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.     

Four-Year Durability of Initial Combination Therapy with Sitagliptin and Metformin in Patients with Type 2 Diabetes in Clinical Practice; COSMIC Study

Objectives

We investigated the efficacy of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes for 4 years in clinical practice.

Methods

Between 2009 and 2010, we reviewed 1,178 patients with type 2 diabetes (HbA_1c ≥7.5% or 58 mmol/mol) prescribed initial combination therapy with sitagliptin and metformin. After excluding 288 patients without a second follow-up, 890 individuals (age, 58.0 ± 12.5 years; BMI, 25.4 ± 3.5 kg/m²; HbA_1c, 8.6 ± 1.1%) were followed up with every 3–6 months for 4 years. Homeostasis model assessments for insulin resistance and β-cell function (HOMA-β) were recorded at baseline. The response criterion was HbA_1c reduction by ≥0.8% from baseline or attainment of the target HbA_1c (≤7.0% or 53 mmol/mol). At the end of every year of treatment, changes in HbA_1c from the baseline were assessed.

Results

After 1 year, 72.2% of patients with initial combination therapy had responded, defined as HbA_1c reduction ≥0.8% or attainment of the target HbA_1c ≤7.0%. After 4 years, 35.4% of the patients still showed a response, with an HbA_1c level of 7.0 ± 0.9%. A high HbA_1c level at baseline was the most significant independent predictor of the long-term response (P<0.001). In addition, low HOMA-β was a significant predictor of a greater reduction in HbA_1c. This treatment was generally well tolerated over the 4-year follow-up period, without any serious adverse events.

Conclusions

This real-world follow-up study shows a persistent glucose-reducing effect of initial combination therapy with sitagliptin and metformin for up to 4 years.     

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)     

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)     

Sputum Glucose and Glycemic Control in Cystic Fibrosis-Related Diabetes: A Cross-Sectional Study

Cystic fibrosis-related diabetes affects up to half of cystic fibrosis patients and is associated with increased mortality and more frequent pulmonary exacerbations. However, it is unclear to what degree good glycemic control might mitigate these risks and clinical outcomes have not previously been studied in relation to glucose from the lower airways, the site of infection and CF disease progression. We initially hypothesized that diabetic cystic fibrosis patients with glycosylated hemoglobin (HbA_1c) > 6.5% have worse pulmonary function, longer and more frequent exacerbations and also higher sputum glucose levels than patients with HbA_1c ≤ 6.5% or cystic fibrosis patients without diabetes. To test this, we analyzed spontaneously expectorated sputum samples from 88 cystic fibrosis patients. The median sputum glucose concentration was 0.70 mM (mean, 4.75 mM; range, 0-64.6 mM). Sputum glucose was not correlated with age, sex, body mass index, diabetes diagnosis, glycemic control, exacerbation frequency or length, or pulmonary function. Surprisingly, sputum glucose was highest in subjects with normal glucose tolerance, suggesting the dynamics of glycemic control, sputum glucose and pulmonary infections are more complex than previously thought. Two-year mean HbA_1c was positively correlated with the length of exacerbation admission (p < 0.01), and negatively correlated with measures of pulmonary function (p < 0.01). While total number of hospitalizations for exacerbations were not significantly different, subjects with an HbA_1c > 6.5% were hospitalized on average 6 days longer than those with HbA_1c ≤ 6.5% (p < 0.01). Current clinical care guidelines for cystic fibrosis-related diabetes target HbA_1c ≤ 7% to limit long-term microvascular damage, but more stringent glycemic control (HbA_1c ≤ 6.5%) may further reduce the short-term pulmonary complications.     

Efficacy and Safety of Linagliptin in Black/African American Patients with Type 2 Diabetes: A 6-Month,Randomized, Double-Blind,Placebo-Controlled Study

ObjectiveAlthough black/African American individuals are disproportionately affected by type 2 diabetes, there is scant clinical trial information available on antidiabetes therapies in this group. We compared linagliptin with placebo in black/African American adults who were treatment-naïve or receiving one oral antidiabetes drug.MethodsOf 226 patients randomized to 24 weeks’ linagliptin 5 mg/day or placebo, 208 had baseline and at least one on-treatment glycated hemoglobin (HbA_1c) measurement. Mean baseline HbA_1c was 8.6% in the linagliptin group (n = 98) and 8.68% in the placebo group (n = 110). The primary outcome was change in HbA_1c from baseline to week 24.ResultsBy week 24, mean HbA_1c changes were − 0.84% with linagliptin and − 0.25% with placebo (treatment difference, − 0.58%; P < .001), and more patients in the linagliptin group achieved HbA_1c < 7.0% (26.8% vs. 8.3%; P = .001) or an HbA_1c reduction ≥ 0.5% (54.1% vs. 30.0%; P < .001). Mean weight loss was − 1.1 kg in both groups. During the treatment period, 8 of 98 linagliptingroup patients and 17 of 110 placebo-group patients required rescue therapy (odds ratio, 0.5; P = .14). For postprandial glucose, values were available for few patients (11 placebo, 10 linagliptin), and thus the between-group difference was associated with wide confidence intervals (CIs) (difference, − 1.97 mg/dL; 95% CI, − 53.80 to 49.86; P = .94). In the overall study population, a similar proportion of patients in both groups had adverse events (58.5% vs. 61.7%); most events were mild or moderate and considered unrelated to study drug. Investigator-defined hypoglycemia was rare (3 linagliptin-group patients and 1 placebogroup patient), with no severe events (requiring external assistance).ConclusionThis study confirms that linagliptin is efficacious and well tolerated in black/African American patients with type 2 diabetes. (Endocr Pract. 2014;20: 412-420)     

Effect of Pramlintide on Weight in Overweight and Obese Insulin‐Treated Type 2 Diabetes Patients

Objective: Several randomized, placebo‐controlled, double‐blind trials in insulin‐treated patients with type 2 diabetes have shown that adjunctive therapy with pramlintide reduces hemoglobin (Hb)A_1c with concomitant weight loss. This analysis further characterizes the weight‐lowering effect of pramlintide in this patient population. Research Methods and Procedures: This pooled post hoc analysis of two long‐term trials included all patients who were overweight/obese at baseline (BMI > 25 kg/m²), and who were treated with either 120 μg pramlintide BID (n = 254; HbA_1c 9.2%; weight, 96.1 kg) or placebo (n = 244; HbA_1c 9.4%; weight, 95.0 kg). Statistical endpoints included changes from baseline to week 26 in HbA_1c, body weight, and insulin use. Results: Pramlintide treatment resulted in significant reductions from baseline to week 26, compared with placebo, in HbA_1c and body weight (both, p < 0.0001), for placebo‐corrected reductions of ?0.41% and ?1.8 kg, respectively. Approximately three times the number of patients using pramlintide experienced a ≥5% reduction of body weight than with placebo (9% vs. 3%, p = 0.0005). Patients using pramlintide also experienced a proportionate decrease in total daily insulin use (r = 0.39, p < 0.0001). The greatest placebo‐corrected reductions in weight at week 26 were observed in pramlintide‐treated patients with a BMI >40 kg/m² and in those concomitantly treated with metformin (both, p < 0.001), for placebo‐corrected reductions of ?3.2 kg and ?2.5 kg, respectively. Discussion: These findings support further evaluation of the weight‐lowering potential of pramlintide in obese patients with type 2 diabetes.     

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)     

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)     

Postprandial Dynamics of Plasma Glucose,Insulin, and Glucagon in Patients with Type 2 Diabetes Treated with Saxagliptin Plus Dapagliflozin Add-On to Metformin Therapy

ObjectiveTo analyze changes in plasma glucose, insulin, and glucagon in relation to glycemic response during treatment with dual add-on of saxagliptin (SAXA) plus dapagliflozin (DAPA) to metformin XR (MET) compared with SAXA add-on or DAPA add-on alone to MET in patients with type 2 diabetes mellitus (T2DM) poorly controlled with MET.MethodsDouble-blind trial in adults with glycated hemoglobin (HbAlc) ≥ 8.0 to ≤ 12.0% randomized to SAXA 5 mg/day plus DAPA 10 mg/day (n = 179), or SAXA 5 mg/day and placebo (n = 176), or DAPA 10 mg/day and placebo (n = 179) added to background MET ≥ 1,500 mg/ day. The mean change from baseline in the area under the curve from 0 to 180 minutes (AUC_{0-180 min}) was calculated for glucose, insulin, and glucagon obtained during a liquid meal tolerance test (MTT).ResultsGlucose AUC_{0-180 min} an was reduced more from baseline with SAXA + DAPA + MET (-12,940 mg/dL) compared with SAXA + MET (-6,309 mg/dL) and DAPA + MET (-11,247 mg/dL). Insulin AUC_{0-180 min} significantly decreased with SAXA + DAPA + MET (-1,120 μU/mL) and DAPA + MET (-1,019 μU/mL) and increased with SAXA + MET (661 μU/mL). Glucagon AUC_{0-180 min} only increased with DAPA + MET (2,346 pg/mL). The changes in glucose (P < .0001) and insulin (P = .0003) AUC_{0-180 min} correlated with change in HbA1c, whereas the change in glucagon AUC_{0-180 min} min did not (P = .27).ConclusionsWhen added to background MET, the combination of SAXA + DAPA provided additional reductions in glucose AUC_{0-180 min} and HbA1c without the increase in insulin seen with SAXA and without the increase in glucagon seen with DAPA. Changes in insulin and glucose but not glucagon AUC_{0-180 min} correlated with change in HbA1c. (Endocr Pract. 2014;20:1187-1197)     

Incidence of Type 2 Diabetes in Pre-Diabetic Japanese Individuals Categorized by HbA1c Levels: A Historical Cohort Study

Objective

Reported incidence of type 2 diabetes estimated at the pre-diabetic stage differs widely (2.3–18.1% per year). Because clinicians need to know the risk of incident diabetes after a diagnosis of pre-diabetes, our objective was to estimate precise incidence of diabetes using baseline HbA_1c levels.

Methods

A historical cohort study using electronic medical record data obtained between January 2008 and December 2013. A total of 52,781 individuals with HbA_1c < 6.5% were assigned to one of six groups categorized by baseline HbA_1c level: ≤ 5.5% (n=34,616), 5.6–5.7% (n=9,388), 5.8–5.9% (n=4,664), 6.0–6.1% (n= 2,338), 6.2–6.3% (n=1,257), and 6.4% (n=518). Participants were tracked until a subsequent diagnosis of diabetes or end of follow-up during a period of 5 years.

Results

During the follow-up period (mean 3.7 years), 4,369 participants developed diabetes. The incidence of diabetes in the first year was 0.7, 1.5, 2.9, 9.2, 30.4, and 44.0% in the six HbA_1c groups, respectively. At five years the incidence was 3.6, 8.9, 13.8, 27.5, 51.6, and 67.8%, respectively (p < 0.0001 comparing the HbA_1c ≤5.5% group to the other groups). After adjustment for confounding factors, the hazard ratios compared with the HbA_1c ≤5.5% group were significantly elevated: 2.3 (95%CI 2.0–2.5), 3.4 (95%CI 2.9–3.7), 8.8 (95%CI 8.0–10.1), 26.3 (95%CI 23.3–30.1), and 48.7 (95%CI 40.8–58.1) in the five HbA_1c groups (p < 0.0001).

Conclusion

By fractionating baseline HbA_1c levels into narrower HbA_1c range groups, accuracy of estimating the incidence of type 2 diabetes in subsequent years was increased. The risk of developing diabetes increased with increasing HbA_1c levels, especially with the HbA_1c level ≥ 6.2% in the first follow-up year.     

Patients Achieving Good Glycemic Control (HBA1c <7%) Experience A Lower Rate of Hypoglycemia With Insulin Degludec Than with Insulin Glargine: A Meta-Analysis of Phase 3A Trials

Objective: Meta-analysis to compare hypoglycemia rates of basal insulin degludec (IDeg) with insulin glargine (IGlar) in patients with diabetes achieving good glycemic control (hemoglobin A_1c [HbA_1c] <7% at end of trial).Methods: In a preplanned meta-analysis, patient data from 7 randomized, treat-to-target, 26- or 52-week trials in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) who administered IDeg (n = 2,899) or IGlar (n = 1,431) once daily were analyzed. Using a negative binomial regression model, this meta-analysis compared hypoglycemia rates in patients achieving HbA_1c <7% at end of trial with IDeg (n = 1,347) and IGlar (n = 697).Results: In all trials, IDeg was noninferior to IGlar in HbA_1c reduction from baseline. At end of trial, 2,044 patients (T2DM, n = 1,661; T1DM, n = 383) achieved HbA_1c <7%. The overall confirmed hypoglycemia rate, defined as plasma glucose <56 mg/dL or severe hypoglycemia if requiring assistance, was significantly lower with IDeg versus IGlar (estimated rate ratio [ERR] IDeg:IGlar, 0.86; 95% confidence interval [CI], 0.76 to 0.98). The nocturnal confirmed hypoglycemia rate, defined as occurring between midnight and 6:00 am, was significantly lower with IDeg (ERR, 0.63; 95% CI, 0.52 to 0.77). In the maintenance period (16 weeks onward when average insulin dose and glycemic levels stabilized), the overall confirmed hypoglycemia rate was significantly lower (ERR, 0.79; 95% CI, 0.68 to 0.92) and the nocturnal confirmed hypoglycemia rate was significantly lower (ERR, 0.57; 95% CI, 0.45 to 0.72) with IDeg versus IGlar.Conclusion: Patients with T1DM and T2DM achieved HbA_1c <7% with significantly lower rates of overall and nocturnal confirmed hypoglycemia with IDeg versus IGlar. The lower hypoglycemia rate with IDeg was more pronounced in the maintenance period.Abbreviations: ERR = estimated rate ratio; HbA_1c = hemoglobin A_1c; IDeg = insulin degludec; IGlar = insulin glargine; NPH = Neutral Protamine Hagedorn; PG = plasma glucose; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus     

Falsely Decreased Hba1c in A Type 2 Diabetic Patient Treated with Dapsone

ObjectiveTo discuss a case of a falsely low hemoglobin A_1c (HbA_1c) in a transplant patient treated with dapsone and its implications. HbA_1c is widely used as a measure of glycemic control in diabetic patients. With the increasing transplant population, it is important to be mindful of medications used in this population that can affect HbA_1c and to use other measures of glycemic control to guide treatment decisions.MethodsWe present details of the case and review the relevant literature.ResultsA 61-year-old patient received a liver transplant in 2012 and subsequently was noted to have a falling HbA_1c despite evidence of hyperglycemia based on fingerstick glucose and fructosamine measurements. Review of the medical records revealed that the discordance between HbA_1c and fingerstick glucose levels developed after initiation of dapsone therapy. Dapsone may lead to a falsely low HbA_1c via several mechanisms. Upon cessation of dapsone therapy, the patient’s HbA_1c returned to pre-dapsone levels.ConclusionIt is important to be aware of medications commonly used in transplant patients that may lead to a falsely low HbA_1c level so that incorrect treatment decisions are not made. Fructosamine correlates with HbA_1c and can be used as a measure of glycemic control in transplant patients when HbA_1c cannot be used. (Endocr Pract. 2014;20:e229-e232)     

Relationship between glycated hemoglobin and glucose concentrations in the adult Galician population: selection of optimal glycated hemoglobin cut-off points as a diagnostic tool of diabetes mellitus

Aims/hypothesisTo analyze the relationship between glucose and glycated hemoglobin (HbA_1c) in the adult Galician population, evaluate the use of HbA_1c for the screening and diagnosis of diabetes, and calculate the diagnostic threshold required for this purpose.MethodsWe analyzed data on 2848 subjects (aged 18–85 years) drawn from a study undertaken in 2004 to assess the prevalence of diabetes in Galicia. For study purposes, diabetes was defined using the criteria recommended in 2002. Participants were classified into four glucose-based groups. The relationship between glucose and HbA_1c was described using linear regression models, generalized additive models and Spearman's correlation. Diagnostic capacity was assessed, and optimal HbA_1c cut-off points were calculated as a diabetes marker using the receiver operating characteristic curve.ResultsPrevalence of pre-diabetes, unknown diabetes and known diabetes was 20.86, 3.37 and 4.39%, respectively. The correlations between HbA_1c and fasting glucose were higher than those obtained for HbA_1c and glycemia at 2 h of the oral glucose overload (0.344 and 0.270, respectively). Taking glucose levels as the gold standard, a greater discriminatory capacity was obtained for HbA_1c (area under de cruve: 0.839, 95% confidence intervals: 0.788–0.890). Based on the study criteria, the optimal minimum and maximum HbA_1c values were 5.9% and 6.7%, respectively.Conclusions/interpretationHbA_1c did not prove superior to glycemia for diagnosis of diabetes in the adult Galician population, and cannot therefore be used to replace the oral glucose tolerance test for screening and diagnosis purposes. Indeed, determination of glucose is essential to verify the diagnosis in the majority of cases.     

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)     

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)     

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)     

Heterogeneity of hemoglobin A1d: assessment and partial characterization of two new minor hemoglobins, A1d3a and A1d3b, increased in uremic and diabetic patients, respectively

We have separated and quantified two new minor hemoglobins named HbA_1d3a and HbA_1d3b. The level of HbA_1d3a was significantly higher in uremic than in non-uremic patients (3.00 ± 0.50% vs. 1.28 ± 0.26% of total hemoglobin). It correlated well with carbamylated hemoglobin (r=0.80, n=81, p<0.002) and with plasma urea concentration (r=0.78, n=81, p<0.002). These data and the electrospray ionization mass spectrometric analysis provide strong evidence that HbA_1d3a is an α-chain modified by carbamylation. The HbA_1d3b level in the diabetic patients was found to be 1.6-fold that in non-diabetic subjects (3.00 ± 0.49 vs. 1.90 ± 0.33). This was attributed to HbA_1d3 modified by glycation. Indeed HbA_1d3b correlated significantly with HbA_1c (r=0.71, p<0.002) and with serum glucose level (r=0.62, p<0.002). These two new minor hemoglobins may serve as complements for the objective assessment of averagd long-term uremia and glycemia in uremic and diabetic patients.     

Parámetros de control glucémico en pacientes con diabetes tipo 2 no insulinizados derivados a consulta de Endocrinología,y grado de implementación del consenso nacional sobre el tratamiento de la hiperglucemia

ObjectiveTo assess blood glucose in patients with uncontrolled type 2 diabetes mellitus treated with oral antidiabetic drugs in primary care at the time of referral to specialized endocrinologists, and the degree of implementation of the national consensus guidelines of the Spanish Society of Diabetes by evaluating steps one (S1), two (S2), and three (S3) of the escalating therapy.Material and methodsRetrospective, observational study where 81 endocrinologists evaluated patients ≥40 years of age referred from primary care between July 2012 and July 2013, treated with 1 to 2 oral antidiabetic drugs but no insulin therapy, and with glycosylated hemoglobin (HbA_1c) levels ≥6.5%. Patients also had to have HbA_1c levels and both fasting and postprandial plasma glucose measurements from the previous three months.ResultsA total of 285 patients (57.6% males) were assessed. Mean (SD) age was 63.1 (9.7) years, mean HbA_1c was 8.5 (1.2) %, mean FPG was 171.7 (43) mg/dL, and mean postprandial plasma glucose was 206.8 (50) mg/dL. In primary care, 26.0% of patients were at S1 and 74.0% were at S2. After referral to the endocrinologist, 9.8% of patients moved onto S1, 42.8% onto S2, and 47.4% onto S3. Oral antidiabetic drugs most commonly prescribed in primary care were metformin (90.2%), DPP-4 inhibitors (34.4%), and sulfonylureas (30.5%), while drugs most commonly used in the specialized endocrinology setting were metformin (86%), insulin (56.8%), and DPP-4 inhibitors (49.8%). The most commonly followed guidelines were those of the American Diabetes Association and the consensus guidelines of the Spanish Society of Diabetes, in 77% and 45% of cases respectively.ConclusionsApproximately half the patients treated with oral antidiabetic drugs in primary care are prescribed insulin after referral to an endocrinology specialist. The most commonly followed guidelines in specialized care are the American Diabetes Association guidelines.     

HbA1c Alone Is a Poor Indicator of Cardiometabolic Risk in Middle-Aged Subjects with Pre-Diabetes but Is Suitable for Type 2 Diabetes Diagnosis: A Cross-Sectional Study

Objectives

Glycated haemoglobin A_1c (HbA_1c) measurement is recommended as an alternative to fasting plasma glucose (FPG) for the diagnosis of pre-diabetes and type 2 diabetes. However, evidence suggests discordance between HbA_1c and FPG. In this study we examine a range of metabolic risk features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine which assay more accurately identifies individuals at increased cardiometabolic risk.

Materials and Methods

This was a cross-sectional study involving a random sample of 2,047 men and women aged 46-73 years. Binary and multinomial logistic regression were employed to examine risk feature associations with pre-diabetes [either HbA_1c levels 5.7-6.4% (39-46 mmol/mol) or impaired FPG levels 5.6-6.9 mmol/l] and type 2 diabetes [either HbA_1c levels >6.5% (>48 mmol/mol) or FPG levels >7.0 mmol/l]. Receiver operating characteristic curve analysis was used to evaluate the ability of HbA_1c to discriminate pre-diabetes and diabetes defined by FPG.

Results

Stronger associations with diabetes-related phenotypes were observed in pre-diabetic subjects diagnosed by FPG compared to those detected by HbA_1c. Individuals with type 2 diabetes exhibited cardiometabolic profiles that were broadly similar according to diagnosis by either assay. Pre-diabetic participants classified by both assays displayed a more pro-inflammatory, pro-atherogenic, hypertensive and insulin resistant profile. Odds ratios of having three or more metabolic syndrome features were also noticeably increased (OR: 4.0, 95% CI: 2.8-5.8) when compared to subjects diagnosed by either HbA_1c (OR: 1.4, 95% CI: 1.2-1.8) or FPG (OR: 3.0, 95% CI: 1.7-5.1) separately.

Conclusions

In middle-aged Caucasian-Europeans, HbA_1c alone is a poor indicator of cardiometabolic risk but is suitable for diagnosing diabetes. Combined use of HbA_1c and FPG may be of additional benefit for detecting individuals at highest odds of type 2 diabetes development.