Low-grade risk of hypercoagulable state in patients suffering from diabetes mellitus type 2.

OBJECTIVE: Diabetes, including type 1 and type 2, is associated with the hypercoagulable state. The aim of this study is to evaluate the concentration of selected hemostatic parameters and vascular endothelial growth factor-A (VEGF-A) in diabetic subjects. METHODS: The study was conducted in 62 patients with diabetes. Group I consisted of 27 patients having uncontrolled diabetes with microalbuminuria and Group II included 35 well-controlled diabetic patients. The control group was made up of 25 healthy volunteers. In the citrate plasma, the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombin-antithrombin (TAT) complexes, and D-dimer were assayed. Serum concentrations of VEGF-A, lipid profile, creatinine, and plasma fasting glucose were measured and in the versene plasma the concentration of HbA1c was determined. RESULTS: In the patients with uncontrolled diabetes, higher concentrations of TF, TFPI, and VEGF-A were observed, as compared with the well-controlled diabetics group and the control group. A significantly lower activity of antiplasmin was reported in patients from Group I as compared with the control group. In Group I, using the multivariate regression analysis, the glomerular filtration rate was independently associated with VEGF-A and dependently associated with total cholesterol. CONCLUSIONS: The study showed higher concentrations of TF and TFPI in the patients with uncontrolled diabetes with microalbuminuria, which is associated with rapid neutralization of the thrombin formation, since TFPI inhibits the complex of TF/VIIa/Ca(2+). The manifestation of the above suggestions is the correct TAT complexes and D-dimer, which indicates a low grade of prothrombotic risk in this group of patients, but a higher risk of vascular complications.

Effect of uncontrolled hyperglycemia on levels of adhesion molecules in patients with diabetes mellitus type 2.

OBJECTIVE: Uncontrolled diabetes has become a major cause of mortality and morbidity by reason of vascular angiopathy. The aim of this study was to evaluate the concentrations of soluble forms of vascular adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E-selectin, and thrombomodulin in patients with well-controlled and uncontrolled diabetes type 2. METHODS: The study was conducted on 62 patients with diabetes. Group I consisted of 35 patients with well-controlled diabetes. The second group included 27 patients with uncontrolled diabetes with micro-albuminuria. A control group was made up of 25 healthy volunteers. The concentrations of sVCAM-1, sICAM-1, sE-selectin, and soluble thrombomodulin were assayed in plasma. Serum concentration of creatinine was measured and the plasma concentrations of fasting glucose and glycated hemoglobin (HbA1c) determined. RESULTS: Lower concentrations of ICAM-1 were found in the group of uncontrolled diabetes patients compared with those with well-controlled disease. In patients with uncontrolled diabetes, VCAM-1 levels were significantly higher compared with the group with well-controlled diabetes. In patients with uncontrolled diabetes a positive correlation was obtained between glomerular filtration rate and sE-selectin and a negative correlation between the levels of creatinine and ICAM-1, although there was a positive correlation between (HbA1c) and ICAM-1. CONCLUSIONS: The study confirmed the participation of the inflammatory process associated with impaired vascular endothelial function in the pathogenesis of type 2 diabetes. The opposite effect of uncontrolled hyperglycemia on adhesion molecules suggests different functions of VCAM-1 and ICAM-1 in complications of diabetes.

The number of circulating endothelial progenitor cells in healthy individuals--effect of some anthropometric and environmental factors (a pilot study).

PURPOSE: The aim of the study was the evaluation of the number of circulating endothelial progenitor cells (CEPCs) in healthy people and the assessment of the variability of quantitative of CEPCs after 6 weeks. MATERIAL AND METHODS: The study involved 48 healthy individuals; the group consisted of 24 men and 24 women; the mean age of 34. The criterion for the patients' eligibility for the study was the absence of diabetes, thrombosis and cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Neither did the respondents take any medication that could clearly affect the value of the results. In the whole blood samples the number of circulating endothelial progenitor cells was determined using flow cytometry. During the analysis the fluorescence of 100,000 cells was measured. CEPCs were identified with immunophenotype CD45-, CD31+, CD34+, CD133+. RESULTS: In the study, the median of the number of circulating endothelial progenitor cells in the whole group was 0.41/µL. There was also recorded an increased number of CEPCs after 6 weeks, as compared to the baseline; the difference was significant. There were no differences in the number of CEPCs between the women and the men. There was found no effect on the number of CEPCs factors such as: smoking, physical activity and alcohol consumption. CONCLUSIONS: The study showed that in healthy individuals the gender had no essential effect on the number of endothelial progenitor cells. Based on the demographic and lifestyle data acquired, it is difficult to explain the increase number of CEPCs after 6 weeks.

Gestational diabetes mellitus worsens the profile of cardiometabolic risk markers and decrease indexes of beta-cell function independently of insulin resistance in nondiabetic women with a parental history of type 2 diabetes.

BACKGROUND: Women with a history of both parental type 2 diabetes (pt2DM) and previous gestational diabetes (pGDM) represent a group at high risk of cardiovascular events. We hypothesized that pGDM changes cardiometabolic risk markers levels as well as theirs associations with glucose indices in nondiabetic pt2DM women. METHODS: Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA-IR), beta-cell function, lipid levels, parameters of endothelial dysfunction, and inflammation were evaluated in 55 women with pt2DM, 40 with both pt2DM and pGDM 2-24 months postpartum, and 35 controls. RESULTS: Prediabetes was diagnosed more frequently in women with both pt2DM and pGDM in comparison with women with only pt2DM (10 versus 8, P = 0.04). The pGDM group had higher LDL-cholesterol, sICAM-1, tPa Ag, fibrinogen, and lower beta-cell function after adjustment for HOMA-IR, in comparison with pt2DM group. In pt2DM group postchallenge glucose correlated independently with hsCRP and in pGDM group fasting glucose with HOMA-IR. CONCLUSIONS: pGDM exerts a combined effect on cardiometabolic risk markers in women with pt2DM. In these women higher LDL-cholesterol, fibrinogen, sICAM-1, tPa Ag levels and decreased beta cell function are associated with pGDM independently of HOMA-IR index value. Fasting glucose is an important cardiometabolic risk marker and is independently associated with HOMA-IR.

A preliminary evaluation of VEGF-A, VEGFR1 and VEGFR2 in patients with well-controlled type 2 diabetes mellitus.

OBJECTIVE: Decompensated chronic hyperglycemia often leads to late microvascular complications such as retinopathy, diabetic foot syndrome, and diabetic kidney disease. The aim of this study was to determine the concentration of vascular endothelial growth factor A (VEGF-A) and its receptors in patients with well-controlled diabetes. METHODS: The study was conducted on 31 patients with well-controlled type 2 diabetes without micro- or macroangiopathy. Thirty healthy volunteers were enrolled in a control group. Serum concentrations of VEGF-A, VEGF receptors 1 and 2 (VEGFR1 and VEGFR2), fasting glucose, and lipid profiles were measured, and the plasma concentration of glycated hemoglobin (HbA1c) was determined. RESULTS: No significant differences were observed between the concentration of VEGF-A, VEGFR1 or VEGFR2 in the subject group and that in the control group. Positive correlations were noted between the levels of VEGF-A, VEGFR2, and triglyceride, and there was a negative correlation between the levels of VEGFR2 and high-density lipoprotein (HDL)-cholesterol in the study group. CONCLUSIONS: The concentrations of VEGF-A and its receptors 1 and 2 in patients with well-controlled diabetes are comparable to those of healthy individuals, which may indicate that appropriate control of glucose levels delays the occurrence of vascular complications. A negative correlation between VEGFR2 and HDL-cholesterol levels, and positive correlations between VEGF-A, VEGFR2, and triglyceride levels, suggest that lipid abnormalities occurring in diabetes may be involved in the modulation of angiogenesis.

Heterogeneity of cardiovascular risk factors profile in non-diabetic women 2-24 months post gestational diabetes mellitus.

Previously gestational diabetic (pGDM) women are characterized by high cardiovascular risk (CVR). The aim of this study was to assess the CVR markers levels in non-diabetic pGDM women in relation to time postpartum and to soluble E-selectin (sES) level. We investigated 125 women aged 18-40 years with a history of GDM between 2 and 24 months after their pregnancy. We evaluated age, body mass index (BMI), waist circumference, glucose levels during the oral glucose tolerance test (OGTT), levels of insulin and the parameters of endothelial dysfunction, fibrinolysis activity, low-grade systemic inflammation and lipid profiles. Prediabetes was identified in 38 women (30%), while in the remaining women OGTT results were normal. The tests performed >6 months revealed decreased hs-CRP (p = 0.01), sICAM-1 (p = 0.01), and elevated sES (p = 0.01) >12 months after adjustment for age, BMI, waist circumference and 2 h OGTT glucose. In the subgroup tested ≤12 months after an index pregnancy sES was independently associated with hs-CRP (p < 0.0001) and triglycerides (p = 0.0139). No association was found between sES and remaining parameters in women tested >12 months postpartum. We conclude that the period 2-24 months post GDM is heterogeneous with respect to the CVR markers. The plasma level of hs-CRP could be useful as an important cardiovascular risk marker up to 12 months postpartum in non-diabetic pGDM women.

The role of Hypoxia-inducible factor-1 α , glucose transporter-1, (GLUT-1) and carbon anhydrase IX in endometrial cancer patients.

Hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and carbon anhydrase IX (CAIX) are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients. Materials and Methods. 92 endometrial cancer patients, aged 37-84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections. Results. High significant differences (P = 0.0115) were reported between HIF-1α expression and the histologic subtype of cancer. Higher HIF-1α expression was associated with the higher risk of recurrence (P = 0.0434). The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features. Conclusion. The important role of HIF-1α in the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients.

Serum inhibin A and inhibin B levels in epithelial ovarian cancer patients.

THE AIM: of our study was to examine serum inhibin A and inhibin B concentrations in ovarian cancer patients in relation to clinicopathological features and 5-year survival. MATERIAL AND METHODS: We enrolled 90 epithelial ovarian cancer patients in our study, aged 45-81 years, who underwent optimal cytoreductive surgery. In all patients, serum inhibin A and inhibin B concentrations were measured using a two-step sandwich type enzyme immunoassay before surgery. RESULTS: In the group of patients with ovarian cancer median serum concentration of inhibin A was 3.87 pg/mL (0.96-10.09) and inhibin B was 13.9 pg/mL (5.1-45.0). Median concentrations of inhibin A and B in relation to FIGO stage and histological subtype did not differ significantly. Inhibin A levels were significantly higher in patients with lower grading (G1 and G2) in comparison to those with higher grade G3 (p=0.001). There were no differences in inhibin B concentrations in relation to grading. The Kaplan-Meier analyses demonstrated no differences in survival rate in relation to inhibin A levels, while there was a stepwise impairment of 5-years survival with increased inhibin B level. In the group of patients with inhibin B levels higher than 20 pg/ml the survival rate was lower (p=0,00625, log-rank test). CONCLUSION: 1. Higher inhibin A serum levels were found in patients with highly differentiated ovarian carcinoma compared to the group of patients with a poorly differentiated cancer, which may confirm the influence of inhibin A on cell proliferation processes. 2. A significant importance of inhibin B was demonstrated in the prediction of death within less than a five year period. The probability of survival in patients featuring high inhibin B levels was lower with statistical significance. This may indicate the need for further studies on how to block the inhibin B activation pathway in the ovarian carcinoma therapy.

Stromal derived factor-1 (SDF-1) and its receptors CXCR4 and CXCR7 in endometrial cancer patients.

PURPOSE: One of the most important function of stromal derived factor-1 (SDF-1) and its receptors, is regulating the process of metastasis formation. The aim of our study was to investigate the correlation between SDF-1, CXCR4 and CXCR7 protein levels measured by immunohistochemistry with the clinicopathological features and the survival of endometrial cancer patients. MATERIALS AND METHODS: 92 patients aged 37-84 (mean 65.1±9.5) were enrolled to our study between January 2000 and December 2007. After the diagnosis of endometrial cancer, all women underwent total abdominal hysterectomy, with bilateral salpingoophorectomy and pelvic lymph node dissection. In all patients clinical stage (according to FIGO classification), histologic grade, myometrial invasion, lymph node and distant metastases were determined.Furthermore, the survival time was assessed. Immunohistochemical analyses of SDF-1, CXCR4 and CXCR7 were performed on archive formalin fixed paraffin embedded tissue sections. RESULTS: Statistically significant correlations (p<0.01) were reported between SDF-1 and the clinical stage of disease, lymph node metastases, distant metastases, deep myometrial invasion (≥50%), cervical involvement, involvement of adnexa. Statistically significant correlation (p<0.01) was found between SDF-1 expression and the risk of the recurrence. Higher SDF-1 expression was associated with a higher risk of recurrence (p = 0.0001). The results of CXCR4 and CXCR7 expression didn't reveal any significant differences(p>0.05) between the proteins expression in the primary tumor cells and the clinicopathological features. Moreover, the Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival (OS) with increasing SDF-1 expression. CONCLUSION: The important role of SDF-1 as a predictor of negative clinicopathological characteristics of a tumor suggests that the expression of this stromal factor should be included in the panel of accessory pathomorphological tests and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

Insulin resistance as estimated by the homeostatic method at diagnosis of gestational diabetes: estimation of disease severity and therapeutic needs in a population-based study.

BACKGROUND: Chronic insulin resistance, exacerbated in the course of pregnancy, is an important pathophysiologic mechanism of gestational diabetes mellitus (GDM). We hypothesise that the degree of insulin resistance, assessed at diagnosis of GDM, is a parameter of its pathophysiologic heterogeneity and/or severity. Thus, it offers potential to open new avenues for the personalization of therapy in affected women. METHODS: 1254 Polish Caucasian women with GDM were recruited into the study. The following parameters were assessed in the course of the study: body mass index (BMI), parity, weight gain during pregnancy, glycated haemoglobin, glucose level during an oral glucose tolerance test (OGTT), insulin, insulin resistance and insulin secretion. The severity of GDM was assessed based on insulin use and daily insulin dose during gestation. In order to evaluate insulin secretion and insulin resistance the homeostatic method was used (HOMA-B and HOMA-IR, respectively). We compared all the metabolic parameters and methods of treatment of GDM in women subdivided by quartiles of insulin resistance. RESULTS: The HOMA-IR in the whole population ranged from 0.34 to 20.39. The BMI, fasting insulin, fasting glucose and insulin dose per day increased along with increasing quartiles (HOMA-IR > 1.29). We observed a decrease of HOMA-B in the third quartile (1.92-2.89) compared with the first quartile (0.34-1.29). Insulin treatment was associated with HOMA-IR (<1.29 vs. >2.89), OR: 3.37, fasting glucose (≤6.11 vs. >6.11 mmol/dl), OR: 2.61, age (≤30 vs. >30 y. o.), OR: 1.54, and BMI (<25 vs. ≥25 kg/m2), OR: 1.45. Maximum insulin dose was associated with HOMA-IR, OR: 2.00, after adjustment for family history of diabetes, and 2-h OGTT glucose. CONCLUSION: Insulin resistance assessed by the HOMA index at diagnosis is associated with the severity and pathophysiological heterogeneity of GDM. A HOMA-IR >1.29 points to the major role of insulin resistance, indicating the need for a treatment aimed at improving tissue sensitivity to insulin. A HOMA-IR 1.29-2.89 suggests reduced insulin secretion, which is an indication for the introduction of insulin therapy. A HOMA-IR >2.89 indicates insufficient compensation for insulin resistance, which suggests the need for a treatment aimed at improving susceptibility of tissues to insulin combined with insulin therapy.

Adiponectin and endothelial markers in postmenopausal women taking oral or transdermal hormone therapy.

OBJECTIVE: To assess the concentration of adiponectin, soluble E-selectin, soluble thrombomodulin and tissue activator plasminogen antigen in postmenopausal women who received oral or transdermal hormone therapy. DESIGN: Case-control study. SETTING: Polish university hospitals. POPULATION: Seventy-six healthy postmenopausal women. METHOD: Forty-six women who received oral (n = 26) or transdermal (n = 20) hormone therapy and a control group without such medication (n = 30), all aged 44-58 years. MAIN OUTCOME MEASURES: Plasma concentrations of adiponectin, soluble E-selectin, soluble thrombomodulin and tissue activator plasminogen antigen by enzyme-linked immunosorbent assay. RESULTS: We found a significantly higher concentration of adiponectin in women on oral and transdermal therapy in comparison to the control group and a significantly lower concentration of soluble E-selectin in women who received oral hormone therapy vs. the control group. A significantly higher concentration of tissue activator plasminogen antigen was obtained in the group of women using transdermal menopausal hormone therapy compared with those receiving oral therapy and with the control group. CONCLUSIONS: Reduced levels of soluble E-selectin in women using menopausal hormone therapy could lead to reduction in the intensity of expression of the adhesion factors on the surface of the vascular endothelium. Menopausal hormone therapy might have advantageous effects on vascular endothelial function through adiponectin. Transdermal therapy may have adverse effects associated with elevated tissue activator plasminogen antigen levels and thereby the higher risk of ischemic heart disease.

Elevation of sE-Selectin Levels 2-24 Months following Gestational Diabetes Is Associated with Early Cardiometabolic Risk in Nondiabetic Women.

Objective. We hypothesised that the endothelial dysfunction is associated with early glucose dysregulation and/or atherosclerosis risk factors in nondiabetic women with a previous history of gestational diabetes (pGDM). Material/Methods. Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA), lipids, biomarkers of endothelial dysfunction, and inflammation were evaluated in 85 women with pGDM and in 40 controls 2-24 months postpartum. Results. The pGDM group consisted of 67% normoglycemic women (pGDM-N) and 33% with prediabetic state (pGDM-P). The BMI, waist circumference, fasting and 2 h glucose (OGTT), soluble adhesion molecules, tissue plasminogen activator antigen, high sensitivity C-reactive protein, total-, LDL-cholesterol, and triglycerides/HDL-cholesterol ratio were higher in the pGDM women compared with the controls. After adjustment for BMI and fasting glucose, only higher triglycerides, higher TG/HDL and lower HDL-cholesterol were associated with pGDM. The pGDM-P differed from pGDM-N for only higher triglycerides and TG/HDL. The plasma level of sE-selectin was not independently associated with glucose concentration in pGDM group. sE-selectin level correlated with triglycerides, TG/HDL, plasminogen activator inhibitor-1 antigen, and sICAM-1. Conclusions. sE-selectin level correlated with components of metabolic syndrome, but only the atherogenic lipid profile was independently associated with a previous history of GDM in nondiabetic women 2-24 months postpartum.

Triglycerides as an early pathophysiological marker of endothelial dysfunction in nondiabetic women with a previous history of gestational diabetes.

OBJECTIVE: To investigate whether baseline triglyceride levels are associated with early glucose dysregulation and/or cardiovascular risk in women with a previous history of gestational diabetes. DESIGN: Prospective postpregnancy cohort study. SETTING: Polish university hospitals. SAMPLE: Participants included 125 women with previous gestational diabetes and 40 women with normal glucose regulation during pregnancy. METHODS: All women were studied 2-24 months (mean 12 ± 10 months) after the index pregnancy. Women with previous gestational diabetes were divided into tertiles in accordance with baseline triglyceride levels. MAIN OUTCOME MEASURES: We assessed glucose regulation (oral glucose tolerance test), insulin resistance (homeostasis model assessment), markers of endothelial dysfunction (soluble: intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, tissue plasminogen activator antigen, von Willebrand factor antigen), fibrinolysis (plasminogen activator inhibitor antigen), inflammation (high-sensitivity C-reactive protein) and lipid levels. RESULTS: Women with previous gestational diabetes (78% normal glucose regulation, 22% impaired glucose tolerance) had a high cardiometabolic risk profile compared with control women (100% normal glucose regulation). Baseline triglycerides >0.83 mmol/l were associated with a higher prevalence of impaired glucose tolerance, higher high-sensitivity C-reactive protein and triglyceride/high-density lipoprotein-cholesterol ratio. Triglycerides >1.22 mmol/l were associated with higher body fat indexes, higher insulin resistance, higher levels of endothelial dysfunction biomarkers, higher plasminogen activator inhibitor antigen and dyslipidemia. Only E-selectin was independently associated with triglyceride levels. CONCLUSIONS: Baseline triglyceride levels are a cardiovascular risk marker as well as a pathophysiological parameter independently associated with endothelial dysfunction in nondiabetic women with previous gestational diabetes at 2-24 months after an index pregnancy. Normalization of triglycerides should be included in preventive therapy after a pregnancy complicated by gestational diabetes.

Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy.

OBJECTIVE: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). METHODS: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). RESULTS: We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. CONCLUSIONS: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag, which in turn, can lead to a reduction in fibrinolytic activity.

Impaired fasting glucose as a marker of heterogeneity of gestational diabetes mellitus. A study of 1025 women living in the region of Kuyavia and Pomerania in Poland.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a heterogeneous disease. We hypothesized that fasting hyperglycaemia, defined as impaired fasting glycaemia (IFG), is a marker of metabolic heterogeneity of GDM. The aim of this study was to compare selected metabolic parameters in two groups of women with GDM, one with normal fasting glycaemia (NFG GDM) and another with IFG, to test this hypothesis. MATERIAL AND METHODS: Metabolic parameters of 1025 women with GDM (mean age 29 years): glucose and insulin at 0 OGTT, glucose at 2-h oral glucose tolerance test (OGTT), body mass index before pregnancy, parity, and gestational age at diagnosis of GDM were analyzed. Insulin resistance and beta-cell function were evaluated by HOMA indexes (HOMA-IR and HOMA-B) at the diagnosis of GDM. RESULTS: The IFG GDM group (23%) consisted of isolated IFG (30%), IFG/IGT (60%), and IFG/DM (10%). The NFG GDM group (77%) consisted of isolated IGT (98%) and NFG/DM (2%). Women with IFG GDM were characterized by higher prepregnancy BMI, earlier diagnosis of GDM, higher HOMA-IR (p < 0.03), and lower HOMA-B (p < 0.01) compared to NFG GDM. In the IFGGDM group, DM was characterized by lower HOMA-B compared with isolated IFG and IFG/IGT. In the NFG GDM group, isolated IGT and DM were characterized by similar HOMA-IR and HOMA-B. CONCLUSIONS: Impaired fasting glucose distinguishes more severe metabolic phenotypes of GDM compared toGDM with normal fasting glucose concentrations.

[Heterogeneity of insulin resistance level in gestational diabetes mellitus. Therapeutic implications]. / Zróznicowanie nasilenia insulino- opornosci w cukrzycy ciezarnych. Implikacje terapeutyczne.

OBJECTIVE: The evaluation of insulin resistance (IR) level in population of women with gestational diabetes(GDM) and its relation to treatment of GDM. MATERIALS AND METHODS: 657 GDM women, aged 17-45, treated between the years 2003 and 2005, in Bydgoszcz were studied. Age, pregravid body mass index(BMI), weight gain during pregnancy at the GDM diagnosis, week of GDM diagnosis, week of the beginning of insulin therapy and daily doses of insulin were assessed in the whole population. Daily doses of insulin were evaluated as minimal doses needed at the initial phase of GDM therapy and as maximal doses during gestation. IR was evaluated at the GDM diagnosis, with the use of homeostasis model assessment (HOMA-IR), based on fasting glucose and insulin concentration. RESULTS: 47% women were classified as low HOMA-IR(<2) subpopulation, 50% as intermediate HOMA-IR(2-10) subpopulation, 3% as high HOMA-IR(10-46)subpopulation. Subpopulation with intermediate HOMA-IR had higher BMI, higher weight gain and blood glucose at 0 OGTT compared to subpopulation with low HOMA-IR but lower insulin concentration compared to high HOMA-IR subpopulation. Women in high HOMA-IR subpopulation and in intermediate HOMA-IR subpopulation were twice as often treated with insulin, compared to low HOMA-IR group, accordingly, 58%, 42%, 24%. Daily insulin doses, assessed both minimal and maximal doses, were increasing parallel to HOMA-IR in whole population, accordingly, minimal doses of insulin, 16.0 = -12.7 vs 18.4 vs 20.8 vs 30.8 +/- 30.3 and maximal doses of insulin, accordingly, 39.0 +/- 322.4 vs 50.9 +/- 42.4 vs 70.3 +/- 30.3. CONCLUSION: The studied population of women consisted mainly of subpopulation with low or intermediate HOMA-IR value, in rare cases, of high HOMA-IR value. Our results suggest that adipose tissue is particularly associated with insulin resistance level in subpopulation with intermediate HOMA-IR. Both, frequency of insulin therapy and daily insulin doses are associated with insulin resistance level at the GDM diagnosis.

[Carbohydrate metabolism and aging--controversy of etiopathogenesis and pathophysiology. Part I. Changes of insulin sensitivity]. / Gospodarka weglowodanowa a starzenie sie organizmu--kontrowersje etiopatogenezy I patofizjologii. Czesc I. Zmiany wrazliwosci tkanek na insuline.

Insulin resistance is one of the reasons of increasing carbohydrate metabolism disturbances with aging. Mechanisms of these changes had been partially elucidated. Decreasing of physical activity with increasing of total and abdominal fat are especially important pathogenetic mechanisms. Changes in glucose transporter 4 (GLUT-4) level in skeletal muscles and serum level of insulin like growth factor 1 (IGF-1) could be mechanisms independent of fat tissue. Other mechanisms which could be associated with insulin resistance in aging are related to leptin and adiponectin serum level or changes in mitochondrial energy metabolism and level of advanced glucose end products in diet.

[Carbohydrate metabolism and aging-controversy of ethiopathogenesis and pathophysiology. Part II. Changes in beta-cell function]. / Gospodarka weglowodanowa a starzenie sie organizmu--kontrowersje etiopatogenezy i patofizjologii. Czesc II. Zmiany w czynnosci komórek beta trzustki.

Many studies suggest the decrease of beta-cell function in people older than 60 years. Age-associated defect of beta-cell function can be detected in loading tests, especially with prolonged intravenous infusion glucose infusion. Pathogenetic mechanisms consist abnormalities in insulin processing, insulin secretion, insulin release kinetics with parallel lower insulin secretion capacity and impossibility of increasing insulin release properly to age-increasing insulin resistance. These pathogenetic changes are related to increase of visceral fat deposits and other mechanisms such as defects in beta cell structure, decrease in glucose and incretins sensing and defective course of replication/neogenesis processes.

[Insulin resistance in pregnant type 1 diabetic female. Case report]. / Insulinoopornosc u ciezarnej z cukrzyca typu 1--opis przypadku.

Insulin resistance may coexist with diabetes type 1 and make treatment of diabetes difficult. Case of 24-year-old type 1 diabetic female with insulin resistance features prior to pregnancy is reported. Exacerbating of insulin resistance during pregnancy was manifested by difficulties to overcome excessive weight gain and necessity to initiate treatment with high doses of insulin. The treatment was based on diet with progressive caloric restriction to 800 kcal/day in 35 week of pregnancy. That diet was continued till the delivery in 37 week. The fast acting analog insulin (Humalog) and long acting insulin (Humulin U) were used in treatment of diabetes. Treatment with low calorie diet did not cause negative effects on diabetic female metabolism and on the neonate state.

[Insulin secretion at the diagnosis of gestational diabetes is lower in multiparas than in primiparas]. / Sekrecja insuliny przy rozpoznaniu cukrzycy ciezarnych jest mniejsza u wieloródek niz u pierwiastek.

UNLABELLED: Gestational diabetes mellitus (GDM) has heterogeneous ethiopathogenesis, pathophysiology and clinical features. OBJECTIVES: The aim of the study was to evaluate some of anthropometric parameters, clinical features and indices of insulin resistance and beta cell function in GDM women in first pregnancy and in GDM women in third and following pregnancies. MATERIAL AND METHODS: 877 GDM women, aged 18-48 years were studied. Both groups were compared according to age, BMI before pregnancy, week of GDM diagnosis, weight gain during pregnancy, fasting blood glucose, fasting serum insulin level, HbA1c, insulin resistance and beta-cell function indices. All parameters except BMI were evaluated at GDM diagnosis. RESULTS: Multiparas were older, with higher BMI and lower beta-cell function indices. CONCLUSION: At the moment of GDM diagnosis, insulin secretion evaluated by HOMA indices are lower in multiparas in comparison to primaparas.