Is Diabetes Genetic?

Is Diabetes genetic? Will I be diabetic if my parents are diabetic or my brother, sister or some other close relative is diabetic? Will my kids be diabetic if I have diabetes? These questions haunt the people with diabetes or if one of their close relatives has the disease. The answer to these is partly ‘yes’ and partly ‘no’.

A genetic disease is one which involves the genes in one way or the other. Since diabetes does involve genetic factors, it indeed classifies as a genetic disorder. However, that does not imply that it is a hereditary disorder, or that genes alone are the causative factors. Indeed, while genes play an important role in the pathophysiology of diabetes, there are certain environmental factors that are more important. Moreover, children of diabetic patients may not necessarily be diabetic. To understand how this complex interplay of factors works, lets read up a bit more.

Diabetes and its types

Diabetes results from deficiency or improper utilization of insulin, a hormone synthesised by beta cell of pancreas. This hormone is responsible for maintaining carbohydrate (sugar), protein and fat metabolism in the body. Deficiency or improper utilization of this hormone results in increased levels of glucose and lipids in the blood.

Diabetes is mainly of two types:

Type 1 Diabetes mellitus (T1DM): T1DM, also known as Juvenile diabetes, occurs more commonly in children and young adults and accounts for 5 to 10 percent of all diabetes cases.

Type 2 Diabetes mellitus (T2DM): T2DM occurs in middle age and is the commoner variety, responsible for 90 to 95 percent of the cases of diabetes mellitus.

Both T1DM and T2DM are caused by a combination of genetic and environmental risk factors. The child may inherit the genes for diabetes from a parent, but whether or not he or she has diabetes depends on the presence of certain environmental conditions.

Other rarer forms of diabetes are maturity onset diabetes in the young (MODY) and diabetes due to mutations in mitochondrial DNA. They have autosomal dominant inheritance, i.e. even if one of the parent has this type of diabetes, the child will develop diabetes.

Why and how diabetes occurs?

T1DM is characterized by destruction of beta cell of pancreas, thus producing little or no insulin. The development of the disease is triggered by some environmental factors or triggers, in those who are genetically susceptible. The most important trigger is viral infection. Early weaning of infants from breast-feeding and cold climate are thought to be other triggers. Studies in twins and first degree relatives of individuals with T1DM show some relation to but do not favour a strong correlation with genetics.

Genes that have been identified to be risk factors for T1DM include HLA class II genes, INS, and CTLA-4 gene. With T1DM, the chances of a child inheriting the condition from his mother are lesser, as compared to from a father who has the condition.

In T2DM, the pancreas synthesises insulin in very little amounts and/or if adequate amount of insulin is produced, the body is not able to properly utilize it (known as insulin resistance). T2DM has been shown to have strong genetic component, as seen from studies in twins, and on first degree relatives of individuals with T2DM.

The presence of family history of diabetes i.e. genetic predisposition increases the chances of developing diabetes, but whether or not the person actually develops the disease depends much more on environmental risk factors. These include:

• Obesity
• Lack of exercise
• Older age (³ 45 years).

Other less important environmental risk factors are high triglycerides, low HDL (good) cholesterol, smoking, hypertension, and polycystic ovary syndrome. Also, children are more likely to develop T2DM if the mother is diabetic, rather than if the father is. If both parents have diabetes, the chances of a child getting diabetes are much higher.

Several recent studies on genes (Genome-wide association studies) have identified about 18 genes (including PPAR?, KCNJ11, ABCC8, INS, HNF1A, GCK, HNF4A, and HNF1B) that increase the risk of Type 2 diabetes.

Diagnosis and Laboratory Tests

A person is diagnosed to be a case of diabetes mellitus, if:

• FPG (Fasting plasma glucose) ³ 126 mg/dl (> 7.0 mmol/L) or
• 2 hr PG (Plasma glucose 2 hours after a standard glucose challenge) ³ 200 mg/dl (> 11.1 mmol/L)
• Symptoms of diabetes and Casual plasma glucose (i.e. regardless of time of last meal) concentration ³ 200 mg/dl.

Apart from these, measurements of glycated haemoglobin (HbA1c) have commonly been used to monitor the long-term glycaemic control of patients.

What may happen if you have diabetes?

 Symptoms

Patients may be asymptomatic for years. Those who are symptomatic usually present with excessive thirst (polyuria), excessive urination (polydipsia), increased hunger (polyphagia), fatigue/tiredness, frequent infections or new-onset blurred vision.

Disease outcome/ Complications of diabetes

All forms of diabetes have very serious effects on health. Diabetic patients, if undiagnosed or inadequately treated, develop various acute and chronic complications leading to irreversible disability and death.

Acute complications include diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and hypoglycaemia, all of which may result in potentially serious complications if not promptly diagnosed and treated.

Both type 1 and type 2 diabetes are associated with the same long-term complications. Long-term complications include heart disease (Coronary artery disease and myocardial infarction), blindness, cataracts, glaucoma, kidney disease, nerve damage, stroke, diarrhoea, sexual dysfunction, foot ulcers, infections, non-traumatic amputation of the lower limb and skin changes.

Social, psychological and financial burdens are other implications of the disease.

Can we prevent diabetes?

It is not possible to prevent Type 1 diabetes. However, it is possible to delay or prevent Type 2 diabetes by leading a healthy lifestyle that involves healthy diet and adequate exercise. Exercise helps by controlling weight and improves glucose and fat utilization, which decreases the risk of T2DM.

Treatment

Diabetes is a chronic disease requiring lifelong treatment. There is virtually no permanent cure for diabetes.

In case of type 1 diabetes, lifelong insulin therapy is the only available treatment. The treatment of patients with type 2 diabetes should include diet, lifestyle modifications (exercise, smoking cessation), good glycaemic control (with oral hypoglycaemic agents and/or insulin) and lipid modifying drugs. Individuals with MODY are treated by diet, oral anti-diabetic drugs and sometimes, insulin.

 Current and Future Role of Genetics in Diabetes

Genetics does not currently play a role in the management or prevention of T1DM, as it not possible to prevent type 1 diabetes. In case of type 2 diabetes, many of the current T2DM genes identified are targets of anti-diabetic drugs; hence, genetic testing is useful in cases where those genes are identified. Early diagnosis of MODY may also help reduce the likelihood of long-term complications.

In the near future, the genes responsible for increasing the risk of developing all forms of diabetes will likely be identified. Genetic testing would be then greatly helpful in predicting the individuals at high risk of diabetes, and thus would prove beneficial in the prevention and management of the disease.

Conclusion

• Diabetes is usually caused by a combination of genetic and environmental risk factors
• Genetics and development of diabetes have weak association in case of type 1 diabetes and stronger association in case of type 2 diabetes.
• In case of type 2 diabetes, environmental factors have an even stronger influence than genes on whether or not the individual will actually develop the disease, and healthy diets and active lifestyles will be most beneficial in preventing or delaying diabetes and its complications.
• The question “Is diabetes genetic?” will be best answered in near future by genetic testing studies when the genes for all types of diabetes will be decoded.