Variability of plasma and urine betaine in diabetes mellitus and its relationship to methionine load test responses: an observational study.

BACKGROUND: Since betaine is an osmolyte and methyl donor, and abnormal betaine loss is common in diabetes mellitus (>20% patients), we investigated the relationship between betaine and the post-methionine load rise in homocysteine, in diabetes and control subjects. The post-methionine load test is reported to be both an independent vascular risk factor and a measure of betaine sufficiency. METHODS: Patients with type 2 diabetes (n = 34) and control subjects (n = 17) were recruited. We measured baseline fasting plasma and 4-hour post-methionine load (L-methionine, 0.1 mg/kg body weight) concentrations of homocysteine, betaine, and the betaine metabolite N,N-dimethylglycine. Baseline urine excretions of betaine, dimethylglycine and glucose were measured on morning urine samples as the ratio to urine creatinine. Statistical determinants of the post-methionine load increase in homocysteine were identified in multiple linear regression models. RESULTS: Plasma betaine concentrations and urinary betaine excretions were significantly (p < 0.001) more variable in the subjects with diabetes compared with the controls. Dimethylglycine excretion (p = 0.00014) and plasma dimethylglycine concentrations (p = 0.039) were also more variable. In diabetes, plasma betaine was a significant negative determinant (p < 0.001) of the post-methionine load increase in homocysteine. However, it was not conclusive that this was different from the relationship in the controls. In the patients with diabetes, a strong relationship was found between urinary betaine excretion and urinary glucose excretion (but not with plasma glucose). CONCLUSIONS: Both high and low plasma betaine concentrations, and high and low urinary betaine excretions, are more prevalent in diabetes. The availability of betaine affects the response in the methionine load test. The benefits of increasing betaine intake should be investigated.

Homocysteine, glycine betaine, and N,N-dimethylglycine in patients attending a lipid clinic.

We recruited nondiabetic subjects (n = 158) attending a lipid disorders clinic, a subset of whom (n = 46) had established cardiovascular disease. Glycine betaine, N,N-dimethylglycine, and carnitine were measured in fasting plasma and urine samples. The concentrations and excretions were related to known cardiovascular risk factors in multivariate regression models. The relationships between homocysteine and plasma and urinary glycine betaine were highly significant (P < .002), comparable with the known relationships with folate and plasma creatinine. The regression coefficient for plasma glycine betaine was consistently approximately -0.1 in 5 different regression models (3 best-subsets and forward and backward stepwise regression models) for predicting homocysteine using 23 variables. Plasma glycine betaine was higher in males than in females, and the difference was associated with a difference in percentage of body fat. Its concentration included a constant factor of approximately 20 micromol/L that was independent of any of the variables investigated here. In the total group, body fat, homocysteine, and carnitine were significant predictors of plasma glycine betaine. Carnitine, an important betaine that is involved in lipid metabolism positively correlated with both homocysteine and glycine betaine. In our sample, the urinary excretion of glycine betaine was outside the reference range in 14 of the 158 subjects and the betaine fractional clearances were above the reference range in 23 subjects. Fractional clearance correlated strongly with plasma homocysteine (r = 0.50), and this relationship may be stronger in patients with known vascular disease. Urinary loss of glycine betaine may contribute to hyperhomocysteinemia and the development of cardiovascular disease.

Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure.

BACKGROUND: Fasting and post-methionine load hyperhomocysteinemia are independent risk factors for vascular disease that are common in chronic renal failure. Folate decreases but seldom normalizes fasting total homocysteine (tHcy) concentrations in such patients. Glycine betaine (GB) is known to decrease tHcy in other clinical settings, but whether it is beneficial in chronic renal failure has not been established. METHODS: We conducted a crossover-controlled trial in 36 patients with chronic renal failure to determine if oral GB decreased fasting or post-methionine tHcy concentrations. All subjects received, in randomized sequence, 5-mg folic acid and 50-mg pyridoxine daily, with or without GB 4-g daily, for three months each. Fasting plasma tHcy, GB, folate, B vitamins, serum lipids and creatinine were measured at one and three months, and methionine load tests were performed at the end of each three-month treatment phase. RESULTS: GB and N,N-dimethylglycine (DMG) levels in plasma and urine increased markedly during GB treatment. Fasting tHcy decreased from baseline with both treatments but did not differ between treatments. Post-methionine tHcy decreased with both treatments and was 18% lower on GB than on folate and pyridoxine alone (P < 0.001). There were small increases in lipids during treatment with GB but the ratio of total: HDL cholesterol was unchanged. CONCLUSIONS: GB supplementation had no effect on fasting tHcy in patients with chronic renal failure who were folate and pyridoxine replete, but it significantly decreased tHcy concentrations after methionine loading.