|Abstract or Summary
- The purpose of this study was to determine the relationship between the overall
changes in concentration of plasma pyridoxal 5'-phosphate (PLP), red blood cell PLP (rbc
PLP) and plasma glucose during an oral glucose tolerance test (OGTT) in persons with
diabetes mellitus (DM), and to test the hypothesis that the decrease in plasma PLP concentration
that occurs with increasing plasma glucose would be explained by a subsequent
increase in rbc PLP concentration. A second objective was to compare the distribution
of PLP between the red blood cell and the plasma (as measured by the rbc PLP/
plasma PLP ratio) in persons with diabetes to the distribution in non-diabetic controls.
The third objective was to measure fasting plasma alkaline phosphatase (AP) activity,
and to compare it to fasting plasma PLP concentrations, fasting rbc PLP concentrations,
and the rbc PLP/plasma PLP ratio. The purpose of this third objective was to test the
hypothesis that an increased plasma AP activity in persons with DM would be associated
with decreased plasma PLP and increased rbc PLP concentrations.
The study included 8 persons (3F; 5M) with insulin dependent diabetes mellitus
(IDDM), 9 persons (5F; 4M) with non-insulin dependent diabetes mellitus (NIDDM) and
18 healthy control individuals (9F; 9M). All subjects were given a 75 gm oral D-glucose
dose, and blood was drawn at 0 (fasting), 30, 60 and 120 minutes after the glucose load. Plasma glucose, PLP, insulin, and rbc PLP concentrations were measured at all time
points during the OGTT. Fasting plasma alkaline phosphatase (AP) activity, percent
glycosylated hemoglobin (%GlyHb), and the ratio between fasting rbc PLP and fasting
plasma PLP were also determined.
In general, females with DM were in poorer diabetic control as compared to males
with DM. Mean fasting glucose levels, %GlyHb and body mass index (BMI) were
highest in females with DM as compared to all other groups, and fasting insulin was
nearly 2x higher in females with NIDDM as compared to males with NIDDM.
There was an overall decrease in plasma PLP during the OGTT with increasing
plasma glucose, which agrees with results from other studies. The overall decrease in
plasma PLP (as measured by the negative, cumulative area under the curve: -AUC plp)
was significantly correlated with the overall increase in plasma glucose (as measured by
the positive, cumulative area under the curve: +AUC glu) for all study groups. The
relationship was stronger in all males, and control females as compared to females with
diabetes (p< 0.001 vs. p< 0.01, respectively). This difference was in part explained by
lower mean fasting PLP levels in females with DM (19.3 nmol/L), as compared to males
with DM (47.2nmol/L) and male and female controls (35.4 nmol/L and 34.0 nmol/L,
The changes in rbc PLP during the OGTT were minimal, and did not significantly
correlate with the increase in plasma glucose or the decrease in plasma PLP. Thus, the
acute drop in plasma PLP concentration that occurred during the OGTT was not explained
by a subsequent increase in rbc PLP concentration, as had been hypothesized.
However, the higher than normal % glycosylated hemoglobin levels along with elevated
rbc PLP concentrations in persons with diabetes as compared to controls suggests that
chronically elevated blood glucose can contribute to increased rbc PLP concentrations.
This was the first study to date that has measured rbc PLP in persons with diabetes
mellitus. Rbc PLP values for persons with DM were 20-40% greater than respective control values at all time points during the OGTT. These differences between mean rbc
PLP in persons with DM as compared to control groups were all statistically significant
(p< 0.05) with the exception of the difference in the mean fasting rbc PLP value for
females with NIDDM as compared to controls. The mean values ± standard deviations
(SD) for fasting rbc PLP (nmol/L) were as follows: Females-IDDM, 49.5 ± 6.5;
NIDDM, 39.3 ± 4.9; controls, 31.4 ± 9.0; Males-IDDM, 37.8 ± 10.9; NIDDM, 45.6 ±
12.3; controls, 28.3 ± 4.4. The ratio of fasting rbc PLP concentration to fasting plasma
PLP concentration was 2-3x higher in females with DM as compared to control females
and all male groups. Females with IDDM had a ratio of 3.2, and the ratio for females
with NIDDM was 2.2. The ratios for all male groups, and control females were approximately
1:1, with a range of 0.8-1.2.
The mean fasting plasma AP activity was within the normal range for all study
groups. However, females with DM had higher AP activity (0.543 μkat/L) as compared
to female controls and males with DM (0.408 μkat/L, .425 μkat/L, respectively p<0.05).
There were no significant differences in mean fasting plasma AP activity between any
male group (range 0.390-0.465 μkat/L).
These results suggest that increased plasma glucose levels, increased AP activity,
and overall poor glycemic control contribute to decreased plasma PLP concentrations,
increased rbc PLP concentrations, and possibly to changes in the PLP distribution within