The Dynamics of Carnitine, γ-butyrobetaine and Trimethylamine N-oxide in Diabetics and the Effects of Changes in Renal Function

Objectives: In diabetic kidney disease, vascular disorders progress alongside loss of renal function, possibly due to higher blood concentrations of angiopathic substances, such as gamma-butyrobetaine (γBB), produced by gut microbiota that feed on carnitine in dietary red meat. Therefore, we established the hypothesis that urinary γBB excretion declines with decreasing renal function, causing a rise in blood γBB concentration, leading to aggravated vascular injury.

Methods: Our subjects were non-diabetics with normal renal function (N group) and diabetics with reduced renal function (D group). We measured blood concentration and urinary γBB excretion to compare the groups. We also compared blood γBB levels and urinary γBB excretions in diabetics with diabetic kidney disease (eGFR<30 mL/min/1.73m2, DKD group) with diabetics without DKD (eGFR>30 mL/min/m2, NDKD group).

Results: Blood γBB concentration in the D group was approximately 134.3% compared with the N group. It correlated negatively with eGFR (r = –0.85, p<0.001) and positively with intima-media thickness (IMT, r = 0.79, p<0.001). Blood γBB concentration in the DKD group was approximately 162.7% compared with the NDKD group. However, urinary γBB excretion in the D group was approximately 29.1% compared with the N group, while the DKD group showed approximately 45.7% compared with the NDKD group.

Conclusions: Blood γBB concentration is higher in diabetics, which closely correlates with lower urinary excretion caused by renal hypo function. γBB, which damages blood vessels and aggravates vascular damage, may be implicated in the pathology of cardio renal correlation.