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Published in: Diabetes Therapy 5/2017

Open Access 01-10-2017 | Original Research

Relation Between Different Measures of Glycemic Exposure and Microvascular and Macrovascular Complications in Patients with Type 2 Diabetes Mellitus: An Observational Cohort Study

Authors: Rients P. T. van Wijngaarden, Jetty A. Overbeek, Edith M. Heintjes, Agata Schubert, Joris Diels, Huub Straatman, Ewout W. Steyerberg, Ron M. C. Herings

Published in: Diabetes Therapy | Issue 5/2017

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Abstract

Introduction

This retrospective cohort study investigated the relation between different measures of glycemic exposure and micro- and macrovascular complications among patients with type 2 diabetes.

Methods

The analysis included patients receiving oral antihyperglycemic agents between 1 January 2006 and 31 December 2014 from the General Practitioner Database from the PHARMO Database Network. All recorded HbA1c levels during follow-up were used to express glycemic exposure in four ways: index HbA1c, time-dependent HbA1c, exponential moving average (EMA) and glycemic burden. Association between glycemic exposure and micro-/macrovascular complications was analyzed by estimating hazard ratios and 95% confidence intervals using an adjusted (time-dependent) Cox proportional hazards model.

Results

The analysis included 32,725 patients (median age, 65 years; 47% female). Median follow-up was 5.4 years; median number of HbA1c measurements per patient was 18.0. From all measures, HbA1c at index showed the weakest relation between all micro-/macrovascular complications, with coronary artery disease (CAD) having the highest HR (95% CI): 1.18 (1.04–1.34) for HbA1c ≥64 mmol/mol (8%). The time-dependent HbA1c model showed a significant association only for microvascular complications, with retinopathy having the highest HR (95% CI): 1.55 (1.40–1.73) for HbA1c ≥64 mmol/mol (8%). EMA-defined exposure showed similar findings, although the effect of retinopathy was more pronounced [HR (95% CI): 1.81 (1.63–2.02) for HbA1c ≥64 mmol/mol (8%)] and was also predictive for CAD [HR (95% CI): 1.29 (1.10–1.50) for HbA1c ≥64 mmol/mol (8%)]. A statistically significant relation with glycemic burden was found for all selected micro-/macrovascular complications, with retinopathy having the highest HR (95%): 2.60 (2.19–3.07) for glycemic burden years >3.

Conclusion

This study shows that greater and more prolonged exposure to hyperglycemia increases the risk of micro- and macrovascular complications.

Funding

Janssen Pharmaceutica NV.
Appendix
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Literature
1.
go back to reference Stratton IM, Adler AI, Neil HAW, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405–12.CrossRefPubMedPubMedCentral Stratton IM, Adler AI, Neil HAW, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405–12.CrossRefPubMedPubMedCentral
2.
go back to reference Zhang Y, Hu G, Yuan Z, Chen L. Glycosylated hemoglobin in relationship to cardiovascular outcomes and death in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS One. 2012;7:e42551.CrossRefPubMedPubMedCentral Zhang Y, Hu G, Yuan Z, Chen L. Glycosylated hemoglobin in relationship to cardiovascular outcomes and death in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS One. 2012;7:e42551.CrossRefPubMedPubMedCentral
3.
go back to reference Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care. 1995;18:258–68.CrossRefPubMed Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care. 1995;18:258–68.CrossRefPubMed
4.
go back to reference UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRef UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRef
5.
go back to reference Jeffcoate SL. Diabetes control and complications: the role of glycated haemoglobin, 25 years on. Diabet Med. 2004;21:657–65.CrossRefPubMed Jeffcoate SL. Diabetes control and complications: the role of glycated haemoglobin, 25 years on. Diabet Med. 2004;21:657–65.CrossRefPubMed
6.
go back to reference Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38:140–9.CrossRefPubMed Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38:140–9.CrossRefPubMed
7.
go back to reference Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care. 2013;36:3411–7.CrossRefPubMedPubMedCentral Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care. 2013;36:3411–7.CrossRefPubMedPubMedCentral
8.
go back to reference Yoshida Y, Hagura R, Hara Y, Sugasawa G, Akanuma Y. Risk factors for the development of diabetic retinopathy in Japanese type 2 diabetic patients. Diabetes Res Clin Pract. 2001;51:195–203.CrossRefPubMed Yoshida Y, Hagura R, Hara Y, Sugasawa G, Akanuma Y. Risk factors for the development of diabetic retinopathy in Japanese type 2 diabetic patients. Diabetes Res Clin Pract. 2001;51:195–203.CrossRefPubMed
9.
go back to reference Araki S, Haneda M, Sugimoto T, Isono M, Isshiki K, Kashiwagi A, et al. Factors associated with frequent remission of microalbuminuria in patients with type 2 diabetes. Diabetes. 2005;54:2983–7.CrossRefPubMed Araki S, Haneda M, Sugimoto T, Isono M, Isshiki K, Kashiwagi A, et al. Factors associated with frequent remission of microalbuminuria in patients with type 2 diabetes. Diabetes. 2005;54:2983–7.CrossRefPubMed
10.
go back to reference Lind M, Odén A, Fahlén M, Eliasson B. A systematic review of HbA1c variables used in the study of diabetic complications. Diabetes Metab Syndr. 2008;2:282–93.CrossRef Lind M, Odén A, Fahlén M, Eliasson B. A systematic review of HbA1c variables used in the study of diabetic complications. Diabetes Metab Syndr. 2008;2:282–93.CrossRef
11.
go back to reference Bailey CJ, Day C. Glycaemic memory. Br J Diabetes Vasc Dis. 2008;8:242–7.CrossRef Bailey CJ, Day C. Glycaemic memory. Br J Diabetes Vasc Dis. 2008;8:242–7.CrossRef
12.
go back to reference Lind M, Oden A, Fahlen M, Eliasson B. The true value of HbA1c as a predictor of diabetic complications: simulations of HbA1c variables. PLoS One. 2009;4:e4412.CrossRefPubMedPubMedCentral Lind M, Oden A, Fahlen M, Eliasson B. The true value of HbA1c as a predictor of diabetic complications: simulations of HbA1c variables. PLoS One. 2009;4:e4412.CrossRefPubMedPubMedCentral
13.
go back to reference Maple-Brown LJ, Ye C, Retnakaran R. Area-under-the-HbA1c-curve above the normal range and the prediction of microvascular outcomes: an analysis of data from the Diabetes Control and Complications Trial. Diabet Med. 2013;30:95–9.CrossRefPubMed Maple-Brown LJ, Ye C, Retnakaran R. Area-under-the-HbA1c-curve above the normal range and the prediction of microvascular outcomes: an analysis of data from the Diabetes Control and Complications Trial. Diabet Med. 2013;30:95–9.CrossRefPubMed
14.
go back to reference Rutten GEHM, De Grauw WJC, Nijpels G, et al. NHG-Standaard Diabetes mellitus type 2 (Tweede herziening). Huisarts Wet. 2006;49:137–52. Rutten GEHM, De Grauw WJC, Nijpels G, et al. NHG-Standaard Diabetes mellitus type 2 (Tweede herziening). Huisarts Wet. 2006;49:137–52.
15.
go back to reference Jain AKC, Joshi S. Diabetic foot classifications: review of literature. Med Sci. 2013;2:715–21.CrossRef Jain AKC, Joshi S. Diabetic foot classifications: review of literature. Med Sci. 2013;2:715–21.CrossRef
16.
go back to reference Fincke BG, Miller DR, Turpin R. A classification of diabetic foot infections using ICD-9-CM codes: application to a large computerized medical database. BMC Health Serv Res. 2010;10:192.CrossRefPubMedPubMedCentral Fincke BG, Miller DR, Turpin R. A classification of diabetic foot infections using ICD-9-CM codes: application to a large computerized medical database. BMC Health Serv Res. 2010;10:192.CrossRefPubMedPubMedCentral
17.
go back to reference Gerstein HC, Pogue J, Mann JF, et al. The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis. Diabetologia. 2005;48:1749–55.CrossRefPubMed Gerstein HC, Pogue J, Mann JF, et al. The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis. Diabetologia. 2005;48:1749–55.CrossRefPubMed
18.
go back to reference Adler AI, Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Smith DG. Risk factors for diabetic peripheral sensory neuropathy. Results of the Seattle Prospective Diabetic Foot Study. Diabetes Care. 1997;20:1162–7.CrossRefPubMed Adler AI, Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Smith DG. Risk factors for diabetic peripheral sensory neuropathy. Results of the Seattle Prospective Diabetic Foot Study. Diabetes Care. 1997;20:1162–7.CrossRefPubMed
19.
go back to reference Araki A, Ito H, Hattori A, Inoue J, Sato T, Shiraki M, et al. Risk factors for development of retinopathy in elderly Japanese patients with diabetes mellitus. Diabetes Care. 1993;16:1184–6.CrossRefPubMed Araki A, Ito H, Hattori A, Inoue J, Sato T, Shiraki M, et al. Risk factors for development of retinopathy in elderly Japanese patients with diabetes mellitus. Diabetes Care. 1993;16:1184–6.CrossRefPubMed
20.
go back to reference Cardoso CR, Leite NC, Ferreira MT, Salles GF. Prognostic importance of baseline and serial glycated hemoglobin levels in high-risk patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study. Acta Diabetol. 2015;52:21–9.CrossRefPubMed Cardoso CR, Leite NC, Ferreira MT, Salles GF. Prognostic importance of baseline and serial glycated hemoglobin levels in high-risk patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study. Acta Diabetol. 2015;52:21–9.CrossRefPubMed
21.
go back to reference Rutten GEHM, de Grauw W, Nijpels G, et al. NHG-Standaard Diabetes mellitus type 2 (derde herziening). Huisarts Wet. 2013;56:512–25. Rutten GEHM, de Grauw W, Nijpels G, et al. NHG-Standaard Diabetes mellitus type 2 (derde herziening). Huisarts Wet. 2013;56:512–25.
Metadata
Title
Relation Between Different Measures of Glycemic Exposure and Microvascular and Macrovascular Complications in Patients with Type 2 Diabetes Mellitus: An Observational Cohort Study
Authors
Rients P. T. van Wijngaarden
Jetty A. Overbeek
Edith M. Heintjes
Agata Schubert
Joris Diels
Huub Straatman
Ewout W. Steyerberg
Ron M. C. Herings
Publication date
01-10-2017
Publisher
Springer Healthcare
Published in
Diabetes Therapy / Issue 5/2017
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-017-0301-4

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