Measuring D-Lactate in Blood May Indicate Pancreatic Insufficiency in CF Patients, Study Suggests

Measuring D-Lactate in Blood May Indicate Pancreatic Insufficiency in CF Patients, Study Suggests

Blood levels of D-lactate may be markers of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF), according to preliminary data from a new study.

The research, “Serum Level of D-Lactate in Patients with Cystic Fibrosis: Preliminary Data,” was published in the journal Disease Markers.

CF patients may develop EPI, a condition characterized by a deficiency of exocrine pancreatic enzymes, resulting in inefficient food digestion. Together with impaired motility (contraction of the muscles that mix and propel contents) in the gastrointestinal tract, and lack of appetite, EPI commonly results in the development of malnutrition.

An abnormally high amount of partially digested nutrients leads to the production of a rich mucus that alters the intestinal flora, or microbiota (the community of microorganisms in the gut), which ultimately can lead to small intestinal bacterial overgrowth (SIBO).

An additional factor contributing to SIBO is prolonged antibiotic therapy in patients with respiratory complications. Although intestinal dysbiosis — imbalances in the microbial community — and bacterial overgrowth occur in 30-50% of patients with CF, under-diagnosis of SIBO can lead to malnutrition.

Gut microbiota are the main producers of D-lactate, which is generated upon incomplete absorption of carbohydrates in the small intestine. Build-up of D-lactate may cause metabolic acidosis (a disturbance in the blood’s acidity) and neurologic symptoms such as dysarthria, characterized by slurred or slow speech.

D-lactate is not metabolized by the body, being absorbed into the bloodstream, and excreted through urine.

Consequently, changes in the gut microbiota may lead to elevated serum levels of D-lactate, particularly in patients with EPI, the researchers suggested. However, serum D-lactate levels have not been assessed in CF patients.

Aiming to address this gap, scientists at the Medical University of Silesia, in Poland, assessed D-lactate concentration in relation to CF clinical features and activity, as well as diet composition, in pediatric patients.

The study included 38 CF children (19 boys and 19 girls), with an average age of 7.8 years (ranging from  6 months to 18 years. Patients treated with antibiotics during the previous four weeks were excluded to eliminate potential confounders.

Patients’ body mass index, height and pancreatic efficiency — including the activity of fecal pancreatic elastase (released into the circulation during pancreatic inflammation), and serum levels of glucose and the protein albumin — were assessed.

Parameters of liver damage, cholestasis (reduced bile flow), and intestinal inflammation (fecal levels of the protein calprotectin, suggested as a marker of CF severity) also were evaluated.

Blood samples were collected after overnight fasting, and diet composition was analyzed on the basis of a three-day diary. Clinicians also determined the severity of CF based on the Schwachman-Kulczycki score, taking into account data on physical activity and changes in the respiratory tract, nutrition, and imaging tests.

Thirty-five children exhibited the F508del mutation in the CFTR gene (the most common genetic alteration in CF patients worldwide), 13 children had one copy of the mutated gene (heterozygous mutation), while 22 children had two copies of the mutated gene (homozygous mutation — one gene inherited from the father and one from the mother).

Of the 38 children analyzed, 29 (76.3%) had EPI.

Results showed that the median level of D-lactate was 0.86 micrograms/mL. D-lactate levels were not age-dependent and correlated with CF severity, parameters of pancreatic insufficiency, and gut inflammation.

Specifically, the subgroup with pancreatic insufficiency (29 patients) showed the highest amount of D-lactate (1.05 micrograms/mL). Patients with homozygous F508del mutation showed higher D-lactate level (0.95 micrograms/mL) than the ones with only one gene copy (0.76 micrograms/mL). Patients with an homozygous mutation also showed the most severe clinical conditions.

Sixteen patients (42.1%) showed elevated levels of calprotectin (above 50 micrograms/1 g stool), all with pancreatic insufficiency. Although the elevated levels of D-lactate were proportional to those of fecal calprotectin, the link between them was not statistically significant. The authors attributed this lack of significance to the small size of the study group.

Recurrent infections of the respiratory tract were found in 23 patients (60.5%), and malnutrition in 18 (47.4%).

However, the analysis did not find links between malnutrition, diet composition, and D-lactate levels.

Overall, the researchers concluded that “the observed values of D-lactate in CF subjects with exocrine pancreatic insufficiency may be considered as a potential new marker of exocrine pancreatic insufficiency but without any influence on the clinical course of the disease.”

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