Kidney Disease in T1D Linked to More Frequent, Severe GI Symptoms

Aleksejs Fedulovs, MSN

Credit: ResearchGate

Findings from a recent cross-sectional study are calling attention to greater frequency and severity of gastrointestinal symptoms in patients with type 1 diabetes and progressive diabetic kidney disease (DKD) compared to patients with stable kidney markers.

Results confirmed an association between progressive DKD and diabetic gastroenteropathy, citing significant correlations between gastrointestinal symptom scores, eGFR, and albuminuria.¹

“Diabetic gastroenteropathy as assessed by gastrointestinal symptom scores, instrumental examinations, and biomarkers remains a little studied factor predisposing to or potentiating the progression of DKD,” wrote investigators.¹ “However, such data are of extreme importance for clinical practice, as they could promote the development of novel treatment and prevention options for DKD.”

A condition slowly damaging the kidneys' filtering system, DKD affects about 1 in 3 people with diabetes in the US and can eventually lead to kidney failure. Early treatment may prevent DKD or slow its progression and lower the chance of complications. However, little is known about the factors contributing to the progression of DKD.²

A prospective study of diabetic nephropathy, the longitudinal LatDiane study provided investigators with a cohort of adult patients with type 1 diabetes diagnosed before the age of 40 years with insulin treatment initiated within 1 year of diagnosis and C-peptide levels below 0.3 nmol/L. Follow-up visits and re-assessments of the status of complications of diabetes take place every 3 years. The present study, led by Aleksejs Fedulovs, MSN, of the department of internal medicine at the University of Latvia, sought to assess the association between DKD progression and diabetic gastroenteropathy in type 1 diabetes using patients from this cohort.¹

For inclusion in the present study, patients were required to have type 1 diabetes for at least 8 years and available data on the progression of DKD, including at least 3 yearly serum creatinine measurements and albuminuria measurements available between the baseline visit of the LatDiane study in 2013–2019 and the current study, which took place between January 15, 2021, and August 31, 2022. Patients who were pregnant, had a history of inflammatory bowel disease, celiac disease, acute intestinal infection within 2 months of the planned fecal collection, asymptomatic coeliac disease, clinical signs of acute inflammation, and fever were excluded from the study.¹

Investigators administered a newly developed scale questionnaire assessing gastrointestinal symptoms for patients to fill out during the study visit. It included 17 questions about pain, discomfort, impaired bowel movement, and constipation, which investigators used to calculate the mean value to assess the mean frequency and intensity of gastrointestinal symptoms.¹

In total, 100 patients with type 1 diabetes were enrolled in the study. Progressive DKD, defined by investigators as an eGFR decline exceeding 3 mL/min/1.73 m2/year and/or increase in albuminuria stage over the follow-up period, was prevalent among 27 participants. The remaining 73 were classified as having stable DKD.¹

Among the cohort, the mean age was 42.59 (Standard deviation [SD], 13.18) years, the mean BMI was 25.98 (SD, 4.69) kg/m2, and most participants were female (62%). The majority of participants were non-smokers (63%) and had hypertension (53%) and retinopathy (52%). The mean duration of diabetes was 24.38 (SD, 11.92) years and the mean HbA1c was 8.28% (SD, 1.74).¹

Upon analysis, patients with progressive DKD had greater gastrointestinal symptom scores compared to those with stable DKD (P = .019). Investigators also pointed out 14 (52%) patients with progressive DKD had bowel movement disorders compared to 16 (22%) patients with stable DKD (P < .01).¹

Gastrointestinal scores correlated negatively with estimated glomerular filtration rate (eGFR) (r = −0.335; P = .001), weight (r = −0.236, P = .018), blood erythrocyte counts (r = −0.313, P = .002), and blood hemoglobin (r = −0.321, P = .001). In contrast, they correlated positively with albuminuria (r = 0.245; P = .015), Hba1c (r = 0.305; P = .002), and diabetes duration (r = 0.251; P = .012). Investigators pointed out fecal calprotectin levels did not differ between DKD groups and were not correlated with the gastrointestinal symptom score, eGFR, or albuminuria.¹

Univariate regression analysis revealed increased scores in gastrointestinal symptoms were associated with greater odds of DKD progression (odds ratio [OR], 3.086; 95% confidence interval [CI], 1.209 to 7.879; P = .018). Investigators noted the association remained significant when the model was adjusted for sex and BMI but lost significance when adjusted for sex, BMI, diabetes duration, and HbA1c. In this model, diabetes duration was the only significant predictor of DKD (OR, 1.058; 95% CI, 1.011 to 1.106; P = .014).¹

Patients who had increased calprotectin levels and persistent symptoms of gastrointestinal disorders in the last 2 months were referred to a gastroenterologist for evaluation of indications for endoscopic examination. Among 47 participants who were selected to undergo colonoscopy, 13 had progressive DKD and 34 did not. In total, 21 patients accepted the invitation and went through the procedure, including 4 with progressive DKD and 17 with stable DKD. The most frequent indications for endoscopic examination were abdominal pain (n = 17; 81%), bowel movement disorders (n = 9; 43%), and elevated fecal calprotectin (n = 5; 24%).¹

Colonoscopies were performed for 21 participants, 5 (24%) of which showed abnormal macroscopic findings. The most commonly reported histopathological findings were infiltration with eosinophils, lymphocytes, plasmacytes, the presence of lymphoid follicles, and lymphoid aggregates.¹

“In patients with T1D and progressive DKD, the frequency and severity of gastrointestinal symptoms are higher compared to patients with stable kidney markers, as assessed by gastrointestinal symptom scores. Moreover, gastrointestinal symptom scores correlate with kidney markers. Further research is needed to clarify the causal relationships of the gut-kidney axis in T1D,” concluded investigators.¹

References:

1. Fedulovs A, Tzivian L, Zalizko P, et al. Progression of Diabetic Kidney Disease and Gastrointestinal Symptoms in Patients with Type I Diabetes. Biomedicines. 2023; 11(10):2679. https://doi.org/10.3390/biomedicines11102679
2. Mayo Clinic. Diabetic nephropathy (kidney disease). Diseases & Conditions. October 24, 2023. Accessed October 31, 2023. https://www.mayoclinic.org/diseases-conditions/diabetic-nephropathy/symptoms-causes/syc-20354556