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Research article:

Glucose, blood pressure and cholesterol levels and their relationships to clinical outcomes in type 2 diabetes: a retrospective cohort study

Reference:

Evangelos Kontopantelis, David A Springate, David Reeves, Darren M Ashcroft, Martin Rutter, Iain Buchan, Tim Doran(2015) Glucose, blood pressure and cholesterol levels and their relationships to clinical outcomes in type 2 diabetes: a retrospective cohort study. Diabetologia, doi: 10.1007/s00125-014-3473-8

Link to fulltext article
Abstract
Background: Observational data have been used to inform target levels for modifiable risk factors in type 2 diabetes but these data are limited by confounding. We aimed to describe the shape of observed relationships between risk factor levels and clinically important outcomes in type 2 diabetes after adjusting for multiple confounders. Methods: We used retrospective longitudinal data on 246,544 adults with type 2 diabetes from 600 practices contributing to the Clinical Practice Research Datalink between 2006 and 2012. Proportional hazards regression models quantified the risks of mortality, microvascular or macrovascular events associated with four modifiable risk factors: glycated haemoglobin (HbA1c), systolic and diastolic blood pressure and total cholesterol, while controlling for numerous patient and practice covariates. Findings: U-shaped relationships were observed between all-cause mortality and levels of the four risk factors. The lowest risks were associated with HbA1c 7.25-7.75%; total cholesterol 3.5-4.5 mmol/L; systolic blood pressure 135-145 mmHg; and diastolic blood pressure 82.5-87.5 mmHg. coronary and stroke mortality related to the four risk factors in a positive, curvilinear way, with the exception of blood pressure which related to coronary deaths in a U-shape. Macrovascular events showed a positive and curvilinear relationship with HbA1c but U-shaped for total cholesterol and systolic blood pressure. Microvascular related to the four risk factors in a curvilinear way: positive for HbA1c and systolic blood pressure but negative for cholesterol and diastolic blood pressure. Interpretation: We identified several relationships which, when considered in the light of relevant trial data, support a call for major changes to clinical practice. Most importantly, our results support trial data indicating that normalisation of glucose and blood pressure can lead to poorer outcomes, which makes a strong case for target ranges for these risk factors rather than target levels.
Author for correspondence
Evangelos Kontopantelis
Email for correspondence
E.Kontopantelis@manchester.ac.uk

Code list: res9: meglitinide

15 codes in list

Code Coding system Description Entity type List name multilexcode bnfcode bnfchapter
11316 CPRD_product_code NOVONORM tablets 500 micrograms [NOVO] drug res9: meglitinide 8076001 6010203 Other antidiabetic drugs
11321 CPRD_product_code NOVONORM tablets 1mg [NOVO] drug res9: meglitinide 8076002 6010203 Other antidiabetic drugs
11366 CPRD_product_code NOVONORM tablets 2mg [NOVO] drug res9: meglitinide 8076003 6010203 Other antidiabetic drugs
11483 CPRD_product_code nateglinide tablets 60mg drug res9: meglitinide 11867001 6010203 Other antidiabetic drugs
15955 CPRD_product_code STARLIX tablets 120mg [NOVARTIS] drug res9: meglitinide 11868002 6010203 Other antidiabetic drugs
23945 CPRD_product_code STARLIX tablets 60mg [NOVARTIS] drug res9: meglitinide 11868001 6010203 Other antidiabetic drugs
27125 CPRD_product_code STARLIX tablets 180mg [NOVARTIS] drug res9: meglitinide 11868003 6010203 Other antidiabetic drugs
35561 CPRD_product_code PRANDIN tablets 2mg [NOVO] drug res9: meglitinide 14733001 6010203 Other antidiabetic drugs
36774 CPRD_product_code PRANDIN tablets 1mg [NOVO] drug res9: meglitinide 14732001 6010203 Other antidiabetic drugs
36948 CPRD_product_code PRANDIN tablets 500 micrograms [NOVO] drug res9: meglitinide 14731001 6010203 Other antidiabetic drugs
5678 CPRD_product_code nateglinide tablets 120mg drug res9: meglitinide 11867002 6010203 Other antidiabetic drugs
5989 CPRD_product_code nateglinide tablets 180mg drug res9: meglitinide 11867003 6010203 Other antidiabetic drugs
9707 CPRD_product_code repaglinide tablets 1mg drug res9: meglitinide 8075002 6010203 Other antidiabetic drugs
9748 CPRD_product_code repaglinide tablets 2mg drug res9: meglitinide 8075003 6010203 Other antidiabetic drugs
9865 CPRD_product_code repaglinide tablets 500 micrograms drug res9: meglitinide 8075001 6010203 Other antidiabetic drugs

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