Annunziata Lapolla

Preeclampsia in Lean Normotensive Normotolerant Pregnant Women Can Be Predicted by Simple Insulin Sensitivity Indexes

Certain similarities between preeclampsia and insulin resistance syndrome suggest a possible link between the 2 diseases. The aim of our study was to evaluate 3 insulin sensitivity (IS) indexes (fasting homeostasis model assessment IS [ISHOMA], quantitative insulin sensitivity check index [ISQUICKI], and oral glucose IS [OGIS]) early and late in pregnancy in a large number of normotensive pregnant women with a normal glucose tolerance and to test the ability of these indexes to predict the risk of subsequent preeclampsia. In all, 829 pregnant women were tested with a 75-g, 2-hour oral glucose load in 2 periods of pregnancy: early (16 to 20 weeks) and late (26 to 30 weeks). In early and late pregnancy, respectively, ISHOMA was 1.23±0.05 and 1.44±0.05 (P<0.01), ISQUICKI was 0.40±0.002 and 0.38±0.002 (P<0.01), and OGIS was 457±2.4 mL min−1 m−2 and 445±2.2 (P<0.001), all confirming the reduction in insulin sensitivity during pregnancy. Preeclampsia developed in 6.4% of the pregnant women and correlated positively with the 75th centile of ISHOMA (P=0.001), with a sensitivity of 79% in the early and 83% in the late period and a specificity of 97% in both. ISQUICKI <25th centile was also related with preeclampsia (P=0.001), with a sensitivity of 85% in the early and 88% in the late period and a specificity of 97% in both. Judging from our findings, ISHOMA and ISQUICKI are simple tests that can pinpoint impaired insulin sensitivity early in the pregnancy. Given their high sensitivity and specificity, these indexes could be useful in predicting the development of preeclampsia in early pregnancy, before the disease become clinically evident.

New International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosing gestational diabetes compared with former criteria: a retrospective study on pregnancy outcome.

Diabet. Med. 28, 1074–1077 (2011)

Clinical and socio-economic correlates of quality of life and treatment satisfaction in patients with type 2 diabetes

BACKGROUND AND AIM The aim of the present study was to assess health-related quality of life (HRQOL) and treatment satisfaction in a large, ambulatory based sample of patients with type 2 diabetes. In particular, we evaluated a large array of socio-economic, clinical, and management-related factors, to investigate the extent to which they correlate with physical and psychological well-being, and with treatment satisfaction. METHODS AND RESULTS Patients were requested to fill in a questionnaire including the SF-36 Health Survey (SF-36), the WHO-Well Being Questionnaire (WBQ), and the WHO-Diabetes Treatment Satisfaction Questionnaire (DTSQ). The analyses were based on multivariate analyses, adjusted for patient clinical and socio-demographic characteristics. The study involved 2499 patients, enrolled in 203 diabetes outpatient clinics. Female gender and diabetes complications were associated with worse physical and psychological well-being, while socioeconomic variables were mainly related to general well-being. The perceived frequency of hyperglycemic episodes was negatively associated with all the dimensions explored. Treatment satisfaction was inversely related to female gender, insulin treatment, perceived frequency of hyperglycemic episodes and diabetes complications. Blood glucose self-monitoring, and among patients treated with insulin, self-management of insulin doses and the use of pen for insulin injections, were associated with higher levels of satisfaction. Finally, higher levels of satisfaction were associated with a better perception of physical and psychological well-being. CONCLUSIONS Health related quality of life and treatment satisfaction are associated with each other and are both affected by a complex interplay between clinical and socio-economic variables. Some negative aspects, mainly associated with insulin treatment and poor perceived metabolic control, can be attenuated by a deeper involvement of the patients in the management of the disease.

Analysis of outcome of pregnancy in type 1 diabetics treated with insulin pump or conventional insulin therapy

Abstract.We evaluated the outcome of pregnancies followed between 1990 and 2000 in 93 women with type 1 diabetes, treated with conventional intensive insulin therapy (n=68) or continuous subcutaneous insulin infusion (n=25). We evaluated metabolic control (fasting and 1-hour post-prandial plasma glucose and HbA1c levels), spontaneous or induced abortions, time and mode of delivery, maternal outcome (pregnancy-induced hypertension, preeclampsia, placental insufficiency, hydramnios, hypoglycemic coma, ketoacidosis) and fetal outcome (weight, hypoglycemia, hypocalcemia, hyperbilirubinemia, fetal distress, asphyxia, hyaline membrane disease, polycythemia, shoulder dystocia, malformations). Patients treated with insulin pump more frequently had background retinopathy and clinical neuropathy. No significant differences were observed between the two groups in metabolic control and maternal outcome. Glycemic control, non-optimal in the prepregnancy state, improved significantly during pregnancy, as shown by the progressive reduction in HbA1c levels. As regards fetal outcome, no differences were observed between the two groups in morbidity and especially in malformation rate. Patients with malformed babies did not have optimal metabolic control at conception. Thus, maternal and perinatal outcomes were comparable in patients treated with insulin pump and continuous subcutaneous insulin therapy, and depended on metabolic control. In patients in higher White’s class and with more unstable glycemia, we achieved metabolic control and outcomes comparable with those of women of lower White’s class and more stable glycemic values using the insulin pump. Our data suggest that insulin pump therapy is useful in problematic, complicated cases of women who want a baby.

Matrix-assisted laser desorption/ionization mass spectrometry, enzymatic digestion, and molecular modeling in the study of nonenzymatic glycation of IgG

The glycation-induced functional change of immunoglobulins is of particular interest. The glycation levels of IgG in 10 healthy subjects and 20 diabetic patients with different degrees of metabolic control were studied by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. It reveals the number of glucose molecules that have condensed on the protein, which range from 1 to 5 for healthy subjects, from 5 to 9 for well controlled diabetic patients, and from 10 to 25 for poorly controlled ones. The identification of the most favored glycation sites has been obtained by MALDI analysis of standard and in vitro glycated IgG and plasma protein fraction of a healthy subject after digestion with papain, releasing Fab and Fc fragments of the molecule. Both experiments, as well as molecular modeling of the whole protein, confirm that the most of glucose molecules have condensed on the Fab fragment of IgG, suggesting that the immune deficiency observed in diabetic patients may be explained at the molecular level by a more effective glycation of the Fab fragment, thus inhibiting the process of molecular recognition between antibody and antigen.

Effect of Ethanol, Acetaldehyde, and Acetate on Insulin and Glucagon Secretion in the Perfused Rat Pancreas

The effects of varying concentrations of ethanol (1,10, and 30 mM) and its metabolites (1 mM acetate and 1 and 10 mM acetaldehyde) on insulin and glucagon secretion induced by glucose (11.1 mM) and arginine (20 mM) were studied in isolated perfused pancreas of Sprague-Dawley rats Ethanol and its metabolites did not significantly modify basal secretion of the two hormones. Ethanol reduced glucose-induced insulin secretion by means of a dose-related effect. Arginine-induced insulin output did not seem to be influenced to any significant degree. Acetate and acetaldehyde significantly inhibited glucose and arginine-induced insulin secretion. While ethanol (10 and 30 mM) did not modify glucagon output during arginine perfusion, acetate and acetaldehyde markedly enhanced it. The block of insulin secretion and the increased secretion of glucagon could explain the diabetogenic effect of ethanol demonstrated in vivo. The mechanism by which ethanol acts on the pancreatic β- and α-cells is discussed.

The effect of telemedicine on outcome and quality of life in pregnant women with diabetes

We evaluated the effect of a telemedicine system on maternal and fetal outcome in women with diabetes. A total of 276 pregnant women were enrolled in the study. Women were sequentially assigned to a telemedicine or a control group. There were 88 women with gestational diabetes in the telemedicine group and 115 in the control group; there were 17 women with type 1 diabetes in the telemedicine group and 15 in the control group. Women in telemedicine groups were asked to submit their blood glucose data every week, and had a medical examination at the diabetes clinic once a month. Women in the control groups had a medical examination every two weeks. Subjective outcomes were investigated using the following questionnaires: CES-D for depression, SF-36 for health-related quality of life (QoL), Stress and Distress for the impact of diabetes. Clinical variables and pregnancy outcomes were no different between the two telemedicine groups, whereas women with gestational diabetes in the telemedicine group had a better metabolic control in the 3rd trimester and a lower rate of caesarean sections and macrosomia. As for QoL, women in the telemedicine groups showed lower levels of frustration and concerns about their diabetes, and a better acceptance of their diabetic condition. A questionnaire on the use of the telemedicine system showed a high degree of acceptance (85%). Both telemedicine groups had fewer check-ups at the diabetes clinics. The use of a telemedicine system for glucose monitoring improved pregnancy outcome in women with gestational diabetes and improved QoL in all diabetic pregnancies.

DALI: Vitamin D and lifestyle intervention for gestational diabetes mellitus (GDM) prevention: an European multicentre, randomised trial - study protocol

BackgroundGestational diabetes mellitus (GDM) is an increasing problem world-wide. Lifestyle interventions and/or vitamin D supplementation might help prevent GDM in some women.Methods/designPregnant women at risk of GDM (BMI≥29 (kg/m2)) from 9 European countries will be invited to participate and consent obtained before 19+6 weeks of gestation. After giving informed consent, women without GDM will be included (based on IADPSG criteria: fasting glucose<5.1mmol; 1 hour glucose <10.0 mmol; 2 hour glucose <8.5 mmol) and randomized to one of the 8 intervention arms using a 2×(2×2) factorial design: (1) healthy eating (HE), 2) physical activity (PA), 3) HE+PA, 4) control, 5) HE+PA+vitamin D, 6) HE+PA+placebo, 7) vitamin D alone, 8) placebo alone), pre-stratified for each site. In total, 880 women will be included with 110 women allocated to each arm. Between entry and 35 weeks of gestation, women allocated to a lifestyle intervention will receive 5 face-to-face, and 4 telephone coaching sessions, based on the principles of motivational interviewing. The lifestyle intervention includes a discussion about the risks of GDM, a weight gain target <5kg and either 7 healthy eating ‘messages’ and/or 5 physical activity ‘messages’ depending on randomization. Fidelity is monitored by the use of a personal digital assistance (PDA) system. Participants randomized to the vitamin D intervention receive either 1600 IU vitamin D or placebo for daily intake until delivery. Data is collected at baseline measurement, at 24–28 weeks, 35–37 weeks of gestation and after delivery. Primary outcome measures are gestational weight gain, fasting glucose and insulin sensitivity, with a range of obstetric secondary outcome measures including birth weight.DiscussionDALI is a unique Europe-wide randomised controlled trial, which will gain insight into preventive measures against the development of GDM in overweight and obese women.Trial registrationISRCTN70595832

The redox enzyme p66Shc contributes to diabetes and ischemia-induced delay in cutaneous wound healing

OBJECTIVE The redox enzyme p66Shc produces hydrogen peroxide and triggers proapoptotic signals. Genetic deletion of p66Shc prolongs life span and protects against oxidative stress. In the present study, we evaluated the role of p66Shc in an animal model of diabetic wound healing. RESEARCH DESIGN AND METHODS Skin wounds were created in wild-type (WT) and p66Shc−/− control and streptozotocin-induced diabetic mice with or without hind limb ischemia. Wounds were assessed for collagen content, thickness and vascularity of granulation tissue, apoptosis, reepithelialization, and expression of c-myc and β-catenin. Response to hind limb ischemia was also evaluated. RESULTS Diabetes delayed wound healing in WT mice with reduced granulation tissue thickness and vascularity, increased apoptosis, epithelial expression of c-myc, and nuclear localization of β-catenin. These nonhealing features were worsened by hind limb ischemia. Diabetes induced p66Shc expression and activation; wound healing was significantly faster in p66Shc−/− than in WT diabetic mice, with or without hind limb ischemia, at 1 and 3 months of diabetes duration and in both SV129 and C57BL/6 genetic backgrounds. Deletion of p66Shc reversed nonhealing features, with increased collagen content and granulation tissue thickness, and reduced apoptosis and expression of c-myc and β-catenin. p66Shc deletion improved response to hind limb ischemia in diabetic mice in terms of tissue damage, capillary density, and perfusion. Migration of p66Shc−/− dermal fibroblasts in vitro was significantly faster than WT fibroblasts under both high glucose and hypoxia. CONCLUSIONS p66Shc is involved in the delayed wound-healing process in the setting of diabetes and ischemia. Thus, p66Shc may represent a potential therapeutic target against this disabling diabetes complication.

Evaluation of diagnostic reliability of DCA 2000 for rapid and simple monitoring of HbA1c

Abstract The monitoring of diabetic patients by evaluating glycated protein levels is now widely accepted and performed. The microchromatographic version of the high performance liquid chromatography method is the technique most frequently used in clinical practice. The DCA 200 instrument (Bayer Diagnostics, Milan, Italy), based on an immunochemical technique, has been proposed for the rapid and simple evaluation of HbA1c, using even capillary blood. We evaluated 171 subjects including 22 healthy volunteers, 78 type 2 diabetic patients with different degrees of metabolic control, 11 women affected by gestational diabetes mellitus (GDM), 6 patients with hyperlipemia, 38 patients with chromic renal failure, 13 diabetic patients with chronic renal failure, and 3 patients with hemoglobinopathies. The DCA 2000 model was compared with the Diamat HPLC system. Data from within-run imprecision studies showed excellent precision, for both DCA 2000 and the HPLC system. The correlation between the two different systems, as shown by other statistical evaluations, was good (y = 0.911x + 0.462, r = 0.923). Results from the control group and diabetic patients were used to compare the two methods. Values obtained using the DCA 2000 were significantly lower (p < 0.0001) than those obtained with the HPLC system, in both healthy subjects and diabetic patients. To detect possible interferences, selected samples were analyzed from patients with hyperlipemia, diabetes and chronic renal failure, and hemoglobinopathies. While in the case of hyperlipemia, an acceptable correlation coefficient between the two systems was confirmed (y = 1.047x − 1.236, r = 0.876), in the case of chronic renal failure the correlation turned out to be very low (y = 0.254x + 3.456, r = 0.203). Our results indicate that the DCA 2000 gives accurate and reliable results in the clinical field of interest.