Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals

We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40-70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, pro-insulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A1c, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia.     

Cryptococcosis in tree shrews (Tupaia tana and Tupaia minor) and elephant shrews (Macroscelides proboscides)

OBJECTIVE: To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS: Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17-36 years, body mass index (BMI) 29.9 +/- 0.9 kg/m2, mean +/- SD) and 18 control women (25-47 years, BMI 25 +/- 1.7 kg/m2). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations. MEASUREMENTS: Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay. RESULTS: Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/ hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 +/- 1.3 vs 12.1 +/- 2.3 micrograms/l, mean +/- SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups. CONCLUSIONS: Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.     

Cutaneous reactions at the site of post-infection gp160 vaccination therapy in HIV-1+ patients. Military Medical Consortium for the Advancement of Military Medicine

OBJECTIVES: To define the pathophysiologic characteristics of patients at high risk for coronary heart disease due to an increased ratio of total cholesterol (TC) to high density lipoprotein-cholesterol (HDL-C). DESIGN: Cross-sectional. SETTING: Clinical Research Center. SUBJECTS: One hundred-20 healthy, non-diabetic, normotensive, volunteers were screened for this study. From this pool, 40 individuals (20 females and 20 males) with the highest and the lowest TC/HDL-C ratios were selected for comparison. MAIN OUTCOME MEASURES: Values for body mass index (BMI), ratio of waist to hip girth (WHR), and blood pressure were obtained on all patients. In addition, measurements were made of fasting lipid and lipoprotein concentrations, plasma glucose and insulin responses to an oral glucose challenge, and insulin resistance as assessed by the insulin suppression test. RESULTS: Age, BMI, and WHR were the same in the two groups. However, the group with a high TC/HDL-C ratio had higher (P < 0.05) systolic and diastolic blood pressures. In addition, patients with a high TC/HDL-C ratio had significantly higher (P < 0.001) very low density (VLDL) and low density lipoprotein (LDL)-cholesterol concentrations and lower HDL-cholesterol concentrations, with significant (P < 0.001) correlations between the TC/HDL-C ratio and VLDL (r = 0.60), LDL (r = 0.54), and HDL (r = -0.73) cholesterol concentrations. Patients with a high TC/HDL-C ratio were also significantly (P < 0.05-0.001) more insulin resistant, glucose intolerant with a greater plasma insulin response to oral glucose, and hypertriglyceridemic. CONCLUSIONS: The results indicate that an increase in LDL-cholesterol concentration is not necessarily the major contributor to a high ratio of TC/HDL-C. Furthermore, individuals with this epidemiologic designation are insulin resistant, and liable to all the other abnormalities associated with this metabolic defect.     

Determinants of the kinetics of very low-density lipoprotein apolipoprotein B-100 in non-obese men

1. Apolipoprotein B-100 (ApoB) is the principal structural and functional protein of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease. In the present study we aimed to assess the factors that determine the kinetics of apoB in the very low-density lipoprotein (VLDL) in healthy men. 2. We studied 17 non-obese men who were consuming an ad libitum diet and had the following characteristics: mean (+/-SD) age 45.5 +/- 9.7 years, body mass index (BMI) 25.1 +/- 1.4 kg/m2, waist:hip ratio 0.91 +/- 0.04, serum cholesterol 5.2 +/- 0.6 mmol/L, triglycerides 1.08 +/- 0.53 mmol/L and high-density lipoprotein-cholesterol 1.24 +/- 0.31 mmol/L. Daily dietary intake was as follows: total fat 76 +/- 26 g, carbohydrate 238 +/- 67 g, protein 103 +/- 33 g and alcohol 20 +/- 16 g. 3. The kinetics of VLDL ApoB were studied using a primed, constant infusion (1 mg/kg per h) of 1-[13C]-leucine over 8 h with measurement of isotopic enrichment of ApoB using gas chromatography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoexponential function. The mean (+/-SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 +/- 4.6 mg/kg per day and the fractional catabolic rate (FCR) was 7.9 +/- 5.6 pools/day. The ASR was significantly correlated with the waist:hip ratio (r = 0.60; P = 0.04), but not with age, BMI, weight or nutrient intake. The FCR was significantly and inversely correlated with plasma triglycerides (r = -0.53; P = 0.03) and alcohol intake (r = -0.48; P = 0.05). 4. In conclusion, the hepatic secretion of VLDL ApoB in nonobese, healthy men is primarily determined by the waist:hip ratio, a measure of visceral fat. This is consistent with the hypothesis that the rate of lipid substrate supply in the liver regulates the output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to determine the plasma concentration of triglycerides.     

Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. The Nurses' Health Study

Obesity is an established risk factor for non-insulin-dependent diabetes mellitus (NIDDM). Anthropometric measures of overall and central obesity as predictors of NIDDM risk have not been as well studied, especially in women. Among 43,581 women enrolled in the Nurses' Health Study who in 1986 provided waist, hip, and weight information and who were initially free from diabetes and other major chronic diseases, NIDDM incidence was followed from 1986 to 1994. After adjustment for age, family history of diabetes, smoking, exercise, and several dietary factors, the relative risk of NIDDM for the 90th percentile of body mass index (BMI) (weight (kg)/height (m)2) (BMI = 29.9) versus the 10th percentile (BMI = 20.1) was 11.2 (95% confidence interval (CI) 7.9-15.9). Controlling for BMI and other potentially confounding factors, the relative risk for the 90th percentile of waist: hip ratio (WHR) (WHR = 0.86) versus the 10th percentile (WHR = 0.70) was 3.1 (95% CI 2.3-4.1), and the relative risk for the 90th percentile of waist circumference (36.2 inches or 92 cm) versus the 10th percentile (26.2 inches or 67 cm) was 5.1 (95% CI 2.9-8.9). BMI, WHR, and waist circumference are powerful independent predictors of NIDDM in US women. Measurement of BMI and waist circumference (with or without hip circumference) are potentially useful tools for clinicians in counseling patients regarding NIDDM risk and risk reduction.     

Cytoreductive surgery in ovarian carcinoma patients with a documented previously complete surgical response

The lipoprotein distribution profile was examined in Type 2 (non-insulin-dependent) diabetic patients (n = 52), with particular emphasis on factors influencing low density lipoproteins (LDL). Triglycerides were negatively correlated with LDL-2 (r = 0.34, p < 0.05) and positively correlated with smaller, denser LDL-3 (r = 0.57, p < 0.001). This yielded a highly significant, negative correlation between triglycerides and the LDL-2/LDL-3 mass ratio (r = -0.59, p < 0.001) which is an indication of the presence of smaller LDL particles. Parameters of glycaemic control, in the form of fasting blood sugar and glycated haemoglobin (HbA1c), were also negatively correlated with the LDL-2/LDL-3 mass ratio in univariate analyses; both remained significantly correlated with the mass ratio when corrected for triglycerides. Stepwise multiple regression analysis identified a three-parameter model comprising triglycerides, HbA1c, and high density lipoprotein cholesterol as best defining the variations in the LDL-2/LDL-3 mass ratio (adjusted r2 = 0.52). These observations are consistent with an independent impact of diabetes on the LDL distribution profile and the possibility that the latter may be subjected to multiple pathological influences in diabetic patients.     

Localisation of gelatinase activity in epidermal hoof lamellae by in situ zymography

Several studies have shown that insulin resistance and hyperinsulinemia are associated with many metabolic disorders predisposing to coronary heart disease (CHD). This syndrome has been termed syndrome X. However, it is not completely known whether these relationships are still present in the elderly, or whether other factors such as age, gender, and body fat distribution modulate them. Therefore, we investigated the relationship between fasting plasma insulin, total and regional adiposity, fasting plasma glucose and lipids, plasma plasminogen activator inhibitor-1 (PAI-1), fibrinogen, and coagulation factor VII in a sample of 100 healthy free-living octogenarians-nonagenarians (52 men and 48 women) who were disability-free according to the Katz index. By univariate analysis, fasting insulin correlated positively with all anthropometric measures except the waist to hip ratio (WHR) in women. There was a positive correlation between fasting insulin and fasting glucose (r=.40, P < .01), plasma triglycerides ([TGs] r=.21, P < .05), and PAI-1 levels (r=.33, P < .01), whereas a negative relation was found with high-density lipoprotein cholesterol (HDL-C) and apolipoprotein, A-I (apo A-I) levels (r=-.22 and =-.24, respectively, P < .05). These relationships were weaker and less significant in women. In pooled data, stepwise multiple regression analysis showed an independent relationship of both the body mass index (BMI) and fasting insulin level with TGs (R2=.14), while gender and fasting insulin were the best predictors of HDL-C variance (R2=.17). Furthermore, fasting insulin was the only variable independently related to PAI-1 (R2=.12). Our findings support the existence of a metabolic syndrome even in very old age by showing that high insulin levels are related to various metabolic and hemostatic disorders.     

Hyperinsulinemia and clustering of cardiovascular risk factors in middle-aged hypertensive Finnish men and women

OBJECTIVE: To examine the relationship between hyperinsulinemia and clusters of cardiovascular risk factors in middle-aged hypertensive patients. DESIGN: A population-based study. SETTING: Pieks?m?ki District Health Center, and the Community health Center of the city of Tampere, in central Finland. SUBJECTS: Hypertensive men and women aged 36, 41, 46, and 51 years (n = 18) in the town of Pieks?m?ki, and a normotensive control population of 177 subjects aged 40 and 45 years in the city of Tampere. MAIN OUTCOME MEASURES: Clusters of obesity (body mass index > 30.0 kg/m2), abdominal adiposity (waist:hip ratio > 1.00 for men and > 0.88 for women), hypertriglyceridemia (> 1.70 mmol/l), a low level of high-density lipoprotein cholesterol (< 1.0 mmol/l in men and < 1.20 mmol/l in women) and abnormal glucose metabolism (impaired glucose tolerance or noninsulin-dependent diabetes as defined by World Health Organization criteria) according to statistical quartiles of the fasting plasma insulin concentration. RESULTS: Among the hypertensives, there was a 2.0- to 3.6-fold higher risk of having a clustering of the insulin-resistance associated cardiovascular risk factors compared with that of the normotensives. Among the hypertensive subjects in the highest quartile of fasting plasma insulin there was a six- to 12-fold increase in risk associated with having two or more insulin resistance-associated cardiovascular risk factors compared with the subjects in the lowest quartile. There was a positive correlation between a high number of ascertained risk factors and high levels of fasting plasma insulin. CONCLUSION: In clinical practice, knowledge of the close relationship between risk-factor cluster status and fasting plasma insulin levels offers a tool to evaluate the occurrence of hyperinsulinemia in middle-aged hypertensive men and women.     

A pragmatic test of a simple calorimetric method for determining the fragility of some amorphous pharmaceutical materials

This study was performed in 36 healthy volunteers to define the relationship between plasma concentrations of partially oxidized low density lipoprotein (poxLDL), plasma glucose and insulin responses to oral glucose, and steady-state plasma glucose (SSPG) concentrations after a 180-minute infusion of somatostatin, insulin, and glucose. The concentration of poxLDL was estimated by determining the amount of conjugated dienes formed during in vitro LDL oxidation in the presence or absence of alanine. Under these conditions, the greater the in vitro antioxidant effect of alanine, the lower the amount of poxLDL that was present in plasma. The results demonstrated that plasma poxLDL concentration was significantly correlated with plasma glucose (r=.53, P<.001) and insulin (r=.43, P<.01) responses, SSPG concentrations (r=.53, P<.001), and plasma triglyceride (r=.42, P<.01) and HDL cholesterol (r=-.50, P<.002) concentrations. Furthermore, these relationships persisted when the data were corrected for differences in age, sex, body mass index, and the ratio of waist to hip girth. Of note, there was no correlation between poxLDL and LDL cholesterol concentration. When SSPG was entered along with age, sex, body mass index, and waist-to-hip ratio in a multiple regression model, SSPG alone was a significant prediction of poxLDL (r-=.37, P<.02). The addition of plasma glucose and insulin responses and triglyceride and HDL cholesterol concentrations increased the r2 to only .47. These results show that the amount of poxLDL in plasma is significantly correlated with insulin resistance (ie, SSPG) and its metabolic consequences.     

Lipoprotein lipase gene polymorphism in non-insulin-dependent diabetics: preliminary study

BACKGROUND: Lipoprotein lipase plays a crucial role in plasma lipoprotein metabolism. Several lipoprotein lipase gene polymorphisms have been found associated with lipid levels, premature atherosclerosis and cardiovascular disease. AIM: To investigate, in the Chilean population, the genotype distribution of lipoprotein lipase polymorphisms and its possible association with lipid levels and obesity. PATIENTS AND METHODS: Hind III and Pvu II polymorphism was determined in 45 non-insulin-dependent diabetic patients and in 52 non diabetic controls from Santiago, Chile. RESULTS: Hind III (+/+) polymorphism had a higher frequency in diabetics as compared to controls (0.6 and 0.29 respectively, p = 0.009). The frequency of heterozygous distribution was higher in non diabetic subjects. Controls and diabetics had comparable gene frequencies for the Pvu II genotype distribution. Analyzing the impact of these polymorphisms on plasma lipid levels, Hind III (+/+) genotype was associated with high levels of total cholesterol and triglycerides in both groups. The heterozygote (+/-) or homozygote (-/-) state for Hind III was effectively associated with high levels of HDL cholesterol levels, as compared to the (+/+) genotype. There was no relationship between these genotypes and body mass index and waist to hip ratio. CONCLUSIONS: An association between genetic variation at the lipoprotein lipase locus with high levels of triglycerides and total cholesterol was confirmed. However, no association of these genetic markers with anthropometric measurements was found.     

The accuracy and precision of four infrared aural canal thermometers during cardiac surgery

Hormone replacement therapy has been shown to decrease the risk of coronary heart disease (CHD) in menopausal women. In this cross-sectional study, we addressed the following question: What effects would combined oral hormone replacement therapy have on plasma lipid and lipoprotein profiles independent of the other known CHD risk factors? We analyzed the plasma lipoproteins of two groups of menopausal women who were randomly selected from a large database of individuals. One group (n = 10) was not taking any hormone replacement therapy (NO HRT), while the second group (n = 8) was taking a daily dose of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone orally (PremPro, Wyeth-Ayerst, Philadelphia, PA) for at least 6 months (HRT). The two groups were not different in age, body weight, percent body fat, body mass index (BMI), waist to hip ratio, blood pressure, or insulin and glucose levels. High-density lipoprotein (HDL)-cholesterol was significantly higher (P < .05) in the HRT group. The total cholesterol (TC) to HDL-cholesterol ratio was significantly lower for HRT versus NO HRT (P < .05). Apolipoprotein (apo) A-1, the apo A-1/B ratio, and lecithin:cholesterol acyltransferase (LCAT) activity were significantly higher in HRT (P < .05). Lipoprotein subclass profiles measured by nuclear magnetic resonance (NMR) spectroscopy showed an increase in larger HDL subpopulations (H3 and H4) in HRT (P < .05), which are considered antiatherogenic. No differences were seen in the cholesterol concentration or size of low-density lipoprotein (LDL) subpopulations in HRT compared with NO HRT. These results indicate that the combined estrogen and progesterone treatment leads to beneficial effects on plasma lipoproteins. The beneficial effects include (1) increases in HDL-cholesterol and predominance of HDL2, (2) no adverse effects on LDL subpopulation distribution, and (3) increases in apo A-1 levels and LCAT activity, which indicate an improvement in reverse cholesterol transport.     

Enalapril versus bendroflumethiazide in type 2 diabetes complicated by hypertension

In a double-blind, double-dummy, randomized, multi-centre study, the effects of bendroflumethiazide vs. enalapril on blood pressure, glycaemic control, lipoprotein concentrations and albuminuria were compared in non-proteinuric, hypertensive type 2 diabetic patients; they were treated for 20 weeks with either bendroflumethiazide 2.5-5.0 mg (n = 59) or enalapril 10-20 mg (n = 55). Age, fasting plasma glucose, HbA1c and BMI were similar in the groups. Systolic and diastolic blood pressure were reduced in both groups. Bendroflumethiazide was accompanied by minor but significant elevations in fasting plasma glucose and serum C-peptide. HbA1c was increased during both treatments. Lipoproteins and urinary albumin/creatinine ratio were stable. Bendroflumethiazide caused a decrease in serum potassium and an increase in serum urate. No significant correlations were observed between the decline in blood pressure and changes in the metabolic risk factors. Baseline levels of age, sex, BMI, blood pressure or urinary albumin/creatinine ratio were not related to changes in blood pressure, metabolic parameters or urinary albumin/creatinine ratio.     

Impaired left ventricular relaxation and hyperinsulinemia in patients with primary hypercholesterolemia

Fifteen non-obese patients with familial hypercholesterolemia and fifteen normocholesterolemic subjects matched for age, body mass index, waist/hip ratio, arterial blood pressure and sedentary life style underwent blood sampling for determination of fasting plasma glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides, free fatty acids, apolipoprotein A1 and B. In both groups of subjects we determined erythrocyte membrane microviscosity and performed an echocardiographic study. We demonstrated that hypercholesterolemic patients had a significant increase in fasting plasma total cholesterol (8.9 +/- 0.5 vs. 5.5 +/- 0.3 mmol/l, P less than 0.001), insulin (79 +/- 4 vs. 58 +/- 4 pmol/l, P less than 0.05) and apolipoprotein B (2.2 +/- 0.5 vs. 1.3 +/- 0.5 g/l P less than 0.01). In the echocardiographic study we found a significant impairment in left ventricular relaxation (isovolumic relaxation time (IRT) 106 +/- 6 vs. 73 +/- 7 ms, P less than 0.01). Erythrocyte membrane microviscosity (0.253 +/- 0.004 vs. 0.225 +/- 0.003, P less than 0.05) was also increased in hypercholesterolemic patients. Finally we found that erythrocyte membrane microviscosity correlated with fasting plasma insulin levels (r = -0.46, P less than 0.03) and IRT (r = -0.52, P less than 0.01).     

Perforating granuloma annulare

OBJECTIVE: To assess associations of adiposity with prevalent coronary heart disease (CHD) among elderly men. DESIGN: A cross-sectional epidemiologic study conducted between 1991 and 1993. SUBJECTS: 3741 Japanese-American men from the Honolulu Heart Program who were 71-93 y of age. MEASUREMENTS: CHD included documented myocardial infarction (electrocardiographic and enzyme criteria), acute coronary insufficiency, angina pectoris leading to surgical treatment identified through hospital surveillance, and reported history of heart attach or angina pectoris requiring hospitalization or surgical treatment. BMI was calculated as weight in kg divided by height in square meters. Waist circumference was measured at the horizontal level of the umbilicus and WHR was a ratio of waist circumference to hip circumference measured at the horizontal level of the maximal protrusion of the gluteal muscles. RESULTS: An elevated prevalence of CHD was observed in the elderly men with high BMI, WHR and waist circumference. The significant associations of BMI and waist circumference with CHD persisted after adjustment for fasting glucose, physical activity and pack-years of cigarette smoking but were no longer significant (odds ration (OR) = 1.03, 95% confidence level (CI) 0.94-1.12 and OR = 1.09, CI = 0.99-1.20, respectively) after adjustment for high density lipoprotein cholesterol (HDL-C). Also, the association of BMI with CHD was not found to be independent of abdominal adiposity. However, the associations of WHR and waist circumference remained significant (OR = 1.20, CI = 1.08-1.33 and OR = 1.17, CI = 1.01-1.37, respectively) after additional adjustment for BMI. In addition, the association of WHR with CHD was consistently significant and independent of fasting glucose, physical activity, smoking and HDL-C (OR = 1.11, CI = 1.00-1.23). CONCLUSION: WHR is associated with CHD independent of HDL-C and BMI, whereas the relation of BMI and waist circumference with CHD may be mediated through a relation of BMI and waist circumference with HDL-C level.     

Anti-hyperalgesic effect of an ethanolic extract of propolis in mice and rats

Abdominal obesity, anxiety, and depression have been found to cluster in several studies. To further characterize these associations, the following study was performed. In a population of 51-year-old men (N = 284), measurements of obesity (body mass index [BMI]) and body fat distribution (waist to hip ratio [WHR] and sagittal trunk recumbent diameter [D]) were analyzed in relation to dexamethasone (0.5 mg) inhibition of cortisol secretion, measured as salivary cortisol. Symptoms of anxiety and depression were defined by a validated questionnaire. Furthermore, testosterone, insulin-like growth factor-I (IGF-I), insulin, glucose, and serum lipid levels were measured. Twenty-five men (8.8%) had symptoms of anxiety and depression. BMI, WHR, and D correlated negatively with testosterone, except for BMI in the anxio-depressive (ADP) group. IGF-I showed no significant relationship. Furthermore, fasting insulin and the insulin to glucose ratio correlated positively and high-density lipoprotein (HDL) cholesterol correlated negatively with BMI, WHR, and D in the total study population and in the subgroups. Total and low-density lipoprotein (LDL) cholesterol showed no significant relationships. Correlation coefficients tended to be higher in ADP men. Dexamethasone inhibition showed a negative significant relationship with BMI (rho = -.47, P = .025), WHR (borderline, rho = -.37, P = .086), and D (rho = -.43, P = .046) only in the ADP group. Comparing the ADP group versus the group without anxio-depression (ADO) and high or low BMI (P = .008), WHR (P = .026), and D (P = .012) showed blunted dexamethasone inhibition only in ADP men with high anthropometric measurements. These findings suggest there is a subgroup with elevated BMI, WHR, and D in whom a blunted dexamethasone response is found associated with traits of anxiety and depression, conditions characterized by such an abnormality. The reason for the association might be insufficient control of cortisol secretion, followed by visceral fat accumulation.     

Relationship between insulin-mediated glucose disposal by muscle and adipose tissue lipolysis in healthy volunteers

The present study was performed in 17 nondiabetic subjects and was initiated to determine whether enhanced adipose tissue lipolysis, either basal or catecholamine induced (isoproterenol), and/or resistance to insulin inhibition of isoproterenol-stimulated lipolysis were correlated with resistance to insulin-mediated glucose disposal by muscle. Insulin-mediated glucose disposal was assessed by determining the steady state plasma glucose (SSPG) concentration during the insulin suppression test [180 min infusion of somatostatin (350 micrograms/h), insulin (25 mU/m2min), and glucose (240 mg/m2.min)]. On another occasion, plasma FFA and glycerol concentrations were determined at the end of 3 sequential infusion periods (IP): IP1, somatostatin (350 micrograms/h) plus basal insulin replacement (5 mU/m2.min); IP2, somatostatin (350 micrograms/h), insulin (5 mU/m2.min), and isoproterenol (270 ng/m2.min); and IP3, somatostatin (350 micrograms/h), isoproterenol (270 ng/m2.min), and insulin (10 mU/m2.min). SSPG concentrations correlated with FFA concentrations during all 3 infusion periods after adjustment for age, gender, body mass index, insulin concentration, and ratio of waist to hip girth (IP1:r = 0.61; P < 0.03; IP2: r = 0.70; P < 0.01; IP3: r = 0.65; P < 0.02). Correlations between SSPG and glycerol concentrations were also highly statistically significant (IP1: r = 0.62; P < 0.03; IP2: r = 0.65; P < 0.02; IP3: r = 0.70; P < 0.01). These results demonstrate for the first time that plasma FFA and glycerol concentrations are increased commensurate with the degree of resistance to insulin-mediated glucose disposal at a basal insulin level, in response to isoproterenol stimulation, and after insulin inhibition of isoproterenol-stimulated lipolysis.     

Physical activity, change in blood pressure and predictors of mortality in older South Africans--a 2-year follow-up study

OBJECTIVE: A 2-year follow-up study of a cohort of 200 historically disadvantaged older South Africans was conducted to: (i) characterise current levels of habitual physical activity; (ii) relate physical activity to current risk factors for chronic disease; and (iii) identify risk factors associated with 2-year mortality. The baseline sample, drawn in 1993, was found to have a high prevalence of hypertension (71.7%). RESEARCH DESIGN: Retrospective cohort study. METHODS: A baseline sample of 200 persons aged > or = 65 years, resident in the Cape Peninsula, was randomly drawn by means of a two-stage cluster design. Baseline measurements included: anthropometry, waist/hip ratio, systolic and diastolic blood pressure, body mass index (BMI), serum albumin, serum ferritin, haemoglobin and fasting plasma glucose levels, plasma lipid profiles, oral glucose tolerance test and self-reported health status. Subjects were revisited after 2 years, at which time an adapted version of the Yale Physical Activity Survey was administered and measurements of blood pressure and anthropometry were repeated. STATISTICAL ANALYSES: Spearman's rank-order correlations were used to describe relationships between various current risk factors and physical activity. Logistic regression was used to determine predictors of 2-year mortality from baseline data. RESULTS: At follow-up, 142 of the subjects (66 men, 76 women) were traced and measurements collected. Thirty-two subjects were reported to have died by relatives living in the same household (22 men, 10 women). Levels of reported physical activity in the survivors were two-thirds lower than those reported in a sample of North Americans of similar age. There was an inverse association between age and physical activity (r = -0.31; P < 0.0005) and a positive association between BMI and physical activity (r = 0.29; P < 0.005). There was, however, no association between physical activity and systolic or diastolic blood pressure. In men, BMI in the lower tertile (P = 0.07) and serum ferritin levels were positively associated with increased mortality. Serum albumin levels were protective over the 2-year follow-up period (OR = 0.85; P < 0.05). In women, being diabetic (OR = 4.88; P = 0.06) and having a waist/hip ratio in the upper tertile (OR = 3.26; P = 0.06) were associated with mortality. CONCLUSIONS: Physical activity levels in this sample of older historically disadvantaged South Africans were habitually low. Simple anthropometric assessments incorporating weight and waist/hip ratio, together with serum albumin measurements, may be useful to screen general health risk for older adults at primary care level and provide indications for social or medical intervention. Further, strategies for earlier detection and effective management of diabetes, particularly in older women, may reduce premature mortality in this population.     

Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome

Sixteen nondiabetic women with polycystic ovary syndrome (PCOS) aged 18 to 33 years were studied before and after 8 weeks on metformin (1.5 g/d) therapy to assess whether reducing hyperinsulinemia would reduce the levels of the major inhibitor of fibrinolysis, antigenic plasminogen activator inhibitor type 1 (PAI-1). Compared with six normal control women, PCOS women had a higher body mass index (BMI), waist to hip ratio, fasting insulin (Izero), insulin area under the curve during oral glucose tolerance testing (IA), glucose area under the curve during oral glucose tolerance testing (GA), IA/GA ratio, PAI-1, luteinizing hormone (LH) and ratio of LH to follicle-stimulating hormone (FSH), and free testosterone, and lower high-density lipoprotein (HDL) cholesterol (all P < .025). On metformin, BMI decreased 1.3% (P = .04), Izero 43% (P = .002), IA 31% (P = .03), GA 11% (P = .02), PAI-1 16% (P = .01), lipoprotein(a) [Lp(a)] 42% (P = .004), free testosterone 46% (P = .0006), LH 44% (P = .004), and the LH/FSH ratio 41% (P = .0001). On metformin, absolute and percent reductions in Izero correlated with absolute and percent reductions in PAI-1 (r = .60, P = .015 and r = .64, P = .008). On metformin, by stepwise multiple regression, the absolute reduction in Izero was a significant determinant of the absolute reduction in PAI-1 (partial R2 = 35%, P = .02), and the percent reduction in Izero was a significant determinant of the percent reduction in PAI-1 (partial R2 = 52%, P = .003). Metformin decreases Izero in hyperinsulinemic PCOS patients, reverses the hyperinsulinemia-driven endocrinopathy, decreases PAI-1, and decreases Lp(a), and should thus reduce the increased risk of atherothrombosis in PCOS.     

Abnormal characteristics in young offspring of parents with non-insulin-dependent diabetes mellitus. The Bogalusa Heart Study

Non-insulin-dependent (type II) diabetes has a strong familial component. In 1989-1991, a community-based study of young Caucasian offspring (mean age, 15.3 years) of non-insulin-dependent (type II) diabetics (n = 25) and nondiabetics (n = 27) representing 13 and 12 families, respectively, was conducted in Bogalusa, Louisiana, to determine whether metabolic abnormalities could be detected in early life. All offspring were given a 1-hour oral glucose tolerance test. The offspring of diabetics (versus nondiabetics) had significantly increased measures of body fatness; blood pressure; and fasting levels of glucose, insulin, glucagon, insulin-to C-peptide ratio, and triglycerides. The increases of systolic blood pressure, glucose, and glucagon remained significant after adjustment for differences in body mass index (BM). After glucose challenge, only plasma glucose response was significantly higher in the offspring of diabetics, even after controlling for differences in BMI. None of the offspring of nondiabetics had 30-minute (peak) glucose levels above 161 mg/dl (8.9 mmol/liter), compared with 41% of the offspring from diabetics. High glucose response and BMI were independently associated with parental diabetes. These results indicate that it is possible to identify multiple abnormalities in some offspring of type II diabetics at an early age that may presage the onset of overt adult diabetes.     

Post-transplant hyperlipidaemia: low-dose lovastatin lowers atherogenic lipids without plasma accumulation of lovastatin

PURPOSE: To compare the therapeutic potential of acarbose, metformin, or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus (NIDDM). PATIENTS AND METHODS: Ninety-six patients with NIDDM (35-70 years of age, body mass index (BMI) < or = 35 kg/m2, insufficiently treated with diet alone, glycated hemoglobin (HbA1c; 7% to 11%) were randomized into 3 groups and treated for 24 weeks with acarbose, 3 x 100 mg/day, or metformin, 2 x 850 mg/day, or placebo. Efficacy, based on HbA1c (primary efficacy criterion), fasting blood glucose (BG) and insulin, 1 hour postprandial BG and insulin (after standard meal test), postprandial insulin increase, plasma lipid profile, and tolerability, based on subjective symptoms and laboratory values were determined every 6 weeks. Analysis of covariance was performed for endvalues with adjustment on baseline values. Ninety-four patients were valid for efficacy evaluation. RESULTS: Both active drugs showed the same improvement of efficacy criteria compared with placebo. Baseline adjusted means at endpoint were as follows: BG, fasting and 1 hour postprandial, 9.2 mM and 10.9 mM with placebo, 7.6 mM and 8.7 mM with acarbose, and 7.8 mM and 9.0 mM with metformin; HbA1c was 9.8% with placebo, 8.5% with acarbose, and 8.7% with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. No effect on fasting insulin could be observed. Relative postprandial insulin increase was 1.90 with placebo, 1.09 with acarbose, and 1.03 with metformin. Comparisons: acarbose versus placebo and metformin versus placebo were statistically significant, but not acarbose versus metformin. With respect to lipid profile, acarbose was superior to metformin. Low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio increased by 14.4% with placebo, was unchanged with metformin, but decreased by 26.7% with acarbose. Comparisons: acarbose versus placebo and acarbose versus metformin were statistically significant, but not metformin versus placebo. Slight body weight changes were observed with acarbose (-0.8 kg) and metformin (-0.5 kg), but not with placebo. Acarbose led to mild or moderate intestinal symptoms in 50% of the patients within the first 4 weeks, but in only 13.8% of the patients within the last 4 weeks. CONCLUSIONS: Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM. With respect to plasma lipid profile, especially HDL cholesterol, LDL cholesterol and LDL/HDL cholesterol ratio acarbose may be superior to metformin.