Case-control study comparing serum MOTS-c levels in children with T1DM versus healthy controls, investigating whether MOTS-c correlates with early markers of diabetic kidney disease including microalbuminuria and estimated glomerular filtration rate. Evaluates MOTS-c as a pediatric DKD biomarker. Provides the first pediatric evidence for MOTS-c as an early DKD biomarker in T1DM—establishing whether mitochondrial peptide deficiency precedes or accompanies the earliest stages of nephropathy in children, with implications for earlier DKD detection and for understanding mitochondrial contributions to diabetic renal injury across the lifespan.
Abstract
OBJECTIVE: To compare serum mitochondrial open reading frame of 12S rRNA-c (MOTS-c) levels, a new potential biomarker for oxidative stress, in children with type 1 diabetes mellitus (T1DM) and healthy children. A further aim was to investigate serum MOTS-c levels as a potential early indicator of diabetic kidney disease (DKD) by correlating levels with changes in glomerular filtration and microalbuminuria.
METHODS: Patients with a diagnosis of T1DM and healthy controls were recruited. MOTS-c, urinary albumin excretion, estimated glomerular filtration rate (eGFR), and hemoglobin A1c (HbA1c) were evaluated and clinical features and anthropometric measurements were collected. Patients were stratified according to diabetes duration, presence of albuminuria, glomerular hyperfiltration, eGFR decline and metabolic control.
RESULTS: The T1DM group included 82 [female:male (F:M) 1:1.64] patients while the controls numbered 61 (F:M 1:0.97), with respective mean ages of 14.3±3.3 and 10.6±4.2 years (p<0.01). MOTS-c levels were significantly lower in the T1DM group than controls (76.2±1.3 vs 105.2±7.0, p<0.001). No difference was found in MOTS-c levels between patient subgroups categorized by diabetes duration, obesity, metabolic control, hypertension, hyperlipidemia, glomerular hyperfiltration, decline in eGFR, and presence of microalbuminuria. Simple linear regression indicated that MOTS-c was not predictive for DKD.
CONCLUSION: MOTS-c levels were lower in children with T1DM than in healthy children. However, the lack of association of MOTS-c with renal biomarkers suggested that it is not an effective early marker for DKD. However, this finding suggests that the onset of oxidative damage and mitochondrial dysfunction in T1DM is independent of DKD. In addition, the results suggests that HbA1c and duration of diabetes are significant risk factors for development of microalbuminuria, while changes in eGFR and microalbuminuria continue to serve as indicators of DKD.