Coefficient Of Fat Absorption Research Articles

Long-term evaluation of faecal calprotectin levels in a European cohort of children with cystic fibrosis

ObjectiveIntestinal inflammation with contradictory data on faecal calprotectin (fCP) levels is documented in patients with cystic fibrosis (CF). The aim of this study was to longitudinally evaluate fCP in a...

Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis.

The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption. We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase. The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase. The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.

How macronutrients and pancreatic enzyme supplements dose variability affect fat, protein and starch absorption in children with cystic fibrosis.

low evidence on the dose of enzymatic supplements used in pancreatic enzyme replacement therapy (PERT) is available. assessing if fat, protein and starch absorption could be related to the dose of the enzymatic supplement, the intra-patient variability in the dose and macronutrient intake. Four-day food records and 3-day faecal samples were prospectively collected in 69 children with cystic fibrosis. Pearson correlations between enzyme dose and macronutrient absorption, and beta regression models were applied to explain the results. the supply of protease units per protein intake (PU/g protein) in relation to lipase units per fat intake (LU/g fat) was low and the intra-patient variability in the dose of enzymes was ±1331 LU/g fat. Fat and starch absorption was >90% while for protein it was 81.5%. The coefficient of fat absorption was associated with an interaction between the dose of LU/g fat and its variability among different days. Lipid and protein intake were also determinants of the coefficient of fat absorption. the dose of PERT should be re-adjusted to the amount of dietary fat of every meal (constant LU/g fat) to minimize variability and increase fat absorption. Also, the supply of protease should be increased to prevent from protein malabsorption.

Outcomes and Perioperative Nutritional Management in a Porcine Model of Short Bowel Syndrome.

Short bowel syndrome (SBS) results from significant intestinal loss and is characterized by insufficient absorption of nutrients and fluids. Preclinical large animal SBS models typically require parenteral nutrition (PN) support and may not be appropriate for studying interventions to improve intestinal absorption or adaptation. Here, we describe the development of a porcine SBS model that does not require PN support. Eight male Yorkshire piglets underwent either a 75% or 90% jejunoileal resection (n=5) or no resection (n=3). Continuous enteral nutrition (EN) was provided via a gastrostomy tube. The final SBS model consisted of a 75% resection and nutrition provided via combination EN (60%) and per oral pig chow (40%). Body weight and concentration of fat-soluble vitamins were assessed on postoperative days (POD) 7, 14, and 21. For assessing fat malabsorption, the coefficient of fat absorption (CFA) was calculated following a 72-h stool collection. Resected animals had decreased weight gain compared to unresected controls (POD21+8.3% versus +28.8%, P=0.048). Vitamin D concentration was significantly lower in resected animals compared to controls on POD 7, POD 14, and POD 21. Serum vitamin E concentration was also lower on POD 21. Resected animals developed fat malabsorption with lower CFA (76.5% versus 95.3%, P=0.014). We describe the development of a porcine SBS model that does not require PN support. Piglets in this model gain less weight, demonstrate fat malabsorption, and develop fat-soluble vitamin deficiencies. This model will benefit investigations of intestinal absorption or adaptation while potentially decreasing costs and confounding complications related to PN administration.

Impact of Pancreatic Enzymes on Enteral Fat and Nitrogen Absorption in Short Bowel Syndrome.

Patients with short bowel syndrome (SBS) can have a high morbidity rate. To minimize morbidity, enteral autonomy is the primary goal in clinical management of patients with SBS. This is often difficult to achieve because of significant malabsorption. To date, there are limited therapies that improve absorption in patients with SBS. The impact of pancreatic enzyme replacement treatment on enteral absorption has not been studied in this population and was the primary aim of this study. This was an interventional study in 11 subjects (6 pediatric subjects ages 4.0-17.9 years, 5 adult subjects 18-75 years) that compared enteral absorption in each subject before and after pancreatic enzyme medication (Creon). Coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) were used as markers of enteral absorption of fat and protein, respectively. There was no statistically significant mean change in CFA and CNA before and after pancreatic enzyme medication therapy. Six subjects demonstrated an increase in CFA and 8 subjects demonstrated an increase in CNA after the use of pancreatic enzyme medication therapy. There was no statistically significant improvement in enteral fat and protein absorption in the cohort as a whole, though several subjects demonstrated an improvement. These results suggest that some patients with SBS may benefit from treatment with pancreatic enzymes. Further studies are needed to better evaluate the effect of pancreatic enzyme therapy on enteral absorption in subjects with SBS and to characterize factors that may predict a positive response.

Coefficient of Fat Absorption to Measure the Efficacy of Pancreatic Enzyme Replacement Therapy in People With Cystic Fibrosis: Gold Standard or Coal Standard?

ObjectivesWe sought data on the validity, reliability, responsiveness, and feasibility of the coefficient of fat absorption (CFA) as a measure of pancreatic enzyme replacement therapy (PERT) efficacy in people with cystic fibrosis (pwCF) and reviewed the literature for alternative measures.MethodsWe searched PubMed for the Medical Subject Heading cystic fibrosis and the key words cystic fibrosis, fat absorption, CFA, and fecal fat imbalance; historical articles; and citations in bibliographies.ResultsThe lower the CFA, the greater its variability; thus, it is less variable in healthy individuals who have higher CFA than pwCF. In addition, the test-retest values for CFA are more variable in pwCF than the general population. There is no correlation between CFA and body mass index or PERT dose but CFA is related to gastrointestinal signs and symptoms. Research-quality CFA studies are expensive, time consuming, and odious to pwCF and research staff. Sparse stool tests, breath tests, and blood tests of fat absorption have been studied as potential alternatives to CFA to measure PERT efficacy.ConclusionsBased on the evidence, we conclude that CFA as a measure of the efficacy of PERT is more of a “coal standard” than a gold standard; developing suitable alternatives should be a priority.

An in-line digestive cartridge increases enteral fat and vitamin absorption in a porcine model of short bowel syndrome

Short bowel syndrome (SBS) occurs after intestinal loss resulting in parenteral nutrition dependence and micronutrient deficiencies, which may lead to life-limiting complications. ALC-078 is a cartridge containing immobilized lipase that connects in-line with enteral feeding sets and digests fats in enteral nutrition (EN). In this study, we evaluate the efficacy of ALC-078 to improve fat and nutrient absorption in a porcine SBS model. Fifteen male Yorkshire piglets were assessed. Animals were randomized to no intestinal resection (n=5), 75% resection (n=5), or 75% resection+ALC-078 (n=5). After recovery, animals were treated for 14 days. Piglets received 60% of nutrition from continuous EN and 40% from chow. The degree of fat malabsorption was determined by the coefficient of fat absorption (CFA) following a 72-hstool collection. Body weight, fat-soluble vitamins, and nutritional markers were assessed. Adverse events were similar across the three groups (P=1.00). ALC-078-treated animals had similar weight gain compared to resected piglets. Resected animals had a lower CFA compared to unresected controls (79.3% vs. 95.2%, P=0.01) while there was no significant difference in the ALC-078 animals (87.1% vs. 95.2%, P=0.19). Between Study Days 1 and 15, ALC-078 animals had increased concentrations of vitamin D (12.2 vs. 8.7ng/mL, P=0.0006), and vitamin E (4.3 vs. 2.5mg/L, P=0.03). These markers did not significantly change in untreated resected animals. ALC-078 increases the absorption of fat-soluble vitamins and may improve fat malabsorption. Future studies should determine whether ALC-078 can reduce PN dependence and if these findings translate to human patients with SBS.

Effect of Pancrelipase Therapy on Exocrine Pancreatic Insufficiency Symptoms and Coefficient of Fat Absorption Associated With Chronic Pancreatitis.

The aim of this study was to evaluate whether improvement in coefficient of fat absorption (CFA) with pancreatic enzyme replacement therapy correlates with clinical symptoms in patients with chronic pancreatitis with moderate to severe exocrine pancreatic insufficiency. Data were pooled from 2 randomized double-blind trials of the effects of 1 week of pancrelipase (n = 59) versus placebo (n = 57) on CFA and stool frequency, stool consistency, abdominal pain, and flatulence; 1 trial included a 51-week open-label pancrelipase treatment period (n = 34). Compared with placebo, significantly more patients receiving pancrelipase reported decreased stool frequency at week 1 (72% vs 38%; P < 0.001). Although 30% of patients receiving pancrelipase and 20% receiving placebo reported improved stool consistency, changes in stool consistency, abdominal pain, and flatulence were not different between groups. Mean CFA absolute change from baseline was significantly greater with pancrelipase versus placebo (24.7% vs 6.4%; P < 0.001). Improvements in stool consistency and frequency correlated with CFA improvement. Symptom improvements persisted or further improved through 52 weeks of treatment. Pancrelipase significantly improved exocrine pancreatic insufficiency maldigestive symptoms. Improvements in objective stool symptoms with pancreatic enzyme replacement therapy correlated with CFA improvement at 1 week.

Malnutrition after pancreatic enzyme replacement therapy in chronic pancreatitis: Risk factors in real world practice

BackgroundRCTs that have shown improvement in coefficient of fat absorption with pancreatic enzyme replacement therapy (PERT) have seldom evaluated the impact on overall nutritional status. ObjectiveIn this study we evaluated factors responsible for persistence of malnutrition after PERT. MethodsIn this cross-sectional observational study, patients were enrolled based on predefined enrolment criteria. Patients were divided into those taking PERT regularly (Group A), irregularly (Group B) and not taking (Group C) for at least 3 months. Comprehensive evaluation of anthropometric measurements, nutritional assessment and dietary intake was performed. Malnutrition was measured using the Subjective Global Assessment (SGA) tool. Relationship between PERT status, dietary intake and nutritional status were evaluated using standard statistical methods. Logistic regression was performed to identify factors associated with persistence of malnutrition after PERT. Results377 patients with CP and 50 controls were included. 95 (25.2%) patients with CP were in Group A, 106 (28.1%) in Group B and 176 (46.7%) in Group C. 130 (34.5%) patients were malnourished, of which 76 (58.5%) were continuing PERT. There were no differences in clinical and biochemical nutritional markers between Groups A, B, and C. Calorie deficit and daily intake of calorie, protein, carbohydrates and fats were not different between those with and without PERT, but was significantly less in those with malnutrition. Logistic regression demonstrated inadequate dietary intake as independent risk factor for persistence of malnutrition. ConclusionEven though PERT is effective in PEI, comprehensive nutritional assessment, personalized nutritional counselling and therapy along with PERT is mandatory.

Clinical evaluation of an evidence-based method based on food characteristics to adjust pancreatic enzyme supplements dose in cystic fibrosis

BackgroundPatients with cystic fibrosis (CF) and pancreatic insufficiency need pancreatic enzyme replacement therapy (PERT) for dietary lipids digestion. There is limited evidence for recommending the adequate PERT dose for every meal, and controlling steatorrhea remains a challenge. This study aimed to evaluate a new PERT dosing method supported by a self-management mobile-app. MethodsChildren with CF recruited from 6 European centres were instructed to use the app, including an algorithm for optimal PERT dosing based on in vitro digestion studies for every type of food. At baseline, a 24h self-selected diet was registered in the app, and usual PERT doses were taken by the patient. After 1 month, the same diet was followed, but PERT doses were indicated by the app. Change in faecal fat and coefficient of fat absorption (CFA) were determined. Results58 patients (median age 8.1 years) participated. Baseline fat absorption was high: median CFA 96.9%, median 2.4g faecal fat). After intervention CFA did not significantly change, but range of PERT doses was reduced: interquartile ranges narrowing from 1447-3070 at baseline to 1783-2495 LU/g fat when using the app. Patients with a low baseline fat absorption (CFA<90%, n=12) experienced significant improvement in CFA after adhering to the recommended PERT dose (from 86.3 to 94.0%, p=0.031). Conclusionthe use of a novel evidence-based PERT dosing method, based on in vitro fat digestion studies incorporating food characteristics, was effective in increasing CFA in patients with poor baseline fat absorption and could safely be implemented in clinical practice.

Correction:Improved residual fat malabsorption and growth in children with cystic fibrosis treated with a novel oral structured lipid supplement: A randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0232685.].

Measures of Dietary Fat and Energy Absorption in Healthy Adults.

Existing reference ranges for stool fat and energy absorption were developed using subjects in controlled environments on precise diets. This study measured energy and fat absorption in healthy, community-dwelling adults eating a moderate-to-high fat American diet via stool- and serum-based methods. This was a secondary analysis of healthy subjects recruited as the comparison group in a chronic pancreatitis study. Subjects recorded dietary intake and collected stool over 3-day periods. Stool was analyzed for fat content using the coefficient of fat absorption and for energy content using bomb calorimetry. The malabsorption blood test (MBT) was used to measure dietary fat absorption. Nineteen subjects had mean daily stool measures of 143 g wet weight, 4.1 g of fat, and 178 kcal. The mean coefficients of fat and energy absorption were 96% and 93%, respectively. The mean MBT area under the curve cut-point was greater than 8 mg·h/dL. This study confirms the historical reference range for the coefficient of fat absorption in contemporary healthy, community-dwelling adults on a moderate-to-high fat diet. The study contributes to the development of reference range values for multiple bomb calorimetry-based outcomes of stool energy losses and to the serum-based MBT as a promising method for measuring fat absorption.

Improved residual fat malabsorption and growth in children with cystic fibrosis treated with a novel oral structured lipid supplement: A randomized controlled trial.

In the primary analysis of a 12-month double-blind randomized active placebo-controlled trial, treatment of children with cystic fibrosis (CF) and pancreatic insufficiency (PI) with a readily absorbable structured lipid (Encala™, Envara Health, Wayne, PA) was safe, well-tolerated and improved dietary fat absorption (stool coefficient of fat absorption [CFA]), growth, and plasma fatty acids (FA). To determine if the Encala™ treatment effect varied by severity of baseline fat malabsorption. Subjects (n = 66, 10.5±3.0 yrs, 39% female) with baseline CFA who completed a three-month treatment with Encala™ or a calorie and macronutrient-matched placebo were included in this subgroup analysis. Subjects were categorized by median baseline CFA: low CFA (<88%) and high CFA (≥88%). At baseline and 3-month evaluations, CFA (72-hour stool, weighed food record) and height (HAZ), weight (WAZ) and BMI (BMIZ) Z-scores were calculated. Fasting plasma fatty acid (FA) concentrations were also measured. Subjects in the low CFA subgroup had significantly improved CFA (+7.5±7.2%, mean 86.3±6.7, p = 0.002), and reduced stool fat loss (-5.7±7.2 g/24 hours) following three months of EncalaTM treatment. These subjects also had increased plasma linoleic acid (+20%), α-linolenic acid (+56%), and total FA (+20%) (p≤0.005 for all) concentrations and improvements in HAZ (0.06±0.08), WAZ (0.17±0.16), and BMIZ (0.20±0.25) (p≤0.002 for all). CFA and FA were unchanged with placebo in the low CFA group, with some WAZ increases (0.14±0.24, p = 0.02). High CFA subjects (both placebo and Encala™ groups) had improvements in WAZ and some FA. Subjects with CF, PI and more severe fat malabsorption experienced greater improvements in CFA, FA and growth after three months of Encala™ treatment. Encala™ was safe, well-tolerated and efficacious in patients with CF and PI with residual fat malabsorption and improved dietary energy absorption, weight gain and FA status in this at-risk group.

Association between faecal pH and fat absorption in children with cystic fibrosis on a controlled diet and enzyme supplements dose.

Despite treatment with pancreatic enzyme replacement therapy (PERT), patients with cystic fibrosis (CF) can still suffer from fat malabsorption. A cause could be low intestinal pH disabling PERT. The aim of this study was to assess the association between faecal pH (as intestinal pH surrogate) and coefficient of fat absorption (CFA). Additionally, faecal free fatty acids (FFAs) were quantified to determine the amount of digested, but unabsorbed fat. In a 24-h pilot study, CF patients followed a standardised diet with fixed PERT doses, corresponding to theoretical optimal doses determined by an in vitro digestion model. Study variables were faecal pH, fat and FFA excretion, CFA and transit time. Linear mixed regression models were applied to explore associations. In 43 patients, median (1st, 3rd quartile) faecal pH and CFA were 6.1% (5.8, 6.4) and 90% (84, 94), and they were positively associated (p < 0.001). An inverse relationship was found between faecal pH and total fat excretion (p < 0.01), as well as total FFA (p = 0.048). Higher faecal pH was associated with longer intestinal transit time (p = 0.049) and the use of proton pump inhibitors (p = 0.009). Although the clinical significance of faecal pH is not fully defined, its usefulness as a surrogate biomarker for intestinal pH should be further explored. Faecal pH is a physiological parameter that may be related to intestinal pH and may provide important physiopathological information on CF-related pancreatic insufficiency. Faecal pH is correlated with fat absorption, and this may explain why pancreatic enzyme replacement therapy is not effective in all patients with malabsorption related to CF. Use of proton pump inhibitors is associated to higher values of faecal pH. Faecal pH could be used as a surrogate biomarker to routinely monitor the efficacy of pancreatic enzyme replacement therapy in clinical practice. Strategies to increase intestinal pH in children with cystic fibrosis should be targeted.

Pancreatic Function in Chronic Pancreatitis: A Cohort Study Comparing 3 Methods of Detecting Fat Malabsorption and the Impact of Short-term Pancreatic Enzyme Replacement Therapy.

Reliable pancreatic function tests in patients with chronic pancreatitis (CP) are needed. This cohort study identified malabsorption in people with CP compared with healthy people and then investigated short-term pancreatic enzyme replacement therapy (PERT) and fat malabsorption, nutritional status, and quality of life (QOL). Subjects with CP were evaluated before and after PERT and compared with the healthy cohort using coefficient of fat absorption (CFA), stool bomb calorimetry, and the malabsorption blood test (MBT). Anthropometrics, micronutrients, and QOL data were collected. Group means at baseline and after PERT were analyzed. The 24 subjects with CP had greater stool energy loss (5668 cal/g [standard deviation {SD}, 753] vs 5152 cal/g [SD, 418], P < 0.01), reduced triglyceride absorption (MBT, 8.3 mg·h/dL [SD, 4.3] vs 17.7 mg·h/dL [SD, 10.3], P < 0.001), lower fat intake, and poorer QOL. Differences in CFA were not significant (90.9% [SD, 12.8] vs 95.4% [SD, 9.3]). After PERT, triglyceride absorption (Δ = 1.7 [SD, 3], P < 0.05) and QOL increased. The MBT detected changes in triglyceride absorption in the absence of CFA changes. The MBT may be helpful in guiding PERT initiation in patients with CP before significant morbidity.

Clinical validation of an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy through a prospective interventional study in paediatric patients with Cystic Fibrosis.

BackgroundA method to adjust Pancreatic Enzyme Replacement Therapy in Cystic Fibrosis is not currently available.ObjectivesTo assess the in vivo efficacy of a method to adjust the dose of enzymatic supplement in CF extrapolated from previous in vitro digestion studies (theoretical optimal dose, TOD). Secondly, to assess how individual patient characteristics influence the expected coefficient of fat absorption (CFA) and thus to identify an individual correction factor to improve TOD.MethodsA prospective interventional study in 43 paediatric patients with CF from 5 European centres. They followed a 24h fixed diet with the theoretical optimal dose for each meal. Faecal collection was carried out between colorimetric markers in order to include all the faeces corresponding to the fixed diet. Beta regression models were applied to assess the associations of individual patient characteristics with the CFA.ResultsMedian CFA was 90% (84, 94% 1st, 3rd Q.) with no significant differences among centres. Intestinal transit time was positively associated with CFA (p = 0.007), but no statistical associations were found with and age, gender, phenotype or BMI. Regression model showed no improvement of the in vitro predicted theoretical optimal dose when taking individual patient characteristics into account.ConclusionStrict adherence to the theoretical optimal dose of enzymatic supplement for a prescribed meal, led to median CFA levels at the clinical target of 90% with a low variability between patients. The proposed method can be considered as a first approach for an evidence-based method in PERT dosing based on food characteristics. Results have to be confirmed in free dietary settings.

Reporting a phase II, open-label study assessing the safety and efficacy of MS1819-SD, a recombinant lipase, for the treatment of exocrine pancreatic insufficiency

Background: Chronic pancreatitis is the most common cause of exocrine pancreatic insufficiency (EPI) in adults. EPI is a deficiency in exocrine pancreatic enzymes resulting in an inability to maintain normal digestion. This inadequate digestion, especially fat malabsorption, occurs when intraduodenal levels of lipase fall below 5–10% of normal enzyme output. Furthermore, in EPI due to chronic pancreatitis, decreased bicarbonate output leads to impairment of micelle formation of fats. Fat maldigestion is compounded by decreased pancreatic secretion of lipase and colipase, further dampening hydrolysis of intraluminal fat. Methods: A multicenter, Phase II, open-label, non-randomized study was conducted to investigate the safety of escalating doses (280 mg/day, 560 mg/day, 1120 mg/day and 2240 mg/day) of MS1819 Spray Dried (MS1819-SD, a lipase produced by the LIP2 gene of Yarrowia lipolytica using recombinant DNA technology) in patients with chronic pancreatitis (NCT03481803) and decreased fecal pancreatic elastase-1 (FE-1). Patients ‘washed-out’ their standard of care treatment for EPI establishing a baseline. Each patient subsequently received escalating doses of MS1819-SD in 2-week increments. The total treatment phase ranged from 48 to 60 days. Safety was assessed by adverse event (AE) incidence, including clinical or laboratory abnormalities, and efficacy was determined using Coefficient of Fat Absorption (CFA) change from baseline. Systemic exposure and immunogenicity potential of MS1819 were investigated in patients’ serum. Results: A total of 11 patients (9 males, 2 females) were enrolled in France, Australia and New Zealand. The study mean age was 59.2 years (11.19 standard deviation [SD]) and mean weight was 70.6 kg (12.84 SD). Disease etiology was alcoholism in 4 patients, idiopathic in 3 patients, genetic in 2 patients, auto-immune in 1 patient and gallstone induced pancreatitis for 1 patient. In the highest dose group (2240 mg/day) 4/10 patients reported an AE. One serious AE occurred at this dose but it was not considered to be treatment related (pre-planned removal of stent). A drug-related AE was reported at the 1120 mg dose (slight hepatic cytolysis, mild in nature). No circulating MS1819 was detected hence the mechanism of this adverse event cannot be explained or related to systemic exposure. MS1819 immunogenicity was observed in some patients with post-treatment anti-drug antibodies (ADAs) detected. However, some pre-existing ADAs were also detected and the incidence of ADAs was mild (3/10 patients) with moderate ADA titers. Increases in CFA were reported with all doses of MS1819-SD, these increases were particularly high in patients with baseline CFA <40%. Comparing CFA with FE-1 (24 patients with both recorded at screening) a positive spearman rank correlation of 0.64 (p < 0.001) was obtained. Although the study was not powered to detect a difference in efficacy parameters, the least square mean increase in CFA was 21.8% with MS1819-SD 2240 mg (p = 0.002; per protocol analysis). Conclusion: In general, a favorable safety profile was reported at all doses of MS1819-SD included in the study. Statistically significant and clinically meaningful increases in CFA compared to baseline were recorded. Although the efficacy analysis was pre-planned, the study was not powered to demonstrate differences in the groups and only a small number of patients were included. Favorable trends were also observed on other evaluated endpoints, including the Bristol stool scale, number of daily evacuations and stool weight. Additional studies are warranted to further evaluate the use of MS1819-SD to treat EPI in patients with chronic pancreatitis or cystic fibrosis.

Exocrine pancreatic insufficiency in type 1 and type 2 diabetesmellitus: do we need to treat it? A systematic review

The exocrine and endocrine pancreata are very closely linked both anatomically and physiologically. Abdominal symptoms such as nausea, bloating, diarrhea, steatorrhea, and weight loss can often occur in diabetic patients. Impairments of the exocrine pancreatic function seem to be a frequent complication of diabetes mellitus; however, they are largely overlooked. The aim of this paper is to provide an overview of the current concepts of exocrine pancreatic insufficiency (PEI) in diabetes mellitus. This systematic review provides information on the high prevalence of chronic pancreatic diseases in patients with diabetes; statements that reveal the multifactorial mechanism of PEI development upon violation of glucose uptake are summarized. The main PEI clinical manifestations in diabetes are described, the difficulties of timely detection of EPN are considered, the advantages and disadvantages of the “gold standards” of laboratory diagnostics (determination of the level of fecal elastase 1 and the coefficient of fat absorption, respiratory test using mixed triglycerides, 13C labeled, and secretin-pancreozymin test) in this cohort of patients. The data of randomized researches that studied the effectiveness of enzyme replacement therapy of PEI in patients with diabetes are analyzed. The ability of enzyme replacement therapy to normalize digestion has been confirmed, and its possible effect on glycemia and vitamin D levels in patients with diabetes and EPN has been considered. The reasons for the continuation of taking enzyme preparations are listed.

Fecal fat and energy loss in pancreas exocrine insufficiency: the role of pancreas enzyme replacement therapy

Background: Chronic pancreatitis (CP) can lead to severe pancreatic exocrine insufficiency (PEI). Pancreatic enzyme replacement therapy (PERT) is well established, but knowledge of the physiological response to increasing doses on fecal fat- and energy loss is scarce.Methods: We included 10 patients with CP and established PEI and 12 healthy controls for a prospective interventional study. Subjects received no PERT in the first week followed by four weeks PERT incrementally increasing doses every week. For each week, three-day stool collection followed three days registration of nutritional intake. We measured the fecal output of fat and energy by van de Kamer titration and decomposition vessel calorimetry, respectively. We calculated fecal fat- and energy loss per day, the coefficient of fat absorption (CFA) and coefficient of energy absorption (CEA).Results: Without PERT treatment, CP patients with PEI had significantly higher daily fecal fat and energy loss (p = .022; p = .035) compared to HC. In CP patients, there was a significant reduction of fecal fat and energy loss (p = .045; p = .037) when PERT doses reached maximum intake of 75,000 units per meal. In CP patients, there was a strong positive correlation between fecal loss of energy and fat (r = 0.99), and between fecal loss of energy and daily stool weight (r = 0.97). CFA and CEA correlated negatively with daily fecal fat loss (r = −0.72) and fecal energy loss (r = −0.65).Conclusions: PERT reduces fecal energy and fat loss in patients with CP and PEI. Fecal energy loss in CP patients is strongly dependent on fecal fat loss, and on fecal weight.

Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations

To determine if ivacaftor treatment results in weight gain and improved pulmonary function in people with cystic fibrosis transmembrane conductance regulator gating mutations. Children and adults with cystic fibrosis and at least 1 cystic fibrosis transmembrane conductance regulator gating mutation were evaluated in this observational study before and after 3 months of ivacaftor treatment. Body size and composition, total energy expenditure, resting energy expenditure (REE%) as percent predicted, coefficient of fat absorption (CFA%), fecal calprotectin, fecal elastase, and quality of life were assessed. Some outcomes were explored by pancreatic status. There were 23 patients (5-61 years of age) who completed the study; 70% had pancreatic insufficiency (PI). Patients gained 2.5 ± 2.2 kg (P < .001) with increased (P < .05) fat-free mass (0.9 ± 1.9 kg) and fat mass (1.6 ± 1.5 kg). REE% decreased by 5.5 ± 12.0% (P < .05), fecal calprotectin decreased by 30 ± 40 µg/g stool (P < .01), and total energy expenditure was unchanged. Improvements were greater for PI than patients who were pancreatic-sufficient. CFA% increased significantly only with PI. The change (Δ) in weight was positively correlated with the percent change in forced expiratory volume at 1 second (r = 0.46; P = .028) and ΔCFA% (r = 0.47; P = .032) and negatively with ΔREE% (r = -0.50; P = .017). Together, ΔREE%, ΔCFA%, and the percent change in forced expiratory volume at 1 second explained 58% of the variance in weight gain (adjusted R2 = 0.579; P = .0007). Growth status and muscle strength improved, as did quality of life in several domains. Fecal elastase increased in most patients with pancreatic sufficiency, with no change in those with PI. Mechanisms identified for ivacaftor-associated weight gain were decreased REE, gut inflammation, and fat malabsorption (CFA). ClinicalTrials.gov: NCT02141464.