Normal Hemoglobin A1c Research Articles

1205: Pregnancy outcomes among class 3 obese women with normal and pre-diabetic early hemoglobin A1C

1205: Pregnancy outcomes among class 3 obese women with normal and pre-diabetic early hemoglobin A1C

Metabolic Dysfunction in Continuous-Flow Left Ventricular Assist Devices Patients and Outcomes.

BackgroundMetabolic impairment is common in heart failure patients. Continuous‐flow left ventricular assist devices (CF‐LVADs) improve hemodynamics and outcomes in patients with advanced heart failure; however, the effect of CF‐LVADs on metabolic status is unknown. This study aims to evaluate the changes in metabolic status following CF‐LVAD implantation and measure the correlation of metabolic status with outcomes.Methods and ResultsProspective data on CF‐LVAD patients were obtained. Metabolic evaluation, including hemoglobin A1C, free and total testosterone, thyroid‐stimulating hormone (TSH), and free T4, was obtained before and at multiple time points following implantation. Patients with nonelevated thyroid‐stimulating hormone and normal hemoglobin A1C and testosterone levels were defined as having normal metabolic status. Baseline characteristics, hemodynamics, and outcomes were collected. One hundred six patients were studied, of which 56 had paired data at baseline and 1‐ to 3‐month follow‐up. Before implantation, 75% of patients had insulin resistance, 86% of men and 39% of women had low free testosterone, and 44% of patients had abnormal thyroid function. There was a significant improvement in hemoglobin A1C, free testosterone, and thyroid‐stimulating hormone following implantation (P<0.001 for all). Patients with normal hemoglobin A1C (<5.7%) following implantation had higher 1‐year survival free of heart failure readmissions (78% versus 23%; P<0.001). Patients with normal metabolic status following implantation also had higher 1‐year survival free of heart failure readmissions (92% versus 54%; P=0.04).ConclusionsMetabolic dysfunction is highly prevalent in advanced heart failure patients and improves after CF‐LVAD implantation. Normal metabolic status is associated with a significantly higher rate of 1‐year survival free of heart failure readmissions.

SUN-282 Sertraline-Induced Dyslipidemia and Liver Toxicity in a 17-Year-Old Adolescent

Background: SSRI’s are very common first line drugs used for treatment of anxiety and depression in adults and children. Different drugs in this group have been reported in adults to be associated with increased weight, cholesterol, triglyceride (TG), insulin level and fasting blood glucose. Sertraline-induced liver toxicity has been described clinically and in vitro. Some studies found Fluoxetine to be the safest SSRI in terms of metabolic syndrome with reduction of weight, cholesterol, TG, fasting blood glucose and hemoglobin A1c. SSRI’s side effects have not been examined thoroughly in the pediatric population. Clinical case: 17 year old Caucasian autistic male teen was referred for initial endocrine evaluation with concern about fatty liver, increased liver enzymes, and increased triglyceride. He was started on Sertraline about 6 months prior to presentation for behavioral issues. He was previously on Aripiprazole and Fluoxetine for few years. Lipid panel showed total cholesterol of 186 mg/dl, TG 245 mg/dl, LDL cholesterol 106 mg/dl, and HDL cholesterol 31 mg/dl. Aspartate Aminotransferase (AST) was 50 U/L and Alanine Aminotransferase (ALT) was 111 U/L. Liver US showed fatty infiltration. Detailed work up for liver disease was negative. He had normal hemoglobin A1c of 5.1%, fasting insulin level of 4 mcIU/ml and TSH of 2.4 mcIU/ml. No major weight change was reported. BMI on presentation was normal at 24.42 kg/m² (78%ile based on CDC 2-20 Years BMI-for-age data). Sertraline-related side effects were suspected giving previous normal lipid panel and liver enzymes prior to starting this medication, and recommendation was made to stop it. He was switched back to Fluoxetine. Labs studies improved quickly within few weeks. Studies after 6 month showed total cholesterol of 141 mg/dl, TG 100 mg/dl, LDL cholesterol 87 mg/dl, HDL cholesterol 34 mg/dl, Aspartate Aminotransferase (AST) 19 U/L and Alanine Aminotransferase (ALT) 21 U/L. Conclusion: SSRIs are increasingly prescribed in the pediatric population, and studies are needed to understand their possible metabolic side effects. This is important giving the increased prevalence of obesity and metabolic syndrome in children and adolescents. Clinicians treating with Sertraline should be aware of its possible metabolic side effects and hepatic toxicity. Laboratory studies should be conducted periodically while taking this medication.

Comparison of 2-Hour Oral Glucose Tolerance Test and Hemoglobin A1C in the Identification of Pre-Diabetes in Women with Infertility and Recurrent Pregnancy Loss.

Research question:Does hemoglobin A1C (HbA1C) predict pre-diabetes (pre-DM) in a population of women with infertility and/or recurrent pregnancy loss (RPL), when considering the 75 g, 2-hour oral glucose tolerance test (2h GTT) as the gold standard?Design:Retrospective study of 242 patients with infertility or RPL presenting to a university-affiliated reproductive endocrinology and infertility clinic between January 2012 and December 2016 who underwent screening for disorders of glucose metabolism with a 2h GTT. The prevalence of pre-DM as defined by HbA1C 5.7% to 6.4% and 2h GTT values of 140-199 mg/dL, and predictive values of HbA1C for the identification of pre-DM when compared with 2h GTT, were calculated and compared.Results:Of 242 patients, 188 (77.7%) women had both HbA1C and 2h GTT performed. Of these, 89 (47.3%) tested positive for pre-DM by one or both methods. Of 89 patients, 14 (15.7%) had both an abnormal 2h GTT and an abnormal HbA1C. Only 6 out of 89 (6.7%) patients tested positive for pre-DM by an abnormal 2h GTT in the setting of a normal HbA1C result. Conversely, 69 of these 89 patients (77.5%) tested positive for pre-DM by an abnormal HbA1C in the setting of a normal 2h GTT. The prevalence of pre-DM, as defined by 2h GTT, was 10.6% (20/188) (95% CI, 6.6-16.0), compared with a prevalence of 44.1% (83/188) (95% CI, 36.9-51.6) when pre-DM was defined by HbA1C alone. When the 2h GTT was considered the gold standard for the identification of pre-DM, the negative predictive value (NPV) of HbA1C compared with 2h GTT was 94.3% (95% CI, 88.0-97.9), whereas the positive predictive value (PPV) of HbA1C compared with 2h GTT was only 16.9% (95% CI, 9.5-26.7).Conclusions:Although a normal HbA1C was highly predictive of a normal 2h GTT, the two tests demonstrate poor agreement in the identification of pre-DM in women with infertility and/or RPL. Hemoglobin A1C is superior to the 2h GTT as an initial screening test for pre-DM in this population, since it identified a substantial number of women who would otherwise remain undiagnosed in the setting for a normal 2h GTT alone. However, the long-term clinical relevance of an elevated HbA1C in this population needs to be better defined.

Utility of hemoglobin A1c in detecting risk of type 2 diabetes: comparison of hemoglobin A1c with other biomarkers.

We have previously reported that the risk of type 2 diabetes, early impaired glucose tolerance, and insulin resistance can be predicted using fasting levels of adiponectin, leptin, and insulin. Here, we aimed to evaluate the utility of hemoglobin A1c in detecting the risk of type 2 diabetes compared with other well-known biomarkers. We randomly enrolled 207 volunteers with no history of diseases, who underwent 75-g oral glucose tolerance tests and were stratified into normal, borderline, abnormal, or diabetic groups. Eighty-one participants with normal baseline levels of hemoglobin A1c (<6.0%) were included in the normal groups of both glucose tolerance and insulin resistance. Hemoglobin A1c was significantly correlated with the plasma glucose and insulin resistance index. Leptin, adiponectin, glycoalbumin, and body mass index also were correlated well with plasma glucose levels and insulin resistance index. Normal hemoglobin A1c levels with abnormal glucose tolerance and insulin resistance were noted in 85 and 67 participants, respectively. Hemoglobin A1c did not strengthen the prediction algorithm of diabetes, determined by our proposed biomarkers, leptin, adiponectin, and insulin. In conclusion, hemoglobin A1c is a surrogate biomarker for risk of diabetes, with inadequate predictive value, and should be used in combination with other biomarkers.

2. Craniopharyngioma presenting as bilateral carpal tunnel syndrome

A 35 year-old Caucasian information technology professional developed bilateral hand paraesthesia, increasing in severity over two months. He reported recent onset photophobia. He was obese with a weight of 138 kg and body mass index of 47.5 kg/m 2 . Visual acuity was 6/6 on the right and 6/18 on the left. Visual fields were normal to confrontation. There was no relative afferent pupillary defect and optic discs were normal. There was mild weakness of abductor pollicis brevis and mild sensory disturbance affecting his fingers in the median distribution bilaterally. Phalen’s test was positive. The remaining neurological examination was normal. Nerve conduction studies showed bilaterally prolonged median distal motor latencies (6.5 ms on left, 6.9 ms on right), bilaterally absent sensory potentials at digit two, and prolonged median lumbrical motor latencies compared to the ulnar interosseus, consistent with severe carpal tunnel syndrome (CTS). Blood tests performed in view of the rapid onset of symptoms showed normal haemoglobin A1c and vitamin B12 levels. Thyroid function tests showed a low thyroxine of 3.4 pmol/L (normal range 10–21) and inappropriately normal thyroid stimulating hormone of 3.3 mIU/L (normal range 0.4–4.0), suggestive of secondary hypothyroidism. Further pituitary function tests confirmed panhypopituitarism. MRI brain showed a suprasellar cystic mass with an enhancing wall, suggestive of a craniopharyngioma. Visual field testing was consistent with compression of the optic chiasm. The patient was started on hydrocortisone and thyroxine and underwent transsphenoidal resection of the tumour. His hand paraesthesia and visual symptoms resolved within two weeks. Repeat nerve conduction studies after five months showed significant electrophysiological improvement. Craniopharyngiomas are cystic suprasellar tumours arising from remnants of the craniopharyngeal duct ( Levy, 2004 ). They commonly present with headache, visual field defects, panhypopituitarism and hypothalamic dysfunction resulting in obesity and somnolence. CTS has not previously been reported in this context. There is a modest association between hypothyroidism and CTS ( Shiri, 2014 ). A combination of hypothyroidism and obesity likely predisposed this patient to CTS. Routine screening for thyroid disease is not recommended in patients with CTS due to low yield.

Association between White Blood Cell Counts within Normal Range and Hemoglobin A1c in a Korean Population.

BackgroundWe examined whether white blood cell (WBC) count levels within normal range, could be associated with hemoglobin A1c (HbA1c) levels.MethodsAmong the 11,472 people (≥19 years of age) who participated in the 2011 to 2012 Korea National Health and Nutrition Examination, subjects with chronic disease or illness, including 807 patients with diabetes currently taking anti-diabetic medications and/or 1,149 subjects with WBC levels <4,000 or >10,000/µL were excluded.ResultsOverall, adjusted HbA1c levels increased across the WBC quartiles (5.55%±0.01%, 5.58%±0.01%, 5.60%±0.01%, and 5.65%±0.01%, P<0.001) after adjusting for confounding factors, such as age, gender, fasting plasma glucose, college graduation, smoking history, waist circumference, presence of hypertension, serum total cholesterol, serum triglyceride, and presence of anemia. The adjusted proportions (%) of HbA1c levels of ≥5.7%, ≥6.1%, and ≥6.5% showed significant increases across WBC quartiles (P<0.001, P=0.002, and P=0.022, respectively). Logistic regression analyses of WBC quartiles for the risk of HbA1c levels of ≥5.7%, ≥6.1%, and ≥6.5%, using the variables above as covariates, showed that the odds ratios of the fourth quartile of WBCs were 1.59 (95% confidence interval [CI], 1.35 to 1.89; P<0.001), 1.78 (95% CI, 1.31 to 2.42; P<0.001), and 2.03 (95% CI, 1.13 to 3.64; P=0.018), using the first quartile of WBCs as the reference.ConclusionHbA1c levels were positively associated with WBC levels within normal range in a general adult population.

Hepatogenous diabetes: Is it time to separate it from type 2 diabetes?

By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent "toxic" effect on pancreatic islets resulting in β-cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.

Insulin Resistance and Diabetes Mellitus in Contemporary Cardiac Rehabilitation.

The goal of this study was to determine the prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) in contemporary cardiac rehabilitation (CR) and to compare clinical responses in CR between these subsets of patients with coronary heart disease (CHD). The study cohort included 818 patients enrolled in CR and separated into 3 groups: (1) individuals with normal hemoglobin A1c (HbA1c) (NoIR: HbA1c < 5.7%); (2) individuals with IR (IR: HbA1c ≥ 5.7 to <6.5%); (3) and individuals with T2DM (HbA1c ≥ 6.5%). The combined prevalence of IR (44%) and T2DM (23%) was 67%, which paralleled the prevalence of metabolic syndrome (MetSyn), present in 65% of patients. Women had a higher prevalence of IR and MetSyn than men (73% vs 64%, 72% vs. 63%, respectively) and a greater percentage with an elevated waist circumference (71% vs 60%) (all P < .05). All 3 groups experienced decreases in body weight (NoIR = -2.3 ± 4.0, IR = -1.7 ± 4.0, T2DM = -1.0 ± 4.2 kg) and increases in maximal metabolic equivalents (METs) at exercise testing (NoIR = +2.2 ± 2.5 vs IR = +2.1 ± 2.8 vs T2DM = +1.3 ± 2.3) (all P < .05). Individuals with NoIR achieved greater improvements in weight, body mass index, and METs than patients with T2DM (all P < .05). Selected individuals who participated in a 4-session behavioral weight-loss program lost more than twice the weight as nonparticipants. The combined prevalence of IR and T2DM in patients with CHD enrolled in CR was remarkably high (67%). To reverse the deleterious consequences of IR and T2DM, targeted interventions involving exercise and weight loss need to be a central focus of CR programming.

Relationship between Haemoglobin A1c and Short Term Outcome in Patients with ST-elevation Myocardial Infraction (STEMI)

Introduction: Every year, 17.1 million lives are claimed by the global burden of cardiovascular disease (CVD), 82% of which are in the developing world. Glycated hemoglobin (HbA1c), even at levels considered in the “normal” range, emerged as an independently significant predictor of heart-disease events, stroke, and death over more than a decade.Methodology: After applying the inclusion and exclusion criteria, 113 patients with ST segment elevation myocardial infarction were enrolled in this study after taking informed written consent from the patient or attending guardian. Follow up was done during hospital stay for mortality, arrhythmia, cardiogenic shock, cardiac arrest, congestive heart failure, mechanical complication (eg ventricular septum rupture, wall rupture), left ventricular systolic dysfunction, stroke etc.Result: The median age of patients was 53.4 years (range 22 to 85 years), patients with an HbA1c &gt;6.5% were slightly older than those with HbA1c &lt;6.5%(53.1 vs. 54.6),and 82% were male; and 43% had an HbA1c &gt;6.5%. Patients with elevated HbA1c had more LVSD (54%) (p=0.022), heart failure (81%) (p= &lt; .001). However, patients with HbA1c &gt;6.5% were more likely to have cardiogenic shock as an outcome but it is not statistically significant (p= .528), whereas cardiac arrest, arrythmia and mechanical complication were more among HbA1c &lt;6.5 group but it was not statistically significant. During hospital stay 16 (14%) patients died. Mortality was much higher among all STEMI patients, those with elevated hemoglobin A1c level as an outcome compared to patients with normal haemoglobin A1c level (26% vs. 5%) (p= .002).Conclusion : STEMI patients who has haemoglobin HbA1c level &lt; 6.5 have better in hospital outcome compared to elevated (&gt;6.5) haemoglobin A1c level.Bangladesh Heart Journal 2015; 30(1) : 29-32

Changes in circulating osteocalcin concentration in overweight and obese adult women having normal glucose and hemoglobin A1c levels

Changes in circulating osteocalcin concentration in overweight and obese adult women having normal glucose and hemoglobin A1c levels

Thiol/disulfide homeostasis in patients with idiopathic recurrent pregnancy loss assessed by a novel assay: Report of a preliminary study.

To evaluate the relationship between idiopathic recurrent pregnancy loss (RPL) and oxidative stress (OS) by means of thiol/disulfide homeostasis via a novel technique. Thirty-nine pregnant women diagnosed with idiopathic RPL were compared with 50 healthy pregnant women without a history of abortion. Idiopathic RPL was defined as experiencing two or more consecutive miscarriages prior to 20 weeks of gestation with the presence of normal karyotypes of couple and/or abortus materials, negative maternal screening for anticardiolipin, anti β 2 glycoprotein antibodies and lupus anticoagulant, normal thyroid stimulating hormone, prolactin and hemoglobin A1C levels and normal pelvic sonography and/or hysterosalpingography. A new and fully automated method was used to measure plasma native thiol, total thiol and disulfide levels, based on the reduction of dynamic disulfide bonds to functional thiol groups by sodium borohydrate. Women with idiopathic RPL had significantly lower plasma levels of native thiol (341.89 ± 50.0 μmol/L vs. 390.84 ± 38.5 μmol/L, P < 0.001) and total thiol (386.18 ± 51.7 μmol/L vs. 435.78 ± 42.3 μmol/L, P < 0.001). Disulfide/thiol and disulfide/total thiol ratios were significantly higher in the study group. The native thiol/total thiol ratio was significantly lower in patients with idiopathic RPL. No difference was measured in disulfide, albumin and total protein plasma levels. The main outcome of our study indicates a relation between idiopathic RPL and OS. More importantly, the new method used in our study proposes a promising, practical and daily applicable test for evaluating patients with idiopathic RPL.

Klotho expression in cardiomyocytes in patients at a higher atherosclerotic cardiovascular disease risk

Klotho proteins (α- and β-Klotho) are transmembrane proteins whose extracellular domain is secreted into blood and urine by ectodomain shedding. As such they behave as circulating proteins that regulate cell metabolism, endothelial function and calcium homeostasis, as well as modulating the lifespan connected activity of Fibroblast Growth Factors (FGFs, mainly 21 and 23) and other molecules (1). Recent data have shown that highest levels of plasma circulating Klotho are associated with a lower cardiovascular risk, thereby suggesting a possible role for Klotho in cardiovascular diseases (2). However, although Klotho has been identified in various organs, including kidney, brain, adipose tissue and intestine, it is unknown whether cardiomyocytes express Klotho and FGFs and, if so, whether high cardiovascular risk can be associated with cardiac expression of Klotho, FGFs and other related molecules. We examined myocardial biopsies from 20 patients with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk in the range of 5% to 7.5% and 10 age-matched control subjects with an estimated 10-year ASCVD risk of <5% (3) undergoing cardiac surgery other than coronary artery by-pass. Both groups of patients were statin naive, had normal hemoglobin A1c, normal coronary arteries on left heart catheterization, and had LDL cholesterol levels between 70 and 189 mg/ DL. Using immunohistochemistry methods, we evaluated Klotho and FGFs expression in human cardiomyocytes, and whether higher ASCVD risk influenced the expression of other molecules involved in endoplasmic reticulum stress (GRP78), oxidative stress (SOD1, NFkB) and inflammation (iNOS, eNOS). Cardiomyocytes of patients with a higher ASCVD risk exhibited lower expression of Klotho, but also higher expression of FGFs, as compared to cardiomyocytes of patients with a reduced ASCVD risk. Furthermore, higher ASCVD risk was associated with significantly increased expression of GRP78, SOD1, NFkB and iNOS (all p<0.05). This study shows for the first time that Klotho proteins are inherently expressed in human cardiomyocytes and also that cardiac expression of Klotho is down regulated in higher ASCVD risk patients, while the expression of FGFs and other stress-related molecules involved in myocyte damage, such as GRP78, SOD1, NFkB and iNOS, is significantly increased. Further studies are warranted to investigate the association of klotho, FGFs and related molecules expression with cardiovascular risk.

Graft-Versus-Host Disease After Simultaneous Pancreas–Kidney Transplantation: A Case Report and Review of the Literature

Graft-versus-host disease (GVHD) after solid organ transplantation is rare and usually fatal. We present, to our knowledge, the second successfully treated case in a simultaneous pancreas-kidney (SPK) transplant recipient. A 29-year-old female with end-stage renal disease from type 1 diabetes mellitus received an SPK transplant from a male donor, with rabbit-antithymocyte globulin induction. Twelve days posttransplant, she was readmitted with abdominal pain, nausea and vomiting. She developed leukopenia, abnormal liver enzymes, fever and a skin rash. Skin biopsy showed interface dermatitis consistent with allergic reaction versus GVHD. Fluorescence in situ hybridization of the skin biopsy showed 28% of cells had a Y chromosome confirming GVHD. Short tandem repeats (STR) enriched for CD3+ cells from peripheral blood showed a mixed chimerism. She was successfully treated with a single plasmapheresis to remove antithymocyte globulin, high-dose steroids, photopheresis and high tacrolimus levels (12-15 ng/mL). Five months after transplantation, she has normal renal function and white blood cell count, normal hemoglobin A1C and no evidence of peripheral blood donor chimerism. In conclusion, early diagnosis of GVHD after SPK transplantation may allow successful treatment. STR enriched for CD3+ may be useful to evaluate the response to therapy.

Glucoregulatory function among African Americans and European Americans with normal or pre-diabetic hemoglobin A1c levels

ObjectiveA hemoglobin (Hb) A1c range of 5.7%–6.4% has been recommended for the diagnosis of prediabetes. To determine the significance of such “prediabetic” HbA1c levels, we compared glucoregulatory function in persons with HbA1c levels of 5.7%–6.4% and those with HbA1c<5.7%. MethodsWe studied 280 nondiabetic adults (142 black, 138 white; mean (±SD) age 44.2±10.6 years). Each subject underwent clinical assessment, blood sampling for HbA1c measurement, and a 75-g oral glucose tolerance test at baseline. Additional assessments during subsequent outpatient visits included insulin sensitivity, using homeostasis model assessment (HOMA)-IR and the hyperinsulinemic euglycemic clamp; insulin secretion, using HOMA-B and frequently samples intravenous glucose tolerance test (FSIVGTT) and disposition index (DI); and measurement of fat mass, using DXA. ResultsCompared to subjects with HbA1c<5.7%, persons with HbA1c levels of 5.7%–6.4% were older, and had higher body mass index (BMI) and insulin secretion but similar insulin sensitivity. When the two groups were matched in age and BMI, persons with HbA1c 5.7%–6.4% were indistinguishable from those with HbA1c <5.7% with regard to all measures of glycemia and glucoregulatory function. ConclusionsUnlike glucose-defined prediabetes status, an HbA1c range of 5.7%–6.4% does not reliably identify individuals with impaired insulin action or secretion, the classical defects underlying the pathophysiology of prediabetes. Thus, HbA1c cannot validly replace blood glucose measurement in the diagnosis of prediabetes. If utilized as a screening test due to convenience, aberrant HbA1c values should be corroborated with blood glucose measurement before therapeutic intervention.

Elevated hemoglobin A1c is associated with readmission but not complications.

studies have shown that elevated hemoglobin A1c levels are associated with worse short-term outcomes after cardiac surgery. However, the effect on readmission has not been studied. The primary purpose of this study was to determine the independent effect of hemoglobin A1c level on the readmission rate after cardiac surgery. The secondary purpose was assess its effect on complications and mortality. consecutive patients undergoing coronary artery bypass surgery between April 2007 and August 2010 were divided into 3 groups based on preoperative hemoglobin A1c levels. Outcomes were controlled for demographics, comorbidities, and surgery. 300 (34%) patients had normal hemoglobin A1c levels (<6.0%), 305 (35%) had mildly elevated levels (6.0%-6.9%), and 275 (31%) had markedly elevated levels (≥ 7.0%). Postoperative glucose levels were similar among all 3 hemoglobin A1c groups. Compared to patients with normal hemoglobin A1c levels, those with higher levels were more likely to be readmitted: adjusted odds ratio 2.091 (95% confidence interval: 1.074-4.069, p = 0.036) for hemoglobin A1c 6.1%-6.9%; and adjusted odds ratio 2.089 (95% confidence interval: 1.050-4.155, p = 0.036) for hemoglobin A1c ≥ 7.0. Overall, 381 (43%) patients suffered complications, and hemoglobin A1c levels were similar in those with and without complications (6.8% ± 1.6% vs. 6.9% ± 1.7%, p = 0.837). Mortality was equivalent in all 3 hemoglobin A1c groups. elevated preoperative hemoglobin A1c levels are associated with an increased risk of readmission but not complications.

Heart MRI Identifies Patients At Higher Risk For Severe Pulmonary Edema After Bortezomib Plus Dexamethasone Treatment In Subclinical Heart Amyloidosis

IntroductionPrimary immunoglobulin amyloidosis (AL) is caused by deposition of insoluble amyloidoigenic fibrils of monoclonal light chains, which is often associated with an underlying plasma cell dyscrasia. The heterogeneous clinical manifestations commonly include nephrotic syndrome, hepatic failure, autonomic and sensory neuropathy. Cardiac involvement is most common in immunoglobulin variants of amyloidosis and is associated with significant mortality with survival of 17% by 2 years. Cardiac Magnetic Resonance (CMR) is a non-invasive technique that allows identification of heart involvement in 80% of biopsy proven patients (pts). In systemic amyloidosis with heart involvement, diuretics, despite representing backbone treatment of Congestive Heart Failure (CHF), exacerbation of hypotension and deterioration of cardiac performance are common features.(Dubrey.2012.QJM) Here, we describe a case of a 71 year-old man with subclinical AL amyloidosis who developed severe pulmonary edema during proteosomal inhibition (PI) plus dexamethasone induction. MethodsOur pt presented with mediastinal mass (Fig. 1A) detected by the time of pre-operative evaluation for benign prostate hypertrophy surgery. He has a long-term-history of diabetes type 2 metabolically controlled and normal hemoglobin A1C. Further characterization of his mediastinal mass by chest tomography showed a 48 x 26 x 39 mm mass arising from posterior right lateral tracheal wall. [Display omitted] ResultsBiopsy sections correlating with kappa light chain AL deposition by mass spectrometry (Fig. 2). Biochemical evidence of elevated kappa free light chain (FLC) and biclonal m-protein revealing IgG and IgA kappa protein by serum protein electrophoresis (SPEP) were observed. His bone marrow aspirate and biopsy was consistent with kappa MGUS (5% clonally restricted plasma cells). Despite no clinical or echocardiographic signs of cardiac dysfunction, left ventricle non-CAD scarring suggesting subclinical amyloid deposition was detected by CMR (Fig. 3). In an attempt to induce hematological response, Bortezomib (B) intravenously (IV) at 1.3 mg/m2plus weekly oral dexamethasone were initiated. Severe pulmonary edema associated with hemoptysis developed during cycle (C) 1 day (d) 5 of treatment. His repeated chest angiography showed no evidence of pulmonary embolism. A bronchoscopy failed to revealed tracheal perforation. Progressive resolution of symptoms was achieved after administration of furosemide IV. After recovery, pt completed 4 cycles of B plus dexamethasone and proceeded with autologous stem cell transplantation without recurrent pulmonary edema episodes. [Display omitted] [Display omitted] ConclusionsOur case suggests potential clinical phenotype associated with subclinical heart amyloid deposition, and propensity for acute pulmonary edema associated with PI recognized by CMR. Although pulmonary edema is uncommonly seen associated with PI in the treatment of plasma cell clonal disorders, clinically manifested acute pulmonary edema could result in high mortality (Hishao et al. Ann Pharmacother.2010). Our pt clinical manifestations could represent phenotypic expression of transiently impaired cardiac function as results of brisk elevation of unfolded serum FLC during PI (Obeng.Blood.2006). Lack of further similar episodes after PI re-exposure suggests low apoptotic threshold of secretory clone. Disclosures:No relevant conflicts of interest to declare.

Progress in Filling the Gaps in Bariatric Surgery

THE OBESITY EPIDEMIC IS A MAJOR THREAT TO PUBLIC health. Estimates by the World Health Organization indicate that in 2008 more than 1.4 billion adults or 21% of the world population were overweight, a substantial proportion of whom ( 500 million) were obese, and these numbers continue to increase. Sixty-five percent of the world’s population live in countries where overweight and obesity are linked to more deaths than underweight and malnutrition. For severe obesity, bariatric surgery is the only treatment resulting in significant and sustained weight loss. Nevertheless, only a very small fraction of the eligible candidates undergo surgery. The gaps in the bariatric surgery evidence base contribute to the small fraction of obese patients who undergo surgery. These gaps have included insufficient randomized controlled trials, limits to the generalizability of the reports of bariatric surgical interventions, and uncertainty regarding long-term outcomes. Addressing the various and broad health outcomes resulting from bariatric surgery such as diabetes, hypertension, sleep apnea, psychosocial factors, and many others has proven difficult. In this issue of JAMA, a theme issue on obesity, 3 articles address some of the evidence gaps and add bricks to the wall of data needed to create a solid and respected evidence structure. A prospective cohort study conducted by Adams and colleagues assessed long-term weight loss and health outcomes in severely obese patients undergoing gastric bypass surgery compared with severely obese control patients. There were 418 patients in the Roux-en-Y gastric bypass (RYGB) group compared with 2 control groups; one control group included patients seeking surgery (n=417) and the other included a random sample of severely obese adults (n=321). Although weight loss studies typically are limited by very high dropout rates, a remarkable aspect of the study by Adams et al was the 6-year follow-up rate of 93% in the RYGB group. At 6 years, mean weight loss for RYGB patients was 28% of initial body weight compared with weight gain of 0.2% and 0% in the 2 control groups, respectively. Diabetes remission rates (defined as normal fasting glucose and hemoglobin A1c) were 62% in the RYGB group and 8% and 6% in each of the control groups. Incident cases of diabetes at 6 years were 2% in the RYGB group compared with 17% and 15% in the 2 control groups, respectively. At 6 years of follow-up, the RYGB group showed improvement in all other health outcomes (eg, hypertension, high-density lipoprotein cholesterol) that were examined with the exception of the 36-item Short Form Health Survey mental component summary score. The mortality rate at 6 years was 3% in the RYGB patients compared with 3% in the obese patients evaluated for but who did not undergo surgery and 1% in the other control group of obese adults. Of all deaths, 4 suicides and 2 of the 3 poisonings were in the RYGB cohort. Another important aspect of these findings is that despite the attenuation of weight loss between 2 and 6 years in the RYGB group (shown in Figure 2 of the article), the control of comorbid conditions remained very good. These findings are important because they show in a RYGB cohort and control group with nearly complete follow-up at 6 years that weight loss and associated health benefits following RYGB are durable. The mortality rates in this study were too small to assess statistically, but serve as a reminder of an uncommon but important outcome needing objective monitoring. It is widely held that sleep apnea responds to surgically induced weight loss. In a randomized controlled trial reported in this issue of JAMA, Dixon and colleagues assessed the effect of weight loss with laparoscopic adjustable gastric banding (LAGB) on obstructive sleep apnea (OSA). Sixty obese patients (body mass index of 35-55) with recently diagnosed moderate to severe OSA were randomized and compared with a control group undergoing treatment with a conventional weight loss program. Polysomnography was performed 2 years later in both groups. Patients in the LAGB group lost 27.8 kg (95% CI, 20.9 to 34.7 kg), which was significantly more weight than the 5.1 kg (95% CI, 0.8 to 9.3 kg) lost by patients in the control group (P .001). Both groups experienced reduction in total apneahypopnea index (AHI) at 2 years compared with baseline (25.5 events/hour [95% CI, 14.2 to 36.7 events/hour] in the LAGB group vs 14.0 events/hour [95% CI, 3.3 to 24.6 events/

Evaluation of a novel non‐invasive 13C‐glucose breath test for the identification of diabetes mellitus in cirrhotic patients

Diabetes mellitus (DM) has been reported to worsen the long-term prognosis of cirrhotic patients, and many studies have reported that DM is an independent risk factor for hepatocellular carcinoma. However, an accurate diagnosis of DM is sometimes difficult in cirrhotic patients. Recently, a novel non-invasive (13) C-glucose breath test has been reported to be useful for diagnosing insulin resistance in non-cirrhotic patients. The aim of this study was to evaluate the efficacy of this tool for the identification of DM in cirrhotic patients. Thirty eight cirrhotic patients with normal fasting serum glucose and hemoglobin A1c levels underwent the (13) C-glucose breath test and the oral glucose tolerance test. Blood and breath samples were collected at baseline and at 30, 60 and 120 min after ingestion of 100 mg (13) C-labeled glucose and 75 g glucose. There was a strong correlation between the change in the concentrations at 2 h for the measured (13) C-glucose breath test (2h-BT) and the 2 h plasma glucose level (r = -0.60, P < 0.0001). In a receiver-operator curve analysis using the 2h-BT, the area under the curve was determined to be 0.88, with a sensitivity and specificity (cut-off value of 3.5‰) of 82% and 85%, respectively, for the detection of DM. Multivariate analysis showed the 2h-BT to be an independent parameter to identify DM. The (13) C-glucose breath test is a useful tool and has the potential to become a routine outpatient examination for the screening of DM in cirrhotic patients.

Elevation of fasting morning glucose relative to hemoglobin A1c in normoglycemic patients treated with niacin and with statins

Niacin increases fasting glucose levels, and statins modestly increase the rate of new-onset diabetes. The clinical importance and mechanisms of these effects are not fully explored. On the basis of anecdotal observations, we hypothesized that elevated morning fasting glucose may be accompanied by relatively normal hemoglobin A1c (HbA1c) in patients treated with niacin and other lipid-modifying drugs. We conducted a retrospective cohort analysis to test this hypothesis. The Duke Lipid Clinic database (1994-2007) was screened for simultaneous determinations of fasting morning glucose and HbA1c, yielding 1483 data pairs among 554 subjects. Subjects with diabetes, by clinical diagnosis, medication, or any HbA1c ≥6.5%, or nondiabetes were analyzed separately. Repeated-measures linear regression featured glucose as dependent variable and included terms for HbA1c, drug(s), and their interaction. Regression lines for glucose on HbA1c had altered slopes in the presence of niacin and/or statin use in normoglycemic subjects. The corresponding interaction terms (drug and HbA1c) were significant (niacin P= .026, statin P= .013). Fibrate use had no effect (interaction P= .49). When modeled together, niacin and statin effects were independent. Regression curves in diabetic patients were not affected by lipid medications. Elevated fasting glucose may be accompanied by relatively normal HbA1c in niacin- and statin-treated patients. HbA1c reflects average daily glucose levels and is likely a better measure of the glycemic effect of lipid medications. Because our data were retrospective, confirmation from randomized trials is needed.