Dr Aidin Rawshani

New study on the importance of risk factors for individuals with type 1 diabetes

Contents

A new research study on artificial intelligence and the importance of risk factors in type 1 diabetes: what are the main risk factors, the optimal levels for different risk factors and how they interact with each other

Introduction

Population studies have shown that individuals with type 1 diabetes have an increased risk of premature death and cardiovascular disease compared to the general population. The disease contributes to impaired blood circulation and other organ damage over time. In order to better understand the cause of the shortened life expectancy of these individuals, one needs to study which risk factors are most important for the development of diabetes-related complications and what levels are optimal for these risk factors.

For people with type 1 diabetes, it is still unknown what is considered optimal levels for long-term blood sugar (HbA1c), blood lipids (LDL-C) and upper blood pressure (systolic blood pressure). Scientists and doctors have so far not figured out what is considered to be the most optimal levels for individuals with type 1 diabetes because the recommended national guidelines are based on clinical trials conducted in individuals with type 2 diabetes.

Therefore, there is a clear interest in understanding the prognostic role of increased long-term blood sugar (hyperglycemia), impaired renal function (albuminuria), hypertension (hypertension) and high blood lipidemia (hyperlipidemia).

Researchers from the University of Gothenburg have previously shown that individuals with type 1 diabetes who manage to control multiple risk factors at the same time have a lower risk of acute myocardial infarction and stroke, premature death and heart failure. This means that individuals with type 1 diabetes should always strive to control and optimize as many risk factors as possible to reduce the risk of future complications.

In addition, population studies show that individuals with type 1 diabetes who have blood sugar levels below the recommended national guidelines of 52 mmol/mol still have a 2-fold increased risk of premature death and cardiovascular diseases compared to the general population. This means that even if you are within “optimal” levels of blood sugar at the present time, you still have an increased risk of diabetes-related complications compared to individuals without diabetes.

In a completely new research study, researchers from the University of Gothenburg applied both traditional and new statistical methods to investigate which risk factors are the most important of 17 selected risk factors for cardiovascular diseases. The complications investigated in the current study were death, acute myocardial infarction, stroke and heart failure. The research study was published in one of the most reputable scientific journals, Circulation.

The research study examined the following issues:

  1. Which risk factors have the strongest significance for premature death and cardiovascular disease in people with type 1 diabetes.
  2. What are the optimal levels for the selected risk factors, long-term blood sugar (HbA1c), blood pressure (systolic blood pressure) and blood lipids (LDL-C) in terms of death and cardiovascular disease vascular disease.
  3. In what way do these risk factors interact with each other, an interaction effect involves studying how different levels of a particular risk factor affect another risk factors, interaction is usually explained easiest as a plus one becomes three.
  4. Contributes high blood sugar to the development of other risk factors such as high blood pressure, high blood lipids or poor kidney function (albuminuria).

What is unique about this study is that the research group included artificial intelligence (machine learning models) to better elevate complex interactions between different risk factors. The reason for this is that it has long been suspected that various risk factors for cardiovascular disease contribute to the development of others, for example, that elevated blood sugar levels (hyperglycaemia) have a negative effect on blood pressure and lipids.

Artificial Intelligence (machine learning) is the science that causes computers to learn and improve their learning fully autonomously, for example, to increase the predictability (predictability) of specific events.

Study population and design

The current study included 32.611 patients with type 1 diabetes, the average follow-up time was 10.4 years and the average duration of the disease for 18 years.

This is a registry study which involves including individuals with type 1 diabetes from medical research registers to study different aspects of diabetes. For this study, all individuals with type 1 diabetes registered in the National Diabetes Register (NDR) were included between 1 January 1998 and 31 December 2012. Information on demography, risk factors, drugs, complications and other clinical factors has been recorded for each person at the first inclusion in NDR.

People with type 1 diabetes who met one of the following criteria were excluded from the article: body mass index (BMI) below 18.5 kg/ m2, chronic heart disease, acute myocardial infarction, stroke, heart failure, atrial fibrillation, severe chronic kidney disease (EGFR ≤ 29 mL/ min/1.73 m2) and amputation. The reason that these were excluded was to study which risk factors are most important in individuals with type 1 diabetes who have not yet developed diabetes-related complications.

Results

What risk factors contribute most to future complications in people with type 1 diabetes?

The above figure is based on the traditional statistical models and machine learning models (AI). The results show that the most important risk factors for cardiovascular diseases and premature death are: high long-term blood sugar (HbA1c), poor kidney function (albuminuri/EGFR), duration of the disease (i.e. how many years the person has had the disease), blood pressure and poor blood lipids (LDL-C).

In addition, the risk factors affect the complications of premature death (mortality), acute myocardial infarction, stroke and heart failure. The figures seen next to the color circles in the figure demonstrate how each unit’s increase for different risk factors affects the development of the various complications. To demonstrate what these figures mean and how they should be interpreted, we take as an example the figures seen next to long-term blood sugar (HbA1c) in the column for Mortality, the figures we refer to are 1.02 (1.017 – 1.023) in the first column at the top.

How are the results from the figure above interpreted:

The first figures (1.02) illustrate that for each unit’s increase in long-term blood sugar (HbA1c) the risk of premature death increases by 2% for subjects with type 1 diabetes. To understand how this contributes to the increase in risk, we describe an example of a person with type 1 diabetes who has an HbA1c of approximately 70 mmol/mol. To interpret the increase in risk, we then take 1.02^70, resulting in 3.99 which we round to 4.0. This means that a person with type 1 diabetes who has 70 mmol/mol in HbA1c has about 4 times increased risk of premature death, or 400% increased risk. Similarly, we can figure out what the risk of systolic blood pressure and lipids will be. For renal impairment (albuminuria), we do not need to calculate the risk in this way. For example, the figure shows that poor renal function is associated with 3.6 times increased risk of heart failure (3.63, 95% CI, 3.05 to 4.31), or 360% increased risk.

What are the optimal levels for long-term blood sugar, blood pressure and blood lipids for people with type 1 diabetes?

The above figure shows how different levels of long-term blood sugar (HbA1c), blood pressure (systolic blood pressure) and lipids (LDL-C) contribute to the development of premature death and various cardiovascular diseases. The figure seems intricate but is not very difficult to interpret. The colored lines represent the three above risk factors and each colored line crosses a dashed horizontal line (1.0), the dotted line represents how different levels of risk factors relate to our national recommended guidelines.

To sum up the results, the figures above show that lower levels of long-term blood sugar, blood pressure and blood lipids are associated with significantly lower risk of premature death, acute heart attack, stroke and heart failure because they cross the dotted line. However, it is seen that at too low levels of these risk factors the risk increases again, especially premature death.

What risk factors contribute most to the development of other important risk factors for people with type 1 diabetes?

Another interesting finding from the current research study was that long-term blood sugar (HbA1c) contributes significantly to the development of other important risk factors. According to these results, long-term blood sugar (HbA1c) contributes to the development of hypertension (hypertension), impaired blood lipidemia (dyslipidemia) and poor kidney function (albuminuria).

This means that people with type 1 diabetes who control their blood sugar well have a lower risk of developing other dangerous risk factors in the long term, each of which contributes further to the development of cardiovascular diseases.

How do different risk factors interact in people with type 1 diabetes?

To summarize the results from the figure above, the model shows that at about 40 years of age onwards a strong interaction effect is seen between age and risk factors for blood sugar, blood pressure, blood lipids and kidney function.

This means that important risk factors such as blood sugar, blood pressure, lipids and kidney function have a greater negative impact on the body and the development of various diseases after 40 years of age. Individuals with type 1 diabetes should therefore be particularly experimental as they get older and control their risk factors well with either lifestyle changes or medical treatment once they get older.

Summary

What is new:

  • The absolute main risk factors for premature death and cardiovascular disease in individuals with type 1 diabetes were long-term blood sugar (HbA1c), impaired renal function (albuminuria), duration of the disease (i.e. how many years they had the disease), hypertension (hypertension) and elevated blood lipids (LDL-C).
  • Levels of long-term blood sugar, blood pressure, and blood lipids than current recommended national guidelines are associated with a lower risk of diabetes-related complications.
  • Renal impairment (albuminuria) is associated with 2-4 times increased risk of diabetes-related complications.
  • Each unit ( mmol/l) increase in blood lipids (LDL-C) is associated with 35 -50% higher risk of premature death and cardiovascular disease.
  • There is a clear interaction between age, duration of the disease, blood sugar, blood lipids, blood pressure and kidney function.
  • The cardiovascular risk factors (blood sugar, blood pressure, blood lipids, and the researchers interpret the results as long term blood sugar (HbA1c) most likely contributes to the development of the other risk factors.

What are the clinical implications:

  • The main risk factors for premature death and cardiovascular disease in individuals with type 1 diabetes, excluding age, were mostly conventional and modifiable cardiovascular risk factors. The fact that the risk factors are ‘modifiable’ means that we can improve and normalize the risk factors with either lifestyle changes or medical therapy.
  • This means that an increased clinical focus of these particular risk factors, especially in primary prevention, should lead to the highest possible risk factors. Reduction of risk for premature death and cardiovascular disease in individuals with type 1 diabetes.
  • Long-term blood sugar (HbA1c) and impaired renal function (albuminuria) were the two main risk factors for all diabetes-related complications.
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