Bleeding peptic ulcer occurring in hospitalized patients: analysis of predictive and risk factors and comparison with out-of-hospital onset of hemorrhage.

We reviewed 84 consecutive cases of peptic ulcer hemorrhage, which occurred, in an area of 270,000 people, from 1986 to 1988, in patients already hospitalized for other diseases (in-bleeders). These subjects were compared with a prospective series of 386 patients who initially bled as out-patients and were then admitted (out-bleeders). Of 84 hemorrhages in hospitalized patients, 41 followed major surgery, while 43 were associated with other severe conditions. Bleeding site was duodenal in two thirds. Mean age was 67 +/- 15 years versus 59 +/- 15 among out-bleeders. Fifty percent of in-bleeders had recently received nonsteroidal antiinflammatory drugs (NSAIDs), and one third were on anticoagulants and 10% on corticosteroids; in 39 (46%) bleeding was shown to be persistent or recurrent, 5 (5.9%) underwent endoscopic and 18 (21%) surgical therapy; 29 died (34%). The corresponding figures among out-bleeders were: further bleeding 80 (20.7%), endoscopic therapy 12 (3.1%), surgery 25 (6.5%), deaths 17 (4.4%). As regards in-bleeders, only active bleeding and endoscopic stigmata emerged as statistically significant risk factors for further bleeding. The latter was shown to be significantly related to mortality. The most relevant finding was, however, that NSAIDs and anticoagulants, in association with stress and aging, are very frequently involved in peptic ulcer bleeding of hospitalized patients. The fatal outcome of one third, despite all available treatments, highlights the importance of prevention against drug- and stress-related mucosal damage in in-patients suffering from severe diseases.

Partial recovery of insulin secretion and action after combined insulin-sulfonylurea treatment in type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral agents.

Metabolic control, insulin secretion and insulin action were evaluated in seven Type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral antidiabetic agents before and after two months of combined therapy with supper-time insulin (Ultratard: 0.4 U/kg body weight/day) plus premeal glibenclamide (15 mg/day). Metabolic control was assessed by 24 h plasma glucose, NEFA, and substrate (lactate, alanine, glycerol, ketone bodies) profile. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, hyperglycaemic clamp (+ 7 mmol/l) and 24 h free-insulin and C-peptide profiles. The repeat studies, after two months of combined therapy, were performed at least 72 h after supper-time insulin withdrawal. Combining insulin and sulfonylurea agents resulted in a reduction in fasting plasma glucose (12.9 +/- 7 vs 10.4 +/- 1.2 mmol/l; p less than 0.05) and hepatic glucose production (13.9 +/- 1.1 vs 11.1 +/- 1.1 mumol.kg-1.min-1; p less than 0.05). Mean 24 h plasma glucose was also lower (13.7 +/- 1.2 vs 11.1 +/- 1.4 mmol/l; p less than 0.05). Decrements in fasting plasma glucose and mean 24 h profile were correlated (r = 0.90; p less than 0.01). HbA1c also improved (11.8 +/- 0.8 vs 8.9 +/- 0.5%; p less than 0.05). Twenty-four hour profile for NEFA, glycerol, and ketone bodies was lower after treatment, while no difference occurred in the blood lactate and alanine profile. Insulin secretion in response to glucagon (C-peptide = +0.53 +/- 0.07 vs +0.43 +/- 0.07 pmol/ml) and hyperglycaemia (freeinsulin = 13.1 +/- 2.0 vs 12.3 +/- 2.2 mU/l) did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin regulation of glucose and lipid metabolism in massive obesity.

Eight obese patients and 12 normal individuals underwent a euglycaemic insulin clamp (20 and 40 mU m2-1.min-1) along with continuous infusion of 3-3H-glucose and 1-14C-palmitate and indirect calorimetry. Basal plasma glucose concentration (4.7 +/- 0.3 vs 4.4 +/- 0.2 mmol/l) was similar in the two groups, whereas hepatic glucose production was slightly higher in obese individuals (1.11 +/- 0.06 vs 0.84 +/- 0.05 mmol/min) in spite of higher plasma insulin levels (17 +/- 2 vs 6 +/- 1 mU/l; p less than 0.01). Insulin inhibition of hepatic glucose production was impaired in obese subjects. Glucose disposal by lean body mass was markedly reduced both at baseline (11.7 +/- 1.1 vs 15.6 +/- 0.6 mumol.kg-1.min-1; p less than 0.05) and during clamp (15.0 +/- 1.1 vs 34.4 +/- 2.8 and 26.7 +/- 3.9 vs 62.2 +/- 2.8 mumol.kg-1.min-1; p less than 0.01) Oxidative (12.2 +/- 1.1 vs 17.8 +/- 1 and 16.1 +/- 1.1 vs 51.1 +/- 1.7 mumol.kg-1.min-1; p less than 0.05-0.002) and non-oxidative glucose metabolism (3.9 +/- 1.1 vs 15.0 +/- 2.8 and 12.8 +/- 3.3 vs 38.2 +/- 2.2 mumol.kg-1.min-1; p less than 0.01-0.001) were impaired. Basal plasma concentrations of non-esterified fatty acids (635 +/- 75 vs 510 +/- 71 mumol/l) and blood glycerol (129 +/- 17 vs 56 +/- 5 mumol/l; p less than 0.01) were increased in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose turnover and recycling in diabetes secondary to total pancreatectomy: effect of glucagon infusion.

This study was designed to evaluate whether chronic deficiency of pancreatic glucagon in patients with diabetes secondary to total pancreatectomy (PX) is responsible for the commonly observed increase in blood concentrations of gluconeogenic precursors (alanine, lactate, and pyruvate). Seven PX patients were studied on two different occasions: 1) after an overnight insulin infusion (0.15 mU/kg.min) and 2) after an overnight insulin/glucagon infusion (2 ng/kg.min). Five type 1 diabetic individuals were also studied after a similar overnight insulin infusion. In the morning of each study day, [6-3H]glucose and [1-14C]glucose were rapidly injected for determination of total glucose turnover rate [( 6-3H]glucose) and glucose recycling (difference between [6-3H]glucose and [1-14C]glucose turnover rate). Basal concentrations of hormones, glucose, and intermediary metabolites were measured. After overnight insulin infusion, plasma glucose concentration (3.8 +/- 0.4 vs. 6.8 +/- 1.4 mmol/L), turnover rate (8.4 +/- 1.0 vs. 13.7 +/- 1.9 mumol/kg.min), and percent glucose recycling (5.6 +/- 3.9% vs. 19.0 +/- 3.8%) were significantly lower in PX patients than in type 1 diabetic individuals (P less than 0.05-0.01). On the contrary, blood alanine (459 +/- 93 vs. 263 +/- 28 mumol/L), lactate (1157 +/- 109 vs. 818 +/- 116 mumol/L), and pyruvate (71 +/- 8 vs. 42 +/- 3 mumol/L) were significantly higher than those values in type 1 diabetic patients (P less than 0.05-0.01). Insulin/glucagon infusion increased plasma glucose concentration (8.7 +/- 1.5 mmol/L), total turnover (18.1 +/- 1.7 mumol/kg.min), and percent recycling (20.4 +/- 6.6%) to values similar to those in type 1 diabetic subjects. The change in glucose metabolism was associated with a significant drop in blood concentrations of alanine (179 +/- 24 mumol/L), lactate (611 +/- 25 mumol/L), and pyruvate (30 +/- 3 mumol/L; all P less than 0.05-0.01 vs. insulin infusion alone). In PX patients, the glucose turnover rate was inversely correlated with blood concentrations of both alanine (r = 0.67) and lactate (r = 0.71; P less than 0.01). In conclusion, chronic deficiency of pancreatic glucagon in PX patients 1) is associated with a decreased rate of glucose turnover, 2) causes a marked impairment in glucose recycling (an index of the activity of hepatic gluconeogenesis), and 3) increases blood concentrations of alanine, lactate, and pyruvate. All abnormalities are reversed by glucagon.