DIABETES : Causes & Risk Factors

CAUSES of Diabetes

Diabetes is classified into 4 broad categories: "type 1", "type 2", "gestational diabetes" and "other specific types". The "other specific types" are a collection of a few dozen individual causes. Diabetes is a more variable disease than once thought and people may have combinations of forms.

What causes type 1 diabetes?

Type 1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. Doctors don’t know exactly what causes type 1 diabetes. The majority of type 1 diabetes is of the immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin.
     Scientists think type 1 diabetes is caused by genes and environmental factors, such as viruses, that might trigger the disease. Studies such as TrialNet are working to pinpoint causes of type 1 diabetes and possible ways to prevent or slow the disease.
     Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Although it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living with type 1 diabetes are now adults.
     Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans. Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.
     Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults (LADA) is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than cause.

What causes type 2 diabetes?

Type 2 diabetes—the most common form of diabetes—is caused by several factors, including lifestyle factors and genes.
     Type 2 diabetes usually begins with insulin resistance, a condition in which muscle, liver, and fat cells do not use insulin well. As a result, the body needs more insulin to help glucose enter cells. At first, the pancreas makes more insulin to keep up with the added demand. Over time, the pancreas can’t make enough insulin, and blood glucose levels rise.
     Many people with type 2 diabetes have evidence of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the liver's glucose production.
     Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization.
We are more likely to develop type 2 diabetes if we are not physically active and are overweight or obese. Extra weight sometimes causes insulin resistance and is common in people with type 2 diabetes. The location of body fat also makes a difference. Extra belly fat is linked to insulin resistance, type 2 diabetes, and heart and blood vessel disease. To see if our weight puts us at risk for type 2 diabetes, check out the Body Mass Index (BMI) charts.

What causes gestational diabetes?

Gestational diabetes resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2–10% of all pregnancies and may improve or disappear after delivery. However, after pregnancy approximately 5–10% of women with GDM are found to have DM, most commonly type 2. GDM is fully treatable, but requires careful medical supervision throughout the pregnancy.
     Hormones produced by the placenta contribute to insulin resistance, which occurs in all women during late pregnancy. Most pregnant women can produce enough insulin to overcome insulin resistance, but some cannot. Gestational diabetes occurs when the pancreas can’t make enough insulin.
Having a family history of diabetes makes it more likely that a woman will develop gestational diabetes, which suggests that genes play a role. Genes may also explain why the disorder occurs more often in African Americans, American Indians, Asians, and Hispanics/Latinas.

What else can cause diabetes?

Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production. It is significantly less common than the three main types, constituting 1-2% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.
·         Cystic fibrosis produces thick mucus that causes scarring in the pancreas. This scarring can prevent the pancreas from making enough insulin.
·         Hemochromatosis causes the body to store too much iron. If the disease is not treated, iron can build up in and damage the pancreas and other organs.
·         Some hormonal diseases cause the body to produce too much of certain hormones, which sometimes cause insulin resistance and diabetes.
·         Cushing’s syndrome occurs when the body produces too much cortisol—often called the “stress hormone.”
·         Acromegaly occurs when the body produces too much growth hormone.
·         Hyperthyroidism occurs when the thyroid gland produces too much thyroid hormone.

Comparison of type 1 and 2 diabetes
Feature	Type 1 diabetes	Type 2 diabetes
Onset	Sudden	Gradual
Age at onset	Mostly in children	Mostly in adults
Body size	Thin or normal	Often obese
Ketoacidosis	Common	Rare
Autoantibodies	Usually present	Absent
Endogenous insulin	Low or absent	Normal, decreased or increased
Concordance in identical twins	50%	90%
Prevalence	~10%	~90%

RISK FACTORS For Diabetes

Type 1 diabetes

In type 1 diabetes, the body makes no insulin or not enough of the hormone. This condition occurs in around 5 percent of those with diabetes.
     Doctors treat type 1 diabetes with either insulin injections or an insulin pump alongside dietary management.
The main risk factors for type 1 diabetes include:
o   Family History  :  Having a parent or sibling with type 1 diabetes increases the risk of a person having the same type. If both parents have type 1 diabetes, the risk is even higher.
o   Age :  Type 1 diabetes usually develops in younger adults and children. It is one of the most common chronic conditions that develop in childhood. Children are typically younger than 14 years old when they receive a diagnosis. Type 1 diabetes might occur at any age, although developing type 1 diabetes later in life is rare.
o   Genetics :  Having specific genes may increase the risk of type 1 diabetes. A person's doctor can check for these genes.
o   Diseases of the pancreas :  They can slow its ability to make insulin.
o   Infection or illness :  Some infections and illnesses, mostly rare ones, can damage your pancreas.
o   Viral infections :  Researchers have found that certain viruses may trigger the development of type 1 diabetes by causing the immune system to turn against the body—instead of helping it fight infection and sickness. Viruses that are believed to trigger type 1 include: German measles, coxsackie, and mumps.
o   Early diet :  Researchers have suggested a slightly higher rate of type 1 diabetes in children who were given cow’s milk at a very young age.

Type 2 diabetes

The chances of developing type 2 diabetes depend on a combination of risk factors such as our genes and lifestyle. Although we can’t change risk factors such as family history, age, or ethnicity, we can change lifestyle risk factors around eating, physical activity, and weight. These lifestyle changes can affect our chances of developing type 2 diabetes.
We are more likely to develop type 2 diabetes if we
-          are overweight or obese
-          are age 45 or older
-          have a family history of diabetes
-          are African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, Native Hawaiian, or Pacific Islander
-          have high blood pressure
-          have a low level of HDL (“good”) cholesterol, or a high level of triglycerides
-          have a history of gestational diabetes or gave birth to a baby weighing 9 pounds or more
-          are not physically active
-          have a history of heart disease or stroke
-          have depression
-          have polycystic ovary syndrome, also called PCOS
-          have acanthosis nigricans—dark, thick, and velvety skin around your neck or armpits
We can also take the Diabetes Risk Test to learn about your risk for type 2 diabetes.
To see if the weight puts us at risk for type 2 diabetes, find the height in the Body Mass Index (BMI) charts below. If our weight is equal to or more than the weight listed, we have a greater chance of developing the disease.

If we are not Asian American or Pacific Islander	If we are Asian American	If we are Pacific Islander
At-risk BMI ≥ 25	At-risk BMI ≥ 23	At-risk BMI ≥ 26
Height	Weight	Height	Weight	Height	Weight
4’10”	119	4’10”	110	4’10”	124
4’11”	124	4’11”	114	4’11”	128
5’0”	128	5’0”	118	5’0”	133
5’1”	132	5’1”	122	5’1”	137
5’2”	136	5’2”	126	5’2”	142
5’3”	141	5’3”	130	5’3”	146
5’4”	145	5’4”	134	5’4”	151
5’5”	150	5’5”	138	5’5”	156
5’6”	155	5’6”	142	5’6”	161
5’7”	159	5’7”	146	5’7”	166
5’8”	164	5’8”	151	5’8”	171
5’9”	169	5’9”	155	5’9”	176
5’10”	174	5’10”	160	5’10”	181
5’11”	179	5’11”	165	5’11”	186
6’0”	184	6’0”	169	6’0”	191
6’1”	189	6’1”	174	6’1”	197
6’2”	194	6’2”	179	6’2”	202
6’3”	200	6’3”	184	6’3”	208
6’4”	205	6’4”	189	6’4”	213

The following is a list of disorders that may increase the risk of diabetes:

Genetic defects of β-cell function -  Maturity onset diabetes of the young-  Mitochondrial DNA mutationsGenetic defects in insulin processing or insulin action -  Defects in proinsulin conversion-  Insulin gene mutations-  Insulin receptor mutationsExocrine pancreatic defects -  Chronic pancreatitis-  Pancreatectomy-  Pancreatic neoplasia-  Cystic fibrosis-  Hemochromatosis-  Fibrocalculous pancreatopathy

Endocrinopathies -  Growth hormone excess (acromegaly)-  Cushing syndrome-  Hyperthyroidism-  Hypothyroidism-  Pheochromocytoma-  GlucagonomaInfections -  Cytomegalovirus infection-  Coxsackievirus BDrugs -  Glucocorticoids-  Thyroid hormone-  β-adrenergic agonists-  Statins