To clarify the cause of malformations in infants of diabetic mothers, we measured plasma phosphatidylcholine hydroperoxide (PCOOH), as an index of oxidative stress, in 68 pregnant diabetic women by using chemiluminescense-high performance liquid chromatography (CLHPLC).
The average level of plasma PCOOH in 24 healthy non-pregnant controls was 368.2±114.1 pmol/ml. A significant increase in plasma PCOOH level was found in diabetic non-pregnant women when compared to healthy non-pregnant controls. In normal pregnant women, plasma PCOOH levels were significantly increased in the third trimester compared to normal non-pregnant women. There was a significant increase in plasma PCOOH level in the third trimester when compared to that in the first trimester in pregnant diabetics. No difference was found in the PCOOH levels in diabetic pregnant women compared to that in normal pregnant women during pregnancy. In the first trimester there was no difference in plasma PCOOH levels in diabetic pregnant women when compared to normal pregnant women and to healthy non-pregnant women. None of the infants born from the diabetic mothers examined had malformations. We were unable to find any relation between maternal PCOOH levels and malformations of infants of diabetic mothers.

View full abstract

It is well known that plasma triglyceride (TG) levels are increased in patients with diabetes mellitus. However, several recent publications have disclosed that normoalbuminuric diabetics do not have higher plasma TG levels than nondiabetic subjects when diabetics are classified into subgroups according to the amount of albumin in the urine. This suggests that the hypertriglyceridemia accompanied by diabetes is more closely associated with nephropathy than diabetes per se. To verify this possibility, we measured plasma TG levels in [middle-aged to elderly] non-insulin dependent diabetes mellitus (NIDDM) patients (n=274) with normo-, micro-and overt albuminuria and compared them with those of age-and weight-matched nondiabetic controls (n=66). Plama TG levels in normoalbuminuric NIDDM patients were identical to those in nondiabetic controls (110±6 vs120±7mg/dl), whereas the levels were significantly increased in NIDDM patients with microalbuminuria (157±8mg/dl) and overt albuminuria (169±11mg/dl). In the total NIDDM patients, plasma TG was significantly correlated with the amount of albumin in the urine and body mass index but not with fasting plasma glucose or HbAic levels. Multiple regression analysis revealed that albuminuria has the strongest independent correlation with the TG level. The degree of insulin resistance was determined by measuring the steady-state plasma glucose (SSPG) levels when glucose, insulin and octreotide were continuously infused for 160 min. The SSPG, indicating insulin resistance, was not increased in NIDDM patients with nephropathy compared with patients without nephropathy, and SSPG was not correlated with plasma TG levels in the total NIDDM subjects. These results suggest that diabetic nephropathy including the subclinical stage plays a critical role in the hypertriglyceridemia accompanied by diabetes. Poor glycemic control and increased insulin resistance are not closely associated with the hypertriglyceridemia, at least in middle-aged to elderly JapaneseNIDDM patients.

View full abstract

HLA class II antigen frequencies in 35 non-obese patients with NIDDM, 27 obese patients with NIDDM, and 27 normal controls were determined. The frequencies of HLA-DQA10103, DQB10601, and DR2 were significantly increased in non-obese patients with NIDDM compared with control subjects. The frequency of HLA-DR2-DQA10103-DQB10601, which is known to be a protective haplotype, with IDDM in Japan was significantly increased in non-obese patients with NIDDM. These results suggest that non-obese NIDDM in Japan may be related to HLA class II antigen.

View full abstract

To determine whether urinary excretion of kappa light chain (KLC) can be used as a predictor for development of early diabetic nephropathy, we measured the levels of KLC and albumin in first-voided morning urine samples from 104 non-insulin dependent diabetic patients without overt proteinuria (urinary albumin creatinine ratio (ACR)<150mg/gCr). In the patients with increased excretion of urinary KLC creatinine ratio (KCR)(≥5.8mg/gCr), the ACR was significantly increased in both normoalbuminuric (ACR<20mg/gCr) and microalbuminuric (20≤ACR<150mg/gCr) patients after 5 years, whereas in those with a normal KCR (<5.8mg/gCr), the ACR showed no significant change in either normo-or microalbuminuric patients. The number of patients with an increase in ACR for 5 years was significantly large among the patients with increased KCR. Multiple regression analysis showed that KCR was a significant risk factor for increasing the ACR after 5 years. The KCR showed no significant change in either normo-or microalbuminuric patients for 5 years. These results suggest that urinary excretion of KLC might provide a useful predictive marker for development of early diabetic nephropathy.

View full abstract

To determine the latent effect of diabetes inheritance on central nervous system, thirty diabetic patients were examined (14 male, 16 female). Seventeen patients had a mother with diabetes, and the other thirteen had non-diabetic mothers. They were previously determined to not have the 3243 mitochondrial tRNA mutation in peripheral leukocytes. Patients were tested for parieto-occipital hypoaccumulation of ¹²³I-IMP of brain SPECT, a characteristic neurofinding of mitochondrial diabetes mellitus due to the 3243 tRNA mutation.
Seven (41.2%) out of 17 subjects with maternal inheritance had the parieto-occipital abnormality, whereas one (7.7%) out of 13 subjects with non-maternal inheritance had the abnormality. Seventeen (94.4%) out of 18 patients with diabetes due to mitochondrial tRNA mutation at position 3243 showed the abnormality.
Our results suggest that the maternal inheritance of diabetes is associated with the hypoaccumulation of ¹²³I-IMP of brain SPECT. We speculate that, because the patients with maternal inheritance might have subclinical mitochondrial dysfunction due to unknown mitochondrial DNA abnormalities, the mitochondrial DNA abnormality might cause their subclinical brain damage in the parieto-occipital area.

View full abstract