Diabetes is a much more heterogeneous disease than the current system of classification implies, a review of the subject suggested.
The current subdivision of cases into type 1 or type 2 ”is a gross simplification, and poorly describes the true range of diabetes,” wrote Leif Groop, MD, PhD, of Lund University in Sweden, and his co-authors online Dec. 4 in The Lancet.
”The notion of diabetes has widened in the past few decades with the realization that several different overlapping mechanisms can lead to diabetes, and these mechanisms and manifestations of the disease can be modified by genetic and environmental factors,” the authors wrote.
Chief among the environmental factors are the growing obesity epidemic in some areas of the world, as well as nutritional changes and increasingly sedentary lifestyles.
The disease ”seems to result from a collision between genes and environment,” and the rapid increase in both forms of it, they said, ”suggests that many patients are genetically predisposed to both forms.”
Diabetes is a disorder of chronic hyperglycemia, and has traditionally been classified as type 1, characterized by autoimmune destruction of insulin-secreting beta cells; or type 2, typified by insulin resistance and features of metabolic syndrome. A monogenic subset, maturity-onset diabetes in the young (MODY), characterized by poorly functioning beta cells, has also been noted, they said.
Increasingly, many patients present with features of two or more types. The group with the most heterogeneity and risk of misclassification, they said, is young adults between the ages of 20 and 40.
Until 3 decades ago, all diabetic children and young adults were presumed to have type 1 diabetes. Now, while type 1 is still the most common form of the disease in children, ”the unabated increase in childhood obesity has resulted in the emergence of type 2 diabetes as a new type of pediatric disease,” the authors wrote.
Data from the SEARCH for Diabetes in Youth study, they noted, indicated that the prevalence of type 2 diabetes had increased by 21% in American young people between 2001 and 2009.
Children who develop type 2 diabetes, are, like their adult counterparts, overweight or obese. Onset usually occurs in mid-puberty, and beta cell failure occurs faster than it does in adults, with a mean transition time from pre-diabetes to actual diabetes of approximately 2.5 years compared with 10 years in adults, the authors wrote.
The authors also noted overlap in the two types of diabetes in the population of young people with type 2 diabetes, with a subgroup presenting with pancreatic auto-antibodies, and ketoacidosis detected in nearly 20% of them.
”As type 2 diabetes becomes more common in young age groups, the discriminatory value of ketoacidosis will weaken,” they wrote.
The rise of type 2 diabetes in the younger population also complicates the criteria by which MODY is identified, the authors said, because these criteria also describe most young people with type 2 diabetes.
In adults, the picture is equally complicated. ”The cutoff for age at onset (35 to 40) years, traditionally used to distinguish between type 1 and type 2 diabetes, is of little clinical value nowadays,” they said.
Classification is particularly difficult in the 20- to 50-year age range, during which time diabetes type 1, 2, MODY and secondary diabetes can occur. And while obesity used to be a clue to the presence of type 2 diabetes, the rise in obesity has made this characteristic less helpful as a diagnostic tool.
”Rather than confirming type 2 diabetes, the diagnostic value of these criteria lies in their absence; patients who are not overweight and do not have features of metabolic syndrome do not have type 2 diabetes, and other types of diabetes should be considered,” they said.
Further confusing presentation are the fact that patients with adult onset type 1 diabetes also often have residual beta cell function, making their presentation similar to that of patients with diabetes type 2, and a subgroup of adult patients with diabetes type 2 have pancreatic auto-antibodies.
Other recently identified subtypes in adults include ketosis-prone diabetes in adults, a hybrid form of the disease in which patients have features of both type 1 and type 2 diabetes, and latent autoimmune diabetes of adults (LADA), in which patients tend to be younger, secrete less insulin than those with the type 2 form of the disease, have less evidence of metabolic syndrome, and have a faster progression to insulin dependency than antibody-negative patients, the authors wrote.
Genetic evidence suggests that LADA may be a hybrid form of diabetes, with several studies suggesting that genes associated with both diabetes type 1 and type 2 play a role.
The authors predicted that the range of diabetic subgroups will become even more diverse in the future, noting that ”delineation of these subgroups will assist in the development of individualized therapy.”
From Medpagetoday
Source reference: Groop L, et al ”The many faces of diabetes: a disease with increasing heterogeneity” Lancet 2013; DOI: 10.1016/S0140-6736(13)62219-9.
www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962219-9/abstract
Abstract
The many faces of diabetes: a disease with increasing heterogeneity
Tiinamaija Tuomi MD a b c, Nicola Santoro MD d, Prof Sonia Caprio MD d, Mengyin Cai MD e, Prof Jianping Weng MD e, Prof Leif Groop MD f g Corresponding AuthorEmail Address
Summary
Diabetes is a much more heterogeneous disease than the present subdivision into types 1 and 2 assumes; type 1 and type 2 diabetes probably represent extremes on a range of diabetic disorders. Both type 1 and type 2 diabetes seem to result from a collision between genes and environment. Although genetic predisposition establishes susceptibility, rapid changes in the environment (ie, lifestyle factors) are the most probable explanation for the increase in incidence of both forms of diabetes. Many patients have genetic predispositions to both forms of diabetes, resulting in hybrid forms of diabetes (eg, latent autoimmune diabetes in adults). Obesity is a strong modifier of diabetes risk, and can account for not only a large proportion of the epidemic of type 2 diabetes in Asia but also the ever-increasing number of adolescents with type 2 diabetes. With improved characterisation of patients with diabetes, the range of diabetic subgroups will become even more diverse in the future.
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