Ida Kinalska

Insulin resistance, serum adiponectin, and proinflammatory markers in young subjects with the metabolic syndrome

Insulin resistance is the underlying metabolic abnormality in the metabolic syndrome. The low-grade chronic inflammation may be associated with metabolic risk factors and atherogenesis. The aim of our study was to establish the link between the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) criteria, and insulin sensitivity, serum adiponectin, and parameters of chronic inflammation in young subjects. The group of 223 subjects (mean age, 25.86 +/- 5.49 years; body mass index, 28.04 +/- 6.91 kg/m2) was studied. Oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and estimation of serum adiponectin and proinflammatory factors were performed. The NCEP-defined metabolic syndrome was present in 49 subjects (21.97%). The higher the number of NCEP criteria fulfilled was, the bigger were the decrease in insulin sensitivity (P < .0001) and adiponectin (P < .0001) and the increase in fasting and postload insulin (both Ps < .0001), C-reactive protein (P < .0001), interleukin 18 (P < .0001), interleukin 6 (P < .0001), and soluble tumor necrosis factor-alpha receptors sTNFR1 (P < .0001) and sTNFR2 (P < .0001) observed. Multiple regression analysis revealed that adiponectin and inflammatory factors predicted NCEP score independent of insulin sensitivity (all adjusted beta values between .16 and .32, all Ps < .01). Young subjects with metabolic syndrome demonstrate an increased inflammatory response and lower adiponectin concentration.

Plasma interleukin 8 concentrations in obese subjects with impaired glucose tolerance.

BackgroundInterleukin 8 (IL-8) is a cytokine with atherogenic properties. In vitro studies revealed that it is produced and secreted by human adipocytes. We recently reported that plasma IL-8 is increased in obese subjects with normal glucose tolerance (NGT). The aim of the present study was to measure plasma IL-8 concentrations in subjects with impaired glucose tolerance (IGT).MethodsA total of 44 subjects with marked overweight or obesity (BMI > 27.8 kg/m2), 27 with NGT and 17 with IGT, were recruited for the present study. Plasma IL-8 levels were measured in fasting state, after an oral glucose tolerance test (OGTT) and after euglycemic hyperinsulinemic clamp.ResultsThe studied groups did not differ in fasting IL-8 concentrations. Both OGTT and clamp resulted in a significant increase in plasma IL-8. The change in IL-8 after clamp was similar in both groups. In contrast, after OGTT plasma IL-8 levels (IL-8OGTT) were markedly higher in IGT individuals. In IGT, but not NGT group, IL-8OGTT was positively related to postload glucose and negatively to insulin sensitivity.ConclusionPlasma IL-8 concentrations after glucose load are increased in obese IGT subjects in comparison to normoglycemic weight-matched individuals. Increase in plasma IL-8 might be both insulin-mediated (during clamp) and glucose-mediated (during OGTT).

Effect of glycosaminoglycans on urinary albumin excretion in insulin-dependent diabetic patients with micro- or macroalbuminuria

The aim of this study was to investigate whether sulodexide treatment is capable of influencing urinary albumin excretion rate (UAER) in insulin-dependent diabetes mellitus patients (type I) with micro- or macroalbuminuria. A total of 14-inpatients (seven with micro and seven with macroalbuminuria) were enrolled and were treated first intramuscularly with a 60 mg vial of sulodexide/day for 10 days, and then orally with 25 mg capsules twice a day for 21 days. UAER was estimated before starting treatment (T0), after the i.m. treatment phase (T1) and at the end of the oral treatment (T2). No statistically significant differences in hematochemical and coagulative parameters were registered after treatment, with respect to basal values. On the contrary, a marked decrease in UAER mean values was registered at the end of both the parenteral and the oral treatment periods (T0: 349.9 mg/24 h, range 80-820; T1: 237 mg/24 h, range 7-620; T2: 91.4 mg/24 h, range: 2-306). All the differences were statistically significant (P < 0.001) versus baseline. At T2, a normalisation of UAER was observed in three microalbuminuric and in two macroalbuminuric patients, and a remarkable decrease was found in additional four and five patients, respectively. UAER was found to be still significantly lower than at baseline after 6 weeks of follow-up. This preliminary study suggests that sulodexide is effective in reducing UAER in type I patients with diabetic nephropathy.

CD11a Expression and soluble ICAM-1 levels in peripheral blood in high-risk and overt type 1 diabetes subjects

A pair of correspondent adhesion molecules: LFA-1 (CD11aCD18) and ICAM-1 (CD54) was shown to be involved in autoimmune insulitis in animal models. Anti-LFA-1 or anti-ICAM-1 monoclonal antibodies administered in vivo had a very strong preventive effect on the development of spontaneous diabetes with a marked reduction of insulitis. On the other hand elevated levels of the soluble form of ICAM-1 (sICAM-1) were documented in subjects at risk for type 1 diabetes. Recently sICAM-1 was shown to play an immunoregulatory role as an inhibitor of islet insulitis. The aim of the present study was to evaluate CD11a + mononuclear cells (lymphocytes and monocytes) and soluble sICAM-1 levels in the peripheral blood of subjects with preclinical and overt type 1 diabetes to assess their role in the development of the autoimmune process and their possible associations with the humoral autoimmune markers. The study was carried out in three groups of subjects: 26 first degree relatives of type 1 diabetes patients (prediabetics) with the combinations of autoantibodies against pancreatic B cells (ICA, GADA, IA-2A, IAA), 22 patients with a recent onset of type 1 diabetes and age and sex-matched 24 healthy volunteers (control group). We observed an increased fluorescence intensity of CD11a on mononuclear cells in overt diabetes subjects and a positive correlation between CD11a fluorescence intensity on monocytes and ICA titre. The highest sICAM-1 levels we obtained in the peripheral blood in the prediabetics in comparison to patients with clinical diabetes and the healthy controls. We found a positive correlation between slCAM-1 and values of ICA, GADA and a total number of antibodies present. In conclusion our study suggests that LFA-1 and sCAM-1 play an important role in the pathogenesis of type 1 diabetes. The assessment of the CD11a bearing monocytes and sICAM-1 levels are potential markers of the preclinical stage of the autoimmune diabetes, but further prospective studies in high risk diabetes type 1 subjects are needed.

Serum Soluble Glycoprotein 130 Concentration Is Inversely Related to Insulin Sensitivity in Women With Polycystic Ovary Syndrome

OBJECTIVE Insulin resistance might play a role in the pathogenesis of polycystic ovarian syndrome (PCOS). The family of glycoprotein 130 (gp130) cytokines could influence insulin action. One of these cytokines is interleukin (IL)-6, which exerts a short-term insulin-sensitizing effect, whereas in a long-term period, it might induce insulin resistance. Some other gp130 activators are supposed to have beneficial metabolic effects. Gp130 is present in the circulation in the soluble form (sgp130), which inhibits intracellular gp130 signaling. The aim of the present study was to estimate the relation between sgp130 and insulin sensitivity in women with PCOS. RESEARCH DESIGN AND METHODS We studied 78 women with PCOS (35 lean and 43 obese) and 34 healthy women (18 lean and 16 obese). The euglycemic-hyperinsulinemic clamp and the measurements of serum sgp130, IL-6, soluble IL-6 receptor (sIL-6R), and sex hormones were performed. RESULTS Both obesity and PCOS were characterized by an increased sgp130 (P < 0.0001 and P = 0.0002, respectively). sIL-6R concentration was lower (P = 0.0036) in women with PCOS independently of obesity. Serum sgp130 was negatively correlated with insulin sensitivity when control and PCOS women were analyzed together (r = −0.36, P < 0.0001) and in the PCOS subjects separately (r = −0.34, P = 0.002). In multiple regression analysis, this correlation was significant after adjustment for BMI, waist, percent of body fat, postload glucose and insulin, triglycerides, and high-sensitive C-reactive protein. CONCLUSIONS Serum sgp130 is inversely and independently associated with insulin sensitivity in women with PCOS. An increased serum sgp130 in obesity and PCOS suggests an inhibition of intracellular gp130 signaling in insulin-resistant conditions.

Nicotinamide inhibits enhanced in vitro production of interleukin-12 and tumour necrosis factor-α in peripheral whole blood of people at high risk of developing Type 1 diabetes and people with newly diagnosed Type 1 diabetes

Macrophages and T lymphocytes are the first cells to appear in pancreatic islets in the development of autoimmune diabetes. It has been suggested that cytokines released by monocytes/macrophages, including interleukin-1beta (IL-1beta), interleukin-12 (IL-12) and tumour necrosis factor-alpha (TNF-alpha) could have an initial role in islet B-cell damage. The aim of the present study was to estimate the effect of human insulin and nicotinamide on the levels of monocyte/ macrophage derived cytokines in the peripheral blood of humans at risk of Type 1 diabetes, and in patients with newly diagnosed Type 1 diabetes compared to healthy control subjects. The study was carried out on three groups of subjects: 20 first degree relatives of people with Type 1 diabetes (with two or more antibodies against pancreatic B-cell antigens); 22 patients with recent onset of Type 1 diabetes (duration of the disease 3-6 months); and 25 age- and sex-matched healthy subjects. Cytokine levels (IL-1beta, IL-12, and TNF-alpha) in the supernatants of whole blood cultures incubated with PHA alone (10 microg/ml), or PHA + human insulin (50 microg/ml), or PHA + nicotinamide (100 micromol/l) were quantified by ELISA. In the cultures with nicotinamide the concentration of IL-12 and TNF-alpha was significantly lower in the prediabetic group, diabetic patients, and the healthy controls than in the cultures with PHA only or with PHA + insulin. There were no significant differences in IL-1beta production in the cultures after incubation with the different stimuli in the studied groups and healthy controls. No significant influence of human insulin on macrophage/monocyte cytokines secretion in in vitro cultures of the peripheral blood was found. This suggests that nicotinamide could influence monocyte/macrophage function in peripheral blood by inhibiting production of IL-12 and TNF-alpha.

Glycosaminoglycans urinary excretion as a marker of the early stages of diabetic nephropathy and the disease progression

Diabetes mellitus affects the metabolism of several components of extra‐cellular matrix, including glycosaminoglycans (GAG). Alterations in the metabolism of GAG may play an important role in the development of diabetic complications.

Serum Levels of Interleukin-18—a Potential Marker of Cardiovascular Death—Could Be Determined by Genetic Predisposition

To the Editor: Esposito et al1 recently reported that interleukin (IL)-18 and other proinflammatory cytokines are increased by hyperglycemia in subjects with impaired glucose tolerance, suggesting a causal role for hyperglycemia in the immune activation of diabetes. Moreover, they speculated that IL-18 stimulated by stress hyperglycemia could play a role in acute coronary syndromes. The role of IL-18 in the development of cardiovascular disease was previously identified by a study carried out by Blankenberg et al,2 who found that IL-18 is a strong predictor of cardiovascular death in stable and unstable angina and probably is involved in atherotic plaque destabilization. It is well known that subjects with type 1 diabetes have a 2- to 4-times increased risk of death from coronary heart disease in comparison with nondiabetic age-matched individuals, and hyperglycemia is believed to be a key risk factor in the development of micro- and macrovascular complications. In our recent study (Kretowski et al, unpublished data, 2002), we observed that in …

γδ T-cells alterations in the peripheral blood of high risk diabetes type 1 subjects with subclinical pancreatic B-cells impairment

There is increasing evidence that CD3 + cells bearing gammadelta T-cell receptor (represent the minor subpopulation of the T-cells in the peripheral blood in humans) are involved in autoimmunity development. Gammadelta T-cell receptor (TCR)+ /CD8+ T-cells have been recently found to play a critical role in the pathogenesis and prevention of autoimmune diabetes in the animal model. The aim of the present study was the estimation the gammadelta T-cell subpopulation levels in the peripheral blood of subjects with preclinical and overt type 1 diabetes and their possible associations with the humoral immunity, metabolic parameters and pancreatic B-cells function. The study was carried out in three groups of subjects: 26 first degree relatives of type 1 diabetes patients (prediabetics) with the combinations of autoantibodies against pancreatic B-cells (ICA, GADA, IA-2A, IAA), 22 patients with a recent onset of type 1 diabetes and age and sex-matched 24 healthy volunteers (control group). A decrease was observed in the absolute numbers and percentages of gammadelta+ /CD8+ and gammadelta+ /CD8- T-cell subpopulations in peripheral blood in the prediabetics with the impaired first phase of insulin secretion in comparison to relatives with autoantibodies but still with normal B-cells function, patients with clinical diabetes and healthy controls. In conclusion, the study suggests that the gammadelta T-cells play an important role in the development of insulin-dependent diabetes mellitus (IDDM). It is possible that their levels in the peripheral blood could be an additional marker of preclinical detection of the disease, but further prospective studies in high risk of IDDM subjects are needed.