For decades, type 2 diabetes has been closely connected with overweight and obesity.
That connection is real, but a new study shows why it can also hide a very different form of diabetes affecting large numbers of lean people, particularly in Africa.
A research team led by Amsterdam UMC and the University of Ghana found that body weight may reveal two different routes to the same diagnosis. In heavier patients, the body often struggles to use insulin properly, while in lean patients the pancreas may simply fail to make enough of it.
Insulin is essential for controlling the amount of sugar in the bloodstream. After a meal, the pancreas releases insulin, which acts like a signal telling cells to take in glucose and use or store it.
When cells stop responding well to that signal, the condition is called insulin resistance. This is common in the better-known form of type 2 diabetes and is strongly associated with excess body fat, although genes, age and other factors also matter.
But insulin resistance is not the only way blood sugar can rise. If the pancreas cannot release enough insulin, glucose can remain in the blood even when the body is not strongly resistant to the hormone.
The new research suggests that this second pathway is especially important among lean African adults with type 2 diabetes. That finding challenges a model of the disease largely built from studies in Europe and other wealthier regions.
In many high-income countries, about 90% of people with type 2 diabetes are overweight, according to the researchers. It is therefore understandable that weight and insulin resistance have become central to how doctors and the public think about the condition.
Africa presents a much more complicated picture. Nearly 40% of African adults with type 2 diabetes are lean, and researchers say the proportion can rise to around 60% in some rural communities in Ghana.
That could represent about 10 million lean patients across the continent. First author Sabrina Esmail said these people do not fit the standard model and appear more likely to have too little insulin rather than a poor response to insulin.
To investigate the difference, the scientists examined information from more than 3,300 African adults with type 2 diabetes. Participants came from Ghana, Nigeria and Kenya, and the research also included people of African background living in Europe.
The researchers found meaningful differences in the health problems experienced by lean and heavier patients. Lean people were more likely to develop diabetic eye disease and stroke, while those with higher body weight more often had high blood pressure and increased cardiovascular risk.
Kidney disease was different from this pattern because it occurred at similar levels in both groups. Senior author Felix Chilunga said differences in body fat explained many of the contrasts, strengthening the argument that the two groups may have different disease processes.
The study also points toward different roots of disease. For heavier patients, excess body fat and related metabolic changes can make the body less sensitive to insulin.
For lean patients, the story may sometimes begin much earlier in life. Malnutrition and low birth weight were more common risk factors, and both can affect the development of organs, including the pancreas.
The pancreas contains special cells that make insulin. If early-life conditions limit the development or later function of these cells, a person may have less reserve and become unable to produce enough insulin as an adult.
This possibility has major implications because diabetes treatment is not usually divided according to these two pathways. Across Africa, patients commonly receive standard oral medicines recommended by international guidelines regardless of whether they are lean or overweight.
Metformin, one of the world’s most widely used diabetes medicines, is especially useful for reducing the amount of glucose released by the liver and improving the body’s response to insulin. Other medicines work in different ways, including encouraging the pancreas to release more insulin.
The researchers argue that people whose main problem is limited insulin production may need treatment strategies designed specifically for that biology. However, the best treatment cannot be determined from this study alone, which is why the team is calling for dedicated clinical trials.
The findings could also matter for people of African ancestry living outside the continent. Previous UK Biobank research found that people of African descent reached a similar diabetes risk at a BMI of about 26 as Europeans did at a BMI of 30.
Other studies have reported that African migrants in Europe tend to develop type 2 diabetes at younger ages and often have poorer blood sugar control than local European populations. These differences suggest that relying heavily on weight thresholds developed in European populations could miss important risk.
Charles Agyemang, who led the project, argues that the same treatment mismatch may therefore exist in European clinics. A lean African patient living in London, Amsterdam or another European city may still have a form of diabetes that differs from the classic insulin-resistant pattern.
The study was published in the medical journal Diabetologia by researchers from Amsterdam UMC, the University of Ghana and their collaborators. Its broader message is that two people can receive the same diagnosis while the biological reasons for their illness are quite different.
There are limits to what can be concluded at this stage. The research shows strong differences between groups, but it does not establish a new treatment standard, and it does not mean that every lean patient has insulin deficiency or every heavier patient has severe insulin resistance.
BMI itself is also an imperfect measure because it does not directly show where body fat is stored or how much muscle a person has. Future research will need better biological measurements and randomized treatment trials to determine whether matching medicines to diabetes subtype actually prevents complications.
Even with those cautions, the study highlights a major gap in global diabetes research. Populations in Africa have often been underrepresented in large medical studies, yet findings from other populations are frequently used to guide their care.
If future trials show that lean diabetes responds better to a different treatment plan, the impact could be substantial. Millions of patients could receive care based not simply on the name of their disease, but on what is actually going wrong inside their bodies.
Source: Amsterdam UMC and University of Ghana.
