Ayala Lusky

Elevated serum uric acid — a facet of hyperinsulinaemia

SummaryIn a representative sample of the adult Jewish population in Israel (n=1016) excluding known diabetic patients and individuals on antihypertensive medications, serum uric acid showed a positive association with plasma insulin response (sum of 1- and 2-hour post glucose load levels) in both males (r=0.316, p<0.001) and females (r=0.236, p<0.001). This association remained statistically significant in both sexes (p<0.001) after accounting by multiple regression analysis for age and major correlates of serum uric acid, i.e. body mass index, glucose response (sum of 1- and 2-hour post load levels), systolic blood pressure and total plasma triglycerides. The net portion of the variance of serum uric acid attributable to insulin response was 12% in males and 8% in females, the total variance accountable by all these variables being 17% and 19% respectively. We conclude that elevated serum uric acid is a feature of hyperinsulinaemia/insulin resistance.

Excess mortality and morbidity among small-for-gestational-age premature infants: a population-based study

OBJECTIVE We examined the effect of intrauterine growth restriction on mortality and morbidity in the Israel cohort of very low birth weight premature infants. METHODS The study population included 2764 singleton very low birth weight infants without congenital malformations born from 24 to 31 weeks of gestation during 1995 to 1999. Four hundred six (15%) were born small for gestational age (SGA). The effect of SGA on death, bronchopulmonary dysplasia, and retinopathy of prematurity was assessed using multiple logistic regression analysis. RESULTS After adjustment for perinatal risk factors, SGA infants had a 4.52-fold risk for death (95% CI, 3.24-6.33), a 3.42-fold risk for bronchopulmonary dysplasia (95% CI, 2.29-5.13), and a 2.06-fold risk for grade 3 to 4 retinopathy of prematurity (95% CI, 1.15-3.66). CONCLUSIONS SGA premature infants had an increased risk for death, and major morbidity among survivors was increased.

Coronary artery bypass without cardiopulmonary bypass: Analysis of short-term and mid-term outcome in 220 patients

Two hundred twenty patients, preferentially those with high-risk conditions, underwent coronary artery bypass grafting without cardiopulmonary bypass. Early unfavorable outcome events included operative mortality (7 patients, 3.2%), nonfatal perioperative myocardial infarction (6 patients, 2.7%), cerebrovascular accident (1 patient, 0.4%), and sternal infection (3 patients, 1.4%). There were two deaths (13%) among 15 patients with calcified aorta and four (12%) in 33 patients who underwent emergency operation. Multivariate analysis revealed these two risk factors to be the only predictors of early mortality (odds ratios, 8.0 and 9.8, respectively). Preoperative risk factors such as left ventricular dysfunction (ejection fraction < or = 35%) (40 patients, 18%), congestive heart failure (46 patients, 21%), acute myocardial infarction (59 patients, 27%), cardiogenic shock (7 patients, 3%), age 70 years or older (59 patients, 27%), renal failure (19 patients, 9%), and cerebrovascular accident and carotid disease (11 patients, 5%) were not found to be major predictors of early mortality or unfavorable outcome. During 12 months of follow-up (range 1 to 21 months), there were four cardiac and three noncardiac deaths (1-year actuarial survival 93%) and 17 cases (7.7%) of early return of angina. Calcified aorta, nonuse of the internal mammary artery, reoperation, and diabetes mellitus were independent predictors of unfavorable events. We conclude that coronary artery bypass grafting without cardiopulmonary bypass can be done with relatively low operative mortality, although there seems to be an increased risk for early return of angina. This procedure should therefore be considered for patients with appropriate coronary anatomy, in whom cardiopulmonary bypass poses a high risk. This procedure is still hazardous with calcified aorta or emergency operation.

Effect of past and concurrent body mass index on prevalence of glucose intolerance and Type 2 (non-insulin-dependent) diabetes and on insulin response

SummaryA representative sample (n=2140) of the Israeli Jewish population aged 40–70 (excluding known diabetic patients), whose body mass index had been measured 10 years earlier, underwent an oral glucose tolerance test and redetermination of body mass index. Irrespective of weight changes, high concurrent and high past body mass index values (≥ 27) were associated with similarly increased rates of glucose intolerance as compared with body mass index values < 27 at both time-points (rate ratio 1.76, 90% confidence limits 1.56–1.99). Glucose intolerance here includes borderline and impaired tolerance as well as Type 2 diabetes. The rate of Type 2 diabetes increased only with increasing past body mass index, while concurrent body mass index had no effect [rate ratios: 2.36 (1.48–3.75) and 1.99 (1.48–2.68) respectively for the medium-(23–26.9) versus-low (<23) and high- (≥ 27) versus-medium past body-mass-index categories]. Weight reduction was associated with only slightly reduced rate of glucose intolerance and had no effect on the rate of diabetes. Mean sum insulin (summed 1 and 2 h levels, mU/l) increased significantly with increasing concurrent body mass index (123, 150 and 190 in the low, medium and high categories) with no effect of past body mass index. It also increased significantly (p < 0.001) in all concurrent body mass index categories from normal tolerance through borderline to impaired tolerance, and decreased significantly (p < 0.001) in diabetes relative to impaired tolerance, although it remained above normal. Means of sum insulin within each glucose tolerance level were similar in the two lower concurrent body mass index categories, with markedly higher (p < 0.001) levels in the high body mass index category. All these findings held after accounting for age, sex, ethnic group and use of antihypertensive medications. We conclude that body mass index ≥ 27 leads to early impairment in glucose tolerance. A prolonged period of obesity is apparently required for the development of Type 2 diabetes and its associated reduced insulin response. The reversibility of the deterioration of glucose tolerance seems to be limited.

Pathogen-Specific Early Mortality in Very Low Birth Weight Infants with Late-Onset Sepsis: A National Survey

BACKGROUND Late-onset sepsis (LOS) is an important cause of mortality among very low birth weight (VLBW) infants, and deaths occurring within 3 days after the onset of sepsis can probably be ascribed to sepsis. We examined the association of sepsis due to specific pathogens with the risk for early mortality after the onset of LOS, adjusted for perinatal and neonatal risk factors. METHODS From 1995 through 2001, information about 10,215 infants was gathered and deposited in the Israel National VLBW Infant Database. The study population was composed of 2644 infants, of which each had >or=1 events of LOS (totalling 3462 events). Logistic regression models were used to calculate the crude and adjusted risk for early mortality. RESULTS Early mortality was associated with 179 LOS events (5.2% of 3,462); the range of pathogens associated with these events included coagulase-negative staphylococci (CoNS), which were the cause of 1.8% of LOS events associated with early mortality, and Pseudomonas species, which were the cause of 22.6% of such events. Early mortality after LOS, adjusted for neonatal risk factors, was significantly associated with sepsis due to certain pathogens: Pseudomonas species (odds ratio [OR], 12.3); Klebsiella species (OR, 6.3); Serratia species (OR, 6.2); Escherichia species (OR, 4.3); Enterobacter species (OR, 4.1); and Candida species (OR, 3.2), compared with sepsis due to CoNS . In addition, lower gestational age, lower chronological age, small size for gestational age, and grade 3-4 intraventricular hemorrhage, each had an independent association with early mortality. CONCLUSIONS Klebsiella sepsis and Pseudomonas sepsis were associated with a 6.3-fold and 12.3-fold increased risk of early mortality, respectively, and accounted for 41.9% of all early deaths associated with LOS. Considering the aggressive nature of sepsis caused by these pathogens, empiric antibiotic therapy active against these organisms is worth consideration for VLBW infants with presumed LOS.

A prospective comparison of the outcome of triplet pregnancies managed expectantly or by multifetal reduction to twins

OBJECTIVE Our aim was to compare the outcome of triplet pregnancies managed expectantly or by multifetal reduction to twins. STUDY DESIGN From January 1984 through January 1992, 140 triplet gestations were diagnosed before the ninth gestational week. Multifetal pregnancy reduction was performed at the patients request in 34 women. The remaining 106 triplet pregnancies were managed expectantly. All patients were prospectively followed up and delivered in a single perinatal department. RESULTS Loss of the entire pregnancy before 25 gestational weeks occurred in 20.7% of the triplet pregnancies managed expectantly as compared with 8.7% in the group with reduction to twins. A successful pregnancy as defined by the discharge home of at least one infant occurred in 88.2% of the group with reduction to twins and 74.5% of the triplets managed expectantly. Fetal reduction to twins was associated with a significantly lower incidence of the following: prematurity (p < 0.001), low-birth-weight infants (p < 0.001), and very-low-birth-weight infants (p < 0.001). Pregnancy complications and neonatal morbidity and mortality were less in the group with reduction to twins. CONCLUSIONS Multifetal pregnancy reduction of triplet pregnancies to twins resulted in improved pregnancy outcome without an excess loss of the entire pregnancy as compared with the outcome of triplet gestations managed expectantly.

Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs.

Responsiveness to antihypertensive medications was investigated cross-sectionally in 559 individuals comprising all treated hypertensive patients identified within a representative sample (n=3,532, aged 40-70 years) of the Jewish population in Israel. A rate of dosage score (a summed ranking of dosages of all drugs taken) of two or more increased significantly with increasing levels of body mass index (BMI) from 37.5% in levels less than 23, 54.9% in levels 23.0-29.9, and 76.4% in levels of 30 or greater (/?<0.0001). Multivariate analyses, adjusting for age, gender, arm circumference, and ethnic group, confirmed the independent effect of BMI on dosage score (p<0.001). At each level of dosage score, mean blood pressure levels were equivalent at all levels of BMI after adjusting for potential confounders. This indicates that achieved blood pressure level and not BMI itself was the main determinant of the higher dosing regimens prescribed at higher levels of BMI. In representative subgroups, glucose tolerance (n=372) and hyperinsulinemia (n=190) were determined and were found to be positively associated with a dosage score of two or more (p<0.05) independently of BMI. These effects could not be accounted for by poor compliance or by altered drug absorption or disposition since overnight urinary drug excretion and plasma drug concentrations 2 hours after ingestion, measured in 80 randomly selected patients from the study group, were not different across BMI categories at similar dosages. These findings indicate that obesity, even at mild levels, as well as glucose intolerance and hyperinsulinemia, is associated with decreased responsiveness to antihypertensive medications, perhaps as a manifestation of the insulin resistance that characterizes these conditions.

Hyperinsulinemia is characterized by jointly disturbed plasma VLDL, LDL, and HDL levels. A population-based study.

Plasma very low density llpoproteln (VLDL) cholesterol and trlglycerlde, low density llpoproteln (LDL) cholesterol and trlglycerldea, high density llpoproteln (HDL) cholesterol, glucose and Insulin response (sums of 1- and 2-hour postload oral glucose levels), body mass Index (BMI), and blood pressure were determined In a representative sample (n = 542) of the adult Israeli Jewish population. Persons with diabetes or on antlhypertenslve medications were excluded. Total VLDL and LDL fractions were estimated from their cholesterol and trlglyceride subtraction levels that were standardized relative to the mean of the reference group (participants free of glucose Intolerance, obesity, and hypertension – the GOH conditions). Hyperinsulinemia and disturbed levels of VLDL and LDL were defined as levels equal to or greater than the 75th percentile and those of HDL, equal to or less than the 25th percent Me of their respective reference group distributions. When VLDL was disturbed jointly with LDL and HDL, the mean Insulin response adjusted for age, gender, glucose response, BMI, blood pressure, and smoking was high compared to the reference group (166.0 vs.122.5, p < 0.001). With Isolated disturbed VLDL, or disturbed LDL and HDL but normal VLDL, the mean Insulin response resembled the reference group. The adjusted risk ratio for this jointly disturbed llpoproteln profile among hyperinsullnemlc Individuals was 3.4 (95% confidence limits 2.6 to 4.4, p < 0.001) with no further association with the GOH conditions. We conclude that hyperlnsullnemia is characterized by an atherogenlc llpoproteln profile.

Significance of High HbA1 Levels in Normal Glucose Tolerance

The significance of high hemoglobin A1 (HbA1) levels (≥8.0%) found in 12.1% of 648 individuals with normal glucose tolerance constituting a part of a representative population sample was examined. Measurement error in HbA1 and/or glucose-tolerance levels was precluded by HbA1 remaining in the same range over 3.5 yr in 89.7% of 29 individuals with initially high and 68.1% of 22 individuals with initially low (<6.5%) HbA1. Rate of deterioration to glucose intolerance (6.9%) in the high group during that period resembled the rate (11.8%) in a control group (n = 279). Fasting plasma glucose significantly accounted for only 2.4% of total HbA1 - population variance. No correlation of HbA1 was found with other correlates of glucose tolerance or with daily caloric intake and physical activity. A small but significant increment in HbA1 was associated with smoking (7.1 vs. 6.8%, P < .01) and with clinically overt atherosclerosis (7.3 vs. 6.9%, P < .01). We conclude that factors unrelated to glucose metabolism are the main determinants of HbA1 level in normal glucose tolerance and play an important role in diabetes as well. These factors have bearing on evaluation of diabetic control by HbA1 and possibly on risk for diabetic complications.

Hyperinsulinemia, sex, and risk of atherosclerotic cardiovascular disease.

BackgroundThe possibility that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease (CVID) was first suggested 20 years ago. During the last decade, this possibility has received support from three large prospective studies. Methods and ResultsIn the present study, the association between CVID, glucose intolerance, obesity, and hypertension (the GOH conditions) and hyperinsulinemia was examined crosssectionally in a representative sample (n = 1,263) of the adult Jewish population aged 40–70 years in Israel. Previously known diabetics were excluded. CVID comprising clinical or ECG evidence of ischemic heart disease, as well as clinical evidence of cerebrovascular or peripheral vascular disease, was identified in 97 men and 39 women. A significant (p < 0.01) hyperinsulinemia- sex interaction was found for CVD rate, with the adjusted risk ratios (followed by 95% confidence limits), relative to the rate in 298 normoinsulinemic women, being 1.15 (0.68–1.95) in 328 normoinsulinemic men, 0.85 (0.48–1.49) in 277 hyperinsulinemic women, and 2.27 (1.33–3.08) in 360 hyperinsulinemic men. Age-adjusted CVD rates in men versus women were: a) similar and low among all normoinsulinemic normotensives and hyperinsulinemics free of any of the GOH conditions (all rates .6.5%); b) similar and high among normoinsulinemic hypertensives (13.4% versus 10.4%); c) significantly higher in men among hyperinsulinemic normotensives with glucose intolerance and/or obesity (15.2% versus 3.3%; p = 0.02) and all hyperinsulinemic hypertensives (21.5% versus 12.8%; p = 0.04). These trends remained significant after adjusting for age, ethnic group, and blood lipids. ConclusionsTherefore, hyperinsulinemia was associated with excess CVII risk in men but not in women, and all excess CVD risk in men was confined to hyperinsulinemic individuals in the presence of glucose intolerance, obesity, or hypertension.