Koji Machida

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.

Serum fatty acid composition in normal Japanese and its relationship with dietary fish and vegetable oil contents and blood lipid levels

A survey was conducted on 110 normal Japanese adults (55 men and 55 women) to determine their caloric intake, dietary fat content and its origin (animal, plant, or marine). In addition, their blood lipid levels and fatty acid compositions were examined. Men in their 30s-50s consumed 2,600-2,800 calories and 60 g of fats, while women in the same age range consumed 2,000-2,200 calories and 52-58 g of fats. In both sexes, caloric, fat, and cholesterol intakes were lower for those in their 60s but protein and crude fiber consumption remained generally unchanged. When the dietary fats were classified according to origin, men and women in their 30s were found to consume less oil of marine origin. This appeared to be the result of a western style diet for Japanese adults in their 30s. Compared with men, women exhibited lower blood lipid levels. As age increased, the total cholesterol level of the blood rose in women. Thus the blood lipid level was generally equal in the two groups in their 60s. There was a positive correlation between the blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels and dietary consumption of fish oil. The marine/plant lipid ratio was positively correlated with the blood EPA/arachidonic acid ratio. Therefore, it was believed that the origin of the dietary fats consumed is a factor in determining the blood fatty acid profile. The linoleic acid (18:2), arachidonic acid (20:4), and 18:2 + 20:4 contents were negatively correlated to the total cholesterol level in the blood but positively correlated to the HDL-cholesterol level. Polyunsaturated fatty acids (18:2 + 20:4 + 20:5 + 22:6) were negatively correlated with the blood triglyceride level. From the findings presented above, we concluded that dietary fats not derived from animal sources should be classified into fish and vegetable oils to evaluate their dietary significance. We also noted that Japanese in their 30s consume less fish oil, indicating the western trend in their dietary lipid consumption.

Dietary analysis of Japanese patients with chronic pancreatitis in stable conditions

In order to examine the malnutritional condition of outpatients with pancreatitis, a dietary investigation was conducted in Japanese patients with chronic pancreatitis (n=38) and healthy subjects (n=35) of the same age for 3–7 consecutive days, and the characteristics of their food intake were examined. The patients with pancreatitis took in less calories, fat, carbohydrate, and protein than the healthy subjects, by 900 kcal, 20g, 150g, and 20 g, respectively. On the other hand, the fat energy ratio in the patients was 20%, similar to that in the healthy subjects. Also, when the fat intake was classified according to origin, i.e., animal, marine, or plant, the proportions for animal (g) and plant (g) were low, while marine fat accounted for a significantly higher percentage than in the healthy subjects. The intake of cholesterol and Ca in the patients was significantly smaller than that in the healthy subjects, but no significant difference was observed in the intake per body weight of proteins and Ca. It seems, possible that the low calorie, low protein, low fat, and low carbohydrate intake may be factors in the malnutritional condition of the patients with chronic pancreatitis. Analysis of covariance and principal component analysis showed that the body weight of the patients was closely correlated with decreases of caloric intake and intake of carbohydrate. The above results revealed that low body weight in patients with chronic pancreatitis was closely related to the decrease of calorie and carbohydrate intake, in addition to maldigestion and malabosorption of nutrients.

Effect of omeprazole on changes in gastric and upper small intestine pH levels in patients with chronic pancreatitis

Gastric and upper small intestine pH levels were measured continuously over 24 hours in patients with chronic pancreatitis, and values obtained before and after the administration of omeprazole were compared. Additionally, omeprazole was administered for 2 weeks and the fecal excretion of fat was compared before and after drug therapy. Postprandial gastric pH levels, initially 2.9 to 3.2, increased by 1.6 to 2.1 after treatment. Postprandial upper small intestine pH levels, initially 5.1 to 5.5, increased by 0.7 to 1.0. The lowest pH value of the upper small intestine was 2.2 to 2.4 postprandially; this was increased by > 1.0 after omeprazole, and the amplitude of pH variation was reduced. The cumulative proportions of intraintestinal pH strata of < or = 3, < or = 4, or < or = 5, and higher, initially being 16.4% to 17.1%, 27.4% to 31.7%, and 52.6% to 57.8%, respectively, were remarkably improved after drug treatment. Gastric pH and upper small intestine pH levels showed a positive correlation; an increase in gastric pH levels by 2 corresponded to an increase in small intestine pH levels by 1. After omeprazole administration, mean fecal excretion of fat was decreased to 4.1 +/- 2.6 g/d (range, 1.1 to 9.8 g/d) from 6.5 +/- 3.9 g/d (range, 1.6 to 13.5 g/d). Decreases in excretion of fat averaged 3.4 g/d (range, 2.2 to 4.5 g/d) in patients with steatorrhea. It was concluded that steatorrhea due to chronic pancreatitis can be improved to some extent by improving upper small intestine pH levels following the elevation of gastric pH levels after administration of omeprazole.

Bile acid malabsorption as a cause of hypocholesterolemia seen in patients with chronic pancreatitis

SummaryA determination of caloric consumption based on a dietary survey table, fat and cholesterol intake, and analyses of fecal fatty acids and neutral sterols, and bile acid analysis (gas chromatographic method) were conducted on 33 subjects (including 17 patients with chronic pancreatitis and 16 normal controls). The factors related to hypocholesterolemia in chronic pancreatitis (CP) patients were investigated and the following conclusions were obtained: (1) The total caloric intake and fat consumption by the CP patients were significantly lower with the exception of cholesterol consumption. (2) Significant increases were noted in fecals fat, neutral sterols, and bile acid excretion by the CP patients. (3) A significant positive correlation was noted between the total cholesterol and body mass index (BMI), reaffirming that the cholesterol level can be used as an indicator of nutritional status. (4) A significant negative correlation was noted between the serum total cholesterol and fecal bile acid excretion. These findings indicate that CP patients suffer from neutral sterol malabsorption, in addition to dietary fat maldigestion and bile acid malabsorption. Furthermore, bile acid malabsorption is cited as a factor in the development of hypocholesterolemia in CP patients.

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.

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.