Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables

OBJECTIVE: Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not invariably so when the degree of obesity is taken into account. We have therefore investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN: Cross-sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight-matched controls. PATIENTS: Twenty-four obese (Pob, mean BMI +/- SD 30.6 +/- 3.3 kg/m2) and 25 non-obese (Pnob, 22.2 +/- 2.3 kg/m2) women with PCOS. Twenty obese (Cob, 30.2 +/- 3.5 kg/m2) and 20 non-obese (Cnob, 21.4 +/- 1.5 kg/m2) controls. MEASUREMENTS: Fasting concentrations of plasma free fatty acids, serum cholesterol and triglycerides in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) in relation to insulin sensitivity index (M/I; assessed with the euglycaemic insulin clamp), glucose tolerance (k-value; intravenous glucose tolerance test), basal serum hormone concentrations, and body fat distribution (skinfolds and waist hip ratio). RESULTS: Plasma concentrations of free fatty acids were markedly higher in Pob than in the other groups (all P < 0.001). The lipoprotein lipids did not differ between Pob and Cob, or between the non-obese groups, whereas both obese groups had higher serum concentrations of triglycerides, totally and in VLDL, and lower HDL-cholesterol than their non-obese counterparts. Pob also had higher serum levels of total and LDL-cholesterol than Pnob. Pob had a more pronounced subcutaneous truncal-abdominal adiposity, higher fasting insulin levels and lower M/I than the other groups, and a lower k-value than Cob. Cob had higher levels of fasting insulin than Cnob. Free fatty acid levels correlated with the k-value (inversely) in both women with PCOS and controls, and with M/I (inversely), age and testosterone levels in PCOS. Stepwise regression analysis for the total population, comparing endocrine, anthropometric and metabolic explanatory variables, showed that the serum levels of HDL-cholesterol and triglycerides were mainly correlated with body fat distribution (both) and fasting insulin levels (triglycerides), and levels of total and LDL-cholesterol with BMI and age. CONCLUSIONS: Plasma free fatty acid correlations were markedly increased in obese women with PCOS, closely associated with the lower insulin sensitivity and lower glucose tolerance in these women. In spite of these profound metabolic aberrations, the lipoprotein lipid profile was not significantly more abnormal in obese women with PCOS than in their weight-matched controls.     

Aldosterone in obesity

Plasma aldosterone levels were measured in adults whose body mass index ranged from lean to obese. Blood was drawn while subjects rested supine for 30-90 minutes. Aldosterone was higher in obese subjects, but could not be explained by renin or K+. The best predictors of plasma aldosterone were abdominal obesity measured as waist/hip ratio or by CT scan, and insulin resistance measured by insulin or oral glucose tolerance tests, or euglycemic clamp. In one cohort, these correlations were limited to women; in the other, they were also found in men. In the women with a strong correlation between aldosterone and visceral fat, aldosterone also correlated with cortisol and DHEA-S. The data are consistent with an effect of visceral fat on adrenal steroidogenesis. Visceral adipocytes have a high rate of triglyceride turnover, and their circulation drains directly to the liver. In an experiment based on these characteristics, rat hepatocytes responded to fatty acids by releasing an unidentified secretagogue that stimulated aldosterone production by rat adrenal glomerulosa cells. The clinical data suggest that aldosterone participates in hypertension associated with the "Insulin Resistance Syndrome". The adrenal in viscerally obese subjects may be driven by a secretagogue released from the liver by fatty acids from abdominal adipocytes.     

Insulin resistance and essential hypertension in Vietnamese subjects

Several epidemiological and experimental studies suggest that essential arterial hypertension is associated with hyperinsulinism and insulin resistance in obese subjects and also in subjects with normal body weight. Undernutrition remains frequent in adult Vietnamese people and mean body mass index is around 18.5 kg/m2 in Vietnam. The aim of this study was to look for insulin resistance in hypertensive Vietnamese subjects, despite a markedly lower BMI in Vietnam than in occidental countries. One hundred and eight hypertensive patients (51 men and 57 women) over 40 years (mean = 65.4 years) were compared with 36 healthy subjects (23 men and 13 women) over 40 years (mean = 63.8 years). Hypertensive patients had significantly higher BMI (20.5 +/- 0.3 (SEM) kg/m2 vs 18.4 +/- 0.4 kg/m2; p < 0.01), thicker triceps skinfold (1.26 +/- 0.07 cm vs 0.71 +/- 0.07 cm; p < 0.001) and not significantly different waist/hip ratio (0.88 +/- 0.01 vs 0.85 +/- 0.01). Blood glucose at fasting and 2 hours after 75 g glucose taken orally were similar in hypertensive and normotensive subjects. Plasma insulin at fasting and 2 hours after glucose were significantly higher in hypertensive patients (44.4 +/- 5.1 pmol/L vs 21.6 +/- 3.2 pmol/L; p < 0.05 and 271.1 +/- 21.6 pmol/L vs 139.1 +/- 15.2 pmol/L; p < 0.001). Thus, despite under-nutrition, hypertensive Vietnamese patients have a moderate but significant increase in BMI and fat mass without predominant abdominal localization, and a state of insulin-resistance, compared with normotensive healthy subjects.     

Postprandial triglyceride response in visceral obesity in men

Although metabolic disturbances are often observed in obese patients, increased accumulation of visceral adipose tissue (AT) has been shown to be more closely associated with high fasting triglyceride (TG) and insulin levels as well as with low HDL cholesterol concentrations than with excess body fatness per se. Interestingly, the fasting concentration of plasma TGs has been shown to be an important determinant of the magnitude and duration of the postprandial TG response. Yet little is known about the respective contributions of obesity versus excess visceral AT to the variation in postprandial TG clearance. In the present study, we examined potential differences in postprandial triglyceride-rich lipoprotein (TRL) responses in subjects characterized by high versus low levels of visceral AT. In a sample of 43 men (mean age: 41.3 +/- 9.6 years), we found that both excess body fat and visceral obesity were associated with increased postprandial TG responses in total TRL (r = 0.33-0.45). We also found a strong relationship between fasting plasma TG levels and postprandial total TRL-TG concentrations (r = 0.79, P < 0.0001). When matched for total body fat mass, individuals with high levels of visceral AT (> or =130 cm2; n = 10) as assessed by computed tomography were characterized by increased medium- and small-TRL-TG responses (P < 0.05) compared with subjects with low visceral AT accumulation (<130 cm2; n = 10). Moreover, this elevated response of small-TRL triglycerides noted in men with high levels of visceral AT was not accompanied by a concomitant increased retinyl palmitate response in this TRL fraction, suggesting that visceral obesity in men is accompanied by higher postprandial VLDL production than is found in obese men with lower levels of visceral AT. Increased postprandial insulin and free fatty acid (FFA) responses were also noted in men with high levels of visceral AT. Finally, postheparin plasma lipoprotein lipase activity was negatively correlated with the total-TRL-TG response in a subsample of 32 individuals (r = -0.37, P < 0.05). The results of the present study suggest that visceral obesity is associated with an impaired postprandial TG clearance. Furthermore, the exaggerated postprandial FFA response observed in subjects with high visceral AT suggests that visceral obesity may contribute to fasting and postprandial hypertriglyceridemia by altering FFA metabolism in the postprandial state.     

Zinc and flunitrazepam modulation of GABA-mediated currents in rat suprachiasmatic neurons

We know that upper body obesity is associated with metabolic complications, but we don't know how regional body fat distribution influences postprandial lipemia in obese adults. Thus, this study explored the respective effects of android or gynoid types of obesity and fasting triglyceridemia on postprandial lipid metabolism and especially triglyceride-rich lipoproteins. Twenty-four obese and 6 lean normotriglyceridemic women (control), age 24-57 yr, were enrolled. Among obese women with an android phenotype, 9 exhibited normal plasma triglyceride levels (mean: 1.38 mmol/L) (NTAO), and 7 displayed a frank hypertriglyceridemia (mean: 2.40 mmol/L) (HTAO). The 8 patients with a gynoid phenotype had normal triglyceride levels (mean: 1.00 mmol/L) (GO). All were given a mixed test meal providing 40 g triglycerides. Serum and incremental chylomicron triglycerides 0-7 h areas under the curve (AUCs) as well as triglyceride levels in apoB-48-containing triglyceride-rich lipoprotein (TRLs) or chylomicrons were significantly higher in HTAOs and NTAOs than in GOs and controls postprandially. The size of chylomicron particles was bigger in controls and GOs than in HTAOs and NTAOs postprandially. Android obese subjects showed abnormally elevated fasting apoB-48 and apoB-100 triglyceride-rich lipoprotein (TRL) levels. Most abnormalities that were found correlated to plasma levels of insulin and apoC-III. In conclusion, an abnormal postprandial lipid pattern is a trait of abdominal obesity even without fasting hypertriglyceridemia.     

Attenuated GLP-1 secretion in obesity: cause or consequence?

BACKGROUND: Hypersecretion of insulinotropic factors such as glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1) have been postulated to account for the hyperinsulinaemia of obesity. AIMS: To examine the role of GLP-1 and GIP in obese women and matched controls. SUBJECTS: Six lean and six obese women subjects matched for age. METHODS: The gut hormone, plasma glucose, and serum triglyceride responses were studied over 180 minutes after oral carbohydrate and fat meals. Heparin (10,000 units) was given intravenously at 120 minutes. RESULTS: There was pronounced attenuation of plasma GLP-1 secretion to oral carbohydrate in the obese compared with lean subjects but no such difference in response to oral fat load. There were no differences in the plasma GIP responses to carbohydrate or fat feeding. There was an apparent fall in plasma GLP-1 values in all subjects after administration of heparin. CONCLUSION: Postprandial GLP-1 secretion in response to oral carbohydrate is considerably attenuated in obese subjects. The cause of this attenuation of GLP-1 secretion is not known although we suggest that both this fall and the overall reduction in GLP-1 values in obese subjects may be related to an increase in plasma non-esterified fatty acids.     

Neural network subtyping of depression

OBJECTIVE: To examine the mechanisms by which weight loss improves glycemic control in overweight subjects with NIDDM, particularly the relationships between energy restriction, improvement in insulin sensitivity, and regional and overall adipose tissue loss. RESEARCH DESIGN AND METHODS: Hyperinsulinemic glucose clamps were performed in 20 subjects (BMI = 32.0 +/- 0.5 [SEM] kg/m2, age = 48.4 +/- 2.7 years) with normal glucose tolerance (NGT) (n = 10) or mild NIDDM (n = 10) before and on the 4th (d4) and 28th (d28) days of a reduced-energy (1,100 +/- 250 [SD] kcal/day) formula diet. Body composition changes were assessed by dual energy x-ray absorptiometry and insulin secretory changes were measured by insulin response to intravenous glucose before and after weight loss. RESULTS: In both groups, energy restriction (d4) reduced fasting plasma glucose (FPG) (delta FPG: NGT = -0.4 +/- 0.2 mmol/l and NIDDM = -1.1 +/- 0.03 mmol/l, P = 0.002), which was independently related to reduced carbohydrate intake (partial r = 0.64, P = 0.003). There was a marked d4 increase in percent of insulin suppression of hepatic glucose output (HGO) in both groups (delta HGO suppression: NGT = 28 +/- 15% and NIDDM = 32 +/- 8%, P = 0.002). By d28, with 6.3 +/- 0.4 kg weight loss, FPG was further reduced (d4 vs. d28) in NIDDM only (P = 0.05), and insulin sensitivity increased in both groups (P = 0.02). Only loss of abdominal fat related to improvements in FPG (r = 0.51, P = 0.03) and insulin sensitivity after weight loss (r = 0.48, P = 0.05). In contrast to insulin action, there were only small changes in insulin secretion. CONCLUSIONS: Both energy restriction and weight loss have beneficial effects on insulin action and glycemic control in obesity and mild NIDDM. The effect of energy restriction is related to changes in individual macronutrients, whereas weight loss effects relate to changes in abdominal fat.     

Insulin sensitivity in familial hypercholesterolemia

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of visceral fat accumulation on uric acid metabolism in male obese subjects: visceral fat obesity is linked more closely to overproduction of uric acid than subcutaneous fat obesity

We investigated the relationship between uric acid (UA) metabolism and fat distribution in 36 obese men with a mean +/- SD age of 38 +/- 16 years and mean body-mass index (BMI) of 34 +/- 4 kg/m2. Subjects were divided into two groups: subcutaneous fat obesity (SFO) and visceral fat obesity (VFO), according to their abdominal fat distribution based on the results of computed tomography (CT). SFO was defined as having a ratio of visceral fat area (VFA) to subcutaneous fat area (V/S) of less than 0.4, and VFO was defined as having a V/S ratio > or = 0.4. The levels of serum total cholesterol (T-Chol), triglyceride (TG), and fasting plasma glucose (FPG), and the diastolic blood pressure (dBP) were significantly higher in the VFO group than in the SFO group. Serum UA levels were much higher in both the SFO and VFO groups than in the non-obese control group (492 +/- 107 and 474 +/- 90 v 309 +/- 48 micromol/L, respectively). The 24-hour urinary urate excretion (u-UA24h) and the UA clearance (Cua) to creatinine clearance (Ccr) ratio were significantly higher in the VFO group than in the SFO group (3.75 +/- 1.43 v 2.69 +/- 1.12 mmol/d, P < .05; and 5.9% +/- 2.0% v 3.6% +/- 1.7%, P < .001, respectively). The frequency of hyperuricemia was markedly higher in both the SFO and VFO groups compared with the control group (71% and 73% v 0%, respectively). Although the high serum UA level seemed to be related to low u-UA24h in 80% of SFO subjects with hyperuricemia, this was the case in only 10% of VFO subjects. While 44% of VFO subjects with hyperuricemia were designated as an overproduction type. These results suggest that the mechanism of hyperuricemia in obesity may be affected by the difference in body fat distribution and that the assessment of body fat distribution and types of hyperuricemia is crucial for the treatment of obese patients with hyperuricemia.     

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).     

Non-invasive continuous glucose monitoring in Type I diabetic patients with optical glucose sensors. Non-Invasive Task Force (NITF)

Glucose intolerance is influenced by body fat mass, as well as muscle fiber composition. To examine the relation between the metabolic profile and muscle morphology in this condition, we performed muscle biopsies and hyperglycemic clamps to determine insulin secretion and clearance, and the insulin effects on glucose disposal and nonesterified fatty acids (NEFA) in 45 glucose intolerant persons (body mass index [BMI], 27.8 +/- 3.0 kg/m2) and 45 normoglycemic controls (BMI, 25.8 +/- 2.7 kg/m2) (P = .001). After adjustment for BMI, glucose-intolerant subjects had lower first-phase insulin release (726 v 954 pmol/L, P = .04). Glucose-intolerant subjects and controls differed in fasting insulin, insulin clearance, and insulin sensitivity to glucose disposal before, but not after, standardizing for BMI. During the clamp, glucose-intolerant subjects had less NEFA suppression and elevated levels of NEFA compared with controls (85% +/- 9% v 90% +/- 6%, P = .02; and 70 +/- 42 micromol/L v 45 +/- 28 micromol/L, P = .01). Glucose-intolerant subjects also had a higher percentage of insulin-insensitive, type 2b muscle fibers, which are not adapted for fat oxidation (7% +/- 9% v 9% +/- 9%, P = .003). BMI was not associated with NEFA suppression or the percentage of type 2b muscle fibers in either group. In conclusion, glucose-intolerant persons have impaired first-phase insulin release, an elevated percentage of type 2b muscle fibers, and increased NEFA availability. Reduced insulin clearance, hyperinsulinemia, and insulin resistance were associated with small increments in BMI.     

Characteristics of young offspring of type 2 diabetic parents in a biracial (black-white) community-based sample: the Bogalusa Heart Study

The impact of race (black-white) and family history of type 2 diabetes mellitus on metabolic characteristics in early life was examined in a community-based sample from Bogalusa, LA. Study subjects included offspring of type 2 diabetics (n = 53, 47% black) and nondiabetics (n = 52, 40% black), with the mean age of each group ranging from 14.2 to 15.6 years. Offspring were given a 1-hour oral glucose tolerance test. Measures of body fatness such as body weight, body-mass index (BMI; weight/height2), and triceps and subscapular thicknesses were significantly higher only in white offspring of diabetics versus nondiabetics; measures of abdominal fat (waist circumference and waist-to-hip ratio) were significantly higher among offspring of diabetics of both races. Among the measures of glucose homeostasis, basal glucose, insulin, insulin-to-C-peptide ratio (a measure of hepatic insulin extraction), insulin resistance index (derived from basal glucose and insulin levels), and glucose response after glucose challenge were higher in the offspring of diabetics of both races. The differences in insulin-to-C-peptide ratio and glucose response remained significant after adjusting for BMI; further, these two variables were independently associated with parental diabetes in both races. Waist-to-hip ratio, glucose response, C-peptide response (a measure of insulin secretion) were lower, and basal insulin-to-C-peptide ratio and postglucose suppression of free fatty acids greater in blacks versus whites, regardless of status of parental diabetes. Black-white differences in postglucose suppression of free fatty acids disappeared after adjusting for BMI. Thus, blacks and whites with parental type 2 diabetes show multiple abnormalities in parameters governing glucose homeostasis early in life, and some of these traits differ between the races, regardless of status of parental diabetes.     

Fasting hyperinsulinemia and cardiovascular disease risk factors in nondiabetic adults: stronger associations in lean versus obese subjects. Atherosclerosis Risk in Communities Study Investigators

The association between hyperinsulinemia and atherogenic risk factors has not been well studied in blacks and may be different for obese versus lean individuals. To investigate this possibility and to confirm the associations of hyperinsulinemia with cardiovascular disease risk factors in blacks and whites, we analyzed the joint associations of fasting serum insulin and obesity with risk factors in the Atherosclerosis Risk in Communities (ARIC) Study (1,293 black men, 4,797 white men, 2,033 black women, and 5,445 white women). Insulin values > or = 90th percentile (> or = 21 microU/mL) constituted hyperinsulinemia; body mass index (BMI) values > or = 27.3 kg/m2 for women and > or = 27.8 for men constituted obesity. Participants with hyperinsulinemia in all four race-sex groups had more atherogenic levels of most risk factors studied than those with normoinsulinemia. Among black men and women, mean levels of triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) B, glucose, and fibrinogen (men only) were higher in hyperinsulinemic lean participants as compared with the normoinsulinemic obese group. Furthermore, most associations between insulin level and risk factors were stronger among lean versus obese subjects. For example, among lean black men, the difference in mean triglyceride concentration between those with hyperinsulinemia and those with normoinsulinemia was 147 - 99 = 48 mg/dL; among obese black men, the difference was 155 - 121 = 34 mg/dL (P < .05 for the interaction). Generally, similar negative interactions between BMI and insulin concentration were also observed among whites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced coronary vasoconstriction in the Syrian myopathic hamster supports the microvascular spasm hypothesis

This study examines the relation between blood pressure and insulin resistance in obese, sedentary middle-aged and older men. Eleven hypertensive and 17 normotensive subjects of comparable age (58.6 +/- 1.0 years, mean +/- SEM), percent body fat (27.7 +/- 0.7%), and maximal aerobic capacity (30.2 +/- 0.9 mL.kg-1.min-1) participated in this study. Glucose disposal (M, milligrams per kilogram of fat-free mass per minute) determined during a three-dose hyperinsulinemic euglycemic clamp was lower in the hypertensive than normotensive subjects at the low (M at 120 pmol/m2.min: 2.3 +/- 0.2 versus 3.2 +/- 0.3, P = .06), intermediate (M at 600 pmol/m2.min: 8.0 +/- 0.6 versus 10.4 +/- 0.6, P = .02), and high (M at 3000 pmol/m2.min: 13.5 +/- 0.5 versus 15.5 +/- 0.7, P = .04) insulin infusion rates. The calculated insulin concentration necessary for a half-maximal effect (EC50) was greater in the hypertensive than normotensive subjects (1164 +/- 168 versus 864 +/- 66 pmol/L, P = .03). In this population of normotensive and hypertensive men, systolic, diastolic, and mean arterial blood pressures were related to glucose disposal at these insulin infusion rates (r = -.35 to -.46, P < .05) as well as the EC50 (r = .42 to .44, P < .05). Thus, hypertensive obese, sedentary older men have a reduction in both sensitivity and maximal responsiveness to insulin that is directly related to the severity of hypertension independent of obesity and physical fitness.     

Medical and health impact of complex emergencies: implications for the International Society of Nephrology Disaster Relief Task Force

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery POI; and after reaching stable body weight, at least 2 years after surgery POII. A group of 7 control subjects (C), matched groupwise for sex, age and BMI with POII patients, was also studied. The M value at POI was significantly higher than at Ob (49.12 +/- 8.57 vs 18.14 +/- 8.57 mumol.kg-1.min-1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 +/- 7.23 vs 9.42 +/- 3.91 mumol.kg-1.min-1) and was not significantly different between POII and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/- 77.6 mumol.1(-1). The same applied to basal plasma triglycerides (2.07 +/- 0.77 vs 1.36 +/- 0.49 vs 0.80 +/- 0.19 g.1(-1). Weight decreased mainly in the late postoperative period (POI to POII 124.28 +/- 11.22 to 69.71 +/- 11.78, 83% of total decrement), rather than in the early postoperative period (Ob to POI 135.25 +/- 14.99 to 124.28 +/- 11.22 kg, 17% of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance.     

Mechanism of glucose intolerance during fasting: differences between lean and obese subjects

Oral glucose tolerance tests were performed on 14 lean and 14 obese nondiabetic subjects before and after a 6-day fast. In addition, insulin tolerance tests were performed on 8 lean and 8 obese subjects before and after starvation. Both in lean and obese subjects glucose tolerance deteriorated during starvation, but much more so in the lean population. During fasting, insulin elevation after a glucose load was significantly delayed in lean subjects but not in the obese. Circulating levels of factors known to affect glucose tolerance, such as glucagon, growth hormone, free fatty acids, and ketone bodies were higher in fasting lean than in fasting obese individuals. In normals fasting resulted in a significant decrease of the blood glucose response to insulin injection, whereas in fasting obese subjects glucose response was unchanged. The results obtained suggest that the effect of fasting on insulin release and insulin sensitivity was more pronounced in lean than in obese subjects, which resulted in greater deterioration of glucose tolerance in the lean population.     

Reduced adipocyte insulin sensitivity in Caucasian and Asian subjects with coronary heart disease

The association between insulin resistance and coronary heart disease (CHD) is strong in the British Indian-Asian population. Adipocyte metabolism may contribute to both insulin resistance and CHD. We examined insulin-stimulated glucose uptake in adipocytes and in vivo insulin sensitivity using the fasting insulin resistance index (FIRI) in 60 subjects (45 Caucasian and 15 Asian) with CHD and 30 Caucasian subjects without CHD. In 25 CHD subjects (18 Caucasian and 7 Asian), the relationship between adipocyte insulin sensitivity and non-esterified fatty acid (NEFA) suppression to oral glucose was examined. Compared with controls, the CHD subjects had higher values of fasting insulin [51 (46 to 54) pmol l(-1) vs 36 (31 to 41) pmol l(-1) p< 0.01] and FIRI [1.65 (1.5 to 1.79) vs 1.06 (0.89 to 1.23), p < 0.01]. Among the CHD subjects, the Asians had higher values than Caucasian [insulin 58 (48 to 67) pmol l(-1) vs 48 (44 to 53) pmol l(-1) p < 0.01, FIRI 1.89 (1.44 to 2.13) vs 1.62 (1.4 to 1.79), p< 0.01)]. Insulin-stimulated glucose uptake in adipocytes was lower in the CHD than control subjects [56 (50 to 62) vs 115 (75 to 132) attomol min(-1).mm2, p < 0.05], being most reduced among the Asians. It was positively correlated with postprandial NEFA suppression and negatively with insulin release. In conclusion, abnormalities of adipocyte function and insulin sensitivity occur in CHD and may contribute to its aetiology.     

Pulsed-field gel electrophoresis genomic fingerprinting of hospital Escherichia coli bacteraemia isolates

To study the effects of massive weight loss on insulin secretion, we analysed the oscillations of fasting peripheral insulin levels in obese patients who underwent vertical banded gastroplasty as treatment for morbid obesity. Patients were studied before and 6 months after surgery. Serial measurements of plasma free insulin levels were obtained in duplicates from 0 to 60 min at one-minute intervals. Insulin levels were then analysed by autocorrelation and Fourier transformation. In normal controls and obese patients, the first oscillatory insulin component was detected between 10 and 14 min. Compared to obese controls (n = 4), overt Type 2 diabetic patients (n = 4) had reduced amplitudes of insulin pulses and no oscillatory component. These defects were not as pronounced in patients with impaired glucose tolerance (IGT) after an oral glucose tolerance test (OGTT) (n = 5). When detected, the periodicity of the oscillations occurred at different periods. In 3/5 IGT patients, the first positive peak of correlation was found at 13.3 +/- 2.3 min. Weight loss (mean +/- SD) after 6 months was 24.3 +/- 3.7 for subjects with normal glucose tolerance (NGT), 37.9 +/- 9 for those with IGT and 29.8 +/- 5 kgs for Type 2 diabetic subjects. After weight loss, insulin oscillatory activity was detected in 4/5 IGT patients, with a period of 13 +/- 3 min. Weight loss did not reverse the defects observed in obese diabetic patients despite a significant reduction in peripheral insulin levels from 28.6 +/- 6 to 15.6 +/- 6 mU/l (p < 0.05). Insulin values remained higher than in obese controls (7.82 +/- 2, p < 0.05), and Type 2 patients remained mildly hyperglycaemic. These findings indicate that beta-cell activity is abnormal in Type 2 diabetic patients. The absence of modification after weight loss suggests that inherent beta-cell defects may contribute to hyperglycaemia.     

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.     

Improvement of lipid profile in type 2 (non-insulin-dependent) diabetes mellitus by insulin-like growth factor I

Type 2 (non-insulin-dependent) diabetes mellitus is associated with increased glucose, insulin, total and VLDL-triglyceride, and often total and LDL-cholesterol levels which promote vascular disease. Recombinant human insulin-like growth factor-I which mimics many effects of insulin, decreased insulin, total and VLDL-triglyceride, and total and LDL-cholesterol levels in healthy man as well as glucose and insulin levels in Type 2 diabetic patients. We, therefore, investigated total and fractionated triglyceride and cholesterol levels, lipoprotein(a), non-esterified fatty acid, and apolipoprotein levels in eight Type 2 diabetic patients during five control, five treatment, and three wash-out days. They received a constant diet throughout and daily 2 x 120 micrograms insulin-like growth factor-I/kg s.c. during the treatment period. Fasting total and VLDL-triglyceride, total and LDL-cholesterol control levels were (mean +/- SD) 3.1 +/- 2.6, 1.3 +/- 1.0, 6.3 +/- 1.3, and 4.5 +/- 1.1 mmol/l and decreased to 1.6 +/- 0.8, 0.6 +/- 0.4, 5.0 +/- 1.0, and 3.5 +/- 1.1 mmol/l, respectively, on the last treatment day (p < 0.01). During therapy, fasting lipoprotein(a) levels and the postprandial area under the triglyceride curve decreased by 48 +/- 22 and 32 +/- 18% of control (p < 0.01), respectively. In conclusion, insulin-like growth factor-I lowered lipid levels in Type 2 diabetic patients directly or indirectly or both because of decreased glucose and insulin levels. Long-term trials would be of interest with respect to the cardiovascular risk in Type 2 diabetes and patients with hyperlipidaemia.