Diagnosis of fat absorption with 14C-tripalmitate/3H-palmitic acid.

In 44 normal subjects, in 89 patients with chronic pancreatitis, of whom 23 had elevated faecal fat, and in 19 patients with various diseases of the small gut investigations with 14C-tripalmitate and 3H-palmitic acid, dissolved in 1.0 g Indian corn oil/kg, were performed. Serum lipid activity of 14C and 3H was measured 4, 6, and 8 h later. Compared with absolute values of triglyceride absorption (percentage dose of 14C-lipid activity/l serum), relative values (14C/3H ratio of the serum lipids) led to a significantly better discrimination between the control group and patients, attributable to a much smaller normal range. Compared with fatty acid absorption, triglyceride absorption was lowered in all cases of pancreatic steatorrhoea, in most cases of chronic pancreatitis, and in some cases of intestinal malabsorption. While the proposed procedure seems to be sensitive and reliable in the detection of maldigestion, a distinction between maldigestion and malabsorption is apparently uncertain.     

Occurrence of Metabolic Osteopathy in Patients with Chronic Pancreatitis

Introduction: Chronic pancreatitis is an inflammatory disease manifested by maldigestion and, in an advanced stage, by malabsorption. The aim of our research was to monitor the occurrence of metabolic osteopathies (osteopenia, osteoporosis and osteomalacia) in patients with chronic pancreatitis. Patients and Methods: The group consisted of 73 patients (17 women and 56 men) in different stages of chronic pancreatitis. In all patients we determined serum concentrations of Ca, P, 25-OH vitamin D, 1,25-(OH)₂ vitamin D, alkaline phosphatase and its bone isoenzyme. Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) in the lumbar spine (U-U) and in the proximal femur. When bone pathology was identified by DXA, we determined the other to exclude other causes of secondary osteopathy and the 24-hour loss of calcium and phosphorus in the urine. Results: Osteopathy was found in 39% of patients, i.e. osteopenia in 26%, osteoporosis in 5% and osteomalacia in 8% of cases. Conclusion: The occurrence of relatively high percentages of metabolic osteopathies in patients with chronic pancreatitis may correlate, namely in advanced stages of the disease, with the malabsorption of vitamin D to the enterohepatic circulation. In initial forms of pancreatitis, it is not possible to exclude pro- gression of osteopathy due to changes of the intestinal flora, with disturbance of vitamin D absorption to the intestinal mucosa.     

Fecal triglyceride excretion is not excessive in pancreatic insufficiency

Steatorrhea can result from maldigestion or malabsorption. As the pathophysiology underlying impaired digestion differs from impaired absorption, it is important to differentiate these two disorders. It is generally accepted that patients with maldigestion excrete an excessive amount of triglyceride and patients with malabsorption excrete an excess of the lipolytic product of triglyceride, fatty acid. The two-step Sudan stain has been used as a simple test to differentiate these disorders. The validity of the test has not yet been established. In this study, fecal fatty acid and triglyceride were measured after extraction and thin-layer chromatographic separation. Our results indicate that in adult patients with pancreatic insufficiency, the fecal triglyceride content does not differ from the controls. However, a fivefold to sixfold increase in fecal fatty acid content in patients with pancreatic insufficiency was revealed. As patients with maldigestion do not excrete an excess of undigested triglyceride, it is not possible to differentiate maldigestion from malabsorption by quantifying fecal triglyceride and fatty acid.     

Hypertriglyceridaemia and abnormalities of triglyceride catabolism persisting after pancreatitis

Thirty-three patients referred consecutively following an attack of pancreatitis at least six weeks earlier (acute pancreatitis in 10 patients and chronic pancreatitis in 23 patients) had an intravenous fat tolerance test to determine their capacity to catabolise circulating triglycerides. Hypertriglyceridaemia was present in 14 patients (42%), including 5 with acute pancreatitis and 9 with chronic pancreatitis. the highest serum triglyceride level was 6.2 mmol/l and none of the patients had chylomicronaemia at the time of examination. Four of the patients with hypertriglyceridaemia had impaired triglyceride clearance (29% of those with hypertriglyceridaemia, representing 12% of the patients as a whole). These four patients were indistinguishable from the others with hypertriglyceridaemia on clinical or routine biochemical grounds. Although triglyceride clearance in the other 10 patients with hypertriglyceridaemia was lower on average (P<0.04) than in the subgroup of patients with normal levels of serum triglycerides, the clearance values were within the normal range and did not correlate with the serum triglyceride levels. We conclude that an intravenous lipid tolerance test is a useful means of identifying patients with a defect in triglyceride catabolism, who might be vulnerable to a further attack of pancreatitis due to massive hypertriglyceridaemia in certain circumstances. In the majority of patients found to have hypertriglyceridaemia after an attack, the serum lipid disturbance is unlikely to be the direct cause of the attack, but may be an epiphenomenon of some process that is linked to acute and chronic pancreatitis.     

Chronic pancreatitis

Opinion statement Management of chronic pancreatitis is a difficult endeavor for the clinician due to a variety of reasons. These include the variable presentation of symptoms such as chronic pain, recurrent pain, pain associated with malabsorption due to maldigestion, or even maldigestion alone in 15% of patients. It is paramount that the clinician and patient devise appropriate treatment based on prevailing symptoms, and anatomical/functional alterations in the pancreas. Concentrating on symptoms allows the best opportunity to improve the patient’s quality of life. Having an understanding of the patient’s anatomical and functional derangement will assist the clinician in targeting treatment particular to the individual. Awareness of complications associated with chronic pancreatitis is important to allow detection and treatment as they are encountered. Treatment of chronic pancreatitis involves a stepwise approach. Treatment options that are the least invasive and are proven to work should be tried first, and if they are unsuccessful, appropriate alternative treatments can be employed. First-line therapy involves analgesics, non-narcotic and narcotic, in conjunction with pancreatic enzymes. For the pain-predominant cases, this includes nonenteric-coated enzyme supplements. For the individual with maldigestion as the predominant symptom, this includes entericcoated enzyme supplements. This initial trial should be continued for 3 to 6 months. If this fails to provide adequate improvement, then individualized treatment should involve surgical options and if appropriate in specific instances, endoscopic approaches.     

Assimilation of Wheat Starch in Patients with Chronic Pancreatitis Positive Effect of Enzyme Replacement

Pancreatic insufficiency due to chronic pancreatitis may lead to symptomatic malabsorption of both starch and fat. The absorption capacity of wheat starch has not been studied previously in patients with chronic pancreatitis, although this carbohydrate is a quantitatively important component of the Western diet. We studied the absorption of wheat starch and the effect of pancreatic enzyme substitution in seven patients with chronic pancreatitis and steathorrea. The malabsorption was determined from hydrogen breath tests with lactulose standards as reference. Without enzyme substitution, wheat starch (50 g) was absorbed to a lesser extent than in healthy controls (p < 0.05). The mouth-to-cecum transit time was prolonged and correlated positively to the fat excretion before substitution with pancreatic enzymes (s` = 1). The enzyme substitution increased the absorption of wheat starch to values seen in healthy controls (p < 0.05) and reduced the mouth-to-cecum transit time by 19.8%.     

Diagnosis of lipid malabsorption in patients with chronic pancreatitis: a new indirect test using postprandial plasma apolipoprotein B-48

OBJECTIVE: This study was done to evaluate a new test for fat malabsorption caused by chronic pancreatitis. Postprandial plasma apolipoprotein B-48 was measured as an indicator of the intestinal assimilation of exogenous lipid. METHODS: Twenty-three patients with chronic pancreatitis, including 19 insulin-treated diabetic patients, were compared with 14 healthy subjects and seven type-1 diabetic patients. Each was given a test meal containing 40 g lipid; the triglyceride apolipoprotein B-48 concentrations in chylomicrons were determined 240 min later. RESULTS: The postprandial chylomicron apolipoprotein B-48 concentrations in the three groups were statistically different at 240 min: pancreatitis versus controls, p < 0.01, and pancreatitis versus type-1 diabetes subjects, p < 0.01. The delta plasma apo B-48, the change in apolipoprotein B-48 between 0 and 240 min, was significantly smaller in chronic pancreatitis patients than in controls (p < 0.001) and type-1 diabetes subjects (p < 0.001). The sensitivity of the test was better than 89% for a delta apo B-48 threshold value of 0.42 mg/dl. CONCLUSIONS: This new indirect test is relatively simple to use and could be practical for evaluating exogenous lipid malabsorption due to chronic pancreatitis.     

A study of malabsorption in pancreatic cancer

The type, incidence, and severity of malabsorption in patients with pancreatic cancer were investigated. The following absorption tests were performed; pancreatic function diagnostant (PFD) test, measurement of serum carotene levels, and 5 gd-xylose absorption test. Rates of abnormality in the tests were 75.7% of 37, 54.2% of 48, and 54% of 50 patients with pancreatic cancer, respectively. In particular, a marked decrease of values in the xylose absorption test was characteristic and more often recognized in patients with carcinoma of the pancreas with occlusion of the superior mesenteric vein. The presence of malabsorption (disturbed transport through the portal vein), in addition to maldigestion of nutrients, is suggested to induce severe malnutrition in patients with pancreatic cancer.     

Pancreatic enzyme replacement therapy

The relative efficacy of three commercial pancreatic enzyme supplements in improving fat absorption was studied using the [¹⁴C]triolein breath test in 12 patients with chronic pancreatitis. Two of the supplements were enteric coated. The one nonenteric coated product was studied twice: with and without ranitidine coadministration. Doses complied with the manufacturers recommendations. Baseline studies included pentagastrinstimulated gastric acids, 72-hr fecal fat excretion, and [¹⁴C]triolein absorption while not on supplementation. Acid outputs were variable (BAO: 0.3–4.1 meq/hr; MAO: 3.5–34.6 meq/hr). Three patients had mild steatorrhea (i.e., <10 g/day) and the remaining severe fat malabsorption (56.9±41.5 g/day). Although fat absorption was significantly improved by all three supplements, the nonenteric coated preparation was most effective (P< 0.001). However, laboratory analysis demonstrated that lipase content was four times greater, ie, 17,000 IU/4 tablets. Pretreatment with ranitidine failed to further improve the absorption in patients given nonenteric supplements but was effective in those found to have high or normal acid outputs (P<0.001). Our results suggest that the recommended dosage of enteric coated preparations is insufficient for adult patients with severe chronic pancreatitis. Secondly, the marked variability of acid secretion in such patients possibly accounts for the variability of results obtained by others on the usefulness of coadministration of antacids and H₂ antagonists. Routine measurement of gastric acid secretion status may help optimize the choice and form of pancreatic enzyme supplementation.     

Fructose and Sorbitol Malabsorption in Ambulatory Patients with Functional Dyspepsia Comparison with Lactose Maldigestion/Malabsorption

The aim of this study was to study sugarmaldigestion/malabsorption in patients with functionaldyspepsia using H breath testing. End-expiratory breathH after separate 2 challenges with lactose (25 g), fructose (25 g), and sorbitol (5 g) were usedto determine malabsorption, as well as small boweltransit time (SBTT). Five hundred twenty patients withfunctional dyspepsia received all three challenges. Smaller groups were also tested after lactulose(10 g, N = 36) and glucose (50 g, N = 90) challenges.Fructose and sorbitol were closely linked with respectto absorption and malabsorption status. Only in the case of lactose maldigestion/malabsorption wasthere a greater than random prevalence of malabsorption(P < 0.001) for fructose and sorbitol. In contrast tolactose, ethnic origin did not influence fructose or sorbitol malabsorption, and femalespredominated among fructose and sorbitol malabsorbers.In Jews, the prevalence of lactosemaldigestion/malabsorption decreased in the age group of25-55 and subsequently rose after 55, while fructose and sorbitolmalabsorption decreased progressively with advancingage. With respect to small bowel transit time (SBTT), inthe case of sorbitol and lactulose, it was significantly greater (P < 0.05) than those for fructoseand lactose. Multiple sugar malabsorptions are commonwhen lactose maldigestion/malabsorption ispresent.     

Alterations in plasma levels of apolipoprotein A-IV in various clinical entities

The serum levels of apolipoprotein A-IV (apo A-IV) were measured by rocket immunoelectrophoresis in disease-free humans, at fasting and after oral and intravenous fat administration. The studies were extended to patients with chronic pancreatitis, malabsorption syndrome, to postoperative patients on total parenteral nutrition and to patients with liver diseases, cholestasis, diabetes mellitus and chronic renal failure. Oral fat ingestion resulted in an increase of apo A-IV levels which remained elevated even when the postprandial hypertriglyceridemia had disappeared. A transient increase in apo A-IV levels was observed after intravenous fat infusion but the level declined simultaneously with decreases in triglyceride levels. Levels of serum apo A-IV were decreased under conditions where decreased fat intake or malabsorption of nutrients might have been present, such as in patients with chronic pancreatitis, malabsorption syndrome, acute hepatitis in the early stage, obstructive jaundice and in postoperative patients on total parenteral nutrition. On the other hand, the apo A-IV levels were high in patients with chronic renal failure and in those with diabetes mellitus and proteinuria.     

Serum radioactivity of 14C-triolein and 3H-oleic acid ingested in a test meal:a rapid test of pancreatic exocrine insufficiency.

A double-tracer technique to estimate lipid digestion was investigated. 3H-labelled oleic acid and 14C-labelled triolein were ingested in a test meal. The serum radioactivity of 3H after ingestion of labelled oleic acid depends on absorption and metabolism of free fatty acids, while serum radioactivity of 14C from triolein, in addition to the former, depends on triglycerol digestion. This study shows that the ratio between 3H and 14C 2h after the test meal gives a good qualitative and quantitative estimation of lipid digestion: the 3H/14C ratio in patients with maldigestion is significantly higher than for normals (P less than 0.01), the predictive value of the 3H/14C ratio in the diagnosis of maldigestion is high, that of a positive result being 1.0 and that of a negative 0.93, and quantitatively the 3H/14C ratio shows a highly significant correlation with faecal fat (P less than 0.001). The test is very easy to perform, lasts for only 2 h, and is without discomfort to the patient or nursing and laboratory staff. It gives information like or superior to that of faecal fat measurement.     

Assimilation of wheat starch in patients with chronic pancreatitis. Positive effect of enzyme replacement.

Pancreatic insufficiency due to chronic pancreatitis may lead to symptomatic malabsorption of both starch and fat. The absorption capacity of wheat starch has not been studied previously in patients with chronic pancreatitis, although this carbohydrate is a quantitatively important component of the Western diet. We studied the absorption of wheat starch and the effect of pancreatic enzyme substitution in seven patients with chronic pancreatitis and steathorrea. The malabsorption was determined from hydrogen breath tests with lactulose standards as reference. Without enzyme substitution, wheat starch (50 g) was absorbed to a lesser extent than in healthy controls (p less than 0.05). The mouth-to-cecum transit time was prolonged and correlated positively to the fat excretion before substitution with pancreatic enzymes (sigma = 1). The enzyme substitution increased the absorption of wheat starch to values seen in healthy controls (p less than 0.05) and reduced the mouth-to-cecum transit time by 19.8%.     

Intestinal absorption of phosphatidylcholine and triglyceride after ileal resection

The intestinal absorption of (14C)oleoyl moieties in triglyceride and phospholipid was investigated by means of (14C)phosphatidylcholine and (14C)triolein breath tests. In patients who had undergone ileal resection the absorption of both phosphatidylcholine and triglyceride was subnormal, as reflected by a lower production of 14CO2. In healthy subjects the production of expiratory 14CO2 after oral administration of (14C)phosphatidylcholine was slightly higher than after administration of (14C)triolein. This was also observed in the patient group, indicating that the absorption of both triglyceride and phospholipid was decreased to similar extents, although triglyceride absorption tended to be more affected after major ileal resection. In patients with lipid malabsorption the proportion of linoleic acid in serum phosphatidylcholine was subnormal, and the decrease was correlated to the decrease in lipid absorption. The concentration in serum of selenium, alpha-tocopherol, and carotene but not of ascorbic acid and retinol was subnormal after ileal resection.     

Helicobacter pylori infection and food-cobalamin malabsorption

Two entities of considerable recent interest,Helicobacter pylori infection of the stomach and food-cobalamin malabsorption, are each intimately associated with gastric abnormalities. A possible connection between the two entities thus suggested itself and prompted us to study 98 subjects with low serum cobalamin levels but normal Schilling test results and 17 controls with normal cobalamin levels. Food-cobalamin absorption was measured with the egg yolk-cobalamin absorption test (EYCAT) and was abnormal in 56 of the 115 subjects. IgG antibody toH. pylori was found in 78% of the 27 patients with severe food-cobalamin malabsorption (EYCAT <1.0% excretion), compared with only 45% of 29 subjects with mild malabsorption (EYCAT 1.0–1.99%) and 42% of 59 subjects with normal absorption (EYCAT 2.0%) (x²=9.52,P<0.01). Antibody-positive patients had lower EYCAT excretion values than those without antibody (2.03±1.83% vs 3.11±2.13%,t=2.913,P=0.005). While Hispanic patients tended to malabsorb food cobalamin more frequently than did white or black patients, and men were more often antibody-positive than women, race, sex, or age characteristics were not responsible for the significant association between serologic evidence ofH. pylori infection and severe malabsorption of food cobalamin. The association that we describe suggests that gastritis induced byH. pylori predisposes to a more severe form of food-cobalamin malabsorption, among its other effects on gastric status.This study was supported by grant DK-32640 from the National Institutes of Health, by the NIH National Center for Research Resources of the General Clinical Research Centers grant MO1 RR-43, by the Medical Research Service of the Department of Veterans Affairs, and by the Procter & Gamble Company.     

Overview and diagnosis of malabsorption syndrome

"Malabsorption" syndrome is the term widely used to describe the end result of either impaired breakdown of nutrients (maldigestion) or defective mucosal uptake and transport of adequately digested nutrients (true malabsorption). The latter may affect a broad range of nutrients (ie, panmalabsorption) or individual nutrients or groups of nutrients (ie, specific malabsorption). This review discusses the etiology and pathophysiology of malabsorption. A diagnostic approach to malabsorption is proposed. Other articles review specific disorders such as celiac disease, bacterial overgrowth, and chronic pancreatitis.     

Determinants of Accelerated Small Intestinal Transit in Alcohol-Related Chronic Pancreatitis

Patients with chronic pancreatitis may have abnormal gastrointestinal transit, but the factors underlying these abnormalities are poorly understood. Gastrointestinal transit was assessed, in 40 male outpatients with alcohol-related chronic pancreatitis and 18 controls, by scintigraphy after a liquid meal labeled with ^99mtechnetium-phytate. Blood and urinary glucose, fecal fat excretion, nutritional status, and cardiovascular autonomic function were determined in all patients. The influence of diabetes mellitus, malabsorption, malnutrition, and autonomic neuropathy on abnormal gastrointestinal transit was assessed by univariate analysis and Bayesian multiple regression analysis. Accelerated gastrointestinal transit was found in 11 patients who showed abnormally rapid arrival of the meal marker to the cecum. Univariate and Bayesian analysis showed that diabetes mellitus and autonomic neuropathy had significant influences on rapid transit, which was not associated with either malabsorption or malnutrition. In conclusion, rapid gastrointestinal transit in patients with alcohol-related chronic pancreatitis is related to diabetes mellitus and autonomic neuropathy.     

Plasma apolipoprotein A-IV levels decrease in patients with chronic pancreatitis and malabsorption syndrome

An immunochemical method was developed for measurements of serum levels of apolipoprotein A-IV (apo A-IV). Using this technique, we found decreased levels of apo A-IV in patients with chronic pancreatitis and malabsorption syndrome and these low levels of apo A-IV in a patient with malabsorption syndrome were overcome after appropriate oral nutrition. Thus, measurements of apo A-IV may provide a good index for the assessment of fat intake and absorption.     

The serum 14C-triolein/3H-oleic acid assimilation test for differential diagnosis of maldigestion and malabsorption

In 125 consecutive patients the measurement of serum radioactivities after simultaneous ingestion of 14C-triolein and 3H-oleic acid was investigated as a test of lipid assimilation. The sum of the 2-h and 4-h concentrations of 14C in serum (se(2 + 4)14C) was most useful as an index of lipid assimilation, and the 2-h serum 3H/14C ratio (se-3H/14C) reflected lipid digestion. Normal values were se(2 + 4)14C greater than or equal to 1.0% of the dose ingested per litre serum and se-3H/14C less than 1.3. Se(2 + 4)14C correlated significantly with faecal fat (r = -0.56, P less than 0.001) and indicated malassimilation in 26 of the 50 patients with a faecal fat excretion greater than 7 g/day. False-negative values appeared mainly in the patients with moderate steatorrhoea and gastrointestinal anastomoses. Only one false-positive se(2 + 4)14C value was found. Se-3H/14C was abnormal in 24 of the 34 patients with maldigestion with 2 false-positive results. When the results of se(2 + 4)14C and se-3H/14C were combined, the predictive value of the test result 'normal lipid assimilation' was 0.75, that of the test result 'maldigestion' was 0.93, and that of 'malabsorption' was 0.71. It is concluded that the serum 14C-triolein/3H-oleic acid assimilation test is convenient and inexpensive and may be useful when quantitative faecal collections are not available.     

Serum studies in man after administration of vitamin A acetate and vitamin A alcohol: II In subjects suffering from disturbances of absorption and digestion

Vitamin A acetate and vitamin A alcohol, triolein I¹³¹, oleic acid I¹³¹, and fat balance tests have been assessed in studies on cases of coeliac disease, pancreatic insufficiency, and some disorders of the small intestinal wall.

In coeliac disease a very low serum carotene and flat vitamin A absorption curves have been noted. The contrast between vitamin A acetate and alcohol curves has been clearly shown in cases of pancreatic disorder showing maldigestion. The correlation between vitamin A and triolein I¹³¹ absorption (0·89) is closer than that between vitamin A and fat balance.

In assessing intestinal absorption serum carotene figures are of value only if very low figures are found.