Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma

AimEvaluate pretreatment hemoglobin values as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy.BackgroundAnemia is one of the most prevalent laboratory abnormalities in oncological disease. It leads to a decrease in cellular oxygen supply, altering radiosensitivity of tumor cells and compromising therapeutic outcomes.Materials and MethodsRetrospective evaluation of patients with HNSCC treated with cCRT. Primary and secondary endpoint was to evaluate the correlation of Hb levels (≥12.5 g/dL or <12.5 g/dL) at the beginning of cCRT with overall survival (OS) and progression-free survival (PFS), respectively.ResultsA total of 108 patients were identified. With a median follow-up of 16.10 months median OS was 59.70 months for Hb ≥12.5 g/dL vs. 14.13 months for Hb <12.5 g/dL (p = 0.004). PFS was 12.29 months for Hb ≥12.5 g/dL and 1.68 months for Hb <12.5 g/dL (p = 0.016).ConclusionsIn this analysis, Hb ≥12.5 g/dL correlated with significantly better OS and PFS. Further studies are needed to validate these findings.     

Prevalence of Anemia Among Unselected Adults with Diabetes Mellitus and Normal Serum Creatinine Levels

ObjectiveTo determine the prevalence of anemia in a cohort of patients with diabetes and normal serum creatinine concentration in a primary care clinic.MethodsWe undertook a retrospective cohort study, comparing adult patients who had diabetes, with or without anemia. Patients older than 18 years who had diabetes were identified by using the computerized database for the years 2006 and 2007 in a primary care clinic. Patients with hemoglobin levels < 13.7 g/dL (men < 60 years old), ≤ 13.2 g/dL (men ≥ 60 years old), or < 12.2 g/dL (women) with no known cause of anemia were identified and compared with patients who had diabetes but not anemia. All patients had normal serum creatinine levels (men ≤ 1.5 mg/dL and women ≥ 1.4 mg/dL).ResultsOf 594 eligible patients with diabetes, 192 (32%) had anemia. Older age, higher serum urea and creatinine levels, lower estimated glomerular filtration rates, and reduced serum iron levels were more common in the patients with diabetes who had anemia than in those without anemia. The prevalence of anemia was higher in patients treated with “glitazones,” insulin, and angiotensin receptor blockers in comparison with those receiving other orally administered hypoglycemic medications. In stepwise logistic regression analysis, only serum creatinine, age, and use of glitazones retained statistical significance.ConclusionIn a community clinic, the prevalence of anemia in unselected patients with diabetes and normal serum creatinine levels was 32%. Factors associated with anemia were older age, higher serum creatinine levels, and use of glitazone therapy. (Endocr Pract. 2009;15:714-719)     

Evaluation of Admission Blood Glucose Levels in The Intensive Care Unit

ObjectiveTo assess the availability and clinical value of blood glucose (BG) testing at the time of admission to the intensive care unit (ICU) after such testing was implemented as routine care in the ICU.MethodsWe studied ICU admission BG testing rates and the prevalence of hyperglycemia. In this effort, we assessed the frequency of baseline BG testing in 330 consecutive patients during a period of 3 months and then implemented routine BG monitoring in 1,147 consecutive ICU patients during a 7-month period.ResultsOf the total study population, 25% had previously diagnosed diabetes (PDD). At baseline, 70% had BG measured within 4 hours before or after ICU admission (99% of patients with and 60% of patients without PDD). After implementation of routine BG monitoring, there was a significant increase in testing (70% before versus 87% after, /40.001; 70% during the baseline 3-month period versus 93% in the final 3 months of the study, P < 0.001). In patients without PDD, 41% had BG levels ≥ 140 mg/dL, and 8% had BG concentrations ≥ 200 mg/dL. Overall in the ICU setting, 57% of BG values ≥ 140 mg/dL and 33% of BG levels > 200 mg/dL were in patients without PDD. Frequencies of BG testing by admission diagnosis included the following (at baseline and during the final 3 months after implementation of routine BG tests): post-surgical status (46%, 85%), peripheral vascular disease (51%, 90%), neurologic disease (52%, 83%), gastrointestinal disease (58%, 91%), infection (69%, 100%), and diabetes (100%, 100%).ConclusionRates of routine BG testing are low in ICU patients without PDD. Elevations in BG levels were detected in 41% of our study patients without PDD, suggesting that routine implementation of BG monitoring in an ICU will identify patients at increased risk for hyperglycemia-associated higher morbidity and mortality. (Endocr Pract. 2007;13:705-710)     

Phase II study of two dose schedules of C.E.R.A. (Continuous Erythropoietin Receptor Activator) in anemic patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy

Background

C.E.R.A. (Continuous Erythropoietin Receptor Activator) is an innovative agent with unique erythropoietin receptor activity and prolonged half-life. This study evaluated C.E.R.A. once weekly (QW) or once every 3 weeks (Q3W) in patients with anemia and advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.

Methods

In this Phase II, randomized, open-label, multicenter, dose-finding study, patients (n = 218) with Stage IIIB or IV NSCLC and hemoglobin (Hb) ≤ 11 g/dL were randomized to one of six treatment groups of C.E.R.A. administered subcutaneously for 12 weeks: 0.7, 1.4, or 2.1 μg/kg QW or 2.1, 4.2, or 6.3 μg/kg Q3W. Primary endpoint was average Hb level between baseline and end of initial treatment (defined as last Hb measurement before dose reduction or transfusion, or the value at week 13). Hematopoietic response (Hb increase ≥ 2 g/dL or achievement of Hb ≥ 12 g/dL with no blood transfusion in the previous 28 days determined in two consecutive measurements within a 10-day interval) was also measured.

Results

Dose-dependent Hb increases were observed, although the magnitude of increase was moderate. Hematopoietic response rate was also dose dependent, achieved by 51% and 62% of patients in the 4.2 and 6.3 μg/kg Q3W groups, and 63% of the 2.1 μg/kg QW group. In the Q3W group, the proportion of early responders (defined as ≥ 1 g/dL increase in Hb from baseline during the first 22 days) increased with increasing C.E.R.A. dose, reaching 41% with the highest dose. In the 6.3 μg/kg Q3W group, 15% of patients received blood transfusion. There was an inclination for higher mean Hb increases and lower transfusion use in the Q3W groups than in the QW groups. C.E.R.A. was generally well tolerated.

Conclusion

C.E.R.A. administered QW or Q3W showed clinical activity and safety in patients with NSCLC. There were dose-dependent increases in Hb responses. C.E.R.A. appeared to be more effective when the same dose over time was given Q3W than QW, with a suggestion that C.E.R.A. 6.3 μg/kg Q3W provided best efficacy in this study. However, further dose-finding studies using higher doses are required to determine the optimal C.E.R.A. dose regimen in cancer patients receiving chemotherapy.     

Association Between Blood Glucose Levels and Development of Candidemia in Hospitalized Patients

ObjectiveTo examine the relationship between blood glucose levels in hospitalized patients and the risk of occurrence of candidemia.MethodsWe undertook a retrospective review of medical records and hospital computerized database information to compare blood glucose levels in 48 patients with nosocomial candidemia and 144 contemporaneous matched control subjects without candidemia at a tertiary teaching hospital.ResultsThe proportions of days (for patients with candidemia versus control subjects without candidemia) with blood glucose levels ≥ 100 mg/dL (293 of 325 [90%] versus 849 of 1,007 [84%]; P = .009), ≥ 140 mg/dL (184 of 325 [57%] versus 507 of 1,007 [50%]; P = .049), and ≥ 200 mg/dL (80 of 325 [25%] versus 163 of 1,007 [16%]; P = .001) were significantly higher during the 7 days preceding the diagnosis of candidemia than during a 7-day period of hospitalization of control subjects. Blood glucose levels exceeding 200 mg/dL for 4 or more days of the week preceding the diagnosis of candidemia were significantly associated with its development (P = .04; odds ratio, 2.44; and 95% confidence interval, 1.01 to 5.94).ConclusionInpatient hyperglycemia is an important—and potentially modifiable—risk factor for development of nosocomial candidemia. These findings have implications for innovative infection control strategies that focus on glycemic control. (Endocr Pract. 2009;15:111- 115)     

Influence Of Diabetes And Hyperglycemia On Duration Of Stay In Patients Hospitalized With Congestive Heart Failure

ObjectiveTo analyze the influence of diabetes and hyperglycemia on duration of stay in patients hospitalized with congestive heart failure (CHF).MethodsWe conducted a retrospective review of data for patients admitted during a 6-month period with CHF to a community teaching hospital in Baltimore, Maryland. Patients were divided into diabetic and nondiabetic groups, and patients with diabetes were stratified by mean fasting plasma glucose levels into the following groups: < 110 mg/dL, 110 to 180 mg/dL, and > 180 mg/dL. The primary outcome was duration of hospitalization. Other variables included sex, age, ejection fraction, admission glucose, brain natriuretic peptide, creatinine, and other comorbidities.ResultsThe study cohort consisted of 142 patients, 49% of whom had diabetes. The duration of hospitalization was 3.23 days in the patients with diabetes versus 3.11 days in those without diabetes (P = .875). Patients with diabetes were significantly younger (71.8 versus 76.6 years; P = .027) and had a higher baseline mean creatinine level (1.4 versus 1.2 mg/dL; P = .010). Patients with diabetes in the 110 to 180 mg/dL blood glucose group had shorter hospitalizations than did those in the < 110 mg/dL group (2.94 versus 3.41 days; P = .259). Only 9 patients had blood glucose levels > 180 mg/dL, and these patients had the longest hospitalizations (mean duration, 3.78 days).ConclusionThe prevalence of diabetes was higher in our study than in previously published studies of patients with CHF. Although patients with diabetes did not have significantly longer hospitalizations than those without diabetes, they were significantly younger and had higher baseline creatinine values. Hyperglycemia was an infrequent phenomenon among patients without diabetes. The patients with diabetes in the 110 to 180 mg/dL blood glucose group had shorter hospitalizations than did those in the < 110 mg/dL group, although this difference did not reach statistical significance. Many of the initial studies of tight glucose control were conducted in the surgical intensive care unit, but recently published evidence has raised doubt about applying these results to medical patients. We conclude that there may be no significant benefit in terms of duration of hospitalization in assigning patients with diabetes who have CHF exacerbations to tight glucose control regimens. A more liberal approach of maintaining glucose levels at 110 to 180 mg/dL may be acceptable. (Endocr Pract. 2008;14:691-696)     

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)     

Association of Lower Serum Cholesterol Levels with Higher Risk of Osteoporosis in Type 2 Diabetes

ObjectiveTo determine whether a correlation exists between bone mineral density and circulating lipoprotein levels and whether these variables are independently associated with osteoporosis in patients with type 2 diabetes.MethodsIn a cross-sectional analysis, 159 patients with type 2 diabetes were compared with 70 patients without diabetes selected from an outpatient endocrinology clinic in a tertiary care institute during a 1-year period. Variables were gathered through history, physical examination, and laboratory findings, including blood chemistry studies and dual-energy x-ray absorptiometry.ResultsOf the 229 study patients, 86 (37.6%) had osteoporosis. In the patients with diabetes, the mean ± SD of age, weight, total cholesterol, and low-density lipoprotein (LDL) cholesterol in those with and without osteoporosis was 72.3 ± 10.4 years versus 63.6 ± 11.0 years, 74.2 ± 14.4 kg versus 83.7 ± 15.5 kg, 178.4 ± 33.7 mg/dL versus 194.1 ± 33.9 mg/dL, and 100.0 ± 27.1 mg/dL versus 114.2 ± 30.2 mg/dL, respectively (P < 0.01 for all variables). After adjustment for other variables, multiple logistic regression analysis showed that the presence of diabetes was associated with a lower risk of osteoporosis. Similarly, older age and lower body weight, LDL levels, and serum calcium levels were independently associated with lumbar spine osteoporosis in patients with diabetes, in comparison with older age and lower weight in patients without diabetes. Lower weight and older age were associated with femoral neck and total hip osteoporosis in patients with diabetes, in comparison with only older age in patients without diabetes.ConclusionThe presence of type 2 diabetes is associated with a lower risk of osteoporosis. In patients with type 2 diabetes, a lower LDL level is more likely to be associated with osteoporosis at the lumbar spine. (Endocr Pract. 2007;13:620-628)     

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)     

Safe and Simple Emergency Department Discharge Therapy for Patients with Type 2 Diabetes Mellitus and Severe Hyperglycemia

ObjectiveTo investigate the safety and effectiveness of 2 simple discharge regimens for use in patients with type 2 diabetes mellitus (DM2) and severe hyperglycemia, who present to the emergency department (ED) and do not need to be admitted.MethodsWe conducted an 8-week, open-label, randomized controlled trial in 77 adult patients with DM2 and blood glucose levels of 300 to 700 mg/dL seen in a public hospital ED. Patients were randomly assigned to receive glipizide XL, 10 mg orally daily (G group), versus glipizide XL, 10 mg orally daily, plus insulin glargine, 10 U daily (G + G group). The primary outcome was to maintain safe fasting glucose and random glucose levels of < 350 and < 500 mg/dL up to 4 weeks and < 300 and < 400 mg/ dL, respectively, thereafter and to have no return ED visits (responders).ResultsBaseline characteristics were similar between the 2 treatment groups. The primary outcome was achieved in 87% of patients in both treatment groups. The enrollment mean blood glucose values of 440 and 467 mg/dL in the G and G + G groups, respectively, declined by the end of week 1 to 298 and 289 mg/dL and by week 8 to 140 and 135 mg/dL, respectively. Homeostasis model assessment of b-cell function and early insulin response improved 7-fold and 4-fold, respectively, in responders at the end of the 8-week study.ConclusionSulfonylurea with and without use of a small dose of insulin glargine rapidly improved blood glucose levels and b-cell function in patients with DM2. Use of sulfonylurea alone once daily can be considered a safe discharge regimen for such patients and an effective bridge between ED intervention and subsequent follow-up. (Endocr Pract. 2009;15:696-704)     

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)     

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

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

A cross-sectional survey among patients and prescribers on insulin dosing irregularities and impact of mild (self-treated) hypoglycemia episodes in Spanish patients with type 2 diabetes as compared to other European patients

Background and objectiveIn Spain, data suggest that 13.8% of adults have diabetes. Two important aspects in diabetes management are mild hypoglycemic episodes and poor treatment adherence. This study assesses the impact of missed insulin doses and prevalence of mistimed and reduced insulin doses and mild hypoglycemia in patients with type 2 diabetes treated with basal insulin analogues in Spain, and compares the data collected to pooled data from 8 other European countries (OECs).Materials and methodsGAPP2 was an international, online, cross-sectional study of diabetic patients aged ≥40 years treated with long-acting insulin analogues and their healthcare professionals. Patients and healthcare professionals were recruited from online research panels. Data reported in Spain are compared to pooled data from 8 OECs.ResultsIn Spain, 1–3% of patients reported they had reduced, missed, or mistimed at least one insulin does in the previous month. Significantly more OEC patients reported dosing irregularities (15–23%; all P < 0.01). In Spain, 77% of patients were worried and 59% felt guilty for missing a dose of basal insulin, while 24% reported that they were very worried about nocturnal hypoglycemia. Significantly fewer OEC patients reported worrying (47%; P < 0.01) and feeling guilty (37%; P < 0.01) about missing an insulin dose, or worry about nocturnal hypoglycemia (12%; P < 0.01).ConclusionsIn Spain, patients with type 2 diabetes report fewer dosing irregularities and hypoglycemic episodes as compared to patients from OECs. However, Spanish patients appear to have a reduced quality of life related to hypoglycemia as well as worry and guilt related to insulin dosing irregularities.     

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)     

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)     

Hemoglobin A1C,Mean Glucose,and Persistence of Glycation Ratios in Insulin-Treated Diabetes

ObjectiveDetermine the relationship between mean glucose (MG), as assessed by continuous glucose monitoring (CGM), and hemoglobin A_1c (A1C) in insulin-requiring adults in a clinical practice setting and examine the persistence of this relationship over time.MethodsIn this retrospective record review in a diabetes practice, a linear regression model was developed using data sets from all patients with ≥ 1 available download of a Dexcom SevenPlus CGM device in which there was > 50% utilization in the 60 days prior to a laboratory A1C. Persistence of the MG to A1C relationship was examined in patients with ≥ 2 data sets available.ResultsA total of 139 patients had ≥ 1 data set available for evaluation, and 101 patients had ≥ 2 data sets (range, 2 to 6; total, 279). The slope of the MG versus A1C curve was 19.5 mg/dL for each 1% change in A1C, with an intercept of 17.7 mg/dL. Although 88% of the measured MG values were within 15% of the A1C-predicted MG, there was substantial variation in individuals, with differences as large as ± 26%. The MG to A1C (MG:A1C) ratio, which is a measure of glycation, was normally distributed, with a median of 21.6. Spearman correlation coefficients for the MG:A1C ratio on repeated measures ranged from 0.52 to 0.73, demonstrating persistence.ConclusionThe relationship between MG and A1C is linear in a population but can vary between individuals. The MG:A1C ratio was normally distributed, tended to persist in individuals over time, and thus could be useful to identify apparent high and low glycators. Glycemic goals may need to be modified in such patients. (Endocr Pract. 2014;20:252-260)     

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)     

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 Prediabetes Using Fasting Insulin Levels

ObjectiveTo determine whether patients with prediabetes can be accurately and easily identified in clinical settings using a predictive clinical and laboratory model.MethodsThis retrospective study examined demographic and laboratory data from patients who had undergone 2-hour glucose testing for suspected prediabetes or diabetes between 2000 and 2004. Patients who met the diagnostic criteria for diabetes mellitus were excluded. Prediabetes was defined as a fasting glucose concentration ≥ 100 mg/dL and ≤ 125 mg/dL or a 2-hour postprandial glucose concentration ≥ 140 mg/dL and < 200 mg/dL. Multivariate logistic regression was conducted to identify calculated or measured clinical and laboratory attributes that predict the presence of prediabetes, including fasting insulin quartiles, homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index.ResultsOf 965 patients, 287 (29.7%) had prediabetes. The study population primarily consisted of white, obese, female patients. A multivariate model revealed that compared with the referent lowest quartile of fasting insulin (m = 4.9 [± SD] ± 1.2 mIU/mL), subsequent insulin quartiles increased the likelihood of identifying prediabetes (quartile 2: m = 8.0 ± 0.8 mIU/mL, odds ratio [OR] = 2.076, confidence interval [CI] = 1.241-3.273; quartile 3: m = 12.2 ± 1.7 mIU/mL, OR = 3.151, CI = 1.981-5.015; quartile 4: m = 25.9 ± 12.4 mIU/mL, OR = 5.035, CI = 3.122-8.122). Older age and increased diastolic blood pressure also contributed modestly to this model. Further analysis using the area under the curve revealed that at a fasting insulin level > 9.0 mIU/mL, prediabetes would be correctly identified in 80% of affected patients. A second model revealed that increased HOMA-IR index (OR = 1.303, CI = 1.205-1.410) and older age (OR = 1.037, CI = 1.024-1.05) predicted prediabetes.ConclusionsThe most robust model, which used fasting insulin levels, may provide the most utility as a clinical tool because the highest quartiles suggest significantly greater likelihood of identifying prediabetes. (Endocr Pract. 2010;16:47-52)     

A Prospective Trial of U500 Insulin Delivered by Omnipod in Patients With Type 2 Diabetes Mellitus and Severe Insulin Resistance

ObjectiveTo test the effectiveness and safety of U500 regular insulin delivered by continuous subcutaneous insulin infusion (CSII) via the Omnipod insulin delivery system in patients with uncontrolled type 2 diabetes mellitus and severe insulin resistance.MethodsIn this prospective, 1-year, proof-of-concept trial, patients with insulin-requiring type 2 diabetes who had a hemoglobin A1c level of 7.0% or higher and severe insulin resistance (average insulin requirement, 1.74 units of insulin per kilogram each day; range, 1.4 to 2.64 units of insulin per kilogram [average insulin dose, 196.4 units daily]) were identified at routine office visits at Mountain Diabetes and Endocrine Center in Asheville, North Carolina, between December 2007 and August 2008. All patients had been on intensive insulin therapy with or without oral agents for more than 3 months. All patients were switched from baseline failed therapy to U500 regular insulin by continuous subcutaneous insulin infusion via Omnipod. Effectiveness was assessed by hemoglobin A1c measurement and 72-hour continuous glucose monitoring at baseline and at weeks 13, 26, and, 52 and by treatment satisfaction assessed by the Insulin Delivery Rating System Questionnaire at baseline and at week 52 while on U500 via Omnipod.ResultsTwenty-one adults were enrolled (mean age, 54 years; mean duration of diabetes, 4 years; mean body mass index, 39.4 kg/m2; mean insulin requirement, 1.7 U/ kg per day; and mean hemoglobin A1c, 8.6%) whose previous treatment with U100 insulin regimens had failed. Twenty patients completed the study. Treatment with U500 insulin via Omnipod significantly reduced hemoglobin A1c by 1.23% (P < .001) and significantly increased the percentage of time spent in the blood glucose target range (70- 180 mg/dL) by 70.75% as assessed by continuous glucose monitoring (P < .001) without a significant increase in hypoglycemia. Patients were satisfied with treatment with U500 insulin via Omnipod, and 14 patients elected to remain on treatment at study completion.ConclusionsU500 insulin delivered subcutaneously continuously via Omnipod is a safe and effective method of insulin delivery in the very insulin-resistant type 2 diabetic population. (Endocr Pract. 2010;16:778-784)