Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75)

Aims/hypothesis: the relative importance of glucose and blood pressure control in type 2 diabetes remains uncertain. We assessed interactive effects of glycaemia and systolic blood pressure (SBP) exposure on the risk of diabetic complications over time.

Subjects, materials and methods: HbA1c and SBP, measured annually for a median of 10.4 years in 4,320 newly diagnosed type 2 diabetic patients from the UK Prospective Diabetes Study (UKPDS), were categorised as updated mean values <6.0, 6.0–6.9, 7.0–7.9 or ≥8.0%, and <130, 130–139, 140–149 or ≥150 mmHg, respectively. Clinical outcomes were UKPDS predefined composite endpoints.

Results: the incidence of the ‘any diabetes-related endpoint’ in the lowest (HbA1c <6.0%, SBP <130 mmHg) and highest (HbA1c ≥8%, SBP ≥150 mmHg) category combinations was 15 and 82 per 1,000 person-years, respectively, and 24 and 120 per 1,000 person-years in a Poisson model adjusted to white Caucasian male sex, age 50 to 54 years and diabetes duration of 7.5 to 12.5 years. Updated mean HbA1c and SBP effects were additive in an adjusted proportional hazards model with risk reductions of 21% per 1% HbA1c decrement and 11% per 10 mmHg SBP decrement. Endpoint rates obtained in the 887 patients randomised in both the glycaemia and hypertension intervention trial arms were consistent with the observational data. Those allocated to both intensive glucose and tight blood pressure control policies had fewer events than those allocated to either policy alone or to neither (p for trend 0.024).

Conclusions/interpretation: risk of complications in type 2 diabetes is associated independently and additively with hyperglycaemia and hypertension. Intensive treatment of both these risk factors is required to minimise the incidence of complications.

Blood pressure, Complications, Glycaemia, Risk, Type 2 diabetes, UKPDS

10.1007/s00125-006-0297-1

0012-186X

1761-1769

Stratton, I.M.

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Cull, C.A.

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Adler, A.I.

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Matthews, D.R.

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Neil, H.A.W.

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Holman, R.R.

d03ac9f9-2f1d-40c9-827f-939b8b05b25f

August 2006

Stratton, I.M.

772f25b9-23c0-4240-a3f6-1e76b03b172f

Cull, C.A.

ae95233f-ce25-4c32-a5b9-368419e07826

Adler, A.I.

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Matthews, D.R.

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Neil, H.A.W.

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Holman, R.R.

d03ac9f9-2f1d-40c9-827f-939b8b05b25f

Stratton, I.M., Cull, C.A., Adler, A.I., Matthews, D.R., Neil, H.A.W. and Holman, R.R. (2006) Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75). Diabetologia, 49 (8), 1761-1769. (doi:10.1007/s00125-006-0297-1).

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More information

Accepted/In Press date: 22 March 2006

e-pub ahead of print date: 31 May 2006

Published date: August 2006

Additional Information: Funding Information: Fig. 2 Incidence of the UKPDS primary composite ‘any diabetes-related endpoint’ by intention-to-treat, as rate per 1,000 person-years, in the 887 patients randomised in a factorial design between the four different interventions: a conventional or intensive glucose control policy and a less tight or tight BP control policy. Only endpoints that occurred following each patient’s randomisation into the BP control study are included. Those allocated to both the intensive glucose and the tight BP control policies had fewer events than those allocated to either policy alone or to neither (p for trend 0.024) Acknowledgements The late Professor R. C. Turner designed and was the inspiration for the UKPDS. The cooperation of the patients and many NHS and non-NHS staff at the centres is much appreciated. We would like to thank H. McElroy and S. E. Manley for their assistance in the production of this manuscript. The major grants for this study were from the UK Medical Research Council, British Diabetic Association, the UK Department of Health, The National Eye Institute and The National Institute of Digestive, Diabetes and Kidney Disease in the National Institutes of Health, USA, The British Heart Foundation, Novo-Nordisk, Bayer, Bristol Myers Squibb, Hoechst, Lilly, Lipha and Farmitalia Carlo Erba. Other funding companies and agencies, the supervising committees, and all participating staff are listed in an earlier paper [1]. Funding bodies did not participate in writing the paper.

Keywords: Blood pressure, Complications, Glycaemia, Risk, Type 2 diabetes, UKPDS