Dr. Ahmad Shahzad
Founder | Lyallpur Diabetes Foundation
Consultant Diabetologist | Educator | Advocate for Preventive Care
Diabetes is a widespread chronic disease that occurs in millions across the globe of all ages. It is widely known as the disease associated with diet, lifestyle, and obesity, but another question has recursed lately, is diabetes hereditary? It has been found that family history and inherited genes may be a big influence on the risk of a person, but it is not the only cause. The interplay of genetics and environment brings about the knowledge of why one individual develops diabetes and another does not, even in the same family.
Understanding Diabetes
Diabetes is a long-time disease in which the level of blood sugar (glucose) is above normal. It occurs when the pancreas fails to generate adequate insulin or keeps on failing to utilize the insulin generated. Insulin is a hormone that is used as a key to open body cells to receive glucose in the food and use it as energy. Lack or poor functioning of insulin causes glucose to be in the blood, resulting in high blood sugar (hyperglycemia) that may cause other health challenges once not well addressed.
The Role of Genetics in Diabetes
In diabetes, especially in type 2 diabetes (T2D) genetics is an important part of the risk and development. The family and twin studies demonstrate a heritability range of 20-80 in diabetes, and the first-degree relatives are thrice as likely to assume the condition compared to their counterparts with no family history of the illness. It has a strong genetic component, with monozygotic twins being more concordant on T2D than dizygotic twins. Concordance in identical twins has been found as high as 40-50 percent in type 1 diabetes (T1D), suggesting a genetic role, but also the factor of environmental impact.
Several specific genes have been identified that influence diabetes risk:
- TCF7L2: It is known to influence insulin release and glucose production and is one of the strongest genetic predisposing factors in T2D.
- CAPN10: It is involved in the risk of T2D, particularly among certain populations.
- PPARG: Mutations in this gene may predispose diabetes and are associated with the body response to some diabetes treatments.
- KCNJ11: Involved insulin secretion and mutations in this gene are the cause of neonatal diabetes and factors in the development of T2D.
- HLA genes: These genes are mainly involved in T1D, and they help in the immune system and predisposition to autoimmune diabetes.
Genetic predisposition contributes to how the body metabolizes glucose, insulin released by beta cells, and insulin resistance. Gene-environmental interaction is also essential because in the event of genetic predispositions, environmental factors such as obesity, diet and lack of physical activity play an important role in predicting whether the predisposition can be developed as diabetes. Genes can also influence behavior and metabolism that combine with the risk factors in the environment.
Type 1 Diabetes: Is It Genetic?
T1D has familial and genetic attributions, but one gene does not cause it. It is a complicated disease that is caused by both genes and environment. Research suggests that genetics is about 50 percent of the risk of developing T1D.
HLA gene region, including HLA-DRB1, HLA-DQA1, and HLA-DQB1 in leukocyte antigen, on chromosome 6p21 is the major genetic risk factors of T1D. These genes are very important in immune system functioning. Types or haplotypes of these HLA genes predispose a person to develop an autoimmune attack on insulin-producing beta cells in the pancreas. An example is the haplo type DR3-DQA10501-DQB10201 and DR4-DQA10301-DQB10302 being greatly favorable to increase risks of T1D by 40% to 50%.
Beyond HLA, there are over 90 non-HLA gene loci that affect T1D risk, notably including INS, CTLA4, PTPN22 and IL2RA among others.
Although the risk genes predispose individuals, they are not a certain cause of T1D in everyone. The role of environmental factors, which seem to be critical in the onset of the diseases in genetically vulnerable individuals, include viral infections, early diet and perhaps climate.
Type 2 Diabetes: Is It Genetic?
T2D has a large genetic component with heritability estimates between 20 and up to 80 percent depending on the population and the study. A family history is a strong risk factor: lifetime incidence is up to 40% when one of the parents has T2D and up to 70% when both parents have it. The relatives of individuals with T2D have approximately three-fold increased risks of developing T2D than those without a family history.
The concordance rate (both twins having T2D) is approximately 70 in identical (monozygotic) twins and 20-30 in fraternal (dizygotic) twins, as twin research indicates, which is supported by the importance of heredity.
T2D is polygenic and has numerous genes that have a low impact. GWAS have found over 60 loci associated with T2D risk with the strongest association observed in TCF7L2. Additional genes linked to obesity also cause T2D because obesity is a leading cause of T2D.
Although genes are highly determinative, environmental factors and lifestyle, including diet and exercise, as well as body weight are highly influential to T2D risk. The relation between genes and the environment will dictate whether a person will develop T2D or not.
Monogenic Diabetes: When Genes Are Direct Cause
Monogenic diabetes A rare form of diabetes, directly genetic in origin, caused by mutation or variant of a single gene. In contrast to type 1 and 2 diabetes, which are caused by many genes and environmental factors, monogenic diabetes is caused by a problem with a single gene that interferes with the production or regulation of insulin in the body.
There are two main types of monogenic diabetes:
- 1Maturity-Onset Diabetes of the Young (MODY): Normally prevalent under age 25 and transmitted in autosomal dominant pattern which means that a parent who has that type of mutation has 50 percent possibility of passing it to his/her offspring. Approximately 1-5 % of cases of diabetes are due to DY, and they are usually marked by a family history of diabetes over many generations. These genes are most often HNF1 A, HNF4A, and GCK that influence the production of insulin and the work of the pancreas.
- Neonatal Diabetes Mellitus (NDM): Typically occurs in the initial six months of life and will be either impermanent or permanent. KCNJ11/ABCC8, in KCNJ11, a gene located on chromosome 11, and in ABCC8, a gene located on chromosome 8, KCNJ11 and ABCC8 may exhibit mutations either naturally or without inheritance from our parents.
The genetic mutation in monogenic diabetes can be related to the pancreas, insulin, limitation, insulin emission or insulin producing cell functions. As monogenetic diabetes is caused by a single genetic factor, genetic testing is essential to its diagnosis to make the appropriate treatment interventions and differentiate it from type 1 or type 2 diabetes.
You may also like to read: Importance of Blood Sugar Monitoring in Diabetes
Genetic Testing and Risk Assessment
Diabetes risk genetic testing entails examination of the genetic variants (primarily type 2 diabetes or T2D) of specific gene sequences. New technology has led to the discovery of several single nucleotide polymorphisms (SNPs) associated with the risk of diabetes. It is common to find tests that test several SNPs in order to give genetic risk score (GRS) of an individual to diabetes.
Such tests may be valuable in screening those at greatest risk early on, and, as some further action would then be possible, in lifestyle modification and increased surveillance. It is also used to distinguish between different forms of diabetes, e.g. monogenic diabetes; in such applications, genetic testing assists in identifying the appropriate treatment.
Genetic risk scores, however, provide only a small incremental predictive advantage beyond traditional clinical risk factors in age, body mass index (BMI), family history, and blood glucose levels. Currently, genetic testing is being used merely as a supplement to traditional methods of assessing clinical risk, rather than as an alternative.
Genetic testing can also help personalize treatment by informing how genetically determined differences can respond to diabetes medication, towards precision medicine in diabetes treatment.
Final Thoughts
In conclusion, the answer to is diabetes genetic is both yes and no. Heredity can play a major role in promoting diabetes especially when one of the parents, siblings or close relatives has the condition. But hereditary risk is but half the situation, and other environment, behavioral habits and all-round wellbeing are an equal factor. Your genes may not be changed, but you can do certain things like maintaining a balanced diet, engaging in exercising activities and checking the levels of blood sugar in the body to mitigate the risk of contracting diabetes. Learning more about your family history makes it possible to take precautions and consult a doctor in time, which will lead to improved long-term health.