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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: microvascular_complications
84 codes in list
| Code | Coding system | Description | Entity type | List name | type | ||
|---|---|---|---|---|---|---|---|
| 1Z13.00 | Read | Chronic kidney disease stage 4 | diagnostic | microvascular_complications | 4 | ||
| 1Z14.00 | Read | Chronic kidney disease stage 5 | diagnostic | microvascular_complications | 4 | ||
| 1Z1H.00 | Read | Chronic kidney disease stage 4 with proteinuria | diagnostic | microvascular_complications | 4 | ||
| 1Z1H.11 | Read | CKD stage 4 with proteinuria | diagnostic | microvascular_complications | 4 | ||
| 1Z1J.00 | Read | Chronic kidney disease stage 4 without proteinuria | diagnostic | microvascular_complications | 4 | ||
| 1Z1J.11 | Read | CKD stage 4 without proteinuria | diagnostic | microvascular_complications | 4 | ||
| 1Z1K.00 | Read | Chronic kidney disease stage 5 with proteinuria | diagnostic | microvascular_complications | 4 | ||
| 1Z1K.11 | Read | CKD stage 5 with proteinuria | diagnostic | microvascular_complications | 4 | ||
| 1Z1L.00 | Read | Chronic kidney disease stage 5 without proteinuria | diagnostic | microvascular_complications | 4 | ||
| 1Z1L.11 | Read | CKD stage 5 without proteinuria | diagnostic | microvascular_complications | 4 | ||
| 2BBa.00 | Read | O/E- non-referable retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBk.00 | Read | O/E - right eye stable treated prolif diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBl.00 | Read | O/E - left eye stable treated prolif diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBo.00 | Read | O/E - sight threatening diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBP.00 | Read | O/E - right eye background diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBQ.00 | Read | O/E - left eye background diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBr.00 | Read | Impaired vision due to diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBR.00 | Read | O/E - right eye preproliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBS.00 | Read | O/E - left eye preproliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBT.00 | Read | O/E - right eye proliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBV.00 | Read | O/E - left eye proliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| 2BBY.00 | Read | O/E - referable retinopathy | diagnostic | microvascular_complications | 1 | ||
| C104.11 | Read | Diabetic nephropathy | diagnostic | microvascular_complications | 3 | ||
| C104z00 | Read | Diabetes mellitus with nephropathy NOS | diagnostic | microvascular_complications | 3 | ||
| C106.12 | Read | Diabetes mellitus with neuropathy | diagnostic | microvascular_complications | 2 | ||
| C106.13 | Read | Diabetes mellitus with polyneuropathy | diagnostic | microvascular_complications | 2 | ||
| C108D00 | Read | Insulin dependent diabetes mellitus with nephropathy | diagnostic | microvascular_complications | 3 | ||
| C109600 | Read | Non-insulin-dependent diabetes mellitus with retinopathy | diagnostic | microvascular_complications | 1 | ||
| C109611 | Read | Type II diabetes mellitus with retinopathy | diagnostic | microvascular_complications | 1 | ||
| C109612 | Read | Type 2 diabetes mellitus with retinopathy | diagnostic | microvascular_complications | 1 | ||
| C109A00 | Read | Non-insulin dependent diabetes mellitus with mononeuropathy | diagnostic | microvascular_complications | 2 | ||
| C109A11 | Read | Type II diabetes mellitus with mononeuropathy | diagnostic | microvascular_complications | 2 | ||
| C109B00 | Read | Non-insulin dependent diabetes mellitus with polyneuropathy | diagnostic | microvascular_complications | 2 | ||
| C109B11 | Read | Type II diabetes mellitus with polyneuropathy | diagnostic | microvascular_complications | 2 | ||
| C109C00 | Read | Non-insulin dependent diabetes mellitus with nephropathy | diagnostic | microvascular_complications | 3 | ||
| C109C11 | Read | Type II diabetes mellitus with nephropathy | diagnostic | microvascular_complications | 3 | ||
| C109C12 | Read | Type 2 diabetes mellitus with nephropathy | diagnostic | microvascular_complications | 3 | ||
| C109H00 | Read | Non-insulin dependent d m with neuropathic arthropathy | diagnostic | microvascular_complications | 2 | ||
| C109H11 | Read | Type II diabetes mellitus with neuropathic arthropathy | diagnostic | microvascular_complications | 2 | ||
| C109H12 | Read | Type 2 diabetes mellitus with neuropathic arthropathy | diagnostic | microvascular_complications | 2 | ||
| C10F600 | Read | Type 2 diabetes mellitus with retinopathy | diagnostic | microvascular_complications | 1 | ||
| C10F611 | Read | Type II diabetes mellitus with retinopathy | diagnostic | microvascular_complications | 1 | ||
| C10FA00 | Read | Type 2 diabetes mellitus with mononeuropathy | diagnostic | microvascular_complications | 2 | ||
| C10FA11 | Read | Type II diabetes mellitus with mononeuropathy | diagnostic | microvascular_complications | 2 | ||
| C10FB00 | Read | Type 2 diabetes mellitus with polyneuropathy | diagnostic | microvascular_complications | 2 | ||
| C10FB11 | Read | Type II diabetes mellitus with polyneuropathy | diagnostic | microvascular_complications | 2 | ||
| C10FC00 | Read | Type 2 diabetes mellitus with nephropathy | diagnostic | microvascular_complications | 3 | ||
| C10FC11 | Read | Type II diabetes mellitus with nephropathy | diagnostic | microvascular_complications | 3 | ||
| C10FH00 | Read | Type 2 diabetes mellitus with neuropathic arthropathy | diagnostic | microvascular_complications | 2 | ||
| F171100 | Read | Autonomic neuropathy due to diabetes | diagnostic | microvascular_complications | 2 | ||
| F171z00 | Read | Peripheral autonomic neuropathy due to disease NOS | diagnostic | microvascular_complications | 2 | ||
| F366.00 | Read | Polyneuropathy | diagnostic | microvascular_complications | 2 | ||
| F367.00 | Read | Peripheral neuropathy | diagnostic | microvascular_complications | 2 | ||
| F372.00 | Read | Polyneuropathy in diabetes | diagnostic | microvascular_complications | 2 | ||
| F372000 | Read | Acute painful diabetic neuropathy | diagnostic | microvascular_complications | 2 | ||
| F372100 | Read | Chronic painful diabetic neuropathy | diagnostic | microvascular_complications | 2 | ||
| F372.11 | Read | Diabetic polyneuropathy | diagnostic | microvascular_complications | 2 | ||
| F372.12 | Read | Diabetic neuropathy | diagnostic | microvascular_complications | 2 | ||
| F372200 | Read | Asymptomatic diabetic neuropathy | diagnostic | microvascular_complications | 2 | ||
| F374z00 | Read | Polyneuropathy in disease NOS | diagnostic | microvascular_complications | 2 | ||
| F37y100 | Read | Axonal sensorimotor neuropathy | diagnostic | microvascular_complications | 2 | ||
| F37z.11 | Read | Polyneuropathy unspecified | diagnostic | microvascular_complications | 2 | ||
| F3y0.00 | Read | Diabetic mononeuropathy | diagnostic | microvascular_complications | 2 | ||
| F420.00 | Read | Diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| F420000 | Read | Background diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| F420100 | Read | Proliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| F420200 | Read | Preproliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| F420600 | Read | Non proliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| F420700 | Read | High risk proliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| F420800 | Read | High risk non proliferative diabetic retinopathy | diagnostic | microvascular_complications | 1 | ||
| F420z00 | Read | Diabetic retinopathy NOS | diagnostic | microvascular_complications | 1 | ||
| F422z00 | Read | Proliferative retinopathy NOS | diagnostic | microvascular_complications | 1 | ||
| Fyu6B00 | Read | [X]Other mononeuropathies of lower limb | diagnostic | microvascular_complications | 2 | ||
| Fyu7C00 | Read | [X] Polyneuropathy, unspecified | diagnostic | microvascular_complications | 2 | ||
| FyuAC00 | Read | [X]Autonomic neuropathy/endocrine+metabolic diseases CE | diagnostic | microvascular_complications | 2 | ||
| K02..12 | Read | Nephropathy - chronic | diagnostic | microvascular_complications | 3 | ||
| K03..00 | Read | Nephritis and nephropathy unspecified | diagnostic | microvascular_complications | 3 | ||
| K03..11 | Read | Nephritis and nephropathy unspecified | diagnostic | microvascular_complications | 3 | ||
| K03..12 | Read | Nephropathy, unspecified | diagnostic | microvascular_complications | 3 | ||
| K054.00 | Read | Chronic kidney disease stage 4 | diagnostic | microvascular_complications | 4 | ||
| K055.00 | Read | Chronic kidney disease stage 5 | diagnostic | microvascular_complications | 4 | ||
| K08yA00 | Read | Proteinuric diabetic nephropathy | diagnostic | microvascular_complications | 3 | ||
| N035.00 | Read | Neuropathic arthropathy | diagnostic | microvascular_complications | 2 | ||
| N242300 | Read | Neuropathic pain | diagnostic | microvascular_complications | 2 |
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