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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: anticoagulants
76 codes in list
| Code | Coding system | Description | Entity type | List name | multilexcode | bnfcode | bnfchapter |
|---|---|---|---|---|---|---|---|
| 13348 | CPRD_product_code | Marevan 5mg tablets (Mercury Pharma Group Ltd) | drug | res9: anticoagulants | 1710003 | 2080200 | Oral Anticoagulants |
| 13501 | CPRD_product_code | Dindevan 50mg Tablet (Goldshield Pharmaceuticals Ltd) | drug | res9: anticoagulants | 1706003 | 2080200 | Oral Anticoagulants |
| 13502 | CPRD_product_code | Dindevan 10mg Tablet (Goldshield Pharmaceuticals Ltd) | drug | res9: anticoagulants | 1706001 | 2080200 | Oral Anticoagulants |
| 13503 | CPRD_product_code | Phenindione 50mg tablets | drug | res9: anticoagulants | 4443003 | 2080200 | Oral Anticoagulants |
| 13504 | CPRD_product_code | Phenindione 25mg tablets | drug | res9: anticoagulants | 4443002 | 2080200 | Oral Anticoagulants |
| 13505 | CPRD_product_code | Phenindione 10mg tablets | drug | res9: anticoagulants | 4443001 | 2080200 | Oral Anticoagulants |
| 13644 | CPRD_product_code | Dindevan 25mg Tablet (Goldshield Pharmaceuticals Ltd) | drug | res9: anticoagulants | 1706002 | 2080200 | Oral Anticoagulants |
| 15006 | CPRD_product_code | Sinthrome 4mg Tablet (Alliance Pharmaceuticals Ltd) | drug | res9: anticoagulants | 861002 | 2080200 | Oral Anticoagulants |
| 15376 | CPRD_product_code | Acenocoumarol 4mg tablets | drug | res9: anticoagulants | 3250002 | 2080200 | Oral Anticoagulants |
| 1781 | CPRD_product_code | Warfarin 5mg tablets | drug | res9: anticoagulants | 4382003 | 2080200 | Oral Anticoagulants |
| 17965 | CPRD_product_code | Marevan 500microgram tablets (Mercury Pharma Group Ltd) | drug | res9: anticoagulants | 7754001 | 2080200 | Oral Anticoagulants |
| 23078 | CPRD_product_code | Warfarin 1mg Tablet (WB Pharmaceuticals Ltd) | drug | res9: anticoagulants | 965009 | 2080200 | Oral Anticoagulants |
| 30202 | CPRD_product_code | Warfarin wbp 1mg Tablet (Boehringer Ingelheim Ltd) | drug | res9: anticoagulants | 1093001 | 2080200 | Oral Anticoagulants |
| 30203 | CPRD_product_code | Warfarin wbp 3mg Tablet (Boehringer Ingelheim Ltd) | drug | res9: anticoagulants | 1093002 | 2080200 | Oral Anticoagulants |
| 31511 | CPRD_product_code | Warfarin 3mg Tablet (WB Pharmaceuticals Ltd) | drug | res9: anticoagulants | 965010 | 2080200 | Oral Anticoagulants |
| 31937 | CPRD_product_code | Warfarin 5mg tablets (Teva UK Ltd) | drug | res9: anticoagulants | 1968011 | 2080200 | Oral Anticoagulants |
| 33711 | CPRD_product_code | Warfarin 5mg Tablet (WB Pharmaceuticals Ltd) | drug | res9: anticoagulants | 965011 | 2080200 | Oral Anticoagulants |
| 34019 | CPRD_product_code | Warfarin 1mg tablets (IVAX Pharmaceuticals UK Ltd) | drug | res9: anticoagulants | 1985009 | 2080200 | Oral Anticoagulants |
| 34086 | CPRD_product_code | Warfarin 3mg Tablet (Celltech Pharma Europe Ltd) | drug | res9: anticoagulants | 668010 | 2080200 | Oral Anticoagulants |
| 34087 | CPRD_product_code | Warfarin 1mg Tablet (Celltech Pharma Europe Ltd) | drug | res9: anticoagulants | 668009 | 2080200 | Oral Anticoagulants |
| 34088 | CPRD_product_code | Warfarin 5mg Tablet (Celltech Pharma Europe Ltd) | drug | res9: anticoagulants | 668011 | 2080200 | Oral Anticoagulants |
| 34095 | CPRD_product_code | Warfarin wbp 5mg Tablet (Boehringer Ingelheim Ltd) | drug | res9: anticoagulants | 1093003 | 2080200 | Oral Anticoagulants |
| 34299 | CPRD_product_code | Warfarin 1mg tablets (Teva UK Ltd) | drug | res9: anticoagulants | 1968009 | 2080200 | Oral Anticoagulants |
| 34416 | CPRD_product_code | Warfarin 1mg tablets (Kent Pharmaceuticals Ltd) | drug | res9: anticoagulants | 3836009 | 2080200 | Oral Anticoagulants |
| 34417 | CPRD_product_code | Warfarin 3mg tablets (Teva UK Ltd) | drug | res9: anticoagulants | 1968010 | 2080200 | Oral Anticoagulants |
| 34418 | CPRD_product_code | Warfarin 5mg tablets (Generics (UK) Ltd) | drug | res9: anticoagulants | 3681011 | 2080200 | Oral Anticoagulants |
| 34517 | CPRD_product_code | Warfarin 1mg tablets (Generics (UK) Ltd) | drug | res9: anticoagulants | 3681009 | 2080200 | Oral Anticoagulants |
| 34526 | CPRD_product_code | Warfarin 3mg tablets (Generics (UK) Ltd) | drug | res9: anticoagulants | 3681010 | 2080200 | Oral Anticoagulants |
| 34576 | CPRD_product_code | Warfarin 1mg Tablet (Lagap) | drug | res9: anticoagulants | 2910009 | 2080200 | Oral Anticoagulants |
| 34691 | CPRD_product_code | Warfarin 5mg Tablet (Regent Laboratories Ltd) | drug | res9: anticoagulants | 3691011 | 2080200 | Oral Anticoagulants |
| 34758 | CPRD_product_code | Warfarin 3mg tablets (IVAX Pharmaceuticals UK Ltd) | drug | res9: anticoagulants | 1985010 | 2080200 | Oral Anticoagulants |
| 34864 | CPRD_product_code | Warfarin 5mg tablets (IVAX Pharmaceuticals UK Ltd) | drug | res9: anticoagulants | 1985011 | 2080200 | Oral Anticoagulants |
| 34918 | CPRD_product_code | Warfarin 5mg tablets (Actavis UK Ltd) | drug | res9: anticoagulants | 2288011 | 2080200 | Oral Anticoagulants |
| 36099 | CPRD_product_code | Warfarin 1mg/5ml oral suspension | drug | res9: anticoagulants | 15434001 | 2080200 | Oral Anticoagulants |
| 38041 | CPRD_product_code | Warfarin sodium 5mg/ml oral suspension | drug | res9: anticoagulants | 16023001 | 2080200 | Oral Anticoagulants |
| 38044 | CPRD_product_code | Warfarin 5mg/5ml oral solution | drug | res9: anticoagulants | 16022001 | 2080200 | Oral Anticoagulants |
| 39119 | CPRD_product_code | Rivaroxaban 10mg tablets | drug | res9: anticoagulants | 16574001 | 2080200 | Oral Anticoagulants |
| 39444 | CPRD_product_code | Dabigatran etexilate 110mg capsules | drug | res9: anticoagulants | 16025001 | 2080200 | Oral Anticoagulants |
| 39503 | CPRD_product_code | Dabigatran etexilate 75mg capsules | drug | res9: anticoagulants | 16026001 | 2080200 | Oral Anticoagulants |
| 39639 | CPRD_product_code | Xarelto 10mg tablets (Bayer Plc) | drug | res9: anticoagulants | 16581001 | 2080200 | Oral Anticoagulants |
| 39755 | CPRD_product_code | Pradaxa 110mg capsules (Boehringer Ingelheim Ltd) | drug | res9: anticoagulants | 16028001 | 2080200 | Oral Anticoagulants |
| 39866 | CPRD_product_code | Warfarin 1mg tablets (Almus Pharmaceuticals Ltd) | drug | res9: anticoagulants | 5120009 | 2080200 | Oral Anticoagulants |
| 40143 | CPRD_product_code | Warfarin 500microgram tablets (A A H Pharmaceuticals Ltd) | drug | res9: anticoagulants | 4369009 | 2080200 | Oral Anticoagulants |
| 42474 | CPRD_product_code | Pradaxa 75mg capsules (Boehringer Ingelheim Ltd) | drug | res9: anticoagulants | 16027001 | 2080200 | Oral Anticoagulants |
| 43407 | CPRD_product_code | Warfarin 3mg tablets (A A H Pharmaceuticals Ltd) | drug | res9: anticoagulants | 2058010 | 2080200 | Oral Anticoagulants |
| 43408 | CPRD_product_code | Warfarin 1mg tablets (A A H Pharmaceuticals Ltd) | drug | res9: anticoagulants | 2058009 | 2080200 | Oral Anticoagulants |
| 43409 | CPRD_product_code | Warfarin 5mg tablets (A A H Pharmaceuticals Ltd) | drug | res9: anticoagulants | 2058011 | 2080200 | Oral Anticoagulants |
| 43655 | CPRD_product_code | Warfarin sodium oral solution | drug | res9: anticoagulants | 14470001 | 2080200 | Oral Anticoagulants |
| 4446 | CPRD_product_code | Acenocoumarol 1mg tablets | drug | res9: anticoagulants | 3250001 | 2080200 | Oral Anticoagulants |
| 44866 | CPRD_product_code | Warfarin sodium 1mg/ml oral supension SF | drug | res9: anticoagulants | 18272001 | 2080200 | Oral Anticoagulants |
| 45 | CPRD_product_code | Warfarin 1mg tablets | drug | res9: anticoagulants | 4382001 | 2080200 | Oral Anticoagulants |
| 46632 | CPRD_product_code | Dabigatran etexilate 150mg capsules | drug | res9: anticoagulants | 18784001 | 2080200 | Oral Anticoagulants |
| 46678 | CPRD_product_code | Pradaxa 150mg capsules (Boehringer Ingelheim Ltd) | drug | res9: anticoagulants | 18785001 | 2080200 | Oral Anticoagulants |
| 46924 | CPRD_product_code | Phenindione 10mg tablets (Mercury Pharma Group Ltd) | drug | res9: anticoagulants | 3552009 | 2080200 | Oral Anticoagulants |
| 47207 | CPRD_product_code | Rivaroxaban 20mg tablets | drug | res9: anticoagulants | 19045001 | 2080200 | Oral Anticoagulants |
| 47353 | CPRD_product_code | Rivaroxaban 15mg tablets | drug | res9: anticoagulants | 19043001 | 2080200 | Oral Anticoagulants |
| 47566 | CPRD_product_code | Apixaban 2.5mg tablets | drug | res9: anticoagulants | 18831001 | 2080200 | Oral Anticoagulants |
| 47925 | CPRD_product_code | Xarelto 20mg tablets (Bayer Plc) | drug | res9: anticoagulants | 19046001 | 2080200 | Oral Anticoagulants |
| 47944 | CPRD_product_code | Warfarin 1mg tablets (Actavis UK Ltd) | drug | res9: anticoagulants | 2288009 | 2080200 | Oral Anticoagulants |
| 48070 | CPRD_product_code | Warfarin sodium tablets | drug | res9: anticoagulants | 16994001 | 2080200 | Oral Anticoagulants |
| 48134 | CPRD_product_code | Xarelto 15mg tablets (Bayer Plc) | drug | res9: anticoagulants | 19044001 | 2080200 | Oral Anticoagulants |
| 48869 | CPRD_product_code | Warfarin 1mg/ml oral suspension sugar free | drug | res9: anticoagulants | 37790020 | 2080200 | Oral Anticoagulants |
| 50000 | CPRD_product_code | Warfarin 1mg/ml oral suspension sugar free (A A H Pharmaceuticals Ltd) | drug | res9: anticoagulants | 41649020 | 2080200 | Oral Anticoagulants |
| 51484 | CPRD_product_code | Warfarin 1mg tablets (Bristol Laboratories Ltd) | drug | res9: anticoagulants | 2298020 | 2080200 | Oral Anticoagulants |
| 51496 | CPRD_product_code | Warfarin 1mg tablets (Phoenix Healthcare Distribution Ltd) | drug | res9: anticoagulants | 2299020 | 2080200 | Oral Anticoagulants |
| 51509 | CPRD_product_code | Warfarin 1mg tablets (APC Pharmaceuticals & Chemicals (Europe) Ltd) | drug | res9: anticoagulants | 38963020 | 2080200 | Oral Anticoagulants |
| 5305 | CPRD_product_code | Sinthrome 1mg tablets (Alliance Pharmaceuticals Ltd) | drug | res9: anticoagulants | 861001 | 2080200 | Oral Anticoagulants |
| 53740 | CPRD_product_code | Eliquis 2.5mg tablets (Bristol-Myers Squibb Pharmaceuticals Ltd) | drug | res9: anticoagulants | 18832001 | 2080200 | Oral Anticoagulants |
| 53745 | CPRD_product_code | Warfarin 3mg tablets (Bristol Laboratories Ltd) | drug | res9: anticoagulants | 2302020 | 2080200 | Oral Anticoagulants |
| 53752 | CPRD_product_code | Warfarin 1mg tablets (Alliance Healthcare (Distribution) Ltd) | drug | res9: anticoagulants | 2297020 | 2080200 | Oral Anticoagulants |
| 54066 | CPRD_product_code | Apixaban 5mg tablets | drug | res9: anticoagulants | 46752020 | 2080200 | Oral Anticoagulants |
| 61 | CPRD_product_code | Warfarin 3mg tablets | drug | res9: anticoagulants | 4382002 | 2080200 | Oral Anticoagulants |
| 6262 | CPRD_product_code | Warfarin 500microgram tablets | drug | res9: anticoagulants | 11055001 | 2080200 | Oral Anticoagulants |
| 833 | CPRD_product_code | Warfarin 3mg/5ml oral solution | drug | res9: anticoagulants | 13574001 | 2080200 | Oral Anticoagulants |
| 8466 | CPRD_product_code | Marevan 1mg tablets (Mercury Pharma Group Ltd) | drug | res9: anticoagulants | 1710001 | 2080200 | Oral Anticoagulants |
| 8467 | CPRD_product_code | Marevan 3mg tablets (Mercury Pharma Group Ltd) | drug | res9: anticoagulants | 1710002 | 2080200 | Oral Anticoagulants |
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