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To evaluate beta-cell function in patients with pancreatic cancer, the glucagon stimulation test was performed in seven patients with pancreatic adenocarcinoma, seven patients with type I diabetes mellitus, seven patients with type II diabetes mellitus, and in seven healthy controls. C-peptide serum levels were determined before and after a 1-mg i.v. glucagon injection. Basal C-peptide values were normal or slightly increased in pancreatic cancer and type II diabetic patients and low in type I diabetic patients. Following glucagon stimulation, no significant increase was observed in C-peptide values of type I diabetics and pancreatic cancer patients, whereas significant increases occurred in controls and type II diabetics. It is concluded that the altered beta-cell function found in pancreatic cancer patients may lead to hyperglycemia, which is frequently associated with this tumor type.

The metabolic effects of a three-month treatment with a high-fiber diet (15 grams of guar-gum added to a standard diet) were investigated in seven type 1 diabetic subjects, with a moderately poor metabolic control. HbA1c levels, daily insulin requirement, cholesterol, triglyceride, amino acid and intermediate metabolite concentrations were evaluated before and following the high fiber diet, both in the postabsorptive state at euglycemia and during a euglycemic, hyperinsulinemic, hyperaminoacidemic clamp. Insulin-mediated glucose utilization, an index of insulin-sensitivity, was also measured during the clamp. Following the diet, no differences in HbA1c levels (7.6 +/- 0.7%----7.3 +/- 0.6%), daily insulin requirement (50 +/- 5----51 +/- 3 U/d), triglyceride, amino acid and intermediary metabolite concentrations in the basal, euglycemic state, were observed. Only cholesterol concentrations decreased significantly (from 165 +/- 12 to 142 +/- 12 mg/dl, P less than 0.01) after the diet. During the clamp, the concentrations of all measured substrates were comparable before and after high fiber treatment. Insulin-mediated glucose disposal was also unchanged by guar-gum treatment. Patients' body weights were not modified by the diet. In conclusion, our study shows that a high fiber diet, obtained with the addition of 15 grams of guar-gum to a standard diet, is of no benefit to IDDM either as regards the metabolic control or insulin sensitivity. Only cholesterol levels were decreased. Therefore, the costs and benefits of these diets in the treatment of IDDM should be reconsidered.

Carbohydrates (CHO) are a major determinant of post-prandial blood glucose in the diet of people with Type 1 diabetes mellitus, but patients frequently fail to evaluate CHO food content. Poor education is thought to contribute heavily to this failure. Our aim was to plan and evaluate a simple educational program to improve dietary knowledge and teach how to count CHO in Type 1 diabetic subjects. Forty-eight patients (age 27+/-1 yr, diabetes duration 11+/-1 yr, HbA1c 9%) attended 4 interactive meetings held at monthly intervals. The targets of the course were: 1) to identify sources of CHO, fats and proteins; 2) to count CHO and to split them among meals; 3) to assume CHO-rich foods without changing daily calorie or carbohydrate intake; 4) to modify the diet so as to correct hypoglycaemic events. To evaluate the effect of the course, patients completed a 7-day food record and answered a questionnaire covering the targets of the course at baseline, at the end of the course and 7 months later. After the course dietary knowledge improved significantly. The number of patients who weighed foods, estimated CHO food content and correctly distributed CHO among meals also increased. After the course patients reacted better when faced with hypoglycaemia. The knowledge acquired persisted 7 months after the end of the course. Therefore, we conclude that a simple teaching program can improve diet knowledge in Type 1 diabetics and establish a sustained habit of counting CHO.

Between 1976 and 1994, 318 patients underwent surgical closed retro-endoperitoneal drainage and post-operative lavage for acute necrotizing severe pancreatitis. The main indication was sepsis (66.4%). The ratio between operated on and the overall number of observed patients has been progressively shifting towards medical treatment. Furthermore in the operated group the timing of surgery has been delayed step by step. The Authors discuss improvements in the understanding of the etiological and therapeutical aspects of the disease which has had a better outcome in recent years, survival rate of 91.4%. The personal option for the closed surgical approach is based on the progressive improvement of the technique and on the good results obtained both in terms of mortality and associated morbidity; as regards the latter problem the open techniques seems to be related to a higher complication rate than the closed one.

OBJECTIVE To assess kidney function and AER in patients with PD. RESEARCH DESIGN AND METHODS Thirty-three patients with PD (age 52 ± 7 yr, duration of disease 11 ± 6 yr, BMI 24 ± 3 kg/m2) and 33 patients with IDDM were matched for sex, BMI, and duration of disease. GFR and RPF were determined by single injection of [51Cr]EDTA and [125I]hippurate. AER was measured by radioimmunoassay in a single timed overnight urine collection. RESULTS GFR and RPF were, respectively, 113 ± 35 and 441 ± 145 ml · min−1 · 1.73 m2 in patients with PD and 123 ± 30 and 549 ± 94 (P < 0.001) in IDDM. FF was significantly higher in patients with PD (0.26 ± 0.05 vs. 0.22 ± 0.03; P < 0.001). Prevalence of hyperfiltration (GFR > 135 ml · min−1 · 1.73 m2) was similar in both groups (30% in patients with PD vs. 28% in those with IDDM). Geometric mean of urinary AER was 10.4 μg/min (range 1–186) in patients with PD and 11.2 (1–198) in IDDM patients. Some 30.3% of patients with PD and 18% of those with IDDM were microalbuminuric (AER > 20 μg/min). By multiple regression analysis, AER was significantly related to systolic (P < 0.04) and diastolic blood pressure (P < 0.01) and to BMI (P < 0.03) in patients with PD. Retinopathy was more frequent in microalbuminuric patients with PD than in those without elevated AER. CONCLUSIONS We suggest that early renal abnormalities occur similarly in patients with PD and IDDM.

A retrospective analysis of blood glucose control was performed in 17 type 1 diabetic patients who regularly monitored their blood glucose concentration by visual strips over a period of 3-83 months. Analysis was performed by a patient management software loaded on a personal computer. In this cohort of patients the average daily blood glucose reading was 1.6 +/- 0.3. Blood glucose readings were collected more frequently following meal ingestion (40.3%) than in the post-absorptive state (24.6%; P less than 0.05). Blood glucose concentration fluctuated from a basal level of 146 +/- 5 mg/dl to 167 +/- 4 mg/dl in the post-prandial phases with an average daily value of 156 +/- 2 mg/dl. Blood glucose values below 80 mg/dl were evenly distributed throughout the day, while hyperglycemia (greater than 300 mg/dl) occurred more commonly after meals (42%). Daily blood glucose was higher during weekends (164 +/- 5 mg/dl) than during weekdays (155 +/- 2 mg/dl; P less than 0.05). A weak correlation was found between the number of blood glucose readings/day and daily blood glucose level. These results suggest that long-term maintenance of satisfactory metabolic control is attainable in type 1 diabetic patients and that this is mainly dependent upon subject self awareness.

The presence or absence of histological signs of cholestasis (on the basis of liver specimens obtained by means of liver biopsy) was compared with total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, ornithine carbamoyltransferase, serum glutamic oxaloacetic transaminase levels and LP-X test in 157 patients suffering from different liver diseases. The LP-X test was positive in 93% of the 59 cases in whom histological evidence of cholestasis was observed and negative 95% of the 98 cases in whom histological examination was negative. LP-X concurs more frequently with the histological picture than do total bilirubin and alkaline phosphatase. These data confirm that LP-X test is more specific than the tests traditionally used to demonstrate or exclude cholestasis. An increment in gamma-GT levels was observed in 97% of the patients with a positive LP-X test. These clinical results have been discussed in the light of recent data regarding the mechanism of lipoprotein-X formation and the possible relationships between LP-X and gamma-glutamyl transpeptidase.

We evaluated the effect of a diet rich in natural (NF) or extractive fibres (guar gum) on 12 male IDD (insulin-dependent diabetes) out-patients. The treatment lasted for 2 months. During the first month the patients were on an isocaloric diet containing 30 g of fibres and then they were randomly subdivided into two groups. One group followed an isocaloric diet rich in fibres (70 g/day), the second group an isocaloric diet enriched by guar (9 g of guar added to 30 g of natural fibres/day). Reduced serum levels of HbA1c and several amino acids showed that metabolic control significantly improved under each dietary regimen.

The authors describe one case of paraganglioma of the posterior mediastinum successfully removed after being discovered accidentally in a young male patient who showed no symptoms attributable to the tumor. The latter was a round mass, about 6 cm in diameter, richly vascular, located in the right costomediastinal gutter. Histologically it was a functionally silent paraganglioma originating from the intrathoracic aortosympathetic paraganglia, these being part of the very numerous groups of the paragangliar system distributed segmentally into metamers, particularly in the adrenal medulla. According to the more recent views, chemodectoma or paraganglioma (chromaffine or non-chromaffine, functionally active or silent) and pheochromocytoma (functionally active or silent, adrenal or extra-adrenal) constitute a group of tumors sharing the same tissue matrix, namely paragangliar cells.

The incidence of diabetic retinopathy was evaluated by means of fluorescein angiography in 54 patients with diabetes secondary to chronic pancreatitis or to pancreatectomy. Thirty-one percent of the patients had background retinopathy; none had proliferative retinopathy. The percentage of patients with retinopathy was the same in groups with or without a family history of diabetes. There was no correlation between the degree of metabolic control, the levels of C-peptide, glucagon, growth hormone, and the presence of retinopathy. Retinopathy was correlated with the duration of diabetes. In conclusion, diabetes caused by pancreatitis or pancreatectomy has a significant prevalence of retinopathy, which has more benign characteristics and slower evolution than the retinopathy in patients with primary diabetes.

Twenty subjects with familial hypercholesterolemia (12 Type IIa and 8 Type IIb), previously treated with Colestipol for 16 months, were subjected to therapy with Colestipol (15 g/day) + clofibrate (2 g/day) for 15 months. During the second treatment period these patients continued to follow the isocaloric hypocholesterolemic diet initiated during the original trial. In Type IIa patients, the association of these drugs enhanced the decrease in plasma cholesterol levels. The total mean decrease was -40 +/- 17 mg/dl (P less than 0.05). In Type IIb patients, on the other hand, the association of clofibrate with Colestipol induced an increase in plasma cholesterol levels. The total mean increase was +24 +/- 7 mg/dl (P less than 0.05). A markedly significant decrease in plasma triglyceride levels was observed in this group (- 107 +/- 30; P less than 0.01). These results seem to indicate that, in Type IIa, clofibrate increased the resin's hypocholesterolemic effect. In Type IIb, on the other hand, the association of these drugs did not seem to be indicated since a marked hypotriglyceridemic effect was accompanied by an increase in plasma cholesterol levels. These results are briefly discussed in the light of recent data obtained on the effects of Colestipol and clofibrate on lipoprotein metabolism.

Near-normal plasma daily glucose profile was induced by Continuous Subcutaneous Insulin Infusion (CSII) treatment in order to evaluate its influence on diabetic somatic and autonomic neuropathy. Twelve insulin-dependent diabetic subjects with somatic neuropathy were studied before and after a short term CSII treatment of 10 days. Four out of these subjects, all affected by autonomic neuropathy, were followed for 1 yr with controls dvery four months. Metabolic equilibrium was monitored by mean daily plasma glucose (MPDG) profile and by Glycosylated Hemoglobin (GHb) evaluation. Somatic neuropathy was studied assessing conduction velocity at peroneal motor (PMCV) nerve, ulnar motor (UMCV), ulnar sensory (USCV) and sural sensory (SSCV) nerves. Autonomic neuropathy was assessed by means of a battery of five cardiovascular autonomic tests: Valsalva Manoeuvre (VR), Deep Breathing (DB), Lying-to-Standing (LS), Sustained HandGrip (SHG) and Postural Hypotension (PH). Short-term CSII treatment induced a near normalization of metabolic parameters, a significant improvement in VR (p < 0.05) and DB (p

Results related to long term treatment with Colestipol (a new resin sequestering bile acids) in 23 subjects with familial hypercholesterolaemia, 12 with Type IIA, 8 with Type IIB and 3 homozygotes are reported. Patients were given 15 g/day active drug for a period of 12 months and a double dose (30 g/day) for a successive period of 4 months along with a low cholesterol, low saturated fat, polyunsaturated fat-rich diet. Mean cholesterol decrease was --42 +/- 18 mg/dl (P less than 0.05) after 12 months of 15 g/day Colestipol and --69 +/- 17 mg/dl (P less than 0.01) after the following 4 months of 30 g/day Colestipol. The difference between the two periods of treatment (15 g and 30 g/day was not statistically significant. A slight but not significant increase in triglyceride levels was observed. Serum uric acid showed a significant increase throughout the entire period of treatment. No malabsorption syndrome or signs of toxicity were seen. Most frequent side effects were constipation, nausea, and metheorism which, with the exception of 4 cases which were withdrawn from the study, were reported as being transitory and mild.

The effect of imidazole-2-hydroxibenzoate on urinary excretion rates of glycosaminoglycans and albumin in 22 insulin-dependent diabetics with albumin excretion rates under 300 mg/day was evaluated in a 165-day double blind crossover study. Unlike placebo, the drug reduced glycosaminoglycan and albumin excretion rates significantly after 40 and 60 days of treatment, and the effects were significantly intercorrelated. Moreover, a parallel reduction in urinary excretion of N-acetyl-beta-D-glucosaminidase was also observed. These pharmacological effects may have a positive impact on the subsequent natural history of diabetic nephropathy.

Metformin's hypolipidemic effects (2.55 g/day for 3 months) have been studied in 19 subjects with Fredrickson's Type IV hyperprebetalipoproteinemia. The majority of patients were above ideal body weight (relative body weight = 118 +/- 2.7 %). Eleven of the subjects presented chemical diabetes, 5 fasting hyperglycemia, and 3 normal glucose tolerance. After treatment with metformin, body weight showed a slight, but significant reduction (--2.4 +/- 0.3 kg). Glucose tolerence was not substantially altered while basal glucose was significantly reduced in the 5 subjects with fasting hyperglycemia. Basal plasma insulin was significantly reduced in all the patients following metformin treatment. Insulin response to OGTT was slightly reduced in the subjects with fasting hyperglycemia. Independent of the patients' glucose tolerance, metformin treatment induced a marked decrease in plasma triglycerides (-- 40 %) and a reduction in plasma cholesterol (-- 12 %). No correlation was found between triglyceride and cholesterol reduction and body weight, glucose, and plasma insulin variations. Like phenformin, metformin acts not only on glucose metabolism and insulin secretion but on lipid metabolism as well.

To the Editor.— In a previous study we found a higher than normal glycosaminoglycan (GAG) excretion in patients with insulin-dependent diabetes (IDD), who have daily albumin excretion levels less than 25 mg (17 μg/min), 1 a value that borders on the normal range for albuminuria. This abnormality was paralleled by a higher urinary activity of lysosomal glycohydrolases involved in GAG metabolism, as well as a normal excretion of brush border enzymes not related to GAG turnover. We therefore proposed a renal origin for GAG, perhaps due to a derangement in GAG turnover in the renal basement membrane. 2 Since GAG is the major determinant of the anion layer of the glomerular basement membrane, 3,4 this finding might mirror an early decrease in membrane selectivity, which could underlie the appearance of microalbuminuria. Report of a Study.— To test this hypothesis, we evaluated urinary GAG excretion during a 24-hour period in 25