Cardiovascular outcomes in type 1 and type 2 diabetes: the current evidence
Cardiovascular disease (CVD) is more common in people with type 1 and type 2 diabetes than among the general population. The increasing global burden of diabetes means that many more people are now at risk of CVD, but individual risk and outcomes depend upon many factors. An article by Annika Rosengren and Pigi Dikaiou of the University of Gothenburg, Sweden, in a recent issue of Diabetologia, reviews the current evidence on cardiovascular outcomes in type 1 and type 2 diabetes. Dr Susan Aldridge reports.
The largest increases in type 2 diabetes are occurring in low and middle-income countries, where rates now exceed those in high-income countries in some instances. And, as type 2 is being diagnosed at a younger age, more people are living longer with the condition and its risk of CVD.
Type 1 diabetes is on the increase, for reasons which are not yet entirely clear, with nearly half of all new cases occurring in high-income countries. However, it’s previously been estimated that the proportion of diabetes that is type 1 is between 5 and 15%, but this was based upon data from high-income countries. Now that data is coming in from low and middle-income countries, it looks as if this figure should be revised downwards to around 2%.
A recent global study revealed that around 60% of people with type 1 diabetes are above 40 years old, which is when CVD risk factors are highly prevalent and CVD complications start to become apparent. So increased prevalence of type 1 and type 2 diabetes among adults means more people are exposed to higher risk of CVD. The challenge now for clinicians and people with diabetes is how best to mitigate this risk.
Risk factors for CVD in diabetes
Cardiovascular disease comprises coronary heart disease, including myocardial infarction, various kinds of stroke, heart failure and peripheral artery disease. The excess risk of CVD in people with diabetes depends, to a large extent, on the presence or absence of other factors. Factors that apply to everyone, irrespective of diabetes status, are elevated LDL cholesterol, hypertension and smoking. Other factors are more specific to diabetes, such as HbA1c and micro- and macroalbuminuria.
Then there are the non-modifiable risk factors – age, sex and type of diabetes. Older people with diabetes have a higher absolute risk for CVD compared with younger people with diabetes, but relative risk is lower when comparing individuals with and without diabetes of the same sex and age. Women with type 1 diabetes have a 40% greater excess risk of mortality from any cause and twice the excess risk of vascular events compared with men who have type 1.
Type 2 diabetes confers a greater risk of CVD in women than in men, with women having a 27% higher risk of stroke and 44% higher risk of coronary heart disease than men. Therefore, women with diabetes of either type lose much of their normal female protection against CVD.
In type 1 diabetes, optimal levels of modifiable risk factors are associated with a lower risk of CVD. A cohort study based upon the Swedish National Diabetes Registry followed up 33,333 individuals with type 1 diabetes and 166,529 individuals without diabetes, matched for age, sex and location, for a mean of 10.4 years. Those with diabetes who had five risk factors at target – HbA1c, blood pressure, LDL cholesterol, micro- or macroalbuminuria and smoking – had 1.8 times the risk of acute myocardial infarction than the controls. Those who had none of these five risk factors at target had 12.3 times the risk.
A similar association was found for heart failure and even when all the risk factors were on target, excess risk of heart failure remained significantly higher in the diabetes group than in the control group.
The importance of keeping blood glucose levels under control is well established. In type 1 diabetes, there was the Diabetes Control and Complications Trial, which compared participants assigned to intensive versus conventional glucose-lowering therapy for a mean of 6.5 years. During 30 years of follow-up, those on intensive therapy had a reduction in CVD incidence of around one third compared with those on conventional therapy.
For those with type 2 diabetes, there is also support for intensive blood glucose control as a key factor in reducing CVD risk. A meta-analysis of five randomised controlled trials showed that intensive versus conventional glycaemic control significantly reduced CVD, but not all-cause mortality.
However, predisposition to CVD in type 1 diabetes is only partially attributable to traditional risk factors. Cardiovascular risk scores work for the general population and those with type 2 diabetes but are poorly applicable to type 1. One reason may be underlying arterial dysfunction. For instance, pulse pressure, which reflects arterial stiffness, has been found to increase at a younger age in type 1 diabetes compared with healthy control individuals. Reduced coronary flow reserve has also been shown in young individuals with type 1 diabetes, again in comparison with healthy controls.
Most of the literature on diabetes and cardiovascular outcomes relates to type 2 diabetes. In a meta-analysis of records of nearly 700,000 people from 102 studies, hazard ratios for diabetes versus no diabetes were 2.00 for coronary heart disease (CHD), 2.27 for ischaemic stroke, 1.56 for haemorrhagic stroke and 1.73 for other vascular deaths.
In comparison, a meta-analysis of 10 studies, involving 166,207 people with type 1 diabetes and matched controls from the general population, showed an overall relative risk for CHD of 9.38 and 6.37 for myocardial infarction for type 1 diabetes compared with the general population. The risks were higher for those with younger onset of the condition, reflecting the toxic impact of long-standing hyperglycaemia among those diagnosed during an era when there were fewer options for glucose lowering.
Comparing cardiovascular risk between people with type 1 and type 2 diabetes is difficult, not only because of the difference in phenotype – many other factors are involved. Age is one. In one study involving 36,869 individuals with type 1 diabetes and 457,473 with type 2 diabetes, mean age at entry was 35.3 years for those with type 1 and 65.2 years for type 2.
Duration of diabetes was much longer for those with type 1 diabetes, at 20 years, compared with just 5.7 years for those with type 2. Meanwhile, a study of 1.2 million people on the Australian diabetes registry showed that median age of those with type 1 diabetes was 22.3 years with a duration of 17.6 years, while the corresponding figures for type 2 were 58.2 years and 10.3 years. These stark differences in length of exposure to hyperglycaemia illustrate the difficulties of making comparisons.
So, irrespective of the type of diabetes, onset at a young age means longer exposure to hyperglycaemia and a higher risk of micro- and macrovascular complications. Even so, compared with type 1 diabetes, there is a much higher presence of CVD risk factors in individuals with early onset type 2.
There have been relatively few studies comparing CVD outcomes in those with type 1 and type 2 diabetes, so it is hard to make general conclusions. The authors do provide a table and description of those studies that have been done, which could make for useful extra reading. A couple of highlights are presented here to give a flavour of the findings.
Young-onset type 2 diabetes has been named as one of the most serious health challenges of the 21stcentury and recent years have seen the greatest relative increases in type 2 diabetes incidence and prevalence among younger adults. It’s been suggested that younger onset type 2 diabetes represents a more aggressive phenotype, with more rapid deterioration in beta cell function. A study comparing individuals from the USA and India with young-onset type 1 and type 2 diabetes, aged < 20 years, found that age of onset of type 2 in the USA was 14.7 years and 16.1 years in India. Participants with young-onset type 2 in the USA were more often female and had lower socioeconomic status. And USA participants with type 1 or type 2 diabetes had a higher BMI than their Indian peers. For instance, in the type 2 cohort, 79% of the USA participants were obese compared with 37% of the Indian participants.
Meanwhile, a recent study compared all 11,863 young adults < 40 years with type 1 diabetes from the database of the Hungarian National Health Insurance Fund and compared them with 47,931 individuals with type 2 diabetes of similar age. Those with type 1 diabetes had twice the risk of dying compared with those with type 2, but there was no difference in the risk of myocardial infarction. By contrast, data from the Korean National Health Insurance Service dataset were used to study CVD and mortality in individuals aged 20 or older without baseline CVD. Rates of incident myocardial infarction, hospitalisation for heart failure, atrial fibrillation and all-cause death were significantly higher among those with type 1.
Trends in CVD outcomes
CVD in the population is an ever-changing issue as there has been a marked decline in death from heart disease over the last decades. In the general population, there has been significant progress on CVD prevention and treatment in many parts of the world. Cancer now surpasses CVD as a main cause of death in high-income countries.
A study also found that major CVD-associated mortality had declined in the late 1980s up to 2015 in adults with diabetes, especially among men. Large reductions were found in mortality from ischaemic heart disease and stroke, although trends in heart failure did not change. Nearly all the decline in the death rate among adults was caused by reduction in vascular disease-related deaths, which accounted for almost half of deaths in people with diabetes in the early 1990s, falling to around one third of deaths from 2010 to 2015.
One study analysed over one million Australians with diabetes, of whom 7.3% had type 1, registered on the National Diabetes Service Scheme between 2000 and 2011. There was a decrease in CVD in both types of diabetes, but this was not consistently seen across age groups, with younger people < 40 years old with type 1 seeing smaller improvements in CVD-related and all-cause mortality than those aged 40 to 70 years. Worryingly, those with type 2 and < 40 years experienced an increase in all-cause mortality and no decline in CVD-related death.
The improvements in CVD, as cited above, are not paralleled by obesity rates, which are increasing globally, or by rates of CVD in low to middle-income countries, which are also increasing. And, in the USA, there have been increasing numbers of cardiometabolic deaths – heart disease, cerebrovascular disease and diabetes – in adults < 65 years, which have been linked to the recently observed decline in life expectancy there.
Despite declining rates of CVD among those with type 1 and type 2 diabetes and the general population, growing rates of people with both types of diabetes is leading to a continuing increase in the numbers with cardiometabolic disorders around the world. This will offset the progress in many countries on prevention and treatment of CVD, and may lead to stalling of increasing life expectancy.
For type 2 diabetes, increased incidence has an obvious link to rising rates of obesity and early onset type 2 diabetes is particularly dangerous in terms of complications, including CVD. For type 1 diabetes, the cause for the rise in incidence is probably multifactorial. The larger variation in incidence, with a predominance of cases in high-income countries, suggests that obesity may also play a role here.
As stated above, comparisons between those with type 1 and type 2 diabetes with respect to their CVD risk are difficult to make as they are dependent on other factors, some modifiable and some not. Findings on CVD outcomes so far are highly dependent on context and are inconclusive. So the continuing comparison of outcomes is still of professional and public interest, particularly for people with diabetes.
What will matter most in determining CVD risk management in any person with diabetes is their individual risk, depending on age, duration of diabetes and other factors. Glycaemic control, control of lipids and hypertension, and a healthy lifestyle are key. These efforts, especially with respect to glycaemic control, should start early and should include identification and treatment of CVD risk factors, as is recommended in multiple diabetes management guidelines.
To read this paper, go to: Rosengren A, Dikaiou P. Cardiovascular outcomes in type 1 and type 2 diabetes. Diabetologia online 14 January 2023. https://doi.org/10.1007/s00125-022-05857-5
To learn more, enrol on the EASD e-Learning course ‘Cardiovascular health and diabetes’: https://easd-elearning.org/courses/cardiovascular-health-and-diabetes/
Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.