Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes: The DCCT/EDIC study

Ian H. de Boer, Xiaoyu Gao, Patricia A. Cleary, Ionut Bebu, John M. Lachin, Mark E. Molitch, Trevor Orchard, Andrew D. Paterson, Bruce A. Perkins, Michael W. Steffes, Bernard Zinman, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group

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Abstract

Background and objectives In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes. Design, setting, participants, & measurements We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30–299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m 2 on two consecutive visits), and subclinical cardiovascular disease. Results At least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification. Conclusions In type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.

Original languageEnglish (US)
Pages (from-to)1969-1977
Number of pages9
JournalClinical Journal of the American Society of Nephrology
Volume11
Issue number11
DOIs
StatePublished - Jan 1 2016

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Albuminuria
Type 1 Diabetes Mellitus
Albumins
Kidney
Confidence Intervals
Diabetes Complications
Cardiovascular Diseases
Carotid Intima-Media Thickness
Renin-Angiotensin System
Type 2 Diabetes Mellitus
Coronary Vessels
Epidemiology

Keywords

  • albumins
  • albuminuria
  • cardiovascular disease
  • cardiovascular diseases
  • carotid intima-media thickness
  • chronic kidney disease
  • coronary vessels
  • diabetes
  • diabetes mellitus, type 1
  • diabetes mellitus, type 2
  • disease progression
  • kidney
  • progression of chronic renal failure
  • renin-angiotensin system
  • risk

Cite this

de Boer, I. H., Gao, X., Cleary, P. A., Bebu, I., Lachin, J. M., Molitch, M. E., ... Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group (2016). Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes: The DCCT/EDIC study. Clinical Journal of the American Society of Nephrology, 11(11), 1969-1977. https://doi.org/10.2215/CJN.02870316

Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes : The DCCT/EDIC study. / de Boer, Ian H.; Gao, Xiaoyu; Cleary, Patricia A.; Bebu, Ionut; Lachin, John M.; Molitch, Mark E.; Orchard, Trevor; Paterson, Andrew D.; Perkins, Bruce A.; Steffes, Michael W.; Zinman, Bernard; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group.

In: Clinical Journal of the American Society of Nephrology, Vol. 11, No. 11, 01.01.2016, p. 1969-1977.

Research output: Contribution to journalArticle

de Boer, IH, Gao, X, Cleary, PA, Bebu, I, Lachin, JM, Molitch, ME, Orchard, T, Paterson, AD, Perkins, BA, Steffes, MW, Zinman, B & Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group 2016, 'Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes: The DCCT/EDIC study' Clinical Journal of the American Society of Nephrology, vol. 11, no. 11, pp. 1969-1977. https://doi.org/10.2215/CJN.02870316
de Boer, Ian H. ; Gao, Xiaoyu ; Cleary, Patricia A. ; Bebu, Ionut ; Lachin, John M. ; Molitch, Mark E. ; Orchard, Trevor ; Paterson, Andrew D. ; Perkins, Bruce A. ; Steffes, Michael W. ; Zinman, Bernard ; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group. / Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes : The DCCT/EDIC study. In: Clinical Journal of the American Society of Nephrology. 2016 ; Vol. 11, No. 11. pp. 1969-1977.
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abstract = "Background and objectives In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes. Design, setting, participants, & measurements We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30–299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m 2 on two consecutive visits), and subclinical cardiovascular disease. Results At least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95{\%} confidence intervals [95{\%} CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95{\%} CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95{\%} CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95{\%} CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification. Conclusions In type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.",
keywords = "albumins, albuminuria, cardiovascular disease, cardiovascular diseases, carotid intima-media thickness, chronic kidney disease, coronary vessels, diabetes, diabetes mellitus, type 1, diabetes mellitus, type 2, disease progression, kidney, progression of chronic renal failure, renin-angiotensin system, risk",
author = "{de Boer}, {Ian H.} and Xiaoyu Gao and Cleary, {Patricia A.} and Ionut Bebu and Lachin, {John M.} and Molitch, {Mark E.} and Trevor Orchard and Paterson, {Andrew D.} and Perkins, {Bruce A.} and Steffes, {Michael W.} and Bernard Zinman and {Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group}",
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TY - JOUR

T1 - Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes

T2 - The DCCT/EDIC study

AU - de Boer, Ian H.

AU - Gao, Xiaoyu

AU - Cleary, Patricia A.

AU - Bebu, Ionut

AU - Lachin, John M.

AU - Molitch, Mark E.

AU - Orchard, Trevor

AU - Paterson, Andrew D.

AU - Perkins, Bruce A.

AU - Steffes, Michael W.

AU - Zinman, Bernard

AU - Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background and objectives In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes. Design, setting, participants, & measurements We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30–299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m 2 on two consecutive visits), and subclinical cardiovascular disease. Results At least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification. Conclusions In type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.

AB - Background and objectives In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes. Design, setting, participants, & measurements We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER continuously <30 mg/d), sustained microalbuminuria (AER, 30–299 mg/d on two consecutive visits), macroalbuminuria (AER≥300 mg/d), or remitted microalbuminuria (transition from sustained microalbuminuria to AER<30 mg/d on two consecutive visits). We tested associations of time-updated albuminuria status with adjudicated clinical cardiovascular events, the development of reduced GFR (<60 ml/min per 1.73 m 2 on two consecutive visits), and subclinical cardiovascular disease. Results At least one cardiovascular event occurred in 184 participants, and 98 participants developed reduced eGFR. Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were each associated with higher risk of cardiovascular events (adjusted hazard ratios [HRs] and 95% confidence intervals [95% CIs]: 1.79 [1.13 to 2.85], 2.62 [1.68 to 4.07], and 2.65 [1.68 to 4.19], respectively) and reduced eGFR (adjusted HRs [95% CIs], 5.26 [2.43 to 11.41], 4.36 [1.80 to 10.57], and 54.35 [30.79 to 95.94], respectively). Compared with sustained microalbuminuria, remission to normoalbuminuria was not associated with reduced risk of cardiovascular events (adjusted HR, 1.33; 95% CI, 0.68 to 2.59) or reduced eGFR (adjusted HR, 1.75; 95% CI, 0.56 to 5.49). Compared with normoalbuminuria, sustained microalbuminuria, remitted microalbuminuria, and macroalbuminuria were associated with greater carotid intima-media thickness, and macroalbuminuria was associated with a greater degree of coronary artery calcification. Conclusions In type 1 diabetes, microalbuminuria and macroalbuminuria are associated with higher risks of cardiovascular disease and reduced eGFR, but achieving a remission of established microalbuminuria to normoalbuminuria does not appear to improve outcomes.

KW - albumins

KW - albuminuria

KW - cardiovascular disease

KW - cardiovascular diseases

KW - carotid intima-media thickness

KW - chronic kidney disease

KW - coronary vessels

KW - diabetes

KW - diabetes mellitus, type 1

KW - diabetes mellitus, type 2

KW - disease progression

KW - kidney

KW - progression of chronic renal failure

KW - renin-angiotensin system

KW - risk

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U2 - 10.2215/CJN.02870316

DO - 10.2215/CJN.02870316

M3 - Article

VL - 11

SP - 1969

EP - 1977

JO - Clinical Journal of the American Society of Nephrology

JF - Clinical Journal of the American Society of Nephrology

SN - 1555-9041

IS - 11

ER -