Assessment of Urinary Betaine as a Marker of Diabetes Mellitus in Cardiovascular Patients

Abstract

Abnormal urinary excretion of betaine has been demonstrated in patients with diabetes or metabolic syndrome. We aimed to identify the main predictors of excretion in cardiovascular patients and to make initial assessment of its feasibility as a risk marker of future diabetes development. We used data from 2396 patients participating in the Western Norway B-vitamin Intervention Trial, who delivered urine and blood samples at baseline, and in the majority at two visits during follow-up of median 39 months. Betaine in urine and plasma were measured by liquid-chromatography-tandem mass spectrometry. The strongest determinants of urinary betaine excretion by multiple regression were diabetes mellitus, age and estimated glomerular filtration rate; all p<0.001. Patients with diabetes mellitus (n = 264) had a median excretion more than three times higher than those without. We found a distinct non-linear association between urinary betaine excretion and glycated hemoglobin, with a break-point at 6.5%, and glycated hemoglobin was the strongest determinant of betaine excretion in patients with diabetes mellitus. The discriminatory power for diabetes mellitus corresponded to an area under the curve by receiver-operating characteristics of 0.82, and betaine excretion had a coefficient of reliability of 0.73. We also found a significant, independent log-linear relation between baseline betaine excretion and the risk of developing new diabetes during follow-up. The good discriminatory power for diabetes, high test-retest stability and independent association with future risk of new diabetes should motivate further investigation on the role of betaine excretion in risk assessment and long-term follow-up of diabetes mellitus.

Prospective Associations of Systemic and Urinary Choline Metabolites with Incident Type 2 Diabetes

“…Higher urine betaine concentrations have previously been observed among patients with T2D or the metabolic syndrome (10,11 ), and increased urinary betaine and sarcosine concentrations were found among patients with T2D vs patients with maturity-onset diabetes of the young (26 ), indicating a role of IR. Accordingly, the current study showed that the highly correlated urine betaine, dimethylglycine, and sarcosine concentrations were all positively associated with HOMA2-IR and incident T2D, and that urine sarcosine was the urinary choline metabolite most strongly associated with new-onset disease.…”

“…Also, several studies have found very high urinary betaine concentrations among patients with diabetes (10,11 ). We previously observed strong positive correlations between urine betaine, dimethylglycine, and sarcosine among patients with coronary heart disease and found that high urine betaine was associated with new-onset diabetes during follow-up for approximately 3 years (11 ).…”

“…The collection of anamnestic, clinical, and routine biochemical information has been described (11,12 ). We measured plasma TMAO, choline, betaine, and dimethylglycine; serum sarcosine; and urine choline, betaine, dimethylglycine, and sarcosine by LC-MS/MS (14 ) or GC-MS/MS (15 ).…”

“…Moreover, the intestinal microflora take part in turning dietary choline into trimethylamine N-oxide (TMAO) (8 ), and higher plasma TMAO concentrations have been observed among patients with T2D than among those without T2D (9 ). Also, several studies have found very high urinary betaine concentrations among patients with diabetes (10,11 ). We previously observed strong positive correlations between urine betaine, dimethylglycine, and sarcosine among patients with coronary heart disease and found that high urine betaine was associated with new-onset diabetes during follow-up for approximately 3 years (11 ).…”

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…Four studies addressing various samples was conducted on vitamin B complexes [346][347][348][349], a review on folate, vitamin B6 and B12 was conducted on methods for analysis in humans [350], four studies were conducted on vitamin B6 [351][352][353][354], two on folate [355,356], five on vitamin B12 [357][358][359][360][361] and one on betaine (from choline) [362]. These studies have been outlined below in Table 3-2.…”