Yusuke Tandoh

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis

SummaryConclusionPancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled, that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes).BackgroundWe sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis.MethodsUrinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied.ResultsThe urinary CPR excetion in controls was 94.9±20.5 μg/d. The urinary CPR excretion in calcific pancreatitis was 12.8±7.4 μg/d and it resembled that in IDDM (9.4±5.8 μg/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5±30.1 μg/d, being similar to that in NIDDM (49.3±21.0 μg/d).The plasma glucagon level in calcific pancreatitis was 64.1±15.9 ρg/mL, which was significantly lower than the values in IDDM (111.2±50.2 ρg/mL) and NIDDM (96.7±21.9 ρg/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4±29.6 ρg/mL) were significantly lower than that in controls (12.9±21.6 ρg/mL).The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.

Changes in plasma fatty acid profile in Japanese patients with chronic pancreatitis.

The serum zinc, prealbumin, retinol-binding protein and carotene concentrations and the plasma fatty acid composition were determined to assess the nutritional condition of 24 patients with chronic pancreatitis compared with that of 20 healthy controls. The daily food intake and faecal fat excretion of the two groups were also measured. In the chronic pancreatitis group, the calorie and fat intakes were significantly lower than those of the controls. Serum levels of zinc, prealbumin and carotene were also significantly lower than those of the controls. Percentages of plasma linoleic and arachidonic acids were low, while percentages of palmitoleic acid, eicosapentaenoic acid and docosahexaenoic acid were high. Fish oil intake correlated negatively with plasma linoleic acid concentration (P < 0.05). The above results indicate that the relatively high intake of fish oil and the relatively low intake of dietary fat in Japanese patients with chronic pancreatitis with a mild degree of steatorrhoea results in an abnormally low plasma level of linoleic acid.

Faecal lipid excretion levels in normal Japanese females on an unrestricted diet and a fat-restricted diet measured by simultaneous analysis of faecal lipids

Faecal lipid excretion was determined in 16 females on an unrestricted diet and on a fat-restricted diet using a chromatographic method for the simultaneous analysis of faecal lipids. The fat-restricted diet reduced the total quantity of faeces and the amounts of fatty acids, neutral sterols and bile acids excreted were almost halved compared with when on an unrestricted diet. This indicates that dietary fat, fibre and cholesterol affect the amount of faecal bile acid, neutral sterol and fatty acid excretion. The amount of cholesterol/animal sterols excreted and the percentage of primary bile acids were, however, similar for both the fat-restricted and unrestricted diets.

Effects of high-lipase pancreatin on fecal fat, neutral sterol, bile acid, and short-chain fatty acid excretion in patients with pancreatic insufficiency resulting from chronic pancreatitis

SummaryConclusionsSteatorrhea was almost completely stopped and malabsorption of neutral sterols and shortchain fatty acids was reduced by treatment of high-lipase pancreatin in Japanese patients with pancreatic insufficiency whose dietary fat consumption is low.MethodsFifteen patients with chronic pancreatitis complicated by steatorrhea who consumed an average of 48 g of dietary fats a day were selected as subjects and given 3 g of high-lipase pancreatin (lipase, 379,800 USP U/g), at each meal (total daily dose is 9 g) for a mean duration of 28.5 d. Fecal output and fecal fat neutral sterol, bile acid, and short-chain fatty acid excretion were determined before and after the course of pancreatin therapy.ResultsPancreatin administration resulted in significant reductions (P<0.01) in fecal output (from 243.2 to 149.1 g), excretion of fecal fat, (from 12.3 to 3.9 g), animal sterols (from 816.3 to 604.6 mg), and shortchain fatty acids (from 52.6 to 18.5 mM). In contrast, no marked changes were recorded in fecal excretion of β-sitosterol (a plant sterol), bile acids, or the hydroxy fatty acid fraction. Fecal fat and short-chain fatty-acid excretion showed strong correlations with fecal output.

No negative feedback regulation between plasma CCK levels and luminal tryptic activities in patients with pancreatic insufficiency

SummaryThe study was conducted on five healthy subjects and six patients with calcifying pancreatitis (CP) and steatorrhea. Following overnight fasting, one tube each was placed in the stomach and the upper part of the small intestine, respectively. Through the gastric tube, a test meal that included 30 g of fat (total calories, 625 kcal, 500 mL) was infused over a span of 30 min. Every 30 min (up to 150 min), fluid samples in the upper small intestine were collected and chilled, and the amylase, trypsin, and lipase levels were determined. In addition, in the case of the CP patients, a high-potency pancreatin preparation was infused into the stomach together with the test meal. In order to determine the plasma CCK level, blood sample were collected before test meal infusion and at 10, 20, 30, 45, 60, 90, 120, and 150 min subsequent to infusion. The plasma CCK was extracted using a Sep-Pak C-18 cartridge and analyzed with radioimmunoassay using an OAL-656 antibody. The result was converted to the CCK-8 level and expressed in pg/mL. The enzyme activities in the upper small intestine of the CP patients after test meal administration amounted to 22.8 (amylase), 10.8 (trypsin), and 16.9% (lipase) compared with the corresponding figures for the normal subjects. Following administration of a high-potency pancreatin in patients with CP, enzyme activities in the upper small intestine increased to 132.2 (amylase), 38.7 (trypsin), and 45.3% (lipase) compared with levels in the normal subjects. However, the healthy subjects and the CP patients, both with and without treatment with supplementary exogenous enzymes, all exhibited similar profiles in the plasma CCK response to stimuli. Based on these findings, we concluded that a negative feedback mechanism does not exist between the tryptic activity of the upper small intestine and the CCK secretory response in patients with chronic pancreatitis.

Effects of FL-386 on Faecal Lipid Excretion in Humans

A newly synthesized inhibitor of pancreatic lipase and micelle formation, FL-386, was administered at a dose of 400 mg (in the diet, for seven consecutive days) to nine healthy adult volunteers, and changes in faecal mass, frequency of defaecation, and properties of the stools were observed. High performance liquid chromatography and gas-liquid chromatography were used to analyse the faeces for short-chain carboxylic acids, neutral sterols, bile acids, fats and hydroxyfatty acids. FL-386 had little effect on the amounts and composition of short-chain carboxylic acids, neutral sterols, and bile acids excreted, nor did it produce changes in the composition of fatty acids, or the percentages of hydroxyfatty acids in the stool. However, in those patients treated with FL-386, the faecal mass was increased, and stools were softer and contained increased amounts of fatty acids. The compound did not produce particularly fatty stools. It was concluded that FL-386 induces slight disturbance in the digestion and absorption of dietary lipids.

Effects of Pancreatic Digestive Enzymes, Sodium Bicarbonate, and a Proton Pump Inhibitor on Steatorrhoea Caused by Pancreatic Diseases

Forty-five patients with pancreatic steatorrhoea (27 with calcified pancreatitis, 13 with non-calcified pancreatitis, two with pancreaticoduodenectomy, one with total pancreatectomy, and two with pancreatic cancer) were divided into four groups and given the following medication for 2 to 4 weeks: 4 to 6 g/day of sodium bicarbonate (group I); 9 g/day of high-lipase pancreatin (lipase, 56 600 U/g, Fédération Internationale Pharmaceutique (FIP); group II); 12 to 24 tablets or 9.0 g of commercial pancreatic enzyme preparations (group III); or 50 mg of omeprazole (group IV). Faecal fat excretion was evaluated before and after drug administration. Faecal fat excretion was reduced by 2.9 g (range, 1.7 to 5.0 g) in group I; 8.8 g (range, 2.9 to 39.9 g) in group II; 10.8 g (range, 2.3 to 21.8 g) in group III; and 4.3 g (range, 3.6 to 5.6 g) in group IV. The pancreatic digestive enzyme preparation was more effective than sodium bicarbonate and agents that raise the pH of the upper small intestine (such as proton-pump inhibitors) in reducing faecal fat excretion. The results indicate that all of the preparations used are effective against mild pancreatic steatorrhoea. If the condition is more advanced, however, a massive dosage of pancreatic digestive enzyme and possibly the combined use of an agent to raise the pH of the upper small intestine are likely to be effective.