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The Haptoglobin genotype predicts cardio-renal mortality in type 1 diabetes.

ABSTRACT: The Haptoglobin (HP) 2-2 genotype increases cardiovascular diabetes complication incidence. In type 1 diabetes, HP 2-2 also predicts declining kidney function and end-stage renal disease. We investigated whether HP 2-2 predisposes to cardio-renal mortality, while considering other causes of death as competing risks.Individuals with type 1 diabetes and HP data available (n=486; mean baseline age, 27 and duration, 19 years) were selected for study. Vital status was assessed as of 8/31/2014. The underlying cause of death was determined and classified based on standardized procedures.During 25 years of follow-up, 79 (16.3%) cardio-renal deaths and 43 (8.8%) deaths related to other causes occurred. Although total mortality did not differ by HP (25.4% with HP 1 versus 24.6% with HP 2-2, p=0.84), a greater proportion of HP 2-2 carriers exhibited a cardio-renal death (19.0 versus 14.2, p=0.05). In time-to-event analyses, HP 2-2 was associated with a statistically significant increase of the sub-distribution hazard ratio for cardio-renal mortality (HR=1.64, p=0.03), although this effect was somewhat attenuated after multivariable adjustment (HR=1.58, p=0.05).Our results suggest that in addition to predicting the incidence of cardio-renal complications, HP 2-2 also increases susceptibility for cardio-renal mortality in type 1 diabetes. These findings require validation in other cohorts.

SUBMITTER: Costacou T

PROVIDER: S-EPMC4761325 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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The Haptoglobin genotype predicts cardio-renal mortality in type 1 diabetes.

Costacou Tina T Orchard Trevor J TJ

Journal of diabetes and its complications 20151114 2

<h4>Aims</h4>The Haptoglobin (HP) 2-2 genotype increases cardiovascular diabetes complication incidence. In type 1 diabetes, HP 2-2 also predicts declining kidney function and end-stage renal disease. We investigated whether HP 2-2 predisposes to cardio-renal mortality, while considering other causes of death as competing risks.<h4>Methods</h4>Individuals with type 1 diabetes and HP data available (n=486; mean baseline age, 27 and duration, 19 years) were selected for study. Vital status was ass ...[more]

PMID: 26684170

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Project description:BACKGROUND:The prognosis for young people diagnosed with diabetes during childhood remains poor and this is mainly related to the long-term risk of developing vascular complications.Microalbuminuria identifies subjects at risk for diabetic nephropathy (DN) and cardiovascular disease (CVD). It is often detected in adolescence but is rarely treated before the age of 18 years, as at the end of puberty albumin excretion may decline and in some subjects will return into the normal range. However, evidence indicates that subjects with both transient and persistent microalbuminuria have experienced renal damage during puberty and thus reno-protection to prevent long-term complications is warranted. In adults with diabetes and microalbuminuria, the use of angiotensin converting enzyme inhibitors (ACEI) and Statins is increasing, and in order to determine whether these agents are of value in the adolescent population a large randomized controlled clinical trial is needed. METHODS/DESIGN:The Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) is a multi-center, randomized, double-blind, placebo-controlled trial of ACEI and Statin therapy in adolescents with type 1 diabetes. 500 high-risk adolescents, defined on the basis of their albumin excretion, are randomized to receive either ACEI (Quinapril) or Statins (Atorvastatin) or combination therapy or placebo for 3-4 years. There will also be a parallel open observational study, based on the follow-up of 400 low-risk non-randomized adolescents. The major endpoint of the study is the change in albumin excretion; secondary endpoints include markers of CVD, renal function, retinopathy, quality of life combined with assessment of compliance and potential health economic benefits. DISCUSSION:AdDIT will provide important data on the potential renal and cardiovascular protective effects of ACEI and Statins in high-risk adolescents. Long-term follow-up of the randomized subjects will provide direct evidence of disease outcomes, in addition to the data on early surrogate measures of DN and CVD. Follow-up of non-randomized low-risk subjects will determine the potential impact of intervention on DN and CVD. AdDIT will help to determine whether, in addition to encouraging young people to achieve good glycaemic control, pharmacological cardio-renal protection should also be implemented. EUDRACT NUMBER: 2007-001039-72 TRIAL REGISTRATION NUMBER:ISRCTN91419926.

Project description:BackgroundGlycocalyx lines the inner surface of the capillary endothelium. Capillaroscopy enables visualization of the sublingual capillaries and measurement of the Perfused Boundary Region (PBR) as an estimate of the glycocalyx. Novel software enables assessment of the PBR estimated at a fixed high flow level (PBR-hf) and an overall microvascular assessment by the MicroVascular Health Score (MVHS). Damaged glycocalyx may represent microvascular damage in diabetes and assessment of its dimension might improve early cardio-renal risk stratification.AimTo assess the associations between PBR, PBR-hf and MVHS and cardio-renal risk factors in persons with type 1 diabetes (T1D); and to compare these dimensions in persons with T1D and controls.MethodsCross-sectional study including 161 persons with T1D stratified according to level of albuminuria and 50 healthy controls. The PBR, PBR-hf and MVHS were assessed by the GlycoCheck device (valid measurements were available in 136 (84.5%) with T1D and in all the controls). Higher PBR and PBR-hf indicate smaller glycocalyx width. Lower MVHS represents a worse microvascular health.ResultsThere were no associations between PBR, PBR-hf or MVHS and the cardio-renal risk factors in persons with T1D, except for higher PBR-hf and lower MVHS in females (p = 0.01 for both). There was no difference in PBR, PBR-hf or MVHS in persons with normo-, micro- or macroalbuminuria. The PBR was higher (2.20±0.30 vs. 2.03±0.18μm; p<0.001) and MVHS lower (3.15±1.25 vs. 3.53±0.86μm; p = 0.02) in persons with T1D compared to controls (p≤0.02). After adjustment for cardio-renal risk factors the difference in PBR remained significant (p = 0.001).ConclusionsThe endothelial glycocalyx dimension was impaired in persons with T1D compared to controls. We found no association between the endothelial glycocalyx dimension and the level of albuminuria or cardio-renal risk factors among persons with T1D. The use of the GlycoCheck device in T1D may not contribute to cardio-renal risk stratification.

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The Haptoglobin genotype predicts cardio-renal mortality in type 1 diabetes.

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The Haptoglobin genotype predicts cardio-renal mortality in type 1 diabetes.

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