Patient-Led Versus Physician-Led Titration of Insulin Glargine in Patients with Uncontrolled Type 2 Diabetes: A Randomized Multinational Atlas Study

ObjectiveSelf-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents.MethodsPatient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA_1c) at week 24 in the patient-led versus physician-led titration groups.ResultsPatient-led titration resulted in a significantly higher drop in HbA_1c value at 24 weeks when compared with physician-led titration (− 1.40% vs. − 1.25%; mean difference, − 0.15; 95% confidence interval, − 0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (− 2.85 mmol/L vs. − 2.48 mmol/L; P = .001). The improvements in HbA_1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; P < .001). Target HbA_1c of < 7.0% without severe hypoglycemia was achieved in 40.0% and 32.9% in the patient-led and physician-led groups, respectively (P = .086). Severe hypoglycemia was not different in the 2 groups (0.7%), with an increase in nocturnal and symptomatic hypoglycemia in the patient-led arm.ConclusionPatient-led insulin glargine titration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided. (Endocr Pract. 2015;21:143-157)     

Effects of Colesevelam,Rosiglitazone, or Sitagliptin on Glycemic Control and Lipid Profile in Patients with Type 2 Diabetes Mellitus Inadequately Controlled by Metformin Monotherapy

ObjectiveTo evaluate the glycemic effect of colesevelam, rosiglitazone, or sitagliptin when added to metformin monotherapy in patients with type 2 diabetes mellitus (DM) and to examine the effects of these antidiabetes agents on lipid and lipoprotein levels.MethodsThis 16-week, open-label pilot study conducted between May 2007 and April 2008 at 20 sites in the United States, 7 sites in Mexico, and 6 sites in Colombia, enrolled adults with inadequately controlled type 2 DM (glycated hemoglobin [HbA_1c], 7.0%-10.0%) on a stable metformin regimen (1500-2550 mg daily for ≥ 3 months). At Week 0, participants were randomly assigned 1:1:1 to open-label colesevelam hydrochloride, 3.75 g daily; openlabel rosiglitazone maleate, 4 mg daily; or open-label sitagliptin phosphate, 100 mg daily, in addition to existing metformin therapy. The primary efficacy variable was the change in HbA_1c from baseline to Week 16 with last (postbaseline) observation carried forward.ResultsIn total, 169 participants were randomly assigned to treatment groups (colesevelam, n = 57; rosiglitazone, n = 56; and sitagliptin, n = 56), and 141 participants (83.4%) completed the study. Least-squares mean reductions in HbA_1c from baseline were observed in all groups at Week 16 last observation carried forward (colesevelam, -0.3% [P <.031]; rosiglitazone: -0.6% [P <.001]; sitagliptin: -0.4% [P <.009]) At study end, 10 of 56 participants (17.9%) in the colesevelam group, 19 of 54 (35.2%) in the rosiglitazone group, and 15 of 55 (27.3%) in the sitagliptin group achieved HbA_1c < 7.0%. Colesevelam significantly reduced mean low-density lipoprotein (LDL)-cholesterol levels relative to baseline (11.6%), whereas levels were significantly increased with rosiglitazone and sitagliptin at Week 16 last observation carried forward (7.8% and 7.7%, respectively). Twenty-two of 52 participants (42.3%) in the colesevelam group, 12 of 51 (23.5%) in the rosiglitazone group, and 13 of 53 (24.5%) in the sitagliptin group achieved LDL cholesterol < 100 mg/dL at Week 16 last observation carried forward.ConclusionAll 3 antidiabetes agents significantly improved glycemic control, but only colesevelam also significantly reduced LDL-cholesterol levels in patients with type 2 DM. (Endocr Pract. 2010;16:53-63)     

A Comparison of Twice-Daily Biphasic Insulin Aspart 70/30 and Once-Daily Insulin Glargine in Persons With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Therapy: A Randomized,Open-Label Study

ObjectiveTo compare efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) with insulin (glargine) in type 2 diabetic patients who were not maintaining glycemic control on basal insulin and oral antidiabetic drugs.MethodsIn a 24-week, open-label, parallel-group trial, type 2 diabetic patients who were not maintaining glycemic control on basal insulin (glargine or neutral protamine Hagedorn) + oral antidiabetic drugs were randomly assigned to twice-daily BIAsp 30 + metformin or oncedaily glargine + metformin + secretagogues (secretagogues were discontinued in the BIAsp 30 arm).ResultsOne hundred thirty-seven patients were randomly assigned to the BIAsp 30 group and 143 patients were randomly assigned to the glargine group. Of 280 patients randomized, 229 (81.8%) completed the study. End-of-trial hemoglobin A_1c reductions were − 1.3% (BIAsp 30) vs − 1.2% (glargine) (treatment difference: 95% confidence interval, − 0.06 [− 0.32 to 0.20]; P = .657). Of patients taking BIAsp 30, 27.3% reached a hemoglobin A_1c level < 7.0% compared with 22.0% of patients taking glargine (treatment difference: P = .388). Glucose increment averaged over 3 meals was lower in the BIAsp 30 arm (treatment difference: − 17.8 mg/dL, P = .001). Fasting plasma glucose reductions from baseline were − 13.8 mg/ dL (BIAsp 30) vs − 42.5 mg/dL (glargine) (P = .0002). Final minor hypoglycemia rate, insulin dose, and weight change were higher in the BIAsp 30 arm (6.5 vs 3.4 events/patient per year, P <.05; 1.19 vs 0.63 U/kg; and 3.1 vs 1.4 kg, P = .0004, respectively).ConclusionsDespite not receiving secretagogues, patients taking BIAsp 30 + metformin achieved similar hemoglobin A_1c levels and lower postprandial plasma glucose compared with those receiving glargine + metformin + secretagogues. The large improvement in the glargine group suggests the patients were not true basal failures at randomization. While switching to BIAsp 30 improves glycemic control in this patient population, remaining on basal insulin and optimizing the dose may be equally effective in the short term. (Endocr Pract. 2011;17:41-50)     

Preadmission Glycemic Control and Changes to Diabetes Mellitus Treatment Regimen After Hospitalization

ObjectiveTo evaluate treatment patterns associated with diabetes medication regimen changes after hospitalization on the basis on preadmission hemoglobin A_1c levels.MethodsIn this retrospective database analysis, patients with a diabetes diagnosis, hospitalization, and documented hemoglobin A_1c level within the 90 days leading up to hospital admission were identified in an administrative claims database. Treatment regimens were assessed before and after hospitalization. The proportion of patients who had progression, reduction, or no change in therapy was compared across hemoglobin A_1c subgroups: hemoglobin A_1c < 7.0%, hemoglobin A_1c 7.0%-7.9%, and hemoglobin A_1c ≥ 8.0%.ResultsFour hundred patients were included (192 in hemoglobin A_1c < 7.0% group, 94 in hemoglobin A_1c 7.0% 7.9% group, and 114 in hemoglobin A_1c ≥ 8.0% group). Demographically, hemoglobin A_1c subgroups did not differ significantly (mean age, 57 years; 47.5% male). With respect to therapeutic regimen overall, 28%, 24%, and 48% of patients experienced progression, reduction, and no change, respectively. Across hemoglobin A_1c subgroups, 37.7% of patients in the hemoglobin A_1c ≥ 8.0% subgroup had therapy progression compared with 26% and 20.2% in the hemoglobin A_1c < 7.0% and hemoglobin A_1c 7.0%-7.9% subgroups, respectively (P = .032 and P = .006, respectively). Within the progression category, progression via insulin initiation was significantly higher in the hemoglobin A_1c ≥ 8.0% subgroup (55.8%) than in the hemoglobin A_1c < 7.0% subgroup (16%, P < .001), but not significantly higher than in the hemoglobin A_1c 7.0%-7.9% subgroup (36.8%, P = .084). In the hemoglobin A_1c ≥ 8.0% subgroup, a lower percentage of patients, 35.1%, experienced no therapy change than in both the hemoglobin A_1c < 7.0% subgroup (52.6%) and the hemoglobin A_1c 7.0%-7.9% subgroup (54.3%) (P = .003 and P = .006, respectively). There was no difference between subgroups in reduction of therapy.ConclusionsA higher proportion of patients with a hemoglobin A_1c level ≥ 8.0% had progression of their antidiabetes therapy after hospitalization and fewer patients had no change in therapy than those in lower hemoglobin A_1c subgroups. These data suggest that clinicians may be using hemoglobin A_1c measurements to guide discharge planning treatment decisions. (Endocr Pract. 2012;18:371-375)     

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)     

Colesevelam Hydrochloride Added to Background Metformin Therapy in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis from 3 Clinical Studies

ObjectiveTo evaluate the glucose- and lipid-altering efficacy of colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM).MethodsThis post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo- controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin.ResultsIn this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive colesevelam HCl and 341 to receive placebo. In comparison with placebo, colesevelam HCl significantly reduced hemoglobin A_1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P < .001 for both), as well as significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%) (P < .0001 for all). Median triglyceride levels were increased with colesevelam HCl (median treatment difference: + 12.8%; P < .0001). In comparison with placebo, colesevelam HCl significantly increased apo A-I (mean treatment difference: + 3.3%; P < .0001), whereas the mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated.ConclusionWhen added to metformin-including therapy, colesevelam HCl significantly reduced A1C and fasting glucose, as well as levels of LDL-C, TC, non- HDL-C, and apo B in patients with inadequately controlled T2DM. (Endocr Pract. 2011;17:933-938)     

Effect of Glargine Insulin Delivery Method (Pen Device Versus Vial/Syringe) on Glycemic Control and Patient Preferences in Patients with Type 1 and Type 2 Diabetes

ObjectiveTo evaluate the effects of two different glargine insulin delivery methods (pen device vs. vial/ syringe) on glycemic control and patient preferences in a randomized, open-label, crossover, comparative effectiveness study.MethodsThirty-one patients discharged from the hospital were recruited for this study. In the hospital, all patients were treated with a basal-bolus insulin regimen. Upon discharge, 21 patients received glargine by pen device for 3 months and were then switched to vial/syringe for the next 3 months (group 1). Group 2 consisted of 10 patients discharged on vial/syringe and converted to pen device after 3 months. Hemoglobin A_1c (HbA_1c) was measured at enrollment and at 3 and 6 months. A questionnaire assessing patient preference was administered at 3 and 6 months.ResultsGroups 1 and 2 had similar baseline HbA_1c (10.7 ± 2.2% and 11.2 ± 2.5%, respectively) and similar reduction in HbA_1c at 3 months (7.8 ± 1.7% and 7.3 ± 1.4%, respectively; P < .001 vs. baseline). However, after crossover, the changes in HbA_1c from 3 to 6 months were significantly different between groups. HbA_1c increased to 8.5 ± 2.0% at 6 months in group 1 after switching to the vial/syringe but remained unchanged (7.1 ± 1.6%) in group 2 after switching to a pen device (P < .01, group 1 vs. group 2). Patient questionnaires after each phase of the trial revealed that patients found the pen device more convenient and were more likely to recommend this insulin delivery method to someone else.ConclusionPatients switching to a glargine pen device achieved lower HbA_1c at the 6-month follow-up. Patients in both groups overwhelmingly preferred glargine pens over vials/syringes. (Endocr Pract. 2014;20:536-539)     

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)     

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)     

Reduced Risk of Hypoglycemia with Insulin Degludec Versus Insulin Glargine in Patients with Type 2 Diabetes Requiring High Doses of Basal Insulin: A Meta-Analysis of 5 Randomized Begin Trials

ObjectiveThis meta-analysis of 5 trials from the Phase 3a insulin degludec (IDeg) clinical trial program evaluated the risk of hypoglycemia in a subset of subjects with type 2 diabetes (T2D) who required high basal insulin doses at the end of the trials.MethodsThis meta-analysis compared glycated hemoglobin (HbA_1c), fasting plasma glucose (FPG), basal insulin dose, body weight, and rates of overall and nocturnal confirmed hypoglycemia in a pooled population of T2D subjects using > 60 U basal insulin at trial completion. Five Phase 3a, open-label, randomized, treat-to-target, confirmatory 26-or 52-week trials with IDeg (n = 2,262) versus insulin glargine (IGlar) (n = 1,110) administered once daily were included. Overall confirmed hypoglycemia was defined as self-measured blood glucose < 56 mg/dL or any episode requiring assistance; nocturnal confirmed hypoglycemia had an onset between 00:01 and 05:59 am.ResultsMore than one-third of IDeg-(35%) and IGlar-(34%) treated T2D subjects required > 60 U of basal insulin daily at the ends of the trial. Patients achieved similar mean HbA_1c values (estimated treatment difference [ETD] IDeg - IGlar: 0.05%, P = .44) while mean FPG values were lower with IDeg than IGlar (ETD: - 5.9 mg/ dL, P = .04) at end-of-trial. There was a 21% lower rate of overall confirmed hypoglycemic episodes for IDeg (estimated rate ratio [RR] IDeg/IGlar: 0.79, P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes for IDeg (RR: 0.48, P < .01).ConclusionIn this post hoc meta-analysis, more than 30% of subjects with T2D required > 60 U/day of basal insulin at the end of the trials. In these individuals, IDeg achieves similar HbA_1c reduction with significantly less overall and nocturnal confirmed hypoglycemia compared with IGlar. (Endocr Pract. 2014;20:285-292)     

Effect of Bromocriptine-Qr On Glycemic Control in Subjects with Uncontrolled Hyperglycemia On One or Two Oral Anti-Diabetes Agents

ObjectiveTo investigate the effect of Bromocriptine QR on glycemic control in patients with type 2 diabetes whose glycemia is poorly controlled on one or two oral anti-diabetes agents.MethodsFive hundred fifteen Type 2 Diabetes Mellitus (T2DM) subjects (ages 18 to 80 and average body mass index [BMI] of 32.7) with baseline HbA1c ≥ 7.5 and on one or two oral anti-diabetes (OAD) medications (metformin, sulfonylurea, and/or thiazolidinediones) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 24 week treatment period. Study investigators were allowed to adjust, if necessary, subject anti diabetes medications during the study to attempt to achieve glycemic control in case of glycemic deterioration. The impact of bromocriptine-QR treatment intervention on glycemic control was assessed in subjects on any one or two OADs (ALL treatment category) (N = 515), or on metformin with or without another OAD (Met/OAD treatment category) (N = 356), or on metformin plus a sulfonylurea (Met/SU treatment category) (N = 245) 1) by examining the between group difference in change from baseline a) concomitant OAD medication changes during the study, and b) HbA1c and 2) by determining the odds of reaching HbA1c of ≤ 7.0% on bromocriptine-QR versus placebo.ResultsSignificantly more patients (approximately 1.5 to 2-fold more; P < .05) intensified concomitant anti diabetes medication therapy during the study in the placebo versus the bromocriptine-QR arm. In subjects that did not change the intensity of the baseline diabetes therapy (72%), and that were on any one or two OADs (ALL), or on metformin with or without another OAD (Met/OAD), or on metformin plus sulfonylurea (Met/SU), the HbA1c change for bromocriptine-QR versus placebo was − 0.47 versus + 0.22 (between group delta of − 0.69, P < .0001), − 0.55 versus + 0.26 (between group delta of − 0.81, P < .0001) and − 0.63 versus + 0.20 (between group delta of − 0.83, P < .0001) respectively, after 24 weeks on therapy. The odds ratio of reaching HbA1c of ≤ 7.0% was 6.50, 12.03 and 11.45 (P < .0002) for these three groups, respectively.ConclusionIn T2DM subjects whose hyperglycemia is poorly controlled on one or two oral agents, bromocrip tine-QR therapy for 24 weeks can provide significant added improvement in glycemic control relative to adding placebo. (Endocr Pract. 2012;18:931-943)     

Evolución clínica a 5 años desde el inicio de la insulinoterapia en pacientes con diabetes tipo 2 en España: resultados del estudio EDIN

ObjectivesThe primary study objective was to assess the proportion of patients with type 2 diabetes and an HbA_1c value ≤ 6.5% from the start of insulin therapy to five years later in the outpatient setting in Spain.Material and methodsThis was an observational, multicenter, naturalistic study with retrospective collection of clinical data. Investigators were endocrinologists or internal medicine specialists from all over Spain. During standard clinical care, patients started insulin therapy, which was continued for at least 5 years.ResultsThe clinical records of 405 patients were reviewed. The final analysis set included records from 346 patients. At baseline (start of insulin therapy), 51.2% of patients were female; mean (SD) age was 64.6 (9.0) years; body mass index, 29.8 (4-5) kg/m²; time since diagnosis, 8.8 (6.8) years; HbA_1c, 9.4% (1.5); fasting glucose, 223.7 (55.9) mg/dL; and mean 2-hour postprandial glucose, 293.6 (71.0) mg/dL. When insulin therapy was started, < 1.0% of patients had an HbA_1c value ≤ 6.5%. At 5 years, 10.3% of patients achieved the HbA_1c goal of ≤ 6.5% (mean, 7.72%). All glucose parameters (HbA_1c, fasting glucose, and 2-hour postprandial glucose) improved at 5 years as compared to values at the start of insulin therapy.ConclusionsGlucose parameters improved over time in patients with type 2 diabetes in this naturalistic study. However, blood glucose control exceeded the internationally recommended target values. These results therefore suggest that there is still some margin for improvement in outpatient care in Spain.     

Effect of Hospital Admission on Glycemic Control 1 Year After Discharge

ObjectiveTo assess the effect of hospital admission on glycemic control in patients with diabetes up to 1 year after discharge.MethodsWe retrospectively studied 826 adults with diabetes admitted to a tertiary care medical center and with available hemoglobin A_1c (A1C) values for 6 months before admission and 1 year after discharge. We compared them with 826 nonhospitalized adults with diabetes matched for age, sex, race, comorbidity, and baseline A1C level. We determined the change in A1C value relative to hospitalization and baseline A1C level by using multivariate random effects models for repeated measures. Logistic regression analysis was performed to determine predictors of achieving recommended A1C levels at 1 year.ResultsPatients with baseline A1C levels ≥ 9% had an adjusted rate of change in A1C value of − 0.10% per month (95% confidence interval [CI], − 0.18 to − 0.022; P = .012) during the course of 1 year, without significant differences between hospitalized and nonhospitalized patients in the mean rate of change. Hospitalized patients, however, were less likely to achieve an A1C goal of ≤ 7% at 1 year (odds ratio, 0.68; 95% CI, 0.55 to 0.86; P < .001) or an A1C of < 8% at 1 year (odds ratio, 0.62; 95% CI, 0.48 to 0.81; P < .001) in comparison with the nonhospitalized patients.ConclusionDespite an overall trend toward improved glycemia over time, hospitalized patients with uncontrolled diabetes were less likely to achieve glycemic targets at 1 year in comparison with matched nonhospitalized patients. These results suggest a missed opportunity to improve long-term glycemic control in hospitalized patients with diabetes. (Endocr Pract. 2012;18:456-463)     

Initial Combination Therapy with Metformin and Colesevelam for Achievement of Glycemic and Lipid Goals Min Early Type 2 Diabetes

ObjectiveTo evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes.MethodsIn this 16-week, randomized, double-blind, placebo-controlled study, adults with type 2 diabetes (hemoglobin A1c [A1C] values of 6.5% to 10.0%) and hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels ≥ 100 mg/dL) were randomly assigned (1:1) to colesevelam (3.75 g/d) or placebo in combination with open-label metformin (850 mg/d; uptitrated at week 2 to 1, 700 mg/d). The primary efficacy evaluation was change in A1C from baseline to study end (week 16 with last observation carried forward).ResultsIn total, 286 patients were randomized: metformin/colesevelam (n = 145) or metformin/placebo (n = 141). Mean A1C was reduced by 1.1% with metformin/ colesevelam (from 7.8% at baseline to 6.6% at study end) and by 0.8% with metformin/placebo (from 7.5% to 6.7%), resulting in a treatment difference of -0.3% at study end (P = .0035). In addition, metformin/colesevelam significantly reduced LDL-C (-16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), apolipoprotein B (-8.0%), and high-sensitivity C-reactive protein (-17%) and increased apolipoprotein A-I (+ 4.4%) and triglycerides (+ 18.6%) versus metformin/placebo (P < .01 for all). The proportions of patients who achieved recommended goals with metformin/colesevelam versus metformin/placebo, respectively, were as follows: A1C < 7.0% (67% versus 56% [P = .0092]), LDL-C < 100 mg/dL (48% versus 18% [P < .0001]), and composite A1C < 7.0% + LDL-C < 100 mg/dL (40% versus 12% [P < .0001]). Safety and tolerability were similar between the treatment groups.ConclusionMetformin plus colesevelam may be a valid option for initial therapy to achieve glycemic and lipid goals safely in early type 2 diabetes. (Endocr Pract. 2010;16:629-640)     

Value of Hemoglobin A1C In Diagnosing Diabetes Mellitus within a Chronic Disease Management System Illustrated by the Receiver Operating Characteristic Curve

ObjectiveTo develop a receiver operating characteristic (ROC) curve of glycosylated hemoglobin (HbA_1c) for diagnosing diabetes mellitus within a chronic disease management system.MethodsA case-control study including medical records from January 1, 1997, to December 31, 2005, was conducted at the Sioux Falls Veterans Affairs Medical Center. Medical records for the case group (patients with diabetes) were selected based on 1 of 3 criteria: International Classification of Diseases, Ninth Revision, Clinical Modification or Current Procedural Terminology codes specific for type 1 and type 2 diabetes; patients’ use of medications (oral hypoglycemic agents, antidiabetes agents, or insulin); or results from random blood or plasma glucose tests (at least 2 measurements of blood glucose ≥ 200 mg/dL). Records for the control group were selected based on patients having HbA_1c measured, but not meeting the above diagnostic criteria for diabetes during the study period. Records for cases and controls were randomly frequency-matched, one-to-one. The control group was randomly divided into 5 sets of an equal number of records. Five sets of an equal number of cases were then randomly selected from the total number of cases. Each test data set included 1 case group and 1 control group, resulting in 5 independent data sets.ResultsIn total, 5040 patient records met the case definition in the diabetes registry. Records of 15 patients who were prescribed metformin only, but did not meet any other case criteria, were reviewed and excluded after determining the patients were not diabetic. The control group consisted of 5 sets of 616 records each (totaling 3080 records), and the case group consisted of 5 sets of 616 records each (totaling 3080 records). Thus, each of the 5 independent data sets of 1 case group and 1 control group contained 1232 records. The case group was predominantly composed of white men (mean age, 69 years; mean body mass index, 31 kg/m²). Demographic data were similar for control patients. The ROC curve revealed that a HbA_1c ≥ 6.3% (mean + 1 SD) offered the most accurate cutoff value for diagnosing type 2 diabetes mellitus, with the following statistical values: C statistic, 0.78; sensitivity, 70%; specificity, 85%; and positive likelihood ratio, 4.6 (95% confidence interval, 4.2-5.0).ConclusionA HbA_1c value ≥ 6.3% may be a useful benchmark for diagnosing diabetes mellitus within a chronic disease management system and may be a useful tool for monitoring high-risk populations. (Endocr Pract. 2010;16:14-20)     

Aerobic Fitness and Glycemic Variability in Adolescents with Type 1 Diabetes

ObjectiveThis study examines the association of fitness on glycemic variability (GV) in adolescents with type 1 diabetes mellitus (T1DM). GV has been associated with high frequency of hyper-and hypoglycemia.MethodsNineteen adolescents with T1DM, ages 14 to 19 years, underwent aerobic fitness testing to determine their maximal aerobic capacity (VO₂ max). A continuous glucose monitoring (CGM) device was placed on each subject and worn for 3 to 5 days until a return visit when the subjects underwent a 1-hour treadmill exercise session. Mean amplitude of glycemic excursion (MAGE) was calculated from the CGM data collected between the 2 study visits. Metabolic equivalent (MET), a measure of accumulated metabolic workload during the exercise session, was also calculated.ResultsMean VO₂ max was 46.6 ± 6.8 mL/kg/min, with a range of 34.8 to 57.0 mL/kg/min. Mean MET during the exercise session was 577.2 ± 102.4 and ranged from 354.3 to 716.2 METs. There was an inverse association between VO₂ max and MAGE (r = − 0.46; 95% confidence interval [CI], − 0.01 to − 0.76; P = .048). MET load and MAGE also had an inverse relationship (r = − 0.48; 95% CI, − 0.03 to − 0.77; P = .037).ConclusionGV is inversely associated with fitness and MET load. Aerobic fitness should be promoted in adolescents with T1DM not only because of its multiple beneficial effects but also due to a possible association with GV, leading to fewer extremes in hypo-and hyperglycemia. (Endocr Pract. 2014;20:566-570)     

Trace elements,oxidative stress and glycemic control in young people with type 1 diabetes mellitus

Trace elements and oxidative stress are associated with glycemic control and diabetic complications in type 1 diabetes mellitus. In this study, we analyzed the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 33 type 1 diabetic patients with optimal and suboptimal glycemic control (HbA_1C < 9.0%) and 40 patients with poor glycemic control (HbA_1C ≥ 9%) and 27 age- and sex-matched non-diabetic controls to evaluate the differences between these markers in different glycemic control states. Diabetic patients, especially poor-glycemic-control subjects (HbA_1C ≥ 9%), exhibited significantly lower levels of serum zinc and increased levels of serum copper (and, therefore, increased serum copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG, relative to non-diabetic subjects. Furthermore, significant correlations existed in these patients between the serum copper, serum copper-to-zinc ratio, and urinary MDA (all p < 0.001) and the levels of urinary 8-OHdG (p = 0.007) and HbA_1C. Our results suggest that high serum copper levels and oxidative stress correlate with glycemic control. Therefore, strict glycemic control, decreased oxidative stress, and a lower copper concentration might prevent diabetic complications in patients with type 1 diabetes mellitus.     

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)     

Practice Patterns in Screening for Metabolic Disease in Women with PCOS of Diverse Race-Ethnic Backgrounds

ObjectivesWomen with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity.MethodsPCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code. Screening rates for metabolic disorders were determined by the presence of blood tests (hemoglobin A1c [HbA_1c], lipid profile, alanine aminotransferase/aspartate aminotransferase [ALT/AST]).ResultsIn 2006, ≤ 25% of PCOS patients underwent recommended screening tests: HbA1c 18%; lipid profile < 20%; ALT/AST ≤ 25%. By 2011, only HbA1c testing had increased (18% to 21%). Obesity increased from 35% to 40%, while other metabolic disorders remained stable. Black women had the highest rates of obesity and HTN in 2011 (Obesity: Black 48%, Hispanic 44%, White 33%, Other 31%, P < .0001; HTN: Black 18%, Hispanic 9%, White 10%, Other 7%, P < .0001). Blacks and Hispanics were screened more often with ALT/AST testing (Black 27/27%, Hispanic 28/27%, White 23/22%, Other 17/18%, P = .02/.03). Screening rates were higher in the endocrine clinic for all metabolic disorders than in other clinics (P < .05).ConclusionDespite the publication of recommendations in 2005, screening rates for metabolic disease in women with PCOS remained low across all race-ethnicities in 2011. (Endocr Pract. 2014;20:855-863)     

Chromium Effects on Glucose Tolerance and Insulin Sensitivity in Persons at Risk for Diabetes Mellitus

ObjectiveTo investigate the effects of daily chromium picolinate supplementation on serum measures of glucose tolerance and insulin sensitivity in patients at high risk for type 2 diabetes mellitus.MethodsWe conducted a randomized, double-blind, placebo-controlled, modified cross-over clinical trial with 6-month sequences of intervention and placebo followed by a 6-month postintervention assessment. Adult patients with impaired fasting glucose, impaired glucose tolerance, or metabolic syndrome were enrolled. Participants received 6-month sequences of chromium picolinate or placebo at 1 of 2 dosages (500 or 1000 mcg daily). Primary outcome measures were change in fasting plasma glucose, 2-hour plasma glucose during oral glucose tolerance testing, fasting and 2-hour insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included anthropometric measures, blood pressure, endothelial function, hemoglobin A_1c, lipids, and urinary microalbumin.ResultsFifty-nine participants were enrolled. No changes were seen in glucose level, insulin level, or HOMA-IR (all P > .05) after 6 months of chromium at either dosage level (500 mcg or 1000 mcg daily) when compared with placebo. None of the secondary outcomes improved with either chromium dosage compared with placebo (P > .05).ConclusionsChromium supplementation does not appear to ameliorate insulin resistance or impaired glucose metabolism in patients at risk for type 2 diabetes and thus is unlikely to attenuate diabetes risk. (Endocr Pract. 2011;17:16-25)