Is there any link between insulin resistance and inflammation in established preeclampsia?

Both insulin resistance and inflammation may contribute to the onset of preeclampsia. They also could be interrelated. We studied the relationship between inflammatory cytokines and markers of insulin resistance. During their third trimester, 22 proteinuric preeclamptic women and 16 normotensive controls underwent intravenous glucose tolerance test (minimal model). Preeclamptic women were more insulin-resistant (P = .009), and they had higher levels of serum soluble tumor necrosis alpha receptor II (TNFalpha RII) (P = .002), triglycerides (P = .006), uric acid (P = .001), and leptin (P = .002) than did the controls. However, the study groups did not differ in serum TNFalpha, C-reactive protein (CRP), interleukin-6 (IL-6), sex hormone-binding globulin (SHBG), and high-density lipoprotein-2 (HDL(2))-cholesterol. In multiple regression analysis only SHBG (P = .01) and triglycerides (P = .0036) were associated with insulin sensitivity independently of body mass index (BMI), weight gain, HDL(2)-cholesterol, CRP, TNFalpha, and TNFalpha RII, IL-6, and leptin. We conclude that insulin resistance and the inflammatory markers studied were not associated in established preeclampsia.     

Arterial stiffness and insulin resistance

Insulin resistance is associated with increased cardiovascular morbidity and mortality. The mechanism(s) underlying this association are poorly understood. Increased arterial stiffness is the main cause of the most prevalent form of hypertension, systolic hypertension. Hypertension is also commonly observed in individuals with insulin resistance. In cross-sectional epidemiological studies such as the Atherosclerosis Risk in Communities study, hyperinsulinemia was independently associated with increased arterial stiffness. Recent mechanistic studies performed in humans in vivo have suggested that increased stiffness could be yet another facet of insulin resistance. Insulin, at physiological concentrations, acutely diminishes wave reflection in the aorta in vivo. This action of insulin precedes any changes in peripheral blood flow, vascular resistance, ejection duration or heart rate, and therefore implies that insulin acutely diminishes stiffness in arteries greater than those controlling peripheral vascular resistance. This effect is blunted in insulin-resistant conditions such as obesity and type 1 diabetes. These data suggest that the inability of insulin to normally diminish arterial stiffness could provide a mechanistic link between insulin resistance and systolic hypertension.     

Fatty liver: a novel component of the metabolic syndrome

Although the epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, not all obese develop the syndrome and even lean individuals can be insulin resistant. Both lean and obese insulin resistant individuals have an excess of fat in the liver which is not attributable to alcohol or other known causes of liver disease, a condition defined as nonalcoholic fatty liver disease (NAFLD) by gastroenterologists. The fatty liver is insulin resistant. Liver fat is highly significantly and linearly correlated with all components of the metabolic syndrome independent of obesity. Overproduction of glucose, VLDL, CRP, and coagulation factors by the fatty liver could contribute to the excess risk of cardiovascular disease associated with the metabolic syndrome and NAFLD. Both of the latter conditions also increase the risk of type 2 diabetes and advanced liver disease. The reason why some deposit fat in the liver whereas others do not is poorly understood. Individuals with a fatty liver are more likely to have excess intraabdominal fat and inflammatory changes in adipose tissue. Intervention studies have shown that liver fat can be decreased by weight loss, PPARgamma agonists, and insulin therapy.     

Role of proprotein convertases in the pathogenic processing of the amyloidosis-associated form of secretory gelsolin.

Familial amyloidosis of the Finnish type (FAF) is caused by two proteolytic cleavages of mutant gelsolin leading to the accumulation of FAF amyloid in the patients' tissues. Here, we demonstrate that, in mouse pituitary corticotropic AtT20 cells, the enzyme responsible for the first cleavage of mutant secretory FAF gelsolin to FAF amyloid precursor is present in reasonable amounts. Furthermore, in At T20 cells stably expressing alpha1-PDX a potent inhibitor of most proprotein convertases, this cleavage was inhibited The present data provide strong evidence that proprotein convertases, possibly furin or PC5, are involved in the initialpathological cleavage of mutant secretory FAF gelsolin leading ultimately to the amyloid disease.     

Duodenogastric Bile Reflux in Patients with Gastric Ulcer

The duodenogastric bile reflux rate in 33 patients with gastric ulcer is compared with the rates in 33 non-ulcer patients. Duodenogastric bile reflux was measured by a non-invasive isotope method using ^99mTc-diethyliminodiacetic acid. Reflux occurred significantly oftener in the ulcer patients (27 of 33) than in the non-ulcer patients (14 of 33) (p < 0.01) but did not differ significantly in quantity between these two groups. The results suggest that the magnitude of bile reflux cannot be used to distinguish between ulcer patients and non-ulcer patients.     

Gene dose effect of the DQB1*0201 allele contributes to severity of coeliac disease

Objective. Coeliac disease (CD) susceptibility has been shown to be associated with the HLA alleles DQA1*0501 and DQB1*0201. This HLA-associated risk has been estimated to account for 29–40% of the genetic component of CD. Conflicting data have been published on the gene dose effect of these HLA alleles on the risk and severity of CD. In this study the aim was to investigate the association between the number of HLA risk alleles and the severity of CD. Material and methods. Fifty-four Finnish CD families, including 144 CD patients mainly diagnosed in adulthood (94.4%), were enrolled in the study. The association between the number of DQA1*0501 and DQB1*0201 alleles and villous atrophy, symptoms and laboratory parameters at the time of diagnosis, and the association with villous atrophy after one year of treatment on a gluten-free diet were studied. Results. The homozygosity for the DQB1*0201 allele was associated with a more severe form of CD assessed by more severe villous atrophy (p=0.011), younger age (p=0.036), more severe diarrhoea (p=0.048) and a lower level of blood haemoglobin at the time of diagnosis (p=0.010). Furthermore, the homozygosity for the DQB1*0201 allele was associated with a slower recovery of villous atrophy after a gluten-free diet (p=0.041). In contrast, the DQA1*0501 allele did not have a significant association with the severity of CD. Conclusions. Our results demonstrate a gene dose effect of the DQB1*0201 allele on the clinical heterogeneity of CD and on the rate of recovery from villous atrophy in patients on a gluten-free diet.     

Assessment of Thoracolumbar Rotation in Ankylosing Spondylitis: A Simple Tape Method

Results of a ‘new’ method for thoracolumbar rotation by tape (TRPav), simple instrumental rotation (TRi), the modified Schober test and thoracolumbar flexion (ThFL) were correlalated with radiological changes in patients with ankylosing spondylitis (AS). TRPav showed a significant radiological correlation (Ls-r: 0.38; Th-r: 0.31), while the instrument method (TRi) did not; both the Schober test and ThFL, again, correlated fairly highly (Ls-r: 0.71, 0.62; Th-r: 0.49, 0.42). Both inter- and intratester reliability of the tests was good (Bland and Altman plots). Thoracolumbar rotation is one of the three principal levels of spinal motion and seems to be less affected by age. TRPav proved a valid and reliable method for measuring thoracolumbar rotation and clinically is a non-invasive, quick and easy complement to AS measurement methodologies. Received: 20 April 1998 / Accepted: 5 October 1998     

The effect of nitecapone, a new antioxidant, on myocardial function after aortic cross-clamping in experimental heart ischemia

During aortic cross-clamping, the myocardium suffers from global ischemia, which is followed by reperfusion after declamping. The generation of free oxygen radicals increases during reperfusion, resulting in arrhythmias and impaired cardiac function. This study was conducted to evaluate the effect of a novel antioxidant nitecapone (NC) on cardiac reperfusion injuryin vivo. Twelve pigs were anesthetized and after sternotomy the aorta and the right atrium were cannulated for cardiopulmonary bypass. The heart was arrested with either +4°C crystalloid cardioplegia alone in the control group (n=6) or cardioplegia with NC (50 µM) added in the NC group (n=6). Cardioplegia was added every 20 minutes. After 1 hour of aortic crossclamping, blood samples for oxidative stress analysis were taken, and hemodynamic profile surveillance continued for 90 minutes. Heart rate (p=0.04) and left ventricular end diastolic pressure (LVEDP) (p=0.04) were significantly lower in the NC group than in the C group after aortic declamping. Cardiac output and myocardial contractility (dP/dt_max) were also enhanced in the group receiving NC, but the difference was not statistically significant. At 30 minutes after reperfusion, the coronary production (coronary sinus-aorta) of thiobarbituric acid reactive substances correlated inversely with cardiac output (r=–0.90,p=0.001) and stroke volume (r=–0.82,p=0.007). The effect of NC on lipid peroxidation seems to be modest and therefore the target of NC is unclear. NC would appear, however, to be a beneficial additive in the crystalloid cardioplegia in terms of functional recovery.