Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study

Rossing, Peter; Hougaard, Philip; Borch‐Johnsen, Knut; Parving, Hans Henrik

doi:10.1136/bmj.313.7060.779

Cited by 414 publications

(336 citation statements)

References 37 publications

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“…In the current study we chose to study young adults with type 1 diabetes, so the population is very similar in characteristics to the control non-diabetic group, except for measures of hyperglycaemia. Exclusion of those with extant cardiovascular disease or diabetic nephropathy was designed to avoid participants in whom vascular injury was already advanced and in whom endothelial repair mechanisms might therefore have been activated by arterial wall damage in the form of atherosclerotic plaque [39][40][41]. Nevertheless it is impossible to be sure that some individuals in our type 1 diabetic population did not have more significant disease (indeed in both populations).…”

Section: Discussionmentioning

confidence: 99%

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

et al. 2009

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Aims/hypothesis Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima-media thickness (CIMT). Methods We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured. Results CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46-69%; p=0.004-0.043). In people with type 1 diabetes, FMD was reduced by 45% (p<0.001) and CIMT increased by 25% (p<0.001), these being correlated (r=−0.25, p=0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r =0.25, p = 0.037) and CD34+ (r=0.34, p=0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r=−0.27, p=0.028 and r=−0.24, p=0.048, respectively). Conclusions/interpretation These findings suggest that abnormalities of endothelial function in addition to proinflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events.

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Section: Discussionmentioning

confidence: 99%

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

et al. 2009

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“…The presence of micro-and macroalbuminuria predict all-cause mortality [19,[21][22][23][24], and microalbuminuria is an independent predictor of cardiovascular mortality in patients with diabetes [22,23,25]. At a lower cut-off value, urinary albumin was predictive of the development of ischemic heart disease [26] as well as cardiovascular mortality in the general population [27,28].…”

Section: Discussionmentioning

confidence: 99%

Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow-up

et al. 2005

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Aims/hypothesis: To study whether urinary orosomucoid excretion rate (UOER) predicts mortality in normoalbuminuric patients with diabetes at 5 years of follow-up, and to investigate the relationship between orosomucoid in serum and urine. Methods: A cohort of 578 patients with diabetes (430 type 2, 148 type 1) was followed prospectively for an average of 5 years. UOER was measured in timed overnight urine samples. Results: Eightytwo patients with type 2 diabetes and 17 patients with type 1 diabetes died. Among patients with type 2 diabetes, 251 (58%) had normoalbuminuria; increased UOER independently predicted cardiovascular mortality (OR 4.94, 95% CI 1.60−15.22; p<0.006) in those with normoalbuminuria and in the entire cohort of patients with type 2 diabetes (odds ratio 3.63, 95% CI 1.50−8.81; p<0.005). Patients with increased UOER had a higher all-cause mortality than those with normal UOER (log-rank test, p<0.001 for type 2 patients; p<0.04 for type 1 patients). In patients with type 1 diabetes, there were five cardiovascular deaths and no significant predictive value of UOER. Patients with increased UOER had a subclinical increase in serum orosomucoid. Conclusion/interpretation: Increased UOER was an independent, powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes and in the entire cohort of patients with type 2 diabetes. There were indications of UOER as being a valuable marker in type 1 diabetes that showed differences in survival between patients with normal versus increased UOER. Serum orosomucoid was associated with UOER; UOER may be a marker of lowgrade inflammation in patients with diabetes.

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“…We subject the resulting initial condition to validation. Each of these stages is also associated with increased mortality rates, mainly due to cardiovascular disease [61][62][63][64]; and these are particularly high for macroalbuminuria [65,66].…”

Section: First Five Yearsmentioning

confidence: 99%

“… YLLs based on deaths from the nephropathy model, because albuminuria is the best predictor of all-cause mortality in type 1 diabetes [65]. These deaths includes those from macrovascular complications such as myocardial infarctions and strokes;  YLDs from the nephropathy model (for macroalbuminuria and ESRD);…”

Section: First Five Yearsmentioning

confidence: 99%

See 1 more Smart Citation

Requisite models for strategic commissioning: the example of type 1 diabetes

Airoldi¹,

Bevan²,

Morton³

et al. 2008

Health Care Manage Sci

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A developing emphasis of health care reforms has been creating organisations with responsibilities for strategic commissioning of services for defined populations. Such organisations must set priorities in aiming to meet their populations' needs subject to a budget constraint. This requires estimates of the health benefits and costs of different interventions for their populations. This paper outlines a framework that does this and shows how this requires modelling to produce estimates in a way that is transparent to commissioners, of requisite complexity to produce sound estimates for priority setting using routinely available data. The example illustrated in this paper is an intervention that would improve glucose control in the English population with type 1 diabetes. It takes many years for a change in glucose management to deliver maximum benefits; hence the intervention is not good value-for-money in the short run. We aim to give a more strategic view of the costs and benefits modelling costs and benefits in a steady-state model which suggests that the intervention is good value-for-money in the long run.

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Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study

Cited by 414 publications

References 37 publications

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow-up

Requisite models for strategic commissioning: the example of type 1 diabetes

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