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)     

Hemoglobin Maintenance with use of Extended Dosing of Epoetin Alfa in Patients with Diabetes and Anemia of Chronic Kidney Disease

ObjectiveTo compare the efficacy of extended epo-etin alfa dosing in maintaining hemoglobin (Hb) concentrations in patients with and without diabetes as the primary cause of chronic kidney disease.MethodsWe undertook a post hoc analysis of the Clinical Evaluation of PROCRIT® for Maintenance Phase Treatment of Patients With Anemia Due to Chronic Kidney Disease (PROMPT) study. The study patients had chronic kidney disease but were not receiving dialysis, had stable Hb levels of ≥ 11.0 g/dL, and had been receiving epoetin alfa for ≥ 2 months. Patients received 1 of 4 epoetin alfa dosing regimens administered subcutaneously for up to 16 weeks: 10,000 U once weekly (QW), 20,000 U every 2 weeks (Q2W), 30,000 U every 3 weeks (Q3W), or 40,000 U every 4 weeks (Q4W). The primary end point was the percentage of patients able to achieve Hb maintenance, defined as a mean Hb level of ≥ 11.0 g/dL from week 2 to final measurement.ResultsAmong 445 evaluable patients, 201 had diabetes and 244 did not have diabetes. Mean baseline Hb was 11.9 g/dL in both groups. The percentage of patients achieving Hb maintenance, stratified by epoetin alfa dosing regimen, was similar in patients with and those without diabetes: QW (90.2% versus 96.5%), Q2W (91.1% versus 87.9%), Q3W (80.0% versus 75.7%), or Q4W (79.2% versus 72.5%). The incidence of adverse events was low and comparable between patients with and those without diabetes.ConclusionApproximately 90% of patients with and without diabetes in the QW and Q2W groups and more than 70% in the Q3W and Q4W groups maintained mean Hb levels of ≥ 11.0 g/dL from week 2 to final measurement. These results demonstrated that patients with diabetes responded in a similar manner as patients without diabetes to extended dosing of epoetin alfa up to Q4W. (Endocr Pract. 2007;13:251-259)     

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)     

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)     

Trace elements in bipolar disorder

IntroductionTrace elements may play an important role in bipolar disorders. The objective of this study is to determine serum copper and zinc, blood lead and cadmium and urine lead, cadmium and thallium concentrations in patients diagnosed with bipolar disorders and to compare these levels with those of a healthy control group.Materials and methodsA total of 25 patients diagnosed with bipolar disorder and 29 healthy subjects participated in this study. Serum copper and zinc concentrations were measured using flame atomic absorption spectrometry; the blood lead and cadmium concentrations were measured by electrothermal atomization atomic absorption spectrometry with Zeeman background correction; urine lead, cadmium and thallium concentrations were measured by inductively coupled plasma mass spectrometry.ResultsMedian blood and urine lead and cadmium levels were significantly higher among the bipolar patients than among the control group: Blood lead (μg/dL): patient median: 3.00 (IQR: 1.40–4.20); control median (μg/dL): 2.20 (IQR: 0.90–3.00) p = 0.040. Blood cadmium (μg/L): patient median: 0.39 (IQR: 0.10–1.15); control median: 0.10 (IQR: 0.10–0.17) p < 0.001. The median of cadmium (μg/L) in patients who smoked (1.20 IQR: 0.44–2.30) was higher than that in non-smokers (0.12 IQR: 0.10–0.34) p < 0.001. There was a statistically significant increase (p = 0.001) in zinc levels among patients in the manic phase (mean 111.28, SD: 33.36 μg/dL) with respect to the control group (mean 86.07, SD: 12.39 μg/dL).ConclusionsThe results suggest that there could be higher levels of some toxic trace elements in the group of patients with bipolar disorder than in the healthy control group.     

Role of serum concentration of VEGFR1 and TIMP2 on clinical outcome in primary cervical cancer: Results of a companion protocol of the randomized,NOGGO–AGO phase III adjuvant trial of simultaneous cisplatin-based radiochemotherapy vs. carboplatin and paclitaxel containing sequential radiotherapy

ObjectiveAim of the present study was to analyze the expression-profile of IGF1, IGFBP3, sICAM1, sVCAM1, MMP2, MMP9, TIMP2, VEGFA, VEGFD, VEGFC and VEGFR1 in patients with high-risk FIGO-stage Ib-IIb cervical cancer.MethodsSerum from 68 cervical cancer patients treated within a phase-III-trial with either simultaneous cisplatin radiochemotherapy or sequential systemic carboplatin and paclitaxel followed by percutaneous irradiation was analyzed by ELISA. Both target expression and correlation with important clinicopathological factors were analyzed following standard statistic procedures.ResultsAll 68 patients underwent a primary radical hysterectomy with pelvic and/or paraaortic lymphadenectomy. 85.3% of the extirpated tumors had clear surgical margins (R0). Increased levels of VEGFR1, TIMP2 and MMP2 were significantly associated with positive surgical margins (p = 0.004, p = 0.018 and p = 0.004, respectively). High concentration of MMP2 and TIMP2 correlated additionally with an advanced age at time of diagnosis (p = 0.001 and p = 0.007, respectively). For the cut-off value of 100 pg/ml, an increased VEGFR1 was significantly associated with poor overall (OS) and progression-free (PFS) survival (p = 0.017 and p = 0.015, respectively). A TIMP2 concentration of lower than 90 ng/ml was significantly associated with poorer OS and PFS (p = 0.009 and p = 0.043, respectively). In the multivariate analysis, TIMP2 expression in serum was the only independent prognostic factor for OS (p = 0.032, HR = 6.51, 95% CI = 1.17–36.01).ConclusionsExpression-profile of specific biomarkers associated with tumor invasion, cell migration and angiogenesis seems to be of prognostic value for both OS and PFS in patients undergoing surgery due to primary cervical cancer. Further analyses are warranted to allow an implementation of such markers into clinical practice.     

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

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

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)     

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)     

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)     

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)     

Obstructive Sleep Apnea Predisposes to Nonalcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome

ObjectiveSome studies have shown a higher prevalence of nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) in patients with polycystic ovary syndrome (PCOS). The objective of this study was to assess NAFLD in PCOS women with and without OSA. A possible role of high serum androgen levels in the development of OSA in PCOS women was also investigated.MethodsBiochemical, hormonal, and polysomnography parameters were determined in 38 premenopausal PCOS patients. NAFLD was evaluated by ultrasound. Testosterone was measured by an immunoassay.ResultsSerum androgen levels and the prevalence of NAFLD (83.3% vs. 26.9%; P < .001) were higher in patients with OSA than those without OSA. The mean apnea-hypopnea index (AHI) was higher in patients with NAFLD than in those without NAFLD (16.87 events [ev]/h vs. 1.57 ev/h; P < .002). On multivariate logistic regression, where body mass index ≥ 30 kg/m², homeostasis model assessment for insulin resistance ≥ 2.7, and OSA (AHI ≥ 5 ev/h) were independent variables, only OSA was an independent predictor of NAFLD (odds ratio [OR], 7.63; P = .044). Free testosterone levels ≥ 1.07 ng/dL were also independently associated with OSA (OR, 8.18; P = .023).ConclusionIn PCOS women, the occurrence of OSA strongly predisposes them to development of NAFLD and a worse metabolic profile; hence, treatment of OSA might be beneficial for NAFLD. (Endocr Pract. 2014;20:244-251)     

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)     

Improvement in Pancreatic β-Cell Function with Vitamin D and Calcium Supplementation in Vitamin D-Deficient Nondiabetic Subjects

ObjectiveThere are varied reports on the effect of vitamin D supplementation on β-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on β-cell function and plasma glucose levels in subjects with vitamin D deficiency.MethodsNondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented.ResultsThirty-seven patients with 25-OHD deficiency participated in the study. The baseline and postvitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (− 0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (− 20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (− 4.88 ± 10.65 mg/dL); and homeostasis model assessment-2–percent β-cell function C-peptide secretion (HOMA-2–%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, − 3.751; P < .0001), 25-OHD (Z, − 4.9; P < .0001), intact PTH (Z, − 4.04; P < .0001), fasting plasma glucose (Z, − 2.7; P < .007), and HOMA-2–%B C-PEP (Z, − 1.923; P < .05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged.ConclusionOptimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and β-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis. (Endocr Pract. 2014;20:129-138)     

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)     

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)     

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)     

Early adulthood body mass index,cumulative smoking,and esophageal adenocarcinoma survival

BackgroundSmoking and obesity are esophageal adenocarcinoma (EAC) risk factors. However, the same risk factors may also affect biological aggressiveness and cancer outcomes. Our study evaluated the combined effects of early-adulthood obesity and cumulative smoking on the EAC survival.Patients and methodsIn two EAC cohorts, Toronto (TO; N = 235) and Boston (BO; N = 329), associations between early adulthood body mass index (EA-BMI), BMI at 1 year prior to diagnosis (BMI-1), and smoking with overall survival (OS) were assessed using Cox proportional hazard models, adjusted for relevant covariates.ResultsBoth cohorts were predominantly Caucasian (89%), male (88%), ever-smokers (73%) with locally advanced/metastatic EAC (78%), and good ECOG performance status (90%); median packyears was 34; median EA-BMI, 24; median BMI-1, 25. No relationships with survival were found with BMI-1. For smoking and EA-BMI, TO, BO, and combined TO-BO analyses showed similar associations: smoking conferred worse OS in the combined TO-BO cohort, with adjusted hazard ratios (aHR) of 1.22 (95%CI: 1.15–1.43;p < 0.0001) for each 20 pack-year increase. Likewise, EA-BMI ≥25 was associated with worse OS (EA-BMI of 25− < 30, aHR = 1.84,95%CI: 1.37–2.48; and EA-BMI > 30, aHR = 2.78, 95%CI: 1.94–3.99). Risk of death was also increased in remotely underweight patients with EA-BMI < 18.5 (aHR = 2.03,95%CI: 1.27–3.24), when compared to normal-EA-BMI (18 ≤ EA-BMI < 25).ConclusionsTwo key modifiable behaviors, elevated BMI in early adulthood and heavy cumulative smoking history are independently associated with increased mortality risk in two North American cohorts of EAC patients.     

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)     

Elevated Fructosamine Levelsin Acquired Immunodeficiency Syndrome

ObjectiveTo investigate whether the mechanism of increased glycation in acquired immunodeficiency syndrome (AIDS) is due to an alteration in a circulatory plasma enhancer.MethodsWe assessed glycation of serum protein and hemoglobin in patients with AIDS without altered carbohydrate metabolism. Fasting concentrations of glucose, ethanol, vitamin E, fructosamine, hemoglobin, hemoglobin A1c (A1C), and partial pressure of alveolar oxygen (Pao₂) were determined in 50 men with AIDS and in 25 age-matched healthy men in whom normal glucose tolerance was established by oral glucose tolerance tests.ResultsFasting serum glucose was not significantly different between the men with AIDS (87 ± 4 mg/dL) and the healthy male volunteers (84 ± 6 mg/dL); however, A1C (6.9 ± 0.2%) and serum fructosamine levels (288 ± 15 μmol/L) were significantly higher (P < .01) in the patients with AIDS than in the normal subjects (A1C, 5.6 ± 0.1%; fructosamine, 204 ± 14 μmol/L). Moreover, both A1C and fructosamine concentrations were significantly higher (P < .01) in the patients with AIDS than in the normal subjects divided into subgroups on the basis of fasting plasma glucose concentrations (70 to 79 mg/dL, 80 to 89 mg/dL, and 90 to 99 mg/dL). None of the study participants had anemia (hemoglobin < 12 g/dL) or hypoxia (Pao₂ < 95 mm Hg), and serum ethanol was undetectable. Furthermore, vitamin E concentrations were not significantly different between the patients with AIDS (25 ± 3 mg/L) and the normal subjects (22 ± 4 mg/L).ConclusionOn the basis of this study, glycation of some circulating proteins appears to be enhanced in AIDS and may be induced by an undetermined plasma enhancer, inasmuch as known circulating factors promoting glycation were absent. (Endocr Pract. 2008;14:686-690)