The European Association for the Study of Diabetes
HbA1c reduction improves CVD and mortality outcomes in Type 2 diabetes
MedWire News – European Association for the Study of Diabetes (Lisbon, Portugal), September 15th, 2011:The importance of glycemic control for reducing mortality and the risk for cardiovascular disease (CVD) was discussed in an open presentation session held on the third day of the 47th European Association for the Study of Diabetes (EASD) conference.
More specifically, researchers outlined how rapid elevations in glycated hemoglobin (HbA1c) are linked to increased arterial stiffness, how insulin treatment is associated with high mortality in patients with diabetes and coronary artery disease (CAD), and how sulfonylureas increase CVD risk over metformin treatment in Type 2 diabetes.
Fast HbA1c elevation increases arterial stiffness
Nanna Borup Johansen, Steno Diabetes Center, Gentofte, Denmark
Johansen presented results from a substudy of the Anglo–Danish–Dutch study in general practice of Intensive Treatment and complicatION prevention in Type 2 diabetic patients identified by screening (ADDITION)-Denmark trial, carried out to assess links between changes in HbA1c over time and arterial stiffness, which is a strong predictor of CVD [1].
The methods of the ADDITION-Denmark trial have previously been published. The current study included 896 participants who did not have diabetes at baseline and who were followed-up for 7.1 years on average for changes in arterial stiffness, as measured using pulse wave velocity (PWV).
At baseline, mean HbA1c was 5.7%. Average change in HbA1c per year was 0.02%.
Over the follow-up period, 188 individuals were diagnosed with Type 2 diabetes, 54 of whom were prescribed antihyperglycemic medication.
Johansen and colleagues found that a yearly increase in HbA1c of 0.1% was associated with a 0.24 m/s higher PWV at 7 years.
Age was also a significant predictor of arterial stiffness, with each additional year corresponding to an increase in PWV of 0.12 m/s.
The effect of HbA1c change on PWV was independent of HbA1c level at baseline, noted Johansen, and adjustment for incident diabetes actually increased the effect of change in HbA1c on PWV from 0.24 m/s to 0.36 m/s.
“To prevent aortic stiffness in people at high diabetes risk, even small increases in HbA1c should be avoided,” said Johansen.
Insulin, sulfonylurea use linked to raised mortality and CVD
Anna Norhammar, Karolinska University Hospital, Stockholm, Sweden; Ying Qiu, Merck Sharp & Dohme Corp., New Jersey, PA, USA
Patients with Type 2 diabetes who undergo percutaneous coronary intervention (PCI) to treat CAD are known to have increased mortality compared with nondiabetic patients undergoing the same procedure [2].
Insulin treatment, as opposed to other therapies, has been suggested as a marker of poor prognosis following PCI in diabetic patients.
Norhammar and colleagues investigated this further by analyzing data from 14,080 Type 2 diabetic patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and the National Diabetes Registry (NDR) in Sweden.
Patients were enrolled into the registries between 2001 and 2009 and underwent coronary angiography for suspected CAD.
Mortality was assessed at 6.0 months and 4.1 years and was significantly higher in those treated with insulin alone at both time points than those given other therapies. Patients treated with insulin and oral antihyperglycemic (OA) drugs had intermediate risk for death between that of patients treated with OA drugs alone and insulin alone.
More specifically, mortality rates at 4.1 years were 31.4%, 23.8%, 17.9%, and 20.2%, in patients treated with insulin alone, insulin plus OA drugs, OA drugs alone, or diet alone, respectively.
“Even after consideration of risk factors and more severe diabetes state, mortality rate is increased in patients treated with insulin,” said Norhammar.
She concluded: “The role of insulin in this context needs further evaluation.”
Whilst metformin has been associated with favorable CVD outcomes in some previous studies [3], sulfonylureas have been linked to adverse CVD outcomes in others [4].
In the final presentation of this session, Ying Qiu discussed the risks of CVD events (ischemic heart disease [IHD], myocardial infarction, stroke, transient ischemic attack, and peripheral arterial disease) associated with a first prescription of a sulfonylurea or metformin on diagnosis with Type 2 diabetes.
In total, 8502 patients were recruited, of whom half were treated with a sulfonylurea and half with metformin. They were all aged 65 years or above (mean age 75 years), as it is known that sulfonylurea use tends to increase in older adults owing to gastrointestinal side effects reported with metformin in this age group, making them an important group in which to clarify the possible adverse CVD effects of sulfonylureas.
After a mean follow-up period of 2 years and after controlling for baseline variables such as age, gender, body mass index, and presence of comorbidities, the patients taking sulfonylureas had a significantly higher incidence of CVD events than those taking metformin, at 12.4% versus 10.4%.
This amounts to a significant 23% increase in risk for CVD events in these patients, said Qiu. This difference was mainly due to a significantly higher rate of IHD in patients taking sulfonylureas, at 7.2% compared with 5.5% in those taking metformin, noted Qiu, who added that older age and male gender also increased the risk for CVD events.
Finally, patients who were prescribed sulfonylureas also had a significantly shorter time to a first CVD event than those prescribed metformin, she concluded.
References
1. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 2010;55:1318–1327.
2. Norhammar A, Lagerqvist B, Saleh N. Long-term mortality after PCI in patients with diabetes mellitus: results from the Swedish Coronary Angiography and Angioplasty Registry. EuroIntervention 2010;5:891-897.
3. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–865.
4. Schramm TK, Gislason GH, Vaag A, et al. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. Eur Heart J 2011;32:1900–1908.
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Publicerad: |2011-09-21|