Glycine alleviates liver injury induced by deficiency in methionine and or choline in rats.

OBJECTIVES: Nonalcoholic steatohepatitis (NASH) is an advanced stage of non-alcoholic fatty liver disease (NAFLD) from steatosis. Methionine and choline are important amino acids play a key role in many cellular functions. Glycine is a non-essential amino acid having multiple roles in many reactions. This study aimed to investigate liver damage induced by feeding male albino rats either methionine deficient (MD), choline deficient (CD), or MCD diets. And to clarify the alleviatory effect of dietary glycine supplementation (5%) on reduced complications caused by feeding each of the deficient diets. MATERIAL AND METHODS: Nutritional status, liver functions, lipids profile, hepatic oxidative stress, hepatic antioxidant enzymes, tumor markers and hepatic fatty acid transport protein gene were assessed. RESULTS: Rats fed with either MD or MCD diet had less body weight gain unlike rats fed the CD diet. Liver injury was detected in deficient groups by elevating plasma ALT, AST, ALP, total and direct bilirubin, albumin and protein levels. Lipid accumulation was more prominent in rats fed the MCD or CD diet than in those fed the MD diet. Fatty acid transport protein (FATP) was significantly elevated in the different glycine supplemented groups. CONCLUSION: Oral administration of glycine confers a significant protective effect by optimizing all the assessed parameters and gene expression.

Ethnic differences in in vitro glyceride synthesis in subcutaneous and omental adipose tissue.

Considerable evidence suggests that there are ethnic differences in lipid metabolism between African American and Caucasian women, which may result in increased synthesis of fat in adipose tissue. The purpose of this study was to measure the in vitro rates of [14C]glucose incorporation into the glyceride-glycerol backbone of triglycerides (TG) and diglycerides (DG) in abdominal subcutaneous (SAT) and omental adipose tissue (OAT). Morbidly obese [African American (n = 15): body mass index (BMI) = 45 +/- 2.3; Caucasian (n = 18): BMI = 51 +/- 2.3] and preobese [African American (n = 7): BMI = 27 +/- 1.0; Caucasian (n = 7): BMI = 25 +/- 1.0] women were examined in this study. There were no significant differences in the rates of synthesis of either TG or DG in SAT of either preobese or obese women. On the other hand, both preobese and obese African American women had higher rates of synthesis of TG in OAT compared with their Caucasian counterparts. This increase in TG synthesis in OAT was not due to differences in cell size or rates of reesterification. Thus African American woman have an increased capacity to synthesize TG in OAT compared with Caucasian women, which may contribute to the higher prevalence of obesity in African American women.

Plasma cholesteryl ester transfer protein activity is not linked to insulin sensitivity.

Plasma cholesteryl ester transfer protein (CETP) activity has been reported to decline during a hyperinsulinemic-euglycemic clamp. It has been suggested that this suppressive effect of acute hyperinsulinemia is linked to whole body insulin sensitivity, and that the insulin resistance that accompanies obesity leads to high plasma CETP activity found in obese subjects. In the present study, we used 2 experimental approaches to examine the putative link between CETP and insulin action. First, we examined if the clamp-induced suppression of plasma CETP activity is linked to whole body insulin sensitivity. Plasma CETP activity was measured at the beginning and end of a 2-hour hyperinsulinemic-euglycemic clamp in 18 nondiabetic individuals before and after an exercise training regimen that improved insulin sensitivity without weight loss. CETP activity decreased in response to the clamp procedure in 16 of 18 subjects, and on average, by 9% (P <.001). While training decreased plasma CETP activity (10%, P <.05), the improvement in insulin sensitivity had no statistical effect on the clamp-induced suppression of plasma CETP activity (training*clamp, P =.26). Second, we examined if insulin resistance is associated with an elevation in fasting plasma CETP activity when the influence of adiposity and diabetes were negated. Plasma CETP activity was measured in 41 women (12 insulin-sensitive lean; 8 insulin-resistant lean; 10 insulin-sensitive obese; 11 insulin-resistant obese). The level of insulin sensitivity had no significant effect on fasting plasma CETP activity, but CETP levels were 25% higher in obese subjects (P <.01). Thus, neither experimental approach provided evidence that plasma CETP levels are linked to insulin and insulin sensitivity. These data suggest that the elevated CETP activity found in obese patients is less associated with hyperinsulinemia and the accompanying insulin resistance, but rather is more related to some other metabolic complication of obesity.

Influence of moderate chronic wine consumption on insulin sensitivity and other correlates of syndrome X in moderately obese women.

Epidemiologic studies indicate that alcohol consumption is associated with improved insulin sensitivity; however, scant experimental evidence confirms this observation. To determine the effects of regular moderate wine consumption on insulin sensitivity, 20 overweight women (body mass index [BMI], 29.8 +/- 2.2 kg/m2) participated in a 20-week free-living randomized crossover trial. The subjects, serving as their own controls, consumed wine (190 mL red wine, 13% vol/vol ethanol, 5 days per week) for 10 weeks and abstained for 10 weeks or vice versa. The dependent variables (body weight, BMI, percent body fat, blood pressure, fasting blood glucose and insulin, blood lipids, dietary intake, and insulin sensitivity by intravenous glucose tolerance test [IVGTT]) were measured at the pretest, at the 10-week crossover, and at the 20-week completion of the study. Data were analyzed at the pretest and at completion of the wine drinking and abstention periods of the study using ANOVA by order of treatment. Fasting glucose remained unchanged (mean +/- SD; P > .05) throughout the experiment (pretest, drinking, and abstention, 91.1 +/- 9.2, 91.6 +/- 9.1, and 88.5 +/- 11.2 mg/dL), as did the measures of insulin sensitivity, fasting insulin (pretest, drinking, and abstention, 8.6 +/- 3.3, 8.6 +/- 4.1, and 9.1 +/- 4.7 microU/mg) and the insulin sensitivity index (3.60 +/- 2.96, 3.25 +/- 2.17, and 3.30 +/- 1.84). Body composition and blood lipids also remained unchanged (P > .05) during treatment. Moderate wine consumption at this dose in overweight women did not improve or impair insulin sensitivity, nor did it change any of the known correlates of insulin sensitivity, including body weight and composition, blood lipids, and blood pressure.

Insulin does not regulate the promoter of cholesteryl ester transfer protein (CETP) in HIRc/pCETP-CAT cells.

Cholesteryl ester transfer protein (CETP) is a plasma enzyme involved in cholesterol metabolism. As a potential target in the treatment of atherosclerosis, a number of studies have focused how this enzyme is regulated. It has been postulated that insulin may regulate CETP gene expression, and these effects may be mediated through CCAAT/enhancer binding protein alpha (C/EBPalpha). The present study examines the effects of insulin on the activity of the CETP promoter in rat fibroblasts expressing the human insulin receptor (HIRc). HIRc cells were stably transfected with a chimeric construct containing 3.2 kb of the CETP promoter attached to the bacterial chloramphenicol acyltransferase gene (pCETP-CAT) without significantly affecting the expression of the insulin receptor. CAT activity was 8-fold higher in cultured HIRc/pCETP-CAT in the presence of 100 mg/dL LDL cholesterol, than those cultured without cholesterol (p < 0.05). However, culturing these cells in the presence of 100 nM insulin did not result in any change in CAT activity when compared to control cells. In HIRc/pCETP-CAT cells transiently transfected with a construct that constitutively expressed C/EBPalpha protein, a 3-fold increase in CAT activity was observed when compared to cells transiently transfected with non-specific DNA (p < 0.05). However, no observable effect on the CETP promoter was observed in the presence of insulin. Thus, in HIRc/pCETP-CAT cells, we were unable to substantiate the hypothesis that insulin regulates CETP gene transcription. These results suggest that the effects of insulin on CETP expression regulation may be downstream of transcription.

Differential expression of cholesteryl ester transfer protein in the liver and plasma of fasted and fed transgenic mice.

Because cholesteryl ester transfer protein (CETP) is considered a potential target in the treatment of atherosclerosis, several reports have focused on the regulation of this enzyme, and there is evidence that insulin may be a regulatory factor. The present study examines the differential expression of the human CETP gene between physiologic conditions that are accompanied by low (fasted) and high (fed) insulin levels. CETP expression was examined in plasma and tissues of transgenic mice expressing the human CETP minigene after 12 hours of fasting (n = 20) or ad libitum feeding (n = 20) with normal mouse chow. Plasma cholesteryl ester transfer activity (CETA) was 20% higher in fed than in fasted mice, reflecting higher levels of CETP (P < 0.05). This observation was accompanied by higher liver mRNA in fed mice (100%, P < 0.05), as determined by ribonuclease protection assays, as well as by higher CETA (23%, P < 0.05) and CETP mass (29%, P < 0.05) in the particulate fraction of liver homogenates. These parameters of liver CETP expression correlated well with each other, as well as with plasma CETA. CETP in the liver particulate fraction was found as a doublet (approximately 70 and 65 kDa), which resolved to a single band (approximately 60 kDa) upon deglycosylation. No differences in CETP expression were observed in pooled adipose tissue samples from fed and fasted mice. Insulin and glucose were not related to any plasma or tissue parameter of CETP expression. In summary, the concerted, differential expression of CETP in the liver of fed and fasted transgenic mice appears to contribute to higher plasma CETP levels in fed mice, but the precise role of insulin and glucose in regulating CETP expression under fasted and fed conditions needs to be defined.

Effect of short-term exercise training on leptin and insulin action.

The purpose of the study was to determine the effect of short-term exercise training (7 consecutive days for 60 min/d at 75% maximal oxygen consumption [VO2 max]), which did not change body mass on fasting plasma leptin concentration and insulin action. Young, lean subjects (n = 16; age, 21.9 +/- 0.6 years; body fat, 17.5% +/- 1.5%) and older subjects with relatively more adipose tissue (n = 14; age, 58.6 +/- 1.4 years; body fat, 28.3% +/- 1.3%) were studied (mean +/- SE). Fasting plasma leptin was significantly (P < .05) related to adiposity (fat mass, r = .58; % body fat, r = .76) in this population. Body mass did not change (P < .05) in any of the groups with training (71.8 +/- 2.5 v 71.9 +/- 2.5 kg). The insulin sensitivity index (SI determined from an intravenous glucose tolerance test (IVGTT) improved significantly (P < .05) in both the young group (4.8 +/- 0.6 v6.9 +/- 0.8 x 10(-4)/ min (microU/mL) and the older group (3.2 +/- 0.6 v 5.9 +/- 1.0 x 10(-4)/min (microU/mL)). Fasting leptin did not change with training in either group (10.4 +/- 1.6 v 9.2 +/- 1.0 ng/mL). These findings suggest that exercise does not independently affect the fasting plasma leptin concentration and the improvement in insulin action with exercise is not associated with an alteration in fasting leptin in healthy sedentary lean and relatively lean subjects.

Lipoprotein subpopulation distributions in lean, obese, and type 2 diabetic women: a comparison of African and white Americans.

OBJECTIVE: Abnormal subpopulation distributions of plasma lipoproteins have been reported in white American (WA) women with obesity and type 2 diabetes that explain part of the elevated rate of cardiovascular disease in these patients. This study examined if these perturbations also occur in obese and diabetic African American (AA) women and compared the lipoprotein profiles with WA counterparts. RESEARCH METHODS AND PROCEDURES: We determined the lipoprotein subpopulation distribution in the plasma of 51 lean women (29 WA, 22 AA, body mass index [BMI] < 30), 50 obese women (27 WA, 23 AA, BMI > 30), and 43 obese women with type 2 diabetes (27 WA, 16 AA), by nuclear magnetic resonance spectroscopy. RESULTS: AA diabetic women, like WA diabetic women, had a larger average very low density lipoprotein (VLDL) size, elevated levels of small low density lipoprotein cholesterol (LDL-C), and lower levels of small high density lipoprotein cholesterol (HDL-C), when compared to lean controls (p<0.05). These differences were accompanied by higher VLDL-triglycerides (TG) and LDL-C in WA (p<0.05), but not in AA. Although the effects of obesity and diabetes on lipoprotein subpopulation were fairly similar for AA and WA, some racial differences, particularly with respect to HDL, were observed. DISCUSSION: The atherogenic perturbations in lipoprotein profiles of obese AA women, particularly those with diabetes, were relatively similar to those found in WA women and may be contributing to the increased rate of cardiovascular disease (CVD) in AA with obesity and diabetes. The parameters of subpopulation distribution may provide better markers for CVD than lipid concentrations alone, particularly in AA women. Furthermore, subtle racial differences in lipoprotein profiles suggest that race-specific criteria may be needed to screen patients for CVD.

Impact of insulin resistance on lipoprotein subpopulation distribution in lean and morbidly obese nondiabetic women.

The purpose of this study was to examine the effects of insulin resistance on the lipoprotein subpopulation distribution of very-low-density, low-density, and high-density lipoproteins (VLDL, LDL, and HDL) in lean and morbidly obese nondiabetic women. Lean women (body mass index [BMI], 20 to 27 kg/m2) stratified by BMI were divided into insulin-sensitive (SL, n = 12) and insulin-resistant (RL, n = 8) groups according to Bergman's minimal model, SI. A group of obese women (BMI, 30 to 53 kg/m2), also stratified by BMI, were divided into insulin-sensitive (SO, n = 10) and insulin-resistant (RO, n = 11) groups in a similar fashion. Resistant groups were similar to sensitive groups (SL v RL and SO vRO) in age, weight, percent body fat, and waist circumference, ie, total and regional adiposity. VLDL, LDL, and HDL subpopulation distributions were determined in fasting plasma samples by nuclear magnetic resonance (NMR) spectroscopy. The average particle sizes of all 3 classes of lipoproteins were similar for the SL and RL groups. In contrast, RO subjects had larger VLDL, smaller LDL, and smaller HDL, than SO subjects (P < .05). Lower concentrations of large LDL and large HDL were found in RO compared with SO subjects (P < .05). In obese women, but not in lean women, VLDL size was associated with plasma insulin (r = .60, P < .005), while LDL size and HDL size were negatively correlated with plasma insulin (r = -.39, P < .05 and r = -.38, P < .05) and positively correlated with SI (r = .54, P < .01 and r = .42, P < .05). These results suggest that in obese women, insulin resistance may be involved in the formation of lipoprotein subpopulation distributions that are associated with vascular disease.

A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?

SUMMARY BACKGROUND DATA: We previously reported, in a study of 608 patients, that the gastric bypass operation (GB) controls type 2 diabetes mellitus in the morbidly obese patient more effectively than any medical therapy. Further, we showed for the first time that it was possible to reduce the mortality from diabetes; GB reduced the chance of dying from 4.5% per year to 1% per year. This control of diabetes has been ascribed to the weight loss induced by the operation. These studies, in weight-stable women, were designed to determine whether weight loss was really the important factor. METHODS: Fasting plasma insulin, fasting plasma glucose, minimal model-derived insulin sensitivity and leptin levels were measured in carefully matched cohorts: six women who had undergone GB and had been stable at their lowered weight 24 to 30 months after surgery versus a control group of six women who did not undergo surgery and were similarly weight-stable. The two groups were matched in age, percentage of fat, body mass index, waist circumference, and aerobic capacity. RESULTS: Even though the two groups of patients were closely matched in weight, age, percentage of fat, and even aerobic capacity, and with both groups maintaining stable weights, the surgical group demonstrated significantly lower levels of serum leptin, fasting plasma insulin, and fasting plasma glucose compared to the control group. Similarly, minimal model-derived insulin sensitivity was significantly higher in the surgical group. Finally, self-reported food intake was significantly lower in the surgical group. CONCLUSIONS: Weight loss is not the reason why GB controls diabetes mellitus. Instead, bypassing the foregut and reducing food intake produce the profound long-term alterations in glucose metabolism and insulin action. These findings suggest that our current paradigms of type 2 diabetes mellitus deserve review. The critical lesion may lie in abnormal signals from the gut.

Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus.

OBJECTIVE: This report documents that the gastric bypass operation provides long-term control for obesity and diabetes. SUMMARY BACKGROUND DATA: Obesity and diabetes, both notoriously resistant to medical therapy, continue to be two of our most common and serious diseases. METHODS: Over the last 14 years, 608 morbidly obese patients underwent gastric bypass, an operation that restricts caloric intake by (1) reducing the functional stomach to approximately 30 mL, (2) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet, and (3) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy. Even though many of the patients were seriously ill, the operation was performed with a perioperative mortality and complication rate of 1.5% and 8.5%, respectively. Seventeen of the 608 patients (< 3%) were lost to follow-up. RESULTS: Gastric bypass provides durable weight control. Weights fell from a preoperative mean of 304.4 lb (range, 198 to 615 lb) to 192.2 lb (range, 104 to 466) by 1 year and were maintained at 205.4 lb (range, 107 to 512 lb) at 5 years, 206.5 lb (130 to 388 lb) at 10 years, and 204.7 lb (158 to 270 lb) at 14 years. The operation provides long-term control of non-insulin-dependent diabetes mellitus (NIDDM). In those patients with adequate follow-up, 121 of 146 patients (82.9%) with NIDDM and 150 of 152 patients (98.7%) with glucose impairment maintained normal levels of plasma glucose, glycosylated hemoglobin, and insulin. These antidiabetic effects appear to be due primarily to a reduction in caloric intake, suggesting that insulin resistance is a secondary protective effect rather than the initial lesion. In addition to the control of weight and NIDDM, gastric bypass also corrected or alleviated a number of other comorbidities of obesity, including hypertension, sleep apnea, cardiopulmonary failure, arthritis, and infertility. Gastric bypass is now established as an effective and safe therapy for morbid obesity and its associated morbidities. No other therapy has produced such durable and complete control of diabetes mellitus.

Effects of exercise training on the chemical composition of plasma LDL.

The purpose of the present study was to determine the effects of exercise training on the chemical composition of plasma low-density lipoprotein (LDL). Thirteen men (mean age +/- SE, 47.2 +/- 1.5 years) were examined before and after 14 weeks of endurance-oriented exercise training (3 to 4 d/wk, 30 to 45 min/d). Although calculated plasma LDL concentrations remained unaltered (3.49 +/- 0.24 versus 3.65 +/- 0.23 mmol/L), changes in the chemical composition of LDL (increased LDL free cholesterol, cholesterol ester, and phospholipid content) were associated with a reduction in adiposity, umbilical girth, and basal plasma insulin and glucose concentration with training intervention. Increases in LDL molecular weight and particle diameter were associated with a reduction in fat mass, plasma triglyceride concentration, and basal plasma glucose concentration with physical activity. The LDL lipid-to-protein ratio also increased (P < .01) with training by 7%, primarily due to an increase in LDL free cholesterol content (P < .01). These findings indicate the formation of LDL particles that are more cholesterol enriched and protein poor with exercise training, which provides additional evidence for the cardioprotective effect of long-term physical activity.

Coronary heart disease risk factors in morbidly obese women with normal glucose tolerance.

OBJECTIVE--To examine if the risk for CHD increases progressively with increases in the BMI of normoglycemic, hyperinsulinemic, morbidly obese women (BMI > or = 35 kg/m2). RESEARCH DESIGN AND METHODS--Insulin sensitivity was evaluated by calculating an ISI following an OGTT. There was a significant linear relationship between ISI and BMI fitted by two straight lines intersecting at a point corresponding to a BMI of 29.7 +/- 1.5 kg/m2. Significant linear relationships between insulin sensitivity and BMI were obtained below and above this breakpoint. Similarly, a breakpoint for the relation between dBP and BMI corresponding to a BMI > or = 33.7 +/- 3.4 kg/m2 was obtained. Significant linear relationships between BMI and plasma fasting glucose, triglyceride, cholesterol, HDL cholesterol, sBP, or dBP were not observed in the women with a BMI > 35 kg/m2. RESULTS--Compared with lean (BMI < 27) women of similar age, the morbidly obese patients appear to be at a higher risk for CHD. This is suggested by statistically significant increases in fasting insulin (mean +/- SD; 187 +/- 137 vs. 64.2 +/- 16.2 pM) and triglyceride levels (128 +/- 78.1 vs. 73 +/- 25 mg/dl), sBP (132 +/- 114 vs. 104 +/- 15.8) and dBP (84 +/- 72 vs. 67 +/- 2.1 mmHg), and decreases in HDL cholesterol (1.03 +/- 0.44 vs. 1.29 +/- 0.82 mM) and apo A-I (91 +/- 55 vs. 122 +/- 35 mg/dl) concentrations. CONCLUSIONS--It appears that there may be a threshold of body mass up to which insulin sensitivity is associated with CHD risk. Above this threshold, there does not appear to be a progressive increase in the risk factors for CHD with increases in BMI.

Effects of exercise cessation on lipids and lipoproteins in distance runners and power athletes.

The purpose of this study was to determine the effects of short-term exercise cessation on lipid and lipoprotein profile and insulin sensitivity in highly trained runners (n = 12; mean age 19.9 years) and power athletes (n = 12; mean age 24.4 years). Following 14 days of exercise cessation, running time to exhaustion and maximal oxygen uptake decreased by 9.2% and 4.8% (P < 0.05) in the runners, while in the power athletes one repetition maximum squat and bench press did not change (P > 0.05). No changes occurred in body composition. Data from a 2-h oral glucose tolerance test revealed an impairment of the glycemic state in all athletes (P < 0.05). In contrast, exercise cessation did not significantly (P > 0.05) alter plasma levels of cholesterol, triglycerides, and low density (LDL) and high density lipoprotein (HDL). No changes were observed in HDL2, HDL2b, and HDL3 subfractions, LDL diameter, and qualitative LDL pattern (P > 0.05). These data thus suggest that despite a decrease in insulin sensitivity, short-term exercise cessation, independent of exercise mode, was insufficient to alter plasma lipid and lipoprotein profiles in well-trained athletes.

Is type II diabetes mellitus (NIDDM) a surgical disease?

Since February 1, 1980, 515 morbidly obese patients have undergone the Greenville gastric bypass (GGB) operation. Of these, 212 (41.2%) were euglycemic, 288 (55.9%) were either diabetic or had glucose intolerance, and 15 (2.9%) were unable to complete the evaluation. After the operation, only 30 (5.8%) patients remained diabetic (and 20 of these improved), 457 (88.7%) became and have remained euglycemic, and inadequate data prevented classification of the other 28 (5.4%). The patients who failed to return to normal glucose values were older and their diabetes was of longer duration than those who did. The effect of the GGB was not only limited to the correction of abnormal glucose levels. The GGB also corrected the abnormal levels of fasting insulin and glycosylated hemoglobin in a cohort of 52 consecutive severely obese patients with non-insulin-dependent diabetes. The GGB effectively controls weight. If morbid obesity is defined as 100 pounds over ideal body weight, 89% of the patients are no longer "morbidly" obese within 2 years. In most patients, the control of the weight has been well maintained during the 11 years of follow-up; most of the upward creep in weight of 20.8% between 24 and 132 months was from the 49 (9.5%) patients who had staple line breakdowns between the large and small gastric pouches. Non-insulin-dependent diabetes, previously considered a chronic unrelenting disease, can be controlled in the severely obese by the gastric bypass. Whether the correction of glucose metabolism affects the complications of diabetes is unknown. Whether the gastric bypass should be considered for patients with advanced non-insulin-dependent diabetes but who are not severely obese deserves consideration. The GGB has an unacceptably high rate of staple line failure. Accordingly, the authors have recently changed their procedure to one that divides the stomach rather than partitions it with staples.

Surgical treatment of obesity and its effect on diabetes: 10-y follow-up.

Since 1980 we have performed the identical Greenville gastric bypass (GGB) procedure on 479 morbidly obese patients with an acceptable morbidity and a mortality rate of 1.2%. The weight loss in the series was well maintained over the follow-up period of 10 y. The GGB can control non-insulin-dependent diabetes mellitus (NIDDM) in most patients. The group of 479 patients included 101 (21%) with NIDDM and another 62 (13%) who were glucose impaired. Of these 163 individuals, 141 reverted to normal and only 22 (5%) remained with inadequate control of their carbohydrate metabolism. Those patients who were older or whose diabetes was of longer duration were less likely to revert to normal values. The gastric bypass operation is an effective approach for the treatment of morbid obesity. Along with its control of weight, the operation also controls the hyperglycemia, hyperinsulinemia, and insulin resistance of the majority of patients with either glucose impairment or frank NIDDM.

Influence of morbid obesity and non-insulin-dependent diabetes mellitus on high-density lipoprotein composition and subpopulation distribution.

The chemical composition, subpopulation distribution and peak hydrated density of high-density lipoprotein (HDL) were examined in 18 morbidly obese women with either normal glucose tolerance or with non-insulin-dependent diabetes mellitus (NIDDM), and in 15 age-matched lean control subjects. Similar measurements were made in the morbidly obese subjects after gastric bypass surgery for weight loss. In the diabetic group, HDL was relatively protein-enriched and cholesterol- and cholesterol ester-poor compared with the lean controls. The same trend was seen in the nondiabetic group, although the cholesterol ester difference was not significant. In both cases, both electrophoretic and density gradient analysis showed that plasma HDL contained more of the HDL3 and less of the HDL2 subfractions than that for the lean controls. Following surgery in the diabetic group, the protein percentage of HDL decreased, and that of cholesterol ester increased; for the nondiabetic group, the protein decreased and phospholipid increased. In the diabetic group, a shift of the electrophoretic HDL subpopulation distribution toward more HDL2 accompanied these changes. Average hydrated peak density of HDL shifted from the HDL3 to the HDL2 range for the diabetic group following surgery; for the nondiabetic group the peak density also decreased but still remained within the HDL3 range. In all cases, the differences seen were more pronounced among the diabetic patients. These changes in the properties of HDL after gastric bypass surgery may favorably influence the risk for coronary heart disease usually associated with diabetes.

Effects of fitness level and the regional distribution of fat on carbohydrate metabolism and plasma lipids in middle- to older-aged men.

Many cross-sectional studies have demonstrated the influences of fitness level or the regional distribution of fat on lipid and carbohydrate metabolism; however, the relative contribution of these two variables in the same subjects has not been extensively examined. The purpose of this study was to determine the impact of regional adiposity on plasma lipids and carbohydrate metabolism in middle- to older-aged men with a wide range of fitness levels. Forty-six sedentary and exercise-trained men (age [mean +/- SE], 52.8 +/- 0.88 years) were included in this study. Fitness level was assessed by (a) time to exhaustion, and (2) maximal oxygen uptake achieved during an incremental treadmill test. Plasma lipid levels were determined in the basal, fasting state. Carbohydrate metabolism was evaluated by the glucose and insulin responses (total glucose and insulin areas under the curve, insulin sensitivity index [ISI]) to a 75-g, 2-hour oral glucose tolerance test (OGTT). Abdomen to hip ratio (AHR) was used as the index of regional adiposity. Multiple regression analysis indicated that fitness level and the percentage of body fat were significant predictors (approximately 56% of total variance) for total insulin area under the curve and the ISI. A comparison between the sedentary and trained subjects showed that training resulted in an improved ISI at an equal AHR. Fitness level was also the only significant multiple regression predictor for high-density lipoprotein (HDL)-cholesterol (25% of total variance) and accounted for the greatest amount of variance in triglyceride levels (34%), although AHR was also a significant predictor (6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipogenic potential of liver from morbidly obese patients with and without non-insulin-dependent diabetes.

Intra-abdominal liver biopsies were obtained during surgery from fasted obese patients with non-insulin-dependent diabetes mellitus (NIDDM), obese normoglycemic controls, and lean controls. Lipid synthesis was studied in freshly isolated hepatocytes and liver homogenates from the three groups of subjects. Incorporation of 3H2O into the lipids of hepatocytes was determined in the absence and presence of insulin (0.1 mumol/L). The activities of five enzymes involved in fatty acid synthesis, and the incorporation of 14C-glycerol-3-phosphate into lipids were determined in liver homogenates. Basal lipid synthesis by hepatocytes was not different in the three groups of patients. Insulin stimulated lipogenesis by 8% +/- 30% in the lean controls, 33% +/- 8% in the obese controls and 17% +/- 6% in the NIDDM patients. No significant differences in the activities of the five enzymes that are involved in de novo fatty acid synthesis among the three groups of patients were observed. Similarly, incorporation of 14C-glycerol-3-phosphate by liver homogenates, in the presence of saturating or submaximal concentrations of fatty acids, did not differ among the three groups. These results show that under the experimental conditions of this study, including the fasted state of the patients, the basal capacity of liver of NIDDM patients to synthesize fatty acids or glycerides is the same as that of liver from obese and lean controls. Thus, it is likely that an increase in fatty acid flux into a liver with normal lipogenic potential may contribute to the increased synthesis of triglycerides by the liver of these patients in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)