The aim of this study was to compare mortality and incidence of end-stage renal disease (ESRD) in patients with type 1 (insulin-dependent) diabetes who had attended a diabetes center with those who had not. The cohort consisted of a total of 1430 patients diagnosed with Type 1 diabetes at 18 years or younger, and between 1965 and 1979. This population-based cohort in Japan was subdivided into two groups: patients who had visited a large diabetes center in Tokyo (n=162) and those who had not (n=1212). Mortality and incidence of ESRD were compared between the two subgroups as of January 1, 1990. Crude mortality was 1.95 per 1000 person-years (95% CI: 0.49-5.06) for those who had visited the center and 6.05 (4.86-7.41) for those who had not. A multivariate Cox proportional hazard model showed that the patients who had visited the center were three times less likely to die (hazard ratio: 0.31, 95% CI: 0.10-0.98) than those who had not. Crude incidence of ESRD was 1.32 (0.22-4.09) and 5.86 (4.65-7.26) for those who had visited the center and for those who had not, respectively. After adjusting for covariates, the patients who had visited the center were five times less likely to develop ESRD (hazard ratio: 0.19, 0.05-0.78) than those who had not. Education and treatment of type 1 diabetes with an integrated management system under specialists and a multidisciplinary team appears to be associated with a better prognosis.

Academic Medical Centers↗

PubMedDate not supplied

Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with Type 1 diabetes.

We investigated whether serum levels of N-(carboxymethyl)lysine (CML), non-CML advanced glycation endproducts (AGEs), or pentosidine are associated with severity of diabetic microvascular complications in patients with Type 1 diabetes. Serum levels of CML, non-CML AGE, and pentosidine were measured by an enzyme-linked immunosorbent assay in 38 males and 47 females aged 31+/-8 years (mean+/-S.D.) with Type 1 diabetes for 18.7+/-7.0 years. There was a significant correlation between serum levels of CML or non-CML AGE and current HbA(1c) level (P<.01 and P<.05, respectively). The serum levels of non-CML AGE, but not CML or pentosidine, were significantly increased as normal renal status advanced to microalbuminuria, clinical nephropathy, and hemodialysis (P<.0001) and were positively correlated with urinary albumin excretion (UAE) in patients with Type 1 diabetes (P<.0001). A significant elevation of serum non-CML AGE was found in association with the severity of diabetic retinopathy (P<.0001). We found in the present study that CML levels were also increased in the stage of simple retinopathy, the early stage of clinically evident retinopathy (P<.05). Serum levels of non-CML AGE were significantly associated with the severity of diabetic nephropathy and retinopathy, suggesting a role of non-CML AGE in the progression of microvascular complications in patients with Type 1 diabetes. Since serum levels of CML were significantly increased in patients with simple retinopathy, CML may participate in the initiation of diabetic retinopathy.

Adult↗

PubMedDate not supplied

AGE down-regulation of monocyte RAGE expression and its association with diabetic complications in type 1 diabetes.

Advanced glycation end product (AGE) engagement of a cell surface receptor for AGE (RAGE) has been implicated in the development of diabetic complications. In this study, we determined the RAGE mRNA levels in monocytes from type 1 diabetic patients and analyzed their relationship with diabetic vascular complications. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the monocyte expression of RAGE mRNA was significantly lower in patients with retinopathy than in those without retinopathy and was also significantly down-regulated in patients with nephropathy in comparison with those without nephropathy. Experiments with monocyte-enriched cultures revealed that RAGE mRNA and protein levels were down-regulated by the exposure to glyceraldehyde-derived AGE-the recently identified high-affinity RAGE ligand. Accordingly, we then assayed for the serum levels of glyceraldehyde-derived AGE as well as those of carboxymethyllysine (CML)-the known RAGE ligand and related them to the monocyte levels of RAGE mRNA. This screen revealed a negative correlation between the two parameters. The results thus suggest that the decrease in monocyte RAGE expression can be at least partly accounted for by the ligand engagement and may be a factor contributing to the development of diabetic vascular complications.

Adolescent↗

PubMedDate not supplied

Potentiation of mitogenic activity of platelet-derived growth factor by physiological concentrations of insulin via the MAP kinase cascade in rat A10 vascular smooth muscle cells.

Hyperinsulinemia has been shown to be associated with diabetic angiopathy. Migration and proliferation of vascular smooth muscle cells (VSMC) are the processes required for the development of atherosclerosis. In this study, we attempted to determine whether insulin affects mitogenic signaling induced by platelet-derived growth factor (PDGF) in a rat VSMC cell line (A10 cells). PDGF stimulated DNA synthesis which was totally dependent on Ras, because transfection of dominant negative Ras resulted in complete loss of PDGF-stimulated DNA synthesis. Initiation of DNA synthesis was preceded by activation of Raf-1, MEK and MAP kinases (Erk 1 and Erk2). Treatment of the cells with PD98059, an inhibitor of MAPK kinase (MEK) attenuated but did not abolish PDGF-stimulated DNA synthesis, suggesting that MAPK is required but not essential for DNA synthesis. PDGF also stimulated phosphorylation of protein kinase B (Akt/PKB) and p70 S6Kinase (p70S6K) in a wortmannin-sensitive manner. Rapamycin, an inhibitor of p70S6K, markedly suppressed DNA synthesis. Low concentrations of insulin (1-10 nmol/l) alone showed little mitogenic activity and no significant effect on MAPK activity. However, the presence of insulin enhanced both DNA synthesis and MAPK activation by PDGF. The enhancing effect of insulin was not seen in cells treated with PD98059. Insulin was without effect on PDGF-stimulated activations of protein kinase B (Akt/PKB) and p70S6K. We conclude that insulin, at pathophysiologically relevant concentrations, potentiates the PDGF-stimulated DNA synthesis, at least in part, by potentiating activation of the MAPK cascade. These results are consistent with the notion that hyperinsulinemia is a risk factor for the development of atherosclerosis.

Animals↗

PubMedDate not supplied

Measurement of HRQL using EQ-5D in patients with type 2 diabetes mellitus in Japan.

OBJECTIVES: We measured the health-related quality of life (HRQL) of diabetes mellitus patients using the Japanese version of EQ-5D, and examined the relationship between clinical condition and health status. METHODS: A study was conducted on 220 patients with type 2 diabetes mellitus at a hospital in Saitama Prefecture on the day of their visit from November 17 to December 24, 1998. Patients evaluated their health status using five dimensions (5D) and a visual analog scale (VAS). The EQ-5D score was calculated based on the 5D responses using the Japanese version of the value set. RESULTS: There were no responses of "extreme problem." The frequency of "some problem" was significantly higher in patients with complications than in those without for mobility (27.4% and 14.4%) and anxiety/depression (25.7% and 13.5%). The mean EQ-5D score was 0.846 (95% confidence interval [CI] 0.817-0.874) in patients with complications versus 0.884 (95% CI 0.855-0.914) in those without complications. There was no statistically significant difference between VAS scores according to the presence or absence of diabetic complications, but a significant difference in VAS scores was seen according to the presence or absence of retinopathy. CONCLUSION: These findings suggest the value of measuring health status in diabetes mellitus patients, because it is able to comprehensively evaluate the patient's health condition, and add another dimension to the subjective symptoms and laboratory data.

Adult↗