Can HbA1c be Used to Screen for Glucose Abnormalities Among Adults with Severe Mental Illness?

Aim: Prediabetes and type 2 diabetes are highly prevalent among individuals with serious mental illness and increased by antipsychotic medication. Although widely recommended, many obstacles prevent these patients from obtaining a proper screening for dysglycemia. Currently, glycated hemoglobin (HbA1c), fasting glucose, and 2-hour glucose levels from the oral glucose tolerance test are used for screening prediabetes and type 2 diabetes. The objective of this study was to investigate if HbA1c could be used as the only screening test among individuals with serious mental illness. Methods: Cross sectional study comparing the sensitivity of HbA1c, fasting glucose, and 2-h oral glucose tolerance test to detect dysglycemias in serious mental illness participants referred for metabolic complications. Results: A total of 84 participants (43 female; aged: 38.5±12.8 years; BMI: 35.0±6.8 kg/m²) was included. Regarding prediabetes, 44, 44 and 76% were identified by HbA1c, fasting glucose, and 2 h- oral glucose tolerance test respectively and for type 2 diabetes, 60, 53 and 66% were identified by HbA1c, fasting glucose and 2 h-oral glucose tolerance test. The overlap between the 3 markers was low (8% of participants for prediabetes and 26% for Type 2 diabetes). Sensitivity of HbA1c were moderate (range 40-62.5%), while its specificity was excellent (92-93%). Conclusion: The present study indicates a low agreement between HbA1c, fasting glucose and 2-h oral glucose tolerance test. It appears that these markers do not identify the same participants. Thus, HbA1c may not be used alone to detect all glucose abnormalities among individuals with serious mental illness.

Platelet-activating factor acetylhydrolase in human seminal plasma.

OBJECTIVE: To search for the presence of platelet-activating factor (PAF) acetylhydrolase activity in human seminal plasma. DESIGN: Experimental. SETTING: Reproductive laboratory in a university-affiliated hospital research center. PARTICIPANTS: Human male volunteers were selected on the basis of apparent normal health. RESULTS: Human seminal plasma contained significant levels of PAF-acetylhydrolase activity. Enzymatic hydrolysis of PAF displayed typical kinetics and was a calcium-independent process. Platelet-activating factor acetylhydrolase in seminal plasma was associated with a very high-density lipoprotein fraction. Enzymatic activity was independent of sperm count and motility. CONCLUSION: Human seminal plasma contains significant levels of PAF acetylhydrolase. This enzyme may be an important factor in the regulation of PAF concentration and activity.

Production and induction of beta-lactamase during growth of Pseudomonas aeruginosa in biological fluids.

beta-Lactamase production in biological fluids was evaluated by using an antibiotic-resistant Pseudomonas aeruginosa strain. Enzyme production was low in plasma or ascitic fluid and high in urine. Induction of beta-lactamase by imipenem was studied by using an inducible P. aeruginosa strain. Induction was lower in biological fluids than in Mueller-Hinton broth.

Selection of resistance by piperacillin during Pseudomonas aeruginosa endocarditis.

The mechanisms responsible for emergence of resistance during antimicrobial therapy were investigated in isolates obtained from a patient suffering from Pseudomonas aeruginosa endocarditis. The strain was first isolated from blood cultures obtained upon admission of the patient. It was sensitive to piperacillin, ticarcillin and tobramycin. Piperacillin-tobramycin therapy was therefore instituted and led to a rapid improvement of the patient's condition. Unfortunately, the patient subsequently became febrile again and blood cultures continued to yield P. aeruginosa. However, the organism isolated was now resistant to piperacillin and other penicillins tested. Cell-free extracts of the pre- and post-therapy isolates were analyzed for their beta-lactamase activity. The susceptible pre-therapy strain did not produce significant levels of beta-lactamase. In contrast, the post-therapy strain produced high levels of the enzyme. Induction experiments indicated that the production of beta-lactamase was constitutive in the post-therapy isolate. Thus, piperacillin therapy has led to the selection of resistant mutants which produced high levels of beta-lactamase constitutively. This was associated with relapse of the infection and therapeutic failure.

Iron metabolism during infection and neoplasia.

Invasion of the vertebrate host by microorganisms or neoplastic cells triggers a variety of metabolic responses. One of them, the hypoferremic response, is the decrease in serum iron levels. This hypoferremia is observed not only during infections of various etiologies and neoplasia but also during trauma, myocardial infarction, surgery, and inflammation. The hypoferremic response thus appears to be a consistent and predictable biochemical response to pathogenesis. Hypoferremia has been shown to be of great protective value to the host against infection and neoplasia. Suppression of the iron-withholding ability of the host by excess iron is associated with a greater incidence and severity of infection and neoplasia. The potential therapeutic applications of the hypoferremic response are discussed.

Isolation and purification of canadaphore, a siderophore produced by Helminthosporium carbonum.

A new siderophore was isolated and purified from the spent growth medium of the fungus Helminthosporium carbonum by solvent extraction and reverse phase high pressure liquid chromatography. This new molecule has been assigned the name Canadaphore. Canadaphore was detected in culture filtrates after 15 days of growth and production was maximal after growth of H. carbonum to maximal stationary phase in modified Fries basal medium. Production of Canadaphore was completely suppressed when the organism was grown in medium supplemented with iron. Mass spectral analysis yielded a molecular mass of 680 Daltons for the iron-Canadaphore complex and 627 Daltons for the iron-free molecule. Spectroscopic analysis indicates that Canadaphore is a siderophore of the hydroxamate type.

Ceruloplasmin and regulation of transferrin iron during Neisseria meningitidis infection in mice.

The role of ceruloplasmin (ferroxidase I; EC 1.16.3.1) in iron metabolism during experimental Neisseria meningitidis infection was investigated. Plasma ceruloplasmin activity was found to increase greatly in mice during the convalescence phase of iron-controlled infection and after a plasma hypoferremia had occurred. Ceruloplasmin activity-deficient animals became hypoferremic as a result of an impaired release of iron from the reticuloendothelial system as shown by impaired return of reticuloendothelial system-processed heme iron in these mice. Hypoferremia in ceruloplasmin activity-deficient mice was associated with an increased resistance to N. meningitidis infection, an effect reversed readily by ceruloplasmin supplementation or iron addition. This evidence implicated ceruloplasmin activity as an important component in the regulation of the plasma transferrin iron pool and suggested that an important role of additional ceruloplasmin as an acute-phase protein might be related to the requirement of additional transferrin iron. This study also provided further evidence of the importance of transferrin iron and host hypoferremia in bacterial infection.

Mechanism of impaired iron release by the reticuloendothelial system during the hypoferremic phase of experimental Neisseria meningitidis infection in mice.

Hypoferremia, the reduction of plasma transferrin iron levels during infection, has been shown to control Neisseria meningitidis infection in mice. The exact nature of the mechanism that regulates this response has been obscure. We have previously shown that hypoferremia does not result from an accelerated removal of iron from the plasma transferrin pool. In this study, we have examined the processing of iron by the reticuloendothelial system during infection. Normal and hypoferremic meningococcus-infected mice were injected with 59Fe-labeled erythrocytes. Kinetics of uptake and redistribution of the label indicated that during the hypoferremic phase of the infection, reticuloendothelial system-processed iron was not returned to the plasma transferrin pool. Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of heme-derived iron into the intracellular ferritin pool during the hypoferremic phase of the infection. These findings indicate that this withholding of iron within the intracellular pool leads to hypoferremia and therefore denies the extracellular pathogen its essential iron.

Turnover in the transferrin iron pool during the hypoferremic phase of experimental Neisseria meningitidis infection in mice.

Mouse transferrin was used to specifically label the plasma transferrin iron pool for studies of iron kinetics in normal mice and infected mice during the hypoferremic phase of experimental meningococcal infection. The plasma transferrin iron pool of normal mice was found to be very dynamic, with a half-life of iron in the pool of 0.7 h. Iron left the plasma pool, entered the bone marrow, and was released into the blood in erythrocytes. Iron from the transferrin pool also entered the liver and spleen and was presumably in the reticuloendothelial system components of these organs. Most of the iron that had been supplied as transferrin iron was found in erythrocytes by 48 h after injection. Studies with mice infected with Neisseria meningitidis strain M1011 revealed similar kinetics for transferrin iron. There was no redistribution of iron within the various iron pools as a result of infection. Iron turnover in the plasma transferrin pool during the hypoferremic phase was similar to control rates, and iron leaving the pool entered its normal erythroid compartments. The lack of accelerated turnover of plasma iron and the finding that plasma iron was not rerouted to storage compartments during the hypoferremic phase provided good evidence that lactoferrin and leukocytic endogenous mediator were not directly involved in redirecting transferrin iron. Our evidence has implicated an impaired return of reticuloendothelial system-processed iron to the transferrin pool during the hypoferremic response. This appears to be a logical point in the erythroid iron cycle for host-mediated iron sequestration, as the reticuloendothelial system is involved in iron storage and may regulate iron levels in the plasma transferrin pool under normal conditions.

A sensitive and convenient assay procedure for transferrin and its application to the purification of mouse transferrin.

A sensitive procedure employing 55Fe binding was developed for the assay of transferrin. This procedure took advantage of the pH dependence and reversibility of iron binding by transferrin and was applicable to both human and mouse transferrins. Excess iron, after saturation of the transferrin iron-binding sites with 55Fe, supplied as Fe-citrate, was efficiently removed by its binding to Amberlite CG-400 anion-exchange resin. Mouse transferrin was purified from plasma using a combination of ammonium sulphate fractionation and ion-exchange chromatography. Two peaks of pure transferrin were obtained by DEAE-Sepharose chromatography. Mouse transferrin was found to have a molecular weight of 80 000.