Type 2 diabetes is often closely associated with excess weight, but that picture does not fit everyone. New research suggests the disease may develop differently in many African adults who have type 2 diabetes despite being lean.
In an observational study of 3,331 African adults with type 2 diabetes, researchers found that lean participants had lower insulin levels and showed signs that their pancreas was producing less insulin. Those with overweight or obesity showed more insulin resistance. The two groups also had different patterns of diabetes-related health problems. The findings raise questions about whether treatment could eventually be better tailored to these differences, but the study did not test medications or show that current treatments are inappropriate.
The study, published in Diabetologia, combined data from two large research projects involving adults from Ghana, Nigeria and Kenya, as well as Ghanaians living in Ghana and Europe. Researchers classified participants with a BMI below 25 as lean and those with a BMI of 25 or higher as having overweight or obesity. About 35% of the participants were in the lean group.
That proportion is notable because type 2 diabetes is commonly portrayed as a disease tied primarily to excess body weight. Previous research cited by the authors estimates that nearly 40% of African adults with type 2 diabetes are lean.
“This means that there are an estimated 10 million lean patients on the African continent who do not fit the standard picture,” said first author Sabrina Esmail of Amsterdam UMC.
The study found several important differences between the groups.
Lean participants generally had lower insulin levels and lower measures of pancreatic function. They also had less insulin resistance than participants with overweight or obesity, supporting the idea that difficulty producing enough insulin may play a larger role in their diabetes.
That does not mean the disease falls neatly into two completely separate categories. Type 2 diabetes can involve both insulin resistance and problems producing enough insulin. The researchers describe lean type 2 diabetes in African populations as a potentially distinct form of the disease rather than a definitively separate condition.
The health problems associated with diabetes also differed.
After accounting for factors including age, sex, education and diabetes treatment, lean adults had a 36% higher prevalence of diabetic retinopathy, an eye condition caused by damage to blood vessels in the retina, compared with participants with overweight or obesity. They also had a 41% higher prevalence of stroke.
At the same time, lean participants had less hypertension and a lower estimated 10-year risk of cardiovascular disease. Rates of chronic kidney disease did not differ significantly between the groups.
Those seemingly contradictory findings are part of what makes the study important. Having a lower body weight did not simply translate into a uniformly lower risk of diabetes complications.
“From this we concluded that lean patients more often develop eye damage, known as retinopathy, and strokes,” said senior author Felix Chilunga of Amsterdam UMC. “People who are overweight, by contrast, more often have high blood pressure and an increased risk of cardiovascular disease. Chronic kidney disease occurred equally often in both groups.”
Researchers also examined whether differences in lifestyle, insulin levels and body composition could help explain the patterns they observed. Body fat percentage accounted for much of the difference between groups for several outcomes, although the study cannot determine exactly why those differences developed.
The findings add to earlier research suggesting that the roots of type 2 diabetes may differ across populations and body sizes. The study authors note that early-life factors such as malnutrition and low birth weight have been linked more closely with lean type 2 diabetes in some African populations, while diet, inactivity and excess body weight may play a greater role in other forms of the disease. Those earlier findings were not directly tested in the current analysis.
The potential treatment implications remain much less certain.
Current diabetes guidelines in many African countries generally recommend similar first-line medications regardless of body size or the biological pathway contributing most to the disease. The researchers argue that if some lean patients primarily struggle to produce enough insulin, rather than being highly resistant to insulin, their ideal treatment could ultimately be different.
But this study cannot answer that question.
It was a cross-sectional observational analysis, meaning researchers compared participants and their health conditions rather than following them through different treatment strategies. It did not test whether metformin, insulin or other diabetes medications work better in one group than another. It also cannot establish that existing treatment contributed to the higher rates of retinopathy or stroke seen among lean participants.
“We are calling for targeted clinical trials to determine which treatment works best for this large and often overlooked group of patients,” Chilunga said.
There are also limits to how broadly the results should be applied. The study focused specifically on African populations, including adults living in Ghana, Nigeria and Kenya and Ghanaian migrants in Europe. It does not show that all lean people with type 2 diabetes have the same biological pattern or complication risks.
Still, the findings reinforce a larger point: body size alone may not tell clinicians enough about what is driving a person's type 2 diabetes. Further research could help determine whether differences in insulin production, insulin resistance and body composition should play a larger role in deciding how the disease is treated.
The analysis was supported by an Amsterdam Public Health Global Health seed grant and, in part, by the Intramural Research Program of the National Institutes of Health.
The RODAM study was funded by the European Commission's Framework Programme 7. The AADM study received support for participant recruitment from the NIH Office of Research on Minority Health. One researcher also received support through a National Institute of Diabetes and Digestive and Kidney Diseases Pathway to Independence Award.