Zahava Fuchs

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.

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.

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.

Familial aggregation of haematological neoplasms: a controlled study.

Summary. Advances in molecular biology techniques suggest that many haematological neoplasms originate from a transformation process at the level of the haemopoietic pluripotential stem cell. While familial aggregation has been reported for many haematological neoplasms, most studies were uncontrolled and examined the presence of the same haematological neoplasm as the index case. We assessed the familial aggregation of all haematological neoplasms in 4061 family members of 189 patients with various haematological neoplasms and two control groups: 955 relatives of 36 patients with non‐malignant haematological disorders and 508 relatives of 33 patients with type II diabetes mellitus. Data collection included self‐administered questionnaires. The odds ratio for haematological neoplasms among relatives of the index cases adjusted for age, sex, ethnicity, number of relatives in the family, and degree of familial linkage in the study group versus the two control groups was 3.62 (95% confidence interval, 1.44‐9.07; P<0.01). The vast majority of the haematological neoplasms among family members did not belong to the same histopathological category as the index cases. The data support the hypothesis of a genetic predisposition to haematological neoplasms. The fact that the aggregation is not disease specific is consistent with a defect in the pluripotent haemopoietic stem cell.

The Effect of a Communal Lifestyle on Depressive Symptoms in Late Life

Objectives: This study compares depression levels among lifetime kibbutz members (n = 525) and old-age kibbutz residents (n = 366) with a comparable national sample (n = 412) and assesses the relationship between depression and individual differences related to lifetime in a kibbutz (e.g., health) and those related to current living conditions (e.g., social network). Methods: The analysis is based on data from the Cross-Sectional and Longitudinal Aging Study conducted in Israel between 1989 and 1992 and the follow-up during 1993 and 1994. Results: The findings indicate significantly lower depressive symptomatology among women, but not among men, residing in kibbutz communities. The women’s lower level of depressive symptoms appears to be a result of better physical and mental functioning among kibbutz members and of such favorable lifestyle characteristics as frequent contact with their children among old-age kibbutz residents. Discussion: Both lifetime and current living conditions contribute to better mental health of women in the kibbutz at older ages.

Senile cataract and glucose intolerance: the Israel Study of glucose Intolerance Obesity and Hypertension (The Israel GOH Study).

Association of “senile” cataract (SC) with glucose intolerance (impaired tolerance and diabetes) was assessed by sex and age in a random population sample comprising 930 individuals aged 40–70 yr, who underwent concurrent oral glucose tolerance test and ophthalmoscopy. The eye examination was performed without knowledge of the glucose tolerance status. SC was defined as lens opacification preventing visualization of the eyeground or as surgical aphakia due to SC. To assess the independent effect of hyperglycemia, glycosylated hemoglobin (HbA1) was determined in 769 participants. In men, no association was found between SC, glucose intolerance, and HbA1. In women of all ages, glucose intolerance was associated with an SC risk ratio of 6.1 (95% confidence limits 3.3–11.1; P < 0.001). Furthermore, SC was associated in women with increased HbA1 independently of the effect of glucose intolerance (P < 0.01). These findings confirm the reported association of SC with diabetes (although unlike the Framingham and HANES population studies, the association was confined in women), indicate its presence at all degrees of glucose intolerance, and suggest a possible independent role of nonenzymatic glycosylation in its pathogenesis.

Depressive Symptoms Among Community-Dwelling Oldest-Old Residents in Israel

The authors examined the rate and correlates of depressive symptoms among community-dwelling oldest-old citizens in Israel with a sample of about 1,200 Jewish Israelis age 75-94. The estimated national rate of depressive symptoms was 43.5%. Significantly higher rates of depressive symptoms were found in women (52%, vs. 29.5% for men) and those of low educational level, low income, and Middle Eastern or North African origin. Having more depressive symptoms was associated with 1) all measures of impaired health status; 2) the psychosocial factors of living alone or with a nonspouse, having no available caretaker, and social and physical inactivity; 3) the following health behavior and habits: poor sleep, skipping meals, sexual inactivity, and drinking no alcohol; and 4) traumatic life events and immigration after age 20. The rate of depressive symptoms is relatively high among oldest-old citizens in Israel, possibly because of the immigrant nature of this population.

Smoking accounts for adverse effect of antihypertensive medications on plasma lipids. A population-based study.

Mean plasma levels of total cholesterol, high density lipoprotein cholesterol, total-to-high density lipoprotein cholesterol ratio, and total triglycerides were determined in a representative sample of the adult Israeli Jewish population, excluding known diabetics and individuals with overt atherosclerotic morbidity (n = 1,153). Levels were compared in normotensive and untreated and treated hypertensive individuals by glucose tolerance category and smoking, after adjustment for sex, age, and body mass index. In the presence of normal glucose tolerance, lipid levels in the nonsmoking normotensive and treated hypertensive groups were similar, whereas in the smoking, treated hypertensive group, lipids were significantly affected, as indicated by the respective adjusted mean levels (mg/dl): total cholesterol, 219, 221, and 240; high density lipoprotein cholesterol, 45.0, 43.6, and 42.0; ratio, 5.2, 53, and 6.0; and triglycerides, 114, 107, and 144. In individuals with glucose intolerance, trends were the same with the exception of triglycerides, which were significantly elevated in the nonsmoking, treated hypertensive group also; the respective values were 217, 225, and 257 for total cholesterol; 45.1, 44.9, and 41.4 for high density lipoprotein cholesterol; 5.2, 5.5, and 6.8 for the ratio; and 133, 152, and 187 for triglycerides. Lipid disturbances in treated smokers were not due to heavier smoking or differences in dietary intake. We conclude that disturbance of plasma lipid profile in treated hypertensive individuals may be mainly due to an interaction with smoking, with an additional effect of glucose intolerance.