Genetic findings in 'type 1.5' diabetes may shed light on better diagnosis, treatment

May 4, 2017
A depiction of the double helical structure of DNA. Its four coding units (A, T, C, G) are color-coded in pink, orange, purple and yellow. Credit: NHGRI

Researchers investigating a form of adult-onset diabetes that shares features with the two better-known types of diabetes have discovered genetic influences that may offer clues to more accurate diagnosis and treatment.

Latent autoimmune diabetes in adults (LADA) is informally called "type 1.5 diabetes" because like type 1 diabetes (T1D), LADA is marked by circulating autoantibodies, an indicator that an overactive immune system is damaging the body's insulin-producing beta cells. But LADA also shares clinical features with type 2 diabetes (T2D), which tends to appear in adulthood. Also, as in T2D, LADA patients do not require insulin treatments when first diagnosed.

A study published April 25 in BMC Medicine uses genetic analysis to show that LADA is closer to T1D than to T2D. "Correctly diagnosing subtypes of diabetes is important, because it affects how physicians manage a patient's disease," said co-study leader Struan F.A. Grant, PhD, a genomics researcher at Children's Hospital of Philadelphia (CHOP). "If patients are misdiagnosed with the wrong type of diabetes, they may not receive the most effective medication."

Grant collaborated with European scientists, led by Richard David Leslie of the University of London, U.K.; and Bernhard O. Boehm, of Ulm University Medical Center, Germany and the Lee Kong Chian School of Medicine, a joint medical school of Imperial College London and Nanyang Technological University, Singapore.

Occurring when patients cannot produce their own insulin or are unable to properly process the insulin they do produce, diabetes is usually classified into two major types. T1D, formerly called , generally presents in childhood, but may also appear first in adults. T2D, formerly called non-insulin-dependent diabetes, typically appears in adults, but has been increasing over the past several decades in children and teens. Some 90 percent or more of all patients with diabetes are diagnosed with T2D.

Grant and many other researchers have discovered dozens of genetic regions that increase diabetes risk, usually with different sets of variants associated with T1D compared to T2D. The current study, the largest-ever genetic study of LADA, sought to determine how established T1D- or T2D-associated variants operate in the context of LADA.

The study team compared DNA from 978 LADA patients, all adults from the U.K. and Germany, to a control group of 1,057 children without diabetes. Another set of control samples came from 2,820 healthy adults in the U.K. All samples were from individuals of European ancestry.

The researchers calculated scores to measure whether LADA patients had genetic profiles more similar to those of T1D or T2D patients. They found several T1D genetic regions associated with LADA, while relatively few T2D gene regions added to the risk of LADA. The genetic risk in LADA from T1D risk alleles was lower than in childhood-onset T1D, possibly accounting for the fact that LADA appears later in life.

One variant, located in TCF7L2, which Grant and colleagues showed in 2006 to be among the strongest genetic risk factors for T2D reported to date, had no role in LADA. "Our finding that LADA is genetically closer to T1D than to T2D suggests that some proportion of patients diagnosed as adults with type 2 diabetes may actually have late-onset type 1 diabetes," said Grant.

Grant said that larger studies are needed to further uncover genetic influences in the complex biology of diabetes, adding, "As we continue to integrate genetic findings with clinical characteristics, we may be able to more accurately classify subtypes to match with more effective treatments."

Explore further: More diabetes-associated, non-associated autoantibodies in T1D

More information: Rajashree Mishra et al, Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes, BMC Medicine (2017). DOI: 10.1186/s12916-017-0846-0

Related Stories

More diabetes-associated, non-associated autoantibodies in T1D

September 6, 2016
(HealthDay)—Patients with type 1 diabetes have more diabetes-associated autoantibodies (DAAs) and non-DAAs than patients with type 2 diabetes, according to a study published online Aug. 29 in Diabetes Care.

Antibody affinity is decisive in Type 1 diabetes in adults

March 11, 2014
Patients with LADA – a form of autoimmune type 1 diabetes in adulthood – can be distinguished from patients with non-autoimmune type 2 diabetes by means of the antibody reaction affinity to the enzyme glutamic acid decarboxylase ...

Researchers find biomarker that could help predict the onset of type 1 diabetes

March 28, 2017
A significant finding has been made by the 3U Diabetes Consortium, of Dublin City University, Maynooth University and the Royal College of Surgeons in Ireland (RCSI), which has the potential to contribute to the identification ...

Serum trypsinogen levels down in type 1 diabetes

January 26, 2017
(HealthDay)—Patients with type 1 diabetes have significantly lower serum trypsinogen levels than those without type 1 diabetes, according to a study published online Jan. 23 in Diabetes Care.

Chronic hepatitis B prevalence higher in those with T2DM

December 23, 2016
(HealthDay)—Patients with type 2 diabetes have higher prevalence of chronic hepatitis B virus infection (CHB), according to a study published online Dec. 8 in the Journal of Diabetes Investigation.

New immune cell subset associated with progression to type 1 diabetes

October 11, 2016
A study conducted at the University of Eastern Finland revealed that a recently described T cell subset may have a central role in the development of type 1 diabetes. These so called follicular T helper cells were found to ...

Recommended for you

Personalized blood sugar goals can save diabetes patients thousands

December 11, 2017
A cost analysis by researchers at the University of Chicago Medicine shows treatment plans that set individualized blood sugar goals for diabetes patients, tailored to their age and health history, can save $13,546 in health ...

Kidney disease increases risk of diabetes, study shows

December 11, 2017
Diabetes is known to increase a person's risk of kidney disease. Now, a new study from Washington University School of Medicine in St. Louis suggests that the converse also is true: Kidney dysfunction increases the risk of ...

Type 2 diabetes is not for life

December 5, 2017
Almost half of the patients with Type 2 diabetes supported by their GPs on a weight loss programme were able to reverse their diabetes in a year, a study has found.

Skipping breakfast disrupts 'clock genes' that regulate body weight

November 30, 2017
Irregular eating habits such as skipping breakfast are often associated with obesity, type 2 diabetes, hypertension and cardiovascular disease, but the precise impact of meal times on the body's internal clock has been less ...

Type 2 diabetes has hepatic origins

November 28, 2017
Affecting as many as 650 million people worldwide, obesity has become one of the most serious global health issues. Among its detrimental effects, it increases the risk of developing metabolic conditions, and primarily type ...

Critical link between obesity and diabetes has been identified

November 28, 2017
UT Southwestern researchers have identified a major mechanism by which obesity causes type 2 diabetes, which is a common complication of being overweight that afflicts more than 30 million Americans and over 400 million ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.