Fetal and infant growth and impaired glucose tolerance at age 64.

OBJECTIVE--To discover whether reduced fetal and infant growth is associated with non-insulin dependent diabetes and impaired glucose tolerance in adult life. DESIGN--Follow up study of men born during 1920-30 whose birth weights and weights at 1 year were known. SETTING--Hertfordshire, England. SUBJECTS--468 men born in east Hertfordshire and still living there. MAIN OUTCOME MEASURES--Fasting plasma glucose, insulin, proinsulin, and 32-33 split pro-insulin concentrations and plasma glucose and insulin concentrations 30 and 120 minutes after a 75 g glucose drink. RESULTS--93 men had impaired glucose tolerance or hitherto undiagnosed diabetes. They had had a lower mean birth weight and a lower weight at 1 year. The proportion of men with impaired glucose tolerance fell progressively from 26% (6/23) among those who had weighted 18 lb (8.16 kg) or less at 1 year to 13% (3/24) among those who had weighed 27 lb (12.25 kg) or more. Corresponding figures for diabetes were 17% (4/23) and nil (0/24). Plasma glucose concentrations at 30 and 120 minutes fell with increasing birth weight and weight at 1 year. Plasma 32-33 split proinsulin concentration fell with increasing weight at 1 year. All these trends were significant and independent of current body mass. Blood pressure was inversely related to birth weight and strongly related to plasma glucose and 32-33 split proinsulin concentrations. CONCLUSIONS--Reduced growth in early life is strongly linked with impaired glucose tolerance and non-insulin dependent diabetes. Reduced early growth is also related to a raised plasma concentration of 32-33 split proinsulin, which is interpreted as a sign of beta cell dysfunction. Reduced intrauterine growth is linked with high blood pressure, which may explain the association between hypertension and impaired glucose tolerance.     

Reduced final height and indications for insulin resistance in 20 year olds born small for gestational age: regional cohort study.

OBJECTIVE: To investigate whether the association between low birth weight and increased risk of developing impaired glucose tolerance, insulin resistance, hypertriglyceridaemia, and hypertension in middle age is apparent by the age of 20 in people born small for gestational age. DESIGN: Regional cohort study. SETTING: Maternity registry, Haguenau, France. SUBJECTS: 236 full term singleton babies born small for gestational age (birth weight or length, or both, below third centile) during 1971-8 and 281 with normal birth weight (between 25th and 75th centile). All subjects were contacted and evaluated at a mean (SD) age of 20.6 (2.1) years. MAIN OUTCOME MEASURES: Adult height; concentrations of glucose, insulin, and proinsulin during an oral glucose tolerance test; lipid and fibrinogen concentrations; and blood pressure. RESULTS: After sex and target height were adjusted for, subjects who had been born small for gestational age were significantly shorter at age 20 than those with a normal birth weight (men 4.5 cm shorter (95% confidence interval 6.0 to 3.0 cm); women 3.94 cm shorter (5.2 to 2.7 cm)). After sex and body mass index were adjusted for, mean plasma glucose concentration 30 minutes after a glucose load, fasting insulin concentration (in women), and insulin and proinsulin concentrations 30 and 120 minutes after a glucose load were significantly higher in subjects who had been born small for gestational age than in those with a normal birth weight. Mean lipid and fibrinogen concentrations and blood pressure were not different between the two groups. CONCLUSIONS: Intrauterine growth retardation has long term consequences such as reduced final height Raised insulin and proinsulin concentrations are present in young adults born small for gestational age and could be markers of early changes in insulin sensitivity.     

Growth in utero and serum cholesterol concentrations in adult life.

OBJECTIVE--To see whether reduced rates of fetal growth are related to raised serum cholesterol concentrations in adult life. DESIGN--Follow up study of men and women whose size at birth had been recorded. SETTING--Jessop and Northern General Hospitals, Sheffield. SUBJECTS--219 men and women born in the Jessop Hospital during 1939-40. MAIN OUTCOME MEASURES--Serum concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. RESULTS--Men and women who had had a small abdominal circumference at birth had raised serum concentrations of total and low density lipoprotein cholesterol and apolipoprotein B. This was independent of the duration of gestation. Serum concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval 0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The corresponding figure for serum low density lipoprotein cholesterol was 0.26 mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07). Small head and chest circumferences at birth and short length were each associated with raised serum low density lipoprotein cholesterol concentrations but the trends disappeared in a simultaneous regression with abdominal circumference at birth. The association between abdominal circumference at birth and low density lipoprotein cholesterol concentration was independent of social class, current body weight, cigarette smoking, and alcohol consumption. CONCLUSION--Raised serum cholesterol concentrations in adult life are associated with impaired growth during late gestation, when fetal undernutrition has a disproportionate effect on liver growth. Impaired liver growth may permanently alter low density lipoprotein cholesterol metabolism.     

Insulin resistance in offspring of hypertensive parents.

OBJECTIVE--To determine if insulin resistance is present in normotensive adults at increased risk of developing hypertension. DESIGN--Normotensive subjects with at least one hypertensive parent were paired with offspring of normotensive parents (controls), being matched for age, sex, social class, and physical activity. SETTING--Outpatient clinic. SUBJECTS--30 paired subjects (16 men and 14 women) with and without a family history of hypertension, aged 18-32, with a body mass index < 25 kg/m2, with blood pressure < 130/85 mm Hg, and not taking drugs. INTERVENTIONS--Euglycaemic glucose clamp (two hour infusion of insulin 1 mU/kg/min) and intravenous glucose tolerance test (injection of 100 ml 20% glucose). MAIN OUTCOME MEASURES--Insulin mediated glucose disposal and insulin secretion. RESULTS--The offspring of hypertensive parents had slightly higher blood pressure than did the controls (mean 117 (SD 6) v 108 (5) mm Hg systolic, p = 0.013; 76 (7) v 67 (6) mm Hg diastolic, p = 0.017). Their insulin mediated glucose disposal was lower than that of controls (29.5 (6.5) v 40.1 (8.6) mumol/kg/min, p = 0.002), but, after adjustment for blood pressure, the difference was not significant (difference 6.9 (95% confidence interval -1.5 to 15.3), p = 0.10). Insulin secretion in the first hour after injection of glucose was slightly but not significantly higher in the offspring of hypertensive patients (9320 (5484) v 6723 (3751) pmol.min/l). The two groups had similar concentrations of plasma glucose (5.2 (0.3) v 5.1 (0.4) mmol/l), serum cholesterol (4.4 (0.8) v 4.6 (0.8) mmol/l), serum triglyceride (0.89 (0.52) v 0.68 (0.27) mmol/l), and serum low density lipoprotein cholesterol (2.81 (0.65) v 2.79 (0.61) mmol/l). The offspring of hypertensive parents, however, had lower serum concentrations of high density lipoprotein cholesterol (1.24 (0.31) v 1.56 (0.35) mmol/l, p = 0.002) and higher serum concentrations of non-esterified fatty acids (0.7 (0.4) v 0.4 (0.4) mmol/l, p = 0.039). CONCLUSIONS--Young normotensive subjects who are at increased risk of developing hypertension are insulin resistant.     

Glucose tolerance, plasma lipoproteins and tissue lipoprotein lipase activities in body builders

Oral glucose tolerance, insulin binding to erythrocyte receptors, serum lipids, and lipoproteins, and lipoprotein lipase activities of adipose tissue and skeletal muscle were measured in nine body builders (relative body weight (RBW) 118 +/- 4%), eight weight-matched (RBW 120 +/- 5%) and seven normal-weight controls (RBW 111 +/- 3%). The body builders had 50% higher relative muscle mass of body weight (% muscle) and 50% smaller relative body fat content (% fat) than the two other groups (P less than 0.005). Maximal aerobic power was comparable in the three groups. In the oral glucose tolerance test (OGTT), blood glucose levels, and plasma insulin levels were lower (P less than 0.05) in the body builders than in weight-matched controls. Insulin binding to erythrocytes was similar in each group. On the basis of multiple linear regression analysis, 87% of the variation in plasma insulin response could be explained by body composition (% muscle and % fat) and VO2max. Plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) triglyceride concentrations were significantly lower in the body builders than in weight-matched controls. In comparison with the normal-weight group, the body builders had a lower total cholesterol level. High density lipoprotein (HDL) cholesterol, its subfractions (HDL2 and HDL3 cholesterol) and lipoprotein lipase (LPL) activities of adipose tissue and skeletal muscle were comparable in all three groups. Partial correlation analysis showed a positive relationship between plasma total triglyceride, total cholesterol and LDL cholesterol on the other hand and the % fat on the other.(ABSTRACT TRUNCATED AT 250 WORDS)     

绝经后女性高尿酸血症患者性激素结合球蛋白与血尿酸的相关研究

目的：研究绝经后女性高尿酸血症患者血浆中性激素结合球蛋白（sexhormonebindingglobulin,SHBG）水平与血尿酸水平的相关性。方法：选取绝经后女性404例,其中高尿酸血症组204例,正常对照组200例,测量所有研究对象体重、身高、腰围、臀围、收缩压（SBP）、舒张压（DBP）,并计算体重指数（BMI）和腰臀比（WHR）,检测血尿酸（UA）、空腹血糖（FBG）、总胆固醇（TG）、甘油三酯（TC）低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、雌激素（E2）、雄激素（T）、空腹胰岛素（INS）及SHBG,并计算胰岛素抵抗指数（Homa-IR）。结果：与绝经后女性尿酸正常者相比,高尿酸血症的患者UA,WHR,TC,FBG,INS,Homa-IR明显升高（P〈0．01）,DBP,WAIST和LDL升高（P〈0．05）,SHBG水平明显下降（P〈0．01）;SHBG与INs、uA、TG呈显著负相关（P〈0．05）,SHBG与E2呈显著正相关P〈0．01）。结论：绝经后女性中高尿酸血症患者的低血浆SHBG水平与高血尿酸水平显著相关,血浆SHBG水平下降与胰岛素抵抗可能高度相关,低sHBG可能作为绝经后女性患高尿酸血症的高危因素。     

Intrauterine growth retarded progeny of pregnant sows fed high protein:low carbohydrate diet is related to metabolic energy deficit

High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR). To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW) at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP), adequate (12.1%, AP), and high (30%, HP) protein levels, made isoenergetic by adjusted carbohydrate content. At -5, 24, 66, and 108 days post coitum (dpc) fasted blood was collected. At 92 dpc, diurnal metabolic profiles were determined. Fasted serum urea and plasma glucagon were higher due to the HP diet. High density lipoprotein cholesterol (HDLC), %HDLC and cortisol were reduced in HP compared with AP sows. Lowest concentrations were observed for serum urea and protein, plasma insulin-like growth factor-I, low density lipoprotein cholesterol, and progesterone in LP compared with AP and HP sows. Fasted plasma glucose, insulin and leptin concentrations were unchanged. Diurnal metabolic profiles showed lower glucose in HP sows whereas non-esterified fatty acids (NEFA) concentrations were higher in HP compared with AP and LP sows. In HP and LP sows, urea concentrations were 300% and 60% of AP sows, respectively. Plasma total cholesterol was higher in LP than in AP and HP sows. In AP sows, LW correlated positively with insulin and insulin/glucose and negatively with glucagon/insulin at 66 dpc, whereas in HP sows LW associated positively with NEFA. In conclusion, IUGR in sows fed high protein:low carbohydrate diet was probably due to glucose and energy deficit whereas in sows with low protein:high carbohydrate diet it was possibly a response to a deficit of indispensable amino acids which impaired lipoprotein metabolism and favored maternal lipid disposal.     

Total cholesterol,low density lipoprotein cholesterol,and high density lipoprotein cholesterol and coronary heart disease in Scotland.

OBJECTIVE--To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN--Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING--Edinburgh, Scotland. SUBJECTS--107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION--The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES--Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS--Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION--Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes.     

Effective lipid lowering diets including lean meat

The plasma lipid and lipoprotein responses to two modified isoenergetic diets including meat were studied in 15 free living men with hyperlipidaemia (mean plasma cholesterol and triglyceride concentrations 8·1 and 3·4 mmol/l). A reference diet (diet A, 42% energy from fat, ratio of polyunsaturated to saturated fatty acids (P:S ratio) 0·2) was compared with a fat reduced diet (diet B, 35% energy from fat, P:S ratio 0·5) and with a further fat modified diet supplemented with fibre (diet C, 27% energy from fat, P:S ratio 1·0). Daily intake of meat and meat products (180 g/day) was the same in each dietary period; that in diet A had a fat content typical of the average British diet, whereas that in diets B and C was based on very lean meat and meat products. During consumption of diet B the plasma cholesterol concentration fell by 8·6% and low density lipoprotein cholesterol by 11%. During consumption of diet C plasma cholesterol fell by 18·5% and low density lipoprotein cholesterol by 23·8%. Triglyceride and high density lipoprotein cholesterol concentrations and body weight did not change appreciably during the study.A modified diet including a moderate amount of lean meat and meat products is compatible with a reduced lipoprotein mediated risk of atherosclerotic heart disease.     

The effects of 20 days bed rest on serum lipids and lipoprotein concentrations in healthy young subjects

The effects of 20 days bed rest (BR) on serum lipids and lipoprotein concentrations were investigated in 23 healthy young subjects (13 males and 10 females, aged 19 to 25 yr.). After 20 days BR, VO2max was reduced in both genders, but body composition did not change. The ratio of glucose area to insulin area during an oral glucose tolerance test decreased gradually throughout BR, which suggested a decrease in insulin sensitivity. Estimated changes in plasma volume from the beginning of BR were largest at day 3 of BR (-9.1% in females and -3.4% in males) and seemed to return the initial level at the end of BR in both genders. The increase in serum triglycerides and the decrease in high density lipoprotein (HDL) cholesterol, and apolipoprotein AI were observed in both genders during BR. In a smaller study of 4 males and 5 females, 20 days BR was associated with a decrease in HDL, cholesterol, a decrease in apolipoprotein AI and apolipoprotein AII, decrease in a plasma postheparin lipoprotein lipase activity and an increase in very low density lipoprotein triglyceride. Overall, the data suggested that the decrease in lipoprotein lipase activity and insulin sensitivity may contribute to the impairment in HDL metabolism.     

Comparison of high fibre diets,basal insulin supplements,and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.     

Alcohol consumption and its relation to cardiovascular risk factors in British women.

OBJECTIVE--To examine the relation between alcohol consumption and risk factors for coronary heart disease in women. DESIGN--Cross sectional study of a stratified random sample of the population grouped into five categories of habitual alcohol consumption. SETTING--People registered with general practitioners at two large health centres in east Bristol, England. SUBJECTS--1048 women aged 25-69 years. MAIN OUTCOME MEASURES--Fasting plasma concentrations of insulin, total cholesterol, total triglycerides, and high density lipoprotein cholesterol, including its subfractions HDL2 and HDL3, and body mass index. RESULTS--Compared with non-drinkers women consuming a moderate amount of alcohol (1-20 g/day) had lower plasma concentrations of triglycerides, by 0.19 mmol/l (95% confidence interval 0.07 to 0.35); cholesterol, by 0.4 mmol/l (0.19 to 0.61); and insulin, by 1.4 mU/l (0.43 to 1.97) and a lower body mass index, by 1.2 kg/m2 (0.43 to 1.97). They also had higher concentrations of high density lipoprotein cholesterol, by 0.09 mmol/l (0.03 to 0.15); HDL2 cholesterol by 0.05 mmol/l (-0.02 to 0.10) and HDL3 cholesterol, by 0.06 mmol/l (0.06 to 0.11). All these were independent of body mass index, smoking habits, and taking oral contraceptives. CONCLUSIONS--Moderate alcohol consumption is associated with lower levels of cardiovascular risk factors in women. Insulin may have a central role.     

Effect of Family History of Type 2 Diabetes on White Blood Cell Count in Adult Women

Objective: To evaluate the effect of a first‐degree family history of type 2 diabetes on white blood cell (WBC) count, a risk factor for atherosclerotic vascular disease, in glucose‐tolerant adult women Research Methods and Procedures: WBC count was measured in 174 normal weight, overweight, and obese female offspring of type 2 diabetic patients (FH⁺) and 174 age‐ and BMI‐matched female controls with no family history of type 2 diabetes (FH^?). Other measurements included fat mass (FM), measured by body impedance analysis; central fat accumulation, evaluated by waist circumference; insulin resistance, estimated by homeostatic model assessment for insulin resistance (HOMA_IR); systolic and diastolic blood pressure; and fasting concentrations of glucose, insulin, and lipids. Results: WBC count, waist circumference, systolic blood pressure, and fasting levels of glucose, insulin, and triglycerides were significantly higher in FH⁺ than in FH^? subjects. In FH⁺ individuals, WBC count was positively associated with BMI, FM, waist circumference, HOMA_IR, and triglyceride and insulin concentrations, and negatively correlated with age and high‐density lipoprotein‐cholesterol. In FH^? subjects, WBC count was directly associated with BMI, FM, waist circumference, and triglyceride and insulin concentrations, and inversely correlated with age and high‐density lipoprotein‐cholesterol. After multivariate analyses, WBC count maintained a significant association with age, systolic blood pressure, and HOMA_IR in FH⁺ subjects and with age, BMI, FM, and triglycerides in FH^? individuals. Discussion: This study indicates that WBC count is increased in adult women with genetic predisposition to type 2 diabetes, and its main correlates are insulin resistance in FH⁺ and adiposity in FH^? individuals.     

Visceral adiposity is associated with serum retinol binding protein-4 levels in healthy women

Objective: Retinol binding protein‐4 (RBP4) has been reported to impair insulin sensitivity throughout the body. We investigated the relationship between serum RBP4 levels and adiposity indices as well as metabolic risk variables. Research Methods and Procedure: We recruited a total of 102 healthy women 21 to 67 years old. We assessed body composition by computed tomography and divided the study population into four groups based on body weight and visceral fat area (non‐obese without visceral adiposity, non‐obese with visceral adiposity, obese without visceral adiposity, and obese with visceral adiposity). Serum RBP4 levels were measured by radioimmunoassay. Results: Despite similar levels of total body fat, non‐obese women had lower systolic blood pressure, total cholesterol, triglyceride (TG), low‐density lipoprotein (LDL)‐cholesterol levels, insulin resistance indices, and RBP4 levels than non‐obese women with visceral adiposity and had higher high‐density lipoprotein‐cholesterol levels. Similarly, obese women without visceral adiposity had lower blood pressure, total cholesterol, TG levels, insulin resistance indices, and RBP4 levels than obese women with visceral adiposity. In addition, despite having increased body fat, obese women without visceral adiposity had lower TGs, insulin resistance indices, and serum RBP4 levels than non‐obese women with visceral adiposity. By step‐wise multiple regression analysis, visceral fat areas and LDL‐cholesterol levels independently affected RBP4 levels. Discussion: We determined that serum RBP4 levels are independently associated with visceral fat and LDL‐cholesterol levels. These results suggest that, irrespective of body weight, visceral obesity is an independent predictor of serum RBP4 levels, and RBP4 may represent a link between visceral obesity and cardiovascular disease.     

Impact of Obesity and Body Fat Distribution on Cardiovascular Risk Factors in Hong Kong Chinese

Objective: Body fat distribution has been reported to differentially contribute to the development of cardiovascular risk. We report the relative associations between general and central obesity and risk factors in 2893 Chinese subjects recruited from the Hong Kong population. Research Methods and Procedures: Anthropometric parameters [waist circumference (WC) and BMI], surrogate measures of insulin resistance (fasting plasma glucose and insulin, oral glucose tolerance test, 2 hours glucose and insulin), fasting lipids (total, low‐density lipoprotein‐cholesterol, high‐density lipoprotein‐cholesterol, and triglycerides) and systolic and diastolic blood pressure were measured. General obesity was classified as BMI ≥25.0 kg/m² and central obesity as a WC ≥80 or ≥90 cm in women and men, respectively. Results: A total of 39.2% of the population was found to be obese. Obesity per se increased the levels of the risk factors, but central adiposity contributed to a greater extent to adverse high‐density lipoprotein‐cholesterol, triglyceride, and insulin resistance levels. There was a continuous relationship between increasing obesity, both general and central, and cardiovascular risk, with lowest risk associated with the lowest indices of obesity. In the 1759 nonobese subjects divided into quartiles of BMI or WC, the levels of the cardiovascular risk factors still significantly increased with increasing quartiles of adiposity. Discussion: Central adiposity appears to contribute to a greater extent than general adiposity to the development of cardiovascular risk in this population. The relationship between obesity parameters and risk is a continuum, with risk factors significantly increasing even at levels usually considered nonobese. These observations support the proposed redefinition of overweight and obesity in Asian populations using lower cut‐off points.     

Plasma lipid and coagulation factor concentrations in insulin dependent diabetics with microalbuminuria.

OBJECTIVE--To determine whether insulin dependent diabetics with microalbuminuria have significant abnormalities in concentrations of lipoproteins, apolipoproteins AI and B, fibrinogen, and clotting factor VII which could result in increased cardiovascular risk. DESIGN--Case-control study. SETTING--Outpatient department of a metabolic ward. PATIENTS--Group of 20 insulin dependent diabetics with urinary albumin excretion rates greater than 30 micrograms/min (microalbuminuria) and 20 individually matched insulin dependent diabetics with normal urinary albumin excretion rates (below 30 micrograms/min) matched for age, sex, and duration of diabetes. INTERVENTIONS--Fasting venous blood samples were taken for determination of concentrations of glucose, glycated haemoglobin, lipoproteins, apolipoproteins AI and B, fibrinogen, and factor VII. Height, weight, arterial pressure, and usual insulin dose were recorded, and each patient was given a dietary questionnaire to be completed at home. END POINT--Comparison of blood pressure and concentrations of lipoproteins, apolipoproteins AI and B, and fibrinogen in the diabetics with microalbuminuria and the controls. MEASUREMENTS AND MAIN RESULTS--Patients with microalbuminuria had significantly higher concentrations of low density lipoprotein cholesterol (mean 3.33 (SE 0.20) v 2.84 (0.12) mmol/l) and very low density lipoprotein cholesterol (0.30 (0.05) v 0.17 (0.03) mmol/l) than controls but significantly lower concentrations of high density lipoprotein 2 subfraction cholesterol (0.32 (0.04) v 0.54 (0.04) mmol/l). Concentrations of total triglyceride (1.11 (0.14) v 0.68 (0.08) mmol/l), very low density lipoprotein triglyceride (0.56 (0.10) v 0.30 (0.05) mmol/l), apolipoprotein B (0.88 (0.06) v 0.67 (0.03) g/l) and fibrinogen (2.2 (0.1) v 1.9 (0.1) g/l), and diastolic arterial pressure (80 (2) v 74 (2) mm Hg), were also higher in patients with microalbuminuria. CONCLUSIONS--Cardiovascular risk factors--namely, disturbances in lipoprotein and apolipoprotein concentrations, increased fibrinogen concentration, and increased arterial pressure--are already present in insulin dependent diabetics with microalbuminuria. The increased risk of coronary heart disease in patients with clinical proteinuria may result from prolonged exposure to these risk factors, which are present before any impairment of renal function.     

K121Q PC‐1 Gene Polymorphism Is Not Associated with Insulin Resistance in a Spanish Population

Objective : To investigate the effect of the K121Q plasma cell membrane glycoprotein (PC‐1) polymorphism on the components of the insulin resistance syndrome in a population‐based nationwide multicenter study in Spain. Research Methods and Procedures : The subjects of the study were 293 nonrelated adults (44.7% men and 55.3% women) ages 35 to 64 years randomly chosen from a nationwide population‐based survey on obesity and related conditions, including insulin resistance and cardiovascular risk factors. Obesity‐related anthropometric measurements included blood pressure, oral glucose tolerance test, lipid profile (total cholesterol, high‐density lipoprotein‐ and low‐density lipoprotein‐cholesterol, and triglycerides), plasma leptin, insulin levels by radioimmunoassay, and insulin resistance (homeostasis model assessment). K121Q PC‐1 genotypes were determined by restriction fragment‐length polymorphism‐polymerase chain reaction. Results : Overall Q allele frequency was 0.14, with no differences between obese and nonobese individuals (0.15 vs. 0.13). After adjustment for sex, age, BMI, and degree of glucose tolerance, the Q allele was associated with high plasma leptin and triglyceride levels, but not with insulin resistance. Discussion : The results showed that the K121Q PC‐1 polymorphism in the Spanish population has no significant impact on insulin sensitivity.     

Long term metabolic effects of two dietary methods of treating hyperlipidaemia.

OBJECTIVES--To compare the long term metabolic effects of two diets for treating hyperlipidaemia. DESIGN--Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months. SETTING--Lipid clinic of tertiary referral centre in Naples. SUBJECTS--63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30. INTERVENTIONS--Two test diets with reduced saturated fat (8%) and cholesterol (approximately 200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats. MAIN OUTCOME MEASURES--Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal. RESULTS--In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/l, P < 0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P < 0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P < 0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P < 0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet. CONCLUSIONS--Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.     

Effect of the prostaglandin E1 analog enisoprost on glucose and lipid metabolism in patients with type II diabetes mellitus.

Short-term studies have suggested that analogs of prostaglandin E may have favorable effects on the carbohydrate and lipid metabolism in patients with type II diabetes mellitus. The present study was undertaken to investigate the long-term effects of a prostaglandin E1 analog on the regulation of glycemic control and plasma lipids. Twenty patients with type II diabetes received enisoprost, 300 mcg/day, for three months. Fasting serum glucose, glycosylated hemoglobin, insulin and C-peptide levels as well as triglyceride, total cholesterol, high density lipoprotein cholesterol and its subfractions, apolipoproteins B and AI and post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. During the first month, enisoprost treatment caused significant decreases in plasma glucose (baseline = 8.72 +/- 0.39 mmol/L, 4 week = 7.78 +/- 0.5 mmol/L, change = -0.94 +/- 0.28 mmol/L, p less than 0.01) and total cholesterol (baseline = 5.30 +/- 0.23 mmol/L, 4 week = 5.01 +/- 0.26 mmol/L, change = -0.28 +/- 0.06 mmol/L, p less than 0.05). The decrease in cholesterol level was due to a reduction in high density lipoprotein, specifically in high density lipoprotein2 fraction (baseline = 1.29 +/- 0.1 mmol/L, 4 week = 1.12 +/- 0.08 mmol/L, change = -0.018 +/- 0.04 mmol/L, p less than 0.05 for the former and baseline = 0.40 +/- 0.06 mmol/L, 4 week = 0.27 +/- 0.03 mmol/L, change = -0.12 +/- 0.03 mmol/L, p less than 0.05 for the latter): All of these values returned to the pretreatment levels despite continuation of enisoprost.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of oral agent or insulin treatments on the plasma lipoproteins and the plasma lipoprotein lipase activator in diabetic patients

The structure and the metabolism of plasma lipoproteins are altered in diabetes mellitus. Insulin or oral agent treatments affect the lipoprotein metabolism in addition to improving hyperglycemia. However, it is not clear whether the alterations seen in lipoproteins during treatment are related to the degree of diabetic control or to the mode of diabetic treatment. The effects of insulin or oral agent treatments on the plasma lipoproteins and lipoprotein lipase activator were compared in a strictly defined non-obese, non-insulin dependent diabetic patient. Both treatment groups had similar plasma triglyceride, total cholesterol, low and high density lipoprotein cholesterol, and lipoprotein lipase activator levels. Lipoprotein lipase activator contents of the very low density lipoproteins correlated positively with their triglyceride (r = 0.803 in insulin, r = 0.828 in oral agent treated patients) and protein (r = 0.713 in insulin, r = 0.862 in oral agent treated patients) contents. The findings of this study indicated that plasma lipid levels, very low density lipoprotein compositions, and lipoprotein lipase activator contents were not significantly different in non-obese, non-insulin dependent diabetic patients treated with either oral hypoglycemic agents or insulin.