Neonatal diabetes tied to gene defect

April 23, 2001

An international team of researchers has identified the cause of a rare form of diabetes that affects newborn children. In a Brief Report in the May 24, 2001, issue of The New England Journal of Medicine, a team led by geneticists and physicians from the Universities of Chicago and Bergen, Norway; in collaborations with physicians from San Raffaele Scientific Institute, Italy, describe two cases of neonatal diabetes resulting from a complete deficiency of glucokinase, an enzyme that plays a crucial role in the regulation of blood-sugar levels.

Permanent neonatal diabetes mellitus is a rare disorder, occurring in about one in 400,000 live births. The two children described in the paper required insulin treatment beginning soon after birth.

"We believe this is the most common cause of permanent neonatal diabetes and urge physicians to look for glucokinase mutations in infants with diabetes, especially if the child has relatives with elevated blood sugar," said senior author Graeme Bell, Ph.D., professor of biochemistry & molecular biology, medicine, and human genetics and a member of the Howard Hughes Medical Institute at the University of Chicago.

In 1992, a team led by Bell discovered that glucokinase mutations were one cause of a sub-type of diabetes called maturity onset diabetes of the young (MODY). That defect appears to be relatively common and underdiagnosed.

"Finding glucokinase mutations that result in relatively mild disease as well as severe neonatal diabetes makes us suspect that there is a spectrum of glucose-regulation disorders that can be traced to different abnormalities of this gene," said Bell.

The parents of the Norwegian child were first cousins. The mother had type-1 diabetes and the father had elevated glucose levels, which he controls with diet. The patient's sister developed type-1 diabetes at age seven. The child, a girl, also had situs inversus, an unusual, probably genetic, condition in which the internal organs are arranged abnormally.

The Italian child, also a girl, has required insulin treatment since birth. She has no other health problems. Her mother has elevated blood-sugar levels and her father has impaired glucose tolerance, an early sign of diabetes.

Both children have mutations in both of their copies of the glucokinase gene. Both Norwegian parents and the sister with diabetes have one abnormal copy. Several other family members who have diabetes or hyperglycemia also have one abnormal copy.

The Italian girl has two copies of a different mutation of the same gene. Both parents have one copy of the same mutation.

Tests showed that both the Norwegian and Italian mutations rendered the enzyme inactive. Neither child with neonatal diabetes secrets any insulin.

The genetics of diabetes have proved to be very complex. Bell's team has isolated four different genes that cause MODY and last year pinpointed the first of several genes that increase susceptibility to the most common form of diabetes.

"This new role for glucokinase is another piece of the puzzle," he said. Not only are there many genes involved but "different mutations and combinations may cause differing forms of the disease."
Researchers from The University of Pennsylvania; The National Hospital, Oslo, Norway; and Vanderbilt University, Nashville, Tennessee, contributed to this study.

Funding for the study came from the National Institutes of Health, the Norwegian Research Council, the Norwegian Diabetes Council, the Novo Nordic Foundation, the Unger-Vetlesen Charitable Fund, the U.S.-Norway Fulbright Foundation, the Telethon Foundation, the Blum-Kovler Foundation and the Howard Hughes Medical Institute.

University of Chicago Medical Center

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to