Cardiovascular risk of young growth-hormone-deficient adolescents. Differences in growth-hormone-treated and untreated patients

OBJECTIVE: To determine whether postprandial lipids, coagulation factors and homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD) adolescents. METHODS: Fifteen GHD adolescents on GH replacement were studied. Ten untreated GHD adolescents and 15 healthy subjects served as controls. Fasting lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1, homocysteine, folate and vitamin B12 levels were measured. Cholesterol and triglycerides were measured 4 h after a high fat meal. RESULTS: Fasting and postprandial triglycerides and homocysteine levels of untreated GHD patients were increased compared to those of GH-treated GHD subjects and healthy controls; fibrinogen concentrations were elevated in both treated and untreated adolescents. CONCLUSIONS: GHD adolescents present an abnormal fasting and postprandial lipid profile. In addition, the increased fibrinogen and homocysteine levels are suggestive of the accumulation of cardiovascular risk factors early on in life.     

Effect of enprostil on plasma glucose, insulin and lipid metabolism in patients with non-insulin-dependent diabetes mellitus

Measurements of various aspects of glucose, insulin and lipid metabolism were made before and after the administration of enprostil (a synthetic dehydroprostaglandin E2) for one week to ten patients with non-insulin-dependent diabetes mellitus (NIDDM). Both fasting (P less than 0.01) and postprandial (P less than 0.001) plasma glucose concentrations were significantly lower after one week of enprostil, and 24 hour urinary glucose excretion was reduced from (mean +/- SEM) 47 +/- 14 to 25 +/- 9 g/day. There was no change in either fasting or postprandial insulin concentration, but the postprandial GIP response was also significantly reduced (P less than 0.001). In addition, there were significant reductions in postprandial plasma free fatty acid (P less than 0.05) and triglyceride (P less than 0.001) concentrations, associated with a modest fall in fasting plasma triglyceride (P less than 0.05) and cholesterol (P less than 0.07) concentrations when measured after one week of treatment with enprostil. These results raise the possibility that enprostil may be of some benefit in the treatment of patients with non-insulin-dependent diabetes.     

Effect of feeding on circulating micronutrient concentrations in the Burmese python (Python molurus).

Burmese pythons (Python molurus) regulate digestive performance and metabolism with the ingestion of each meal. To explore the python's postprandial responses, we monitored the concentrations of blood micronutrients and homocysteine during fasting and for 15 days after feeding. Plasma folate concentrations peaked with a 270% increase over fasting levels 3 days after feeding, whereas plasma B-12 peaked with a 66% increase within 1 day. Erythrocyte folate concentrations were highest 15 days after feeding with a 44% increase. The major plasma folate was 5-methyltetrahydrofolate during fasting and was non-5-methyltetrahydrofolate during digestion, whereas erythrocytes contained polyglutamyl forms of non-5-methyltetrahydrofolate. Plasma homocysteine concentrations peaked with a 56% increase 3 days after feeding, and were markedly greater than those of mammals. Plasma zinc and copper did not change significantly. Plasma zinc concentrations were 20 times greater than plasma copper and approximately 30 times higher than those of mammals. Pythons showed a significant postprandial decline of 25% in hematocrit. Plasma pyridoxal 5'-phosphate (coenzyme form of vitamin B-6) was not detected probably due to its tight protein binding. Most micronutrient concentrations appear to plateau 3 days after feeding, suggesting that pythons have relatively rapid homeostasis of micronutrients despite the ingestion of large meals.     

High-volume exercise program in obese bariatric surgery patients: a randomized, controlled trial

Weight regain is a problem among many bariatric surgery patients. Whether a high-volume exercise program (HVEP), a strategy to limit weight regain, is feasible in these patients is unknown. The feasibility of an HVEP in obese post-bariatric-surgery patients was determined by randomizing 33 Roux-en-Y gastric bypass (RYGB) and gastric banding (GB) surgery patients with a mean BMI of 41 ± 6 kg/m2 to an HVEP or control group for 12 weeks. The HVEP group was instructed to expend ≥ 2,000 kcal/week in moderate-intensity exercise. All patients were counseled to limit energy intake. Treatment effect was assessed by repeated measures analysis. During the last 4 weeks of the study, 53% of the HVEP group expended ≥ 2,000 kcal/week and 82% expended ≥ 1,500 kcal/week. Step count, reported time spent and energy expended during moderate physical activity, maximal oxygen consumption relative to weight, and incremental area under the postprandial blood glucose curve were significantly improved over 12 weeks in the HVEP group compared to controls (group-by-week effect: P = 0.009-0.03). Both groups reported significant improvement in some quality-of-life scales. Changes in weight, energy and macronutrient intake, resting energy expenditure (REE), fasting lipids and glucose, and fasting and postprandial insulin concentrations were not different between the two groups. HVEP is feasible in about 50% of the patients and enhances physical fitness and reduces postprandial blood glucose in bariatric surgery patients.     

Relationships among biomarkers of one-carbon metabolism

One-carbon metabolism is a network of metabolic pathways, disruption of which has been associated with cancer and other pathological conditions. Biomarkers of these pathways include homocysteine (HCY), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). A better understanding of the relationships between these biomarkers is needed for their utilization in research. This study investigated the relationships between fasting concentrations of plasma HCY, SAM, SAH and the ratio of SAM:SAH, and serum folate, vitamin B(12) and creatinine in a healthy adult population. A cross-sectional study recruited 678 volunteers; only subjects with complete data (n = 581) were included in this analysis. Correlations were used to examine bivariate relationships among the biomarkers and multivariate linear regression determined independent relationships with HCY, SAM and SAH treated as dependent variables in separate models. Multivariate logistic regression examined determinants of a low SAM:SAH ratio (defined as having a SAM:SAH ratio in the bottom quartile and SAH value in the top quartile). HCY correlated inversely with folate and vitamin B(12) and weakly correlated with SAH and creatinine. Both SAM and SAH correlated with creatinine but were independent of serum folate and vitamin B(12). In multivariate analyses, folate, vitamin B(12), creatinine, sex and age were associated with HCY; age and creatinine were determinants of SAM, and sex and creatinine determinants of SAH. Finally, male sex and increasing creatinine levels were associated with having a low SAM:SAH ratio. Findings suggest that HCY, SAM and SAH are relatively independent parameters and reflect distinct aspects of one-carbon metabolism.     

Total plasma homocysteine determination by liquid chromatography before and after methionine loading: Results in cerebrovascular disease

Elevated homocysteine (HCY) levels in tissues and blood are associated with premature occlusive diseases. A number of techniques have been developed to assay HCY, including high-performance liquid chromatography (HPLC) with fluorimetric or electrochemical detection, and radioenzymatic methods. The present study evaluated the adaptation of a liquid chromatographic, ion-exchange technique with postcolumn derivatization using ninhydrin. Fasting and moreover post-methionine load total plasma HCY were assayed in 50 patients three months after a stroke and in 20 age-matched controls. Ion-exchange liquid chromatography was performed on an amino acid analyzer using a modified procedure to improve methionine and HCY separation. HCY values in the fasting state were moderately but significantly increased (P<0.05) in the patients compared to the controls: 10.5±3.4 versus 9.3±2.3 μmol/l. The difference between the two groups was amplified in post-load HCY results, which were significantly increased (P<0.05) in the patients: 41.6±17.8 versus 29.2±5.5 μmol/l in controls. The relationship between cerebrovascular disease and impaired HCY metabolism has previously been emphasized by other investigators. Our findings suggest that certain inherited and/or acquired HCY disorders observed in the fasting state (14%) and especially in post-methionine load conditions (32%) may occur during acute disease, and that total plasma HCY can be determined by ion-exchange chromatography even after oral methionine loading.     

Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years.

OBJECTIVE--To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations. DESIGN--Case control study over three years. SETTING--An 800 bed general municipal hospital. SUBJECTS--85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography. INTERVENTIONS--All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate. MAIN OUTCOME MEASURE--Postprandial lipoprotein metabolism. RESULTS--The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) mumol/l.h; 95% confidence interval of difference 4.37 to 11.82). CONCLUSION--Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease.     

Effects of atorvastatin on fasting and postprandial complement component 3 response in familial combined hyperlipidemia

VLDL overproduction by enhanced hepatic FFA flux is a major characteristic of familial combined hyperlipidemia (FCHL). The postprandial complement component 3 (C3) response has been associated with impaired postprandial FFA metabolism in FCHL. We investigated the effects of 16 weeks of treatment with atorvastatin on postprandial C3 and lipid changes in 12 FCHL patients. Atorvastatin significantly lowered fasting plasma C3 and triglyceride (TG) in FCHL. Fasting TG and insulin sensitivity were the best predictors of fasting and postprandial C3. Postprandial triglyceridemia and C3 response, estimated as area under the curve (AUC), were significantly lowered by atorvastatin by 19% and 12%, respectively, albeit still elevated, compared with 10 matched controls. Postprandial FFA-AUC and postheparin plasma lipolytic activities remained unchanged after atorvastatin, suggesting no major effect on lipolysis. After atorvastatin, postprandial hydroxybutyric acid-AUC, which was elevated in untreated FCHL patients, was decreased, reaching values similar to those in controls. The present data show reduction of postprandial hepatic FFA flux in FCHL by atorvastatin, providing an additional mechanistic explanation for the reduction of VLDL secretion reported previously for atorvastatin. This was accompanied by a decrease in fasting plasma C3 concentrations and a blunted postprandial C3 response to an acute oral fat load.     

Effect of folic acid deficiency upon lymphocyte subsets from lymphoid organs in mice.

1. Three groups of weanling C57BL/6 female mice were fed one of two folate-deficient diets (0 and 0.1 mg folic acid/kg diet) or a normal folate-containing diet (2 mg folic acid/kg diet) for 8 weeks. A control pair-fed group was introduced with the most severe folate-deficient diet. Seven mice were fed the 0 mg folic acid/kg diet for 8 weeks, then rehabilitated (R) on the 2 mg folic acid/kg diet for 10 days. 2. Mice fed 0 mg folic acid/kg diet were severely folate-deficient (SFD), whereas mice fed 0.1 mg folic acid/kg diet were moderately folate-deficient (MFD), as shown by their folate status parameters. 3. Thymus weight, thymocyte content and positive immature CD4+8+ cells were decreased in SFD mice compared to controls. These values were normalized after 10 days of rehabilitation. 4. Mesenteric lymph node cells were apparently not affected by folate deficiency. 5. The proportion of Thy-1+ splenocytes was mildly lower in SFD mice than in controls. In R mice, mean spleen weight and spleen cellularity were increased compared to the other groups, but the proportions of Thy-1+, CD4+8- and CD4-8+ cells were markedly lower than control values.     

Assisting effects of lithium on hypoglycemic treatment in patients with diabetes

In this article, we report the assisting effect of lithium on hypoglycemic treatment in patients with diabetes. Thirty-eight diabetic patients, 15 male and 23 female, aged 20–70 yr, 33 noninsulin-dependent diabetesmellitus (NIDDM) patients, and 5 insulin-dependent diabetesmellitus (IDDM) patients, were recruited in this study. Fasting and 1-h postprandial blood glucose (BG) profiles were undertaken from three groups of patients with diabetes before and after short-term of treatment of lithium carbonate. Group I was treated with diet only, Group II with oral hypoglycemic agents (OHA), and Group III with insulin. The fasting blood glucose (FBG) level and 1-h postprandial blood glucose (1-h PBG) level before and after treatment of lithium were: Group I: FBG: 7.67 ± 0.48 vs 7.13 ± 0.82; 1-h PBG 15.13 ± 0.88 vs 10.33 ± 0.96; Group II: FBG: 8.84 ± 0.67 vs 6.04 ± 0.57; 1-h PBG: 12.33 ± 0.72 vs 9.95 ± 0.82; Group III: FBG: 10.87 ± 0.83 vs 6.83 ± 0.79; 1-h PBG: 12.45 ± 0.93 vs 9.17 ± 1.00 mmol/L, respectively. The FBG and PBG of all three groups decreased significantly after lithium treatment, except the FBG in Group I. These data suggest that combined with other therapy, lithium could improve glucose metabolism in most patients with diabetes. Our results suggest that lithium has an assisting hypoglycemic effect on antidiabetic treatment.     

Effect of nutrient ingestion on glucagon-like peptide 1 (7-36 amide) secretion in human type 1 and type 2 diabetes.

Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.     

Chronic dietary fat and cholesterol inhibit the normal postprandial stimulation of plasma cholesterol metabolism

The response of parameters of plasma cholesterol metabolism was studied in baboons adapted either to a low-fat, low-cholesterol diet or a high-fat, high-cholesterol diet. Animals adapted to the low-fat diet responded to a single low-fat or high-fat meal, as do normal humans, by a stimulation of cholesterol transport from blood cells to plasma, a stimulation of esterification of cholesterol, and a stimulation of cholesteryl ester transfer to very low and low density lipoproteins. While fasting rates of esterification and transfer increased as a result of diet-induced hypercholesterolemia, the postprandial response was reversed, so that postprandial metabolism was characterized by a movement of cholesterol from plasma to blood cells, an inhibition of cholesterol esterification, and a net transfer of cholesteryl esters from VLDL and LDL to HDL. These data indicate that the effects of postprandial lipemia on plasma cholesterol metabolism critically depend upon fasting plasma cholesterol levels.     

Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids

Long chain n-3 fatty acids present in fish oils have been shown to reduce fasting plasma triglyceride and very low density lipoprotein levels in normal and hyperlipidemic human subjects. The present studies were designed to examine whether dietary n-3 fatty acids influence chylomicron formation and metabolism in healthy volunteers. In the first study seven subjects were fed either saturated fat, vegetable oil, or fish oil-based diets for 4 weeks each, and test meals containing 50 g of the background fat were administered after the second week of each diet. The postprandial rise in triglyceride levels was significantly lower following the fish oil test meal as compared to the saturated fat or vegetable oil test meals. In the second study, six subjects eating their usual home diets were given two fat tolerance tests. The first contained saturated fat and the second, given 1 week later, contained fish oil. There was no difference in the postprandial triglyceride response between the fish oil and the saturated fat meals. A third study was then conducted with eight volunteers in which saturated fat and fish oil test meals were administered during saturated fat and fish oil background diets in a crossover design. The presence of fish oil in the background diet reduced postprandial lipemia regardless of the type of fat in the test meal. Although there was no effect of the fish oil diet on the lipoprotein lipase and hepatic lipase activity of postheparin plasma measured in vitro, stimulation of in vivo lipolysis was not ruled out. Our results suggest that chronic (but not acute) intake of fish oil may inhibit the synthesis or secretion of chylomicrons from the gut. However, accelerated clearance due to decreased VLDL competition cannot be excluded.     

Prior exercise and postprandial substrate extraction across the human leg

Prior exercise decreases postprandial plasma triacylglycerol (TG) concentrations, possibly through changes to skeletal muscle TG extraction. We measured postprandial substrate extraction across the leg in eight normolipidemic men aged 21-46 yr. On the afternoon preceding one trial, subjects ran for 2 h at 64 +/- 1% of maximal oxygen uptake (exercise); before the control trial, subjects had refrained from exercise. Samples of femoral arterial and venous blood were obtained, and leg blood flow was measured in the fasting state and for 6 h after a meal (1.2 g fat, 1.2 g carbohydrate/kg body mass). Prior exercise increased time averaged postprandial TG clearance across the leg (total TG: control, 0.079 +/- 0.014 ml.100 ml tissue(-1).min(-1) ; exercise, 0.158 +/- 0.023 ml.100 ml tissue(-1).min(-1), P <0.01), particularly in the chylomicron fraction, so that absolute TG uptake was maintained despite lower plasma TG concentrations (control, 1.53 +/- 0.13 mmol/l; exercise, 1.01 +/- 0.16 mmol/l, P < 0.001). Prior exercise increased postprandial leg blood flow and glucose uptake (both P < 0.05). Mechanisms other than increased leg TG uptake must account for the effect of prior exercise on postprandial lipemia.     

Increased plasma apoA-IV level is a marker of abnormal postprandial lipemia: a study in normoponderal and obese subjects.

Plasma apolipoprotein A-IV (apoA-IV) levels are found elevated in hypertriglyceridemic patients. However, the relationship between plasma apoA-IV level and postprandial lipemia is not well known and remains to be elucidated. Thus, our objective was to study the relationship between plasma apoA-IV and postprandial TG after an oral fat load test (OFLT). Plasma apoA-IV was measured at fast and during an OFLT in 16 normotriglyceridemic, normoglucose-tolerant android obese subjects (BMI = 34.6 +/- 2.9 kg/m(2)) and 30 normal weight controls (BMI = 22.2 +/- 2.3 kg/m(2)). In spite of not statistically different fasting plasma TG levels in controls and obese patients, the former group showed an altered TG response after OFLT, featuring increased nonchylomicron TG area under the curve (AUC) compared with controls (516 +/- 138 vs. 426 +/- 119 mmol/l x min, P < 0.05). As compared to controls, obese patients showed increased apoA-IV levels both at fast (138.5 +/- 22.4 vs. 124.0 +/- 22.8 mg/l, P < 0.05) and during the OFLT (apoA-IV AUC: 79,833 +/- 14,281 vs. 68,176 +/- 17,463 mg/l x min, P < 0.05). Among the whole population studied, as among the control and obese subgroups, fasting plasma apoA-IV correlated significantly with AUC of plasma TG (r = 0.60, P < 0.001), AUC of chymomicron TG (r = 0.45, P < 0.01), and AUC of nonchylomicron TG (r = 0.62, P < 0.001). In the multivariate analysis, fasting apoA-IV level constituted an independent and highly significant determinant of AUC of plasma TG, AUC of chymomicron TG, AUC of nonchylomicron TG, and incremental AUC of plasma TG. In conclusion, we show a strong link between fasting apoA-IV and postprandial TG metabolism. Plasma fasting apoA-IV is shown to be a good marker of TG response after an OFLT, providing additional information on post-load TG response in conjunction with other known factors such as fasting TGs.     

Plasma chromium concentrations in normal infants and cystic fibrosis patients

Plasma Cr concentrations have been studied in normal children aged 0–14 yr. Levels ranged from 0.65 to 0.88 μg/1 and did not change with age. Plasma concentrations of CF patients given 0.5–0.75 μg Cr/kg/d in addition to their diet were similar to normal values. There was no correlation between these plasma values and growth retardation.     

Nocturnal free fatty acids are uniquely elevated in the longitudinal development of diet-induced insulin resistance and hyperinsulinemia

Obesity is strongly associated with hyperinsulinemia and insulin resistance, both primary risk factors for type 2 diabetes. It has been thought that increased fasting free fatty acids (FFA) may be responsible for the development of insulin resistance during obesity, causing an increase in plasma glucose levels, which would then signal for compensatory hyperinsulinemia. But when obesity is induced by fat feeding in the dog model, there is development of insulin resistance and a marked increase in fasting insulin despite constant fasting FFA and glucose. We examined the 24-h plasma profiles of FFA, glucose, and other hormones to observe any potential longitudinal postprandial or nocturnal alterations that could lead to both insulin resistance and compensatory hyperinsulinemia induced by a high-fat diet in eight normal dogs. We found that after 6 wk of a high-fat, hypercaloric diet, there was development of significant insulin resistance and hyperinsulinemia as well as accumulation of both subcutaneous and visceral fat without a change in either fasting glucose or postprandial glucose. Moreover, although there was no change in fasting FFA, there was a highly significant increase in the nocturnal levels of FFA that occurred as a result of fat feeding. Thus enhanced nocturnal FFA, but not glucose, may be responsible for development of insulin resistance and fasting hyperinsulinemia in the fat-fed dog model.     

The longitudinal effect of inhibiting fatty acid oxidation in diabetic rats fed a high fat diet.

This study was designed to examine the time-course of response to inhibition of fatty acid (FA) oxidation in rats rendered mildly diabetic with streptozotocin and fed a high fat diet (50% of energy derived from fat). Etomoxir, a specific carnitine palmitoyltransferase (CPT-1) inhibitor, was administered subcutaneously (12.5 mg/kg) to inhibit long chain fatty acid oxidation. Diabetic and non-diabetic control rats were maintained on the high fat diet. Following an overnight fast, glucose, free fatty acid (FFA) and triglyceride (TG) concentrations were determined after three days, one week and four weeks of treatment. The effect of Etomoxir treatment in reducing fasting glucose concentrations was not evident until after one week, while fasting FFA and TG concentrations were already reduced after three days treatment. All of these changes were maintained over the four week period (P less than 0.001), resulting in reduced levels of fasting plasma glucose (17.6 +/- 2.4 vs 22.3 +/- 1.9 mmol/l), fasting plasma TG (0.32 +/- 0.07 vs 0.98 +/- 0.14 mmol/l) and fasting serum FFA (1.52 +/- 0.26 vs 3.51 +/- 0.69 mEq/l). In addition, the improvements in glucose and lipid levels were accompanied by restored rates of growth towards that of non-diabetic control rats. These results suggest that the short term inhibition of FA oxidation improves fasting glucose, FFA and TG concentrations in diabetic rats fed a high fat diet.     

4周有氧运动与饮食控制对肥胖女青少年血清IGF-1和IGF-1结合蛋白-3水平的影响

目的：研究4周中等强度有氧运动结合饮食控制对肥胖女青年、少年血清总胰岛素样生长因子1（IGF-1）、IGF-1结合蛋白3（IGFBP-3）水平和IGF-1活性的影响及其在体脂减少和糖脂代谢改善中的作用。方法：招募9名18~19岁肥胖女青年和30名14~16岁肥胖女少年,进行全封闭的4周中等强度有氧运动结合饮食控制干预。运动项目有游泳、跑步、健身操等,每周运动6 d,每天运动4 h,每运动30 min,休息5 min。运动强度从第1周的低强度（运动后即刻心率约100~120次/分）递增至第2~4周的中强度（运动后即刻心率约120~140次/分）。根据基础代谢率给予每日1 400或1 600 kcal的总能量。另招募正常体重女青年和女少年各9名作为对照组。检测肥胖女青年、少年在4周干预前、后和对照组女青年、少年的体重、身体质量指数（BMI）、腰围、空腹血糖、胰岛素和血脂水平以及血清总IGF-1和IGFBP-3的水平和IGF-1活性。结果：①与对照组相比,肥胖女青年、少年的血清总IGF-1和IGFBP-3水平均降低且肥胖女少年的IGF-1活性降低;②4周中等强度有氧运动结合饮食控制在显著降低肥胖女青年、少年的体脂、腰围和改善糖脂代谢的同时,降低血清IGFBP-3水平、增加IGF-1活性,但血清总IGF-1水平没有显著改变。且相关性分析显示IGF-1活性增加可能与肥胖女青年的腰围减少有关,但血清IGFBP-3水平的降低和IGF-1活性的增加与糖脂代谢的改善没有显著相关性。结论：4周中等强度有氧运动结合饮食控制降低肥胖女青年、少年的血清IGFBP-3水平、增加IGF-1活性;且IGF-1活性的增加可能与运动结合饮食控制降低肥胖女青年的腰围有关。     

Is Metabolic Flexibility Altered in Multiple Sclerosis Patients?

Objectives

Metabolic flexibility is defined as ability to adjust fuel oxidation to fuel availability. Multiple sclerosis (MS) results in reduced muscle strength and exercise intolerance. We tested the hypothesis that altered metabolic flexibility contributes to exercise intolerance in MS patients.

Methods

We studied 16 patients (all on glatiramer) and 16 matched healthy controls. Energy expenditure (EE), and carbohydrate (COX) and lipid oxidation (LOX) rates were determined by calorimetry, before and after an oral glucose load. We made measurements either at rest (canopy device) or during 40 min low-grade (0.5 W/kg) exercise (metabolic chamber). We also obtained plasma, and adipose tissue and skeletal muscle dialysate samples by microdialysis to study tissue-level metabolism under resting conditions.

Results

At rest, fasting and postprandial plasma glucose, insulin, and free fatty acid levels did not differ between patients and controls. Fasting and postprandial COX was higher and LOX lower in patients. In adipose, fasting and postprandial dialysate glucose, lactate, and glycerol levels were higher in patients vs. controls. In muscle, fasting and postprandial dialysate metabolite levels did not differ significantly between the groups. During exercise, EE did not differ between the groups. However, COX increased sharply over 20 min in patients, without reaching a steady state, followed by an immediate decrease within the next 20 min and fell even below basal levels after exercise in patients, compared to controls.

Conclusions

Glucose tolerance is not impaired in MS patients. At rest, there is no indication for metabolic inflexibility or mitochondrial dysfunction in skeletal muscle. The increased adipose tissue lipolytic activity might result from glatiramer treatment. Autonomic dysfunction might cause dysregulation of postprandial thermogenesis at rest and lipid mobilization during exercise.