Genetics and Diabetes

What’s your risk? Researchers report that, while much has been learned about what genetic factors make one more susceptible to developing diabetes than another, many questions remain to be answered.

A school nurse anxiously wants to know if there is a reason why several children from her small grade school have been diagnosed with type 1 (juvenile onset) diabetes. Is it an epidemic? Will there be more cases? Is a recent chicken pox outbreak to blame?

A man in his 50s develops type 2 diabetes. His mother developed diabetes in her 60s. Should this man’s brother and sister be concerned, too? What about his children’s chances of developing diabetes?

A married couple wants to have children, but they are concerned because the husband has type 1 diabetes. They wonder what the risk is for their child to have diabetes.

A couple has three young children. One of the children develops type 1 diabetes. There’s no history of diabetes anywhere in either parent’s families. Is this just a fluke? What are the chances for the other children to develop diabetes?

Chances are if you or a loved one have diabetes, you may wonder if you inherited it from a family member or you may be concerned that you will pass the disease on to your children.

While some people are more likely to get diabetes than others, and in some ways type 2 (adult onset diabetes) is simpler to track than type 1 (juvenile onset) diabetes, the pattern is not always clear.

Type 1 and genetics

Just who is at risk for developing type 1 diabetes? Here’s a sampling of what Dr. Warram, a Lecturer in Epidemiology at Harvard School of Public Health, said is known: If an immediate relative (parent, brother, sister, son or daughter) has type 1 diabetes, one’s risk of developing type 1 diabetes is 10 to 20 times the risk of the general population; your risk can go from 1 in 100 to roughly 1 in 10 or possibly higher, depending on which family member has the diabetes and when they developed it. If one child in a family has type 1 diabetes, their siblings have about a 1 in 10 risk of developing it by age 50.

The risk for a child of a parent with type 1 diabetes is lower if it is the mother - rather than the father - who has diabetes. “If the father has it, the risk is about 1 in 10 (10 percent) that his child will develop type 1 diabetes - the same as the risk to a sibling of an affected child,” Dr. Warram says. On the other hand, if the mother has type 1 diabetes and is age 25 or younger when the child is born, the risk is reduced to 1 in 25 (4 percent) and if the mother is over age 25, the risk drops to 1 in 100 - virtually the same as the average American.

If one of the parents developed type 1 diabetes before age 11, their child’s risk of developing type 1 diabetes is somewhat higher than these figures and lower if the parent was diagnosed after their 11th birthday. About 1 in 7 people with type 1 has a condition known as type 2 polyglandular autoimmune syndrome. In addition to type 1 diabetes, these people have thyroid disease, malfunctioning adrenal glands and sometimes other immune disorders. For those with this syndrome, the child’s risk of having the syndrome, including type 1 diabetes, is 1 in 2, according to the American Diabetes Association (ADA).

Caucasians (whites) have a higher risk of type 1 diabetes than any other race. Whether this is due to differences in environment or genes is unclear. Even among whites, most people who are susceptible do not develop diabetes. Therefore, scientists are studying what environmental factors may be at work. Genes influencing the function of the immune system are the most closely linked to type 1 diabetes susceptibility, regardless of race. One of those genes is HLA-DR. Most Caucasians with diabetes carry alleles (gene variants) 3 and/or 4 of the HLA-DR gene. The HLA-DR7 allele plays a role in diabetes in blacks, while HLA-DR9 allele is important in diabetes among Japanese.

Climate and Clusters

Among Caucasians, diabetes risk varies geographically. In general, the risk is higher in Northern Europeans than Southern Europeans. While climate may contribute to this, the fact that Sardinia in the Mediterranean also has a high risk goes against this theory.

Generally, the number of new cases over time fluctuates up and down, making it difficult to find an overall pattern. In recent decades, there has been an increase in type 1 diabetes in the United States and Europe.

While Asians generally have a much lower incidence of type 1 diabetes, Japan is also experiencing an increasing incidence. “The gene pool doesn’t change much within one generation, so there must be an environmental or behavioral factor involved,” Dr. Warram says.

Temporal clusters of type 1 diabetes cases (i.e. those that occur around the same time - whether within families, a school or a geographical region), prompt people to suspect an environmental agent. However, no consistent explanation has come up for these clusters, and it is impossible to rule out the possibility of just coincidence.

Given the fact that the development of diabetes takes many years in most cases, a clustering in time seems more likely due to chance than a common cause, Dr. Warram says. “From what we know, the autoimmune process leading to the destruction of insulin-producing beta cells in the pancreas is quite long.

People can have antibodies signaling damage to the beta cells for many years without developing diabetes,” Dr. Warram says.

Trauma as a Trigger

Some people have questioned whether a body trauma, like a car crash, or a viral infection like mumps, could trigger the onset of type 1 diabetes. “As the demands on the body increase, it can tip the body’s insulin production system over the edge,” Dr. Warram says. But the trauma itself did not “cause” the diabetes, he says.

Much has been said about a possible link between Coxsackie virus, which causes human diseases such as meningitis, and the triggering of type 1 diabetes. “You can’t dismiss the fact that sometimes the virus has been present, but its connection with the diabetes is unclear,” Dr. Warram says. Scientists do have some significant evidence that mumps does not trigger diabetes, however.

A Maryland study showed that despite a great decline in mumps cases after the mumps vaccine was introduced 30 years ago, the incidence of type 1 diabetes did not change. Some scientists believe early diet may have a role. Prolonged breastfeeding is less common in children who developed type 1 diabetes.

While some studies have pointed to exposure to cow’s milk, Dr. Warram says much remains to be learned before we can assess the importance of this mechanism. To be prudent, mothers of infants at high risk of developing diabetes may want to breastfeed as long as possible and rely on cow’s milk only in moderation after the baby is weaned.

Tracking Type 2 Diabetes:

Patients with type 2 diabetes are more likely to know of a relative with diabetes than patients with type 1 and, therefore, suppose that diabetes “runs in the family.” To some extent the appearance of “clustering” of type 2 diabetes in families is simply the consequence of the fact that type 2 is so much more common than type 1 diabetes in the general population.

Moreover, the occurrence of multiple cases in a family may reflect shared “environmental risk factors,” such as obesity and sedentary lifestyle, and does not imply necessarily the sharing of a diabetes gene. In general, the risk of diabetes for a sibling of a patient with type 2 diabetes is about the same as that in the general population.

However, there are some exceptions to this general statement. If the patient developed diabetes despite being lean, then the sibling’s risk is about twice the general population risk. Or, if the patient has a parent with type 2 diabetes, the sibling’s risk is almost three times the general population risk. If both parents have type 2 diabetes, the sibling has a fourfold risk, or nearly a 50% chance of developing diabetes.

The genetics of type 2 diabetes is complex. While type 2 diabetes may have a strong genetic basis in some patients (something less than a third of them), the development of diabetes in most patients is dependent upon the effects of environmental and behavioral factors (obesity and sedentary lifestyle) on an underlying susceptibility that is poorly understood.

06 September 2020

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