Low plasma levels of pancreatic polypeptide in obesity.

Plasma levels of pancreatic polypeptide (PP) were studied in a group of 22 normal and 22 obese subjects after an overnight fast. In a second group of 10 normal and 13 obese adults, PP secretion was stimulated by a protein-rich meal. The results indicate lower fasting PP values in the obese subjects and a decreased response during the second phase of the meal-induced secretion. This could suggest a possible role of PP in obesity.

Relationship between intravenous ethanol, alcohol-induced inhibition of pancreatic secretion and plasma concentration of immunoreactive pancreatic polypeptide, vasoactive intestinal peptide, and somatostatin in man.

We have studied in seven men, consuming less than 50 g alcohol daily, the effect of intravenous (i.v.) ethanol on (a) hormonally (secretin + CCK PZ) submaximally stimulated pancreatic secretion and (b) blood levels of pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and somatostatin. After intravenous ethanol (600 mg/kg), pancreatic secretion decreased in all subjects and plasma levels of PP and VIP increased significantly. Moreover, there was a significant correlation between the mean inhibition of chymotrypsin output and the mean increase in PP plasma levels during the first 45 min following ethanol infusion. Therefore i.v. infusion of alcohol elicits release of PP and VIP and PP release could explain in part at least the alcohol-induced pancreatic inhibition observed in non-alcoholic men.

[Comparison of various types of islet cell antibodies in diabetes as a function of its cause and duration]. / Comparaison de divers types d'anticorps anti-îlots dans le diabète en fonction de la cause et de la durée d'évolution.

Three types of pancreatic islet cell antibodies (ICA) have been described in insulin-dependent diabetic patients: IgG-ICA directed against cytoplasmic antigens, complement-fixing antibodies (CF ICA) and islet cell surface antibodies (ICSA) directed against membrane antigens. They can be detected by indirect immunofluorescence methods using human pancreas sections for IgG-ICA and isolate rat live islet cells for ICSA. Distribution of these 3 types of antibodies and correlations within individual patients were investigated in non-diabetic controls, in patients with idiopathic diabetes of various duration and in patients whose diabetes was associated with autoimmune diseases, chronic pancreatitis or haemochromatosis. The respective incidences of IgG-ICA and ICSA were: 5.4% and 15.8% in controls, 67.3% and 64.3% in patients with recent onset diabetes, 22.6% and 21.5% in old-standing diabetes, 63% and 50% in auto-immune diabetes, 12.5% and 7.2% in diabetes from chronic pancreatitis, and 5.6% and 7.6% in diabetes from haemochromatosis. In contrast with these correlations within groups, individual concordances were only 67%. CF ICA were relatively rare and almost exclusively present in IgG-ICA positive patients (30% of all cases); they seem to constitute a sub-group of IgG-ICA. It is concluded that IgG-ICA and ICSA are equally frequent in each type or duration of insulin-dependent diabetes and that they are not associated with secondary diabetes. The lack of concordance in individual patients indicates that the anti-pancreatic immune response is not homogeneous.

[Decrease in the serum level of the C3 complement component in noninsulin dependent diabetes of recent onset]. / Diminution du taux sérique du composant c3 du complément dans le diabète insulinodépendant récent.

Complement components C3, C4 and C3A were measured by immuno-diffusion in plasma of 36 recent onset insulin-dependent diabetics (IDD) and compared to plasma complement levels of 19 long-standing IDD and 18 non diabetic controls. A significant decrease of C3 and a mild increase of C3A was found in recent-onset diabetes group. However these variations could not be correlated with IgG-islet cell antibodies, C3--fixing islet cell antibodies or A--B HLA antigens. No significant difference was found between long-standing IDD and controls for the 3 complement components. In conclusion, the decrease of C3, found in 30% of recent onset IDD, might be due to increase complement consumption either by the insulitis process or by circulating immune complexes.

Pancreatic polypeptide secretion in diabetic patients with idiopathic haemochromatosis.

In order to investigate the endocrine pancreatic dysfunction resulting from iron overload, plasma pancreatic polypeptide (PP) response to a protein-rich meal was studied in 10 healthy controls and 30 insulin-dependent (type I) diabetic patients: ten with idiopathic haemochromatosis (IH), ten with chronic pancreatitis and ten with idiopathic type I diabetes. While fasting plasma PP levels were slightly higher in diabetic with IH (40,8 +/- 7 pmol/l) than those in controls (27,1 +/- 3) on in type I diabetics (31,3 +/- 3) they were similar after the meal (peak level 95 +/- 18, 139 +/- 23, 100 +/- 36 respectively). In contrast the mean PP level was low in diabetics with chronic pancreatitis in the fasting state (15.9 +/- 3.6 pmol/l) and did not rise following the meal. These findings suggest that there is no PP cell injury in diabetics with IH.

Type II diabetes in young subjects. A study of 90 unrelated cases.

Type II, non insulin dependent diabetes mellitus is commonly diagnosed after the age of 45 years. For this reason it was previously called maturity onset diabetes. Type II diabetes occurring in young subjects has generally been described in selected pedigrees. The purpose of this work was to review data from all the unrelated type II diabetics (with fasting hyperglycemia) diagnosed before the age of 45 and observed in our department over the last four years. A total of 90 such patients including 44 men and 46 women were included in this study. Of 43 cases diagnosed before the age of 30, there were 30 women compared to only 16 women out of 47 cases diagnosed between 30 and 45 years (p less than 0.001). At the time of diagnosis 42 patients had a relative body weight lower than 120%. In 66,7% of the cases, one parent was a known diabetic. The rate of diabetes in the sibships was 50%. Differences in family history of diabetes were not observed in relation to age or weight at diagnosis. Comparison with a series of 150 conventional type II diabetics in whom diagnosis was made between 45 and 60 years of age showed a significantly greater frequency of obesity (86%) and fewer diabetic parent (36%). The mean apparent duration of diabetes was 14 years (range 5-42). Microangiopathy was not infrequent in these diabetic patients. Twenty-three patients had retinopathy, proliferative in 8 cases, and 3 were blind. Nine had renal insufficiency, severe in 3 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Islet transplantation in diabetic rats. Long-term follow-up of glucose tolerance.

Inbred Lewis rats made diabetic by streptozotocin were transplanted with 430-870 islets from syngenic donors via the portal vein. Though fasting plasma glucose was normal, the tolerance to glucose given intraperitoneally (IPGTT) or orally (OGTT) remained impaired one month after transplantation. The higher the number of islets, however, the better the glucose tolerance. The results of IPGTT and OGTT in each animal correlated. Fasting plasma insulin levels were within the normal range suggesting that the action of insulin on the liver and its degradation by the liver is impaired due to the limited number of hepatocytes subjected to high insulin concentrations. Eight months after transplantation, the plasma insulin and glucose responses to OGTT were still unchanged while those of the less physiological IPGTT were worse. Thus, the functional capacity of the transplanted endocrine tissue does not appear to change with time.

[The artificial pancreas in surgery. An attempt to simplify intra- and post-operative insulin therapy]. / Le pancréas artificiel en chirurgie. Recherche d'une simplification de l'insulinothérapie per et post-opératoire.

The insulin requirements of 10 insulin-dependent diabetic patients were evaluated during and after surgery (including 4 caesarian sections) by connecting the patients with an artificial pancreas. Considerable variations were observed in the intra-operative period. In contrast, the amounts of insulin released during the immediate post-operative period were more regular and reproducible (mean: 2.36 U/h for a glucose intake of 200-250 g/24 h). A satisfactory control of glycaemia was obtained with this dosage in 7 insulin-dependent post-operative patients without using an artificial pancreas. It would therefore seem that in most cases continuous insulin infusion combined with direct measurement of capillary glycaemia could replace an artificial pancreas and make the intra- and post-operative care of diabetic patients simpler and more effective.

Impaired pancreatic polypeptide response to insulin hypoglycemia in obese subjects.

We have studied the effect of insulin hypoglycemia on the secretion of pancreatic polypeptide (PP) in 14 obese subjects with normal glucose tolerance and in 6 normal controls. Infusion of insulin 0.1 U/kg/h in controls and 0.12 U/kg/h in the obese, for one hour, produced a progressive hypoglycemia, similar in both groups (nadir 2 mmol/l at 50 min). The secretion of PP was less in obese subjects than in controls (peak 116 mmol/l vs 184 pmol/l, P less than 0.01) (integrated secretion sigma delta PP 288 vs 472 pmol/l, P less than 0.01) and was also delayed in the obese subjects beginning at 50 min instead of 40 min. The secretion of glucagon and of C-peptide were not different in the two groups, but the integrated response of ACTH was higher in the obese (sigma delta ACTH 52 pmol/l vs 25 pmol/l, P less than 0.01). The secretory response of growth hormone (STH) was smaller in the obese group (peak 8.6 +/- 1.28 vs 21.4 +/- 6.4 ng/ml, P less than 0.01). The reduced secretion of PP in obese subjects could be due to impaired sensitivity to hypoglycemia of the central control mechanism for PP release. The similarity of the reductions in the secretion of both PP and STH support this hypothesis, although a reduction in the secretory capacity of pancreatic PP cells cannot be excluded.

[Initial remission period in insulin-dependent diabetes in the young subject]. / La phase de rémission initiale du diabète insulinodépendant du sujet jeune.

Occurrence of a remission after initiation of insulin treatment in insulin dependent diabetes (type I) of recent onset is a well known phenomenon. It may be more or less complete up to insulin withdrawal. In newly diagnosed IDD requiring insulin for ketoacidosis or primary failure of oral agents and with a duration of symptoms of less than 6 months, initiation of optimized insulin therapy was followed by suppression of insulin (with or without the use of oral agents) in two thirds of cases for a mean period of 12 months while blood glucose and glycosylated haemoglobin remained normal. As therapeutic reversal of the etiopathological mechanism of IDD is foreseen it is relevant to define the characteristics of cases with remission induced by intensified insulin treatment, and the mechanisms by which they may be explained. Current knowledge on these questions will be analysed in this review. Furthermore it appears that withdrawing insulin for a mean period of 12 months does not hamper the subsequent control of diabetes.

[Multiple hepatic cysts in rat rendered diabetic by streptozotocin and treated by islets of Langerhans grafts: the role of streptozotocin]. / Polykystose hépatique chez le rat rendu diabétique par la streptozotocine et traité par greffe d'îlots de Langerhans: rôle de la streptozotocine.

This study is based on the investigation by light and electron microscopy of hepatic biopsies from 14 rats rendered diabetic by streptozotocin and treated by portal embolization of islets of Langerhans. Macroscopically, voluminous projecting cysts were observed, sometimes occupying a whole lobe. By light microscopy, the cysts were lined with canalicular-type epithelium. Ultrastructural studies confirmed the canalicular nature of these cells and cilia were frequently observed. The presence of identical cysts in rats rendered diabetic by streptozotocin but not treated by embolization proves that this product is the agent responsible for the induction of this adenomatosis.

[Evaluation of the acceptability of 2 methods for self monitoring of blood sugar by a group of insulin-dependent diabetic patients]. / Evaluation de l'acceptabilité de deux méthodes d'autosurveillance glycémique par un groupe de diabétiques insulinodépendants.

In order to evaluate the advantages and disadvantages of two methods of blood glucose self-monitoring (either direct semi-quantitative reading on Haemoglukotest 20-800 or quantitative reading of Dextrostix strips using a reflectance-meter, Glucometer) 20 insulin-dependent diabetics selected according to the quality of the management of their own diabetes were asked to try both methods for 3 months and then fill a questionnaire assessing their acceptance. Analysis of the responses shows that home blood glucose monitoring is well accepted even after one year by patients aware of the necessity of a good glycemic control. It is specially useful for the adaptation of insulin doses and less so for identification of hypoglycemic attacks. Haemoglukotest 20-800 is appreciated for its easy utilization specially during professional life and outside leisure. However, the reflectance-meter Glucometer is preferred by most patients because they feel it is more reliable and safe.

Sustained initial remission induced by intensive insulin treatment in type I diabetes. Possible role of the genetic background.

A remission defined by the possibility of temporarily discontinuing insulin therapy while blood glucose remains normal is not infrequently observed after intensive insulin therapy in newly diagnosed acute type I diabetes in the South of France. In order to analyze possible factors of such a remission, 47 newly diagnosed ketotic diabetics under 35 years of age and of Caucasian origin were enrolled in a prospective study. They were given continuous s.c. insulin infusion for two weeks and oral agents were introduced on day 8. In 16 patients insulin could not be withdrawn. In 31 insulin was stopped for more than 3 months (mean 12.3, range 3-35) while blood glucose remained below 6 mmol/l fasting (mean 5.3) and 7.8 post-prandial (mean 5.1) and glycosylated Hb below 8.5% (mean 6). At presentation, diabetics who later went into remission and those who did not, showed no difference in age (22.3 vs 23.1 years), sex ratio, apparent duration of symptoms (1.4 vs 1.6 months), glycosylated hemoglobin (12.0 vs 13.1%) and basal or post-prandial C-peptide values or presence of islet cell antibodies. No differences were observed in the frequency of DR3 and DR4 antigens in the two groups but diabetics who developed a remission bore the A 19.2 antigen (9/31 vs 1/16) and the B18 one (11/31 vs 1/16) more frequently, A 19.2 and B18 being associated in 7 cases of this group. This increased frequency in the remission group of HLA antigens, more often observed in diabetics of Mediterranean origin, suggests that differences in the genetic background may be associated with a difference in the evolution of the disease.

Cold reacting antilymphocyte antibodies in type I (insulin dependent) diabetes.

Non HLA antilymphocyte antibodies have been detected in numerous auto-immune illnesses and notably in type I (insulin dependent) diabetes. In order to ascertain their role in this illness, the actual frequency of this phenomenon has been estimated. The privileged cellular target has been determined. Finally correlations with the other immunogenetic markers of diabetes have been investigated. Non HLA antilymphocyte antibodies are frequent, above all at the beginning of the illness (32.4% before 6 months, 10% after 5 years). The cellular target is mainly composed of B lymphocytes. B lymphocyte enrichment of cellular suspensions leads to better method sensitivity (70.3% positive reactions at the beginning of the illness). No correlation was found with presence of anti islet cell antibodies or anti coxsackie B virus antibodies (IgM). Association with the HLA DR3 phenotype is relatively frequent but does not attain statistical significance.

Kinetics of fast haemoglobin in diabetic rats.

This study was designed to examine the appearance and disappearance kinetics of glycosylated haemoglobin during abrupt changes of blood glucose in the rat. The concentration of the fast haemoglobin component, which has similar chromatographic and electrophoretic profiles to human haemoglobin A1, was measured after the induction of diabetes by streptozotocin and its cure by syngeneic intraportal islet transplantation. Fast haemoglobin was increased in 12 diabetic rats compared with 22 controls (15.8 +/- 0.8 versus 8.2 +/- 0.3%, mean +/- SEM). In a group with mild diabetes (n = 8, blood glucose less than 22 mmol/l), fast haemoglobin rose to 13.7 +/- 1.0% by week 8. In a group with severe diabetes (n = 4, blood glucose greater than 22 mmol/l), fast haemoglobin rose more quickly (in 3 weeks) to a higher level (18.2 +/- 3.3%) and changed little thereafter. This suggests a saturable system in which the rate of increase and final value depend upon the degree of hyperglycaemia. After islet transplantation, fast haemoglobin returned to normal in 4 weeks (n = 5, 17.6 +/- 1.4 to 9.4 +/- 0.9%). This delay is shorter than expected from the red cell lifespan (around 60 days), suggesting that haemoglobin glycosylation may be partly reversible. These results suggest that in unstable diabetes the interpretation of haemoglobin A1 levels is not as simple as was supposed previously.