Diabetes and Pancreas: Why So Difficult? Potential Mechanisms of Elevated Serum Pancreatic Enzymes.

Diabetes mellitus has been associated with a higher risk of exocrine pancreas disorders despite inconsistencies among studies, presumably due to the presence of several (often unmeasured) confounding factors. As a direct consequence of this uncertainty, the relationship between anti-diabetic therapies and pancreatic adverse reactions is difficult to evaluate and remains far from being clarified. Indeed, the on going debate on the safety of incretin-based therapies does not lie in any definite conclusion. Serum level of amylases and lipase reflects the balance between production from different tissues and clearance, but it may be also influenced by numerous molecular, cellular, and systems mechanisms. The present review tries to provide an overview of potential biochemical pathways that may underlie pancreatic hyperenzymemia in health and diabetes mellitus.

Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery.

Insulin is a life-saving medication for people with type 1 diabetes, but traditional insulin replacement therapy is based on multiple daily subcutaneous injections or continuous subcutaneous pump-regulated infusion. Nonphysiologic delivery of subcutaneous insulin implies a rapid and sustained increase in systemic insulin levels due to the loss of concentration gradient between portal and systemic circulations. In fact, the liver degrades about half of the endogenous insulin secreted by the pancreas into the venous portal system. The reverse insulin distribution has short- and long-term effects on glucose metabolism. Thus, researchers have explored less-invasive administration routes based on innovative pharmaceutical formulations, which preserve hormone stability and ensure the therapeutic effectiveness. This review examines some of the recent proposals from clinical and material chemistry point of view, giving particular attention to patients' (and diabetologists') ideal requirements that organic chemistry could meet.

Improving CardioCheck PA analytical performance: three-year study.

BACKGROUND: Cardiovascular prevention requires a diagnostic approach for population-based screening programmes aimed at early identification of modifiable risk factors. Dyslipidaemia, which is a major risk factor for cardiovascular disease, remains largely undiagnosed and undertreated. Point-of-care testing (POCT) provides immediate results for clinical decision-making, however, quality assessment is essential to ensure system performance requirements. CardioChek PA (CCPA), a portable whole blood analyser for rapid lipid measurement, has been on the market since 2002 but with limited evidence of performance levels. The aim of the study was to assess analytical performance issues of the device and possibly contribute to their solution. METHODS: Over a 3-year period, we repeatedly evaluated CCPA accuracy, precision, and discrepancies between instruments and between test strip lots by comparison with laboratory method. At our initial evaluation, the CCPA analyser underestimated total cholesterol (bias 6.5%) and gave within-assay CVs above 6% for all lipid fractions. Our results solicited sequential improvements to the CCPA system by the manufacturer up to the performance level certified by the Cholesterol Reference Method Laboratory Network in 2013: total error 1.3% for total cholesterol and 3.1% for high density lipoprotein (HDL) cholesterol. CONCLUSIONS: POCT diagnostic tests need continuous quality management, including both quality control and quality assurance, to monitor the analytical process. A 3-year external quality surveillance provided information useful in improving POCT performance. As a result, the device is now adequate for use in screening programmes aimed at early detection of lipid disorders.

Malnutrition, anorexia and cachexia in cancer patients: A mini-review on pathogenesis and treatment.

Malnutrition, anorexia and cachexia are a common finding in cancer patients. They become more evident with tumor growth and spread. However, the mechanisms by which they are sustained often arise early in the history of cancer. For malnutrition, these mechanisms can involve primary tumor or damage by specific treatment such as anticancer therapies (surgery, chemotherapy, radiotherapy) also in cancers that usually are not directly responsible for nutritional and metabolic status alterations (i.e. bone tumors). For anorexia, meal-related neural or hormonal signals and humoral signals related to body fat or energy storage and the interaction of these signals with the hypothalamus or the hypothalamic inappropriate response play a pathogenetic role. Some cytokines are probably involved in these mechanisms. For cachexia, the production of proinflammatory cytokines by tumour cells is the initial mechanism; the main biochemical mechanisms involved include the ubiquitine proteasome-dependent proteolysis and heat shock proteins. Treatment includes pharmaceutical and nutritional interventions.

Sitagliptin as add-on therapy in insulin deficiency: biomarkers of therapeutic efficacy respond differently in type 1 and type 2 diabetes.

BACKGROUND: Sitagliptin has been proven to be effective and safe as add-on to insulin in adult patients with type 2 diabetes and absolute insulin deficiency. Recently, it has been suggested to extend the use of dipeptidyl-peptidase-4 inhibitors to type 1 diabetes. The aim of this study was to evaluate and compare the effects of a long-term, fixed-dose combination of sitagliptin and metformin as add-on to insulin on body mass index, fasting plasma glucose, fructosamine, HbA(1c), lipids, and daily dose of insulin in both type 1 diabetes and insulin-treated type 2 diabetes. METHODS: We recruited 25 patients with type 1 diabetes (mean age 51 ± 10 years, mean disease duration 26 ± 13 years) and 31 insulin-treated type 2 diabetic patients (mean age 66 ± 8 years, mean disease duration 19 ± 9 years), who received sitagliptin with metformin as a fixed-dose combination (50/1000 mg once or twice daily) or sitagliptin (100 mg once daily, if intolerant to metformin) in addition to ongoing insulin therapy for 46 ± 19 weeks and 56 ± 14 weeks, respectively. RESULTS: After 21 ± 9 weeks, patients with type 1 diabetes had a significantly lower body mass index, fasting plasma glucose, fructosamine, HbA(1c), and daily insulin requirement. After 49 ± 17 weeks, they maintained their weight loss and total daily insulin dose and showed a significant reduction in low-density lipoprotein cholesterol levels, whereas their HbA(1c) had returned to baseline values. In patients with type 2 diabetes, long-term treatment remained weight-neutral but had persistent beneficial effects on short-term, intermediate-term, and long-term biomarkers of metabolic control, as well as on low-density lipoprotein cholesterol levels and insulin requirement. CONCLUSION: Clinical outcomes differed according to type of diabetes in terms of quality and over time. In type 2 diabetes, the combination therapy significantly improved metabolic control and the lipid profile, and decreased insulin requirements, even in the absence of clinically significant weight loss. In type 1 diabetes, the combined therapy only temporarily improved metabolic control, but significantly decreased body weight, low-density lipoprotein cholesterol levels, and insulin requirements.

Study of skin vasomotion in type 1 diabetic patients and of its possible relationship with clinical and laboratory variables.

Vascular oscillation (vasomotion) occurs in the microcirculation and is thought to be a significant contributor to tissue perfusion. Our aim was to assess skin vasomotion (SV) of type 1 diabetic patients (T1D-pts) and its relationship with clinical or laboratory variables of the studied T1D-pts. Forearm endothelial-, sympathetic- and myogenic-dependent SV were assessed basally and after 3 min of forearm ischemia in 40 T1D-pts and 50 healthy controls, by spectral analysis of laser-Doppler (LD) signal at the frequency ranges of 0.009-0.02 Hz, 0.021-0.06 Hz and 0.061-0.2 Hz, respectively. Post-ischemic per cent increase (PI%-increase) in power spectral density (PSD) of skin endothelial- and sympathetic-dependent VS was significantly reduced in T1D-pts compared to controls (p < 0.0005, p < 0.0001, respectively). Linear regression analysis showed a significant positive relationship between PI%-increase of endothelial-dependent SV and heart rate variation during laying-standing test (R = 0.65, p = 0.00001), and a negative relationship between PI%-increase in PSD of skin LD signal 0.009-1.6 Hz spectrum and glycated haemoglobin serum levels (R = 0.44, p = 0.0036) in T1D-pts. These results are consistent with reduced skin endothelial- and sympathetic-dependent stimulated SV and with relationships between some clinical or laboratory variables and SV parameters in the T1D-pts studied.

Peripheral microvascular dysfunction as an independent predictor of atherosclerotic damage in type 1 diabetes patients: a preliminary study.

It has been recently hypothesized that peripheral microvascular dysfunction may contribute to atherosclerotic damage (AD) in diabetic patients. In order to test this hypothesis, we assessed forearm skin post-occlusive reactive hyperaemia (skin-PORH), an index of peripheral microvascular function, using laser-Doppler flowmetry, in 40 type 1 diabetes patients (T1D-pts), aged 49 ± 11 years, with no known cardiovascular complications, and in 50 age and sex-matched healthy control subjects (CS). T1D-pts also underwent carotid arteries ultrasound scanning (Ca-US) and ankle-brachial index (ABI) measurement. An arbitrary index of AD (AD-index), ranging from "0" (normal ABI, normal Ca-US) to "3" (abnormal ABI, one or more plaques at the Ca-US), was determined in T1D-pts. Linear and multiple regression analyses were performed to identify independent predictors of AD in T1D-pts. T1D-pts had a lower skin-PORH compared with CS (p = 0.015). In T1D-pts AD-index resulted to be negatively related with skin-PORH (R = 0.44; p < 0.005) or deep-breathing test (DBT) (R = 0.53; p < 0.0005), and positively related with systolic arterial pressure (R = 0.31; p < 0.05), microalbuminuria (R = 0.46; p < 0.005), patients' age (R = 0.51; p < 0.001) and diabetes duration (R = 0.39; p < 0.05). At the multiple regression analysis skin-PORH (R = 0.36; p < 0.005), patients' age R = 0.24; p < 0.05) and DBT (R = 0.4 - p < 0.005) resulted to be independent predictors of AD-index in T1D-pts. These preliminary findings support the hypothesis that peripheral microvascular dysfunction may contribute to AD in T1D-pts.

Differences in circadian time structure of diastolic blood pressure between diabetes mellitus and essential hypertension.

BACKGROUND: Abnormal circadian blood pressure patterns have been associated with cardiovascular disease in diabetes mellitus. We have described that the acrophase of diastolic blood pressure (DBP) registered in type 1 diabetes (T1D) patients was significantly earlier than normal and DBP ecphasia was more pronounced in patients with lower heart rate variability during deep breathing. The aim of this study was to compare the circadian rhythm characteristics of BP among different groups: normotensive (NT) control subjects, patients affected by T1D and type 2 diabetes (T2D), and patients with essential hypertension (HT). FINDINGS: We retrospectively evaluated ambulatory blood pressure monitoring records in 30 NT, 20 T1D, 20 T2D, 20 HT whose fasting plasma glucose and HbA1c were contemporaneously measured. The four groups were well-matched regarding age, gender, and BMI.Systolic blood pressure (SBP) and DBP midline-estimating statistic of rhythm were higher in T1D, T2D, and HT groups. DBP ecphasia was present only in the diabetic individuals: the acrophase of DBP occurred four hours earlier than normal in T1D group, whereas two hours earlier in T2D group. In a multiple regression analysis, only HbA1c and SBP acrophase were statistically significant correlates of DBP acrophase. CONCLUSIONS: People with diabetes mellitus, both type 1 and type 2, have their circadian acrophase of DBP occurring 2-4 hours earlier than normotensive and hypertensive subjects. Altered circadian timing of DBP, potential trigger of cardiovascular events, seems to be a distinguishing feature of diabetes mellitus and correlates with the previous 2-3 months of glycaemic control.

Circadian rhythm of blood pressure in diabetes mellitus: evidence, mechanisms and implications.

Circadian misalignment has been implicated in the development of diabetes mellitus and cardiovascular disease. Circadian rhythms of blood pressure (BP) and heart rate (HR) have long been known and the mechanisms controlling them have been actively investigated in physiology and disease. In this respect, the introduction of 24-hour ambulatory blood pressure monitoring (ABPM) has enabled a more accurate assessment of circadian BP patterns in order to solve diagnostic uncertainty or to establish dipper status. However, attention has been mainly focused on measures of extent (midline estimating statistic of rhythm, MESOR, and amplitude) rather than timing (acrophase) of changes within a cycle. The review summarises 1) evidence for altered characteristics of BP rhythm (in particular, phase shifts along the time axis) in animal and human diabetes mellitus, 2) the mechanisms that have been supposed to underlie the observed changes in cardiovascular function before diabetes onset and during progression of the disease, and 3) the adverse consequences that may result from an altered circadian BP rhythm.

Altered proportions of naïve, central memory and terminally differentiated central memory subsets among CD4+ and CD8 + T cells expressing CD26 in patients with type 1 diabetes.

Type 1 diabetes is an autoimmune process predominantly T-cell mediated. CD26 plays a role in T-cell costimulation, migration, memory development, thymic maturation and emigration patterns. In peripheral blood from 55 patients with type 1 diabetes and 20 healthy controls, CD4(+) and CD8(+) T cells expressing CD26 were differentiated into naïve (N, CD45RA(+)CCR7(+)), central memory (CM, CD45RA(-)CCR7(+)), effector memory (EM, CD45RA(-)CCR7(-)), and terminally differentiated effector memory (TEMRA, CD45RA(+)CCR7(-)). In type 1 diabetes, CD4(+) and CD8(+) T cells expressing CD26 showed a distinctive differentiation profile: percentages and absolute numbers of CM and N cells were reduced, whereas those of TEMRA cells were markedly increased. The indices of intermediate- and long-term glycaemic control were associated negatively with the number of CM and N cells while positively with the number of TEMRA cells. The considerable accumulation of TEMRA T cells in our patients suggests life-long stimulation by protracted antigen exposure (viruses, other agents or residual self-antigens?) or a homeostatic defect in the regulation/contraction of immune responses.

Exploring leukocyte mitochondrial membrane potential in type 1 diabetes families.

Proper cellular function requires the maintenance of mitochondrial membrane potential (MMP) sustained by the electron transport chain. Mitochondrial dysfunction is believed to play a role in the development of diabetes and diabetic complications possibly because of the active generation of free radicals. Since MMP can be investigated in clinical settings using fluorescent probes and living whole blood cells, mitochondrial membrane alterations have been observed in some chronic disorders. We have used the mitochondrial indicator 5,5',6,6'-tetra chloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) in conjunction with flow cytometry to measure the MMP in peripheral blood granulocytes from type 1 diabetes (T1D) families. The intracellular ROS levels and the respiratory burst activity were also measured. Leukocyte MMP was elevated in 20 T1D patients and their 20 non-diabetic siblings compared with 25 healthy subjects without family history of T1D. Fasting plasma glucose was the only correlate of MMP. If confirmed by further observations, the functional implications of mitochondrial hyperpolarisation (probably different among different cells) will require extensive investigation.

Thiol signalling network with an eye to diabetes.

Redox regulatory system controls normal cellular functions. Controlled changes in redox couples potential serve as components for signal transduction, similarly to the phosphorylation cascade. Cellular redox biology requires both compartimentalisation and communication of redox systems: the thermodynamic disequilibrium of the major redox switches allows rapid and sensitive responses to perturbations in redox environments. The many oxidation states of sulphur are found in numerous sulphur species with distinct functional groups (thiols, disulphides, polysulphides, sulphenic, sulphinic and sulphonic acids, etc.), which participate in a complicated network of sulphur-based redox events. Human diseases such as diabetes mellitus and its cardiovascular complications have been associated with increased production of reactive oxygen species and perturbations of thiol redox homeostasis. The review surveys literature related to some etiopathogenic aspects and therapeutic perspectives. The dual toxic-protective property of sulphydryl-donor molecules in experimental settings proposes the general problem of designing antioxidants for therapeutic use.

Circadian blood pressure variability in type 1 diabetes subjects and their nondiabetic siblings - influence of erythrocyte electron transfer.

BACKGROUND: Normotensive non-diabetic relatives of type 1 diabetes (T1D) patients have an abnormal blood pressure response to exercise testing that is associated with indices of metabolic syndrome and increased oxidative stress. The primary aim of this study was to investigate the circadian variability of blood pressure and the ambulatory arterial stiffness index (AASI) in healthy siblings of T1D patients vs healthy control subjects who had no first-degree relative with T1D. Secondary aims of the study were to explore the influence of both cardiovascular autonomic function and erythrocyte electron transfer activity as oxidative marker on the ambulatory blood pressure profile. METHODS: Twenty-four hour ambulatory blood pressure monitoring (ABPM) was undertaken in 25 controls, 20 T1D patients and 20 siblings. In addition to laboratory examination (including homeostasis model assessment of insulin sensitivity) and clinical testing of autonomic function, we measured the rate of oxidant-induced erythrocyte electron transfer to extracellular ferricyanide (RBC vfcy). RESULTS: Systolic blood pressure (SBP) midline-estimating statistic of rhythm and pulse pressure were higher in T1D patients and correlated positively with diabetes duration and RBC vfcy; autonomic dysfunction was associated with diastolic BP ecphasia and increased AASI. Siblings had higher BMI, lower insulin sensitivity, larger SBP amplitude, and higher AASI than controls. Daytime SBP was positively, independently associated with BMI and RBC vfcy. Among non-diabetic people, there was a significant correlation between AASI and fasting plasma glucose. CONCLUSIONS: Siblings of T1D patients exhibited a cluster of sub-clinical metabolic abnormalities associated with consensual perturbations in BP variability. Moreover, our findings support, in a clinical setting, the proposed role of transplasma membrane electron transport systems in vascular pathobiology.

Preserved endothelial-dependent and endothelial-independent skin vasodilator responses in relatives of type 1 diabetes patients.

Since increased plasma and cell levels of oxidative products have been found in non diabetic relatives of type 1 diabetic patients, we hypothesized the occurrence of an endothelial dysfunction in these subjects. To verify this hypothesis we investigated the skin blood flow responses to iontophoresis of both the endothelial-dependent vasodilator acetylcholine (ACh) and the endothelial-independent vasodilator sodium nitroprusside (SNP) in 31 non diabetic healthy relatives (DR) (14 siblings, 17 parents) of 17 type 1 diabetic patients. Twenty healthy control subjects (CS) without a family history of diabetes, matched for age (+/-5 years) and gender, were also investigated. DR and CS did not significantly differ either in basal skin blood flux (6.75+/-0.72 PU and 5.78+/-0.37 PU, respectively) or in skin vasodilator response to both ACh (728+/-53% and 711+/-44%, respectively) and SNP iontophoresis (758+/-71% and 731+/-64%, respectively). This finding is consistent with a preserved skin microvascular endothelial function in the studied subjects. However, since previous data suggest that both nitric oxide (NO) and prostacyclin released form the cutaneous vascular endothelium have an interchanging compensatory role in controlling the skin vasodilator response to ACh iontophoresis, our finding does not allow a defect in NO dependent skin vasodilatation to be excluded in the studied relatives of diabetic patients.

Proposal open for discussion: defining agreed diagnostic procedures in experimental diabetes research.

BACKGROUND: Animal experimentation has a long tradition in diabetes research and has provided invaluable benefits with regard to insulin discovery and treatment assessment. METHODS: The review focuses on chemical-induced diabetes in rats and surveys the protocols of diabetes induction, diabetes diagnosis, and glucose tolerance evaluation in a selection of recent research. RESULTS: This brief review of techniques in experimental diabetes highlights that there is no uniformity, whereas standardisation of procedures is desirable so that comparability will exist among experiments carried out in different settings. CONCLUSIONS: On this basis, questions are put and standards are proposed. It would be a platform to promote the exchange of ideas through expert consultation about practical issues related to animal research and a basis on which standards can be set according to user requirements and animal respect.

Erythrocyte transmembrane electron transfer in haemodialysis patients.

BACKGROUND AND AIMS: Patients with chronic renal failure, especially those treated with haemodialysis, have an increased risk of developing atherosclerotic vascular disease probably as a result of enhanced oxidative stress. The human cell membrane possesses electron transfer systems which protect against extracellular pro-oxidant challenge. We evaluated (1) the erythrocyte velocity of ferricyanide reduction (RBC vfcy) in 25 uraemic patients (aged 25-71 years; 14 males), (2) the changes induced by a single haemodialysis session and (3) biomarkers of oxidative stress. METHODS AND RESULTS: Before and after a mid-week dialysis session, we measured RBC vfcy, erythrocyte glutathione (RBC GSH), plasma and red cell membrane malondialdehyde (P and RBC MDA), plasma sulphydryl groups (P SH), plasma vitamin C levels and haemolysis percentage. Pre-dialysis RBC GSH (0.68+/-0.13 vs 0.80+/-0.13 mg/mL, p<0.01), P SH (266+/-74 vs 406+/-78 micromol/L, p<0.01) and plasma vitamin C (7.0+/-5.1 vs 21.5+/-8.5mg/L, p<0.001) were lower than in 25 age-sex-matched healthy controls; P MDA (1.57+/-0.52 vs 0.54+/-0.29 nmol/mL, p<0.001), RBC MDA (0.42+/-0.13 vs 0.34+/-0.16 nmol/mL, p<0.05) and haemolysis (1.2+/-0.3 vs 0.7+/-0.3%, p<0.001) were increased. Baseline RBC vfcy did not differ from normals (13.1+/-5.2 vs 12.9+/-3.2 mmol/mL/h). Following dialysis, RBC vfcy (to 8.9+/-4.5 mmol/mL/h, p<0.001) decreased, as well as P MDA, RBC MDA and plasma vitamin C (to 2.5+/-1.4 mg/L, p<0.001), whereas P SH groups increased (to 413+/-99 micromol/L, p<0.001); haemolysis percentage remained high. RBC vfcy values were correlated to RBC GSH and vitamin C levels. CONCLUSIONS: Uraemic patients showed signs of oxidative stress. Pre-dialysis RBC vfcy is maintained in the normal range on account of a reduced intracellular content of GSH and in spite of low plasma ascorbate. A single haemodialysis treatment reduced biomarkers of protein and lipid oxidation but markedly impaired transmembrane electron transfer, which could be explained by acute depletion of electron donors.

Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker?

Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na(+)/H(+) exchange and HC(3) (-)/Cl(-) anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs) are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments.So far the activity of erythrocyte PMORs in disease states has not been systematically investigated. This review summarizes present knowledge on erythrocyte electron transfer activity in humans (health, type 1 diabetes, diabetic nephropathy, and chronic uremia) and hypothesizes an integrated model of the functional organization of erythrocyte plasma membrane where electron pathways work in parallel with transport metabolons to maintain redox homeostasis.

Systolic blood pressure response to exercise in type 1 diabetes families compared with healthy control individuals.

OBJECTIVE: Oxidative stress is increased in type 1 diabetes families. Since oxidative damage is a mediator of vascular injury and familial predisposition to hypertension increases the risk of hypertension and diabetic nephropathy, we studied blood pressure responses to exercise and cardiovascular risk factors in type 1 diabetes families. METHODS: Thirty-five type 1 patients, 74 first-degree relatives, and 95 healthy individuals without established coronary heart disease underwent a cycle ergometer test. Examination included medical history, lifestyle questionnaire, body weight, blood pressure, and laboratory tests [fasting plasma glucose and insulin, haemoglobin A1c (HbA1c), plasma lipids, C-reactive protein, fibrinogen, folate, plasma thiols, and albumin excretion rate]. RESULTS: Diabetic patients had higher plasma glucose, HbA1c, folate, and albuminuria, while lower plasma thiols than controls; relatives differed from controls in higher plasma total cholesterol and albuminuria, lower plasma thiols. No patient presented exercised-induced angina. Diabetic patients achieved a higher maximal exercise systolic blood pressure (similar workload); systolic pressure remained high during recovery. Relatives showed higher values of systolic pressure at peak exercise (same workload). The following were associated with an abnormal blood pressure response to exercise: diastolic blood pressure and HbA1c in the control sample; disease duration and fibrinogen in the diabetic group; plasma low-density lipoprotein (LDL) cholesterol, body mass index (BMI), housework, and plasma thiols among relatives. CONCLUSION: An abnormal blood pressure response to exercise testing has been identified for the first time in asymptomatic normotensive non-diabetic relatives of type 1 diabetics, which was associated with indices of metabolic syndrome and oxidative damage. Moreover, in healthy normotensive non-diabetic control individuals (without a family history of type 1 diabetes), the systolic blood pressure response to exercise was significantly correlated with HbA1c levels.

Interatrial right-to-left shunt after lung surgery: diagnostic value of perfusion lung scanning.

A 61-year-old woman presented with platypnea and orthodeoxia after right pneumonectomy for lung cancer. A perfusion lung scan taken after tracer injection in the sitting position showed an extrapulmonary uptake of radioactivity consistent with a right-to-left shunt. Such extrapulmonary uptake was no longer evident when tracer was injected in supine posture. The authors emphasize the value of perfusion lung scanning in the assessment of patients with unexplained dyspnea after thoracic surgery.

Asymptomatic bacteriuria in women with diabetes: influence of metabolic control.

We screened 228 women with diabetes for bacteriuria during the period of January 1997 through December 2000 at Pisa General Hospital (Pisa, Italy). A control group of 146 women without diabetes was also evaluated. The frequency of significant bacteriuria was 17.5% (40 of 228) among women with diabetes and 18.5% (27 of 146) among women in the control group. Seven (13.5%) of 52 and 33 (18.8%) of 176 women with type 1 and in type 2 diabetes, respectively, had significant bacteriuria. The presence of higher glycated hemoglobin levels was the only significant risk factor for significant bacteriuria in women with type 2 diabetes. A similar frequency of bacteriuria in women with and women without diabetes was found. Severe impairment of metabolic control of type 2 diabetes increases the risk of acquiring asymptomatic bacteriuria.