You may have noticed from talking to friends and acquaintances that families often don’t have just one member with diabetes mellitus. Fairly often, more than one person in that family has this condition.
This is no coincidence. But why is this? Could it be because people in the same families tend to eat the same foods and live similar lifestyles? Or is it genetics? Could it be a bit of both? It’s the age-old nature versus nurture question. In this article, we will tackle just that.
First, we will discuss what diabetes is and which symptoms to look out for. We will then talk about the various risk factors that can predispose you to diabetes. Finally, we’ll get into diabetes and its links to genetics.
What is diabetes?
In type 1 diabetes, the body’s immune system destroys pancreatic beta cells. These are the cells that are responsible for insulin secretion.
Insulin is the hormone that carries glucose into your cells for energy. Since the glucose isn’t being effectively carried out of the blood in diabetes, hyperglycemia results, this is the medical term for high blood sugar.
In type 1 diabetes, patients must monitor their blood glucose levels and take insulin injections. The onset of type 1 diabetes is usually in childhood or adolescence.
Type 2 diabetes is when your body doesn’t use insulin properly. The pancreas will make more insulin at first to compensate for insulin resistance. But over time, there simply isn’t enough insulin to control blood sugar levels.
Gestational diabetes is diabetes that develops during pregnancy. This happens because a pregnant woman develops some degree of insulin resistance to ensure there is enough glucose available to the fetus. In some women, this insulin resistance can get out of control and lead to gestational diabetes.
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What are the symptoms of diabetes?
The symptoms of diabetes include the following:
- Increased thirst
- Frequent urination
- Constant hunger
- Unexplained weight loss
- Fatigue
- Irritability
- Blurred vision
- Sores that are slow to heal
- Frequent infections (of the skin, vagina, gums, etc.)
What are the risk factors for diabetes?
For type 1 diabetes, the Caucasian population is at higher risk. Also at risk are those who live in colder and more northern climates. The onset of type 1 diabetes is more likely during the winter months.
Type 1 diabetes can be triggered by certain viral infections, such as the German measles, Coxsackievirus, or the mumps. You are also at a higher risk of developing type 1 diabetes if you have a family history of this disease.
For type 2 diabetes, those at risk are those over the age of 45, especially if they are overweight or obese. This particularly goes for those with a body mass index of 25 or higher (those with lots of adipose tissue).
The following nationalities are also at higher risk of type 2 diabetes: Asian, Pacific Islander, African, Alaskan, indigenous, Hispanic, and native Hawaiian.
People with depression and/or polycystic ovary syndrome (called PCOS for short) are also at higher risk. Also, at risk are those with cardiovascular health conditions.
These include high blood pressure, heart disease, stroke, low high-density lipoproteins (“good” cholesterol, called HDL for short), or high triglycerides (a component of “bad” cholesterol). If you have a family history of type 2 diabetes mellitus, you are also at increased risk of this condition.
Risk factors for gestational diabetes include your family history, lifestyle, environment, and genetic risk factors as well.
Diabetes and genetics
We will be discussing the most common types of diabetes, including type 1, type 2, and gestational diabetes. However, it’s also worth mentioning that there is a type of diabetes called monogenic diabetes. This is relevant here because it is a form of diabetes that results from mutations in a single gene.
One example is what’s called maturity-onset diabetes. The other types of diabetes mentioned here are caused by several genes and lifestyle factors. However, monogenic diabetes is the result of a single gene change. It is a rare condition.
Type 1 diabetes
Researchers say that type 1 diabetes happens due to interactions between both environmental and genetic factors. Genome-wide association studies have found more than 50 genetic variants associated with an increased risk for type 1 diabetes.
The highest risk is due to genes that encode for what’s called the classical Human Leukocyte Antigens (called HLA class ii for short). Looking at HLA regions can be used as part of a prediction strategy for type 1 diabetes.
Other genetic loci also contribute to your genetic susceptibility for type 1 diabetes. Although diabetes type 1 is an autoimmune disease, susceptibility loci on both immune and non-immune genes can contribute to the risk of diabetes.
Gene therapy is actually one of the potential therapeutic alternatives for treating type 1 diabetes. If anything says diabetes is related to genetics, that’s it. There are several types of gene therapy being studied related to diabetes. They are as follows:
- Overexpression of genes and proteins needed against type 1 diabetes
- Transplantation of cells that express the genes against type 1 diabetes
- Stem cell-mediated gene therapy
- Genetic vaccination
- Immunological precursor cell-mediated gene therapy
Insulin gene therapy has shown promise in animal models. This involves the targeted expression of insulin in non beta cells. Liver cells are actually the primary therapeutic target here.
Another type of gene technology that is being investigated for diabetes gene therapy is called CRISPR. This stands for clustered regularly interspaced short palindromic repeat. It is a gene-editing technology that is new and currently under investigation.
Interestingly, there is a significant overlap between genes that are responsible for type 1 diabetes and genes that are expressed in salivary glands. In fact, 87 genes are common in both diabetes and salivary glands.
This suggests that type 1 diabetes impairs salivary secretion by affecting different processes in the salivary tissue. The genetic characteristics of type 1 diabetes could explain why people with diabetes have different saliva composition and dry mouth.
Type 2 diabetes
The etiology of type 2 diabetes is complex. There are certain environmental and genetic factors involved. Polymorphisms in several genes have been associated with this disease all around the world.
One study found that 26 of 41 genes evaluated with genetic testing were associated with type 2 diabetes risk. Disease over the past ten years or so has found that there are at least 75 independent genetic loci responsible for type 2 diabetes.
Although genes certainly play a role in type 2 diabetes, did you know that your environment can affect your genetic expression? Yes, you read that right. Your environment can actually change your gene expression.
This happens via epigenetic mechanisms such as DNA methylation, histone modification, and microRNA regulation. There is evidence to show that epigenetic changes are important in the development of type 2 diabetes.
If you look at the genetic architecture of our skeletal muscle, you will see that it is highly enriched with muscle stretch and super-enhancer genes. Some of these overlap with type 2 diabetes genetic variants. This means that gene receptors in our skeletal muscles affect our genetic predisposition to type 2 diabetes.
There is an abundance of research going on right now concerning type 2 diabetes and genetics. Research in this area is happening so quickly for a few reasons:
- Advances in genotyping efficiency
- Metabolomics profiling
- Bioinformatics approaches
- International collaboration
There is something called genetic sub-phenotyping. Researchers have suggested that this may be a way forward to identify specific individual phenotypes for the prevention and treatment of type 2 diabetes.
Detection of type 2 diabetes sub-phenotypes would help to personalize both screening and care. Studies have shown, over and over again, how a genomic approach to diabetes is valuable. Many small alleles have cumulative effects on your risk for type 2 diabetes.
Gene therapy can help to fix the underlying pathology of type 2 diabetes. It can do this by using the clustered regularly interspaced short palindromic repeat (CRISPR) gene-editing tool.
Based on animal and family-based intervention studies, there appears to be an interaction between nutrient-gene and type 2 diabetes. Case-control, cohort, cross-sectional cohort studies and clinical trials have identified relationships between genetics, diet, and type 2 diabetes.
There appears to be a causative relationship between poor diet in utero, persistent epigenetic changes, and type 2 diabetes. This relationship has been supported by animal studies as well as human observational studies. These studies have found this in different countries and over different periods of time. This shows that a relationship truly is there.
Pharmacogenetic research has been conducted as of late, and may help with the following:
- Identifying new drug targets
- Clarify pathophysiology
- Unravel disease heterogeneity
- Help prioritize specific genes in regions of genetic association
- Contribute to personalized/precision treatment
Most genetic variants associated with type 2 diabetes have modest effects on type 2 diabetes and are shared with major ancestry groups.
Gestational diabetes
In epidemiological studies, both genetic and environmental factors are implicated in gestational diabetes.
Biomarkers for gestational diabetes include single nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs. Certain gene alleles are significantly associated with gestational diabetes, particularly on the melatonin receptor.
Genome-wide association studies have identified several genetic variants that affect gestational glucose homeostasis and metabolism. Researchers have found that gene variants might contribute to gestational diabetes risk by affecting the expression of nearby or distant genes.
One study looked at single nucleotide polymorphisms and found that certain ones had known involvement in pancreatic b cells. Particular pathways could even be linked to diabetes and other biological functions.
Researchers identified four specific single nucleotide polymorphisms. They found that as they increased the number of protective alleles for these SNPs, the risk of gestational diabetes significantly decreased. This occurred in a dose-dependent manner, meaning that as the dose increased, so too did its effect on diabetes risk.
The researchers found that these single nucleotide polymorphisms might contribute to gestational diabetes by affecting the expression of a protein called TMEM18.
A different study looked at the differences in dietary intake between healthy pregnant women and those with gestational diabetes. Interestingly enough, researchers found that there was a genetic association of the bitter taste receptor allele with gestational diabetes.
This explained why women with gestational diabetes in the study consumed significantly more bitter foods than healthy pregnant women. This goes to show how related to genes gestational diabetes truly is.
Certain genes that are associated with gestational diabetes are also associated with type 2 diabetes. There are similarities between the genetic architecture of gestational and type 2 diabetes.
Conclusion
As you can see, diabetes clearly has some genetic component. But it’s not the only factor at play here. The environment, lifestyle, physical activity and diet each have their roles as well.
If we go back to our original question of “is diabetes genetic or due to lifestyle?” the answer is a complex mix of both of these. Yes, when it comes to our genetics, there is only so much we can control. But this doesn’t mean you are at the mercy of your family history.
You can still optimize by manipulating your modifiable risk factors. If you suspect you may have diabetes, or have a family history and want to prevent diabetes, speak to your health care provider.
Diabetes can have harmful consequences on your health, such as diabetic ketoacidosis. Prevention is the best practice and understanding the risk variants can help to reduce the risk of developing this condition.
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