The association between the incidence of diabetic retinopathy and the development of diabetic nephropathy was studied in 110 Type I (insulin-dependent) diabetic patients during a period from 10 years ...before to 5 years after the onset of persistent proteinuria. This group of patients was compared with 110 diabetic patients, who were matched according to sex, age, and diabetes duration, but who were without proteinuria during the observation period. The cumulative incidence of proliferative retinopathy was 74% in patients with clinical nephropathy and 14% in patients free of proteinuria. The incidence of background retinopathy was 93% and 37%, respectively, and the incidence of retinopathy increased dramatically 5 years before the onset of proteinuria. Neither gender, age at onset of diabetes, nor blood pressure seemed to have much influence on the incidence of severe retinopathy. It is concluded that development of clinical diabetic nephropathy implies an extremely high risk of developing severe retinopathy. A common pathogenetic link may be suspected.
In the present study, we tested the hypothesis that variability in the protein tyrosine phosphatase-1B (PTP-1B) gene is associated with type 2 diabetes. Using single-strand conformational ...polymorphism analysis, we examined cDNA of PTP-1B from 56 insulin-resistant patients with type 2 diabetes as well as cDNA from 56 obese patients. Four silent variants, (NT CGA-->CGG) R199R, (NT CCC-->CCT) P303P, 3'UTR+104insG, and 3'UTR+86T-->G, and one missense variant, P387L, were found. Subsequent analysis on genomic DNA revealed two intron variants, IVS9+57C-->T and IVS9+58G-->A, and two missense variants, G381S and T420M. The G381S and 3'UTR+104insG insertion variants were not associated with type 2 diabetes. In an association study, the P387L variant was found in 14 of 527 type 2 diabetic subjects (allelic frequency 1.4%, 0.4-2.4 CI) and in 5 of 542 glucose-tolerant control subjects (allelic frequency 0.5%, CI 0.1-1.1), showing a significant association to type 2 diabetes (P = 0.036). In vitro, p34 cell division cycle (p34(cdc2)) kinase-directed incorporation of gamma-(32)PATP was reduced in a mutant peptide compared with native peptide (387P: 100% vs. 387L: 28.4 +/- 5.8%; P = 0.0012). In summary, a rare P387L variant of the PTP-1B gene is associated with a 3.7 (CI 1.26-10.93, P = 0.02) genotype relative risk of type 2 diabetes in the examined population of Danish Caucasian subjects and results in impaired in vitro serine phosphorylation of the PTP-1B peptide.
Background: Diabetes has been associated with an increased risk of several cancers, notably cancers of the pancreas, liver, endometrium, and kidney. Since most previous studies have involved a ...limited sample size or focused on specific cancer sites, we conducted a comprehensive assessment of the risk of cancer in a nationwide cohort of diabetics in Denmark. Methods: Discharge records of 109 581 individuals hospitalized with a diagnosis of diabetes from 1977 through 1989 were linked with national cancer registry records through 1993. Standardized incidence ratios (SIRs) were calculated for specific cancer sites. Results: The SIRs for primary liver cancer were 4.0 (95% confidence interval CI = 3.5–4.6) in males and 2.1 (95% CI = 1.6–2.7) in females. These SIRs remained elevated with increasing years of follow-up and after exclusion of patients with reported risk factors (e.g., cirrhosis and hepatitis) or patients whose cancers were diagnosed at autopsy. Kidney cancer risk was also elevated, with SIRs of 1.4 (95% CI = 1.2–1.6) in males and 1.7 (95% CI = 1.4–1.9) in females. For both sexes combined, the SIR for pancreatic cancer was 2.1 (95% CI = 1.9–2.4), with a follow-up time of 1–4 years; this SIR declined to 1.3 (95% CI = 1.1–1.6) after 5–9 years of follow-up. Excess risks were also observed for biliary tract and endometrial cancers. The SIRs for kidney and endometrial cancers declined somewhat after exclusion of diabetics with reported obesity. Conclusions: Patients hospitalized with a diagnosis of diabetes appear to be at higher risk of developing cancers of the liver, biliary tract, pancreas, endometrium, and kidney. The elevated risks of endometrial and kidney cancers, however, may be confounded by obesity.
PDF