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)     

Pediatric Diabetic Ketoacidosis with Hyperosmolarity: Clinical Characteristics and Outcomes

Objective: Studies of hyperglycemic emergencies with hyperosmolality, including hyperglycemic hyperosmolar state (HHS) and “mixed presentation” with features of diabetic ketoacidosis (DKA) and HHS, are lacking in children. Objectives were to determine the incidence of DKA, HHS, and mixed presentation in a pediatric population, to characterize complications, and to assess accuracy of associated diagnosis codes.Methods: Retrospective cohort study of 411 hyperglycemic emergencies in pediatric patients hospitalized between 2009 and 2014. Hyperglycemic emergency type was determined by biochemical criteria and compared to the associated diagnosis code.Results: Hyperglycemic emergencies included: 333 DKA, 54 mixed presentation, and 3 HHS. Altered mental status occurred more frequently in hyperosmolar events (P<.0001), and patients with hyperosmolarity had 3.7-fold greater odds of developing complications compared to those with DKA (P =.0187). Of those with DKA, 98.5% were coded correctly. The majority (81.5%) of mixed DKA-HHS events were coded incorrectly. Events coded incorrectly had 3.1-fold greater odds of a complication (P =.02).Conclusion: A mixed DKA-HHS presentation occurred in 13.8% of characterized hyperglycemic emergencies, whereas HHS remained a rare diagnosis (0.8%) in pediatrics. Hyperosmolar events had higher rates of complications. As treatment of hyperosmolarity differs from DKA, its recognition is essential for appropriate management.Abbreviations: AMS = altered mental status; DKA = diabetic ketoacidosis; EMR = electronic medical record; HHS = hyperglycemic hyperosmolar state; ICD-9 = International Classification of Diseases, Ninth Revision; ISPAD = International Society of Pediatric and Adolescent Diabetes; NODM = new-onset diabetes mellitus; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

Diabetes and Prediabetes are Significantly Higher in Morbidly Obese Children Compared With Obese Children

Objective: The objective of this study was to examine the prevalence and characteristics of comorbidities in obese and morbidly obese children with a comparison between the 2 sets of children.Methods: This was a retrospective electronic chart review of obese and morbidly obese children and adolescents as defined by body mass index. We evaluated medical history of comorbid conditions, medication use, and cardiovascular risk markers, including blood pressure, lipid profile, and glycosylated hemoglobin.Results: There were 1,111 subjects (African American = 635; non-Hispanic white = 364; Hispanic = 36; others = 86), of which 274 were obese and 837 were morbidly obese children with a mean age of 12.7 ± 3.37 years. Morbidly obese children had a higher prevalence of prediabetes (19.5% of obese versus 27.3% of morbidly obese; P<.0001) and type 2 diabetes (39.8% of obese versus 52.4% of morbidly obese; P<.0001). Use of medications for treatment of asthma was significantly higher in the morbidly obese group compared with the obese group (21% versus 14%; P = .01).Conclusion: Morbidly obese children have a higher prevalence of diabetes, prediabetes, and use of asthma medications compared with obese children.Abbreviations: AA = African American ADHD = attention deficit hyperactivity disorder BMI = body mass index BP = blood pressure CVD = cardiovascular disease DBP = diastolic blood pressure EMR = electronic medical record GERD = gastroesophageal reflux disease HbA_1c = glycated hemoglobin HDL = high-density lipoprotein HTN = hypertension LDL = low-density lipoprotein NHW = non-Hispanic white SBP = systolic blood pressure T2DM = type 2 diabetes mellitus     

Pathophysiological correlation of arginase-1 in development of type 2 diabetes from obesity in adolescents

BackgroundThere is great interest to understand causal pathophysiological correlation between obesity and diabetes mellitus (DM). Vascular endothelial dysfunction is crucially involved in pathogenesis of vascular complications in DM. Recently, increased arginase expression and activity have been described as underlying mechanisms of endothelial dysfunction in DM and vascular inflammation in obesity. By limiting L-arginine bioavailability to endothelial nitric oxide synthase (NOS III), nitric oxide production is potentially impaired.MethodsWe investigated the impact of plasma from diabetic and obese adolescents on arginase and NOS III expression in cultured human endothelial cells (ECs). A total of 148 male adolescents participated in this study including 18 obese, 28 type 1-, 28 type 2-DM patients, and 74 age-matched healthy volunteers.ResultsA concurrent increase in arginase-1 (1.97-fold) and decrease in NOS III expression (1.45-fold) was observed in ECs exposed to type 2 diabetic plasma compared to control subjects. ECs incubated with type 1 DM plasma had a diminished NOS III level without impact on arginase-1 expression. Urea-assay featured an increased arginase activity in treated ECs with type 1- or 2-DM plasma. Despite increased pro-inflammatory cytokines and chemokines in obese plasma, arginase-1 expression/activity did not change in treated ECs. However, NOS III expression was significantly reduced. Pearson analysis revealed positive correlation between arginase-1, but not NOS III, expression with FBS in ECs treated with type 2-DM plasma.ConclusionsOur data demonstrate that increased arginase-1 expression/activity in ECs, as critical pathogenic factor is correlated with development of obesity-related type 2-DM and linked vascular disease.     

Ketosis-Prone Type 2 Diabetes: Effect of Hyperglycemia on β-Cell Function and Skeletal Muscle Insulin Signaling

ObjectiveTo determine the underlying mechanism for the severe and transient β-cell dysfunction and impaired insulin action in obese African American patients with ketosis-prone diabetes.MethodsThe effect of sustained hyperglycemia (glucotoxicity) and increased free fatty acids (lipotoxicity) on β-cell function was assessed by changes in insulin secretion during a 20-hour glucose (200 mg/m² per minute) and a 48-hour Intralipid (40 mL/h) infusion, respectively. Insulin-activated signaling pathways and pattern of Akt-1 and Akt-2 expression and insulin-stimulated phosphorylation were analyzed in skeletal muscle biopsy specimens. Studies were performed in an obese African American woman within 48 hours after resolution of diabetic ketoacidosis and 1 week after discontinuation of insulin treatment.ResultsDextrose infusion rapidly increased C-pep-tide levels from a baseline of 3.2 ng/mL to a mean of 7.1 ± 0.5 ng/mL during the first 8 hours of infusion; thereafter, C-peptide levels progressively declined. Lipid infusion was not associated with any deleterious effect on insulin and C-peptide secretion. Initial in vitro stimulation of muscle tissue with insulin resulted in a substantial and selectively decreased Akt-2 expression and insulin-stimulated phosphorylation on the serine residue. Improved metabolic control resulted in 70% greater Akt expression at near-normoglycemic remission in comparison with the period of hyperglycemia.ConclusionHyperglycemia, but not increased free fatty acid levels, led to progressive β-cell dysfunction and impaired insulin secretion. Hyperglycemia was also associated with diminished skeletal muscle Akt expression and phosphorylation in an African American woman with ketosis-prone diabetes, and this defect improved notably with aggressive insulin therapy. These results indicate the importance of glucose toxicity in the pathogenesis of keto-sis-prone diabetes in obese African American patients. (Endocr Pract. 2007;13:283-290)     

Increased Risk of Ischemic Stroke after Hyperosmolar Hyperglycemic State: A Population-Based Follow-Up Study

Background

Although much attention has been focused on the association between chronic hyperglycemia and cerebrovascular diseases in type 2 diabetes mellitus (DM) patients, there is no data regarding the risk of ischemic stroke after a hyperosmolar hyperglycemic state (HHS) attack. The objective of this study was to investigate the risk of ischemic stroke in type 2 DM patients after an HHS attack.

Methods

From 2004 to 2008, this retrospective observational study was conducted on a large cohort of Taiwanese using Taiwan’s National Health Insurance Research Database (NHIRD). We identified 19,031 type 2 DM patients who were discharged with a diagnosis of HHS and 521,229 type 2 DM patients without an HHS diagnosis. Using the propensity score generated from logistic regression models, conditional on baseline covariates, we matched 19,031 type 2 DM patients with an HHS diagnosis with the same number from the comparison cohort. The one-year cumulative rate for ischemic stroke was estimated using the Kaplan-Meier method. After adjusting covariates, Cox proportional hazard regression was used to compute the adjusted one-year rate of ischemic stroke.

Results

Of the patients sampled, 1,810 (9.5%) of the type 2 DM patients with HHS and 996 (5.2%) of the comparison cohort developed ischemic stroke during the one-year follow-up period. After adjusting for covariates, the adjusted HR for developing ischemic stroke during the one-year follow-up period was 1.8 (95% C.I., 1.67 to 1.95, P<0.001) for type 2 DM patients with HHS compared with those without HHS.

Conclusion

Although DM is a well-recognized risk factor for atherosclerosis, type 2 DM patients that have suffered a HHS attacks are at an increased risk of developing ischemic stroke compared with those without HHS.     

Hyperinsulinemia Associated With Acanthosis Nigricans,Finger Pebbles,Acrochordons, And The Sign Of Leser-Trélat

ObjectiveTo review common skin manifestations associated with type 2 diabetes mellitus (DM), and to discuss a potential underlying mechanism for these manifestations.MethodsA PubMed literature search was conducted for articles describing the skin manifestations associated with hyperinsulinemia and type 2 DM. A case presentation describes a morbidly obese patient with type 2 DM treated with metformin who developed acanthosis nigricans, finger pebbles, scores of skin tags (acrochordons), and the sign of LeserTrelat (sudden onset shower of seborrheic keratoses) in the absence of internal malignancy.ResultsAcanthosis nigricans, acrochordons, and finger pebbles have been associated with type 2 DM and obesity. While the LeserTrelat sign is classically associated with internal malignancy, it can also be idiopathic. To our knowledge, this the first report of the occurrence of the LeserTrelat sign in a patient with DM absent internal malignancy.ConclusionSeveral skin manifestations can be seen in this patient with DM because of underlying insulin resistance and subsequent stimulation of insulinlike growth factor receptors. Management strategies could include weight loss, diet, and insulinsensitizing pharmacologic therapy. (Endocr Pract. 2013;19:522525)     

Hypoglycemia in childhood type 1 diabetes mellitus: Understanding and managing the dark side of intensive insulin therapy

Background: Despite the availability of advanced insulin delivery systems, blood glucose-monitoring equipment, and insulin analogue formulations, hypoglycemia remains a significant concern in the treatment of children and adolescents with type 1 diabetes mellitus (DM). Furthermore, patients who manage their blood glucose levels most effectively may also be the ones at greatest risk for hypoglycemia.Objective: The aim of this article was to review current issues surrounding the pathophysiology and frequency of hypoglycemia in children and adolescents with type 1 DM.Methods: Relevant articles for this review were identified through a search of MEDLINE (1992–2007; English-language articles only). The search terms used were children, adolescents, hypoglycemia, diabetes, insulin, and continuous subcutaneous insulin infusion.Results: The threat of severe hypoglycemia remains a major obstacle to the effective treatment of type 1 DM. Basalbolus therapy, using continuous subcutaneous insulin infusion or multiple daily injections, is the most effective and flexible method available for maintaining good glycemic control in children as well as in adults. Insulin analogues can be used effectively in these regimens and may be helpful toward addressing risks for hypoglycemia. Patient education should also be given a high priority in addressing the risk of hypoglycemia in children and adolescents with type 1 DM. The development of continuous glucose-monitoring systems offers the potential for an even brighter future for this group of patients.Conclusions: Recent advances in DM technology reduce but do not eliminate the risk of hypoglycemia in youth with type 1 DM. These observations underscore the need for a closed-loop insulin delivery system in which the rate of insulin infusion is regulated by real-time changes in glucose concentrations. (Insulin. 2007;2:157–165)Key words: type 1 diabetes mellitus; hypoglycemia; children; adolescents; insulin analogue; continuous subcutaneous insulin infusion; multiple daily injections; basal-bolus therapy.Accepted for publication 09052007     

Influence of cardiovascular disease risk factors on the relationship between low bone mineral density and type 2 diabetes mellitus in a multiethnic us population of women and men: A cross-sectional study

Introduction: Higher bone mineral density (BMD) has been reported among white women and men with type 2 diabetes mellitus (DM) compared with nondiabetic white individuals, but there is scant evidence for nonwhite persons. It is also not known whether cardiovascular disease (CVD) risk factors may confound any association between BMD and type 2 DM.Objective: The present study examined the relationship between low BMD and type 2 DM in a multiethnic population of women and men while controlling for the influence of osteoporosis and CVD risk factors including body mass index (BMI), cigarette smoking, physical inactivity, total cholesterol and its components, blood pressure, and C-reactive protein.Methods: Data collected from 4929 African American, Mexican American, and white women and men aged 50 to 79 years who participated in the household interview and clinical examinations during the Third National Health and Nutrition Examination Survey were analyzed. CVD risk factors associated with type 2 DM in this study population were included as covariates in gender-specific multiple logistic regression models assessing the relationship between type 2 DM and low BMD while controlling for osteoporosis risk factors. Gender- and race/ethnicity-specific mean BMD values at the total hip for young adults aged 20 to 29 years were used to establish race/ethnicity and gender-specific low BMD T-scores.Results: The final study population included 2505 women and 2424 men. More women and men with type 2 DM than women and men without type 2 DM were nonwhite and had high BMI. Osteoporosis risk factors but not CVD risk factors were associated with low BMD in both women and men. Type 2 DM was not associated with low BMD among women (odds ratio [OR] = 0.77; 95% CI, 0.56-1.08). Based on a statistically significant interaction between type 2 DM status and race/ethnicity, white men with type 2 DM were less likely to have low BMD than were white men without type 2 DM (OR = 0.56; 95% CI, 0.37-0.86; P = 0.01). There was no significant BMD difference between diabetic and nondiabetic nonwhite men.Conclusion: CVD risk factors did not appear to influence the relationship between low BMD and type 2 DM in this study     

Does Clinical Inertia Vary By Personalized A1C Goal? A Study Of Predictors And Prevalence Of Clinical Inertia In A U.S. Managed Care Setting

Objective: Clinical inertia is defined as failure to initiate or intensify therapy despite an inadequate treatment response. We assessed the prevalence and identified the predictors of clinical inertia among patients with type 2 diabetes (T2DM) based on personalized goals.Methods: Three hemoglobin A_1c (A1C) targets (American Diabetes Association A1C <7.0%; modified Ismail-Beigi et al; and Healthcare Effectiveness Data and Information Set) were used when identifying adult patients with T2DM who experienced above-target A1C values during the index period (July 1, 2008 to June 30, 2012) in a U.S. managed-care claims database (IMPACT™). Clinical inertia was defined as no intensification of treatment during the response period. Demographic and clinical characteristics were analyzed to identify predictors of treatment intensification.Results: Irrespective of A1C target, the majority of patients with T2DM (70.4 to 72.8%) experienced clinical inertia in the 6 months following the index event, with 5.3 to 6.2% of patients intensifying treatment with insulin. Patients with a lower likelihood of intensification were older, used >1 oral antidiabetes drug during the baseline period, and had an above-target A1C more recently. Treatment intensification was associated with patients who had point-of-service insurance, mental illness, an endocrinologist visit in the baseline period, or higher index A1C.Conclusion: The prevalence of clinical inertia among patients with T2DM in a U.S. managed-care setting is high and has increased over more recent years. Factors predicting increased risk of clinical inertia may help identify “at-risk” populations and assist in developing strategies to improve their management.Abbreviations:A1C = hemoglobin A_1cADA = American Diabetes AssociationCCI = Charlson Comorbidity IndexGLP-1 = glucagon-like peptide 1HEDIS = Healthcare Effectiveness Data and Information SetICD-9-CM = International Classification of Diseases, 9th Revision, Clinical ModificationOAD = oral antidiabetes drugPCPs = primary care physiciansT2DM = type 2 diabetes mellitus     

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)     

Family History of Diabetes is Associated with Increased Risk of Recurrent Diabetic Ketoacidosis in Pediatric Patients

Objective: To determine the relationship between family history of diabetes mellitus (DM) and diabetic ketoacidosis (DKA) recurrence in youth with established type 1 diabetes mellitus (T1DM).Methods: We performed a retrospective chart review of patients with DKA admitted to a pediatric hospital between January, 2009, and December, 2014. We compared patients with recurrent (≥2 admissions) and nonrecurrent DKA (1 admission) and investigated patient level factors, including family history, that may be associated with DKA recurrence in pediatric patients with established T1DM.Results: Of the 131 subjects in the study, 51 (39%) subjects were in the recurrence group. Age ≥15 years old, public health insurance, and family history of T1DM or type 2 diabetes mellitus were associated with recurrent DKA admissions in both univariable and multivariable analyses. Family history was associated with DKA recurrence, with an incidence rate ratio of 1.5 (95% confidence interval = 1.0 to 2.3; P = .03). The association was not explained by type of familial diabetes, first degree relative status, or whether the family member lived in the household.Conclusion: Recognition that a positive family history of DM may be associated with a higher risk for DKA recurrence in patients with established T1DM may allow for targeted education and focus on a previously unidentified population at increased risk for DKA. Understanding the mechanism underlying the effect of family history of diabetes on the rates of DKA in patients with established T1DM may allow for improved identification and education of patients who may be at risk for DKA recurrence.Abbreviations: CI = confidence interval; DKA = diabetic ketoacidosis; EHR = electronic health record; IBD = inflammatory bowel disease; IRR = incidence rate ratio; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

Patient Behaviors Associated with Optimum Glycemic Outcomes with Sensor-Augmented Pump Therapy: Insights from The Star 3 Study

ObjectiveThe purpose of this analysis was to identify patient behaviors that led to optimum glycemic outcomes in subjects with type 1 diabetes (T1DM) who transitioned from multiple daily injections (MDI) therapy to sensor-augmented pump (SAP) therapy.MethodsSensor-augmented pump Therapy for A1C Reduction (STAR 3), a randomized controlled trial, assigned 485 suboptimally controlled T1DM subjects to either MDI therapy (n = 241) or SAP therapy (n = 244). We categorized subjects in the latter group according to age at enrollment and glycated hemoglobin (A1C) value after using the SAP system for 12 months. Pairwise comparisons of how the pump features were used between SAP subjects with the highest and lowest end-of-study A1C values were made via t tests.ResultsLarger decreases in A1C values were significantly correlated with increasing sensor use in both the adult and pediatric age groups. Subjects in the low-A1C cohorts of both pediatric and adult age groups gave themselves smaller and more frequent boluses and used the Bolus Wizard bolus estimation calculator more frequently than subjects in age-matched high-A1C cohorts. Children in the low-A1C cohort used less insulin than children in the high-A1C cohort. There was no additional hypoglyce-mia in either the adult or pediatric low-A1C cohorts versus their high-A1C counterparts.ConclusionsBoth adult and pediatric patients with T1DM on SAP who use CGM sensors more often will have a greater decrease in their A1C values than those who do not demonstrate these behaviors. Routine use of CGM may lead to smaller and more frequent bolus dosing, enabling this population to safely reach their A1C goals. (Endocr Pract. 2015;21:41-45)     

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)     

Glucose dysregulation in obese children: predictive, risk, and potential protective factors

Objective: The aim of our study was to determine the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (DM2) in obese children and adolescents of Greek origin and compare our data with pertinent literature findings in an attempt to uncover predictive, risk, and preventive factors. Research Methods and Procedures: A total of 117 obese children and adolescents 12.1 ± 2.7 years old underwent a 2‐hour oral glucose tolerance test (OGTT). Insulin resistance (IR) and β‐cell function were estimated using the homeostasis model assessment (HOMA)‐IR and the insulinogenic index, respectively. Results: A total of 17 patients (14.5%) had IGT, and none had DM2. The overall prevalence rates of both IGT and DM2 in our subjects were lower than those reported in a recent multiethnic U.S. study. Nevertheless, the difference between our IGT data and those of the U.S. study was due mostly to the prepubertal subjects (9% vs. 25.4%), whereas no difference was observed in the pubertal population (18% vs. 21%). Fasting glucose, insulin, and HOMA‐IR values were not predictive of IGT. The absolute value of insulin at 2 hours of the OGTT combined with the time‐integrated glycemia (AUCG) can strongly predict IGT, whereas higher area under the curve for insulin (AUCI) values were found to be protective. Discussion: In ethnic groups less prone to diabetes development, IGT or DM2 in obese subjects is more likely to develop at puberty than at the prepubertal stage. It is advisable that physicians caring for obese adolescents perform an OGTT for early detection of IGT because HOMA‐IR values, although higher in IGT subjects and indicative of IR, cannot predict IGT.     

Low Urine Calcium Excretion in African American Patients with Primary Hyperparathyroidism

ObjectiveTo evaluate the prevalence of low urine calcium excretion in African American patients with primary hyperparathyroidism (PHPT), a common disorder associated with bone and renal complications, and to assess the distinction between PHPT and familial hypocalciuric hypercalcemia (FHH), a rare benign genetic disease.MethodsWe conducted a retrospective study on a cohort of 1,297 patients in whom a 24-hour urine study was performed for measurement of urine calcium and creatinine. PHPT was diagnosed if the serum calcium concentration was ≥ 10.5 mg/dL and intact parathyroid hormone (PTH) was ≥ 40 pg/mL. Patients receiving medications that affect urine calcium or with glomerular filtration rate ≤ 30 mL/min were excluded.ResultsNinety-six patients satisfied the diagnostic criteria for PHPT. The African American (n = 70) and non-African American (n = 26) patients did not differ in their mean age, body mass index, glomerular filtration rate, serum PTH, 25-hydroxyvitamin D levels, and 24-hour urine creatinine values. Median values of urine calcium/creatinine (mg/g) were 122 for African American versus 214 for non-African American patients (P = .006). Thirty-one of 70 African American patients (44%) had a urine calcium/creatinine ratio ≤ 100 mg/g, whereas only 2 of 26 non-African American patients (8%) had this value (P = .001).ConclusionThe prevalence of low urine calcium excretion among African American patients with PHPT is unexpectedly high. A threshold of 100 mg/g urine calcium/ creatinine identified 44% of such patients with PHPT as having FHH in this cohort. Therefore, other clinical criteria and laboratory variables should be used to distinguish PHPT from FHH in African American patients with PTH-dependent hypercalcemia. (Endocr Pract. 2011;17: 867-872)     

Prevalence of Hypogonadism in Patients with Type 2 Diabetes Mellitus in an Asian Indian Study Group

ObjectiveTo determine the prevalence of hypogonadism in Asian Indian patients with type 2 diabetes mellitus (T2DM) and to correlate it with components of the metabolic syndrome and microvascular complications of T2DM.MethodsOne hundred consecutive male patients with T2DM between 25 and 50 years of age and 50 age-matched healthy adults without diabetes underwent assessment. Calculated free testosterone was derived by using serum total testosterone and sex hormone-binding globulin. Those patients with 2 calculated free testosterone values less than 64.8 pg/mL were diagnosed as having hypogonadism.ResultsOf the 100 patients with T2DM, 15 (15%) were found to have hypogonadism—7 of 29 (24%) between 31 and 40 years of age and 8 of 67 (12%) between 41 and 50 years old. None of the 4 patients between 25 and 30 years old had hypogonadism. Eleven patients (73%) had hypogonadotropic hypogonadism, and 4 (27%) had hypergonadotropic hypogonadism. Among the control subjects, the prevalence of hypogonadism was 10%. In comparison with Western data, we found a higher prevalence of hypogonadism in patients with T2DM, especially in those in the 4th decade of life. The prevalence of hypogonadism was higher in obese patients, although it did not reach statistical significance. No statistically significant correlation was observed between hypogonadism and age, duration of diabetes, glycemic control, androgen deficiency symptoms, or microvascular complications.ConclusionThe prevalence of hypogonadism was higher in the patients with diabetes than in the control subjects, although the difference did not reach statistical significance. There was no correlation of hypogonadism with components of the metabolic syndrome or microvascular complications of diabetes mellitus. (Endocr Pract. 2009;15:513-520)     

Potential Place of SGLT2 Inhibitors in Treatment Paradigms for type 2 Diabetes Mellitus

Objective: Following the first Food and Drug Administration (FDA) approval in 2013, sodium glucose cotransporter 2 (SGLT2) inhibitors have generated much interest among physicians treating patients with type 2 diabetes mellitus (T2DM). Here, the role in treatment with this drug class is considered in the context of T2DM treatment paradigms.Methods: The clinical trials for the SGLT2 inhibitors are examined with a focus on canagliflozin, dapagliflozin, and empagliflozin.Results: Evidence from clinical trials in patients with T2DM supports the use of SGLT2 inhibitors either as monotherapy or in addition to other glucose-lowering treatments as adjuncts to diet and exercise, and we have gained significant clinical experience in a relatively short time.Conclusion: The drugs appear to be useful in a variety of T2DM populations, contingent primarily on renal function. Most obviously, SGLT2 inhibitors appear to be well suited for patients with potential for hypoglycemia or weight gain. In clinical trials, patients treated with SGLT2 inhibitors have experienced moderate weight loss and a low risk of hypoglycemic events except when used in combination with an insulin secretagogue. In addition, SGLT2 inhibitors have been shown to reduce blood pressure, so they may be beneficial in patients with T2DM complicated by hypertension. SGLT2 inhibitors were incorporated into the 2015 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia and received an even more prominent position in the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive diabetes management guidelines and algorithm.Abbreviations: AE = adverse event A1C = glycated hemoglobin CI = confidence interval CKD = chronic kidney disease DKA = diabetic ketoacidosis DPP-4 = dipeptidyl peptidase 4 eGFR = estimated glomerular filtration rate FDA = Food and Drug Administration FPG = fasting plasma glucose GLP-1 = glucagon-like peptide 1 HDL-C = high-density lipoprotein cholesterol HR = hazard ratio LADA = late-onset autoimmune diabetes of adulthood LDL-C = low-density lipoprotein cholesterol MACE = major adverse cardiovascular events SGLT1 = sodium glucose cotransporter 1 SGLT2 = sodium glucose cotransporter 2 T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus UACR = urine albumin to creatinine ratio     

Factors Associated with Glycemic Control in Patients with Type 2 Diabetes Mellitus in Rural Areas of the United States

Background: According to the US Department of Health and Human Services, an estimated 18.2 million Americans, or 6.3% of the population, has diabetes mellitus (DM). Approximately 90% of these individuals have type 2 DM. The most widely used clinical test for defining glycemic control is measurement of blood glycosylated hemoglobin (AIC).Objective: The goal of this study was to estimate the proportion of diabetic patients who achieved the AIC goal of _<7.0% in a rural western Pennsylvania practice and to determine the factors that influence the achievement of the AIC goal.Methods: This was an observational study conducted in a rural family medicine office in Clarksburg, Pennsylvania. To be included in the study, patients had to have been diagnosed with type 2 DM >2 years prior, had to be aged >18 years, and had to be adhering to a medical nutrition therapy diet. Both univariate analysis and logistic regressions were used to identify the factors that were associated with the outcome.Results: A total of 136 diabetic patients were included in the study (70 men, 66 women; mean [SD] age, 59.7 [15.2] years). AIC of <7.0% was attained in 75.0% (n = 102) of the patients. Although the majority of patients were obese (69.1% [n = 94] with a body mass index >30 kg/m2), weight was not a factor in reaching AIC goal. The data showed that those patients who were older (62.3 vs 51.9 years; P = 0.004), using oral antidiabetic medication (96.1% vs 87.9%; P = 0.100), and not using insulin (86.3% vs 69.7%; P = 0.030) were more likely to achieve AIC goal. The proportion of patients achieving AIC goal levels decreased as the number of oral medications used increased.Conclusions: In this rural area of western Pennsylvania, the majority of our type 2 DM patients achieved glycemic control (ie, AIC <7.0%). The primary care physician, along with a DM care team, should address the issues of diet, exercise, weight management, and other comorbid illnesses to properly manage patients with type 2 DM. (Insulin. 2007;2:134-141)