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Erschienen in: Diabetologia 4/2013

01.04.2013 | Article

HbA1c variability is associated with an increased risk of retinopathy requiring laser treatment in type 1 diabetes

verfasst von: K. Hietala, J. Wadén, C. Forsblom, V. Harjutsalo, J. Kytö, P. Summanen, P.-H. Groop, on behalf of the FinnDiane Study Group

Erschienen in: Diabetologia | Ausgabe 4/2013

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Abstract

Aims/hypothesis

This study aimed to investigate whether variation in long-term glycaemia in type 1 diabetes as measured by HbA1c variability is associated with the cumulative incidence and risk of retinopathy requiring laser treatment.

Methods

The effect of HbA1c variability was assessed in 2,019 Finnish Diabetic Nephropathy (FinnDiane) study patients. The patients were studied in two partially overlapping subcohorts with either verified first laser treatment (n = 1,459) or retinopathy severity graded from ophthalmic records with the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale (n = 1,346). The ratio of intrapersonal SD and mean of serially measured HbA1c was considered an estimate of HbA1c variability.

Results

A subcohort of 1,459 patients did not have laser treatment prior to the first FinnDiane visit and 174 of these patients were treated during a mean follow-up period of 5.2 ± 2.2 years. The 5 year cumulative incidence of laser treatment was 19% (95% CI 15, 24) in the highest quartile of HbA1c variability and 10% (95% CI 7, 12) in the lowest quartile (p < 0.001, Gray’s test) with a corresponding HR of 1.6 (95% CI 1.1, 2.5; p = 0.02) adjusted for renal status, diabetes duration, mean HbA1c, blood pressure, sex and number of HbA1c measurements. In a subcohort of 1,346 patients, 434 patients had proliferative diabetic retinopathy (PDR). Patients in the highest quartile of HbA1c variability had an increased risk of PDR compared with the lowest quartile (HR 1.7 [95% CI 1.3, 2.2]; p < 0.001]).

Conclusions/interpretation

HbA1c variability was associated with an increased cumulative incidence and risk of retinopathy requiring laser treatment in type 1 diabetes.
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Literatur
1.
Zurück zum Zitat Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE (2008) The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 115:1859–1868CrossRefPubMed Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE (2008) The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 115:1859–1868CrossRefPubMed
2.
Zurück zum Zitat Deckert T, Simonsen SE, Poulsen JE (1967) Prognosis of proliferative retinopathy in juvenile diabetics. Diabetes 16:728–733PubMed Deckert T, Simonsen SE, Poulsen JE (1967) Prognosis of proliferative retinopathy in juvenile diabetics. Diabetes 16:728–733PubMed
3.
Zurück zum Zitat Hietala K, Harjutsalo V, Forsblom C, Summanen P, Groop PH (2010) Age at onset and the risk of proliferative retinopathy in type 1 diabetes. Diabetes Care 33:1315–1319CrossRefPubMed Hietala K, Harjutsalo V, Forsblom C, Summanen P, Groop PH (2010) Age at onset and the risk of proliferative retinopathy in type 1 diabetes. Diabetes Care 33:1315–1319CrossRefPubMed
4.
Zurück zum Zitat Hietala K, Forsblom C, Summanen P, Groop PH (2008) Heritability of proliferative diabetic retinopathy. Diabetes 57:2176–2180CrossRefPubMed Hietala K, Forsblom C, Summanen P, Groop PH (2008) Heritability of proliferative diabetic retinopathy. Diabetes 57:2176–2180CrossRefPubMed
5.
Zurück zum Zitat Kilpatrick ES, Rigby AS, Atkin SL (2008) A1C variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care 31:2198–2202CrossRefPubMed Kilpatrick ES, Rigby AS, Atkin SL (2008) A1C variability and the risk of microvascular complications in type 1 diabetes: data from the Diabetes Control and Complications Trial. Diabetes Care 31:2198–2202CrossRefPubMed
6.
Zurück zum Zitat Waden J, Forsblom C, Thorn LM, Gordin D, Saraheimo M, Groop PH (2009) A1C variability predicts incident cardiovascular events, microalbuminuria, and overt diabetic nephropathy in patients with type 1 diabetes. Diabetes 58:2649–2655CrossRefPubMed Waden J, Forsblom C, Thorn LM, Gordin D, Saraheimo M, Groop PH (2009) A1C variability predicts incident cardiovascular events, microalbuminuria, and overt diabetic nephropathy in patients with type 1 diabetes. Diabetes 58:2649–2655CrossRefPubMed
7.
Zurück zum Zitat Fagerudd J, Forsblom C, Pettersson-Fernholm K, Groop PH (2004) Implementation of guidelines for the prevention of diabetic nephropathy. Diabetes Care 27:803–804CrossRefPubMed Fagerudd J, Forsblom C, Pettersson-Fernholm K, Groop PH (2004) Implementation of guidelines for the prevention of diabetic nephropathy. Diabetes Care 27:803–804CrossRefPubMed
8.
Zurück zum Zitat Andersen MK, Lundgren V, Turunen JA et al (2010) Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years. Diabetes Care 33:2062–2064CrossRefPubMed Andersen MK, Lundgren V, Turunen JA et al (2010) Latent autoimmune diabetes in adults differs genetically from classical type 1 diabetes diagnosed after the age of 35 years. Diabetes Care 33:2062–2064CrossRefPubMed
9.
Zurück zum Zitat Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH (2003) Diabetic nephropathy is associated with low-grade inflammation in type 1 diabetic patients. Diabetologia 46:1402–1407CrossRefPubMed Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH (2003) Diabetic nephropathy is associated with low-grade inflammation in type 1 diabetic patients. Diabetologia 46:1402–1407CrossRefPubMed
10.
Zurück zum Zitat Penttila IM, Halonen T, Punnonen K, Tiikkainen U (2005) Best use of the recommended IFCC reference method, material and values in HbA1C analyses. Scand J Clin Lab Invest 65:453–462CrossRefPubMed Penttila IM, Halonen T, Punnonen K, Tiikkainen U (2005) Best use of the recommended IFCC reference method, material and values in HbA1C analyses. Scand J Clin Lab Invest 65:453–462CrossRefPubMed
11.
Zurück zum Zitat Davis MD, Fisher MR, Gangnon RE et al (1998) Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: early Treatment Diabetic Retinopathy Study Report #18. Invest Ophthalmol Vis Sci 39:233–252PubMed Davis MD, Fisher MR, Gangnon RE et al (1998) Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: early Treatment Diabetic Retinopathy Study Report #18. Invest Ophthalmol Vis Sci 39:233–252PubMed
12.
Zurück zum Zitat Scrucca L, Santucci A, Aversa F (2007) Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transpl 40:381–387CrossRef Scrucca L, Santucci A, Aversa F (2007) Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transpl 40:381–387CrossRef
13.
Zurück zum Zitat Zhou B, Fine J, Latouche A, Labopin M (2012) Competing risks regression for clustered data. Biostatistics 13:371–383CrossRefPubMed Zhou B, Fine J, Latouche A, Labopin M (2012) Competing risks regression for clustered data. Biostatistics 13:371–383CrossRefPubMed
14.
Zurück zum Zitat Helve E, Laatikainen L, Merenmies L, Koivisto VA (1987) Continuous insulin infusion therapy and retinopathy in patients with type I diabetes. Acta Endocrinol (Copenh) 115:313–319 Helve E, Laatikainen L, Merenmies L, Koivisto VA (1987) Continuous insulin infusion therapy and retinopathy in patients with type I diabetes. Acta Endocrinol (Copenh) 115:313–319
15.
Zurück zum Zitat Kilpatrick ES, Rigby AS, Atkin SL (2006) The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care 29:1486–1490CrossRefPubMed Kilpatrick ES, Rigby AS, Atkin SL (2006) The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care 29:1486–1490CrossRefPubMed
16.
Zurück zum Zitat DCCT Group (2000) Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 342:381–389CrossRef DCCT Group (2000) Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 342:381–389CrossRef
17.
Zurück zum Zitat McCarter RJ, Hempe JM, Gomez R, Chalew SA (2004) Biological variation in HbA1c predicts risk of retinopathy and nephropathy in type 1 diabetes. Diabetes Care 27:1259–1264CrossRefPubMed McCarter RJ, Hempe JM, Gomez R, Chalew SA (2004) Biological variation in HbA1c predicts risk of retinopathy and nephropathy in type 1 diabetes. Diabetes Care 27:1259–1264CrossRefPubMed
18.
Zurück zum Zitat Chantelau E (1998) Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy. Br J Ophthalmol 82:725–730CrossRefPubMed Chantelau E (1998) Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy. Br J Ophthalmol 82:725–730CrossRefPubMed
19.
Zurück zum Zitat Poulaki V, Qin W, Joussen AM et al (2002) Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF. J Clin Invest 109:805–815PubMed Poulaki V, Qin W, Joussen AM et al (2002) Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1alpha and VEGF. J Clin Invest 109:805–815PubMed
20.
Zurück zum Zitat Ceriello A, Esposito K, Piconi L et al (2008) Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57:1349–1354CrossRefPubMed Ceriello A, Esposito K, Piconi L et al (2008) Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57:1349–1354CrossRefPubMed
21.
Zurück zum Zitat Jones SC, Saunders HJ, Qi W, Pollock CA (1999) Intermittent high glucose enhances cell growth and collagen synthesis in cultured human tubulointerstitial cells. Diabetologia 42:1113–1119CrossRefPubMed Jones SC, Saunders HJ, Qi W, Pollock CA (1999) Intermittent high glucose enhances cell growth and collagen synthesis in cultured human tubulointerstitial cells. Diabetologia 42:1113–1119CrossRefPubMed
22.
Zurück zum Zitat Quagliaro L, Piconi L, Assaloni R et al (2005) Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: the distinct role of protein kinase C and mitochondrial superoxide production. Atherosclerosis 183:259–267CrossRefPubMed Quagliaro L, Piconi L, Assaloni R et al (2005) Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: the distinct role of protein kinase C and mitochondrial superoxide production. Atherosclerosis 183:259–267CrossRefPubMed
23.
Zurück zum Zitat Monnier L, Mas E, Ginet C et al (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295:1681–1687CrossRefPubMed Monnier L, Mas E, Ginet C et al (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295:1681–1687CrossRefPubMed
24.
Zurück zum Zitat Groop PH, Forsblom C, Thomas MC (2005) Mechanisms of disease: pathway-selective insulin resistance and microvascular complications of diabetes. Nat Clin Pract Endocrinol Metab 1:100–110CrossRefPubMed Groop PH, Forsblom C, Thomas MC (2005) Mechanisms of disease: pathway-selective insulin resistance and microvascular complications of diabetes. Nat Clin Pract Endocrinol Metab 1:100–110CrossRefPubMed
25.
Zurück zum Zitat Simo R, Carrasco E, Garcia-Ramirez M, Hernandez C (2006) Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabetes Rev 2:71–98CrossRefPubMed Simo R, Carrasco E, Garcia-Ramirez M, Hernandez C (2006) Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabetes Rev 2:71–98CrossRefPubMed
26.
Zurück zum Zitat Kordonouri O, Danne T, Enders I, Weber B (1998) Does the long-term clinical course of type I diabetes mellitus differ in patients with prepubertal and pubertal onset? Results of the Berlin Retinopathy Study. Eur J Pediatr 157:202–207CrossRefPubMed Kordonouri O, Danne T, Enders I, Weber B (1998) Does the long-term clinical course of type I diabetes mellitus differ in patients with prepubertal and pubertal onset? Results of the Berlin Retinopathy Study. Eur J Pediatr 157:202–207CrossRefPubMed
27.
Zurück zum Zitat Karjalainen J, Salmela P, Ilonen J, Surcel HM, Knip M (1989) A comparison of childhood and adult type I diabetes mellitus. N Engl J Med 320:881–886CrossRefPubMed Karjalainen J, Salmela P, Ilonen J, Surcel HM, Knip M (1989) A comparison of childhood and adult type I diabetes mellitus. N Engl J Med 320:881–886CrossRefPubMed
28.
Zurück zum Zitat Steffes MW, Sibley S, Jackson M, Thomas W (2003) Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 26:832–836CrossRefPubMed Steffes MW, Sibley S, Jackson M, Thomas W (2003) Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 26:832–836CrossRefPubMed
29.
Zurück zum Zitat Summanen P, Kallioniemi V, Komulainen J et al (2007) Diabetic retinopathy. Current care guideline. Duodecim 123:421–422PubMed Summanen P, Kallioniemi V, Komulainen J et al (2007) Diabetic retinopathy. Current care guideline. Duodecim 123:421–422PubMed
30.
Zurück zum Zitat Hutchinson A, McIntosh A, Peters J et al (2000) Effectiveness of screening and monitoring tests for diabetic retinopathy—a systematic review. Diabet Med 17:495–506CrossRefPubMed Hutchinson A, McIntosh A, Peters J et al (2000) Effectiveness of screening and monitoring tests for diabetic retinopathy—a systematic review. Diabet Med 17:495–506CrossRefPubMed
Metadaten
Titel
HbA1c variability is associated with an increased risk of retinopathy requiring laser treatment in type 1 diabetes
verfasst von
K. Hietala
J. Wadén
C. Forsblom
V. Harjutsalo
J. Kytö
P. Summanen
P.-H. Groop
on behalf of the FinnDiane Study Group
Publikationsdatum
01.04.2013
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 4/2013
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2816-6

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