Treatment of morbid obesity with intragastric balloon in association with diet.

BACKGROUND: The BioEnterics Intragastric Balloon (BIB, BioEnterics, Santa Barbara, CA) in association with restricted diet has been used for the treatment of obesity and morbid obesity. METHODS: Since March 1998, 322 BIB were placed in 281 obese and morbidly obese patients; 73 patients were male and 208 female; mean age was 41.6 years (21-70); mean weight was 117.4 kg (67-229); mean BMI was 41.8 kg/m2 (29-81); % excess weight was 62% (10-216). The balloon was inserted and removed endoscopically under general anesthesia. Patients were given a balanced diet of 1000 kcal/day. Also, for 18 months we compared 42 obese patients treated only with 1000 kcal/day diet (group A) with 31 obese patients subjected to BIB for 4 months + 1000 kcal/day diet (group B). RESULTS: After 4 months of balloon treatment, the mean weight loss was 13.9 kg and the mean reduction in BMI was 4.8. Weight loss was greater in male patients. Weight loss was accompanied by an improvement of the diseases associated with obesity, in particular diabetes. In the diet vs BIB + diet study, BIB with diet produced a greater weight loss in a shorter time than diet alone. CONCLUSION: The best indications for BIB were: morbidly obese opatients (BMI > 40) and super-obese patients (BMI > 50) in preparation for bariatric operations; obese patients with BMI 35-40 with co-morbilities in preparation for bariatric surgery; obese patients with BMI 30-35 with a chronic disease otherwise unresolved; patients with BMI < 30 only in a multidisciplinary approach.

Thirty months experience with laparoscopic adjustable gastric banding.

INTRODUCTION: Since June 1996 we performed laparoscopic adjustable silicone gastric banding (LASGB), because of low invasivity, absence of malabsorption, reversibility, and postoperative regulation. MATERIALS AND METHODS: Criteria included body mass index (BMI) >40 or >35 with serious obesity-related conditions. 154 patients underwent LASGB. BMI ranged from 35 to 65.7 (mean 43.7+/-6.2). RESULTS: The laparoscopic procedure was successfully completed in 150 patients (97.4%). One patient was converted to the laparotomic procedure because of hepatomegaly; 4 patients had to be converted for gastric laceration during the laparoscopic approach. In one of these patients, the band was removed 7 days later for sepsis, followed by an uneventful postoperative course. The mean length of postoperative hospitalization was 2.3+/-0.9 days. Per cent of excess weight loss was 42.5+/-22.4 after 1 year. CONCLUSIONS: LASGB was feasible and effective.

Efficacy and safety of acarbose in the treatment of Type 1 diabetes mellitus: a placebo-controlled, double-blind, multicentre study.

AIMS: The aim of the study was to evaluate the efficacy and safety of acarbose in patients with Type 1 diabetes mellitus (DM). METHODS: A multicentre double-blind, randomized, placebo-controlled study was performed. After a 6-week run-in, 121 patients were randomized to acarbose or placebo and to high- or low-fibre diet for 24 weeks. Acarbose dose was 50 mg t.d.s. for the first 2 weeks and 100 mg t.d.s. for the subsequent weeks. RESULTS: At the end of 24 weeks of treatment the intention to treat analysis showed that acarbose compared with placebo decreased 2 h postprandial plasma glucose levels (12.23 +/- 0.83 vs. 14.93 +/- 0.87 mmol/l; F = 6.1, P < 0.02) (least square means +/- SEM). No significant effect of acarbose was recorded on HbA1c or on the number of hypoglycaemic episodes. The effect of acarbose on blood glucose control was not influenced by the amount of carbohydrate and/or fibre intake. The incidence of adverse events were 75% and 39% in acarbose and placebo groups, respectively; they were mild and confined to the gastrointestinal tract. CONCLUSIONS: The use of acarbose in combination with insulin reduces postprandial plasma glucose levels in Type 1 diabetic patients who are not satisfactorily controlled with insulin alone but without significant effect on HbA1c.

Hypocaloric high-protein diet improves glucose oxidation and spares lean body mass: comparison to hypocaloric high-carbohydrate diet.

The aim of the study was to investigate the effects of two hypocaloric (800-kcal) diets on body weight reduction and composition, insulin sensitivity, and proteolysis in 25 normal glucose-tolerant obese women. The two diets had the following composition: 45% protein, 35% carbohydrate (CHO), and 20% fat (HP diet, 10 subjects), and 60% CHO, 20% protein, and 20% fat (HC diet, 15 subjects); both lasted 21 days. A euglycemic hyperinsulinemic (25 mU/kg/h) clamp lasting 150 minutes combined with indirect calorimetry was performed before and after the diet. Both diets induced a similar decrease in body weight and fat mass (FM), whereas fat-free mass (FFM) decreased only after the HC diet. 3-Methylhistidine (3-CH3-HIS) excretion was reduced by 48% after the HP diet and remained unchanged after the HC diet (P < .05). A significant correlation was found between the changes in FFM and in 3-CH3-HIS excretion after the diet (rs = .50, P < .02). Blood glucose remained unchanged, while insulin decreased in both diets. Free fatty acids (FFA) significantly increased only after the HC diet (P < .05). During the clamp period, glucose disposal and glucose oxidation significantly increased after the HP diet and significantly decreased after the HC diet. Opposite results were found when measuring lipid oxidation. In conclusion, our experience suggests that (1) a hypocaloric diet providing a high percentage of natural protein can improve insulin sensitivity; and (2) conversely, a hypocaloric high-polysaccharide-CHO diet decreases insulin sensitivity and is unable to spare muscle tissue.

Peritoneal and subcutaneous absorption of insulin in type I diabetic subjects.

We and others have shown that in type I diabetes, ip insulin delivery results in lower free insulin levels than sc delivery. The aim of this study was to compare the rate of appearance of insulin in the peripheral circulation during ip and sc insulin administration in type I diabetes, in steady state and nonsteady state. To do this, we determined free insulin levels during ip or sc infusion as well as the impulse response of the insulin system after iv injection of a 6-nmol bolus of insulin. Twelve hours after a constant basal insulin infusion (5.5 +/- 1.4 nmol/h) was started, five C-peptide-negative type I diabetic subjects showed a lower systemic rate of appearance of insulin (expressed as a percentage of the administered dose) with ip than sc administration (27 +/- 6% vs. 40 +/- 10%; P < 0.001). In nonsteady state, when the infusion rate was increased from basal to 15 nmol/h (0-150 min) and subsequently to 42 nmol/h (150-300 min), the percent increase in insulin's systemic rate of appearance was higher with ip than sc infusion (P < 0.05 from 60-150 min; P < 0.01 from 150-300 min), indicating faster absorption. Thus, we conclude that insulin is more rapidly absorbed from the peritoneal cavity than from sc tissue. However, with ip administration, a sizable amount of insulin, once absorbed, is extracted before reaching the peripheral circulation, most likely by the liver. This is indirect evidence that ip insulin delivery results in a portal-peripheral insulin gradient in humans.

Bioelectrical impedance in the evaluation of the nutritional status of hemodialyzed diabetic patients.

Bioelectrical impedance is a technique allowing a quick, repeatable and reliable assessment of body composition. This method was applied to detect total body water (TBW), fat (FAT) and fat-free mass (FFM) in 80 normal subjects, 65 diabetic (45 insulin-dependent [IDD], 20 non insulin-dependent [NIDD]) and 34 uremic diabetic patients (20 IDD, 14 NIDD) submitted to hemodialysis three times a week. Uremic patients were tested at the end of the dialytic session. Multivariated analysis adjusted for age, sex and disease showed the following results: body mass index (BMI) increased with age (p < 0.005) and in the presence of NIDD (p < .001); TBW was lower in nephropathic patients (p < 0.05) and in the female sex (p < 0.0001); FFM decreased with age (p < 0.005), female sex (p < 0.0001) and in nonuremic NIDD (p < 0.001). Correspondingly FAT increased with age (p < 0.005), female sex (p < 0.0001) and in nonuremic NIDD (p < 0.001). Sixteen uremic subjects, randomly selected from both IDD and NIDD groups, tested at the beginning and at the end of the same hemodialytic session, showed a significant decrease of TBW which corresponded to the correction of their overhydratation. In our patients uremia does not seem to influence the nutritional status and the bioelectrical analysis could be applied to determine the real dry weight in hemodialyzed diabetic patients.

Effect of soya and cellulose fibers on postprandial glycemic response in type II diabetic patients.

OBJECTIVE: We studied the effect on serum glucose and insulin of a preprandial ingestion of 7 g of soya fibers or of an equal amount of purified cellulose on eight non-insulin-dependent (type II) diabetic patients. RESEARCH DESIGN AND METHODS: Four tests were conducted in each patient in random order. In the first study, soya or cellulose was ingested before a standard breakfast, and postprandial glucose and insulin curves were determined. In the second study, intestinal absorption was investigated by means of a standard D-xylose absorption excretion test after the ingestion of soya or cellulose. RESULTS: Insulin profiles did not differ between the two treatments. The glycemic profiles after soya ingestion were lower than those after cellulose ingestion. The area under the glucose curve and glucose peaks were significantly higher after cellulose ingestion (area under the curve 20.2 +/- 3.88 vs. 15.57 +/- 4.42 mM x min, P = .05; glucose peaks 4.97 +/- 0.76 vs. 3.77 +/- 0.77 mM, P less than 0.02). The xylose tests were in the normal range, indicating that there was no interference with exose absorption, and no statistical difference was found between cellulose and soya treatment. CONCLUSIONS: It is concluded that soya fiber compared with purified cellulose has a favorable effect on the rise of postprandial glycemia in type II diabetic patients; moreover, the use of soya fibers did not carry any untoward side effect.

[Evaluation of an impedance measurement method for determining body composition in diabetic subjects and normal controls]. / Validazione di una metodica di rilevazione impedenziometrica per la valutazione della composizione corporea in soggetti diabetici e controlli normali.

The reproducibility of impedance measurements made using the Human-IM system (Dietosystem, Milan-Italy) was assessed in a group of normal and diabetic subjects on the basis of three tests made under the same experimental conditions on three consecutive days. A total of 22 normal subjects, 29 insulin-dependent (IDD) and 6 noninsulin dependent (NIDD) diabetic patients were included in the study. The coefficient of variation between the three successive tests ranged between 0 and 2.7% (normals 1.1 +/- 0.7%, IDD 1.6 +/- 0.7%, NIDD 1.1 +/- 0.4%), thus confirming the good reproducibility of the method in all groups. There was no significant difference between impedance measurement tests in the two group of diabetic patients with regard to TBW, FAT and FFM. NIDD patients differed from normal subjects due to higher FAT levels, whereas there was no significant difference between IDD patients and normal subjects.

Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes.

In order to compare the effects of intraperitoneal (IP) versus subcutaneous (SC) insulin delivery on plasma lipoproteins, lipoprotein cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) metabolism were compared in five type I diabetic patients while they were receiving continuous IP insulin (CIPII) or continuous subcutaneous insulin infusion (CSII). Each therapy regimen was of at least 1 month duration, and patients were treated in random order. Mean daily plasma insulin was lower on CIPII compared with CSII. CIPII was associated with lower VLDL triglycerides and VLDL apolipoprotein (apo) B, and higher high-density lipoprotein (HDL) and HDL3 cholesterol. The decreased VLDL on CIPII appeared to be the result of both decreased production and increased clearance of VLDL apo B. The results suggest that the more physiologic route of insulin therapy (CIPII) is associated with lipoprotein profiles of lower atherogenic potential.

Glycerol-insulin raises circulating insulin antibodies in type I diabetic patients treated with permanently implanted devices.

The instability of insulin in the reservoirs of implantable insulin delivery devices has been a major obstacle in implementing this form of therapy. To overcome the problem of precipitation, a glycerol-insulin preparation has been used in large-scale long-term clinical trials. The aim of this study was to evaluate the stability of the glycerol-insulin solution and its effects on circulating insulin antibodies in eight type I diabetic patients who were implanted with an Infusaid pump (Infusaid Corporation, Norwood, MA) and followed for 1 year or more. Total insulin requirement did not change throughout the observation period. Plasma free insulin was higher during treatment with glycerol-insulin than with the standard insulin treatment (P less than .02). Insulin antibodies increased in all patients (P less than .05). High-performance liquid HPLC analysis of insulin samples from the pump reservoirs showed the generation of insulin modification products at a daily rate of 1.84%, reaching 40% to 50% of the total reservoir content 3 weeks after refilling; among these products, high molecular weight species accounted for about 15%. It is concluded that glycerol-insulin is not an adequate insulin preparation for use in implanted devices. Insulin deteriorated in the pump reservoirs, and insulin antibody concentration increased in the treated patients. It is believed that this antibody production is favored by circulating insulin fragments and polymers of insulin generated inside the pump reservoirs.

Free-insulin profiles after intraperitoneal, intramuscular, and subcutaneous insulin administration.

The aim of our study was to compare the time course of plasma free-insulin appearance after injection of equal amounts of insulin into the peritoneal cavity above and below the transverse mesocolon, intramuscularly, and subcutaneously. Seven nondiabetic subjects undergoing cholecystectomy received in random sequence 0.2 IU/kg of insulin into the peritoneal cavity above or below the transverse mesocolon. Concentrations of plasma free insulin were compared with those obtained from seven other nondiabetic subjects after repeated injections of equal amounts of insulin intramuscularly and subcutaneously. Intraperitoneal insulin above the transverse mesocolon yielded a faster rise of free insulin, peaking at 15 min, whereas intraperitoneal insulin below the transverse mesocolon produced a somewhat slower rise, peaking at 30 min. The area under the curves between 0 and 15 min was greater after the injection above than below the transverse mesocolon (P less than .05). Intramuscular and subcutaneous insulin injections resulted in a slower rise of plasma free insulin, peaking at 60 and 90 min, respectively. We conclude that the pattern of insulin appearance in the plasma resembles more closely physiologic events after intraperitoneal than after subcutaneous or intramuscular insulin administration.

Reproducibility of cardiovascular autonomic tests in diabetics with and without autonomic dysfunction and in normal controls.

The present study evaluates the reproducibility of five cardiovascular reflex tests, deep breathing (DB), Valsalva maneuver (VM), sustained hand-grip (SHG), postural hypotension (PH) and lying to standing (LS) in normal subjects and in insulin dependent (type I) diabetic patients. The study was carried out in 10 normal subjects, in 10 diabetics with autonomic neuropathy and in 10 diabetics without autonomic neuropathy. The five cardiovascular reflex tests were performed five times on five consecutive days by the same investigator and in identical basal conditions. The intraindividual variability of DB, LS and VM was significantly reduced in diabetics with autonomic neuropathy compared with normal controls, but there was no difference between diabetics without neuropathy and normal controls. The intraindividual variability of PH was significantly increased in diabetics with autonomic neuropathy compared with diabetics without autonomic neuropathy and with normal controls. There was no difference among the three groups in the reproducibility of SHG. In normal subjects the intraindividual variability only exceptionally produced a shift from normal to abnormal values or vice versa; in diabetics with autonomic neuropathy this shift was more frequent.

Chronic continuous intraperitoneal insulin infusion (CIPII) in type I diabetic patients non-satisfactorily responsive to continuous subcutaneous insulin infusion (CSII).

Six unstable C-peptide negative type I diabetic patients who had been previously treated with continuous subcutaneous insulin infusion (CSII) for at least one year without achieving satisfactory metabolic control, were admitted to this study and switched to continuous intraperitoneal insulin infusion (CIPII). The results obtained with the two treatments have been compared from the metabolic and clinical points of view. CIPII produced a decrease in HbA1c (p less than 0.05), in MAGE value (p less than 0.005), in the percentage of blood glucose determinations above 14 mmol/l (p less than 0.05) and below 3.9 mmol/l (p less than 0.05); an increase in serum cholesterol, and a decrease in HDL-cholesterol (p less than 0.05) due to a reduction of the HDL2 fraction (p less than 0.01). A mean body weight reduction of 3 kg was observed during CIPII (p less than 0.01), not related to dietary changes or to a reduction of the daily insulin dose. Twenty-four hour metabolic profiles during CIPII showed lower mean plasma glucose (p less than 0.001), serum free insulin (p less than 0.001), blood beta-OH-butyrate (p less than 0.001), and higher serum glycerol (p less than 0.001) as compared to CSII. It is concluded that CIPII may be of clinical value in the out-patient management of unstable type I diabetic patients, and that metabolic modifications induced by CIPII are not limited to changes in glucose utilization and production, but include changes in triglyceride, cholesterol and lipid metabolism which may have clinical relevance.

Beta-thromboglobulin and fibrinopeptide A in diabetes mellitus as markers of vascular damage.

Beta-thromboglobulin (BTG) and fibrinopeptide A (FpA) were studied in 68 non-insulin dependent diabetic patients (NIDD) aged 32-81 with a mean duration of diabetes of 9 +/- 0.8 SEM years and 44 healthy controls, comparable for age and sex. Diabetic patients were subdivided into subsets according to the presence of microvascular disease, macrovascular disease or the absence of these lesions. Patients with microangiopathy (micro- and/or macrovascular disease) had higher HbA1 (a-c) (p less than 0.01), higher blood pressure (p less than 0.05) than both healthy controls and uncomplicated diabetics. Plasma BTG was higher in diabetic patients than in healthy controls (p less than 0.02), and was higher in complicated than in non-complicated diabetic subjects. Fpa was higher in complicated than in non-complicated diabetes (p less than 0.05). No differences were observed between the two subsets of complicated patients. In conclusion, we have shown that increased plasma- and platelet-BTG levels are present in non-insulin dependent diabetic subjects, with normal renal function and that plasma BTG is higher in patients with than in those without vascular disease. Fibrinopeptide A, a sensitive marker of in vivo fibrin formation, was significantly increased in NIDD with vascular complications.

Effects of metoprolol and propranolol on glucose tolerance and insulin secretion in diabetes mellitus.

Twenty-two hypertensive diabetic patients were admitted to a double-blind, within-patient study, and treated with propranolol 80 mg and metoprolol 100 mg twice daily for 4 weeks according to a cross-over design. Dosages of the two drugs such as to induce comparable cardiovascular effects, did not induce relevant changes of fasting blood glucose levels in patients receiving the oral hypoglycaemic agent glibenclamide (group 1), insulin (group 2) or diet alone (group 3). Glucose tolerance, assessed with a 75 g oral load, was however decreased by propranolol, and not by metoprolol in the glibenclamide-treated group. Glucose-induced insulin secretion was reduced by propranolol and not by metoprolol both in the group treated by diet alone and in the glibenclamide-treated group. It is concluded that cardioselective metoprolol seems to be more suitable than the non-selective propranolol in the treatment of arterial hypertension in diabetic subjects, particularly when sulfonylureas are being used as hypoglycaemic agents.

Chlorpropamide-alcohol flushing in non insulin-dependent diabetes: prevalence of small and large vessel disease and or risk factors for angiopathy.

One hundred and eight non insulin-dependent diabetics were tested for alcohol flushing after chlorpropamide administration (CPAF test). The overall prevalence of patients who flushed at the first challenge was 32%. However, nearly half of them still flushed after alcohol administration, when placebo was given instead of chlorpropamide, so that the prevalence of 'true' flushers was only 17%. Even though the distribution of retinal lesions was similar in 'true' flushers and in non flushers, severe loss of visual acuity was confined to the non flushers and aspecific flushers. The frequency of pathological ECG findings and of peripheral pulse reduction or abolition was significantly higher in the non flushers and aspecific flushers. Blood pressure, serum lipids and hemostatic parameters were similar in the two groups, and therefore do not explain the differences in prevalence of lesions. This study confirms the previous findings of a lower prevalence of large vessel lesions in flushers; however, the prevalence of 'true' CPAF phenomenon in our out-patient population appears to be much lower than previously reported.