A clinical study published May 27 in diabetes care now argues that malnutrition-related diabetes mellitus is indeed a distinct type of diabetes, and that studying it as such can improve the way it is treated. When studying a small sample of healthy, diabetic men from southern India, the authors concluded that diabetic patients with a body mass index (BMI) of 19 kg/mtwo or below with a history of malnutrition have a defect in insulin secretion – a feature previously suspected in these lean diabetic populations.
Suzanne Filteau, a nutritionist with a public health focus at the London School of Hygiene and Tropical Medicine, who was not involved in the work, says it was “conducted with great care”. Her findings, she adds, are consistent with observations that previous studies had suggested but lacked the resources to analyze — namely, in low- and middle-income countries, there is “a diabetes problem among thin people.” [that] It is more related to a lack of insulin production than insulin resistance, and so we need to reconsider how we treat these people.”
Based on current figures on the prevalence of diabetes and epidemiological studies, “we estimate [there are] probably about 80 million people worldwide currently suffer from malnutrition-related diabetes, says Meredith Hawkins, director of the Global Diabetes Institute at the Albert Einstein College of Medicine and one of the leaders of the new study. She says the potentially high prevalence of this type of diabetes in several regions, together with the fact that the WHO has withdrawn it as an official diabetes category, motivated her to study its metabolic profile in detail.
Hawkins and his colleagues teamed up with researchers at Christian Medical College, Vellore, India, and recruited South Indian men between the ages of 19 and 45 to participate in the study. They chose an all-male cohort, in part because this disease is known to primarily affect men. The team selected 73 individuals who fell into five categories: two groups without diabetes (thin and overweight) and three groups previously diagnosed with diabetes and classified by the team as type 1, type 2 or low BMI diabetes.
Type 1 and 2 patients were consistently diagnosed with these forms, explains Hawkins. Low BMI diabetics were defined according to the criteria established by the WHO in 1985, including a BMI equal to or less than 19 kg/mtwo and a history of low birth weight or episodes of malnutrition since childhood. This low BMI group also underwent immunogenetic analysis to rule out other types of diabetes, including all currently known types of young adult-onset diabetes and type 1 itself.
An insulin secretion problem
The team characterized the insulin secretion and resistance of each group. The metabolic profiles of patients with type 1 and type 2 diabetes were in agreement with what is currently known for both categories. That is, in type 1 diabetes, an autoimmune reaction destroys the individuals’ insulin-producing beta cells in the pancreas, resulting in little or no insulin secretion. Meanwhile, in type 2 diabetes, the main problem is insulin resistance, which means that receptors on muscle, fat, and liver cells respond poorly to insulin. Type 2 patients also have a problem with insulin secretion, but it is much milder than in those with type 1.
See “Reprogrammed Cells Treat Diabetes in Mice”
By evaluating insulin production in the first three hours after a meal, the team found that patients with diabetes and a low BMI had significantly less insulin secretion than those with type 2 diabetes, but greater than those with type 1. , insulin resistance was overall significantly lower in patients with lean diabetes than in type 2 diabetes. Some of these lean participants were as insulin resistant as type 2 patients, “and perhaps if we studied hundreds of [them], we would start to see subgroups,” says Hawkins. But for these lean individuals with diabetes, the biggest problem was insulin secretion, not insulin resistance, she notes.
The research team hypothesizes that this failure in secretion may result from decreased beta cell mass, a characteristic that has been linked to low-protein maternal diets in mice. Weaned rats fed a low-protein diet also show a marked defect in insulin secretion. While low protein intake may be the main culprit for impaired beta cell function in malnourished diabetic populations, Hawkins explains that other nutritional deficiencies may also play a role. For example, “many micronutrients like zinc can be extremely important for improving insulin secretion and improving beta cell function,” she says.
Current and future challenges
Viswanathan Mohan, a diabetologist and director of the Madras Diabetes Research Foundation in Chennai, India, who was not involved in this study, says the observations in it are interesting, but he is skeptical that the diabetes described by Hawkins and colleagues is not recognized in categories. Some of these cases could be a type 2 subtype, he says, as it is difficult to distinguish malnutrition-related diabetes from other types of diabetes without a molecular marker. Before labeling this type of diabetes and reviving the previous classification, it will be important to have a genetic, biochemical or hormonal marker to diagnose it, argues Mohan, adding that the new study motivates the search for such a marker.
University of Rwanda endocrinologist Charlotte Bavuma, who was not involved in the study, says it provides insight into the pathophysiology of an unrecognized but real type of diabetes — and one that may go undetected because it is being confused with other types. For example, along with her colleagues, she recently conducted a study in Rwanda that found a higher prevalence of type 1 diabetes compared to type 2. This “is not normal,” she says, and may indicate that many of the types 1 identified cases were in fact diabetes related to malnutrition.
While Bavuma and Filteau note that the results of the new study are difficult to extrapolate to other populations, given the small, single-sex sample size, they say these findings provide insights that could help improve diabetes management in thin individuals with diabetes. malnutrition history. According to Hawkins, these patients may, for example, be candidates for treatment with “medicines safer than insulin”. They can still be given small doses, but not enough to cause their blood sugar to drop to dangerous levels, she notes, adding that “pills to improve insulin secretion,” currently available for people with type 2, may be among viable treatments. for this population.
Hawkins says he hopes this clinical study, along with epidemiological studies over the past few decades, will help to bring back the official recognition of diabetes related to malnutrition, which would facilitate more research and awareness on the subject. Bavuma agrees that this is necessary as the current lack of recognition affects the clinical management of the disease, she says. Prevention and treatment guidelines are primarily based on type 1 and type 2 diabetes, she notes. As a clinician, explaining a patient’s condition to them is a challenge. Patients can learn about common risk factors for diabetes, such as obesity and a sedentary lifestyle, she says, but educational materials do not provide an explanation and preventative measures for her condition. Messages to prevent and treat “diabetes are not covering this population,” concludes Bavuma.