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Obesity commonly accompanies hypertriglyceridemia, and weight reduction is widely recommended for treatment of elevated triglyceride levels. To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range. After reestablishment of a steady state in body weight at the lower level, measurements were made of plasma lipid, lipoprotein, and apolipoprotein levels and the kinetics of low density lipoprotein (LDL) apolipoprotein B-100 (apo B) and apolipoprotein A-I (apo A-I). The patients lost an average of 10.6 +/- 2.1 kg (mean +/- SEM). Plasma triglyceride concentrations fell from 431 +/- 42 mg/dl to 248 +/- 27 mg/dl (p less than 0.001), whereas concentrations of total cholesterol, LDL cholesterol, total apo B, and high density lipoprotein (HDL) cholesterol were unchanged after weight loss. On average, the fractional catabolic rates (FCRs) for LDL were much higher in the patients after weight loss than in 16 normal control subjects (0.55 +/- 0.06 versus 0.31 +/- 0.06 pool/day), and input rates for LDL also were higher for hypertriglyceridemic patients after weight loss (22.2 +/- 2.4 versus 12.8 +/- 2.3 mg/kg.day). Compared with 20 normal control subjects, hypertriglyceridemic patients after weight reduction had persistent low HDL cholesterol levels (32 +/- 2 versus 54 +/- 3 mg/dl) as well as low apo A-I levels (99 +/- 5 versus 122 +/- 4 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistence of abnormalities in metabolism of apolipoproteins B-100 and A-I after weight reduction in patients with primary hypertriglyceridemia. 163 97

The effect of a 50% reduction in food intake on energy expenditure, protein metabolism, glucose cycling, and body composition was investigated in eight moderately overweight men. The prestudy mean calorie and protein intake was determined for eight subjects. They were then maintained on this diet for 6 weeks (mean +/- SEM, 3,269 +/- 75 kcal/d, 20.0 +/- 0.5 g N/d, period I), after which the diet was reduced uniformly in the major foodstuffs by 50% for the next 4 weeks (1,555 +/- 38 kcal/d, 9.6 +/- 5 g N/d, period II). At the end of each period we measured (1) body fat and fat free mass by underwater weighing, (2) 24-hour energy expenditure by indirect calorimetry in a calorimeter, (3) whole body protein synthesis and breakdown rates with 15N glycine, and (4) glucose cycling between glucose and glucose-6-phosphate and fructose cycling between fructose-6-phosphate and fructose-1,6 bisphosphate with 6,6-D2- and 2-D1-labeled glucose. The results were subjects lost 4.0 +/- 0.1 kg fat (by underwater weighing) during the 4 weeks on the reduced-energy regimen. Protein turnover and glucose cycling were reduced by 20% and 15%, respectively. Twenty-four-hour energy expenditure was 2,553 +/- 166 kcal/d for period I and 2,369 +/- 69 kcal/d for period II, giving a difference of 184 +/- 34 kcal/d between the two periods. In conclusion, (1) although energy intake was reduced by 50%, the decrease in energy expenditure was small due to the buffering effect of body fat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of reduced dietary intake on energy expenditure, protein turnover, and glucose cycling in man. 202 34

The study concerns the clinical outcome and later prognosis (regarding permanent insulin treatment) of patients who develop insulin-dependent diabetes mellitus during pregnancy (which is different from gestational diabetes). Sixty-three such patients (27 +/- 1 (SEM) years old) were delivered at the Copenhagen Centre for Diabetes and Pregnancy during the years 1966-1980. Obstetric complications such as toxaemia were seen in 9.5% of these study patients and the perinatal mortality was 6.3%, both percentages being higher than in the general population (1.1%, p less than 10(-7) and 1.0%, p less than 10(-3), respectively), but similar to those observed in patients with Type 1 diabetes diagnosed before pregnancy. In contrast, the frequency of malformations was 1.6%, the same as in the general population (1.4%), but lower than that seen in patients with long-standing diabetes (8.3%, p less than 0.05). At follow-up examination 8 +/- 1 years after diagnosis all patients were diabetic; 77% were insulin treated, having no or virtually no residual B-cell function, and were clearly Type 1 diabetic patients. After delivery 80% of the patients had a remission period (median 256 days) without insulin treatment. This remission period was absent or shortest in patients with the following characteristics (p less than or equal to 0.03): low age, first parity, not overweight, and high blood glucose level at diagnosis. These prognostic parameters should be considered in obligatory, clinical follow-up plans for such patients.
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PMID:Type 1 (insulin-dependent) diabetes mellitus diagnosed during pregnancy: a clinical and prognostic study. 240 79

An association between hyperinsulinemia and hypertension has been suggested by epidemiological surveys. To assess whether this association is independent of the presence of other hyperinsulinemic states, such as obesity and glucose intolerance, we measured the insulin response to oral glucose in a group of middle-aged moderately obese [144 +/- 4% overweight (mean +/- SEM)] patients (n = 18) with essential hypertension (174 +/- 5/104 +/- 2 mm Hg) and normal glucose tolerance. Normotensive subjects (n = 17) with normal glucose tolerance, matched for age and degree of overweight, served as the control group. The mean insulin response to glucose was twice as high in the hypertensive patients (25.8 +/- 0.2 mU/ml X 2 h) as in the normotensive subjects (11.3 +/- 0.2; P less than 0.001), yet the glucose incremental area was 3-fold higher in the former (10.9 +/- 1.0 g/dl X 2 h) than in the latter (3.5 +/- 0.7; P less than 0.001), thus indicating more severe insulin resistance. In the hypertensive group, systolic blood pressure levels were directly correlated with the 2-h plasma insulin values (r = 0.75; P less than 0.001). Furthermore, the 2-h plasma insulin value and the degree of overweight accounted for 65% of the variation in the systolic blood pressure in a multiple regression model (r = 0.81; P less than 0.001). We conclude that in obesity, the occurrence of hypertension marks the presence of additional hyperinsulinemia and insulin resistance, independent of any impairment of glucose tolerance.
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PMID:Evidence for an association of high blood pressure and hyperinsulinemia in obese man. 351 32

To estimate the energy requirement of lean and overweight women, 29 lean (body weight, 59 +/- 1 kg; means +/- SEM) and 18 overweight (94 +/- 5 kg) women consumed a weight-maintenance diet for 8 d. The final 80 h were spent in a whole-body indirect calorimeter. Actual metabolizable energy intake (ME) was measured by analyzing food, feces, and urine. Mean ME was 8.88 +/- 0.13 MJ/d (2123 +/- 30 kcal/d) (lean) and 10.12 +/- 0.29 MJ/d (2419 +/- 70 kcal/d) (overweight). Mean 24-h energy expenditure (24hEE) of the lean (8.58 +/- 0.13 MJ or 2052 +/- 32 kcal) was lower than that of the overweight (10.70 +/- 0.45 MJ or 2558 +/- 108 kcal; p less than 0.001) women. Energy balance was close to zero in both groups. Therefore, 24hEE was used as an estimation of energy requirement. Multiple-regression analysis showed body weight to be the best single predictor of 24hEE. Our data may be useful for prediction of energy requirements of women (aged 20-50 yr) in normal life.
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PMID:Energy requirements and energy expenditure of lean and overweight women, measured by indirect calorimetry. 360 65

To clarify the independent relationships of obesity and overweight to cardiovascular disease risk factors and sex steroid levels, three age-matched groups of men were studied: (i) 8 normal weight men, less than 15% body fat, by hydrostatic weighing; (ii) 16 overweight, obese men, greater than 25% body fat and 135-160% of ideal body weight (IBW); and (iii) 8 overweight, lean men, 135-160% IBW, but less than 15% fat. Diastolic blood pressure was significantly greater for the obese (mean +/- SEM, 82 +/- 2 mmHg) than the normal (71 +/- 2) and overweight lean (72 +/- 2) groups, as were low density lipoprotein levels (131 +/- 9 vs. 98 + 11 and 98 + 14 mg/dl), the ratio of high density lipoprotein to total cholesterol (0.207 +/- 0.01 vs. 0.308 +/- 0.03 and 0.302 +/- 0.03), fasting plasma insulin (22 +/- 3 vs. 12 +/- 1 and 13 +/- 2 microU/ml), and the estradiol/testosterone ratio (0.076 +/- 0.01 vs. 0.042 +/- 0.02 and 0.052 +/- 0.02); P less than 0.05. Estradiol was 25% greater for the overweight lean group (40 +/- 5 pg/ml) than the obese (30 +/- 3 pg/ml) and normal groups (29 +/- 2 pg/ml), P = 0.08, whereas total testosterone was significantly lower in the obese (499 +/- 33 ng/dl) compared with the normal and overweight, lean groups (759 +/- 98 and 797 +/- 82 ng/dl). Estradiol was uncorrelated with risk factors and the estradiol/testosterone ratio appeared to be a function of the reduced testosterone levels in obesity, not independently correlated with lipid levels after adjustment for body fat content. Furthermore, no risk factors were significantly different between the normal and overweight lean groups. We conclude that (a) body composition, rather than body weight per se, is associated with increased cardiovascular disease risk factors; and (b) sex steroid alterations are related to body composition and are not an independent cardiovascular disease risk factor.
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PMID:Body composition, not body weight, is related to cardiovascular disease risk factors and sex hormone levels in men. 365 69

Fifteen patients with non-insulin-dependent diabetes mellitus, poorly controlled on insulin, were enrolled in a weight loss program. Criteria included a fasting plasma glucose concentration greater than 200 mg/dl, age in excess of 65 years, and the presence of obesity. Twelve of the 15 patients were able to complete the program, and the average weight loss of the group was 9 kg. Prior to initiation of the weight loss program the 12 patients were receiving (mean +/- SEM) 52 +/- 5 units of insulin per day and had a mean (+/- SEM) fasting plasma glucose concentration of 258 +/- 10 mg/dl. Insulin treatment was discontinued in all subjects during the weight loss period, and did not need to be resumed when weight stabilization had occurred. On the other hand, reasonable diabetic control could not be maintained without medication, and all patients were started on chlorpropamide during the period of weight stabilization. With this approach, a mean (+/- SEM) fasting glucose concentration of 137 +/- 4 mg/dl was achieved with a daily chlorpropamide dose of 354 +/- 30 mg. This dramatic clinical change took place despite the fact that no patient achieved ideal body weight. These results document the ability of a moderate amount of weight loss to transform patients with non-insulin-dependent diabetes mellitus, who are overweight and older than 65 years of age, from treatment failures to treatment successes.
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PMID:Beneficial effect of moderate weight loss in older patients with non-insulin-dependent diabetes mellitus poorly controlled with insulin. 388 6

Obesity is considered an insulin resistant state. Dietary guar gum supplementation is able to reduce blood glucose and plasma insulin response to a carbohydrate meal. In order to evaluate whether guar is able to reduce hyperinsulinemia and insulin resistance in gross obesity, we studied 9 obese patients, greater than 50% overweight with impaired glucose tolerance before and after 4 + 4 g/day guar for 6 weeks. Six patients repeated the treatment with 8 + 8 g/day guar after a 3-month interval. Guar was added to the usual diet in order to maintain the body weight constant. Pre-treatment and post treatment study included: total specific insulin binding on circulating monocytes; 3H-glucose infusion and euglycemic hyperinsulinemic clamp at approximately 100 microU/ml. The differences between post-treatment and pre-treatment values were not significant for any of the parameters studied. Fasting glucose production was: 2.17 +/- 0.33 SEM (pretreatment) vs 2.18 +/- 0.18 (4 + 4 g/day) vs 2.28 +/- 0.14 (8 + 8 g/day) mg/kg/min; glucose utilization was: 3.52 +/- 0.43 vs 3.22 +/- 0.44 vs 3.49 +/- 0.63 mg/kg/min; total specific insulin binding was: 2.80 +/- 0.20 vs 2.75 +/- 0.25 vs 2.78 +/- 0.31%; body weight was: 101.4 +/- 5.4 vs 100.2 +/- 6.2 vs 100.5 +/- 7.0 kg. These results indicate that dietary guar gum supplementation per se is unable to reduce insulin resistance in gross obesity if overweight is maintained constant.
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PMID:Dietary guar gum supplementation does not modify insulin resistance in gross obesity. 390 31

The thermic effect of food at rest, during 30 min of cycle ergometer exercise, and after exercise was studied in eight lean (mean +/- SEM, 10 +/- 1% body fat, hydrostatically-determined) and eight obese men (30 +/- 2% body fat). The lean and obese mean were matched with respect to age, height, weight, and body mass index (BMI) to determine the relationship between thermogenesis and body composition, independent of body weight. All men were overweight, defined as a BMI between 26-34, but the obese had three times more body fat and significantly less lean body mass than the lean men. Metabolic rate was measured by indirect calorimetry under four conditions on separate mornings, in randomized order, after an overnight fast: 3 h of rest in the postabsorptive state; 3 h of rest after a 750-kcal mixed meal (14% protein, 31.5% fat, and 54.5% carbohydrate); during 30 min of cycling and for 3 h post exercise in the postabsorptive state; and during 30 min of cycling performed 30 min after the test meal and for 3 h post exercise. The thermic effect of food, which is the difference between postabsorptive and postprandial energy expenditure, was significantly higher for the lean than the obese men under the rest, post exercise, and exercise conditions: the increments in metabolic rate for the lean and obese men, respectively, were 48 +/- 7 vs. 28 +/- 4 kcal over 3 h rest (P less than 0.05); 44 +/- 7 vs. 16 +/- 5 kcal over 3 h post exercise (P less than 0.05); and 19 +/- 3 vs. 6 +/- 3 kcal over 30 min of exercise (P less than 0.05). The thermic effect of food was significantly negatively related to body fat content under the rest (r = -0.55), post exercise (r = -0.66), and exercise (r = -0.58) conditions. The results of this study indicate that for men of similar total body weight and BMI, body composition is a significant determinant of postprandial thermogenesis; the responses of obese are significantly blunted compared with those of lean men.
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PMID:Thermic effect of food at rest, during exercise, and after exercise in lean and obese men of similar body weight. 404 28

To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143 +/- 4% ideal body weight; mean +/- SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57 +/- 0.28 pmol.kg-1. min-1) than in healthy control subjects (1.68 +/- 0.17 pmol.kg-1.min-1; p less than 0.01). After ingestion of 25 g glucose, the cumulative insulin production rate exceeded normal values (p less than 0.05), but was below normal with 100 g glucose (p less than 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54 +/- 3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p less than 0.005). Splanchnic output of pyruvate (p less than 0.025), lactate (p less than 0.01), and beta-hydroxybutyrate (p less than 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.
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PMID:Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus. 674 86


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