When you were diagnosed, your clinician probably said you had either Type 1 or Type 2 diabetes. Clear-cut and tidy. Since diabetes typically occurs in two types, you have to fit into one of them. Many people fit clearly into one of these categories, but others do not. And those who fit one type when diagnosed may find these clear lines begin to smudge over time. Are there only two types? Are you the type they said you were? Could you have more than one type of diabetes? Is your original diagnosis still correct after all these years?
A Short History Of Types
Described and treated since ancient times, diabetes has specific characteristics that were recognized long ago. Before the discovery of insulin, people found to have sugar in their urine under the age of 20 usually died in their youth. In contrast, those diagnosed when over the age of 40 could live for many years with this condition.
Beginning in the mid-1920s, those who got diabetes when young (juvenile-onset) started on insulin, and those who got it when older (adult-onset) often were not. However, the mechanisms that led to this difference in treatment were unknown. The only marker that differentiated the two types at that time was the presence in the urine of moderate or large levels of ketones when blood sugars were high. When significant ketones were present because the person could no longer make enough insulin, injected insulin was needed to control the glucose, and they were called insulin-dependent.
|Differences In The Three Major Types Of Diabetes|
|Type 1||Type 1.5/LADA||Type 2|
|Avg. age at start||12||35||60|
|Typical age at start||3-40*||20-70*||35-80*|
|% of all diabetes||10% (25%**)||15%||75%|
|Antibodies||ICA, IA2, GAD65, IAA||mostly GAD65||none|
|Early treatment||insulin is vital, diet & exercise changes helpful||pills or insulin vital, diet & exercise changes helpful||pills helpful, diet & increased activity essential|
|Late treatment||insulin, diet, exercise (occasionally pills)||insulin, pills, diet, exercise||insulin, pills, diet, exercise|
* may occur at any age if all antibody-positive cases are included, i.e. Type 1 and Type 1.5
Type 1 Diabetes
In the early 1980s, a breakthrough showed that early-onset diabetes, now called Type 1 was an autoimmune disease in which the body destroyed its beta cells. Antibodies produced by the immune system signaled a clear cause that distinguished it from adult-onset diabetes.
Type 1 or insulin-dependent diabetes mellitus (IDDM) appears primarily in childhood or adolescence with excessive thirst and urination, loss of weight, and extremely high glucose levels. Other than the recent weight loss, a relatively normal weight is typical when Type 1 diabetes starts. Type 1 occurs in 7 to 22% of all people who have diabetes (See Type 1.5 below). Treatment for this type revolves around replacing the missing insulin delivery with an insulin pump or injections t match diet and exercise.
Many interventions are being attempted to stop the progressive loss of beta cells that to determine which type of diabetes a person has correctly in Type 1 diabetes. Antibodies can often be detected a couple of years before glucose levels rise sufficiently for a diagnosis, and some children with antibodies do not develop Type 1 diabetes. When antibodies are present, there is a 68% probability of developing Type 1 diabetes, and the presence of multiple autoantibodies has the highest predictive value for Type 1 diabetes.1
Type 1.5 or LADA
The older term “juvenile-onset” is no longer used because so many people develop Type 1 as adults. Unfortunately, many Type 1 adults do not immediately require insulin for treatment and are often mistakenly told they have Type 2 diabetes. One in every seven to ten people diagnosed as having Type 2 diabetes have antibodies that indicate they have the slower form of Type 1 diabetes found in adults called Type 1.5 or LADA (latent autoimmune diabetes in adults).
In Type 1.5 diabetes, diabetes develops more slowly because adults often have fewer antibodies destroying the beta cells than children with Type 1 diabetes. They can often be treated with oral medications at first because insulin production may continue for a few years. Early treatment with insulin, however, is an advantage in that it “rests’ the beta cells and prolongs insulin production. With the retention of internal insulin production, glucose levels are easier to control for more years.
Those with Type 1.5 diabetes number about 2 million people in the U.S., about double the million or so people with Type 1 diabetes. The only difference from Type 1 is that there are typically only one or two antibodies present in the blood, rather than three or more. The most common antibody found in Type 1.5 diabetes is the GAD-65 or glutamic acid decarboxylase antibody (See Table 24.1).
Type 1.5 differs from Type 2 in that insulin resistance is often not involved. Compared with Type 2 diabetes, Type 1.5 starts about 15 years earlier (average age 46 rather than 61), excess weight and insulin resistance are usually not involved, and there is often a family history of other autoimmune diseases .2
Type 1.5 should be suspected when an adult does not show other classic signs of Type 2 diabetes, such as high triglyceride levels, low HDL levels, abdominal obesity, or a family history of high blood pressure or gout. When glucose levels are controlled, they usually do not have a high risk for cholesterol, blood pressure, or cardiac and vascular problems typically found in true Type 2 diabetes.
A correct diagnosis is essential because insulin treatment will be required much sooner in Type 1.5 than Type 2 diabetes. In the UKPDS study, 94% of those with Type 1.5 diabetes required insulin six years after being diagnosed compared to only 16% of those with Type 2 diabetes and no antibodies.3 If Type 1.5 is suspected, a GAD-65 antibody test can confirm the diagnosis. When GAD-65 or islet cell antibodies are present, the decline in insulin production is faster, and the person requires insulin earlier than in Type 2.
With the increase in weight seen in the general population, people with Type 1 and 1.5 can develop Type 2 diabetes with its classic signs of insulin resistance. The rising obesity rates in children now make it difficult for clinicians to differentiate Type 1 and Type 2 diabetes in the very young. There is also an increasing tendency for antibodies to appear in obese teens originally diagnosed as having Type 2.
Type 1s can develop characteristics of Type 2 diabetes when they become older and gain weight, and Type 2s can develop characteristics of Type 1 diabetes as insulin production is gradually lost over time or in the young when inflammatory and other processes generate antibodies against their beta cells.
Type 2 Diabetes
In contrast to Type 1, where the immune system destroys beta cells, Type 2 diabetes develops from a gradual decline in the beta cells’ ability to over-produce insulin. Type 2 is a progressive disease in which insulin production has been increased for several years as the body attempts to keep up with the insulin resistance associated with abdominal obesity or apple shape. Insulin production gradually degrades as the beta cells become exhausted.
Type 2 is often part of a metabolic syndrome that includes various signs of insulin resistance: high blood pressure, high total cholesterol (over 200), high triglycerides (also over 200), low levels of HDL or protective cholesterol (under 40 mg/dl), gout, and abdominal obesity.
Treatment for Type 2 diabetes revolves around varied combinations of diet, exercise, medications, and/or insulin injections. Type 2 diabetes can be prevented if a person remains diligent about staying physically active and maintaining a normal weight. In the Diabetes Prevention Program conducted by the NIH, the diagnosis of diabetes was reduced by 58% in the group that did these two things.4 Two classes of diabetes medications, GLP-1 agonists and glitazones, have been shown to slow the loss of beta cells in Type 2 diabetes. When started early, these medications appear to preserve insulin production, delay loss of glucose control,, and delay the need for insulin for at least several years.
At least 90% of people with diabetes have Type 2, and 30% to 40% of them currently use insulin. About 30% of Americans have insulin resistance, and about 30% of these will eventually develop Type 2 diabetes at some time in their lives.
Of all the people with diabetes, roughly 10% will have classic Type 1, 75% will have Type 2 (insulin resistant), and another 15% will have Type 1.5.
Other Types of Diabetes
Other forms of insulin-resistant diabetes also can be seen in gestational diabetes, polycystic ovary disease, acanthosis nigricans, and maturity-onset diabetes of the young or MODY. Insulin resistant diabetes can also be unmasked by medications like prednisone. In rare cases, a type similar to Type1 diabetes but without antibodies may be seen following trauma to the pancreas, following pancreatic surgery, or after exposure to toxins like Agent Orange. This type is insulin-dependent because no insulin can be produced once the pancreas is removed or severely damaged.
Does Your Diabetes Type Ever Change?
Even ignoring the high numbers of people with Type 1.5 who are initially misdiagnosed as Type 2, the lines between Type 1 and Type 2 diabetes often get blurred over time. Due to aging and weight gain in those with Type 1, the progressive nature of beta-cell failure in Type 2, and the mixture of obesity and antibodies in young people, those with one type of diabetes often tend to take on characteristics of the other.
With less exercise and more weight around the middle, some Type 1s become not only insulin-deficient but also insulin resistant. They can develop the cardiac risks associated with Metabolic Syndrome and benefit from medications that lower cholesterol and blood pressure. More insulin is required to control glucose levels, while certain Type 2 medications, like Glucophage (metformin) and GLP-1 agonists, may benefit their control.
On the other hand, as Type 2 diabetes progresses, insulin production may diminish to a point where it can no longer maintain normal glucose levels. Insulin will be required to keep glucose levels under control. Some people with Type 2 eventually become dependent on insulin and can go into ketoacidosis in stressful situations. In fact, ketoacidosis is about twice as common in Type 2 diabetes as it is in Type 1.
Lab Tests Used for Diagnosis
A variety of lab tests and clinical signs help to provide the information needed to determine which type of diabetes a person has correctly.
- Ketones: Ketones are a byproduct produced when the body uses large amounts of fat as fuel. Ketone levels rise when carbohydrate is no longer available as fuel due to a lack of insulin. When a urine or blood test shows moderate or large amounts of ketones, the person has Type 1 or insulin-dependent diabetes. (One rare exception is young, black males who may have ketones present at diagnosis but regain insulin production.) If insulin is injected before ketones are tested, the opportunity to find large amounts of ketones may have passed. Ketones can be tested at home in blood with certain meters, or in the urine with Ketostix or Ketodiastix anytime glucose levels are high.
- Antibodies: Type 1 diabetes is an autoimmune disease, so 80 to 90% of the time, when Type 1 exists, the person is producing antibodies characteristic of Type 1, such as the islet cell, insulin, and GAD-65 antibodies. A blood test shows if these antibodies are present. Free testing is available in the TrialNet Study (http://www.diabetestrialnet.org/PathwayToPrevention/).
- High triglyceride and low HDL: Cholesterol problems characterized by high triglycerides and low HDL are typical of insulin resistance. These markers for Metabolic Syndrome are commonly found in Type 2 diabetes. A routine cholesterol or lipid profile test is used to measure these.
- Uric Acid: The high uric acid level often found in people with gout is a component of insulin resistance. A high uric acid level with a high glucose level is highly likely to be Type 2 diabetes.
- C-peptide: If other tests fail to indicate the type of diabetes, a C-peptide test can reveal how much insulin a person is producing. C-peptide is half of the precursor molecule to the insulin that is split off when insulin is produced by the body. If C-peptide is normal or high, Type 2 diabetes is more likely. If the level is significantly low, Type 1 diabetes is likely. If the level is near normal but low, the person might have early Type 1, Type 1.5, or long-term Type 2 with negligible insulin production. This test should be done when the glucose level is at least 200 mg/dL (11.1 mmol/L).
1 Pihoker C, Lisa K. Gilliam LK, Hampe CS, and Lernmark A. Autoantibodies in Diabetes. Diabetes, December 2005, vol. 54, Suppl 2, pages S52-S61.)
2 Bhatia V and Wolfsdorf JI: Severe hypoglycemia in youth with insulin-dependent diabetes mellitus: frequency and causative factors. Pediatrics 88(6):1187-1193, 1991.
3 Veneman T, Mitrakou A, Mokan M, Cryer P, and Gerich J: Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia. Diabetes 42:1233-1237, 1993.
4 Davis SN, Fowler S, and Costa F: Hypoglycemic Counterregulatory responses differ between men and women with Type 1 diabetes. Diabetes 49:65-72, 2000.