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)     

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)     

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)     

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)     

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)     

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 Insulin Lispro in Obese Patients with Type 2 Diabetes: A Retrospective Meta-Analysis of 7 Randomized Controlled Trials

ObjectiveTo evaluate the efficacy and safety of insulin lispro in the treatment of patients with type 2 diabetes (T2DM) who had a body mass index (BMI) ≥ 30 kg/m² (obese) compared with patients with BMIs < 30 kg/m² (nonobese).MethodsA retrospective analysis of predefined endpoints from 7 randomized clinical trials of T2DM patients treated with insulin lispro was performed. The primary efficacy measure was to assess the noninferiority of insulin lispro in obese patients versus nonobese patients as measured by the change in hemoglobin A1C (HbA_1c) from baseline to Month 3 (n = 1,518), using a noninferiority margin of 0.4%. The secondary measures included overall hypoglycemia incidence and event rates and relative change in body weight.ResultsMean changes in HbA_1c from baseline (9.06% for obese and 8.92% for nonobese) to Month 3 were similar for obese patients (–1.03%) and nonobese (–1.02%), with a least squares (LS) mean difference (95% confidence interval [CI]) of –0.05% (–0.17%, 0.07%; P = .384). The overall incidence of hypoglycemia (53% vs. 63%; P < .001) and rate of hypoglycemia (0.93 vs. 1.76 events per 30 days; P < .001) was significantly lower in obese patients compared with nonobese patients. The 2 BMI cohorts did not demonstrate a significant difference in mean percent changes in body weights (LS mean difference = 0.4% [–0.2%, 0.9%]; P = .202).ConclusionObese patients with T2DM treated with insulin lispro were able to achieve the same level of glycemic control as their nonobese counterparts, with some evidence supporting a reduced risk of hypoglycemia. (Endocr Pract. 2014;20:389-398)     

Characterizing Glucose Changes Antecedent to Hypoglycemic Events in the Intensive Care Unit

ObjectiveTo determine whether patterns of glucose changes before hypoglycemia vary according to the severity of the event.MethodsIn this retrospective analysis, point-ofcare blood glucose (POC-BG) data were obtained from the intensive care units (ICUs) of a convenience sample of hospitals that responded to a survey on inpatient diabetes management quality improvement initiatives. To evaluate POC-BG levels before hypoglycemic events, data from patients who experienced hypoglycemia during their time in the ICU were examined, and their glucose changes were assessed against a comparison group of patients who achieved a glycemic range of 80 to 110 mg/dL without ever experiencing hypoglycemia. Absolute glucose decrease, glucose rate of change, and glucose variability before hypoglycemic events (< 40, 40-49, 50-59, and 60-69 mg/ dL) were calculated.ResultsA total of 128 419 POC-BG measurements from 2942 patients in 89 ICUs were analyzed. Patients who experienced the most severe hypoglycemic episodes had the largest absolute drop in their glucose levels before the event (P < .001). The glucose rate of change before a hypoglycemic event increased with worsening hypoglycemia: mean (± standard deviation) glucose rate of change was-1.69 (± 2.98) mg/dL per min before an episode with glucose values less than 40 mg/dL, -0.56 (± 2.65) mg/dL per min before an episode with glucose values 60 to 69 mg/dL, but only -0.39 (± 0.70) for patients who attained a glucose range of 80 to 110 mg/dL without hypoglycemia (P < .001). Glucose variability before an event progressively increased with worsening biochemical hypoglycemia and was least among patients achieving glucose concentrations in the 80 to 110-mg/dL range without hypoglycemia (P < .001).ConclusionsAntecedent glucose change and variability were greater for patients who experienced hypoglycemia. If monitored, these patterns could potentially alert clinicians and help them take preventive measures. Further examination of how these parameters interact with other predisposing risk factors for hypoglycemia is warranted. (Endocr Pract. 2012;18:317-324)     

Overcoming Clinical Inertia in the Management of Postoperative Patients with Diabetes

ObjectiveTo assess the impact of an intervention designed to increase basal-bolus insulin therapy administration in postoperative patients with diabetes mellitus.MethodsEducational sessions and direct support for surgical services were provided by a nurse practitioner (NP). Outcome data from the intervention were compared to data from a historical (control) period. Changes in basalbolus insulin use were assessed according to hyperglycemia severity as defined by the percentage of glucose measurements > 180 mg/dL.ResultsPatient characteristics were comparable for the control and intervention periods (all P ≥ .15). Overall, administration of basal-bolus insulin occurred in 9% (8/93) of control and in 32% (94/293) of intervention cases (P < .01). During the control period, administration of basal-bolus insulin did not increase with more frequent hyperglycemia (P = .22). During the intervention period, administration increased from 8% (8/96) in patients with the fewest number of hyperglycemic measurements to 60% (57/95) in those with the highest frequency of hyperglycemia (P < .01). The mean glucose level was lower during the intervention period compared to the control period (149 mg/dL vs. 163 mg/dL, P < .01). The proportion of glucose values > 180 mg/dL was lower during the intervention period than in the control period (21% vs. 31% of measurements, respectively, P < .01), whereas the hypoglycemia (glucose < 70 mg/dL) frequencies were comparable (P = .21).ConclusionAn intervention to overcome clinical inertia in the management of postoperative patients with diabetes led to greater utilization of basal-bolus insulin therapy and improved glucose control without increasing hypoglycemia. These efforts are ongoing to ensure the delivery of effective inpatient diabetes care by all surgical services. (Endocr Pract. 2014;20:320-328)     

Update on Inpatient Glycemic Control in Hospitals in the United States

ObjectiveTo provide data on glucose control in hospitals in the United States, analyzing measurements from the largest number of facilities to date.MethodsPoint-of-care bedside glucose (POC-BG) test results were extracted from 575 hospitals from January 2009 to December 2009 by using a laboratory information management system. Glycemic control for patients in the intensive care unit (ICU) and non-ICU areas was assessed by calculating patient-day-weighted mean POC-BG values and rates of hypoglycemia and hyperglycemia. The relationship between POC-BG levels and hospital characteristics was determined.ResultsA total of 49,191,313 POC-BG measurements (12,176,299 ICU and 37,015,014 non-ICU values) were obtained from 3,484,795 inpatients (653,359 in the ICU and 2,831,436 in non-ICU areas). The mean POC-BG was 167 mg/dL for ICU patients and 166 mg/dL for nonICU patients. The prevalence of hyperglycemia (> 180 mg/ dL) was 32.2% of patient-days for ICU patients and 32.0% of patient-days for non-ICU patients. The prevalence of hypoglycemia (< 70 mg/dL) was 6.3% of patient-days for ICU patients and 5.7% of patient-days for non-ICU patients. Patient-day-weighted mean POC-BG levels varied on the basis of hospital size (P < .01), type (P < .01), and geographic location (P < .01) for ICU and non-ICU patients, with larger hospitals (≥ 400 beds), academic hospitals, and US hospitals in the West having the lowest mean POC-BG values. The percentage of patient-days in the ICU characterized by hypoglycemia was highest among larger and academic hospitals (P < .05) and least among hospitals in the Northeast (P < .001).ConclusionHyperglycemia is common in hospitals in the United States, and glycemic control may vary on the basis of hospital characteristics. Increased hospital participation in data collection may support a national benchmarking process for the development of optimal practices to manage inpatient hyperglycemia. (Endocr Pract. 2011;17:853-861)     

Examination of Implementation of Intravenous and Subcutaneous Insulin Protocols and Glycemic Control in Heart Transplant Patients

ObjectivePerioperative glycemic management is particularly challenging in heart transplant (HT) patients who are on high-dose steroids and subject to surgical stress. The objective of the study was to examine the efficacy and safety of perioperative insulin administration in HT patients with and without diabetes.MethodsMedical records of 71 HT patients from June 1, 2005 to July 31, 2009 whose hyperglycemia was managed by our Glucose Management Service (GMS) were analyzed for up to 1 year after HT. Their daily blood glucose (BG) averages on intravenous (IV) insulin drips and subcutaneous (SQ) insulin, hypoglycemia rates, reasons for hypoglycemia, and deviations from insulin protocols were analyzed.ResultsDaily BG averages between diabetic (DM) and nondiabetic (nonDM) patients were not significantly different while on the drip but were significantly different for first 5 days on SQ (P < .05). The daily insulin glargine doses were similar. No patients developed severe hypoglycemia (BG ≤ 40 mg/dL) while on drip, and only 2.8% experienced hypoglycemia on SQ. Among 40 episodes of moderate hypoglycemia while on drip, 15 had nurse deviations from protocol prior to the episode. Posttransition day fasting glucose was at goal (mean 124.7 ± 35.4 mg/dL); however 39.4% (28/71) of patients received a transition insulin glargine dose that was different from the amount indicated by protocol. The likelihood of developing moderate hypoglycemia on SQ was associated with the glargine dose used at the time of transition (odds ratio [OR] 1.03, P = .034).ConclusionInpatient insulin protocols implemented by a GMS are successful in obtaining glycemic control with minimal side effects in patients with and without diabetes, even when they are on a high-dose steroid regimen. (Endocr Pract. 2014;20:527-535)     

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)     

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)     

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)     

Benchmarking Glycemic Control In U.S. Hospitals

ObjectiveReport data on glucose control from 635 U.S. hospitals.MethodsPoint-of-care blood glucose (POC-BG) test data from January through December 2012 from 635 facilities were extracted. Glucose control was evaluated using patient-day–weighted mean POC-BG values. We calculated hypoglycemia and hyperglycemia rates, stratified by presence or absence of intensive care unit (ICU) admission, and we evaluated the relationship between glycemic control and hospital characteristics.ResultsIn total, 51,375,764 POC-BG measurements (non-ICU, 39,197,762; ICU, 12,178,002) from 2,612,966 patients (non-ICU, 2,415,209; ICU, 575,084) were analyzed. The mean POC-BG was 167 mg/dL for non-ICU patients and 170 mg/dL for ICU patients. The prevalence of hyperglycemia (defined as glucose value > 180 mg/dL) was 32.3 and 28.2% in non-ICU and ICU patients, respectively. The prevalence of hypoglycemia (defined as glucose value < 70 mg/dL) was 6.1 and 5.6% in non-ICU and ICU patients, respectively. In non-ICU and ICU settings, the patient-day–weighted mean glucose was highest in the smallest hospitals, in rural hospitals, and in hospitals located in the Northeast (all P < .01). For non-ICU patients, we observed a significant difference in the percentage of patient days with hypoglycemia by geographic region only (P < .001). In ICU patients, the prevalence of hypoglycemia varied significantly by hospital type (P < .03) and geographic region (P < .01).ConclusionIn this largest POC-BG data set analysis conducted to date, glycemic control varied according to hospital characteristics. Our findings remain consistent with previous reports. Among other variables, national benchmarking of inpatient glucose data will need to consider differences in hospital characteristics. (Endocr Pract. 2014;20:876-883)     

Economic and Clinical Impact of Inpatient Diabetic Hypoglycemia

ObjectiveTo assess the clinical and economic impact of hypoglycemia that develops during hospitalization of patients with diabetes.MethodsIn this retrospective cohort study, data from 70 hospitals were used to identify the first inpatient encounter for adult patients with diabetes. Patients were included if all blood glucose measurements were 70 mg/dL or higher during the first 24 hours and their primary discharge diagnosis was for a condition other than hypoglycemia. Those who developed laboratory evidence of hypoglycemia (blood glucose < 70 mg/dL after 24 hours) were compared with patients whose blood glucose values were all 70 mg/dL or higher. An alternative definition of hypoglycemia (blood glucose < 50 mg/dL after 24 hours) was also evaluated. We adjusted for potential confounders with multivariate models.ResultsHypoglycemia had an adverse effect on all outcomes among more than 100 000 diabetic patients. After adjustment, patients with diabetes who developed hypoglycemia had higher charges (38.9%), longer lengths of stay (3.0 days), higher mortality (odds ratio, 1.07; 95% confidence interval, 1.02-1.11), and higher odds of being discharged to a skilled nursing facility (odds ratio, 1.58; 95% confidence interval, 1.48-1.69) than diabetic patients without hypoglycemia (P < .01 for all). In all cases, using the lower threshold (< 50 mg/dL) to define hypoglycemia resulted in similar findings with a larger magnitude of differences.ConclusionsAlthough a direct causal relationship cannot be inferred, these study findings suggest the importance of carefully maintaining euglycemia during hospitalizations. Whether the observed worse outcomes were due to hypoglycemia itself or whether they were a marker of worse outcomes due to other causes requires further research. (Endocr Pract. 2009;15:302-312)     

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)     

Improved Glycemic Control with Insulin Glargine Versus Pioglitazone as Add-On Therapy to Sulfonylurea or Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus

ObjectiveTo compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes.MethodsThis 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite ≥ 3 months of sulfonylurea or metformin monotherapy, to receive add-on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels ≤ 7.0%, and changes from baseline in fasting plasma glucose, body mass index, weight, and serum lipids. The safety analysis included incidence of adverse events and rates of hypoglycemia.ResultsAt end point, insulin glargine yielded a significantly greater reduction in A1C in comparison with pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/ dL; 95% confidence interval, -47.6 to -22.2; P < .0001). In comparison with pioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatmentemergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose < 70 mg/dL and all severe hypoglycemia) (4.97 versus 1.04; P <.0001) and severe hypoglycemia (0.07 versus 0.01; P = .0309). Weight and body mass index changes were similar between the 2 treatment groups.ConclusionThe addition of insulin glargine early in the diabetes treatment paradigm in patients for whom sulfonylurea or metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in < 5% of patients in the insulin glargine treatment group. (Endocr Pract. 2010;16:588-599)     

Menstrual Disorders and Androgen-Related Traits in Young Women with Type 1 Diabetes Mellitus: a Clinical Study

Objective: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM).Methods: Fifty-three women with T1DM (duration 8.0 ± 5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4 ± 4.3 years vs. 21.2 ± 2.7 years vs. 20.8 ± 3.1 years; P>.05) and body mass index (BMI) (22.2 ± 2.7 kg/m² vs. 21.9 ± 2.0 kg/m² vs. 21.4 ± 1.9 kg/m²; P>.05) were prospectively recruited.Results: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 23.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7 ± 1.3 vs. 12.0 ± 1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4 ± 1.2 years). There were no differences in total testosterone (0.43 ± 0.14 ng/mL vs. 0.39 ± 0.14 ng/mL; P>.05), dehydroepiandrosterone sulfate (DHEA-S) (269 ± 112 μg/dL vs. 238 ± 106 μg/dL; P>.05) or Δ4-androstenedione (2.4 ± 1.3 ng/mL vs. 1.9 ± 0.5 ng/mL; P>.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 ± 17 nmol/L vs. 83 ± 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5 ± 12.9 nmol/L; P = .001 compared with T1DM). The free androgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53 ± 0.54 vs. 7.88 ± 1.21 vs. 1.6 ± 0.68; P<.001). FAI was higher in patients with T1DM compared to controls as well (P = .038). There was no difference in DHEA-S concentrations between T1DM and PCOS patients (269 ± 112 μg/dL vs. 297 ± 100 μg/dL; P>.05).Conclusion: Menstrual disorders and androgen-related traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations.     

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)