Glycemic Control and Outcomes of Hospitalization in Noncritically Ill Patients With Type 2 Diabetes Admitted With Cardiac Problems or Infections

ObjectiveAlthough the importance of glycemic control is well established for patients with diabetes hospitalized for surgical problems, it has not been supported by clinical studies for patients with diabetes hospitalized on the medical floors.MethodsWe conducted a retrospective study of 378 patients with type 2 diabetes admitted for cardiac or infectious disease (ID) diagnosis between September 1, 2011, and August 1, 2012. Exclusion criteria included type 1 diabetes, admission to the intensive care unit (ICU), hospital stay shorter than 3 days, and daily glucocorticoid dose > 20 mg of methylprednisolone. The primary composite outcome included death during hospitalization, ICU transfer, initiation of enteral or parenteral nutrition, line infection, deep vein thrombosis, pulmonary embolism, rise in plasma creatinine by 1 or > 2 mg/dL, new infection, an infection lasting for more than 20 days, and readmission within 30 days and between 1 and 10 months after discharge.ResultsPatients were stratified by mean blood glucose (BG) level: group 1 had mean BG of < 180 mg/dL (n = 286; mean BG, 142 ± 23 mg/dL), whereas group 2 had mean BG levels > 181 mg/dL (n = 92; mean BG, 218 ± 34 mg/dL; P < .0001). Group 2 had a 46% higher occurrence of the primary outcome (P < .0004). The rate of unfavorable events was greater in cardiac and ID patients with worse glycemic control (group 2).ConclusionOur data strongly support a positive influence of better glycemic control (average glycemia < 180 mg/dL or 10 mmol/L) on outcomes of hospitaliza-tion in patients with type 2 diabetes. (Endocr Pract. 2014; 20:1303-1308)     

Eating and Glycemic Control Among Critically Ill Patients Receiving Continuous Intravenous Insulin

Objective: Consensus guidelines recommend that intensive care unit (ICU) patients with blood glucose (BG) levels >180 mg/dL receive continuous intravenous insulin (CII). The effectiveness of CII at controlling BG levels among patients who are eating relative to those who are eating nothing by mouth (nil per os; NPO) has not been described.Methods: We conducted a retrospective cohort study of 260 adult patients (156 eating, 104 NPO) admitted to an ICU between January 1, 2014, and December 31, 2014, who received CII. Patients were excluded for a diagnosis of diabetic ketoacidosis or hyperglycemic hyperosmolar nonketotic syndrome, admission to an obstetrics service, or receiving continuous enteral or parenteral nutrition.Results: Among 22 baseline characteristics, the proportion of patients receiving glucocorticoid treatment (GCTx) (17.3% eating, 37.5% NPO; P<.001) and APACHE II score (15.0 ± 7.5 eating, 17.9 ± 7.9 NPO; P = .004) were significantly different between eating and NPO patients. There was no significant difference in the primary outcome of patient-day weighted mean BG overall (153 ± 8 mg/dL eating, 156 ± 7 mg/dL NPO; P = .73), or day-by-day BG (P = .37) adjusted for GCTx and APACHE score. Surprisingly, there was a significant difference in the distribution of BG values, with eating patients having a higher percentage of BG readings in the recommended range of 140 to 180 mg/dL. However, eating patients showed greater glucose variability (coefficient of variation 23.1 ± 1.0 eating, 21.2 ± 1.0 NPO; P = .034).Conclusion: Eating may not adversely affect BG levels of ICU patients receiving CII. Whether or not prandial insulin improves glycemic control in this setting should be studied.Abbreviations: BG = blood glucose; CII = continuous insulin infusion; CV = coefficient of variation; HbA1c = hemoglobin A1c; ICU = intensive care unit; NPO = nil per os; PDWMBG = patient day weighted mean blood glucose     

Decreased Mortality with Tight Glycemic Control in Critically Ill Patients: A Retrospective Analysis in a Large Community Hospital System

ObjectiveTo measure the efficacy and possible adverse consequences of tight blood glucose (BG) control when compared to relaxed control.MethodsA retrospective, observational study was conducted at a community-based teaching hospital system among adult, nonmaternity hospitalized patients admitted to the intensive care unit (ICU). Tight glycemic control of BG was compared with less strict BG control, and the following outcome measurements were compared: BG, average length of stay (ALOS), severe hypoglycemia, and mortality.ResultsBetween 2008 and 2012, 18,919 patients were admitted to the ICU. The mortality rate was significantly lower (P = .0001) in patients with an average BG between 80 and 110 mg/dL (8%) and 111 and 140 mg/dL (9.4%) than in patients with average BG between 141 and 180 mg/dL (12.9%). Using tight glycemic control (80 to 110 mg/dL), the ALOS in the ICU decreased from 4 to 2.9 days (P < .0001) among all patients, and from 4.2 to 2.1 days (P < .0001) among patients who had undergone coronary artery bypass graft. Comparatively, the ALOS for the hospital decreased from 9.4 to 8 days. The incidence of severe hypoglycemia (BG < 40 mg/dL) was higher (P = .01) in the tight BG control group (4.78%) compared with the relaxed control group (3.5%). This rate was lower than in previously published studies that analyzed the use of tight control.ConclusionTight glycemic control using protocolbased insulin administration resulted in a decrease in mortality and ALOS among all patients in the ICU. The incidence of severe hypoglycemic episodes was slightly higher in the tightly controlled group but remained lower than in previously published studies. (Endocr Pract. 2014;20: 907-918)     

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

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

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

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

Association of Glycemic Control Parameters with Clinical Outcomes in Chronic Critical Illness

ObjectiveChronic critical illness (CCI) is a term used to designate patients requiring prolonged mechanical ventilation and tracheostomy with associated poor outcomes. The present study assessed the impact of glycemic parameters on outcomes in a CCI population.MethodsA retrospective case series was performed including 148 patients in The Mount Sinai Hospital Respiratory Care Unit (2009-2010). Utilizing a semi-parametric mixture model, trajectories for the daily mean blood glucose (BG), BG range, and hypoglycemia rate over time identified low- (n = 87) and high-risk (n = 61) hyperglycemia groups and low- (n = 90) and high-risk (n = 58) hypoglycemia groups. The cohort was also classified into diabetes (DM, n = 48), stress hyperglycemia (SH, n = 85), and normal glucose (n = 15) groups.ResultsHospital- (28% vs. 13%, P = .0199) and 1-year mortality (66% vs. 46%, P = .0185) rates were significantly greater in the high- versus low-risk hyperglycemia groups, respectively. The hypoglycemia rate (< 70 mg/dL) was lower among ventilator-liberated patients compared to those who failed to liberate (0.092 vs. 0.130, P < .0001). In the SH group, both hospital mortality (high-risk hyperglycemia 48% and low-risk hyperglycemia 15%, P = .0013) and 1-year mortality (high-risk 74% and low-risk 50%, P = .0482) remained significantly different, while no significant difference in the diabetes group was observed. There were lower hypoglycemia rates with SH compared to diabetes (< 70 mg/dL: 0.086 vs. 0.182, P < .0001; < 40 mg/dL: 0.012 vs. 0.022, P = .0118, respectively).ConclusionTighter glycemic control was associated with improved outcomes in CCI patients with SH but not in CCI patients with diabetes. Confirmation of these findings may lead to stratified glycemic control protocols in CCI patients based on the presence or absence of diabetes. (Endocr Pract. 2014;20:884-893)     

The Synergy to Enable Glycemic Control Following Emergency Department Discharge Program for Adults with Type 2 Diabetes: Step-Diabetes

Objective: To evaluate a diabetes (DM) care delivery model among hyperglycemic adults with type 2 DM being discharged from the emergency department (ED) to home. The primary hypothesis was that a focused education and medication management intervention would lead to a greater short-term improvement in glycemic control compared to controls.Methods: A 4-week, randomized controlled trial provided antihyperglycemic medications management using an evidence-based algorithm plus survival skills diabetes self-management education (DSME) for ED patients with blood glucose (BG) levels ≥200 mg/dL. The intervention was delivered by endocrinologist-supervised certified diabetes educators. Controls received usual ED care.Results: Among 101 participants (96% Black, 54% female, 62.3% Medicaid and/or Medicare insurance), 77% completed the week 4 visit. Glycated hemoglobin A1C (A1C) went from 11.8 ± 2.4 to 10.5 ± 1.9% (P<.001) and 11.5 ± 2.0 to 11.1 ± 2.1% in the intervention and control groups, respectively (P = .012). At 4 weeks, the difference in A1C reduction between groups was 0.9% (P = .01). Mean BG decreased for both groups (P<.001), with a higher percentage of intervention patients (65%) reaching a BG <180 mg/dL compared to 29% of controls (P = .002). Hypoglycemia rates did not differ by group, and no severe hypoglycemia was reported. Medication adherence (Modified Morisky Score©) improved from low to medium (P<.001) among intervention patients and did not improve among controls.Conclusions: This study provides evidence that a focused diabetes care delivery intervention can be initiated in the ED among adults with type 2 diabetes and hyperglycemia and safely and effectively completed in the ambulatory setting. Improvement in short-term glycemic outcomes and medication adherence were observed.Abbreviations: A1C = glycated hemoglobin A1C BG = blood glucose BMI = body mass index CDE = certified diabetes educator CI = confidence interval DM = diabetes mellitus DSME = diabetes self-management education ED = emergency departmentMMAS-8 = Modified Morisky Medication Scale PCP = primary care provider POC = point of care SQ = subcutaneous     

Inpatient Hypoglycemic Events in a Comparative Effectiveness Trial for Glycemic Control in a High-Risk Population

Objective: Inpatient hypoglycemia (glucose ≤70 mg/dL) is a limitation of intensive control with insulin. Causes of hypoglycemia were evaluated in a randomized controlled trial examining intensive glycemic control (IG, target 140 mg/dL) versus moderate glycemic control (MG, target 180 mg/dL) on post–liver transplant outcomes.Methods: Hypoglycemic episodes were reviewed by a multidisciplinary team to calculate and identify contributing pathophysiologic and operational factors. A subsequent subgroup case control (1:1) analysis (with/without) hypoglycemia was completed to further delineate factors. A total of 164 participants were enrolled, and 155 patients were examined in depth.Results: Overall, insulin-related hypoglycemia was experienced in 24 of 82 patients in IG (episodes: 20 drip, 36 subcutaneous [SQ]) and 4 of 82 in MG (episodes: 2 drip, 2 SQ). Most episodes occurred at night (41 of 60), with high insulin amounts (44 of 60), and during a protocol deviation (51 of 60). Compared to those without hypoglycemia (n = 127 vs. n = 28), hypoglycemic patients had significantly longer hospital stays (13.6 ± 12.6 days vs. 7.4 ± 6.1 days; P = .002), higher peak insulin drip rates (17.4 ± 10.3 U/h vs. 13.1 ± 9.9 U/h; P = .044), and higher peak insulin glargine doses (36.8 ± 21.4 U vs. 26.2 ± 24.3 U; P = .035). In the case-matched analysis (24 cases, 24 controls), those with insulin-related hypoglycemia had higher median peak insulin drip rates (17 U/h vs. 11 U/h; P = .04) and protocol deviations (92% vs. 50%; P = .004).Conclusion: Peak insulin requirements and protocol deviations were correlated with hypoglycemia.Abbreviations:DM = diabetes mellitusICU = intensive care unitIG = intensive glycemic controlMELD = Model for End-stage Liver DiseaseMG = moderate glycemic controlSQ = subcutaneous     

High-Dose Glucocorticoid Treatment Does Not Induce Severe Hyperglycemia in Young Patients with Autoimmune Diseases by Cgms

Objective: High-dose glucocorticoids (HDG) are used in the treatment of autoimmune diseases. Glucocorticoids-induced hyperglycemia (GIH) is often described in elderly patients. In young patients with autoimmune diseases, however, the risk for GIH has not been well characterized.Methods: We recruited 24 inpatients (median age, 32 years; interquartile range, 25–42) with exacerbations of autoimmune diseases, receiving 1 to 2 mg/kg/day prednisone or equivalent methylprednisone. Fourteen subjects were naïve to glucocorticoids (group 1) and 10 subjects were on glucocorticoid maintenance (≤15 mg/day prednisone at least 3 months) (group 2) prior to HDG. All subjects were monitored by continuous glucose monitoring system (CGMS) for 3 days.Results: GIH developed in 21 (91%) subjects, 11/13 in group 1 and 10/10 in group 2. The main peak of glucose excursion (128.7 ± 6.4 mg/dL, group 1; 143.9 ± 10.0 mg/dL, group 2) occurred at 2 to 3 pm. Another peak occurred before sleep. Two-hour mean postprandial glucose levels were normal in both groups: breakfast, 105.0 ± 28.4 versus 125.6 ± 24.4 mg/dL, P = .065; lunch, 115.7 ± 21.1 versus 135.9 ± 29.0 mg/dL, P = .082; dinner, 122.8 ± 18.5 versus 137.8 ± 26.4 mg/dL, P = .144 in groups 1 and 2, respectively. There was a positive association between pretreatment hemoglobin A1C and peak glucose levels (P<.0001). Notably, 35% of our subjects experienced early morning hypoglycemia (65.2 ± 2.8 mg/dL).Conclusion: In hospitalized young patients with auto-immune diseases, CGMS data revealed that short-term consistent HDG treatment induced mild hyperglycemia, peaking in the early afternoon and before sleep. Early morning hypoglycemia was found in 35%.Abbreviations: A1C = hemoglobin A1C; AUC = the area under the curve; BG = blood glucose; BMI = body mass index; CGMS = continuous glucose monitoring system; DM = diabetes mellitus; FBG = fasting blood glucose; GA = glycated albumin; GCs = glucocorticoids; GIH = glucocorticoids-induced hyperglycemia; HDG = high-dose glucocorticoids; HOMA-IR = Homeostasis Model Assessment-Insulin Resistance; IG = interstitial glucose; IQR = interquartile range; PUMCH = Peking Union Medical College Hospital; SLE = systemic lupus erythematosus     

Daily Inpatient Glycemic Survey (DINGS): A Process to Remotely Identify and Assist in the Management of Hospitalized Patients with Diabetes and Hyperglycemia

Objective: Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, and overall costs of care in hospitalized patients. At the Stratton VA Medical Center in Albany, New York, a process aimed to improve inpatient glycemic control by remotely assisting primary care teams in the management of hyperglycemia and diabetes was designed.Methods: An electronic query comprised of hospitalized patients with glucose values <70 mg/dL or >350 mg/dL is generated daily. Electronic medical records (EMRs) are individually reviewed by diabetes specialist providers, and management recommendations are sent to primary care teams when applicable. Glucose data was retrospectively examined before and after the establishment of the daily inpatient glycemic survey (DINGS) process, and rates of hyperglycemia and hypoglycemia were compared.Results: Patient-day mean glucose slightly but significantly decreased from 177.6 ± 64.4 to 173.2 ± 59.4 mg/dL (P<.001). The percentage of patient-days with any value >350 mg/dL also decreased from 9.69 to 7.36% (P<.001), while the percentage of patient-days with mean glucose values in the range of 90 to 180 mg/dL increased from 58.1 to 61.4% (P<.001). Glycemic variability, assessed by the SD of glucose, significantly decreased from 53.9 to 49.8 mg/dL (P<.001). Moreover, rates of hypoglycemia (<70 mg/dL) decreased significantly by 41% (P<.001).Conclusion: Quality metrics of inpatient glycemic control improved significantly after the establishment of the DINGS process within our facility. Prospective controlled studies are needed to confirm a causal association.Abbreviations: DINGS = daily inpatient glycemic survey EMR = electronic medical record HbA1c = glycated hemoglobin ICU = intensive care unit VA = Veterans Affairs     

Effect Of A Targeted Glycemic Management Program On Provider Response To Inpatient Hyperglycemia

ObjectiveTo report the results of implementation of a Targeted Glycemic Management (TGM) Service pilot, with the goals of improving clinician awareness of available inpatient glycemic management protocols and improving responsiveness to and frequency of severe hyperglycemia.MethodsPatients with a blood glucose (BG) level ≥ 300 mg/dL who were hospitalized on a general medicine unit during three 12-week periods before, during, and after the TGM pilot were compared for responsiveness by the primary team, percentage of subsequent BG measurements between 80 and 180 mg/dL, and frequency of subsequent severe hyperglycemia (BG levels ≥ 300 mg/dL) and hypoglycemia (BG values < 70 mg/dL).ResultsIn comparison with pre-TGM and post-TGM periods, more patients during the TGM pilot had a modification of their glycemic regimen in response to severe hyperglycemia (49% versus 73% versus 50%, before, during, and after TGM, respectively; P = .044), and the percentage of patients with ≥ 50% of subsequent BG measurements in the desired range (27% versus 53% versus 32%; P = .035) was greatest during the TGM period. The incidence of subsequent severe hyperglycemia (20% versus 9% versus 16%; P = .0004) was lowest during the TGM period; however, the incidence of hypoglycemia was similar in all 3 periods (3.9% versus 3.7% versus 3.7%).ConclusionThese results indicate that a TGM Service can favorably influence glycemic management practices and improve glycemic control, but ongoing intervention is necessary for maintenance of these results. (Endocr Pract. 2011;17:552-557)     

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)     

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 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)     

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)     

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)     

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)     

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)     

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

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

Glucose Variability is an Independent Predictor of Mortality in Hospitalized Patients Treated with Total Parenteral Nutrition

ObjectiveHyperglycemia is associated with increased mortality in critically ill patients treated with total parenteral nutrition (TPN). The role of glucose variability (GV) in predicting outcomes in these patients is not known.MethodsThis retrospective study included medical and surgical patients receiving TPN in a community teaching hospital. GV was calculated by standard deviation (SD) of blood glucose (BG) values and by mean BG daily (Δ) change (daily max – daily minimum).ResultsA total of 276 medical and surgical patients (mean age: 51 ± 18 years), 19% with a history of diabetes mellitus (DM), and 74% with intensive care unit (ICU) admission were treated with TPN. During TPN, the mean daily BG was 142.9 ± 33 mg/dL; frequencies of hypoglycemia < 70 and < 40 mg/dL were 41% and 3%, respectively; and hospital mortality was 27.2%. The mean GV by SD was 38 ± 21 mg/dL and by mean (Δ) change 58 ± 34 mg/dL. GV was significantly higher in deceased patients (SD: 48 ± 25 vs. 34 ± 18 mg/dL and Δ change: 75 ± 39 vs. 51 ± 29 mg/dL, both P < .01) than surviving patients. Multivariate analysis adjusted for age, DM status, gender, APACHE (Acute Physiology and Chronic Health Evaluation) score, mean daily glucose, and hypoglycemia revealed that GV was an independent predictor of hospital mortality (P < .05). The association between GV and mortality was limited to patients without a history of DM and was not present in patients with DM.ConclusionHigh GV is associated with increased hospital mortality independent of the presence and severity of hyperglycemia or hypoglycemia during TPN therapy. Prospective randomized trials are needed to determine if reduction in GV with intensive glycemic control improves clinical outcomes in patients treated with TPN. (Endocr Pract. 2014;20:41-45)