A new study published in the journal of the endocrine society has revealed some interesting insights for diabetes care. The study demonstrated how being overweight or obese contributes to diabetes progression control over time.
A gradual decline leading to faster diabetes progression
We have known for a long time type 2 diabetes is mainly a lifestyle related disease. 80-90% of the people with the disease are also inactive and/or overweight. To understand why being overweight causes type 2 diabetes you need to understand what is happening in your body. Here is a video from Diabetes UK with a nice cameo voice over explaining how this works.
Therefore, insulin helps glucose enter the cells from the blood stream to provide energy for the brain, muscles, central nervous system, organs and so on. Basically, insulin works like a key and the cells are the lock. Insulin binds to the cells and tells them to open up to let glucose in. Fat clogging up the cells means some of the insulin keys no longer fit. This is called insulin resistance. At this point you are producing insulin but less is working properly. As a result, less glucose can get into the cells causing high blood glucose levels.
Your body reacts to this by releasing more insulin. Therefore, people newly diagnosed with type 2 diabetes or pre diabetes tend to have more insulin circulating in their body. As the disease progresses, the brain tells the pancreas to release more and more insulin to counteract rising glucose levels. You essentially need more insulin to achieve similar glucose levels prior to having diabetes.
Eventually, the pancreas can become overworked and tired leading to a reduction in its insulin producing capabilities. Now you have a double effect. You no longer produce enough insulin and the insulin you do produce, doesn’t work efficiently. You can be probably see this may lead to faster diabetes progression if this scenario plays out.
In order to help prevent this scenario, this study wanted to see whether we can predict the progression of type 2 diabetes based on patients maximum body mass index (BMI) before diagnosis.
What did they do
The researchers looked at 410 patients admitted to hospital. They wanted to see if it’s possible to predict how long it takes for patients to lose some insulin producing capacity from the pancreas based on their BMI prior to diagnosis. In other words, can we predict the rate of progression of diabetes based on a persons body weight.
The researchers started by looking back at the participants maximum BMI prior to diagnosis. They then took their date of diagnosis and current BMI.
The researchers then measured the patients insulin producing capabilities. In other words, how much insulin can the patients produce. They measured this using a C-Peptide test. C-Peptides are proteins attached to insulin molecules when they leave the pancreas. Before insulin goes off to do its job around the body, C-Peptides separate from the insulin molecules. Therefore, by measuring C-Peptide, we can indirectly see how much insulin your pancreas is producing. As type 2 diabetes worsens, the pancreas tends to produce less insulin and consequently less C-Peptide.
Remember, the researchers were trying to establish a link between BMI and decline in C-Peptide scores. They therefore separated the patients into 3 groups. Those patients with a maximum BMI prior to diagnosis below 25Kg/m2 , a BMI between 25-30Kg/m2 and a BMI above 30Kg/m2 .
A quick word about BMI ranges. Anything below 18.5Kg/m2 is considered underweight. 18.5-24.9Kg/m2 is normal weight. 25-29.9Kg/m2 is overweight. Finally, a BMI over 30Kg/m2 is obese.
They also separated patients into groups based on their current BMI upon admission into hospital.
What they found
The researchers first showed patients who were overweight or obese prior to diagnosis also tended to remain that way once admitted to hospital. In other words, overweight people tended to stay that way.
However, they could not demonstrate a definitive link between patients pre diagnosis body weight and their diabetes progression. So the researchers could not predict a time fame for the loss of insulin production.
That said, the researchers did find patients with higher BMI’s in hospital also had lower C-Peptide scores. This demonstrated lower insulin production capabilities in patients who are the most overweight. The most overweight patients in hospital were also the most likely to be overweight prior to diagnosis. Therefore, there appears to be a relationship here even though it didn’t reach clinical significance in the study.
Despite this, the study did find people were more likely to develop diabetes earlier in life if they had a higher BMI. This supports what we already know in clinical practice. Lifestyle plays a major part in developing type 2 diabetes. Essentially, the longer you live with type 2 diabetes, the more chance you have of complications. This is because you have to live with higher glucose levels for longer. This then causes damage to your body resulting in problems.
Finally, patients with the lowest C-Peptide scores also had diabetes for the longest time. So the longer you live with type 2 diabetes, the more chance your pancreas will begin to tire out. Therefore, patients diagnosed for the longest period are most likely to see the largest amount of diabetes progression.
What does this mean for patient care
You should try to lose weight if you have diabetes and a high BMI. We used to think type 2 diabetes was only a progressive disease. We now know you can improve the condition with lifestyle changes. However, neglecting the disease appears to lead to a faster decline in your body’s ability to manage your type 2 diabetes.
It also shows prevention is the best cure. Patients who were the most overweight prior to diagnosis, developed diabetes earlier in life. Therefore, losing weight and making lifestyle changes can prevent developing diabetes or at least delay it much later in life. This ultimately reduces the risk of complications. Keep in mind, the longer you have type 2 diabetes, the more likely you are to wear out your pancreas.
The study reiterates two ways type 2 diabetes causes high glucose levels. First is through insulin resistance. As discussed, this is when the body produces more insulin to maintain near normal glucose levels. You are producing insulin but it’s not working very well. Left untreated, your body becomes more resistant to insulin causing higher glucose levels.
Beta cell failure
Over time, your pancreas can start to wear out and produce less insulin. We mentioned this earlier but lets explain the process properly. The pancreas releases insulin from cells called ‘beta cells’. The beta cells can begin to fail when overworked. The brain signals to the pancreas you need more insulin as a result of developing insulin resistance. Over time this can work the beta cells too hard and their function declines.
If you don’t take action to improve your diabetes, this can lead to complete beta cell failure. This process is gradual but eventually means you may need to go onto insulin. Although, not everyone on insulin will experience complete beta cells failure and most people will continue to produce some of their own insulin.
You can still improve your insulin sensitivity through lifestyle change. However, once the beta cells start to fail, you begin to reach a point of no return from an insulin production point of view.
It’s never too late though. Lifestyle change at any point helps. It is the most effective treatment in fact.
Problems with the study
The study does have some problems. It is an obversataonal study. This means the researchers just observe the trends of what is happening in these patients. This is a good thing in the sense it replicates real life. It is a bad thing because they can’t control many variables that may influence their results. Differences in physical activity, smoking, genetics, ethnicity, gender, diet etc are all variables not controlled in the study. They therefore have to apply a bunch of fancy statistics to account for variables that might influence their findings.
The study was also quite difficult to read. It took a few attempts to understand what they did and it’s still not 100% clear. I think the authors could have made it just a bit more transparent.
This is also a small study. Compared to studies conducted by large pharmaceutical companies, 410 participants is tiny. Nonetheless, the results support what many other studies before it have shown. So it is consistent with current knowledge. This is why I felt it appropriate to share the findings.
I do question the main aim the study set out to achieve. Predicting the speed to beta cell failure would be a nice have. However, the study has shown once again that being overweight is a major risk factor for type 2 diabetes. Perhaps that’s all we need to know. Targeting this group of patients early could prevent the progression of the disease regardless of the time frame to beta cell failure.
It is a decent study showing how body weight makes a difference to diabetes progression. Prevention always appears to be the best cure with type 2 diabetes. Preventing or delaying the onset of type 2 diabetes is critical in improving long term health for these patients.
This study could not predict how quickly patients beta cell function would begin to fail based on their pre diagnosis body weight. However, they did find the most overweight patients once diagnosed, did see a quicker drop off in beta cell function. So we can’t predict a time frame but we do know it will happen more quickly.
Weight loss is tricky business. On one hand it is a completely controllable risk factor. Losing weight has so many benefits and this study once again shows this. On the other hand, we have a weight problem in the UK and so we know it’s not easy to do. It’s beyond the scope of this article to go into that. However, cracking this will certainly help to delay and prevent many of the problems we see in type 2 diabetes.
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Journal of the Endocrine Society. 2020;4(4)