B. Lormeau

Elevated Concentrations of Soluble E-Selectin and Vascular Cell Adhesion Molecule-1 in NIDDM: Effect of intensive insulin treatment

OBJECTIVE To evaluate the effects of a 14-day intensive insulin therapy and short-term improvement of glycemic control on serum levels of soluble forms of adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in NIDDM patients with poor glycemic control. RESEARCH DESIGN AND METHODS A total of 16 NIDDM patients were compared with 23 healthy subjects (control group) and investigated before and after intensive insulin treatment. RESULTS On day 0, sE-selectin and sVCAM-1 levels were significantly higher in NIDDM patients than in nondiabetic control subjects (median 87, range 63–115; median 544, range 408–797 vs. 58, 43–80; 443, 395–573 ng/ml, respectively) (P < 0.008 in both cases). On day 15, the fall in sE-selectin levels was significant (P < 0.0001) and at a lesser extent in sVCAM-1 levels (64, 48–85; 506, 417–678 ng/ml, respectively); these levels reached values that no longer differed from those of control subjects (P = 0.23 and 0.15, respectively). Moreover, the fall in sE-selectin was positively associated with the change in LDL cholesterol and the improvement of glycemia. CONCLUSIONS In poorly controlled NIDDM patients, sE-selectin levels are increased and significantly fall to normal after short-term improvement of glycemic control. This suggests that assaying sE-selectin makes it possible to detect endothelium activation and to follow its reversal with euglycemia.

Universal rather than selective screening for gestational diabetes mellitus may improve fetal outcomes

AIM The benefit of treating gestational diabetes mellitus (GDM) has recently been shown. The aim of this study was to compare offspring and maternal health benefits from selective or universal screening for GDM. METHODS The incidence of outcomes was compared in three series of pregnant women: 1) the 159 consecutive women with GDM out of the 1909 women who delivered between October 2000 and September 2001: during this period screening for GDM was based on risk factors (risk factor-GDM); 2) the 265 consecutive women with GDM out of the 2111 women who delivered during the year 2002: during this period screening for GDM was universal (universal-GDM); 3) 1255 women with no GDM during year 2002 (controls). RESULTS After adjustment for age, pregravid body mass index, parity, and ethnicity, the risk of large for gestational age (Odds ratio 2.19[95% confidence interval 1.36-3.54], P < 10(-3)), delivery before 37 weeks of gestation (OR 2.44 [95CI 1.32-4.51], P = 0.004), jaundice (OR 3.31[95CI 1.58-6.93], P = 0.002), hospitalization in the department of pediatrics (OR 2.35 [95CI 1.53-3.61], P < 10(-3)) was higher in the GDM-risk factor group than in the control group, whereas it was similar in the universal-GDM group and the control group. Compared with the control group, the risk of anticipated delivery and hospital stay > 4 days after delivery was increased in the GDM-risk factor group (OR 2.69[1.88-3.84], P < 10(-3); and OR 2.6 [1.82-3.71], P < 10(-3) respectively) and the universal-GDM group (OR 1.54 [1.15-2.07] P = 0.004; and OR 1.49 [1.13-1.97], P = 0.005 respectively). CONCLUSION This observational study suggests that universal rather than selective screening for GDM may improve outcomes. Universal screening might reduce delay of diagnosis and care.

Hyperinsulinemia and hypofibrinolysis: Effects of short-term optimized glycemic control with continuous insulin infusion in type II diabetic patients

A defect in the fibrinolytic system results from an increase in type 1 plasminogen activator inhibitor (PAI-1) in diabetes. It can be considered an independent risk factor for the development of cardiovascular disease. In obese and type II diabetic patients, plasma PAI-1 level correlates with fasting insulinemia. However, during the euglycemic clamp, acute hyperinsulinemia does not increase PAI-1 production. The present study was undertaken to investigate the effect of optimized glycemic control by continuous subcutaneous insulin infusion (CSII) on the hypofibrinolytic state for 14 days in 16 type II diabetic patients with poor metabolic control despite maximal oral antidiabetic treatment. Plasma PAI-1 activity levels decreased from 13.38 +/- 2.85 IU/mL to 6.77 +/- 1.81 IU/mL (P = .002) during CSII, along with a concurrent improvement in insulin sensitivity (index obtained by basal glycemia-nadir glycemia/basal glycemia) during the insulin sensitivity test (0.121 +/- 0.03 v 0.057 +/- 0.02, P = .02). These results suggest that insulin resistance rather than hyperinsulinism may be involved in the hypofibrinolytic state in type II diabetic patients. The positive correlation between the changes in triglycerides and in PAI-1 activity (r = .589, P = .026) strongly suggests a role for triglycerides in the impairment of fibrinolysis, which could be a link between insulin resistance and hypofibrinolysis.

Insulin Sensitivity, Insulin Action, and Fibrinolysis Activity in Nondiabetic and Diabetic Obese Subjects

Because inconsistencies occur with regard to the relative contribution of insulin to the hypofibrinolysis characteristic of obesity and diabetes, we explored the relationship between insulin and fibrinolysis, assessing both insulin sensitivity and insulin action. Seventeen markedly obese subjects (body mass index [BMI], 34.0+/-1.6 kg/m2; 12 nondiabetic and five diabetic) were studied using the three-step euglycemic-hyperinsulinemic clamp technique. Since the circadian rhythm of the fibrinolytic system may obscure a true effect of insulin, variations in fibrinolysis parameters observed during the glucose clamp were compared with those occurring spontaneously because of the circadian rhythm. Compared with six normal-weight subjects (BMI, 21.0+/-0.9 kg/m2), all obese subjects exhibited basal hyperinsulinism (fasting plasma insulin, 16.0+/-1.4 v 9.8+/-1.3 microU/microL, P < .001; fasting plasma C-peptide, 1.4+/-0.2 v 0.5+/-0.2 ng/mL, P < .001), hypofibrinolysis (euglobulin lysis time [ELT], 378+/-29 v 222+/-31 minutes, P=.01; tissue plasminogen activator [tPA] antigen, 7.8+/-0.9 v 4.2+/-0.5 ng/mL, P=.04; plasminogen activator inhibitor type 1 [PAI-1] activity, 22.2+/-2.5 v3.9+/-0.6 AU/mL, P=.004), and marked insulin resistance (M value, ie, the maximal glucose disposal rate, 9.1+/-0.6 v 18.6+/-0.8 mg/(kg x min), P < .001). The M value correlated inversely with tPA antigen (r=-.46, P=.05). During insulin infusion, values for fibrinolysis parameters decreased, but were not different compared with variations due to the circadian rhythm. In conclusion, our findings together with previously reported data reinforce the idea that chronic hyperinsulinism is linked to hypofibrinolysis, but insulin does not seem to acutely regulate the fibrinolysis system.

Impairment of skin vasoconstrictive response to sympathetic activation in obese patients: influence of rheological disorders.

Alterations of cardiac vagosympathetic activity have been suggested in obesity. We have previously shown that the skin vasoconstrictive response to sympathetic activation is reduced in non-insulin-dependent diabetic patients. The present study investigates the skin vasoconstrictive response to sympathetic activation in nondiabetic obese patients and the influence of clinical and rheological factors. Fifty-seven obese and 18 healthy women were investigated. The resting cutaneous blood flow (CBF) and CBF response to three tests that activate the sympathetic nervous system (deep breathing, Valsalva maneuver, and sitting to standing) were measured by a laser Doppler device. The red blood cell (RBC) filtration index (FI) and RBC aggregation were measured using a Hanss hemorrheometer and a Myrenne aggregometer (Myrenne, Roetgen, Germany), respectively. Resting CBF was not significantly different in obese and control subjects. The vasoconstrictive response to the deep-breathing and sitting-to-standing tests expressed as the decrease in CBF was significantly lower in obese patients versus controls (43.9% +/- 3.1% v 73.7% +/- 17.9%, P = .01, and 67.1% +/- 3.8% v 89.8% +/- 12.0%, P = .02, respectively). The spontaneous basal CBF variations and the downward slope of the CBF reduction during the Valsalva and sitting-to-standing tests correlated negatively with age in obese patients (P = .042, .022, and .008, respectively). During the sitting-to-standing test, the percent change in CBF correlated positively with RBC aggregation at a shear rate of 0 and 3 s(-1) (P = .011 and .017, respectively). In conclusion, (1) CBF assessment by laser Doppler flowmetry is an effective noninvasive method to investigate sympathetic nervous function in obese patients; (2) obesity is associated with a significant reduction in the vasoconstrictive response to two tests for sympathetic activation, the deep-breathing and sitting-to-standing tests; (3) the severity of this reduction increases with age; and (4) RBC aggregation may contribute to the increase in the vasoconstrictive response and may thus increase the risk of widespread cardiovascular disease.