Management of hyperglycemia in hospitalized patients in non-critical care setting: an end…

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Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline.

J Clin Endocrinol Metab. 2009 Mar;94(3):709-28

Authors: Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, Service FJ,

OBJECTIVE: The aim is to provide guidelines for the evaluation and management of adults with hypoglycemic disorders, including those with diabetes mellitus. EVIDENCE: Using the recommendations of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, the quality of evidence is graded very low (plus sign in circle ooo), low (plus sign in circle plus sign in circle oo), moderate (plus sign in circle plus sign in circle plus sign in circle o), or high (plus sign in circle plus sign in circle plus sign in circle plus sign in circle). CONCLUSIONS: We recommend evaluation and management of hypoglycemia only in patients in whom Whipple’s triad–symptoms, signs, or both consistent with hypoglycemia, a low plasma glucose concentration, and resolution of those symptoms or signs after the plasma glucose concentration is raised–is documented. In patients with hypoglycemia without diabetes mellitus, we recommend the following strategy. First, pursue clinical clues to potential hypoglycemic etiologies–drugs, critical illnesses, hormone deficiencies, nonislet cell tumors. In the absence of these causes, the differential diagnosis narrows to accidental, surreptitious, or even malicious hypoglycemia or endogenous hyperinsulinism. In patients suspected of having endogenous hyperinsulinism, measure plasma glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, and circulating oral hypoglycemic agents during an episode of hypoglycemia and measure insulin antibodies. Insulin or insulin secretagogue treatment of diabetes mellitus is the most common cause of hypoglycemia. We recommend the practice of hypoglycemia risk factor reduction–addressing the issue of hypoglycemia, applying the principles of intensive glycemic therapy, and considering both the conventional risk factors and those indicative of compromised defenses against falling plasma glucose concentrations–in persons with diabetes.

PMID: 19088155 [PubMed - indexed for MEDLINE]

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Clinical review: Drug-induced hypoglycemia: a systematic review.

J Clin Endocrinol Metab. 2009 Mar;94(3):741-5

Authors: Murad MH, Coto-Yglesias F, Wang AT, Sheidaee N, Mullan RJ, Elamin MB, Erwin PJ, Montori VM

CONTEXT: Drug-induced hypoglycemia is a significant adverse effect that may cause important morbidity. OBJECTIVE: The aim of the study was to systematically review the literature for drugs reported to cause hypoglycemia and assess the quality of evidence and strength of association supporting this causal link. DATA SOURCES: We searched electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) and the drug information system Micromedex through November 2007 and sought additional references from experts. STUDY SELECTION: Studies were eligible if they reported hypoglycemia as a side effect of a drug not used to treat hyperglycemia, regardless of their design, language, size, or follow-up duration. We excluded hypoglycemia caused by industrial exposures, nonpharmacological chemical exposures, alcohol, herbs, nutritional supplements, and in vitro and animal studies. DATA EXTRACTION: Reviewers extracted study characteristics and methodological quality and, when possible, data to estimate the odds of developing hypoglycemia when exposed to the offending agent. DATA SYNTHESIS: We found 448 eligible studies that described 2696 cases of hypoglycemia associated with 164 different drugs. The quality of evidence supporting associations between drugs and hypoglycemia was mostly very low due to methodological limitations and imprecision. The most commonly reported offending drugs were quinolones, pentamidine, quinine, beta blockers, angiotensin-converting enzyme agents, and IGF. CONCLUSIONS: Very low quality evidence substantiates the association between hypoglycemia and the use of numerous nondiabetic drugs.

PMID: 19088166 [PubMed - indexed for MEDLINE]

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Clinical review: Hypoglycemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections.

J Clin Endocrinol Metab. 2009 Mar;94(3):729-40

Authors: Fatourechi MM, Kudva YC, Murad MH, Elamin MB, Tabini CC, Montori VM

CONTEXT: Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear. OBJECTIVE: The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia. DATA SOURCES: We searched electronic databases between 2002 and March 2008. STUDY SELECTION: We selected published randomized trials of CSII vs. MDI. DATA EXTRACTION: Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events. DATA SYNTHESIS: We found 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study HbA1c levels. Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, -0.2%; 95% confidence interval (CI), -0.3, -0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95% CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover trials had nonsignificantly fewer minor hypoglycemia episodes per patient per week (-0.08; 95% CI, -0.21, 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20; P(interaction) = 0.03). Outcomes were not different in patients with type 2 diabetes. CONCLUSIONS: Contemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data.

PMID: 19088167 [PubMed - indexed for MEDLINE]

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Prevalence of elevated hemoglobin A1c among patients admitted to the hospital without a diagnosis of diabetes.

J Clin Endocrinol Metab. 2008 Nov;93(11):4238-44

Authors: Wexler DJ, Nathan DM, Grant RW, Regan S, Van Leuvan AL, Cagliero E

CONTEXT: One in four hospitalized patients has diagnosed diabetes. The prevalence of unrecognized, or undiagnosed, diabetes among hospitalized patients is not well established. OBJECTIVE: Our objective was to determine the prevalence of unrecognized probable diabetes in this patient population determined by elevated hemoglobin A1c (HbA1c) level. DESIGN: We conducted a prospective observational cohort trial with retrospective follow-up of patients with elevated HbA1c levels and no diagnosis of diabetes. HbA1c levels were obtained for all patients. SETTING: The study was conducted at an acute care general hospital. PATIENTS: Patients included 695 adult, nonobstetric patients admitted on 11 d in 2006. MAIN OUTCOME MEASURES: Outcome measures included rate of unrecognized probable diabetes, defined as admission HbA1c of more than 6.1% and no diagnosis of diabetes or treatment with antidiabetic medications before or during their admission and rate of unrecognized diabetes 1 yr after discharge. RESULTS: Eighteen percent of hospitalized patients had elevated HbA1c levels without a diagnosis of diabetes. Random glucose levels poorly predicted elevated HbA1c levels (area under receiver operating characteristic curve, 0.60). Neither diagnosed diabetes nor HbA1c level was associated with length of stay or costs (P>0.1 for all comparisons). Only 15% of patients with elevated HbA1c levels who continued to receive care within the system studied had diabetes diagnosed in the year after the index admission. CONCLUSIONS: Nearly one in five adult patients admitted to a large general hospital had unrecognized probable diabetes, based on elevated HbA1c levels. Random glucose levels during the hospital stay were poorly predictive of this condition. Few hospitalized patients with elevated HbA1c levels were diagnosed within the year after admission.

PMID: 18697862 [PubMed - indexed for MEDLINE]

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Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis.

J Clin Endocrinol Metab. 2008 Nov;93(11):4245-53

Authors: Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, Choi CH, Clayton RN, Courtney CH, Gonc EN, Maghnie M, Rose SR, Soule SG, Tordjman K,

CONTEXT: The diagnostic value of tests for detecting hypothalamic-pituitary adrenal insufficiency (HPAI) is controversial. OBJECTIVE: Our objective was to compare standard-dose and low-dose corticotropin tests for diagnosing HPAI. DATA SOURCES: We searched the PubMed database from 1966-2006 for studies reporting diagnostic value of standard-dose or low-dose corticotropin tests, with patient-level data obtained from original investigators. STUDY SELECTION: Eligible studies had more than 10 patients. All subjects were evaluated because of suspicion for chronic HPAI, and patient-level data were available. We excluded studies with no accepted reference standard for HPAI (insulin hypoglycemia or metyrapone test) if test subjects were in the intensive care unit or if only normal healthy subjects were used as controls. DATA EXTRACTION: We constructed receiver operator characteristic (ROC) curves using patient-level data from each study and then merged results to create summary ROC curves, adjusting for study size and cortisol assay method. Diagnostic value of tests was measured by calculating area under the ROC curve (AUC) and likelihood ratios. DATA SYNTHESIS: Patient-level data from 13 of 23 studies (57%; 679 subjects) were included in the metaanalysis. The AUC were as follows: low-dose corticotropin test, 0.92 (95% confidence interval 0.89-0.94), and standard-dose corticotropin test, 0.79 (95% confidence interval 0.74-0.84). Among patients with paired data (seven studies, 254 subjects), diagnostic value of low-dose corticotropin test was superior to standard-dose test (AUC 0.94 and 0.85, respectively; P<0.001). CONCLUSIONS: Low-dose corticotropin test was superior to standard-dose test for diagnosing chronic HPAI, although it has technical limitations.

PMID: 18697868 [PubMed - indexed for MEDLINE]

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