Kidney Disease and Related Findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Article (PDF Available)inDiabetes care 37(1):24-30 · January 2014with12 Reads
DOI: 10.2337/dc13-2113 · Source: PubMed
OBJECTIVE Kidney disease manifests clinically as elevated albumin excretion rate (AER), impaired glomerular filtration rate (GFR), or both, and is a cause of substantial morbidity and mortality in type 1 diabetes (T1D). The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study tested whether intensive diabetes therapy (INT) aimed at lowering glucose concentrations as close as safely possible to the normal range reduces the risks of kidney disease and other diabetes complications.RESEARCH DESIGN AND METHODS In the DCCT, 1,441 participants with T1D were randomly assigned to INT or conventional diabetes therapy (CON) for a mean duration of 6.5 years. Subsequently, participants have been followed for 18 years in the ongoing observational EDIC. Standardized longitudinal measurements of AER, estimated GFR, and blood pressure were made throughout the DCCT/EDIC.RESULTSDuring the DCCT, INT reduced the risks of incident microalbuminuria (AER 40 mg/24 h) and macroalbuminuria (AER 300 mg/24 h) by 39% (95% CI 21-52%) and 54% (29-74%), respectively. During EDIC years 1-8, participants previously assigned to DCCT INT continued to experience lower rates of incident microalbuminuria and macroalbuminuria, with risk reductions of 59% (39-73%) and 84% (67-92%), respectively. Beneficial effects of INT on the development of impaired GFR (sustained estimated GFR <60 mL/min/1.73 m(2)) and hypertension became evident during combined DCCT/EDIC follow-up, with risk reductions of 50% (18-69%) and 20% (6-21%), respectively, compared with CON.CONCLUSIONS In the DCCT/EDIC, INT resulted in clinically important, durable reductions in the risks of microalbuminuria, macroalbuminuria, impaired GFR, and hypertension.

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Available from: PubMed Central, Jan 02, 2015 · License: CC BY-NC-ND
    • "Tight glucose control is of paramount importance throughout the time course of diabetes in order to most effectively prevent organ complications . For example, studies have shown that poor glucose control in the early stages of diabetes, even if corrected, still may have lasting effects on prognosis of complications long-term [176]. Moreover, glycemic variability is known to associate with adverse diabetes complications [177] and, in type 1 diabetic patients, high glycemic variability predicts microvascular complications [178]. "
    [Show abstract] [Hide abstract] ABSTRACT: Diabetes mellitus (DM) is a metabolic disease defined by elevated blood glucose (BG). DM is a global epidemic and the prevalence is anticipated to continue to increase. The ocular complications of DM negatively impact the quality of life and carry an extremely high economic burden. While systemic control of BG can slow the ocular complications they cannot stop them, especially if clinical symptoms are already present. With the advances in biodegradable polymers, implantable ocular devices can slowly release medication to stop, and in some cases reverse, diabetic complications in the eye. In this review we discuss the ocular complications associated with DM, the treatments available with a focus on localized treatments, and what promising treatments are on the horizon.
    Full-text · Article · Mar 2016
    • "e b i o m e d i c i n e . c o m et al., 2011; DCCT/EDIC research group, 2014; de Boer, 2014 ), suggesting a possible causal link between diabetes and renal outcomes. However , because conventional epidemiological studies are subject to a variety of bias such as confounding or reverse causation, and the RCTs are largely limited by short-term intervention, other novel approaches are needed to investigate the causal relation between T2D and renal dysfunction. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Type 2 diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, whether the association is causal remains unestablished. Research Design and Methods We performed a Mendelian Randomization (MR) analysis in 11,502 participants aged 40 and above, from a well-defined community in Shanghai during 2011–2013, to explore the causal association between T2D and decreased estimated GFR (eGFR) and increased urinary albumin-to-creatinine ratio (uACR). We genotyped 34 established T2D common variants in East Asians, and created a T2D-genetic risk score (GRS). We defined decreased eGFR as eGFR < 90 ml/min/1.73 m² and increased uACR as uACR ≥ 30 mg/g. We used the T2D_GRS as the instrumental variable (IV) to quantify the causal effect of T2D on decreased eGFR and increased uACR. Results Each 1-standard deviation (SD, 3.90 points) increment in T2D_GRS was associated with decreased eGFR: odds ratio (OR) = 1.18 (95% confidence interval [CI]: 1.01, 1.30). In the MR analysis, we demonstrated a causal relationship between genetically determined T2D and decreased eGFR (OR = 1.47, 95% CI: 1.15, 1.88, P = 0.0003). When grouping the genetic loci according to their relations with either insulin secretion (IS) or insulin resistance (IR), we found both IS_GRS and IR_GRS were significantly related to decreased eGFR (both P < 0.02). In addition, T2D_GRS and IS_GRS were significantly associated with Log-uACR (both P = 0.04). Conclusion Our results provide novel evidence for a causal association between T2D and decreased eGFR by using MR approach in a Chinese population.
    Full-text · Article · Feb 2016
    • "For that reason, early detection of diabetic nephropathy may have a pivotal role in the prevention of ESRD in diabetes [19]. While the appearance of microalbuminuria is often the earliest clinical sign of diabetic nephropathy, this classical paradigm has been questioned over the past few years after the demonstration that microalbuminuria does not necessarily imply progressive nephropathy , and may in fact regress to normoalbuminuria [20, 21@BULLET@BULLET], and that CKD stage 3 can develop in the absence of microalbuminuria [7, 22]. Albuminuria is still an important risk factor in diabetes as it is strongly associated with dyslipidemia and cardiovascular disease [23, 24]. "
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