Masatomo Sekiguchi

Apolipoprotein E polymorphism and hyperlipemia in type II diabetics.

The relationship between apolipoprotein E (apoE) polymorphism and plasma lipids and hyperlipemia was investigated in 105 male type II diabetics and 111 male nondiabetics. ApoE phenotypes were determined by a one-dimensional rapid flat gel isoelectric focusing method as described previously. The apoE phenotype frequency in diabetics was similar to that in nondiabetics. The frequency of hyperlipemia was higher in diabetics (56.2%) than in nondiabetics (32.4%). It was highest in the apoE3/2 group of diabetics and nondiabetics, followed by the apoE4/3 and apoE3/3 groups in the order described, indicating that the susceptibility to hyperlipemia differs among the apoE phenotype groups. ApoE3/2 diabetics had significantly higher levels of apoE and very-low-density lipoprotein (VLDL) cholesterol (chol)/VLDL triglyceride (TG) ratios than apoE3/3 diabetics. The effects of diabetes mellitus on plasma lipid levels differed among the various apoE phenotype groups: i.e., plasma total chol and low-density lipoprotein (LDL) chol increased only in apoE3/2 and apoE4/3 diabetics and plasma high-density lipoprotein chol decreased only in apoE3/3 diabetics, as compared with the corresponding apoE phenotype groups of nondiabetics, whereas plasma TG, VLDL TG, and VLDL chol increased in the three apoE phenotype diabetics. Furthermore, an increase of apoEII; apoEIII ratio was observed in apoE3/3 diabetics, particularly in those with hypertriglyceridemia. This study has also shown that the increased apoEII: apoEIII ratio is due to increased sialation of apoE based on the study of sialidase digestion of apo VLDL. We conclude that apoE polymorphism should be taken into consideration when plasma lipoprotein patterns are studied in type II diabetics and that increased sialation of apoE may at least partly contribute to an increased frequency of hypertriglyceridemia in type II diabetics.

Detection of the association between a deletion polymorphism in the gene encoding angiotensin I-converting enzyme and advanced diabetic retinopathy

We investigated the relationship between advanced diabetic retinopathy (ADR) and an angiotensin-converting enzyme (ACE) gene polymorphism in subjects with type 2 diabetes and ADR, pre-proliferative (PrePDR) or proliferative diabetic retinopathy (PDR) without overt nephropathy. Polymerase chain reactions were used to detect insertion/deletion (I/D) polymorphisms of the ACE gene. There was no difference in the frequency of II, ID, or DD genotypes, or of I and D alleles among subjects with type 2 diabetes without diabetic retinopathy (NDR) or with simple diabetic retinopathy (SDR) and non-diabetic controls. There was also no difference in the frequency of ACE genotypes among subjects with type 2 diabetes with NDR, or SDR and ADR. However, the frequency of the ACE DD genotype in ADR was significantly higher than that in controls (chi(2)=6.64, P=0.036). On the other hand, the frequency of the D allele in ADR was significantly higher than that in controls (chi(2)=6.33, P=0.012), NDR (chi(2)=4.18, P=0.041) and SDR (chi(2)=4. 89, P=0.027), respectively. These results indicate a significant relationship between the presence of the D allele polymorphism in the ACE gene and ADR in Japanese subjects with type 2 diabetes and no overt nephropathy.

Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia.

The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulindependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type lib hyperlipoproteinemia, n = 42). The frequencies of apoE4-present phenotypes (apoE4/3, apoE4/4, and apoE4/2) were highest in the type IIa group (51.4%), followed by the type Mb group (38.1%) and the normolipidemic group (16.4%), respectively, whereas the frequency of the most common phenotype, apoE3/3, was lowest in the type IIa group (48.6%), followed by the type lib group (61.9%) and the normolipidemic group (79.9%), respectively. There were significant differences in the apoE phenotype frequencies between the normolipidemic group and the type IIa and Mb groups. The frequency of the ∈4 allele was significantly higher in the type IIa (28.6%) and Mb (20.2%) groups than in the normolipidemic group (8.9%), whereas the frequency of the ∈3 allele was significantly lower in the type IIa (71.4%) and Mb (78.6%) groups than in the normolipidemic group (89.2%). The frequency of the ∈2 allele tended to be lower in diabetic patients with hypercholesterolemia. In addition, these frequencies were also examined in nondiabetic subjects (n = 59). The frequency of the ∈4 allele tended to be higher in hypercholesterolemic diabetic subjects (24.1%) than in hypercholesterolemicnondiabetic subjects (15.3%). These data suggest that diabetic patients with the ∈4 allele may be more susceptible to hypercholesterolemia than diabetic patients without the ∈4 allele and possibly nondiabetic subjects with the ∈4 allele, although the underlying mechanism is unknown.

Polyol pathway in tissues of spontaneously diabetic Chinese hamsters (Cricetulus griseus) and the effect of an aldose reductase inhibitor, ONO-2235

1. Sorbitol and fructose levels were significantly elevated in the lens, the sciatic nerve, the retina and the kidney of diabetic Chinese hamsters and inositol level was significantly decreased in the lens and sciatic nerve of diabetics. 2. The activity of an aldose reductase in the kidney was not different between normal and diabetic Chinese hamsters. 3. An aldose reductase inhibitor (ONO-2235) had no effect in sorbitol, fructose and inositol contents of all these tissues from diabetic Chinese hamsters. 4. These results suggest that diabetic Chinese hamsters produce polyol accumulation in tissues but that there is a clear species-specific difference to inhibition of aldose reductase.