Skeletal muscle insulin resistance in morbid obesity: the role of interleukin-6 and leptin.

BACKGROUND: Although insulin resistance in obesity is established, the link between excess body fat and skeletal muscle insulin resistance is obscure. The aim of this study was to investigate whether cytokines secreted from the subcutaneous adipose tissue are related to the sensitivity of glucose metabolism to insulin in skeletal muscle. METHODS: A meal was given to 14 obese and 10 non-obese women. Plasma samples were taken for 360 min from a forearm vein and from the radial artery for glucose and insulin measurements. Interleukin-6, leptin, TNFα, resistin and adiponectin were measured preprandially from the radial artery and from the superficial epigastric vein. Forearm blood flow was measured with plethysmography. RESULTS: (1) In obese vs non-obese: (a) Glucose uptake by skeletal muscle was decreased (AUC (0-360)369 ± 55 vs. 877 ± 146 µmol/100 g tissue, p=0.001) (b) arterial interleukin-6 (2.5 ± 0.5 vs. 1 ± 0.1 pg/ml, p=0.013) and subcutaneous venous interleukin-6 (5 ± 0.5 vs. 3.4 ± 0.5 pg/ml, p=0.027) were increased (c) arterial leptin (63 ± 7 vs. 5 ± 0.6 ng/ml, p<0.0001) and subcutaneous venous leptin 80 ± 8 vs. 6.5 ± 0.7 ng/ml, p<0.0001) were increased. (2) Arterial interleukin-6 (p=0.002) and subcutaneous venous interleukin-6 (p=0.014) were negatively associated with forearm glucose uptake in obese. (3) No association was found between leptin and forearm glucose uptake, after correcting with fat mass. CONCLUSIONS: In morbid obesity: (1) Subcutaneous adipose tissue releases interleukin-6 which could then mediate insulin resistance in skeletal muscle. (2) Although there is increased secretion of leptin by the subcutaneous adipose tissue, leptin levels are not correlated to the sensitivity of glucose metabolism to insulin in muscle.

Rates of lipid fluxes in adipose tissue in vivo after a mixed meal in morbid obesity.

OBJECTIVE: Although insulin resistance in obesity is established, information on insulin action on lipid fluxes, in morbid obesity, is limited. This study was undertaken in morbidly obese women to investigate insulin action on triacylglycerol fluxes and lipolysis across adipose tissue. SUBJECTS AND DESIGN: A meal was given to 26 obese (age 35+/-1 years, body mass index 46+/-1 kg m(-2)) and 11 non-obese women (age 38+/-2 years, body mass index 24+/-1 kg m(-2)). Plasma samples for glucose, insulin, triglycerides and non-esterified fatty acids (NEFAs) were taken for 360 min from a vein draining the abdominal subcutaneous adipose tissue and from the radial artery. Adipose tissue blood flow was measured with (133)Xe. RESULTS: In obese vs non-obese: (1) Arterial glucose was similar, but insulin was increased (P=0.0001). (2) Adipose tissue blood flow was decreased (P=0.0001). (3) Arterial triglycerides (P=0.0001) and NEFAs (P=0.01) were increased. (4) Lipoprotein lipase was decreased (P=0.0009), although the arteriovenous triglyceride differences were similar. (5) Veno-arterial NEFA differences across the adipose tissue were similar. (6) NEFA fluxes and hormone-sensitive lipase-derived glycerol output from 100 g adipose tissue were not different. (7) Total adipose tissue NEFA release was increased (P=0.02). CONCLUSIONS: In morbid obesity: (a) hypertriglycerinemia could be attributed to a defect in the postprandial dynamic adjustment of triglyceride clearance across the adipose tissue, partly caused by blunted BF; and (b) postprandially, there is an impairment of adipose tissue to buffer NEFA excess, despite hyperinsulinemia.

Psychological condition and quality of life in patients with morbid obesity before and after surgical weight loss.

BACKGROUND: Bariatric surgery results in significant weight loss, improvement or cure of accompanying illnesses, and may lead to important changes in psychological conditions. The aim of this paper is to study the changes in the psychological and emotional lives of patients as well as quality of life during the first 2 years after vertical banded gastroplasty (VBG). METHODS: The study population comprised 59 patients, 45 women (76.3%) and 14 men, between 18 and 64 years old. Patients were asked to complete an SCL-90R questionnaire before VBG. 2 years after VBG, patients were again asked to complete an SCL-90R as well as a BAROS questionnaire. Comparisons were made between loss of weight, alteration in the psychological condition and quality of life postoperatively, within the parameters of sex, age, marital status, level of education, duration of obesity and family history of obesity. RESULTS: Women had a greater degree of depression from obesity than their male counterparts before the procedure (P=0.001), while their postoperative emotional improvement was more marked (P=0.008). The General Mental Health Index was higher in female than male patients (P=0.008). At 2 years after VBG, BMI was significantly reduced (P<0.001). Oversensitivity in personal relationships and anxiety affected patients more both pre- and postoperatively. The averages of all the indexes of the subgroups of the SCL-90R, which relates to psychological condition of patients, showed a statistically significant reduction at 2 years following VBG, indicative of the improvement of the patients' psychosomatic condition. The more weight patients lost, the more their quality of life improved, as evaluated by the BAROS (P<0.001). CONCLUSIONS: The bariatric surgery most satisfactorily improved the patients' psychosomatic condition, as well as their quality of life, during the first 2 years after VBG.

The effect of an eucaloric high carbohydrate diet on circulating levels of glucose, fructose and non-esterified fatty acids in patients with cirrhosis.

Twelve cirrhotic patients and six controls were fed an eucaloric high carbohydrate (CHO) diet for 3 days. Fasting serum triglyceride (TG), non-esterified fatty acids (NEFA), glucose, insulin and glycerol were estimated daily. On the 3rd day of the study we measured NEFA, glucose, insulin, and fructose every 45 min from 07:45 h until 19:45 h, and then every 4 h until 07:45 h the next day. The patients were divided into two groups of six on the basis of plasma lecithin-cholesterol acyltransferase (LCAT) activity: group A cirrhotics (with good liver function--LCAT activity: 40.6-65.7 nmol.ml-1.h-1; mean 48.5), and group B (poor liver function--LCAT: 23.7-32.3; mean 27.4). On the high CHO diet there was an increase in the fasting serum TG with a peak after 2 or 3 days. The increase in serum TG in controls was greater (p less than 0.01) than in either group of cirrhotics. In the controls and in group A most of the extra TG was carried in VLDL; in group B only 39% of the TG increment was found in VLDL. Fasting NEFA fell with 3 days of CHO feeding in the control group (p less than 0.01); they were unchanged in group A, and rose in group B to a significantly higher level than in controls (p less than 0.01). During day 3 when a high CHO diet was fed plasma NEFA levels fell in cirrhotics, and for most of the day the mean NEFA concentration in group B patients was significantly (p less than 0.05) lower than in normals. On day 3 glucose and fructose levels rose after each meal--much more in cirrhotics than in controls (and more in group B than in group A), and for most of the day they were significantly higher in group B patients as compared to the controls (glucose p less than 0.01, fructose p less than 0.001). Our results supported the hypothesis that plasma NEFA would be lower following high CHO meals in cirrhotics than in controls. This suggests that a high NEFA utilisation, which occurs in fasting cirrhotics, is not present throughout the day. Following a CHO meal, we suggest that tissues derive energy directly from the dietary sugars which are present in high concentration during the period of absorption and that this reduces the post prandial requirement for NEFA.

Effects of alpha-glucosidase inhibition on meal glucose tolerance and timing of insulin administration in patients with type I diabetes mellitus.

OBJECTIVE: Miglitol, an alpha-glucosidase inhibitor, delays absorption of carbohydrates. This study was undertaken to determine the potential of this agent as an adjunct to insulin in the treatment of diabetes. RESEARCH DESIGN AND METHODS: Twelve nonobese patients with insulin-dependent (type I) diabetes mellitus were randomly selected from the outpatient diabetes clinic. The patients were made euglycemic with the Biostator, and postprandial hyperglycemia was determined under the following conditions: protocol 1, subcutaneous injection of insulin (13 +/- 1 U) given 60 min before the meal, with insulin dosages determined by the Biostator; protocols 2 and 3 same as protocol 1 but with insulin given at the time of meal ingestion; protocols 4 and 5 same as protocol 1 but with insulin given 30 min before the meal. Miglitol (100 mg) was administered in protocols 2 and 4 and placebo in protocols 3 and 5. RESULTS: When insulin was given 30 min before the meal with miglitol (protocol 4) or placebo (protocol 5), plasma glucose increased from 4.94 +/- 0.16 to 5.94 +/- 0.55 mM and from 5.11 +/- 0.22 to 8.22 +/- 0.72 mM, respectively (P less than 0.01). When insulin was given at the time of the meal with miglitol (protocol 2) or placebo (protocol 3), plasma glucose increased from 5.44 +/- 0.27 to 7.77 +/- 0.5 mM and from 5.72 +/- 0.22 to 10.83 +/- 0.77 mM, respectively (P less than 0.01). When insulin was given 60 min before the meal (protocol 1), plasma glucose initially decreased from 5.61 +/- 0.38 to 4.33 +/- 0.33 mM and then increased to 6.94 +/- 0.66 mM after the meal.(ABSTRACT TRUNCATED AT 250 WORDS)