Insulin sensitivity,insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients

Summary In cirrhotic patients with normal fasting glucose levels both insulin insensitivity and a blunted early insulin response to oral glucose are important determinants of the degree of intolerance to oral glucose. It is not known whether the ability of hyperglycaemia per se to enhance glucose disposal (glucose effectiveness) is also impaired. It is also unclear whether overt diabetes is due to (1) more marked insulin insensitivity; (2) impaired insulin secretion; (3) reduced glucose effectiveness; or (4) a combination of these mechanisms. We used the minimal model to analyse the results of a 3-h intravenous glucose tolerance test to assess glucose effectiveness, insulin sensitivity and insulin responses in 12 non-diabetic cirrhotic patients, 8 diabetic cirrhotic patients and 10 normal control subjects. Fasting blood glucose levels were 4.8±0.2, 7.5±0.6 and 4.7±0.1 mmol/l, respectively. Fasting insulin and C-peptide levels were higher in both cirrhotic patient groups compared with control subjects. The glucose clearance between 6 and 19 min after i.v. glucose was lower in both cirrhotic groups (non-diabetic, 1.56±0.14, diabetic, 0.76±0.06, control subjects, 2.49±0.16 min^–1%, both p<0.001 vs control subjects). Serum insulin peaked at 3 and 23 min in the non-diabetic cirrhotic patients and control subjects; both peaks were higher in the non-diabetic cirrhotic patients and showed a delayed return to basal levels. In the diabetic cirrhotic patients, the first phase insulin and C-peptide response to i.v. glucose was absent; their early (22–27 min) incremental insulin response to i. v. tolbutamide was however similar to that of control subjects but 43% lower than in the non-diabetic cirrhotic patients (p<0.05). Insulin sensitivity was markedly reduced in both cirrhotic groups (non-diabetic, 1.11±0.24×10^–4, diabetic, 0.33±0.53×10^–4, control subjects, 4.37±0.53×10^–4 min^–1 per mU·l^–1, both p<0.001 vs controls). Glucose effectiveness was normal in the non-diabetic cirrhotic patients but 29% lower in the diabetic group. It would appear that overt diabetes develops in those cirrhotic patients who in addition to insulin insensitivity have a marked impairment of insulin secretion. An associated reduction in glucose effectiveness may be a contributory factor.     

Immunologic Identification of Tissue Factor (Thromboplastin) Synthesized by Cultured Fibroblasts

The proliferative capacity of bone marrowcells from thymus-deprived nude mice wasinvestigated in lethally irradiated recipients. Although the colony-forming capacityof these cells was found to be similar tothat of normal littermates, a reduction inthe number of nucleated cells was observed in the bone marrow of nude mice.Moreover when the radioprotective effectof such cells was studied, it was foundthat 5 x 10⁵ or 2 x 10⁶ bone marrowcells from nude mice were less effectivein restoring hemopoiesis and establishingpermanent chimerism than similaramounts of bone marrow cells of normalcontrols. In addition, irradiated animalssurviving after injection of bone marrowcells from nude mice were found to havelower immune responses to SRBC thannormal chimeras. The possibility that mortality of irradiated recipients injected withbone marrow of nude mice is due to thepresence of a latent infective agent or ofsome inhibitory factor of hematopoiesis inthe bone marrow of such nude mice isshown to be improbable. Alternatively it issuggested that nude mice suffer from anintrinsic defect in the proliferative capacityof their bone marrow colony-forming cells(CFUs).

Submitted on February 12, 1973 Revised on March 29, 1973 Accepted on April 20, 1973     

Adult “idiopathic” extrahepatic venous thrombosis

The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a latent myeloproliferative disorder has been reported in adults with idiopathic EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The idiopathic group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17–70) with a median follow up of 96 months (19–372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance.Supported by R Farini Foundation for Gastroenterology Research.     

Mistaken Endobronchial Placement of a Nasogastric Tube During Mandibular Fracture Surgery

A 64-year-old male had an awake right nasal fiber-optic intubation with an endotracheal tube for open reduction and internal fixation of bilateral displaced mandibular fractures. After induction of anesthesia, an 18 Fr nasogastric tube (NGT) was inserted through the left nostril and was secured. The patient required high flow rates to deliver adequate tidal volumes with the ventilator. A chest x-ray done in the postanesthesia care unit revealed a malpositioned NGT in the left lower lobe bronchus, which was immediately removed. The patient was extubated on postoperative day 2. Various traditional methods, such as aspiration of gastric contents, auscultation of gastric insufflations, and chest x-ray are in use to detect or prevent the misplacement of an NGT. These methods can be unreliable or impractical. Use of capnography to detect an improperly placed NGT should be considered in the operating room as a simple, cost-effective method with high sensitivity to prevent possibly serious sequelae of an NGT placed within the bronchial tree.Key words: Nasogastric tube, Misplacement, Oral surgeryPlacement of a nasogastric tube (NGT) preoperatively for decompression of the stomach is common practice to allow drainage of gastrointestinal contents in the case of bowel obstruction, or in other cases when the patient is at risk of aspiration for some other reason. This case report involves a patient who required aspiration precautions via NGT placement for mandibular surgery due to facial trauma; the NGT was later found to be misplaced in the left main stem bronchus as the misplacement was unrecognized intraoperatively. We discuss the necessity of preventing the possible intraoperative and postoperative complications of a misplaced NGT and simple measures to recognize misplacement in patients presenting for similar surgeries.     

Autoantibodies to phosphatidylethanolamine (PE) recognize a kininogen- PE complex

Demonstration of autoimmune antiphospholipid antibodies (aPA) to negatively charged phospholipids (PL) in an enzyme-linked immunosorbent assay (ELISA) requires the presence of certain phospholipid-binding plasma proteins, eg, beta 2-glycoprotein I. We found a requirement for plasma against the electrically neutral or zwitterionic phospholipid, phosphatidylethanolamine (PE). Two of these PE-binding plasma proteins were identified as high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). We studied anti-PE antibody (aPE) seropositive plasma from 13 patients with SLE and/or recurrent spontaneous abortions by using partially purified kininogens and kininogen binding proteins from adult bovine serum isolated by carboxymethyl (CM)-papain affinity chromatography. Eleven of 13 sera recognized a kininogen-PE complex and/or a kininogen-binding protein- kininogen-PE complex. Some aPE-positive patient sera were shown to recognize highly purified HMWK and LMWK by ELISA only when the kininogens were presented on a PE substrate. These aPE sera did not recognize PE, HMWK, or LMWK when they were presented independently as the sole antigens on the ELISA plates. Other aPE-positive sera that did not react with PE-bound HMWK or LMWK reacted with the CM-papain column eluate when it was bound to PE, which suggests that these aPE recognize factor XI or prekallikrein, which normally bind to HMWK. The aPE ELISA reactivity of two patient sera were inhibited by preincubation of the CM-papain column eluate in the ELISA plate. These data show that most aPE are not specific for PE but require the presence of certain PL- binding plasma proteins that are kininogens or proteins in complex with kininogens. Our studies indicate that aPE bind to different plasma proteins than those implicated in anionic PL, aPA ELISA reactivity.     

Progression of Device-Detected Subclinical Atrial Fibrillation and the Risk of Heart Failure

Background

Long-term continuous monitoring detects short-lasting, subclinical atrial fibrillation (SCAF) in approximately one-third of older individuals with cardiovascular conditions. The relationship between SCAF, its progression, and the development of heart failure (HF) is unclear.

ISPD Cardiovascular and Metabolic Guidelines in Adult Peritoneal Dialysis Patients Part I – Assessment and Management of Various Cardiovascular Risk Factors

Cardiovascular disease contributes significantly to the adverse clinical outcomes of peritoneal dialysis (PD) patients. Numerous cardiovascular risk factors play important roles in the development of various cardiovascular complications. Of these, loss of residual renal function is regarded as one of the key cardiovascular risk factors and is associated with an increased mortality and cardiovascular death. It is also recognized that PD solutions may incur significant adverse metabolic effects in PD patients. The International Society for Peritoneal Dialysis (ISPD) commissioned a global workgroup in 2012 to formulate a series of recommendations regarding lifestyle modification, assessment and management of various cardiovascular risk factors, as well as management of the various cardiovascular complications including coronary artery disease, heart failure, arrhythmia (specifically atrial fibrillation), cerebrovascular disease, peripheral arterial disease and sudden cardiac death, to be published in 2 guideline documents. This publication forms the first part of the guideline documents and includes recommendations on assessment and management of various cardiovascular risk factors. The documents are intended to serve as a global clinical practice guideline for clinicians who look after PD patients. The ISPD workgroup also identifies areas where evidence is lacking and further research is needed.     

Endogenous peroxidase in the nuclear envelope and endoplasmic reticulum of human monocytes in vitro: association with arachidonic acid metabolism

The development of peroxidase (PO) reaction in the nuclear envelope (NE) and endoplasmic reticulum (ER) of monocytes differentiating in vitro and its relationship with arachidonic acid metabolism were studied. The PO, as visualized by the diaminobenzidine (DAB) technique, appeared in the NE and ER of the majority of monocytes within 24 hours of culture, with a substantial decrease thereafter. The influence of three major groups of agents--inhibitors of PO, of prostanoids, and of protein biosynthesis--upon the development of the PO reaction was examined. When aminotriazole, a PO inhibitor, was added to the culture medium, the appearance of PO was suppressed in the monocytes. The cyclooxygenase blocker, indomethacin, however, did not influence the development of PO. Also the blockers of protein synthesis, puromycin, cycloheximide, and actinomycin D, did not affect the appearance of PO. The prostanoids released from the monocytes, ie, prostaglandin E and thromboxane B2, were determined by radioimmunoassay and showed a time sequence of secretion that corresponded to the appearance of PO in the cells: a marked increase within the first 24 hours with a substantial decrease thereafter. The presence of the PO inhibitors aminotriazole and sodium azide in the culture medium produced a suppression of prostanoid release from the monocytes comparable with that of indomethacin. The data suggest that the PO in the NE and ER of differentiating monocytes in vitro (1) is associated with arachidonic acid metabolism, and (2) is not formed by de novo protein synthesis but rather by an activation process.     

Sleep architecture variation: a mediator of metabolic disturbance in individuals with major depressive disorder

Remarkable proportions of individuals diagnosed with major depressive disorder (MDD) have comorbid metabolic disturbances (i.e., obesity, type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia), and vice versa. Accumulating evidence suggests that common pathophysiologic pathways such as a chronic, low-grade, proinflammatory state mediate this frequent co-occurrence. However, it remains unclear what traits precede the onset and increase the risk for these pathologic states. The aim of our review was to evaluate the evidentiary base supporting the hypothesis that the increased hazard for metabolic disturbance in MDD subpopulations (and vice versa) is mediated in part by endophenotypic variations in sleep architecture.