Summary-12 PLA = percutaneous laser ablation PCS-12 = Physical Component Summary-12 RF = radiofrequency RFA = radiofrequency ablation SF-12 = Short-Form 12 Health Survey TgAb = anti-thyroglobulin antibody TN = thyroid nodule TRAb = anti-TSH-receptor antibody TSH = thyroid-stimulating hormone US = ultrasound VAS = visual analogue scale     

Low Free (But Not Total) 25-Hydroxyvitamin D Levels in Subjects with Normocalcemic Hyperparathyroidism

Objective: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated parathyroid hormone (PTH) levels with persistently normal calcium levels. The diagnosis of NPHPT assumes the absence of secondary causes of elevated PTH levels. The objective of the current study was to examine levels of free 25-hydroxyvitamin D (25&lsqb;OH]D) in NPHPT subjects and healthy controls.Methods: Ten NPHPT subjects and 20 controls who were age, sex, race, and body mass index (BMI) matched were examined. The diagnosis of NPHPT was made if subjects had (1) a serum calcium level of 8.6 to 10.4 mg/dL, total 25(OH)D 30 to 40 ng/mL, and intact PTH (iPTH) ≥66 pg/mL; and (2) normal renal and liver function. Serum total 25(OH)D levels were measured by radioimmunoassay, and free 25(OH)D levels were determined using an enzyme-linked immunoassay.Results: Mean age of NPHPT subjects was 59.9 ± 5.4 years, and mean BMI was 28.4 ± 2.3 kg/m², which was not significantly different from the mean age and BMI of the control subjects. Mean total 25(OH)D level was 31.9 ± 1.7 ng/mL in NPHPT subjects and did not differ from that of the controls (32.7 ± 3.3 ng/mL; P = .52). However, mean free 25(OH)D was 5.0 ± 0.9 pg/mL in NPHPT subjects, which was 20% lower compared to the mean of the controls (6.2 ± 1.3 pg/mL; P = .013). Serum iPTH levels were inversely correlated with levels of measured free 25(OH)D (r = -0.42; P<.05) but did not correlate with levels of total 25(OH)D (r = -0.14; P>.10).Conclusion: Measured free 25(OH)D levels are lower in NPHPT subjects than in healthy control subjects. We suggest that some NPHPT subjects may actually have secondary hyperparathyroidism based on their free 25(OH) D levels.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CV = coefficient of variation; DBP = vitamin D–binding protein; iPTH = intact parathyroid hormone; NPHPT = normocalcemic primary hyperparathyroidism     

Nonobese Young Females with Polycystic Ovary Syndrome Have Nutritive Microvascular Dysfunction: A Pilot Study

ObjectiveTo investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables.MethodsFourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/ m²) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCV_max), and time taken to reach RBCV_max (TRBCV_max).ResultsSubjects with PCOS had lower RBCV and higher TRBCV_max compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, F < .01) and (5 [5-6] vs. 4 [3-5] s, P < .05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCV_max (ρ = -0.49, P < .05) and to TRBCV_max (ρ = 0.41, P < .05). SHBG correlated with RBCV_max (ρ = 0.52, P < .01) while estradiol (E₂) levels correlated with RBCV (ρ = 0.80, P < .001) and RBCV_max (ρ = 0.46, P < .05).ConclusionMicrovascular dysfunction characterized by reduced RBCV_maxand prolonged TRBCV_maxwas present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction. (Endocr Pract. 2014;20:1281-1289)     

Gender Determines Serum Free Cortisol: Higher Levels in Men

Objective: Because only the free fraction of serum cortisol can readily access glucocorticoid receptors, we investigated whether or not a gender-related difference in serum free cortisol (FC) exists in the basal and adrenocorticotropic hormone (ACTH)-stimulated state.Methods: Serum total cortisol (TC) and FC were measured in 323 subjects (175 men; 148 women). Additionally, the low-dose 1-μg ACTH test was performed in 56 subjects (30 women, 26 men). Subjects were healthy volunteers, recruited in a preventive medicine screening program and an outpatient clinic.Results: Overall, basal serum TC and FC level were ~18 and ~33%, respectively, higher in men than in women (TC, 14.5 ± 0.33 μg/dL vs. 12.3 ± 0.33 μg/dL; P<.0001; FC, 0.68 ± 0.02 μg/dL vs. 0.51 ± 0.02 μg/dL; P<.0001). The higher FC in men relative to women was apparent across a wide age range (17 to 86 years) and persisted after adjustment for age and body mass index. The FC fraction (%FC, out of TC) was concordantly higher in men (5.4 ± 0.09% vs. 4.8 ± 0.3%; P = .046). FC was not related to the estimated menopausal status (women age below and above 47, 50, or 53 years). ACTH-stimulated FC levels were significantly higher in men compared to women, as reflected by the area under the response curve (49.4 ± 3.4 μg × min vs. 39.6 ± 2.2 μg × min; P = .0014).Conclusion: Gender is an unrecognized determinant of serum FC in humans. The possibility of lifelong exposure to the higher bioactive fraction of cortisol under basal conditions or daily stress involving ACTH stimulation should be further investigated in the context of gender-related phenotypic features such as “android” (visceral) fat deposition and longevity.Abbreviations:ACTH = adrenocorticotropic hormoneBMI = body mass indexCBG = cortisol-binding globulinFC = free cortisolHPA = hypothalamic-pituitary-adrenalTC = total cortisol     

ACTN3 Gene R577X Polymorphism Associated with High-Density Lipoprotein Cholesterol and Adiponectin in Rugby Players

Objective: To determine the relationship between the R577X polymorphism of the α-actinin-3 (ACTN3), which may play a role in the individual differences observed in the effects of exercise on health benefits and antiatherogenic markers (i.e., high-density lipoprotein cholesterol [HDL-C] and adiponectin) in athletes.Methods: Seventy-six male rugby players (mean age 19.8 years) were enrolled in this study. Genomic DNA was extracted from peripheral blood samples, and restriction fragment length polymorphism-polymerase chain reactions were conducted to assess ACTN3 genotypes. Body mass index (BMI), waist circumference, serum lipids including HDL-C, and adiponectin levels were measured. Current smoking and alcohol intake habits were evaluated with a questionnaire. All of the parameters were compared between 2 groups displaying frequently observed genotypes: one group consisting of patients having either the R/R or R/X genotype and a second group with the X/X genotype.Results: The frequency of the X allele was 0.55 and the distribution of the genotypes was 35.5% (n = 27) for X/X, 39.5% (n = 30) for R/X, and 25.0% (n = 19) for R/R. Serum HDL-C and adiponectin levels were significantly higher in X/X genotype compared to the R/R or R/X genotype (HDL-C 1.6 ± 0.3 [SD] vs. 1.4 ± 0.2 mmol/L; P<.01, adiponectin 8.8 ± 2.6 vs. 6.9 ± 2.3 μg/mL; P<.01), even after adjustments for confounders (P<.01).Conclusion: There may be a relationship between the ACTN3 genotype and HDL-C and adiponectin levels in rugby players. This may be useful information when determining the individual responses of antiatherogenic markers to exercise.Abbreviations:ACTN3 = α-actinin-3BMI = body mass indexCVD = cardiovascular diseaseHDL-C = high-density lipoprotein cholesterolLDL-C = low-density lipoprotein cholesterolR = arginine (R) at amino acid position 577 of the ACTN3 proteinTC = total cholesterolTG = triglycerideX = truncation at amino acid position 577 of the ACTN3 protein     

Prediction of all-cause mortality with copeptin in cardio-cerebrovascular patients: A meta-analysis of prospective studies

BackgroundMeasurement of the biomarker copeptin may help identify disease severity and risk of mortality for a various diseases. This study sought to determine the relationship between copeptin and all-cause mortality of patients with cardio-cerebrovascular disease.MethodsDatabase of Medline and Web of Science were searched for studies with data involving the baseline copeptin levels and subsequent all-cause mortality outcomes. The pooled HRs of all-cause mortality were calculated and presented with 95%CIs. Subgroup analysis and sensitivity analysis were conducted to explore the possible sources of heterogeneity.ResultsData from 14,395 participants were derived from 28 prospective studies. Higher copeptin significantly increased the risk of all-cause mortality (per unit copeptin: HR = 1.020, 95%CI = 1.004–1.036; log unit copeptin: HR = 2.884, 95%CI = 1.844–4.512; categorical copeptin: HR = 3.371, 95%CI = 2.077–5.472). Subgroup analysis indicated that the risk of all-cause death was higher in cerebrovascular patients (per unit copeptin: HR = 2.537, 95%CI = 0.956–6.731; log unit copeptin: HR = 3.419, 95%CI = 2.391–4.888) than cardiovascular patients (per unit copeptin: HR = 1.011, 95%CI = 1.002–1.020; log unit copeptin: HR = 2.009, 95%CI = 1.119–3.608).ConclusionCopeptin is associated with all-cause mortality of patients with cardiovascular and cerebrovascular disease. Our study suggests that copeptin seems to be a promising novel biomarker for prediction of mortality in cardio-cerebrovascular patients, especially for cerebrovascular patients.     

Vitamin D Insufficiency is Associated With Reduced Parasympathetic Nerve Fiber Function in Type 2 Diabetes

ObjectiveVitamin D insufficiency is prevalent in subjects with type 2 diabetes mellitus (T2DM) and is associated with peripheral neuropathy. However, there are little data regarding vitamin D status in patients with cardiovascular autonomic neuropathy. Our objective was to evaluate the association of cardiovascular autonomic function, 25-hydroxyvitamin D (25[OH]D) insufficiency (i.e., levels < 30 ng/mL), and multiple metabolic parameters in subjects with T2DM.MethodsWe examined 50 individuals with T2DM. Cardiovascular autonomic function (i.e., parasympathetic function) was assessed by RR-variation during deep breathing (i.e., mean circular resultant [MCR] and expiration/inspiration [E/I] ratio). Metabolic parameters included measures of adiposity, glycemic control, insulin resistance, calcium metabolism, and 25(OH)D.ResultsParticipants with 25(OH)D insufficiency (n = 26) were younger (66 ± 9 vs. 60 ± 10 years, P < .05), more insulin resistant, had a higher body mass index (BMI) and lower adiponectin levels. The MCR (39.5 ± 26.3 vs. 27.6 ± 17.2, P < .01) and E/I ratio (1.21 ± 0.17 vs. 1.15 ± 0.09, P < .01) were lower for those with 25(OH)D insufficiency after controlling for age. A stepwise selection procedure regressing MCR and E/I ratio on a number of metabolic parameters resulted in a model identifying age and 25(OH)D insufficiency as significant determinants for both measures. The interaction of age × 25(OH)D insufficiency was also included (MCR model, R² = 0.491, P < .001; E/I ratio, R² = 0.455, P < .001). Neither glycemic control nor other metabolic parameters were selected.ConclusionOur results suggest that 25(OH)D insufficiency is associated with reduced parasympathetic function, with a stronger association in younger persons with T2DM. Studies are needed to determine if vitamin D supplementation into the sufficient range could prevent or delay the onset of cardiovascular autonomic dysfunction. (Endocr Pract. 2015;21:174-181)     

Partial Hospitalization: An Intervention for Youth with Poorly Controlled Diabetes Mellitus

Objective: To examine the efficacy of an integrated medical/psychiatric partial hospitalization program (PHP) to improve glycemic control in youth with both diabetes mellitus and mental health disorders.Methods: This retrospective chart review is of patients admitted to a PHP between 2005–2015 with concerns about diabetes mellitus care. Clinical characteristics, laboratory data, diabetic ketoacidosis hospitalizations, and outpatient clinic visit frequency were collected from the year prior to the year after PHP admission.Results: A total of 43 individuals met inclusion criteria: 22 (51%) were female, 40 (93%) had type 1 diabetes, the mean age was 15.2 ± 2.3 years, and the mean diabetes mellitus duration was 4.6 ± 3.6 years. Of those individuals, 35 of these patients had hemoglobin A1c (HbA1c) data available at baseline, 6 months, and 1 year after PHP. The average HbA1c before PHP admission was 11.3 ± 2.3% (100.5 ± 25 mmol/mol), and decreased to 9.2 ± 1.3% (76.7 ± 14.8 mmol/mol) within 6 months of PHP admission (P<.001). The average HbA1c 1 year after PHP was 10.7 ± 1.7 % (93.3 ± 19.1 mmol/mol). Overall, 24 patients (68%) had lower HbA1c, and 75% of those with improvement maintained an HbA1c reduction of ≥1% (≥10 mmol/mol) at 1 year compared to before PHP.Conclusion: Most patients demonstrated improved glycemic control within 6 months of PHP admission, and many of those maintained a ≥1% (≥10 mmol/mol) reduction in HbA1c at 1 year following PHP admission. This program may represent a promising intervention that could serve as a model for intensive outpatient management of youth with poorly controlled diabetes mellitus.Abbreviations: ADA = American Diabetes Association; DKA = diabetic ketoacidosis; EMR = electronic medical record; HbA1c = hemoglobin A1c; ICD-9 = International Classification of Diseases, 9^th revision; PHP = partial hospitalization program     

Clinical Profile of Nonalcoholic Fatty Liver Disease Among Young Patients With Type 1 Diabetes Mellitus Seen at a Diabetes Speciality Center in India

ObjectiveTo estimate the prevalence and clinical profile of nonalcoholic fatty liver disease (NAFLD) among young type 1 diabetes mellitus (T1DM) patients at a tertiary care diabetes center in India.MethodsElectronic medical records of T1DM patients (age at first diagnosis of T1DM ≤ 25 years) registered between January 1992 and May 2013 who had undergone ultrasonography and denied history of any alcohol intake (n = 736) were reviewed. NAFLD was diagnosed if there was any degree of fatty liver. Retinopathy was initially assessed by direct and indirect ophthalmoscopy and later by retinal photography. Nephropathy was diagnosed if urine protein excretion was > 500 mg/day, and neuropathy was diagnosed if a patient’s vibration perception threshold on biothesiometry was ≥ 20 V.ResultsA total of 204/736 (27.7%) T1DM patients had NAFLD. Compared to T1DM subjects without NAFLD those with NAFLD had higher body mass index (BMI) (18.9 ± 4.2 vs. 20.2 ± 4.7 kg/m², P < .001), waist circumference (67.9 ± 13.2 vs. 71.9 ± 13.3 cm, P < .05), systolic blood pressure (110 ± 15 vs. 116 ± 18 mm Hg, P < .001) and diastolic blood pressure (72 ± 9 vs. 74 ± 10 mm Hg, P < .05), while fasting blood glucose (201 ± 101 vs. 183 ± 101 mg/dL, P < .05) and alkaline phosphatase (419 [12.5] vs. 315 [15.8], P < .001) levels were lower in patients with T1DM with NAFLD. Multiple logistic regression analysis showed a significant association between NAFLD and retinopathy (odds ratio [OR]: 2.01, 95% confidence interval [CI]: 1.13-3.43; P = .017, after adjusting for sex, duration of diabetes, overweight/obesity, hypertension, fasting plasma glucose, nephropathy, and nephropathy (OR: 1.89, 95% CI: 1.02-3.50; P = .042), after adjusting for sex and fasting plasma glucose.ConclusionsThis study suggests that NAFLD is also seen among T1DM patients and that it has an independent and significant association with retinopathy and nephropathy. (Endocr Pract. 2014;20:1249-1257)     

Clinical Markers Implying the Need for Treatment in Women with Gestational Diabetes Mellitus

ObjectiveTo assess the association of the point-of-care hemoglobin A_1c (POC A1C), fasting blood glucose (FBG), and BMI with fetal macrosomia and the need for medication in women with gestational diabetes (GDM).MethodsPOC A1C, FBG, and BMI values at GDM diagnosis and fetal weight at delivery were obtained for women identified from a prospective patient registry. These outcomes were compared between women who did not require medication for GDM and women who did require medication.ResultsMean values of POC A1C, FBG, and BMI in 67 patients who required medication were higher than those in 71 patients who did not require medication (POC A1C: 5.72 ± 0.45% vs 5.35 ± 0.46% [P < .001]; FBG: 97.4 ± 12.3 mg/dL vs 86.4 ± 9.5 mg/dL [P < .001]; BMI: 35.4 ± 6.4 kg/m2 vs 30.4 ± 6.2 kg/m2 [P < .001]). There was a modest correlation between POC A1C and FBG (Spearman rho 0.4, P < .001) and between POC A1C and BMI (Spearman rho 0.366, P < .001). Maternal POC A1C was not correlated with fetal weight at delivery (Spearman rho –0.010, P = .915).ConclusionsHigher POC A1C, FBG, and BMI values were associated with the need for medication in women with GDM. The use of clinical markers to assess glycemic control sooner in pregnancy may lead to the earlier identification of women at risk for GDM and earlier intervention to decrease the risk for complications. (Endocr Pract. 2012;18:62-65)     

Long-Term,Sustained, Lifestyle-Induced Weight Loss in Severe Obesity: the Get-Real Program

Objective: To study the long-term effectiveness of a patient-centered, multidisciplinary lifestyle intervention treatment in patients medically eligible for bariatric surgery.Methods: Using a case-control study design, we compared treatment results for 98 adults (mean body mass index [BMI], 44.2 kg/m²) with the outcomes of 148 controls (mean BMI, 43.0 kg/m²) receiving standard care. The approach included a phased triage for inclusion, followed by 12 lifestyle intervention group sessions alternating with individual visits for behavior, diet, and exercise instructions.Results: At 2 years, weight loss averaged 15.3 ± 1.4 kg (P<.0010) (12 ± 1% of initial body weight [IBW], P<.001; 21 ± 2% of excess body weight [EBW], P<.001) in an intention-to-treat (ITT) analysis; in completers, weight loss was 18.8 ± 1.5 kg (P<.001) (15 ± 1% IBW, P<.001; 26 ± 3% EBW, P<.001). A total of 42 patients lost ≥10% IBW. Controls remained weight stable (P =.35); 3% lost ≥10% IBW. Patients achieving weight loss that would be considered satisfactory for bariatric surgery included 20% who achieved ≥35% EBW loss, 29% who achieved a BMI <35 kg/m² (if starting BMI <50 kg/m²) or BMI <40 kg/m² (if starting BMI ≥50 kg/m²), and 37% who achieved EBW loss ≤50%. These values for completers were 31, 39, and 48%, respectively. In the 55 patients starting the program ≥4 years ago, weight loss maintenance of 12 ± 1% IBW (ITT, 16 ± 1% in completers) was observed.Conclusion: Substantial nonsurgical weight loss, maintained at 2 to 4 years, is achievable in severely obese patients using comprehensive lifestyle approaches; the efficacy/safety trade-off in obesity treatment is an important consideration in interpreting these results.Abbreviations: BMI = body mass index EBW = excess body weight HbA_1c = glycated hemoglobin IBW = initial body weight LOCFA = last observation carried forward analysis