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Cardiovascular disease (CVD) is the most common cause of death in industrialized nations. Type 2 diabetes is a CVD risk factor that confers risk similar to a previous myocardial infarction in an individual who does not have diabetes. In addition, the most common cause of chronic kidney disease (CKD) is diabetes. Together, diabetes and hypertension account for more than two-thirds of CVD risk, and other risk factors such as dyslipidemia contribute to the remainder of CVD risk. CKD, particularly with presence of significant albuminuria, should be considered an additional cardiovascular risk factor. There is no consensus on how to assess and stratify risk for patients with kidney disease across subspecialties that commonly treat such patients. This paper summarizes the results of a consensus conference utilizing a patient case to discuss the integrated management of hypertension, kidney disease, dyslipidemia, diabetes, and heart failure across disciplines.

Background: Several studies have shown that cultured skin fibroblasts from patients with diabetic nephropathy (DN) exhibit a hyperplastic growth phenotype. Increased DNA synthesis in cells from patients with DN may ultimately involve alterations in cell cycle regulatory proteins. p16 protein is a member of INK4 family of cyclin-dependent kinase inhibitors, which plays an important role in cell cycle regulation. In this study, we examined the correlation between p16 protein expression in cultured dermal fibroblasts from type 1 diabetic patients and the presence of DN., Method: Western blot analysis was performed to compare p16 protein expression in skin fibroblasts from patients with DN as compared to control subjects, diabetic patients without DN, and nondiabetic patients with nephropathy. Transcriptional regulation of the p16 gene was assessed using competitive reverse transcription-polymerase chain reaction (RT-PCR). Methylation status of the promoter region of p16 was examined using methylation-specific PCR, and we used single-stranded conformational polymorphism (SSCP)-PCR to assess p16 single-nucleotide polymorphism., Results: Cells from diabetic patients with DN had nondetectable to significantly lower protein expression of p16. Similarly, mRNA expression of p16 was significantly lower in diabetic patients with DN. No hypermethylation of p16 gene was detected, and no abnormal migrating bands were noticed on SSCP-PCR analysis in cells from patients with DN., Conclusion: Our data indicate that cells from patients with DN exhibit significantly lower protein and mRNA expression of p16. This study could have not only important implications for the understanding of the pathogenesis of DN, but also the absence of p16 may ultimately serve as an early marker for DN.

To determine whether there are relationships between nephropathy, retinopathy and putative risk factors at points very early in the development of long-term complications of IDDM, we have analyzed baseline data pertinent to nephropathy in the 726 subjects in the primary prevention cohort and the 715 subjects in the secondary intervention cohort of the DCCT. AER correlated positively with CCr and HbA1c in both cohorts and with degree of retinopathy and duration of IDDM in the secondary cohort. Within the secondary cohort only mean BP and HbA1c levels were significantly increased (P < 0.005) in the 73 subjects with AER > or = 28 micrograms/24 hr compared to the 642 subjects with AER < 28 micrograms/24 hr. Stratification of all subjects in the secondary cohort showed significant associations (P < 0.001) between retinopathy level, AER, duration of diabetes at entry and entry HbA1c. Even very early in the development of retinopathy and nephropathy, there is a relationship between them and with level of metabolic control. The prospective studies of the DCCT are designed to answer the question of whether intensive diabetes treatment will affect the development and/or progression of retinopathy, and, possibly, of nephropathy.