Researchers studied over 82,000 American adults with type 2 diabetes to find better ways to predict serious health problems. They discovered that combining two simple blood tests—one measuring an enzyme called alkaline phosphatase and another measuring kidney function—creates a powerful tool for spotting people at highest risk of dying from heart disease or diabetes complications. The study followed people for over 11 years and found that those with the highest levels of this combination had nearly 2.5 times higher risk of diabetes-related death compared to those with the lowest levels. This new marker could help doctors identify which patients need extra attention and care.

The Quick Take

  • What they studied: Can combining two common blood test results help predict which people with type 2 diabetes are most likely to have serious health problems or die from heart disease?
  • Who participated: 82,091 American adults with type 2 diabetes who were part of a large national health survey. Researchers tracked their health outcomes for an average of 11.4 years (from 1999-2014, with follow-up through 2019).
  • Key finding: People with the highest levels of the combined blood marker had a 47% higher risk of dying from any cause, 44% higher risk of heart disease death, and 150% higher risk of diabetes-related death compared to those with the lowest levels.
  • What it means for you: If you have type 2 diabetes, this research suggests that doctors may be able to use two routine blood tests to better understand your personal health risks. However, this is still new research and needs more testing before it becomes standard medical practice. Talk to your doctor about your individual risk factors.

The Research Details

This was a large observational study using data from the National Health and Nutrition Examination Survey (NHANES), which is a representative sample of the U.S. population. Researchers looked at health information collected between 1999 and 2014, then followed up to see what happened to these people through the end of 2019. They used artificial intelligence (a computer learning system) to identify which blood markers were most connected to death risk, then created a simple formula combining two of those markers: alkaline phosphatase (an enzyme in your blood) and serum creatinine (a measure of kidney function). The researchers used statistical methods to determine at what levels of this combined marker people faced the highest risks.

This approach is important because it combines artificial intelligence with traditional medical research methods. Instead of just looking at one blood test at a time, the researchers created a composite marker that captures information about both heart and kidney function—two systems that are often damaged in people with diabetes. By using a large, nationally representative sample and following people for over a decade, the results are more likely to apply to real-world populations.

Strengths: Very large sample size (82,091 people) makes results more reliable; long follow-up period (11+ years) allows researchers to see actual health outcomes; nationally representative data means findings may apply broadly to American adults with diabetes. Limitations: This is an observational study, so it shows associations but cannot prove that the blood marker directly causes worse outcomes; the study only included data through 2019, so it’s not current; results may not apply to people outside the U.S. or those without diabetes.

What the Results Show

People in the highest group for the combined blood marker (ln[ALP × sCr]) had significantly worse outcomes compared to those in the lowest group. Specifically, they had a 47% higher risk of dying from any cause, a 44% higher risk of dying from heart disease, and a 150% higher risk of dying from diabetes-related complications. These differences were statistically significant, meaning they’re unlikely to be due to chance alone. The relationship between the marker and death risk followed a J-shaped pattern, meaning risk was lowest at moderate levels and increased at both very low and very high levels. The study also found that vitamin D levels explained about 24% of the connection between the combined marker and overall death risk, suggesting that vitamin D may play a role in this relationship.

The artificial intelligence analysis identified three key blood markers related to death risk in diabetes: alkaline phosphatase, serum creatinine, and vitamin D. The researchers focused on the first two because they’re routinely measured in standard blood work and are easy to combine into a simple formula. The finding about vitamin D’s role suggests that people with low vitamin D levels may be at particularly high risk, which could be important for future prevention strategies.

Previous research had shown that both alkaline phosphatase and serum creatinine individually predict worse outcomes in people with diabetes. This study builds on that work by showing that combining these two markers into one composite score may be even more powerful for predicting risk. The inclusion of vitamin D as a mediating factor aligns with other research suggesting vitamin D plays an important role in heart and metabolic health.

This study shows associations but cannot prove cause-and-effect relationships. The data is from 1999-2014, so it doesn’t reflect current medical practices or population characteristics. Results may not apply to people outside the United States, different age groups, or those without type 2 diabetes. The study relied on data collected for other purposes, so some information may not have been measured as precisely as in a study designed specifically for this research. Finally, the artificial intelligence method used to identify the markers was applied to the same data used to test them, which could make the results seem stronger than they actually are.

The Bottom Line

If you have type 2 diabetes, ask your doctor about your alkaline phosphatase and creatinine levels during routine blood work. While this new composite marker shows promise, it’s not yet standard clinical practice, so don’t be surprised if your doctor hasn’t heard of it. Focus on proven diabetes management strategies: maintaining healthy blood sugar levels, managing blood pressure, staying physically active, eating a balanced diet, and maintaining a healthy weight. Ensure adequate vitamin D intake through sunlight exposure, diet, or supplements as recommended by your doctor. This research suggests that vitamin D may be particularly important for people with diabetes.

This research is most relevant to people with type 2 diabetes and their healthcare providers. It may be especially important for those with known kidney problems or heart disease risk factors. People without diabetes don’t need to worry about this marker. If you’re at high risk for diabetes or have prediabetes, focus on prevention strategies rather than this marker.

This marker identifies current risk, not something that will change overnight. If you make lifestyle changes based on these findings (like improving vitamin D levels or better diabetes control), you might see improvements in related health markers within weeks to months. However, the real benefit—reducing risk of serious health events—would take years to demonstrate.

Want to Apply This Research?

  • Track your alkaline phosphatase and creatinine levels from routine blood work every 6-12 months. Create a simple spreadsheet or use your app’s lab tracking feature to record these values and note any changes over time. Also track vitamin D levels if your doctor measures them.
  • Use the app to set reminders for: (1) scheduling regular blood work to monitor these markers, (2) tracking vitamin D intake through food and supplements, (3) logging daily physical activity and diet quality, and (4) monitoring blood sugar levels if you have diabetes. Create a goal to maintain or improve your vitamin D status through dietary sources or supplementation.
  • Set up quarterly or semi-annual check-ins to review your lab results. Use the app to track trends in your markers alongside lifestyle factors (diet, exercise, stress, sleep). Share this information with your healthcare provider to discuss whether any changes to your diabetes management plan are needed. Monitor for any symptoms of kidney or heart problems and report them to your doctor promptly.

This research describes an association between a blood marker combination and health risks in people with type 2 diabetes, but it does not establish a cause-and-effect relationship. The composite marker (ln[ALP × sCr]) is not yet a standard clinical tool and should not be used to replace established diabetes management strategies or medical advice from your healthcare provider. If you have type 2 diabetes or concerns about your health, consult with your doctor before making any changes to your treatment plan. This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition.