http://archinte.jamanetwork.com/ en-us Mon, 28 Nov 2011 00:00:00 GMT Tue, 01 Jan 2013 00:46:26 GMT Silverchair editor@archinte.jamanetwork.com webmaster@archinte.jamanetwork.com http://archinte.jamanetwork.com/article.aspx?articleID=1106019 Mon, 28 Nov 2011 00:00:00 GMT Goff DC. <span class="paragraphSection">Diabetes mellitus (DM) confers very high risk for cardiovascular disease (CVD). Chronic kidney disease (CKD) is a common complication of DM that further increases risk of CVD, the development of end-stage renal disease (ESRD), and other complications. Multiple interventions have been tested in patients with DM with the hope that these interventions might reduce the risk of CVD and microvascular complications. Unfortunately, persons with CKD have been excluded or, at least, underrepresented in these trials. For example, on the one hand, in order to use metformin in a manner consistent with its product label in the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes), we excluded patients with elevated levels of creatinine, and, therefore, most individuals with CKD. On the other hand, the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation) trial included individuals with CKD. The ADVANCE investigators have reported the efficacy of the blood pressure (BP) lowering intervention on cardiovascular and renal outcomes in participants with CKD; however, they have not yet published the results of their glucose-lowering intervention in this subgroup. Nevertheless, the results of the ADVANCE BP-lowering trial in CKD may be informative.</span> 171 21 1927 1928 10.1001/archinternmed.2011.520 http://archinte.jamanetwork.com/article.aspx?articleID=1106019 http://archinte.jamanetwork.com/article.aspx?articleID=1106040 Mon, 28 Nov 2011 00:00:00 GMT Shurraw S, Hemmelgarn B, Lin M, et al. <span class="paragraphSection"><div class="boxTitle">Background</div>Better glycemic control as reflected by lower hemoglobin A_1c (HbA_1c) level may prevent or slow progression of nephropathy in people with diabetes mellitus (DM). Whether a lower HbA_1c level improves outcomes in people with DM and chronic kidney disease (CKD) is unknown.<div class="boxTitle">Methods</div>From all people with serum creatinine measured as part of routine care in a single Canadian province from 2005 through 2006, we identified those with CKD based on laboratory data (estimated glomerular filtration rate [eGFR], <60.0 mL/min/1.73 m²]) and DM using a validated algorithm applied to hospitalization and claims data. Patients were classified based on their first HbA_1c measurement; Cox regression models were used to assess independent associations between HbA_1c level and 5 study outcomes (death, progression of kidney disease based on a doubling of serum creatinine level, or new end-stage renal disease [ESRD], cardiovascular events, all-cause hospitalization).<div class="boxTitle">Results</div>We identified 23 296 people with DM and an eGFR lower than 60.0 mL/min/1.73 m². The median HbA_1c level was 6.9% (range, 2.8%-20.0%), and 11% had an HbA_1c value higher than 9%. Over the median follow-up period of 46 months, 3665 people died, and 401 developed ESRD. Regardless of baseline eGFR, a higher HbA_1c level was strongly and independently associated with excess risk of all 5 outcomes studied (P < .001 for all comparisons). However, the association with mortality was U-shaped, with increases in the risk of mortality apparent at HbA_1c levels lower than 6.5% and higher than 8.0%. The increased risk of ESRD associated with a higher HbA_1c level was attenuated at a lower baseline eGFR (P value for interaction, <.001). Specifically, among those with an eGFR of 30.0 to 59.9 mL/min/1.73 m², the risk of ESRD was increased by 22% and 152% in patients with HbA_1c levels of 7% to 9% and higher than 9%, respectively, compared with patients with an HbA_1c level lower than 7% (P < .001), whereas corresponding increases were 3% and 13%, respectively, in those with an eGFR of 15.0 to 29.9 mL/min/1.73 m².<div class="boxTitle">Conclusions</div>A hemoglobin A_1c level higher than 9% is common in people with non–hemodialysis-dependent CKD and is associated with markedly worse clinical outcomes; lower levels of HbA_1c (<6.5%) also seemed to be associated with excess mortality. The excess risk of kidney failure associated with a higher HbA_1c level was most pronounced among people with better kidney function. These findings suggest that appropriate and timely control of HbA_1c level in people with DM and CKD may be more important than previously realized, but suggest also that intensive glycemic control (HbA_1c level <6.5%) may be associated with increased mortality.</span> 171 21 1920 1927 10.1001/archinternmed.2011.537 http://archinte.jamanetwork.com/article.aspx?articleID=1106040