Ken-ichi Imamura

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.

Correlation between bile acid malabsorption and pancreatic exocrine dysfunction in patients with chronic pancreatitis.

Fecal bile acid and fecal fat were determined in 18 normal subjects and 22 patients with chronic pancreatitis, and the relation of fecal bile acid excretion to exocrine pancreatic dysfunction was studied. In chronic pancreatitis fecal bile acid was approximately three times that of control subjects, and large amounts of primary bile acid were detected. A significant correlation between fecal bile acid excretion and bicarbonate secreted from the pancreas was found. This evidence of bile acid malabsorption was not observed until bicarbonate output was ∼0.05 mEq/h/kg. A slight correlation between fecal bile acid and absorption rates of fat was demonstrated. These results suggest that bile acid malabsorption observed in chronic pancreatitis is related to an impairment of pancreatic bicarbonate secretion.

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.

Faecal triglycerides and fatty acids in the differential diagnosis of pancreatic insufficiency and intestinal malabsorption in patients with low fat intakes.

To investigate possible parameters for the differential diagnosis of steatorrhoea in patients with low fat intakes, faecal specimens were analysed from 15 patients with steatorrhoea due to chronic pancreatitis and seven patients with steatorrhoea due to intestinal malabsorption. The fat intakes of the patients ranged from 30.1 to 60 g, less than the average in American and European patients. The group with pancreatic steatorrhoea showed a significantly lower faecal output than the group with intestinal steatorrhoea but the two groups did not differ significantly in their total faecal fat excretion or concentration. The percentage triglycerides and the molecular ratio of triglycerides to fatty acids in the faeces were significantly higher (P < 0.01) in the group with pancreatic steatorrhoea than in those with intestinal steatorrhoea. The molecular percentage ratio of triglycerides to fatty acids was 6.8 ± 2.2 for the chronic pancreatitis group and 2.4 ± 1.0 for the intestinal malabsorption group; while the respective faecal hydroxy fatty acid contents were 3.1 ± 3.6% and 10.1 ± 3.3% (means ± SDs). These latter two parameters appeared to be the most valuable for distinguishing the two forms of steatorrhoea.

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.

Study on Pancreatic Insufficiency (Chronic Pancreatitis) and Steatorrhea in Japanese Patients with Low Fat Intake

The incidence of steatorrhea is said to be lower and its grade milder in Japanese because their fat intake is lower than that of Europeans and Americans. Failure to take this into account creates difficulties when attempting to compare data on pancreatic exocrine insufficiency in different countries. The authors examined the incidence and grade of steatorrhea in Japanese chronic pancreatitis (CP) patients whose daily fat intake was <40 g (25 patients) or ≥40 g (35 patients). In addition, 23 CP patients with steatorrhea and daily fecal fat excretion ≥5 g were given a pancreatic enzyme preparation at a dose 3–8 times higher than the usual dose to investigate its effect on fecal fat excretion. Among CP patients whose fat intake was <40 g, the incidence of fecal fat excretion <5 g was 56% and that of fecal fat excretion ≥10 g (severe steatorrhea) was 8%. In CP patients whose fat intake was ≥40 g, the incidences were 27.9 and 34.9%, respecetively; a significant increase in the number of affected patients was noted when fat intake was ≥40 g. The fat absorption rate was 76.2% among patients whose fat intake was <40 g and 77.8% among patients whose fat intake was ≥40 g, revealing no significant difference between the two groups. The proportion of CP patients whose fat absorption rate ≦80% was 32% at a fat intake <40 g and 39% at a fat intake ≥40 g, revealing no significant difference between the two groups.

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.