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)     

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)     

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)     

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)     

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

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

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)     

Caracterización y costes asociados al perfil del paciente con diabetes tipo 2 en tratamiento con metformina al que se le añade un segundo fármaco antidiabético oral: estudio de base poblacional

ObjectivesTo determine compliance, metabolic control, complications and healthcare costs of patients treated with metformin started a second antidiabetic drug in patients with type 2 diabetes (T2DM).Patients and methodsDesign multicenter observational retrospective. Patients were evaluated ≥30 years (age), treated with metformin and started a second antidiabetic treatment during 2008-2009. There were 4 patient groups (metformin and another antidiabetic): a) dipeptidyl peptidase-4 inhibitors (IDPP4), b) sulfonylureas, c) glitazones and d) insulin. Main measures: comorbidity, metabolic control, compliance and complications. Patients were followed for 2 years. The cost model differed direct health costs (primary care / specialist) and indirect (labor productivity). Statistical analysis: logistic regression models and ANCOVA, p < 0.05.Results2067 patients were included (mean age: 66.6 years male: 53.1%). 25.1% started a second treatment with IDPP4; 42.9% sulfonylureas, 14.0% glitazones and 18.0% insulin. At 2 years follow-up, patients treated with IDPP4 showed greater adherence vs. 70.3%. 59.9%, 60.3% and 58.4; better control of 64.3% vs. DM2. 62.6%, 62.8% and 50.5% and a decrease of 13.9% compared to hypoglycaemia 40.4%, 37.6% and 58.9% respectively (p < 0.001). The average / unit total costs was €2,321 vs. €2,475, €2,724 and €3,164, respectively, p < 0.001. Rates of cardiovascular events and renal failure were 3.7%, 6.4%, 7.6% and 10.2% respectively.ConclusionsSulfonylureas were the most commonly used drugs. Patients treated with IDPP4 had higher compliance and control of diabetes, with lower rates of hypoglycaemia and healthcare costs.     

Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study

BackgroundChromium is an essential mineral that contributes to normal glucose function and lipid metabolism. This study evaluated the effect of chromium picolinate (CrPic) supplementation in patients with type 2 diabetes mellitus (T2DM).MethodsA four month controlled, single blind, randomized trial was performed with 71 patients with poorly controlled (hemoglobin A1c [HbA1c] > 7%) T2DM divided into 2 groups: Control (n = 39, using placebo), and supplemented (n = 32, using 600 μg/day CrPic). All patients received nutritional guidance according to the American Diabetes Association (ADA), and kept using prescribed medications. Fasting and postprandial glucose, HbA1c, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and serum ferritin were evaluated.ResultsCrPic supplementation significantly reduced the fasting glucose concentration (−31.0 mg/dL supplemented group; −14.0 mg/dL control group; p < 0.05, post- vs. pre-treatment, in each group) and postprandial glucose concentration (−37.0 mg/dL in the supplemented group; −11.5 mg/dL in the control group; p < 0.05). HbA1c values were also significantly reduced in both groups (p < 0.001, comparing post- vs. pre-treatment groups). Post-treatment HbA1c values in supplemented patients were significantly lower than those of control patients. HbA1c lowering in the supplemented group (−1.90), and in the control group (−1.00), was also significant, comparing pre- and post-treatment values, for each group (p < 0.001 and p < 0.05, respectively). CrPic increased serum chromium concentrations (p < 0.001), when comparing the supplemented group before and after supplementation. No significant difference in lipid profile was observed in the supplemented group; however, total cholesterol, HDL-c and LDL-c were significantly lowered, comparing pre- and post-treatment period, in the control group (p < 0.05).ConclusionsCrPic supplementation had a beneficial effect on glycemic control in patients with poorly controlled T2DM, without affecting the lipid profile. Additional studies are necessary to investigate the effect of long-term CrPic supplementation.     

Colesevelam Hydrochloride-Ezetimibe Combination Lipid-Lowering Therapy in Patients with Diabetes or Metabolic Syndrome and a History of Statin Intolerance

ObjectiveTo determine the effectiveness and safety of colesevelam hydrochloride (HCl) and ezetimibe combination therapy in statin-intolerant patients with dyslipidemia and diabetes mellitus (DM) or metabolic syndrome (MS).MethodsWe identified potential study subjects through a computerized text search of patient electronic medical records using the terms colesevelam, WelChol, ezetimibe, and Zetia. Medical records were subsequently reviewed to identify all patients with DM or MS. Baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglyceride levels immediately before the initiation of therapy with colesevelam HCl (1.875 g twice a day) or ezetimibe (10 mg daily) were compared with those after a minimum of 3 months of single drug therapy and after a minimum of 3 months of combination therapy. Drug safety was evaluated by review of transaminase levels and reports of side effects or drug discontinuation.ResultsThe computerized search initially identified 91 electronic medical records; 16 patients fulfilled all study criteria. Baseline patient demographics included a mean age of 62.5 (± 11.8) years and a mean body mass index of 31.4 (± 5.2) kg/m²; 50% of patients were female, 75% had type 2 DM, and 25% had MS. In comparison with baseline, colesevelam HCl-ezetimibe combination therapy was associated with significant reductions in mean levels of total cholesterol (27.5%), LDL-C (42.2%), and non-HDL-C (37.1%). In addition, 50% of patients achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C target of less than 100 mg/dL. Therapy was well tolerated, with no significant changes in mean transaminase levels, no reports of myalgia, and no discontinuation of therapy.ConclusionColesevelam HCl-ezetimibe combination therapy was associated with improved TC, LDL-C, and non-HDL-C lipid profiles and was well tolerated. Such therapy may be a reasonable consideration for statin-intolerant patients with DM or MS who have elevated cholesterol levels. (Endocr Pract. 2007;13:11-16)     

Safety and Efficacy of Exenatide in Combination with Insulin in Patients with Type 2 Diabetes Mellitus

ObjectiveTo evaluate the 1-year efficacy and safety of treatment with exenatide in combination with insulin (a use not approved by the US Food and Drug Administration).MethodsElectronic medical records of 3 private-practice endocrinologists were reviewed to identify patients with type 2 diabetes mellitus (T2DM) receiving insulin who subsequently began exenatide therapy. Patients’ baseline hemoglobin A1c (A1C) levels, weights, lipid profiles, blood pressures, and medication utilization were compared with corresponding data obtained after a minimal duration of 12 months.ResultsWe identified 134 patients with T2DM initiating exenatide therapy in combination with insulin between April 2005 and April 2006. One-year follow-up information was available for 124 patients. Exenatide use resulted in a significant 0.87% reduction in A1C (P < .001), despite a 45% discontinuation of premeal insulin use (P < .001), a 9-U reduction in mean premeal insulin doses (P = .0066), a reduction in the median number of daily insulin injections from 2 to 1 (P = .0053), and a 59% discontinuation rate of sulfonylurea use (P = .0088). Exenatide use was associated with a mean weight loss of 5.2 kg (P < .001), with 72% of evaluable patients losing weight. Forty-eight patients (36%) discontinued exenatide therapy during the first year, primarily attributable to gastrointestinal intolerance. Fourteen patients (10%) experienced hypoglycemia, most of which was mild.ConclusionExenatide in combination with insulin in patients with T2DM was associated with significant reductions in A1C and weight after 1 year of therapy. This was offset, however, by an exenatide discontinuation rate of 36%, primarily due to adverse gastrointestinal effects. (Endocr Pract. 2008;14:285-292)     

Adding Rapid-Acting Insulin or Glp-1 Receptor Agonist to Basal Insulin: Outcomes in A Community Setting

ObjectiveTo evaluate real-world outcomes in patients with type 2 diabetes mellitus (T2DM) receiving basal insulin who initiate add-on therapy with a rapid-acting insulin (RAI) or a glucagon-like peptide 1 (GLP-1) receptor agonist.MethodsData were extracted retrospectively from a U.S. health claims database. Adults with T2DM on basal insulin who added an RAI (basal + RAI) or GLP-1 receptor agonist (basal + GLP-1) were included. Propensity score matching (with a 1 up to 3 ratio) was used to control for differences in baseline demographics, clinical characteristics, and health resource utilization. Endpoints included prevalence of hypoglycemia, pancreatic events, all-cause and diabetes-related resource utilization, and costs at 1-year follow-up.ResultsOverall, 6,718 matched patients were included: 5,013 basal + RAI and 1,705 basal + GLP1. Patients in both groups experienced a similar proportion of any hypoglycemic event (P = .4079). Hypoglycemic events leading to hospitalization were higher in the basal + RAI cohort (2.7% vs. 1.8%; P = .0444). The basal + GLP-1 cohort experienced fewer all-cause (13.55% vs. 18.61%; P < .0001) and diabetes-related hospitalizations (11.79% vs. 15.68%; P < .0001). The basal + GLP-1 cohort had lower total all-cause health care costs ($18,413 vs. $20,821; P = .0002) but similar diabetes-related costs ($9,134 vs. $8,985; P < .0001) compared with the basal + RAI cohort.ConclusionsAdd-on therapy with a GLP-1 receptor agonist in T2DM patients receiving basal insulin was associated with fewer hospitalizations and lower total all-cause costs compared with add-on therapy using an RAI and could be considered as an alternative to an RAI in certain patients with T2DM who do not achieve effective glycemic control with basal insulin. (Endocr Pract. 2015; 21:68-76)     

Exenatide Use in the Management of Metabolic Syndrome: A Retrospective Database Study

ObjectiveTo evaluate the effect of exenatide therapy on cardiometabolic risk factors and anthropometric parameters in patients with metabolic syndrome.MethodsFrom June 2005 to June 2007, we performed a retrospective analysis of data extracted from the records of adult patients with metabolic syndrome being treated with exenatide. Diagnosis of any type of diabetes mellitus was exclusionary. Patients were initiated on exenatide therapy, 5 mcg, 1 hour before their morning and evening meals for the first month and were instructed to titrate up to 10 mcg. Cardiometabolic risk factors (total cholesterol, high-denssity lipoprotein cholesterol, triglycerides, calculated low- density lipoprotein cholesterol, and blood pressure) and anthropometric parameters (absolute body weight, body mass index, and abdominal girth) were measured at baseline and at 16 ± 4 weeks after initiating exenatide therapy. Data collected also included age, sex, metabolic syndrome diagnosis, and other concomitant medication used in the management of endocrine disorders.ResultsThe study population consisted of 299 patients (259 women, 40 men) with an age range of 18 to 74 years. Exenatide treatment was associated with significant reductions in mean body weight (P < .001) and body mass index (P < .001). Weight loss in 76.6% of patients was concomitant with a significant reduction in mean abdominal girth (P < .001). Further analysis revealed significant decreases in mean triglycerides (P < .001), total cholesterol (P < .01), and both systolic (P < .01) and diastolic blood pressure (P < .03). Approximately 60.2% of patients used metformin concomitantly, and half either decreased or discontinued metformin therapy.ConclusionsThis is the first report examining the effect of exenatide on patients with metabolic syndrome. We observed a significant improvement in cardiometabolic risk factors and anthropometric parameters as a result of exenatide over the treatment interval. (Endocr Pract. 2008;14:993-999)     

Tasa estimada de disposición de glucosa en pacientes menores de 18 años con diabetes mellitus tipo 1 y sobrepeso-obesidad

ObjectiveTo assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight.MethodsA total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age.ResultsNo significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3 ± 1.3 vs 10.1 ± 0.8 mg kg^-1min^-1; p < 0.01). Insulin dose was higher in overweight and obese children, especially in IU/m²/day (37.7 vs 36.1 vs 29.4 respectively; p < 0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5 mg/dL respectively; p < 0.01). No correlation was found between waist circumference and the different markers of insulin resistance.ConclusionsValues of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m²/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk.     

Concomitant Oral Antihyperglycemic Agent Use and Associated Treatment Outcomes After Initiation of Insulin Therapy

ObjectiveTo compare outcomes in patients with type 2 diabetes initiating insulin lispro mix 75/25 (75% insulin lispro protamine suspension and 25% lispro) or insulin glargine therapy, stratified by baseline oral antihyperglycemic agent (OHA) use.MethodsWe performed a post hoc analysis of 6-month data from the DURABLE clinical trial, which enrolled patients with hemoglobin A_1c (A1C) levels > 7.0% treated with 2 or more OHAs (metformin, sulfonylurea, and thiazolidinedione), and randomly assigned them to treatment with twice-daily insulin lispro 75/25 or oncedaily glargine.ResultsIn both insulin treatment groups, metformin/ thiazolidinedione-treated patients had significantly greater improvement in A1C levels (-2.19% to -2.36%), lower end point A1C values, and lower rates of occurrence of hypoglycemia in comparison with metformin/sulfonylurea-treated patients (all P < .05). Patients treated with sulfonylurea/thiazolidinedione or metformin/sulfonylurea/thiazolidinedione did not differ significantly from metformin/sulfonylurea-treated patients in A1C change (-1.56% to -1.84%) or rates of occurrence of hypoglycemia.ConclusionIn these post hoc analyses, patients with type 2 diabetes initiating premixed or basal insulin therapy and treated concomitantly with the OHA combination of metformin/thiazolidinedione at baseline demonstrated significantly greater A1C improvement with less hypoglycemia in comparison with patients treated with metformin/ sulfonylurea. (Endocr Pract. 2011;17:563-567)     

Identifying Risk Factors for Severe Hypoglycemia in Hospitalized Patients with Diabetes

ObjectiveSome of the deleterious effects of hypoglycemia in hospitalized patients include increased rates of mortality and longer length of stay. Our primary objective was to identify the risk factors associated with severe hypoglycemia to identify those patients at highest risk.MethodsThe medical records of 5,026 patients with diabetes mellitus (DM) admitted in 2010 were reviewed to identify those patients that developed severe hypoglycemia (blood glucose [BG] < 40 mg/dL). We performed c2 tests to assess statistical significance. Adjusted logical regression was used to determine the risk factors for hypoglycemia in the hospital.ResultsOut of 5,026 DM patients included in our review, 81 experienced severe hypoglycemia (1.6%). Statistically higher proportions of chronic kidney disease (CKD; 69.1% vs. 46.9%, P < .001), congestive heart failure (CHF; 48.1% vs. 28.5%, P < .001), sepsis (49.4% vs. 12.5%, P < .001), insulin use (45.7% vs. 26.04%, P = .000), type 1 DM (21% vs. 5.1%, P = .000), and cirrhosis (14.8% vs. 7.2%, P = .009) were seen in the severe hypoglycemic group compared to the nonsevere hypoglycemic group. Overall, 84% of patients who experienced an episode of severe hypoglycemia in the hospital (BG < 40 mg/dL) had a previous episode of hypoglycemia (BG < 70 mg/dL). The odds ratios (ORs) for type 1 DM, sepsis, previous hypoglycemia, and insulin use were 3.43 (95% confidence interval [CI] 1.81, 6.49), 2.64 (95% CI 1.6, 4.35), 46.1 (95% CI 24.76, 85.74), and 1.66 (95% CI 1.02, 2.69), respectively.ConclusionPrior episodes of hypoglycemia in the hospital, the presence of type 1 DM, insulin use, and sepsis were identified as independent risk factors for the development of severe hypoglycemia in the hospital. (Endocr Pract. 2014;20:1051-1056)     

Add-on therapy with anagliptin in Japanese patients with type-2 diabetes mellitus treated with metformin and miglitol can maintain higher concentrations of biologically active GLP-1/total GIP and a lower concentration of leptin

Metformin, α-glucosidase inhibitors (α-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients. We assessed add-on therapeutic effects of DPP-4I anagliptin in Japanese T2DM patients treated with metformin, an α-GI miglitol, or both drugs on postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of the appetite-suppressing hormone leptin. Forty-two Japanese T2DM patients with inadequately controlled disease (HbA1c: 6.5%–8.0%) treated with metformin (n = 14), miglitol (n = 14) or a combination of the two drugs (n = 14) received additional treatment with anagliptin (100 mg, p.o., b.i.d.) for 52 weeks. We assessed glycemic control, postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of leptin in those patients. Add-on therapy with anagliptin for 52 weeks improved glycemic control and increased the area under the curve of biologically active GLP-1 concentration without altering obesity indicators. Total GIP concentration at 52 weeks was reduced by add-on therapy in groups treated with miglitol compared with those treated with metformin. Add-on therapy reduced leptin concentrations. Add-on therapy with anagliptin in Japanese T2DM patients treated with metformin and miglitol for 52 weeks improved glycemic control and enhanced postprandial concentrations of active GLP-1/total GIP, and reduce the leptin concentration.     

Diabetes Duration and the Efficacy and Safety of Insulin Glargine Versus Comparator Treatment in Patients with Type 2 Diabetes Mellitus

ObjectiveTo evaluate the effect of diabetes duration on efficacy and safety in patients with type 2 diabetes mellitus (T2DM) using insulin glargine versus comparator (oral antidiabetic drugs [OADs], dietary changes, or other insulins).MethodsData were pooled from randomized controlled clinical trials conducted in adults with T2DM with at least 24-week treatment with insulin glargine or a comparator, where predefined insulin titration algorithms were utilized to achieve fasting plasma glucose (FPG) concentrations of ≤ 100 mg/dL. Glycated hemoglobin A1C (A1C), FPG, and insulin dose and safety (hypoglycemia) outcomes were analyzed.ResultsNine studies were included in the analysis of 2,930 patients. Patients with shorter duration of diabetes were more likely to have greater reductions in A1C compared with those who had longer-duration disease (P < .0001). Disease duration did not affect change in FPG concentrations (P = .9017), but lower weight-adjusted insulin dose was correlated with longer-duration disease (P < .0001). Patients with longer-duration diabetes had increased risks of symptomatic hypoglycemia, confirmed hypoglycemia (self-monitored blood glucose < 50 mg/dL and < 70 mg/dL), and nocturnal hypoglycemia (all P < .001). No significant relationship was found between severe hypoglycemia and duration of diabetes. However, treatment with insulin glargine lowered A1C values more effectively than comparator treatments with fewer hypoglycemic episodes.ConclusionPatients with shorter-duration T2DM better achieved target A1C levels and had less hypoglycemia than those with longer disease duration. Insulin glargine was associated with reduced A1C and fewer hypoglycemic events than comparators, regardless of disease duration. (Endocr Pract. 2014;20:120-128)     

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

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

Achievement of therapeutic targets in Mexican patients with diabetes mellitus

Background and aimComplications of diabetes comprise the leading cause of death in Mexico. We aimed to describe the characteristics of management and achievement of therapeutic targets in Mexican patients with diabetes mellitus.MethodsWe analyzed data from 2642 Mexican patients with type 1 (T1D, n = 203, 7.7%) and type 2 diabetes (T2D, n = 2439, 92.3%) included in the third wave of the International Diabetes Management Practices Study.ResultsOf T2D patients, 63% were on oral glucose-lowering drugs (OGLD) exclusively (mostly metformin), 11% on insulin, 22% on OGLD plus insulin, and 4% on diet and exercise exclusively. T2D patients on insulin were more likely to be trained on diabetes, but they were older, had worse control, longer disease duration and more chronic complications than patients on OGLD only. Glycated hemoglobin (HbA1c) < 7% was achieved by 21% and 37% of T1D and T2D patients, respectively. Only 5% of T1D and 3% of T2D attained the composite target of HbA1c < 7%, blood pressure < 130/80 mmHg and low-density lipoprotein cholesterol < 100 mg/dl. T1D patients had less macrovascular but more microvascular complications, compared with T2D patients. Late complications increased with disease duration, so that about 80% of patients after 20 years of diagnosis have at least one late complication. Reaching the target HbA1c < 7% was associated with a reduced number of microvascular but not with less macrovascular complications.ConclusionA great proportion of these Mexican patients with diabetes did not reach therapeutic targets. Insulin was used mostly in complicated cases with advanced disease.     

Population-Based Study of Hypoglycemia in Patients with Type 1 Diabetes Mellitus Requiring Emergency Medical Services

ObjectiveTo report the population burden of hypo glycemia necessitating emergency medical services (EMS) and the long-term outcomes in patients with type 1 diabetes mellitus (T1DM) receiving different insulin treatments.MethodsWe retrieved all EMS calls because of hypoglycemia in patients with T1DM in Olmsted County, Minnesota, between January 1, 2003, and December 31, 2009, and reviewed the related medical records.ResultsDuring the 7-year study period, 531 EMS calls were made involving 208 patients with T1DM (112 men, 96 women; mean age 47 ± 13 years). Of the 208 patients, 137 (66%) were receiving multiple daily insulin (MDI) injections, 50 (24%) were receiving continuous sub cutaneous insulin infusion, 15 (7%) were receiving simple insulin (SI), 4 (2%) were treated with metformin + MDI, and 2 (1%) were not receiving treatment for diabetes (after pancreas transplantation). The last 2 groups were excluded from further analysis because of small sample size. The remaining 3 treatment groups differed by age (P < .02), with the oldest patients receiving SI. Repeated calls, emergency department transportation (EDT), and hospitalization had a 33%, 49%, and 18% frequency, respectively, and did not differ among the treatment groups. In a multivariate model, mortality was significantly associated with treatment type (the SI group had a higher risk for mortality than did the MDI group [P = .03] after exclusion of 27 patients who changed treatment during follow-up), age (P < .0001), and EDT (P = .04).ConclusionThe population burden of EMS-requiring hypoglycemia in patients with T1DM is high. Medical resource utilization was similar among the 3 treatment groups. Mortality was higher in the SI group (limited by small sample size) and among patients requiring EDT and increased with advancing age. Further research could be directed toward understanding the effect of expert evaluation of high-risk patients on long-term outcomes. (EndocrPract. 2012;18:834-841)