Advanced Bone Age and Hyperinsulinemia in Overweight and Obese Children

ObjectiveIn obese children, bone age (BA) tends to significantly exceed chronological age (CA). In vitro studies in mice suggest that insulin may directly modulate skeletal growth. We investigated whether there is an association between fasting insulinand BAmaturationinobesechildren.MethodsThe study cohort comprised 74 overweight and obese children ages 4 to 13 years. BA divided by CA was used as an index for bone advancement. Participants were classified into tertiles based on their BA:CA ratio. Advanced BA maturation was defined as the third tertile, with BA:CA > 1.21. Components of the metabolic syndrome, including fasting insulin, fasting glucose, triglycerides, and high-density lipoprotein (HDL) levels, were measured.ResultsChildren with advanced BA were significantly younger, had a higher body mass index (BMI)-Z score (BMI-Z), and were taller than children with bone advancement in the lower tertiles. Females had a 4.7-fold increased risk for advanced BA compared with males (95% confidence interval [CI], 1.29-17.1; P = .02). Children with a BMI-Z ≥ 1.96 and fasting insulin ≤ 30 μU/L had a 3.6-fold increased risk of advanced BA (95% CI, 1.00-12.8; P = 0.05). Moreover, hyperinsulinemia (fasting insulin > 30 μU/L) was associated with a 6.8-fold increased risk for advanced BA, independent of the degree of obesity (95% CI, 1.45-32.1; P = .01).ConclusionMarked hyperinsulinemia is associated with advanced BA in obese children. Insulin appears to modulate skeletal growth in humans. (Endocr Pract. 2014;20:62-67)     

The Association of Decreased Serum Gdnf Level with Hyperglycemia and Depression in Type 2 Diabetes Mellitus

Objective: Comorbidity of diabetes and depression is a critical problem. Decreased glial-derived neurotrophic factor (GDNF) has been demonstrated in depression, but no evidence of a relationship between GDNF and diabetes has been shown. The present studies were designed to investigate the relationship between GDNF and metabolism.Methods: In Study 1, we performed a case-control study in which subjects with type 2 diabetes mellitus (T2DM), prediabetes (p-DM), and normal glucose tolerance (NGT) were included. In Study 2, we performed a cross-sectional study in 296 patients having pre-existing diabetes in whom the levels of serum GDNF, blood glucose, blood lipids, blood pressure, body mass index, scores from the Patient Health Questionnaire (PHQ-9), the EuroQol-5 scale, and the diabetes distress scale were measured, as well as single-nucleotide polymorphisms of GDNF including rs884344, rs3812047, and rs2075680.Results: In Study 1, serum GDNF concentration was significantly lower in the T2DM group than in the NGT group (NGT: 11.706 ± 3.918 pg/mL; p-DM: 10.736 ± 3.722 pg/mL; type 2 diabetes mellitus &lsqb;T2DM group]: 9.884 ± 2.804 pg/mL, P = .008). In Study 2, significantly decreased serum GDNF levels were observed in subjects with poor glycemic control or depression (glycated hemoglobin &lsqb;HbA1c] <7.0% without depression: 11.524 ± 2.903 pg/mL; HbA1c ≥7.0% without depression: 10.625 ± 2.577 pg/mL; HbA1c <7.0% with depression: 10.355 ± 2.432 pg/mL; HbA1c ≥7.0% with depression: 8.824 ± 2.102 pg/mL, P = .008). Double-factor variance analysis showed that glycemic control and depression were independent factors for the GDNF level. Moreover, the serum GDNF level was significantly inversely associated with the fasting plasma glucose, 2 hours postprandial plasma glucose, HbA1c, and PHQ-9 score.Conclusion: Glycemic dysregulation was an independent factor for the GDNF level. These findings suggest that GDNF level might be involved in the pathophysiology of T2DM and depression through various pathways.Abbreviations: BP = blood pressure; CHO = cholesterol; DDS = diabetes distress scale; DM = diabetes mellitus; EQ-5D = the health-related dimensions of the EuroQol-5 scale; FPG = fasting plasma glucose; GDNF = glial-derived neurotrophic factor; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NGT = normal glucose tolerance; PHQ-9 = Patient Health Questionnaire; p-DM = prediabetes; PPG = postprandial plasma glucose; SNP = single-nucleotide polymorphism; T2DM = type 2 diabetes mellitus; TG = triglyceride     

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     

Diabetes Status and Race are Associated With Cardiovascular Risk Markers in Obese Adolescents

ObjectiveThe objective of this study was to evaluate differences in cardiovascular disease (CVD) risk markers in obese adolescents based on diabetes status and race in order to improve risk-reduction intervention strategies.MethodsThis was a retrospective, cross-sectional study of obese adolescents, age 10 to 21 years, who were evaluated at Children’s of Alabama between 2000 and 2012. Subjects were classified by glycated hemoglobin (HbA_1c) as having normoglycemia, prediabetes, or type 2 diabetes mellitus (T2DM).ResultsThere were a total of 491 African American (AA) or Caucasian American (CA) subjects. Body mass index was not different between HbA_1c and racial groups. Compared to subjects with normoglycemia or prediabetes, subjects with T2DM had higher levels of total cholesterol (TC) (178.6 ± 43.8 mg/dL vs. 161.5 ± 32.5 mg/dL vs. 162.4 ± 30.6 mg/dL; P < .0001) and low-density-lipoprotein cholesterol (107.4 ± 39.2 mg/dL vs. 97.0 ± 31.0 mg/dL vs. 97.5 ± 26.9 mg/dL; P = .0073). Compared with AA subjects, CA subjects had lower high-density-lipoprotein cholesterol (HDL-C) levels (40.4 ± 10.4 mg/dL vs. 44.3 ± 11.9 mg/dL; P = .0005) and higher non-HDL-C levels (129.6 ± 36.2 mg/dL vs. 122.5 ± 37.5 mg/dL; P = .0490). Of the characteristics studied, HbA_1c had the most significant positive association with dyslipidemia and was strongly correlated with both TC (β, 4.21; P < .0001) and non-HDL-C (β, 4.3; P < .0001).ConclusionObese adolescents with T2DM have more abnormal lipoprotein profiles than those with normoglycemia or prediabetes. Obese CA adolescents have more abnormal lipids than obese AA adolescents. HbA_1c was the characteristic most highly associated with abnormal lipoprotein profiles in our subjects. Our results show that CVD risk markers in obese adolescents vary by race and HbA_1c concentration. (Endocr Pract. 2015;21:165-173)     

Exenatide Therapy in Obese Patients With Type 2 Diabetes Mellitus Treated with Insulin

ObjectiveTo evaluate the effect of exenatide on clinical parameters in obese patients with type 2 diabetes mellitus whose hyperglycemia is not adequately controlled despite treatment with oral hypoglycemic agents and insulin.MethodsIn this retrospective analysis, clinical progress of 52 obese patients with type 2 diabetes treated with exenatide, 5 mcg twice daily, in an outpatient setting was reviewed. Treatment initiation was between September and December 2005. Mean follow-up period was 26 weeks. Thirty-eight patients took exenatide regularly (Group A); 14 patients discontinued exenatide because of insurance, personal, or economic reasons (Group B). Measurements at baseline and at follow-up included body weight; blood pressure; and levels of hemoglobin A_1c (HbA_1c), high-sensitivity C-reactive protein (CRP), and plasma lipids. Insulin dosage requirements were assessed.ResultsMean body weight (± standard error of the mean) decreased by 6.46 ± 0.8 kg (P < .001) in Group A and increased by 2.4 ± 0.6 kg in Group B (P < .001). In Group A, mean HbA_1c decreased by 0.6 ± 0.21% (P = .007), and the insulin dosage requirement decreased for rapid-acting and mixed insulins (P < .02). In Group A, means of the following parameters decreased: serum total cholesterol by 8.5 ± 3.3% (P = .03), triglycerides by 26 ± 7.6% (P = .01), systolic blood pressure by 9.2 ± 3.3 mm Hg (P = .02), and high-sensitivity CRP by 34 ± 14.3% (P = .05). These indices did not change in Group B.ConclusionExenatide effectively treats obese patients with type 2 diabetes on insulin, leading to weight loss and reduction in levels of HbA_lc, systolic blood pressure, triglycerides, and high-sensitivity CRP. (Endocr Pract 2007;13:444-450)     

Incidence of Central Diabetes Insipidus in Children Presenting with Polydipsia and Polyuria

Objective: Polydipsia and polyuria are common reasons for referral to the Pediatric Endocrine clinic. In the absence of hyperglycemia, diabetes insipidus (DI) should be considered. The objectives of the study were to determine the prevalence of central DI (CDI) in a group of children presenting for evaluation of polydipsia and polyuria, and to determine if predictive features were present in patients in whom the diagnosis of DI was made.Methods: The study was a retrospective chart review of children presenting to the endocrine clinic with complaints of polydipsia and polyuria over a 5-year period.Results: The charts of 41 patients (mean age 4.9 ± 3.7 years, 28 males) were reviewed. CDI was diagnosed in 8 (20%) children based on abnormal water deprivation test (WDT) results. All but one patient had abnormal magnetic resonance imaging (MRI) findings, the most common being pituitary stalk thickening. Children with DI were older (7.86 ± 4.40 vs. 4.18 ± 3.20 years, P = .01) and had a higher propensity for cold beverages intake and unusual water-seeking behaviors compared to those without DI. Baseline WDT also revealed higher serum sodium (Na) and osmolality.Conclusion: The incidence of CDI in children presenting with polydipsia and polyuria is low. Factors associated with higher likelihood of pathology include older age, propensity for cold beverage intake, and higher baseline serum Na and osmolality on a WDT.Abbreviations:BMI = body mass indexCDI = central diabetes insipidusDI = diabetes insipidusNa = sodiumWDT = water deprivation test     

HbA1c and Blood Pressure Measurements: Relation with Gender,Body Mass Index,Study Field,and Lifestyle in Lebanese Students

Objective: The purpose of this study is to determine the prevalence of prediabetes/diabetes in Lebanese university students and to examine the relationship between both hemoglobin A1c (HbA1c) and blood pressure (BP) and gender, body mass index (BMI), study field, and lifestyle factors.Methods: This cross-sectional study was carried out at the Saint-Joseph University of Beirut. A total of 603 students aged 18 to 25 years were recruited from both the medical science campus (MSC) and the social science campus (SSC) between January, 2016, and May, 2018. Waist circumference (WC), BMI, and BP were determined for each student and HbA1c was measured using the Siemens vintage DCA device. Participants completed a self-administered questionnaire about their eating habits and level of physical activity.Results: The mean age of the population was 20.31 ± 1.76 years. The percentage of participants recruited from the MSC was 59.2%. The prevalence of prediabetes was 2.5%. Lower BMI, WC, and HbA1c values, and higher diastolic BP (DBP) were found in MSC students compared to SSC ones. HbA1c, systolic BP (SBP), and DBP were correlated with BMI (P = .02, P<.0001, and P = .017, respectively). HbA1c was not associated with eating habits or physical activity. DBP was inversely associated with physical activity (P = .002), while SBP was positively associated with fast food consumption (P = .003).Conclusion: The present study shows a low prevalence of prediabetes in Lebanese students. BMI and the study field are the main factors predicting HbA1c and BP. Further studies are needed to extrapolate our results to the overall young Lebanese population.Abbreviations: ADA = American Diabetes Association; BMI = body mass index; BP = blood pressure; DBP = diastolic blood pressure; HbA1c = hemoglobin A1c; HTN = hypertension; MSC = medical science campus; SBP = systolic blood pressure; SSC = social science campus; T2D = type 2 diabetes; US = United States; USJ = Saint-Joseph University; WC = waist circumference     

Thyroid Function and Metabolic Syndrome: A Cross-Sectional Study in Obese and Overweight Patients

Objective: Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In obese patients, serum thyroid-stimulating hormone (TSH) levels tend to be higher than in lean controls. The objective of this study was to assess potential associations between serum TSH levels and MetS as well as individual components of MetS.Methods: This was a cross-sectional observational study of obese and overweight patients seen for initial evaluation at the Boston Medical Center weight-management clinic between February 1, 2013 and February 1, 2014. Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose, hemoglobin A_1c, and lipid levels were obtained from electronic medical records. Associations between serum TSH levels and presence of MetS and its components were assessed.Results: A total of 3,447 patients, 75.6% female and 38% African American, without known thyroid dysfunction, were included. Mean ± SD age was 46.74 ± 15.11 years, and mean ± SD body mass index was 36.06 ± 9.89 kg/m². Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In patients with MetS, the median serum TSH was 1.41 μIU/mL, compared with 1.36 μIU/mL in patients without MetS (P = .45). In multivariate models, there was no significant association between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education, socioeconomic status, and smoking. There were also no significant associations between serum TSH and individual components of the MetS.Conclusion: Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and overweight individuals.Abbreviations: BMI = body mass index FT₄ = free thyroxine HDL-C = high-density-lipoprotein cholesterol HbA_1c = hemoglobin A_1c MetS = metabolic syndrome SE = standard error TSH = thyroid-stimulating hormone     

Prevalencia de alteraciones del metabolismo hidrocarbonado en una población infanto-juvenil con obesidad grave

IntroductionThere is currently a disproportionate increase in childhood and adolescent obesity worldwide, together with other disorders involving substantial cardiometabolic risk in adulthood, such as alterations in carbohydrate metabolism.ObjectiveTo establish the prevalence of prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) after an oral glucose tolerance test, and the prevalence of type 2 diabetes mellitus (DM-2) in a pediatric population with severe obesity. Additionally, we aimed to assess clinical metabolic differences between prediabetic obese patients and obese subjects without prediabetes.Material and methodsA cross-sectional study was carried out in children and adolescents with severe obesity (>97th percentile). The variables studied were age, sex, height, weight, body mass index, waist circumference, fasting plasma glucose and oral glucose tolerance test, insulinemia, insulin resistance assessed by the homeostasis model assessment (HOMA) index, glycated hemoglobin (HbA_1c), triglycerides, high-density lipoprotein cholesterol (HDL), and systolic and diastolic blood pressure.ResultsA total of 133 patients were included: 67 boys (50.4%) and 66 girls (49.6%), with a mean age of 12.17±3.27 years. Fourteen patients (10.52%) had prediabetes (10 IFG, 3 IGT, 1 IFG+IGT): 7 girls and 8 boys, with a mean age of 13.2±3.3 years. One patient had DM2 (0.75%). Patients with prediabetes had significantly higher concentrations of fasting glucose (98±10.76 vs 88.53±6.3 mg/d; p=0.001), insulinemia (35.38±14.22 vs 22.95±14.30 μU/ml; p=0.009) and HOMA index (8.10±3.24 vs 4.89±3.27; p=0.004) than patients without impaired carbohydrate metabolism. These patients also had higher values of HbA_1c, triglycerides, blood pressure and HDL concentrations, although differences were not statistically significant.ConclusionsThe prevalence of prediabetes (IFG/IGT) in children with severe obesity was high (10.52%). These patients should therefore be investigated to establish early diagnosis and appropriate treatment. Obese patients with prediabetes have significantly higher levels of insulin and insulin resistance than individuals without impaired carbohydrate metabolism.     

Identifying Prediabetes Using Fasting Insulin Levels

ObjectiveTo determine whether patients with prediabetes can be accurately and easily identified in clinical settings using a predictive clinical and laboratory model.MethodsThis retrospective study examined demographic and laboratory data from patients who had undergone 2-hour glucose testing for suspected prediabetes or diabetes between 2000 and 2004. Patients who met the diagnostic criteria for diabetes mellitus were excluded. Prediabetes was defined as a fasting glucose concentration ≥ 100 mg/dL and ≤ 125 mg/dL or a 2-hour postprandial glucose concentration ≥ 140 mg/dL and < 200 mg/dL. Multivariate logistic regression was conducted to identify calculated or measured clinical and laboratory attributes that predict the presence of prediabetes, including fasting insulin quartiles, homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index.ResultsOf 965 patients, 287 (29.7%) had prediabetes. The study population primarily consisted of white, obese, female patients. A multivariate model revealed that compared with the referent lowest quartile of fasting insulin (m = 4.9 [± SD] ± 1.2 mIU/mL), subsequent insulin quartiles increased the likelihood of identifying prediabetes (quartile 2: m = 8.0 ± 0.8 mIU/mL, odds ratio [OR] = 2.076, confidence interval [CI] = 1.241-3.273; quartile 3: m = 12.2 ± 1.7 mIU/mL, OR = 3.151, CI = 1.981-5.015; quartile 4: m = 25.9 ± 12.4 mIU/mL, OR = 5.035, CI = 3.122-8.122). Older age and increased diastolic blood pressure also contributed modestly to this model. Further analysis using the area under the curve revealed that at a fasting insulin level > 9.0 mIU/mL, prediabetes would be correctly identified in 80% of affected patients. A second model revealed that increased HOMA-IR index (OR = 1.303, CI = 1.205-1.410) and older age (OR = 1.037, CI = 1.024-1.05) predicted prediabetes.ConclusionsThe most robust model, which used fasting insulin levels, may provide the most utility as a clinical tool because the highest quartiles suggest significantly greater likelihood of identifying prediabetes. (Endocr Pract. 2010;16:47-52)     

Colesevelam Hydrochloride to Treat Hypercholesterolemia and Improve Glycemia in Prediabetes: A Randomized,Prospective Study

ObjectiveTo assess the effect of the bile acid sequestrant colesevelam hydrochloride in patients with hypercholesterolemia and prediabetes.MethodsIn this 16-week, randomized, double-blind study, adults with untreated prediabetes (2-hour postoral glucose tolerance test [OGTT] glucose ≥ 140 to 199 mg/dL, fasting plasma glucose [FPG] ≥ 110 to 125 mg/ dL, or both), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL, and triglycerides < 500 mg/dL were randomly assigned to receive colesevelam (3.75 g/d) or placebo. The primary end point was percent change in LDL-C from baseline to week 16 with last observation carried forward. Secondary end points included change in FPG, hemoglobin A1c (A1C), and 2-hour post-OGTT glucose level from baseline to week 16 and attainment of LDL-C and FPG targets.ResultsIn total, 216 patients were randomized (colesevelam, 108; placebo, 108). In comparison with placebo, colesevelam significantly reduced LDL-C (mean treatment difference, -15.6%), non-high-density lipoprotein cholesterol (-9.1%), total cholesterol (-7.2%), apolipoprotein B (-8.1%) (P < .001 for all the foregoing), FPG (median, -2.0 mg/dL; P = .02), and A1C (mean, -0.10%; P = .02). Colesevelam did not significantly change 2-hour post-OGTT glucose (-1.9 mg/dL; P = .75) or high-density lipoprotein cholesterol (-0.5%; P = .80). In addition, colesevelam significantly increased triglyceride levels relative to placebo (median, 14.3%; P < .001). The proportion of patients achieving target levels with colesevelam versus placebo, respectively, was as follows: LDL-C < 100 mg/dL (29% versus 11%; P < .001), A1C < 6.0% (37% versus 25%; P = .05), FPG < 110 mg/dL (48% versus 56%; P = .97), and normalization of glucose (FPG < 100 mg/dL [40% versus 23%; P = .06]). Colesevelam had a weight-neutral effect and was well tolerated.ConclusionColesevelam is an option for managing the lipid profile and normalizing glucose levels in patients with hypercholesterolemia and prediabetes. Further study is warranted to determine whether colesevelam slows or prevents progression of prediabetes to type 2 diabetes. (Endocr Pract. 2010;16:617-628)     

Prevalence of Elevated Thyroid-Stimulating Hormone Levels in Obese Children and Adolescents

ObjectiveTo determine the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents referred to pediatric endocrinology clinics.MethodsWe undertook a retrospective review of medical records of 191 obese and 125 nonobese children (younger than 18 years old). Data about age, sex, body mass index, TSH, thyroid functions, thyroid antibodies, thyroid size, and medications were collected.ResultsSix obese patients had Hashimoto disease and TSH values from 0.73 to 12.73 mIU/L; they were excluded from the study analyses. Of the remaining 185 obese subjects, 20 (10.8%) had TSH levels > 4 mIU/L, but no control subject measurement exceeded this TSH value. The highest TSH concentration in an obese study subject was 7.51 mIU/L. When obese children with TSH levels > 4 mIU/L were classified in a third group, the mean TSH in the rest of the obese children was comparable with that in the control group (1.98 ± 0.84 [SD] and 1.95 ± 0.80 mIU/L, respectively; post hoc analysis of variance, P = .945). Obese subjects with increased TSH values had a mean body mass index similar to that for obese subjects with normal TSH levels (34.98 ± 6.12 [SD] and 34.29 ± 7.84 kg/m², respectively).ConclusionMild elevation of TSH values in the absence of autoimmune thyroid disease is not uncommon in some obese children and adolescents. This is the second study in the United States to report this observation. Our study did not identify any special characteristics of obese subjects with TSH elevation in comparison with obese children with normal TSH levels and the control group. Current medical knowledge does not support routine screening for thyroid dysfunction in obese children. (Endocr Pract. 2010;16:187-190)     

Efficacy and Safety of Insulin Lispro in Obese Patients with Type 2 Diabetes: A Retrospective Meta-Analysis of 7 Randomized Controlled Trials

ObjectiveTo evaluate the efficacy and safety of insulin lispro in the treatment of patients with type 2 diabetes (T2DM) who had a body mass index (BMI) ≥ 30 kg/m² (obese) compared with patients with BMIs < 30 kg/m² (nonobese).MethodsA retrospective analysis of predefined endpoints from 7 randomized clinical trials of T2DM patients treated with insulin lispro was performed. The primary efficacy measure was to assess the noninferiority of insulin lispro in obese patients versus nonobese patients as measured by the change in hemoglobin A1C (HbA_1c) from baseline to Month 3 (n = 1,518), using a noninferiority margin of 0.4%. The secondary measures included overall hypoglycemia incidence and event rates and relative change in body weight.ResultsMean changes in HbA_1c from baseline (9.06% for obese and 8.92% for nonobese) to Month 3 were similar for obese patients (–1.03%) and nonobese (–1.02%), with a least squares (LS) mean difference (95% confidence interval [CI]) of –0.05% (–0.17%, 0.07%; P = .384). The overall incidence of hypoglycemia (53% vs. 63%; P < .001) and rate of hypoglycemia (0.93 vs. 1.76 events per 30 days; P < .001) was significantly lower in obese patients compared with nonobese patients. The 2 BMI cohorts did not demonstrate a significant difference in mean percent changes in body weights (LS mean difference = 0.4% [–0.2%, 0.9%]; P = .202).ConclusionObese patients with T2DM treated with insulin lispro were able to achieve the same level of glycemic control as their nonobese counterparts, with some evidence supporting a reduced risk of hypoglycemia. (Endocr Pract. 2014;20:389-398)     

Dpp4 Inhibitor Sitagliptin As A Potential Treatment Option In Metformin-Intolerant Obese Women With Polycystic Ovary Syndrome: A Pilot Randomized Study

Objective: Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated the dipeptidyl peptidase 4 inhibitor sitagliptin as a potential treatment option in metformin-intolerant PCOS.Methods: We conducted a 12-week, prospective, randomized, open-label study with 30 obese metformin-intolerant women with PCOS (age 35.0 ± 7.2 years; body mass index, 36.9 ± 5.5 kg/m²). After metformin withdrawal, they were randomized to lifestyle intervention and sitagliptin 100 mg daily (SITA) or lifestyle intervention alone as controls (CON). All participants underwent anthropometric and endocrine measurements and oral glucose tolerance testing. Model-derived indexes of insulin resistance and beta-cell function were calculated.Results: SITA improved beta-cell function as assessed by the homeostasis model assessment for beta-cell function index (HOMA-B) of 45.9 ± 35.8 (P = .001), modified beta-cell function index (MBCI) of 7.9 ± 7 (P = .002), and quantitative insulin-sensitivity check index (QUICKI) of -0.03 ± 0.03 (P = .002). By contrast, beta-cell function decreased in CON. The between-group differences were significant for HOMA-B (P = 0.001), MBCI (P = .010), and QUICKI (P = .025). The conversion rate to impaired glucose homeostasis was prevented in SITA: 3 of 15 subjects had impaired glucose tolerance (IGT) before and after the study. In CON, none had type 2 diabetes (T2D), and 4 had IGT at the beginning. After 12 weeks, IGT was observed in 2 and T2D in 3 subjects.Conclusion: SITA improved beta-cell function and prevented a conversion to IGT and T2D in metformin-intolerant obese PCOS patients.Abbreviations: BMI = body mass index; DPP-4 = dipeptidyl peptidase-4; DXA = dual energy X-ray absorptiometry; GIP = glucose-dependent insulinotropic peptide; GLP-1 = glucagon-like peptide-1; HOMA-B = homeostasis model assessment for beta-cell function; HOMA-IR = homeostasis model assessment of insulin resistance; IAI = insulin action index; IGT = impaired glucose tolerance; IR = insulin resistance; MBCI = modified beta-cell function index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index; PCOS = polycystic ovary syndrome; SHBG = sex hormone–binding globulin; T2D = type 2 diabetes     

Prevalence of Diabetes,Prediabetes, and Stress Hyperglycemia: Insulin Therapy and Metabolic Control in Patients on Total Parenteral Nutrition (Prospective Multicenter Study)

ObjectiveThe prevalence of carbohydrate metabolism disorders in patients who receive total parenteral nutrition (TPN) is not well known. These disorders can affect the treatment, metabolic control, and prognosis of affected patients. The aims of this study were to determine the prevalence in noncritically ill patients on TPN of diabetes, prediabetes, and stress hyperglycemia; the factors affecting hyperglycemia during TPN; and the insulin therapy provided and the metabolic control achieved.MethodsWe undertook a prospective multicenter study involving 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included, and data were collected on demographic, clinical, and laboratory variables (glycated hemoglobin, C-reactive protein [CRP], capillary blood glucose) as well as insulin treatment.ResultsThe study included 605 patients. Before initiation of TPN, the prevalence of known diabetes was 17.4%, unknown diabetes 4.3%, stress hyperglycemia 7.1%, and prediabetes 27.8%. During TPN therapy, 50.9% of patients had at least one capillary blood glucose of > 180 mg/dL. Predisposing factors were age, levels of CRP and glycated hemoglobin, the presence of diabetes, infectious complications, the number of grams of carbohydrates infused, and the administration of glucose-elevating drugs. Most (71.6%) patients were treated with insulin. The mean capillary blood glucose levels during TPN were: known diabetes (178.6 ± 46.5 mg/dL), unknown diabetes (173.9 ± 51.9), prediabetes (136.0 ± 25.4), stress hyperglycemia (146.0 ± 29.3), and normal (123.2 ± 19.9) (P < .001).ConclusionThe prevalence of carbohydrate metabolism disorders is very high in noncritically ill patients on TPN. These disorders affect insulin treatment and the degree of metabolic control achieved. (Endocr Pract. 2015;21:59-67)     

Basal-Bolus Regimen With Insulin Analogues Versus Human Insulin in Medical Patients with type 2 Diabetes: A Randomized Controlled Trial in Latin America

Objective: Few randomized studies have focused on the optimal management of non–intensive care unit patients with type 2 diabetes in Latin America. We compared the safety and efficacy of a basal-bolus regimen with analogues and human insulins in general medicine patients admitted to a University Hospital in Asunción, Paraguay.Methods: In a prospective, open-label trial, we randomized 134 nonsurgical patients with blood glucose (BG) between 140 and 400 mg/dL to a basal-bolus regimen with glargine once daily and glulisine before meals (n = 66) or Neutral Protamine Hagedorn (NPH) twice daily and regular insulin before meals (n = 68). Major outcomes included differences in daily BG levels and frequency of hypoglycemic events between treatment groups.Results: There were no differences in the mean daily BG (157 ± 37 mg/dL versus 158 ± 44 mg/dL; P = .90) or in the number of BG readings within target <140 mg/dL before meals (76% versus 74%) between the glargine/glulisine and NPH/regular regimens. The mean insulin dose in the glargine/glulisine group was 0.76 ± 0.3 units/kg/day (glargine, 22 ± 9 units/day; glulisine, 31 ± 12 units/day) and was not different compared with NPH/regular group (0.75 ± 0.3 units/kg/day [NPH, 28 ± 12 units/day; regular, 23 ± 9 units/day]). The overall prevalence of hypoglycemia (<70 mg/dL) was similar between patients treated with NPH/regular and glargine/glulisine (38% versus 35%; P = .68), but more patients treated with human insulin had severe (<40 mg/dL) hypoglycemia (7.6% versus 25%; P = .08). There were no differences in length of hospital stay or mortality between groups.Conclusion: The basal-bolus regimen with insulin analogues resulted in equivalent glycemic control and frequency of hypoglycemia compared to treatment with human insulin in hospitalized patients with diabetes.Abbreviations: BG = blood glucose BMI = body mass index HbA_1c = glycated hemoglobin NPH = Neutral Protamine Hagedorn T2D = type 2 diabetes     

Impact of Family History of Diabetes on Diabetes Control and Complications

Objective: Our aim was to assess the impact of parental and sibling history of type 2 diabetes (T2D) on patient characteristics, glycemic control, and T2D complications.Methods: This cross-sectional study included adults with T2D. Type 1 diabetes and gestational diabetes patients were excluded. The laboratory data were retrieved from the patients' electronic files, and baseline measurements were obtained by the researchers.Results: The study included a total of 511 T2D patients, with a mean age of 60.1 ± 10.9 years and mean hemoglobin A1c of 8.94 ± 2.1% (74.2 ± 22.9 mmol/mol). Of these patients, 54% were male and 49.7% had a parental history of T2D. The patients with parental history of T2D were diagnosed at a younger age and had a higher body mass index (BMI) (P =.035) and higher waist circumference (WC) (P =.013) than those T2D patients with no parental history. Approximately 60% of the participants had siblings with a history of T2D, and in comparison with those with no sibling history, they had higher prevalence of cerebrovascular accidents (P =.02).Conclusion: Having a parental history of T2D is significantly associated with diagnosis at a younger age and a higher BMI and WC. Having a sibling history of T2D is significantly associated with worse cerebrovascular outcome.Abbreviations: ACR = albumin to creatinine ratio; BMI = body mass index; DBP = diastolic blood pressure; DM = diabetes mellitus; FBG = fasting blood glucose; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; LDL = low-density lipoprotein; SBP = systolic blood pressure; T2D = type 2 diabetes; TG = triglyceride; WC = waist circumference     

Hospital Insulin Protocol Aims For Glucose Control In Glucocorticoid-Induced Hyperglycemia

Objective: To compare the effectiveness of 2 insulin protocols to treat glucocorticoid-induced hyperglycemia in the nonintensive care hospital setting.Methods: A randomized, open-label, parallel-arm study was conducted comparing standard recommended care of complete insulin orders (CIO) (i.e., 3-part insulin regimen of long-acting basal [background], rapid-acting bolus [mealtime], and rapid-acting correction factor) to an experimental group following a regimen of Neutral Protamine Hagedorn (NPH) plus CIO (NPH-CIO). The primary outcome was mean blood glucose (BG), and the secondary outcome was percent of BG in target range of 70 to 180 mg/dL. Hypoglycemia was also evaluated.Results: Sixty-one patients completed 2 to 5 consecutive inpatient days (31 CIO; 30 NPH-CIO). Baseline mean BG results were 237.2 ± 50.2 and 221.9 ± 35.8 mg/dL (P = .30) in the CIO and NPH-CIO groups, respectively. No significant difference in overall mean BG between the 2 groups was detected; however, a significant difference arose on day 3: mean BG 181.8 ± 32.6 mg/dL (CIO) versus 157.2 ± 6.1 mg/dL (NPH-CIO) (P = .03). Moreover, the total daily doses (TDDs) of insulin did not differ: 34.8 ± 43.0 units (CIO) versus 35.8 ± 25.0 units (NPH-CIO) (P = .13). Percent of BG in target was 54.6% (CIO) and 62% (NPH-CIO) (P = .24). Incidence of severe hypoglycemia (<50 mg/dL) was the same in both groups (0.1%).Conclusion: NPH added to 3-part insulin regimen (CIO) may be an effective way to a combat glucocorticoid-induced hyperglycemia, though further research is needed in a larger population.Abbreviations:A1C = hemoglobin A1CBG = blood glucoseCIO = complete insulin ordersDM = diabetes mellitusNPH = neutral protamine HagedornNPH-CIO = neutral protamine Hagedorn plus CIOTDD = total daily dose     

Relationship Between the Environmental Endocrine Disruptor Bisphenol a and Dyslipidemia: A Five-Year Prospective Study

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia.Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL <40 mg/dL). Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Multivariable linear and logistic regression models were used. Data from baseline and follow-up were used for cross-sectional and longitudinal analyses, respectively.Results: In the cross-sectional analysis, compared to subjects in the low BPA tertile, those in the high BPA tertile showed a higher level of LDL cholesterol (108.1 ± 24.4 mg/dL versus 119.5 ± 26.9 mg/dL; P<.05) and a lower level of HDL cholesterol (46.2 ± 11.7 mg/dL versus 39.5 ± 7.5 mg/dL; P<.05). In multivariable linear regression models, Z-transformed BPA was positively associated with LDL cholesterol (β= 0.13, P = .002) and negatively associated with HDL cholesterol (β= -0.28; P<.001). After cross-sectionally adjusting for confounders, subjects in higher BPA exposure was associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, in subjects without low-HDL-cholesterolemia at baseline, each SD increment in baseline BPA was associated with a higher incidence of low-HDL-cholesterolemia after adjustment for confounders (odds ratio [95% confidence interval; CI] 2.76, 95% CI 1.21, 6.29).Conclusion: Cross-sectionally, higher BPA exposure is associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, baseline BPA is an independent predictor of the 5-year incidence of low-HDL-cholesterolemia.Abbreviations: BMI = body mass index; BPA = bisphenol A; CI = confidence interval; CVD = cardiovascular disease; EIMDS = environment, inflammation and metabolic diseases study; HDL = high density lipoprotein; LDL = low density lipoprotein; OR = odds ratio; PPAR = peroxisome proliferator-activated receptor; SBP = systolic blood pressure; TG = triglyceride; Z-BPA = Z-transformed bisphenol A     

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