Plasma beta-thromboglobulin response to insulin-induced hypoglycemia in type I diabetic patients.

The effect of an insulin-induced hypoglycemia was examined in 14 type I diabetic patients. After an overnight blood glucose normalization, each patient received an additional intravenous bolus of 3 U regular insulin at 0900 h (time 0). Blood glucose was continuously recorded up to 180 min. Plasma samples were assayed for beta-thromboglobulin (beta TG, ng/ml), pancreatic glucagon (pg/ml), cortisol (microgram/dl), and growth hormone (ng/ml) 30 min before the insulin stress, at time 0, at blood glucose nadir, and at 180 min. The blood glucose fell from a baseline level of 85.0 +/- 3.2 mg/dl to a nadir value of 39.2 +/- 1.9 mg/dl (P less than 0.001) reached at an average time of 41.4 +/- 4.9 min. Plasma beta TG increased significantly (P less than 0.05) during the insulin stress: 93.4 +/- 23.7 ng/ml at nadir versus 42.5 +/- 5.9 at time 0. Plasma cortisol and growth hormone were significantly increased (P less than 0.02 and P less than 0.01) at nadir compared with time 0 values. Plasma pancreatic glucagon was higher at nadir than at time 0, but the difference was not significant. The present results indicate that in vivo platelet activation can be triggered by hypoglycemic episodes in insulin-treated diabetic patients.

Platelet function in type I diabetes: effects of supplementation with large doses of vitamin E.

Nine Type I diabetic patients were randomized to a double-blind therapeutic trial divided into two study periods of 35 d with either 1 g vitamin E/d or a placebo. Platelet function was estimated at baseline and after treatment from ADP-induced platelet aggregation tests and from generation of oxidative products (TXB2, 12 HETE, and malondialdehyde) after platelet stimulation by 14C arachidonic acid. Platelet function, plasma lipids, and apoproteins were similar before both treatment periods. The vitamin E treatment resulted in 1) diminution of platelet aggregation with ADP 2.5 microM (56 +/- 4 vs 47 +/- 4 cm2, p = 0.05) and 5 microM (70 +/- 5 vs 57 +/- 4 cm2, p less than 0.01); 2) diminution of malondialdehyde release from platelets (6.4 +/- 0.5 vs 5.0 +/- 0.7 nmol/10(9) platelets, p less than 0.02); and 3) diminution in the percentage of 14C TXB2 (38.1 +/- 2.8 vs 33.3 +/- 3.0%, p less than 0.05). No significant changes were observed on placebo. Results indicate that high doses of vitamin E diminish ADP-induced platelet aggregation in Type I diabetic patients and suggest that this effect is partly mediated through a diminution of the cyclooxygenase activity.

Effects of dietary fiber on postprandial glycemic profiles in diabetic patients submitted to continuous programmed insulin infusion.

Conventional (C) or fiber supplemented (F) test breakfast and lunch were given on 3 successive randomized days to six insulin-dependent diabetic patients treated with continuous programmed insulin infusion. Meal distribution was as follows: day 1 (C breakfast and C lunch), day 2 (F breakfast and C lunch), day 3 (F breakfast and F lunch). No rise in blood glucose (BG) was observed after F breakfast (days 2 and 3) while a small rise in BG occurred after the C breakfast (day 1). Significant differences were observed between day 1 and days 2 and 3 for absolute BG values as well as for BG changes (delta BG) from base-line. At lunch slight differences in delta BG were only noted at 45 min (p less than 0.05) between days 2 and 3, while there was no difference between days 1 and 2. Our results indicate that fiber supplementation is useful even in pump-treated insulin-dependent diabetics but that F breakfasts have no influence on the carbohydrate tolerance to the subsequent lunch.

Comparative effects of simvastatin and pravastatin on cholesterol synthesis in patients with primary hypercholesterolemia.

The effects of simvastatin and pravastatin on cholesterol biosynthesis were compared in 26 hypercholesterolemic patients who were randomly allocated to either simvastatin or pravastatin treatment (20 mg once daily) for 6 weeks in a crossover trial. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) lathosterol (latho) concentrations and lathosterol/cholesterol (latho/chol) ratios (the latter two are considered as reliable indices of whole body cholesterol synthesis) were evaluated at the beginning and end of each therapeutic sequence. Reductions in TC and LDL-C were more pronounced (P < 0.001) with simvastatin (TC = -28.0%, LDL-C = -35.6%) than with pravastatin (TC = -19.6%, LDL-C = -25.2%). These results were associated with concomitant decreases in both latho concentrations (-59.0% with simvastatin and -37.0% with pravastatin) and latho/chol ratios (-43.0% with simvastatin and -20.3% with pravastatin). Simvastatin resulted in more marked diminutions of latho concentrations (P < 0.01) and latho/chol ratios (P < 0.05) than pravastatin. These results suggest that the better efficacy of simvastatin on serum cholesterol and LDL cholesterol might result in part from a greater inhibitory action of simvastatin on cholesterol synthesis compared with that of pravastatin.

Evidence for a short-term stimulatory effect of insulin on cholesterol synthesis in newly insulin-treated diabetic patients.

To gain further insight into the effects of insulin on cholesterol synthesis in humans, 19 newly insulin-treated diabetic patients were studied before any insulin treatment (study day 1) and after a few days of optimized glycemic control with a continuous intravenous insulin infusion (study day 2). The patients were divided into two groups according to their clinical characteristics and laboratory disorders. Groups I and II consisted, respectively, of 10 newly diagnosed type I diabetic patients and nine type II diabetic patients with secondary failure to oral antidiabetic drugs. Cholesterol synthesis was estimated from the determination of serum lathosterol, a metabolic precursor in the cholesterol pathway, and from the serum lathosterol to cholesterol ratio. Serum cholesterol (millimolar, mean +/- SEM) remained unchanged in both groups. After insulin therapy (study day 2), serum lathosterol (micromolar) and the serum lathosterol to cholesterol ratio (molar ratio x 10(3)) were significantly increased as compared with baseline (study day 1). Serum lathosterol levels were as follows: 9.9 +/- 2.0 versus 4.1 +/- 0.4 (P < .02) in group I, and 9.9 +/- 0.8 versus 5.7 +/- 0.7 (P < .005) in group II; serum lathosterol to cholesterol ratios were 2.10 +/- 0.39 versus 0.86 +/- 0.11 (P < .005) in group I, and 1.92 +/- 0.12 versus 0.98 +/- 0.10 (P < .001) in group II. The data indicate that in newly insulin-treated diabetic patients, short-term intensive insulin therapy has a stimulatory effect on cholesterol synthesis and even results in cholesterol overproduction.

Failure to achieve tight control of plasma cholesterol and apolipoprotein B with intraperitoneal insulin infusion in type 1 diabetes.

The best route of insulin administration by infusion pumps remains a subject of controversy. For that reason plasma lipids and apolipoproteins were compared in three groups of nine patients who had been treated for several months or years with conventional treatment (group I), continuous subcutaneous insulin infusion (CSII, group II) or continuous intraperitoneal insulin infusion (CPII, group III). Plasma cholesterol and apolipoprotein B remained increased on CPII compared with CSII even when similar satisfactory or even tight diabetic control was achieved with both techniques. This study suggests that cholesterol and perhaps apolipoprotein B biosynthesis by the liver is increased in patients treated with CPII compared to those treated with CSII.

Restored synergistic entero-hormonal response after addition of dietary fibre to patients with impaired glucose tolerance and reactive hypoglycaemia.

Although some dietary fibres (DF) improve glucose tolerance by slowing carbohydrate absorption, other mechanisms are certainly involved. Some of the entero-hormonal responses after DF were investigated in six patients with impaired glucose tolerance and reactive hypoglycaemia. All patients received two different breakfasts, each containing 25 g of starch supplied either as white bread (WB) or a fibre-enriched bread preparation (FB): 4 g hemicellulose and 4 g guar. Metabolic and hormonal responses were evaluated over 5 hours. Compared to WB, the FB had a blunting effect on the resulting blood glucose peak (116 +/- 9 mg/100 ml with FB vs. 148 +/- 15 with WB P less than 0.025) or trough (88 +/- 3 mg/100 ml with FB vs. 79 +/- 5 with WB), and upon the insulin response at 60 min (20 +/- 4 micro U/ml with FB vs. 70 +/- 20 with WB). Gut glucagon immunoreactivity was diminished with FB at 90 min (185 +/- 39 vs. 242 +/- 42 P less than 0.05) and 150 min (180 +/- 39 vs. 242 +/- 40). Pancreatic glucagon was initially similar after FB and WB, but a significant rise was observed with FB at 180 min (116 +/- 17 pg/ml vs. 67 +/- 18 P less than 0.05). The improvement of the blood glucose pattern with DF, especially the suppression of reactive hypoglycaemia, seems to depend partly on reduced and delayed response of the entero-hormonal axis. This in turn results in a better synergistic secretion of insulin and glucagon in the late post-prandial period.

Evidence for 25-hydroxyvitamin D deficiency as a factor contributing to osteopenia in diabetic patients with idiopathic haemochromatosis.

Osteopenia is frequently encountered in the course of idiopathic haemochromatosis. In order to establish the mechanism of this bone disorder, the following parameters were studied in nine diabetic patients wih idiopathic haemochromatosis: (i) the intestinal calcium absorption measured by using a double radiotracer technique; (ii) the bone mineral content (BMC, mg/cm2) determined on the forearm by the Cameron's absorptiometric technique, (iii) the plasma 25 hydroxyvitamin D (25-OH-D ng/ml) by a competitive protein-binding radioassay. The results were compared to those obtained in ten controls and in eight diabetics without haemochromatosis. The patients suffering from haemochromatosis had a significant fall in total fractional absorption of calcium and BMC as compared with controls and diabetics without haemochromatosis. Furthermore plasma 25-OH-D was significantly lower in haemochromatosis patients (5.1 +/- 0.6 ng/ml) than in controls (16.4 +/- 1.3 ng/ml, P less than 0.01) and in diabetics without haemochromatosis (14.2 +/- 1.4 ng/ml, P less than 0.02). These results indicate that haemochromatosis patients exhibit important disturbances in calcium homeostasis, i.e. low concentration of plasma 25-OH-D and reduced intestinal absorption of calcium. The latter abnormalities may well be related to the bone rarefaction observed in these patients.

Calcium absorption following small bowel resection in man. Evidence for an adaptive response.

Seventeen patients who had undergone extensive small bowel resection were studied for calcium absorption (FACa) and plasma vitamin D metabolites. FACa was measured by a double radio-tracer technique and expressed as percentage of total oral dose. FACa was decreased compared with controls (34%, range: 3-46 v 65%, range: 57-73, P less than 0.01). A positive correlation (r = 0.49, P = 0.05) was found between FACa and the remaining length of small bowel (SBL). As wide variations in both SBL and duration after surgery were observed among the seventeen investigated patients, we were led to individualize less heterogeneous subgroups of patients. Better correlations were found when the patients were divided into two subgroups according to whether the time interval between the resection and the investigation was shorter (r = 0.75, n = 11, P less than 0.02) or longer (r = 0.89, n = 6, P = 0.05) than 2 years. In thirteen patients who had a SBL shorter than 100 cm, a positive correlation was observed between FACa and the time interval after surgery (months): r = 0.65, P less than 0.05. Plasma 1,25 (OH)2D was markedly reduced in the whole group (31 pmol l-1, range: 8-108) compared with controls (103 pmol-1, range: 59-134, P less than 0.01). The present study shows that in extensively small bowel resected patients, calcium absorption is reduced, the alteration being dependent both on the length of the remnant small bowel and on the time after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal adaptation in patients with short bowel syndrome. Measurement by calcium absorption.

Functional adaptation of remaining intestine was evaluated in 30 patients with extensive small bowel resection. Calcium and xylose absorption tests were compared. Calcium absorption was measured by a double-radiotracer technique. Serum xylosemia was measured 2 hr after D-xylose ingestion. Patients were divided into two groups according to the time interval between surgery and evaluation: less (group I) or more (group II) than two years. A statistically significant correlation was found between xylosemia and remaining small bowel length (r = 0.71; P less than 0.001) and between calcium absorption and remaining small bowel length (r = 0.75; P less than 0.001) in group I. A significant correlation was also observed between calcium absorption and time after surgery (r = 0.65; P = 0.001) but not for xylose absorption. Calcium absorption value was significantly increased in group II patients compared with group I patients matched for remaining small bowel length (36.2 +/- 12.5% vs 14.5 +/- 9.1%; P less than 0.001) while no difference was observed between the two groups concerning xylose absorption. These data indicate that intestinal calcium absorption continues to increase for more than two years after a major bowel resection in man. The intestine does not seem to recover all its functions at the same time.

Plasma lipid fatty acids and platelet function in insulin-dependent diabetic patients.

Platelet function, estimated from plasma beta-thromboglobulin (beta-TG, ng/ml), is frequently altered in insulin-dependent diabetics (IDDs). As several factors may affect beta-TG, we studied respectively in 15 IDDs, the roles played by: (i) diabetic control evaluated from glycosylated haemoglobin (HbA1); (ii) plasma C-peptide and pancreatic glucagon; (iii) plasma lipids and the relative percentages of fatty acids in total plasma lipids. Plasma beta-TG did not correlate significantly with the first 3 parameters. However, beta-TG was correlated: (i) positively with plasma triglycerides (P less than 0.01), cholesterol (P less than 0.02), phospholipids (P less than 0.05) and total plasma lipids (P less than 0.01) and the percentage of oleic acid (C18 : 1 omega 9) in plasma lipids (P less than 0.01); (ii) negatively with the percentage of linoleic acid (C18 : 2 omega 6) in plasma lipids (P less than 0.02). No correlation was found between beta-TG and the percentages of the other saturated (C16 : 0, C18 : 0), monounsaturated (C16 : 1 omega 7) and polyunsaturated fatty acids (C18 : 3 omega 6, C20 : 3 omega 6 and C20 : 4 omega 6). The present results indicate that beta-TG in IDDs can be markedly improved by all dietary and therapeutic measures which lower plasma lipids and increase the percentage of the linoleic acid in the body.

Plasma lipid fatty acids and platelet function during continuous subcutaneous insulin infusion in type I diabetes.

Eleven insulin-dependent diabetics exhibiting a fair but less than ideal diabetic control (HbA1 = 10.0 +/- 0.6%) were submitted in a random order to two 6 week-study periods of: continuous subcutaneous insulin infusion (CSII) and optimized conventional insulin therapy. Plasma lipids, fatty acids in plasma lipids and platelet function were estimated at baseline and at the end of each study period. Declines in HbA1 were observed at the end of either CSII or conventional period compared with baseline, but the differences were only significant under CSII (P less than 0.02). Plasma lipids and apoproteins remained unchanged at the end of the two study periods compared with baseline. Both CSII and optimized conventional treatment were followed by a significant increase of arachidonate in plasma lipids. A deterioration of the platelet function estimated from ADP or epinephrine-induced platelet aggregation and TxB2 generation by platelets was found under optimized conventional treatment while the platelet function appears to be normal at baseline and under CSII. These data indicate that slight but not sufficient improvements of diabetic control can result in deterioration of the platelet function. It seems that these deleterious effects are mediated through an increased production of arachidonate and in turn of TxB2.