Relationship of insulin resistance to protein-energy malnutrition in patients with alcoholic liver cirrhosis: effect of short-term nutritional support.

Protein-energy malnutrition (PEM) and insulin resistance (IR) are common features of alcoholic liver cirrhosis (ALC). In order to determine a relationship between them, nutritional status and glucose homeostasis were studied in 26 patients with ALC. Nutritional status was assessed through dietary, anthropometric, and biological parameters. An IR index (M/I) was obtained from the euglycemic insulin clamp technique. M/I was significantly correlated with accurate markers of PEM (albumin, transthyretin, and retinol-binding protein) but not with other markers of liver dysfunction. Nine patients were studied before and after nutritional support: M/I was significantly improved as were serum markers of PEM. Other markers of liver dysfunction were also significantly improved. These findings suggest that PEM could be responsible, in part, for IR in patients with ALC who are frequently malnourished. Moreover, nutritional support improved insulin sensitivity in these patients.

Evaluation of fibrosis in the disse space in noncirrhotic alcoholic liver disease.

In 40 alcoholic noncirrhotic patients, we performed a liver biopsy and determined the wedged hepatic vein pressure, the free hepatic vein pressure, and the intrahepatic vein pressure. In 27 of them, the serum concentration of the N-terminal peptide of type III procollagen (PIIIP) and of the laminin P1 fragment was measured. All the liver biopsies were studied by light and transmission electronic microscopy. A score of collagenization of the Disse space (six classes) was performed using transmission electronic microscopy. 37 of the 40 patients had pathological collagenization of the Disse space which was correlated with intrahepatic pressure (p less than 0.01). The lamin P1 blood level in patients (1.38 +/- 0.51 U/ml) was increased, compared to the values of our controls (0.99 +/- 0.10 U/ml, p less than 0.01) and was correlated with the wedge hepatic vein pressure (p less than 0.01). The PIIIP blood level was not significantly increased except when Mallory bodies were found in hepatocytes (p less than 0.05). The laminin P1 blood level seemed to be a good biological marker for detection of liver fibrosis in long-term alcoholic intake.

Refeeding after various times of ingestion of a low protein diet: effects on food intake and body weight in rats.

Rats born of protein-deprived mothers were fed on a low protein (LP) diet (5% casein) from weaning. In each time sequence (0, 1, 3, 5, 8 and 16 weeks after weaning), 12 of them were refed on an isocaloric well-balanced diet (18% casein) for 2 weeks. Food intake, body and adipose tissue weights and protein efficiency ratio (PER) were measured in the refed rats as well as in 12 LP rats. At weaning and after one week, refed (RF) rats immediately increased their food intake. This increase was delayed at weeks 3, 5 and 8 occurred during the second week of refeeding only. At week 16, there was a significant decrease during the first week when compared with LP rats. Body weight increased regularly during each refeeding period without any significant augmentation of the proportion of adipose tissue. During all the experiment (except at week 16), PER in the RF group remained high (about 3 g body weight/g protein) during the first week of refeeding, and fell to 2.0-2.5 g/g during the second week. It was particularly significantly greater than that of the LP rats between week 3 and 5 where an important decrease was observed in this group (1.99 +/- 0.36 vs. 3.23 +/- 0.58 g body weight/g protein during the 1-3 weeks period). It appeared therefore that protein restriction during gestation and lactation in dams had no effect on the mechanisms controlling food intake of their offspring at weaning.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the duration of malnutrition and of nutritional rehabilitation on blood glucose homeostasis and pancreatic hormones in rats.

1. To study the efficiency of rehabilitation after different periods of protein-energy malnutrition, we used as a model preweaning malnourished rats. After weaning, male Wistar rats were fed on a protein-deficient diet (50 g casein/kg) ad lib. for the whole study (DR group) or rehabilitated with normal diet (180 g casein/kg; RR group) from weaning, week 0, or weeks 1, 3, 5, 8 and 16 thereafter. 2. Twelve animals from the DR group were killed at the beginning of each rehabilitation period. The twelve rehabilitated rats were killed after 2 weeks. Body-weight and epididymal adipose tissue weight, blood glucose, plasma immunoreactive insulin (IRI) and immunoreactive glucagon (IRG), and pancreatic contents of IRI and IRG were determined. 3. Food intake of RR rats rose significantly except during the last period where body-weight increased less than that during the previous period. Fat-pad weights increased in the same manner in DR and RR groups. 4. Blood glucose fell and plasma IRG rose significantly without any change in plasma IRI after each rehabilitation period, except during the last period where blood glucose concentrations became stable. Pancreatic IRG and IRI showed the same type of response to those of the plasma. 5. All short-term rehabilitation periods were similarly efficient at producing catch-up growth. High insulin sensitivity of target cells was responsible for good recovery except after long-term malnutrition.

[Endoscopic sclerotherapy versus propranolol after hemorrhage caused by rupture of esophageal varices in patients with cirrhosis. Results of a 4-year randomized study]. / Sclérothérapie endoscopique contre propranolol après hémorragie par rupture de varices oesophagiennes chez le cirrhotique. Résultats à 4 ans d'une étude randomisée.

Between December 1982 and April 1987, we conducted a prospective randomized trial comparing the efficiency of endoscopic sclerotherapy with oral propranolol after variceal hemorrhage in cirrhosis. We present our results after a median follow-up of 3 years (range = 57-231 weeks). The sclerotherapy group (S) consisted of 28 patients and the propranolol group (P), 27 patients. The two groups were similar for age, sex, etiology and severity of liver disease, and severity of hemorrhage; the only difference concerned previous hemorrhages which were significantly more numerous in the S group. Sclerotherapy was performed with polidocanol 1 p. 100. A slow-release preparation of propranolol was used; the average daily dose was 160 mg. Eighteen patients in the S group had at least one hemorrhagic recurrence as opposed to 12 in the P group. This difference was not significant nor was the difference between actuarial curves of no-rebleeding (p = 0.30). No difference was noted concerning total deaths (15 in S versus 12 in P). Cumulative survival curves showed a non-significative difference (p = 0.99) percentages of survival in S and P groups were 75.0 p. 100 and 73.6 p. 100 at 1 year, 67.9 p. 100 and 64.6 p. 100 at 2 years, and 51.1 p. 100 and 52.7 p. 100 at 3 years respectively. Stratification according to Child's group, variceal size and history of variceal hemorrhage did not modify these results. However, male patients had less hemorrhagic recurrences with propranolol than after sclerotherapy. Length of hospitalization was not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein-energy malnutrition in pregnant rats improves the adaptation of the endocrine pancreas in malnourished offspring and induces insulin resistance after rehabilitation.

1. In developing countries, malnutrition begins during pregnancy and lactation. Glucose intolerance is a problem of importance during protein-energy malnutrition (PEM). We therefore studied glucose homeostasis in rats weaned from undernourished mothers. 2. On weaning, 156 male Wistar rats, born from deprived mothers (75 g casein/kg diet), were fed ad lib on either a balanced diet (180 g casein/kg; group DR), or a protein-deficient diet (50 g casein/kg; group DD). At seven time intervals (weeks 0, 1, 3, 5, 8, 16 and 23) twelve rats were weighed, fasted overnight and then decapitated. Blood glucose, plasma insulin (IRI) and glucagon (IRG) levels and pancreatic insulin and glucagon contents were determined. 3. In DR and DD rats blood glucose, which was normal at weaning, dropped in the 1st week and then increased slowly. DR rats were hyperglycaemic from week 16. IRI continually increased during the experiment from near-normal values to hyperinsulinic levels in DR rats; in group DD, it remained stable until week 8 before increasing. IRG, which was very low at weaning, increased to normal levels in the 1st week in group DR; in group DD, it fell slightly during the study. Pancreatic hormone contents were much higher than after normal pregnancy and lactation. 4. We compared these results with those of a previous study with rats born from normal mothers: at weaning in the second experiment the rats were already well adapted to malnutrition. The plasma ratio IRI:IRG in DD rats showed two phases of adaptation: weeks 0-5 when glucose homeostasis did not change and weeks 5-23 when it became increasingly normal. At the end of the experiment DR rats still had a lower body-weight than normal rats but were insulin-resistant.

Effect of parental malnutrition on enzyme content of rat pancreas.

The aim of this study was to assess in rat pups the influence of protein diets ingested by their mothers during gestation and lactation on the enzyme content of the pancreas of the offspring. Rat pups born of either well-nourished mothers or of mothers fed a diet moderately restricted in protein (9% casein w/w) were studied. After weaning, the pups were fed on one of three diets: a well-balanced diet, a 5% casein diet (protein restricted), or a well-balanced diet of a similar caloric value as the protein-restricted diet (pair-fed rat pups). The pups were sacrificed after intervals of one to 25 weeks after weaning. The results showed that the enzyme content of the pancreas increased progressively with time in pups born of malnourished mothers, particularly in pups fed the protein-restricted diet. This suggests prolonged maturation of the pancreas. Pups fed the 5% casein diet had a decreased amylase content per milligram of DNA but not of other enzymes. Malnutrition in the mother increased the ratio of enzymes to DNA and the total pancreatic enzyme content at different times after weaning, indicating that maternal malnutrition had a prolonged effect on the pancreatic enzyme content of the pups' pancreas. This mechanism could play a role in the pathogenesis of tropical chronic calcific pancreatitis in man and explain some of the geographic differences in the incidence of the disease.

Progressive adaptation of the endocrine pancreas during long-term protein deficiency in rats: effects on blood glucose homeostasis and on pancreatic insulin, glucagon and somatostatin concentrations.

Blood glucose, plasma insulin and glucagon, as well as pancreatic insulin, glucagon and somatostatin contents, were measured in control (C group, 18% casein), deprived (D group, 5% casein) and pair-fed (PF) rats at seven intervals during 23 wk after weaning (wk 0). In C rats, plasma and pancreatic insulin showed parallel variations, in D rats, plasma insulin increased normally until wk 3 after weaning, dropped from wk 3 to 8 and was higher in wk 16 and 23 than in wk 8, while pancreatic insulin increased linearly after a significant drop between wk 0 and 1. Insulin variations in D rats were related to protein deficiency until wk 5, but only to energy deficiency thereafter. Circulating and pancreatic glucagon dropped identically for the three groups until wk 5: its role in adaptation to malnutrition is quite irrelevant, although a dysregulation of its secretion was noted. Protein-energy malnutrition induced an increase of pancreatic somatostatin content that was due to the energy deficiency. On the basis of the insulin-to-glucagon ratio, three phases of adaptation to protein-energy malnutrition appeared. From wk 0 to 3, the metabolic priority was growth, whereas glucose homeostasis was secondary, accounting for the early hypoglycemia. From wk 3 to 8 survival was the main priority. After wk 8, the various biochemical parameters stabilized, and growth was parallel to that of normal animals. Protein-energy malnutrition was responsible for a dissociated adaptation of pancreatic hormones.

Nightly amended IRI/BG ratio in fasting test during sleeping periods in subjects with insulinoma and in normal, diabetic and obese subjects.

In order to obtain a dynamic picture of the way abnormal insulinemia, as a function of blood glucose, occurs in the morning in subjects with insulinoma, we have measured amended plasma insulin (IRI)/blood glucose (BG) ratio during the fasting period of 4 sleeping subjects with insulinoma. Healthy subjects and subjects suffering from other diseases were used as reference in order to determine variations of this ratio during the night. BG and IRI were assayed at intervals of 15 or 30 min. Subjects with insulinoma differed from the other subjects by a very elevated ratio dispersion around the mean value with highly significant peaks (greater than 100). Mean value always remained outside the range (7-82) which covers the total range of values measured in healthy and pathological subjects.

28-hour profiles of blood glucose (BG), plasma immunoreactive insulin (IRI) and IRI/BG ratio in four insulinomas.

Nycthemeral variations in blood glucose (BG) and insulinemia (IRI) of four subjects with insulin-secreting pancreatic tumors were determined. Blood samples were drawn every 15 min over a 28-h period. After surgery, two of the subjects were retested. Meals were distributed during testing so that there was a minimum of eight meals per test. The meals before and after surgery were qualitatively, quantitatively and chronologically the same. Even though the circadian profiles of the glycemia and insulinemia varied greatly among the subjects, there were three common characteristics during the noctural period (24 h-8 h): Existence of one or several phases of at least 1 hour where the glycemia was less than 2.78 mmol/l, Existence of IRI peaks, without eating. Existence of a peak or of increased values (as compared to normal values) of the IRI/BG ratio, without eating. The IRI/BG ratio is a very sensitive index for insulin secretion dysfunction as compared to glycemia. The results suggest that the measurement of glycemia and insulinemia of sleeping subjects and then calculation of the IRI/BG ratio is sufficient to affirm the presence of an insulin-secreting adenoma.

[Pneumonia, disseminated intravascular coagulation and colonic hematoma]. / Pneumopathie, coagulation intravasculaire disséminée et hématome colique.

A case of pneumopathy associated with a colonic haematoma and a disseminated intravascular coagulation is reported. No bacteriological or serological evidence of the infection could be found. The rarity of such a pathological association made this case particularly interesting.

Hyperinsulinemia associated with normal C-peptide levels in a woman treated with isoniazide.

The authors report on the observation of a woman treated with isoniazide, who presented clinical symptoms of hypoglycemia during treatment (seating, confusion, anxio-depressive syndrome, lipothymia). After the antitubercular treatment was stopped, a moderate hypoglycemia without clinical manifestations accompanied by a marked hyperinsulinemia and normal C-peptide values was detected during a Conn's test. Serum gel filtration on Sephadex G 50 Fine showed that the measured hyperinsulinemia was effectively due to an insulin excess. This excess did not seem caused by surreptitious insulin injection. This seems to be the consequence of a deficiency in insulin catabolism because the C-peptide level was normal. The possible role of isoniazide on carbohydrate metabolism is discussed.