Stages of type 2 diabetes

Defining and Characterizing the Progression of Type 2 Diabetes


Pancreatic β-cells normally respond to insulin resistance by increasing their output of insulin to meet the needs of tissues. Development of type 2 diabetes essentially stems from a failure of the β-cell to adequately compensate for insulin resistance. The β-cell dysfunction progresses over time and is well advanced by the time a person’s plasma glucose level is in the diabetic range and continues to worsen after diabetes develops (12).

Many obese individuals, who tend to have insulin resistance, progress to diabetes. Yet some do not: their β-cells continue to function adequately and they are able to maintain glucose homeostasis and compensate for increasing insulin resistance with increasing insulin secretion.

Genetic predisposition to β-cell failure

Data strongly support a genetic predisposition to β-cell failure (15). A genetic subtype of the disease characterized by diagnosis at <25 years of age, β-cell dysfunction, an autosomal dominant mode of inheritance, and heterozygous mutations in β-cell transcription factors has been identified as a common cause of early-onset type 2 diabetes (16). Multiple genetic mutations have been identified, and in some affected individuals, a genetic cause for their disease is recognized (17). However, in most patients in clinical practice, it is impossible to identify a genetic abnormality clinically and environmental factors predominate.

Mechanisms responsible for the decline in insulin secretion

Normal β-cell adaptation to insulin resistance can occur through increased insulin secretion from each β-cell and/or an increase in the β-cell mass. Some individuals have a reduced insulin secretion or reduced β-cell mass but normal glucose levels; they have sufficient insulin sensitivity to ensure adequate insulin secretion. In insulin-resistant subjects or subjects with type 2 diabetes, there is inadequate insulin secretion from each β-cell or an inadequate β-cell mass for the levels of prevailing insulin sensitivity (5).

When blood glucose is elevated, insulin secretion is stimulated and glucagon secretion is suppressed. Conversely, when blood glucose is decreased, insulin secretion should be suppressed and glucagon secretion stimulated. All of these actions are highly glucose dependent and critical to maintain normal glycemia in the face of varying insulin needs. They also provide the classic response to a meal. Although the failing β-cell loses its ability to respond to glucose, not all responses are diminished. Insulin secretion, e.g., in response to amino acid stimulation or through stimulation with other hormones such as glucagon-like peptide 1 (GLP-1), is preserved.

β-Cells maintain their responsiveness in the face of insulin resistance through increased insulin secretion in response to meals as well as through a chronic response by increasing β-cell mass (18). Normal-weight and obese individuals maintain a normal and similar 24-h glucose response to meals. However, the groups differ in their mean insulin secretion, which is significantly higher in obese subjects than in their normal-weight counterparts. In addition, insulin secretion in obese subjects fails to return to baseline between meals (19).

Two acquired defects have been implicated with regard to impaired glucose secretion: glucotoxicity, whereby β-cells become sensitized to the presence of glucose, and lipotoxicity, whereby accumulated fatty acids and their metabolic products deleteriously affect β-cells. In glucotoxicity, chronic hyperglycemia depletes insulin secretory granules from β-cells, lessening the amount of insulin available to be released in response to new glucose stimuli. Lowering glucose levels permits regranulation of β-cells and a better acute insulin response follows. In lipotoxicity, prolonged increases in free fatty acid levels adversely affect the conversion of proinsulin to insulin and eventually affect insulin secretion. Fatty infiltration of pancreatic islets may also contribute to β-cell dysfunction, and pancreatic fat correlates negatively with β-cell function (20). But once diabetes occurs, factors additional to pancreatic fat (perhaps glucose toxicity) account for further β-cell function decline. The concepts of gluco- and lipotoxicity remain hypotheses; the exact mechanisms responsible for impaired β-cell function have yet to be conclusively proved. This concept is being tested further in clinical trials such as ORIGIN (21), where insulin will be used early to eliminate glucotoxicity and determine whether early and maintained normoglycemia will decrease disease progression. The concept of remission in diabetes by elimination of glucotoxicity has actually been tested in a few small studies (22).

In addition to glucose and lipid deposition in the pancreas, another local factor may be the accumulation of amyloid, which has long been associated with the development and progression of type 2 diabetes (23).

Thus, in type 2 adipogenic diabetes, excessive carbohydrate and fat intake causes hyperinsulinemia in association with increased hepatic lipoprotein secretion, adipose tissue growth, and increased free fatty acid levels in genetically susceptible individuals. Together with episodes of postprandial hyperglycemia, elevated free fatty acid levels cause muscle and liver insulin resistance and increase hepatic glucose production. The same stimuli also facilitate β-cell compensation by promoting insulin secretion and biosynthesis as well as β-cell growth. In late stages, however, the progressive rise in insulin resistance, combined with alterations in β-cell gene expression and signaling induced by rising levels of free fatty acids, cause β-cell failure. Overt diabetes occurs as a result of this β-cell decompensation, with altered insulin secretion and apoptosis as possible contributing factors.

β-Cell mass deficits

Although β-cell function is paramount, decreasing β-cell mass is an important factor in progression of type 2 diabetes. β-Cell mass is increased by neogenesis, as well as replication and hypertrophy. In individuals who do not have diabetes, these activities are counterbalanced by apoptosis and necrosis, thereby maintaining a balance in β-cell mass. In individuals who are obese or insulin resistant, the number of islets and β-cells, in the presence of increased insulin demand, increase with some degree of hypertrophy (18). Several factors and mechanisms regulate β-cell mass, and only in a minority of diabetic patients does one single etiological factor underlie the failure of the β-cell. The various factors regulating mass are summarized in Fig. 3 (24). In animal models of insulin resistance, there is both replication of existing β-cells and neogenesis from ductal precursor cells. In the Zucker diabetic fatty rat model, Pick et al. (25) determined β-cell mass and replication rates. In nondiabetic but obese rats, the size of the islets increased. In contrast, obese diabetic rats showed slight decreases in islets and in the amount of insulin stained, whereas glucagon was either maintained or increased (25). The β-cell replication rate was significantly greater in Zucker diabetic fatty rats than in either lean control or obese nondiabetic animals. In addition, increased apoptosis, rather than decreased neogenesis, is the major factor responsible for reduction in β-cell mass (25).

Figure 3

Factors regulating β-cell mass (24).

In human autopsy pancreatic tissue (18), subjects with impaired fasting glucose and type 2 diabetes had a relatively reduced β-cell mass, whether they were lean or obese. Obese subjects without diabetes had an ∼50% increase in relative β-cell volume. Obese subjects with impaired fasting glucose or type 2 diabetes had 40 and 63% deficits, respectively, in relative β-cell volume than obese subjects without diabetes. These in vivo findings suggest that a decreased number of β-cells, rather than a decreased volume of individual cells, causes β-cell volume decrease. Subjects with impaired fasting glucose also had decreased relative β-cell volume, suggesting that this is an early process and mechanistically important in the development of type 2 diabetes (18). In another recent autopsy study, there was a significant curvilinear relation between β-cell volume and fasting blood glucose level, and β-cell deficiency was associated with a steep increase in blood glucose with further decrement in β-cell mass (26).

Abnormalities in the pancreatic islets may also contribute to deficits in β-cell mass with type 2 diabetes. Insulin secretion from islets of organ donors who had diabetes was significantly less than that of control subjects, and islet yield decreased as disease duration lengthened (27).

Imaging studies substantiate that the pancreas declines in size as type 2 diabetes progresses. More than 20 years ago, we used ultrasound to show some decrease in early type 2 disease and a significant decrease in later-stage disease with declining β-cell function and mass (28). Using computerized tomography, Goda et al. demonstrated that pancreatic volume and pancreatic volume index were greatest in the healthy group and lowest in type 1 diabetes, although subjects with type 2 disease did not differ significantly compared with control subjects (29).

Does the amount of pancreatic mass matter or can the residual mass take on the load? An intriguing insight is provided by a study on donors of pancreatic tissue. Hemipancreatectomy for the purpose of organ donation has been associated with a 25% risk of developing abnormal glucose tolerance or diabetes in the year after surgery (30), and 43% of healthy humans who underwent hemipancreatectomy have impaired fasting glucose, impaired glucose tolerance, or diabetes on follow-up. These findings are compatible with the notion that a loss of 50% of pancreatic function is associated with the development of diabetes. Matveyenko et al. (31) studied the effect of an ∼50% deficit in β-cell mass on carbohydrate metabolism in dogs. After partial pancreatectomy, both basal and glucose-stimulated insulin secretion were decreased through the mechanism of a selective ∼50 and ∼80% deficit in insulin pulse mass, respectively. These defects in insulin secretion were partially offset by decreased hepatic insulin clearance (P < 0.05). Partial pancreatectomy also caused an ∼40% decrease in insulin-stimulated glucose disposal. Thus, an ∼50% deficit in β-cell mass can recapitulate the alterations in glucose-mediated insulin secretion and insulin action in humans with IFG and IGT, supporting a mechanistic role of a deficit in β-cell mass in the evolution of IFG/IGT and diabetes.

β-Cell inflammation in type 2 diabetes

Inflammation is not in itself a disease, but a manifestation of disease that may prevent spread of infections or promote organ regeneration. Equally, it may exacerbate disease by tissue destruction due to inflammatory mediators, reactive oxygen species, and complement components (32). Pancreatic islets from type 2 diabetic patients are known to have amyloid deposits, fibrosis, and increased cell death (18,32,33), associated with an inflammatory response. Pancreatic α-cells produce increased IL-1α and other inflammatory factors in response to glucotoxicity and nutrients (32,34,35).

α-Cell pancreatic function

Although the focus herein has been on β-cell function, some attention must be paid to α-cell pancreatic function in the progression of diabetes. Glucose and a variety of hormones and substrates work to regulate glucagon secretion in a coordinated manner, and abnormalities of α-cells may reflect impaired glucose sensing. In type 2 diabetes, relative glucagon hypersecretion occurs at normal and elevated levels of glucose and an impaired response to hypoglycemia. The incretin hormone GLP-1, which promotes assimilation of ingested nutrients via a glucose-dependent stimulation of insulin release, apparently improves α-cell glucose sensing. Thus, GLP-1–based therapies improve α-cell function and may also prove to be useful in improving glycemic control in diabetes (36).

Microvascular and macrovascular complications

Longer survival times and development of type 2 diabetes at younger ages increase the risk of developing duration-dependent complications. In UKPDS 16, 18% of patients, all of whom were presumed to be clinically healthy, had a clinical end point within 6 years of diagnosis.

UKPDS 35 showed highly significant associations between development of diabetes complications, including death, across the broad range of exposure to glycemia, with no evidence of a threshold. Conversely, each 1% reduction in mean A1C was associated with reduction in risk of 21% for any end point related to diabetes (P < 0.0001) (1).

The role of complications on disease progression and failure has not been well studied. A change in insulin sensitivity and clearance is well recognized in renal failure and clearance is well recognized. However, the impact of these changes on the natural history of diabetes itself needs to be studied. Many patients with established complications tend to be poorly controlled, and factors such as glucose toxicity may play a role in disease progression as discussed above. In addition, various cardiovascular drugs such as diuretics and β-blockers may affect β-cell function adversely.

Type 2 diabetes mellitus is a metabolic disorder that results in hyperglycemia (high blood glucose levels) due to the body:

  • Being ineffective at using the insulin it has produced; also known as insulin resistance and/or
  • Being unable to produce enough insulin

Type 2 diabetes is characterised by the body being unable to metabolise glucose (a simple sugar). This leads to high levels of blood glucose which over time may damage the organs of the body.

From this, it can be understood that for someone with diabetes something that is food for ordinary people can become a sort of metabolic poison.

This is why people with diabetes are advised to avoid sources of dietary sugar

The good news is for very many people with type 2 diabetes this is all they have to do to stay well. If you can keep your blood sugar lower by avoiding dietary sugar, likely you will never need long-term medication

Type 2 diabetes was formerly known as non-insulin-dependent or adult-onset diabetes due to its occurrence mainly in people over 40. However, type 2 diabetes is now becoming more common in young adults, teens and children and accounts for roughly 90% of all diabetes cases worldwide.

How serious is type 2 diabetes?

Type 2 diabetes is a serious medical condition that often requires the use of anti-diabetic medication, or insulin to keep blood sugar levels under control. However, the development of type 2 diabetes and its side effects (complications) can be prevented if detected and treated at an early stage.

In recent years, it has become apparent that many people with type 2 diabetes are able to reverse diabetes through methods including low-carb diets, very-low-calorie diets and exercise.

For guidance on healthy eating to improve blood glucose levels and weight and to fight back against insulin resistance, join the Low Carb Program

Following pre-diabetes or metabolic disorder, type 2 diabetes can potentially be avoided through diet and exercise.

What causes type 2 diabetes?

Type 2 diabetes occurs when the hormone insulin is not used effectively by the cells in your body. Insulin is needed for cells to take in glucose (sugar) from the bloodstream and convert it into energy.

Ineffective use of insulin results in the body becoming resistant to insulin – also known as insulin resistance, which in turn causes blood sugar levels to rise ( hyperglycemia ).

In advanced stages, type 2 diabetes may cause damage to insulin producing cells in the pancreas, leading to insufficient insulin production for your body’s needs.

Type 2 diabetes risk factors

A number of factors can increase the risk of developing type 2 diabetes.

These include:

  • Being overweight or obese
  • Having a waist size of 31.5 inches or more (women) or more than 37 inches (men)
  • Eating an unhealthy diet
  • Physical inactivity
  • Having a first-degree relative with type 2 diabetes
  • Having high blood pressure or raised cholesterol levels
  • Being of South Asian and African-Caribbean descent
  • Smoking

The likelihood of developing type 2 diabetes is also influenced by genetics and environmental factors. For example, research shows that:

  • If either parent has type 2 diabetes, the risk of inheritance of type 2 diabetes is 15%
  • If both parents have type 2 diabetes, the risk of inheritance is 75%


Type 2 diabetes has become one of the biggest long term health conditions in the UK and the world. Over 2 million people in the UK have type 2 diabetes.

The symptoms of type 2 can come on very slowly and often the signs can be dismissed as simply getting old. The sooner diabetes can be diagnosed the better as damage can sometimes be done to the body by diabetes before it is diagnosed.

With type 2 diabetes being so common we can all do with knowing the risk factors and symptoms.

The common risk factors are body size: being overweight and particularly if you’re carrying extra weight round your middle.

Age: people’s risk of type 2 diabetes goes up with age. Having a close family member such as a parent or sibling with type 2 diabetes.

Ethnicity: people with an Asia, Middle Eastern or African-Caribbean background have a higher risk. High blood pressure is also closely associated with type 2 diabetes

Remember symptoms can come on very gradually. Don’t be tempted to think that if you’ve had these symptoms for a long time that they must be normal.

Type 2 diabetes may either be diagnosed by a urine test or a blood test.

If these methods are not clear cut, you may be asked to take an oral glucose tolerance test.

There are a wide range of treatment options to control type 2 diabetes. Some people may be able to control diabetes through lifestyle changes alone. Some people may be put onto tablets. Others may go onto injections, such as insulin

When you’re diagnosed with diabetes you will most likely need to make some changes to your lifestyle. Cut down on smoking and drinking. Take more physical activity – preferably each day. Eat a healthy, balanced diet – which you may find needs to be lower in carbohydrate than you might be used to.

Download a FREE blood glucose chart for your phone, desktop or as a printout.

Is there an age where I’m more at risk of type 2?

Type 2 diabetes used to be known as adult-onset diabetes as it was primarily seen in middle-aged adults over the age of 40.

However, in recent years, cases of type 2 diabetes have become more common in young adults, teens and children. This increase has been connected to climbing levels of obesity

  • See our guide on diabetes risk factors for more information.

Symptoms and diagnosis

The most common symptoms of type 2 diabetes are:

  • Excessive thirst
  • Frequent urination
  • Increased hunger
  • Extreme tiredness
  • Sudden loss of muscle mass

Some of these symptoms are the same for type 1 diabetes, but in type 2 diabetes they tend to develop more slowly over a period of months or years, making it harder sometimes for people to recognise them as signs of an underlying illness.

In fact, many people have type 2 diabetes for a long period of time before being diagnosed with the disease.

Type 2 diabetes is frequently diagnosed following the results of either a fasting plasma glucose test or an oral glucose tolerance test. The condition can also be detected through a general health check with your GP.

The condition can be detected through diabetes screening or may be picked up as part of other health checks.

Type 2 diabetes treatment

First line treatment for type 2 diabetes typically includes a combination of diet modification with regular and appropriate exercise.

The NICE guidelines (NG28) state that treatment for type 2 diabetes should take into account an individual’s needs and preferences into account. People with diabetes should be given the opportunity to make informed decisions about their care and work together with healthcare professionals.

The NICE guidelines encourage having high-fibre, low-glycemic-index (low-GI) carbohydrate in the diet. This allows a good amount of flexibility and it is possible to follow a range of diets, including lower-carb and low-calorie, whilst ensuring you get a good source of low-GI foods such as vegetables, beans and pulses.

Your health team should help you with setting recommendations for carbohydrate and alcohol intake that work for you.

Low carb

Adopting a lower-carb diet can help with weight loss and lowering of blood glucose levels. This is because metabolised carbohydrate turns into glucose in the bloodstream and has an impact on blood sugar.

  • Speak to others following a low-carb diet in the Low Carb forum
  • Join the free Low Carb Program for people with type 2 diabetes

Low calorie

Meanwhile, a 2011 Newcastle University study, known as the Newcastle diet, examined the benefits of a low-calorie diet. This involved reducing food intake to 600 calories per day for 8 weeks. After 3 months, 7 of the 11 people studied were free of type 2 diabetes.

  • Speak to people following the Newcastle diet in the Low Calorie forum

A growing number of Diabetes Forum members have reversed their type 2 diabetes through both of the aforementioned methods.

Blood glucose testing

People with type 2 diabetes can benefit greatly from testing their blood sugar levels as this provides immediate feedback on how food, lifestyle and illness affects blood glucose levels. Regular, structured blood glucose testing (also known as self-monitoring of blood glucose or SMBG) has been shown to improve long-term diabetes control by reducing HbA1c and the risk of complications.


People with type 2 diabetes may also be prescribed tablets and/or injectable medication. Metformin is one of the most commonly prescribed drugs for people with type 2 diabetes and helps the body to better respond to insulin.

Other drug treatments are also available, including:

  • Byetta
  • Victoza
  • Bydureon

Some people with type 2 diabetes, usually those who have had type 2 diabetes for a number of years, may also be moved onto insulin injections

  • For more information on diabetes drug treatments, see our Medication section

Maintaining good control of blood glucose levels, as well as blood pressure and cholesterol levels, is vital in reducing the risk of diabetic complications If you are overweight, weight loss can often help to lessen the extent of diabetes symptoms.

Type 2 diabetes and complications

Like type 1 diabetes, type 2 diabetes carries the risk of diabetes complications over time.

The most common complications of type 2 diabetes include:

  • Heart disease
  • Stroke
  • Kidney disease (nephropathy)
  • Eye disease (retinopathy)
  • Nerve damage (neuropathy), which raises the risk of amputation

In fact, by the time they are diagnosed, 50% of people with type 2 diabetes show early signs of these health conditions.

The list of complications, which also includes depression and sexual dysfunction, is not pleasant but their risks can be reduced through good diabetes control and attending all diabetic screening appointments.

As with many chronic diseases, early diagnosis of type 2 diabetes is beneficial for treatment. Before type 2 diabetes develops, most patients exhibit pre-diabetic symptoms, and if treatment commences at this stage, diabetes of this type can be preventable.

  • Almost 1 in 3 people with type 2 diabetes develops overt kidney disease
  • Within 20 years of diagnosis of type 2 diabetes, 60% of people diagnosed have some degree of retinopathy

In terms of short term complications of diabetes, ketoacidosis is rare amongst type 2 diabetics. However, non-ketonic hyperglycemia is one threat type 2 diabetics should be aware of.

Impact of type 2 diabetes

As stated above, type 2 diabetes can lead to a greater chance of health problems which could in some cases affect your ability to work and could therefore affect your personal income.

Another factor to bear in mind is that increased care may be needed, from your family or from a carer, particularly as you get older.

With the right support and good diabetes management, the potential negative effects of type 2 diabetes can be minimised.

The NHS and type 2 diabetes

Type 2 diabetes is already one of the most common long term health conditions and the prevalence of type 2 diabetes in the UK is growing year on year.

The cost of treating a growing number of people with type 2 diabetes, and the health complications associated with the condition, is estimated to cost the NHS around £12 billion a year on direct and indirect care.

Famous people with type 2 diabetes

Famous people with type 2 diabetes include:

  • Blues musician BB King
  • Acclaimed director George Lucas
  • British comedian Jimmy Tarbuck
  • Music producer and American Idol judge Randy Jackson
  • Grammy-award winning singer Patti LaBelle
  • CNN anchor Larry King
  • Tom Hanks

Type 2 diabetes statistics

According to the International Diabetes Federation (IDF), more than 371 million people across the globe have diabetes and this figure is predicted to rise to over 550 million by 2030

Of the total global diabetes rate, 90% are living with type 2 diabetes but it is estimated that up to half of these people are unaware of their condition (undiagnosed diabetes).

In the UK, more than 2.7 million people are diagnosed with type 2 diabetes whilst a further 750,000 people are believed to have the symptoms but are yet to be diagnosed with the disease.

Health professionals usually call Type 2 diabetes a chronic, progressive illness. “Chronic” means you’ll always have it. “Progressive” means you will almost certainly get worse. The best you can hope for is to slow its progression through your diet, exercise, and oral medicine or insulin.


The diagnosis of a chronic, progressive condition can feel like having a curse put on you. If you have to get worse, if you can’t avoid complications and premature death, then why struggle with your diet and managing your diabetes? In the words of Jenny Ruhl, a blogger with LADA (latent autoimmune diabetes of adults, sometimes called “Type 1.5” diabetes), “If there is nothing you can do, it is rational behavior to shift your energy elsewhere and enjoy life – including the foods you love – while you can.”

Although experts have called both Type 1 and Type 2 diabetes “chronic” and “progressive” for decades, some people with diabetes disagree. A Diabetes Self-Management Blog reader named Dennis wrote, “Last November I weighed 288 with an of 7.1%. Diabetic complications had set in. Today, with a very low-carbohydrate diet, my is 5.6%. I’ve lost 35 pounds, my sugars are under control, and all my symptoms are gone!” (The HbA1c test gives an indication of average blood glucose level over the past 2–3 months. The American Diabetes Association advises most people with diabetes to aim for an HbA1c level below 7% to prevent complications.)

On the same note, a reader named Bob wrote, “By limiting carbs, my dropped from an 8.6% to a most recent reading of 4.9%.” And Terri posted, “I am a diabetic who eats a low-carb vegan diet. I am far healthier now at 53 than ever before and maintain perfect glucose control.”

Reports like these are called “anecdotal evidence” and are usually discounted by scientists. But even some doctors who used to consider diabetes a death sentence are now saying that Type 2 diabetes can be reversed, even cured (more on what “cured” means later).

In a talk published by online resource Medscape in December 2003, diabetes expert Roy Taylor, MD, professor of medicine at Newcastle University in the United Kingdom, stated that even good blood glucose control doesn’t slow the progression of complications much. Dr. Taylor said that the United Kingdom Prospective Diabetes Study (UKPDS, a landmark 20-year study published in 1998) showed that “intensive therapy made a difference” in eye damage, “but not a staggering difference, …abnormal nerve function continues to progress.” Intensive blood glucose control, furthermore, “does not seem to be able to stop kidney damage.”

The UKPDS findings led Dr. Taylor and many others to conclude that ultimately, nothing can be done to stop the damage caused by Type 2 diabetes, so people who have it essentially got the message, “Do the best you can; we’ll help you with drugs, but you’ll go downhill anyway.”

But times change. On June 24, 2011, Dr. Taylor’s research group released a paper called “Reversal of Type 2 Diabetes: Normalization of beta cell function in association with decreased pancreas and liver triacylglycerol.” The paper details how 11 study subjects who were put on a 600-calorie diet for eight weeks regained normal insulin function, had normal lab results, and stopped taking all diabetes medicines, some after only one week. Quoted in the United Kingdom’s Daily Telegraph, Taylor said, “While it has long been believed that someone with Type 2 diabetes will always have the disease, and that it will steadily get worse, we have shown that we can reverse the condition.”

Starvation isn’t the only approach that may reverse Type 2 diabetes. In his book The Blood Sugar Solution, Mark Hyman, MD, writes that you don’t need an extreme diet, you don’t necessarily need weight loss, and you don’t need surgery. He says that just cutting out or drastically reducing starches and sugars, and exercising more, will reverse Type 2 diabetes in about 80% of people.

In thousands of anecdotal reports, people like Dennis and Terri say they have reduced or eliminated their diabetes medicines, brought their glucose and cholesterol numbers into the normal range, and rid themselves of symptoms and complications such as fatigue, neuropathy, eye damage, and protein in their urine. Others have reported less dramatic but still significant improvements.

At least four approaches, other than extreme caloric restriction, are claimed to reverse Type 2 diabetes in many people. Most involve dietary changes (often along with exercise), and they include low-carbohydrate diets, vegan diets, traditional diets for native peoples, and bariatric surgery. Let’s look at the evidence for each of these approaches.

Low-carb diets

In his book Dr. Bernstein’s Diabetes Solution: The complete guide to achieving normal blood sugars, (first published in 1997 and updated periodically since then), Richard Bernstein, MD, recounts how he stabilized his Type 1 diabetes and reversed most of its complications with a low-carbohydrate diet.

Bernstein discovered through self-monitoring that if he ate only very small amounts of slowly digested carbohydrates (those with a very low glycemic index), he could cover them with insulin and keep his blood glucose in the normal range. He found that his patients with Type 2 diabetes also had big spikes in after-meal blood glucose when they ate carbohydrate. They saw great improvement when they adopted his low-carb diet, even when insulin injections weren’t in the picture.

Since then, scores of books, articles, and Web sites have appeared that promote low-carb diets for diabetes. A group of people in the United Kingdom with both Type 1 and Type 2 diabetes created the Web site Low Carb Diabetic to report how they normalized their blood glucose levels. They write, “While some medications can help to reduce blood glucose, a reduction of the foods in the diet which raise levels in the first place can be sufficient to normalize them. Medication can therefore often be reduced and in some cases (Type 2 diabetics only) eliminated altogether.”

One Duke University study followed 82 obese people with Type 2 diabetes who were assigned to either a very-low-carb or a low-calorie diet. After six months, the low-carb group had a lower average HbA1c level and had lost more weight than the low-calorie group, and 95% were able to reduce or totally eliminate their diabetes medicines. Eric Westman, MD, director of Duke’s Lifestyle Medicine Program and lead author of the study, said, “If you cut out the carbohydrates, your blood sugar goes down, and you lose weight, which lowers your blood sugar even further. It’s a one-two punch.”

There are a wide variety of low-carb diets and books available, including Conquer Diabetes and Prediabetes by Steve Parker, MD; The Blood Sugar Solution by Mark Hyman, MD; and The 30-Day Diabetes Cure by Stefan Ripich, ND. You can also read dozens of diabetes blogs and Web sites that focus on low-carb diets (see “Resources”).

Vegetarian and vegan diets

Vegetarian diets and vegan diets (no meat, eggs, or dairy) are known to help prevent diabetes. One two-year study of 25,000 people in the United States and Canada found that vegans had only one-fourth the risk of developing diabetes as nonvegetarians.

Dr. Neal Barnard, a professor at the George Washington University School of Medicine and president of the Physicians Committee for Responsible Medicine, is a leading proponent of a vegan diet for diabetes. On PCRM’s Web site, you can see many “success stories” of people who have regained normal glucose numbers on a vegan diet. One former police officer reports, “My dropped from over 9% to 5.3%, my cholesterol dropped from 221 to 148 points, and I have lost 74 pounds” over a six-year period.

In a Czech study published in 2011, 74 people with Type 2 diabetes were randomly assigned to either a vegetarian or a conventional diabetes diet. Both diets had the same low number of calories. Over 24 weeks, 43% of people in the vegetarian group were able to reduce their diabetes medicines, compared with only 5% in the conventional group. The vegetarian group lost more weight and had much better insulin sensitivity.

You might notice that a vegan diet is about as far as you can get from a typical low-carb diet, which is often heavy in animal products. How could they both be effective against diabetes? The connection may be that both diets, when done right, are low in refined grains and sugars. Many vegans eat a lot of carbs, but in a diabetes diet they tend to come from vegetables, fruits, beans, and nuts, not breads and sugars.

Traditional native diets

No group in the world has been hit harder by Type 2 diabetes than Native Americans and Pacific Islanders. To improve their health, some have gone back to their traditional diets. Although no major studies have been published on this topic, many people who take this approach seem to improve their health, including their diabetes.

The Waianae Diet Program is a community-based approach that uses a traditional Hawaiian diet to reduce chronic disease in Native Hawaiians. A study published in the American Journal of Clinical Nutrition reported that people on a native diet (low in fat, high in complex carbohydrate) lost significant weight and reduced their cholesterol and blood pressure, even though they were encouraged to eat as much as they wanted. The study did not examine glucose levels, but in other studies, blood glucose often corresponds to improvements in these other measurements.

According to Native American leader Liz Gray, “Before the 1930’s and 1940’s, diabetes was not a plague on the Native American population…The biggest problem is the federal food program. Those foods are totally stripped of nutrients, and that’s all that the tribes on the reservations have.”

Some Native Americans are replacing government food with traditional foods. In an article called “Native American Traditions Return to Heal Diabetes,” New American Media reports on Wisconsin tribes that are replacing packaged food with food “harvested from the land, such as maple syrup, venison, perch, and wild rice. In the woods, there’s wild turkey, partridge, bear, and rabbit. Local waters have plenty of walleye, pan fish, trout, and other fish. And the reservation thrives with wintergreen, leeks, apples, juneberries, and other plants to harvest.” One Native American, Bob Wilmer, said that his cholesterol and glucose numbers are great because of both the food and the physical activity involved in obtaining it. He says more and more people are “trying to fight the epidemic of Type 2 diabetes in Indian Country through a return to traditional foods, exercise, and public health education.” These programs are taking off in tribes throughout the United States, Canada, and the Pacific Islands.

Bariatric surgery

Bariatric (“weight-loss”) surgery such as gastric bypass and gastric banding frequently puts Type 2 diabetes into remission. This means that the signs of diabetes disappear – often within days, before any significant weight is lost. This phenomenon was completely unexpected when it was first discovered a few years ago and has led to a surge in the number of surgeries performed.

How does weight-loss surgery reverse diabetes? Some experts believe remission occurs because the surgery affects gut hormones, which somehow impact pancreas function. This could be happening, but Dr. Taylor thinks the remission might actually occur because the surgery severely limits what people can eat. This hypothesis was the inspiration for his 600-calorie diet study. To date, no one knows what the exact mechanism is, but it is clear that bariatric surgery has let tens of thousands of people stop taking their diabetes medicines.

Bariatric surgery has significant side effects and risks, however, which may include digestive problems, nutrient deficiencies, and even death. Dr Iain Frame, director of research at Diabetes UK, which supported the 600-calorie diet study, noted that the study’s positive outcome “shows that Type 2 diabetes can be reversed on a par with successful surgery without the side effects.”

What about complications?

Dr. Bernstein has found that when blood glucose levels are controlled, the body starts to heal itself and many complications improve. Most reversible seems to be neuropathy in the feet. Sexual dysfunction seems highly reversible as well, based on studies that have examined the topic. Retinopathy (eye disease) and nephropathy (kidney disease) also seem to improve when blood glucose levels come down.

Some complications, however, may be more difficult to reverse. A complication that has progressed beyond a certain point may persist even upon a return to normal blood glucose levels, since some tissue damage can be irreversible. If you are blind or experiencing kidney failure, it is highly unlikely that these problems will disappear entirely. It is always possible, though, that there will be noticeable improvement, no matter how “far along” your diabetes is.

Too good to be true?

The idea of reversing Type 2 diabetes is still considered somewhat extreme. Opposing voices raise several objections, such as the following:

No studies. The evidence of success is almost all anecdotal, critics say, so it can’t be given much credit. Actually, there are several studies, including the ones cited in this article, but they are small. There aren’t any large, well-controlled, multicenter studies on dietary approaches like those that exist for drugs.

There will probably never be any large studies on reversing Type 2 diabetes with food and exercise because they are too difficult to conduct, because most doctors currently don’t even accept the premise, and because there is no product to sell if an intervention is deemed successful. Richard Kahn, MD, former Chief Science and Medical Officer of the American Diabetes Association, said, “It’s very difficult to study long-term diet changes in the real world, where people often don’t know exactly what they’re eating.”

In Dr. Taylor’s 600-calorie-per-day study, all the meals were liquid and given to subjects by study administrators. Along with green, nonstarchy vegetables, this was all they could eat. To repeat these methods for a study of 10,000 people would be expensive and difficult.

The data say progression is inevitable. Maybe not, actually. True, most people with Type 2 diabetes do experience progression of the disease and complications. But reversal proponents say that this is because they stay on high-carbohydrate diets.

Jenny Ruhl points out that “although the UKPDS did show that even patients with good control deteriorated over time, ‘good control’ was defined to mean test values near 7.0%. This is only mediocre control at best. It corresponds to an average blood sugar over 155 and frequent spikes over 200.” Ruhl goes on to explain, “It is very likely that most UKPDS participants spent hours with their blood sugars over 300 mg/dl…people who eat a lower-carbohydrate diet can keep their sugar below the 140 mg/dl level” where blood vessel damage is believed to start.

Follow-up is too short. There’s no telling how long the benefits of these diets will last because they haven’t been studied for long enough. In weight-loss diets, 90% to 95% of dieters regain all the weight they have lost within five years, and usually within two years. It is possible that diabetes reversal will also fail over time for most people. In the case of starvation diets like Dr. Taylor’s, very few people can stay on them for an extended period. In his study, 4 of the 11 subjects had relapsed to diabetes-level blood glucose levels after only three months. Most of the rest probably have by now.

According to health writer Kimberly Pollock, a Dutch study found that “83% of gastric bypass patients and 62% of gastric banding patients were able to stop taking medication for their diabetes within a few days of surgery. Even at one- and two-year follow-ups, those patients remained off medication. However, by the 10-year follow-up, only 36% of all patients were able to maintain normal blood glucose levels without medicine.”

But many low-carb, vegetarian/vegan, and traditional diets are not calorie-restrictive and may be sustainable. They are described by proponents not as diets but as permanent lifestyle changes. Some of Dr. Ripich’s successful readers say that the new foods they have adopted on his diet are much more enjoyable than the sweets and starches they have given up. Some followers of Dr. Bernstein’s approach have been sticking with it for 20 years or longer, with normal or near-normal blood glucose levels throughout that time.

It’s too difficult. Some critics say that very few people can stay on programs like these. Changing eating habits is hard, especially when your friends, coworkers, and family members continue to eat in ways that are unhealthy for you. Sweets and starches are widely available, cheap, and tasty. Healthy food is harder to get, more expensive, and less familiar to many people’s tastes. Getting exercise is also hard for many people, especially when they’re not used to it, when they’re too busy or too tired, or when their environment doesn’t provide an easy way to do it. So it may be unrealistic to expect many people to make these changes.

Many people who claim to have reversed diabetes, however, say it was no great feat. The Low Carb Diabetic Web site’s authors claim that they all have normal glucose numbers and that it “wasn’t hard to accomplish.” Diabetes Self-Management Blog reader Anna writes that after she was diagnosed with Type 2 diabetes 11 years ago, she changed her diet and exercise patterns and has been off all drugs, with normal glucose numbers, for more than 5 years. “It can be done, and it actually can be done quite easily,” she says.

Anna points out that “reversal” doesn’t mean you can forget all about diabetes. “You will never be able to lounge on a sofa popping bonbons” she writes, “but you will also not have to be a prisoner to drugs and symptoms and worry over a future consumed by illness.”

People can’t change or don’t want to change. Doctors often prescribe weight loss to patients, who usually don’t lose it or don’t maintain whatever loss they achieve. So many doctors have the sense that people can’t change. But weight loss is a bad indicator of what people are capable of doing in other areas, simply because it is so difficult; our bodies try very hard to regain lost weight. If given a goal that they can actually accomplish, many people are willing to make changes and to work hard in the process.

It doesn’t work for everyone. This is certainly true. According to Dr. Hyman, about 20% of people experience nutrient deficiencies, chronic infections, intolerance of dairy or gluten, chemical toxicities, low thyroid function, or other problems that can reduce the effectiveness of lifestyle changes and will need correction before diabetes can be reversed. Other people who supposedly have Type 2 diabetes may actually have Type 1 or MODY (maturity-onset diabetes of the young, or monogenic diabetes) and will continue to need insulin, although lifestyle changes may still improve blood glucose control. Drs. Bernstein, Hyman, Parker, and Ripich all advise seeking help from a doctor when making any changes to your self-management routine.

It’s too late for many people. It’s true that the more damage a person’s pancreas, liver, or blood vessels have suffered, the slower recovery is likely to be. Some complications may not be totally reversible. If you read any of the books or Web sites listed in “Resources,” though, you will probably find stories of people whose diabetes was more advanced than yours but who still managed to reverse it to some degree. And by following their examples, perhaps you can, too.

Also in this article:

  • Resources

How Type 2 Diabetes Can Change Over Time

; Thinkstock (2)

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You probably already know that type 2 diabetes can cause long-term damage if you don’t control it, but it’s also important to understand that even well-controlled diabetes progresses over time — meaning you may have to adjust your treatment plan more than once.

The key to learning about the progression of diabetes is to understand the role of your pancreas, which produces insulin. For people with type 1 diabetes, the pancreas does not make any insulin, so they must take it through injections. With type 2, the pancreas doesn’t make enough insulin or the cells don’t respond to it adequately, according to the National Library of Medicine. This means that the body has trouble moving sugar from the blood into cells to be used for energy. Diet, exercise, and medication, if prescribed, can all help those with type 2 diabetes lower their blood sugar levels and help their bodies use insulin made by the pancreas, according to the American Diabetes Association (ADA).

If blood sugar levels remain high, you may be at risk for such diabetes complications as vision loss, heart disease, nerve damage, foot or leg amputation, and kidney disease, the ADA says,. However, proper diabetes management can help prevent or delay the onset of these complications.

What Types of Changes to Expect

Your medications, diet, and exercise goals may need to be adjusted over time. “Initially the pancreas produces extra insulin to make up for insulin resistance, but in most people, the pancreas eventually is unable to make the extra insulin to keep blood sugar levels normal,” says Marc Jaffe, MD, an endocrinologist in practice with Kaiser Permanente in San Francisco.

After a type 2 diabetes diagnosis, your doctor will set blood sugar goals for you, recommend lifestyle changes, and perhaps prescribe medications to help manage blood sugar levels, Dr. Jaffe says. “Because type 2 diabetes usually progresses over time, even people who don’t need medications at first are likely to need medications eventually,” he notes.

The next step in diabetes management, if these strategies aren’t working, is to change or add medication or add insulin, according to the 2017 Standards of Medical Care in Diabetes, published in the January 2017 issue of Diabetes Care. Your blood sugar goals might also be adjusted, based on your overall health and history with diabetes control, according to the guidelines. For some people who are obese, bariatric surgery might also be an option.

The guidelines also note that because many people with type 2 diabetes will eventually need insulin, insulin therapy should not be feared or viewed as meaning that you’ve failed at managing your diabetes.

“This is a progression of the disease and not to be thought of as something that you caused,” says Erin Palinski-Wade, RD, a certified diabetes educator in Franklin, New Jersey, and author of 2 Day Diabetes Diet.

Tailoring Your Diabetes Management Plan as You Age

Not only does diabetes itself progress, Palinski-Wade points out, but your body also changes over time. For example, you may experience complications from diabetes, like nerve pain, or develop osteoarthritis, which could make exercise more challenging, she notes. Those kinds of changes in your body would lead to adjustments in your diabetes management plan.

As you age and experience certain life changes, like being diagnosed with another health condition or experiencing new physical limitations, it can help to see a certified diabetes educator. This member of your diabetes care team can help you adjust your healthy eating, exercise, and medication management plan to help account for any new life changes.

A diabetes educator can help you stay on track with a diabetes-friendly lifestyle as you age and keep you on track with:

  • Eating healthfully. Your diet should be individualized, but people with diabetes can also benefit from Palinski-Wade’s advice to “focus on filling your plate halfway with plant-based foods such as vegetables at all meals.” She also urges people to learn to read labels and understand portion sizes — skills that will serve you well throughout your life.
  • Aiming for a healthy weight. If you’re overweight, losing weight can help improve your diabetes control and help reduce your risk for related health complications. According to the ADA, losing just 10-15 pounds can make a big difference in diabetes management. Check with your doctor for a specific recommendation for you.
  • Checking your blood sugar. As you get older, your target blood sugar range may change. What’s more, “as diabetes progresses, people may need to start checking or increase the frequency of checking their blood sugar levels, especially when blood sugar levels are high or low, hard to control, or in people who take insulin,” says Jaffe.
  • Staying active. Incorporating a mix of aerobic activity and resistance training into your exercise plan can help to improve insulin sensitivity, which allows your body to use insulin more efficiently, according to the ADA.

It can be challenging to live with a chronic condition like diabetes, but taking care of yourself each day and checking in with your doctor and diabetes educator regularly can help you stay on top of your diabetes management.

Fighting Progression of Type 2 Diabetes: Beta Cell Is Key

It’s great, as usual, to be at the European Association for the Study of Diabetes Annual Meeting. A great amount of discussion is going on about the role of the beta cell in the pathogenesis of type 2 diabetes and how we are going to work to prevent the progressive loss of beta-cell function and mass that characterizes the disease.

It’s clear that everybody recognizes that the beta cell is the key feature of why we get hyperglycemia as well as why we see a progression of the disease. With the approaches we are currently using, this disease results in a progressive loss of the ability of the beta cell to secrete insulin, along with loss of the beta cells that are responsible for making this critical hormone.

We’ve used many, many different approaches until now to try to prevent this loss of beta-cell function. We have a variety of classes of agents that have addressed the beta cell directly as well as indirectly, perhaps by reducing the load of the beta cell so that the demand for it to produce and secrete insulin is decreased.

What we’ve learned through a lot of these interventions is that although we can maintain glycemic control for a period of time, inevitably there will be progression and we will need to add agents.

Every patient with type 2 diabetes has beta-cell dysfunction, and every patient with type 2 diabetes needs to be aggressively treated to slow progression.

The different agents that we’ve used seem to have variable degrees of ability to slow progression. For example, the sulfonylureas, while being capable of stimulating insulin secretion, seem to drive the beta cell towards that inevitable loss of function far more rapidly than other approaches such as metformin or the thiazolidinediones.

In fact, if an individual were to live long enough, every patient with type 2 diabetes will have ultimate beta-cell failure that requires insulin-replacement therapy. We are losing patients to cardiovascular disease even with the more aggressive control of blood pressure and lipids, many of them before they’ve progressed to beta-cell failure.

The challenge is to come up with new approaches that would allow us to slow this progression. The traditional thinking, where one provides agents that stimulate the cell to secrete insulin, may not be optimal. We may need to start thinking of new approaches that would allow the beta cell to rest some and, therefore, be able to live longer.

Studies looking at individuals with prediabetes have identified that the beta cell is already defective. With interventions that improve insulin sensitivity, we can typically slow the progression to diabetes. Similarly, if we intervene in individuals with diabetes to reduce the demand on the beta cells with approaches as simple as aggressive lifestyle changes, we can slow progression.

We need to clearly focus on these areas to try to prevent our patients from getting progressive hyperglycemia due to progressive beta-cell loss and, ultimately, the diabetic complications that we traditionally see with the disease.

We’ve been seeing recently that a number of the agents that are used to treat type 2 diabetes, including GLP-1 receptor agonists and SGLT2 inhibitors, may offer hope in reducing diabetic complications in individuals with very advanced disease. Although this is very useful information, we have yet to fully understand how this is happening. The challenge for all of us is to find approaches that can be used earlier in the disease, perhaps with these classes of agents or others that would not allow us to worry about late-stage disease.

In my mind, the beta cell is the key. We’re going to have to aggressively target it. We don’t necessarily have to target it by stimulating it as much as resting it.

Every patient with type 2 diabetes has beta-cell dysfunction, and every patient with type 2 diabetes needs to be aggressively treated to slow progression. Failure to treat our patients aggressively is going to allow accelerated progression and ultimately result in failure and insulin therapy.

In association with the Endocrine Society

Diabetes Forecast

David Mack/Science Source

Garry Bieringer was 50 when his doctor told him he had type 2 diabetes. The diagnosis, based on a routine blood test, came as a surprise: Bieringer hadn’t noticed any symptoms. “The doctor just came in and said, ‘I think you have diabetes,’ ” Bieringer recalls.

In the 16 years since, Bieringer’s gone through a process that may be discouragingly familiar to many people with type 2, which affects nearly 28 million Americans. Every few years, his diabetes treatment changes. “It’s my pattern,” he says. “Once I start, after a little while the medication loses effectiveness.”

At first Bieringer took metformin, the drug typically used first to control blood glucose levels in people with type 2 diabetes. After a few years, two more drugs—pioglitazone (Actos) and glyburide (Micronase)—were added to his medication cocktail.

Six years went by, and Bieringer’s doctor recommended a change. The pills that had worked at first were no longer enough to control his blood glucose. Today, he’s no longer on pioglitazone or glyburide. Instead, he takes metformin, injections of a long-acting insulin, fast-acting insulin shots before meals, and a daily shot of exenatide (Byetta), a drug designed to increase his body’s insulin secretion and slow his digestion.

Like many people with type 2 diabetes, Bieringer had a hard time hearing the news that he needed to move from oral medication to shots. “I felt I was failing,” he says. “But my diabetes educator said I wasn’t failing. It was just my body reacting.” Those words of wisdom helped Bieringer come to grips with the steadily increasing demands of his condition.

Chain of Events

For people with type 2, the years after diagnosis almost inevitably bring more intense regimens of oral medication, and sometimes insulin or other injectables as well. “Diabetes is a progressive disease, and often the first agent is not sufficient,” says Kieren Mather, MD, an Indiana University endocrinologist.

Researchers understand the basics of type 2 well. It all comes down to how the body makes and uses insulin, the hormone that tells the body’s cells to absorb glucose from the bloodstream as fuel.

Insulin is produced by beta cells, specialized cells located in the pancreas. When the pancreas can’t produce enough insulin to control blood glucose, diabetes results. “Type 2 diabetes is caused by multiple metabolic defects, but the fundamental problem is the inability of beta cells to make enough insulin for the body’s needs,” says Ravi Retnakaran, MD, an endocrinologist at the Lunenfeld-Tanenbaum Research Institute at Toronto’s Mount Sinai Hospital.

There are two factors at play. First, the body becomes less sensitive to insulin’s commands. That’s what’s called insulin resistance. Second, to get the body’s attention, the “signal” has to get louder—the beta cells in the pancreas have to pump out more insulin, in other words. “What changes is beta cell response,” says Mather. “At first, it improves, to keep things normal in the face of insulin resistance.” If sensitivity to insulin doesn’t improve, the beta cells work harder to produce more insulin.

Unlike people with type 1 diabetes, people with type 2 still have functioning beta cells in the early stages of the disease. Patients usually have no idea their pancreas is struggling to keep up until a doctor flags their blood glucose levels. “People have often had diabetes for longer than they realize,” Retnakaran says. “Diabetes is silent.”

Because of their insulin resistance, people in the early phases of type 2 diabetes might even have highly functional beta cells—but not functional enough. “In a person who’s now officially diabetic, beta cell function might be twice what a nondiabetic individual has, but still not sufficient for that person,” Mather says.

As long as there are still functional beta cells, type 2 diabetes can be treated by tackling the body’s insulin resistance. Exercise and weight loss have been shown to make the body more responsive to its own insulin. Metformin works in other ways to keep less of your body’s stored glucose from entering the blood.

But as Bieringer’s experience shows, as time goes on, metformin might not be enough. With insulin resistance still an issue, it’s hard for the pancreas to sustain its above-normal insulin output. “For whatever reason, the function of beta cells worsens over time,” Retnakaran says.

As the beta cells pump out more and more insulin to compensate for the body’s insulin resistance, they sometimes start to falter and fail. “The typical course is that the patient will require more and more antidiabetic medications over time, in the absence of which sugars will rise,” says Retnakaran. “Meanwhile the beta cells are worsening.”

That beta cell failure is responsible for what can feel like an unwinnable race for people with type 2 diabetes. “The overload leads to progressive dysfunction,” Mather says. “It’s like heart disease—the pancreas keeps working too hard and wears out.”

The Theory of Everything

Despite decades of research in thousands of labs around the world, why some people’s beta cells wear out and some don’t is still a mystery. “There’s a change in beta cell function, but we don’t know what makes it so some people can compensate and other people ,” says Mather. “There a lot of ideas, but not a lot of clear evidence.”

One theory is that as the beta cells falter early in type 2, the rising level of glucose in the blood causes a sort of chain reaction. The high glucose is toxic to the beta cells, hastening their failure and death. As they die, blood glucose gets harder to control—and the process speeds up. Research has shown that lowering glucose levels is enough to bring back some beta cell function.

Another possibility is that the immune system is playing a role in beta cell decline. In this scenario, the beta cells might be under attack from the immune system. It’s not unlike what happens in type 1 diabetes, except in the case of type 2, high levels of glucose in the blood might be what sets off the immune reaction. “Perhaps high glucose makes the beta cells poke their heads up above the Whac-a-Mole hole, and now they’re a target,” Mather says. “It may be that there’s a systemic inflammation, and a targeted immune response.”

Genetics could also play a role. Researchers have connected over 70 different genes to type 2 diabetes, though the interplay between them all is nearly impossible to tease apart.

Most frustrating, the answer could be “all of the above.” And it varies from person to person. To slow or halt type 2’s advance, it’s not enough to deal with just the immune system, or obesity. “What makes type 2 diabetes such a difficult problem to solve is that there are so many paths that lead to the same destination,” Mather says. “Maybe we have to block three or four main pathways to have an effect.”

Shifting Into Reverse

Researchers are working to figure out the best way to slow or even change the course of type 2’s progression. There’s lots of evidence, for example, that type 2 diabetes may be reversible. One major clue comes from work with people who have had gastric bypass surgery, a type of bariatric surgery that permanently removes some of the stomach and bypasses some of the small intestine to help patients lose weight.

In 1995, East Carolina University surgeon Walter Pories, MD, published a study showing that a specific type of gastric bypass surgery could reverse type 2 diabetes in 80 percent of patients. People saw their need for insulin injections drop to nothing in a matter of days after the surgery.

Data collected over decades suggested that the remission wasn’t just the result of dramatic weight loss. The surgery does something profound to the patients’ endocrine systems along the way, somehow bringing the pancreas and its failed beta cells back to life.

If they can figure out what’s going on, doctors might be able to replicate the effects of gastric bypass without surgery, slowing or reversing the steady progression of type 2. “There’s something about fuel supply, or hormones, that allows a complete reset and recovery of beta cell function,” says Mather. “It’s a huge clue as to what’s going on, but we don’t have the answer yet.”

A recent American Diabetes Association–funded study led by endocrinologist David Bernlohr, PhD, and surgeon Sayeed Ikramuddin, MD, both at the University of Minnesota–Twin Cities, suggests the remarkable results may have something to do with the parts of the digestive tract bypassed in the surgery, but they’re also pursuing the possibility that calorie restriction plays a role—they just don’t know how yet.

Retnakaran, meanwhile, thinks that some of the factors that lead to type 2 might be reversible using much less dramatic means. He is testing the counterintuitive idea that prescribing insulin injections soon after a type 2 diagnosis—rather than waiting for years until the beta cells have given out—might help slow or even halt the progression of the disease.

To test the theory, Retnakaran is running a series of experiments, working with people recently diagnosed with type 2 to see if giving them insulin soon after diagnosis can “reset” their system. “People are getting insulin early, for a short period of time. A short course, just two to four weeks, addresses this reversible dysfunction and achieves remission of diabetes,” he says.

The idea is that the injected insulin gives the body’s stressed beta cells a break, allowing them to recuperate and recover. And because the beta cells are still functional, they smooth out the ups and downs of insulin injections, reducing the risk of hypoglycemia and the long-term damage caused by high blood glucose. Says Retnakaran: “We’re basically bringing into the ballpark so beta cells can handle the rest themselves.”

Mather is working on a similar study that starts even earlier, lowering glucose in people with prediabetes to see if they can head off type 2 altogether.

Necessary Upkeep

Past experiments with early insulin therapy have shown that remission isn’t permanent. Three months later, type 2 diabetes is back in a third of patients; a year later, the effects have worn off in more than half. Retnakaran’s hoping to show the technique can still be a useful tool. “We’ve done something good, but the effects are transient,” Retnakaran says. “Maybe we need to treat diabetes very intensely early on, then come back with maintenance.”

Until researchers unravel the secrets of beta cell decline, doctors recommend the time- and lab-tested approach of diet and physical activity to keep the body’s microscopic insulin factories working for as long as possible. “Exercise and weight loss improve beta cell function, improve insulin sensitivity, and delay progression ,” says Mather. “Keeping the load on the beta cells as low as it can be is the best approach.”

Beta Cell Decline

The body becomes resistant to its insulin.

The beta cells pump out more insulin
to makeup for insulin resistance.

Beta cells begin to fail and can’t keep pace
with insulin needs. Diabetes is diagnosed.

At diabetes diagnosis, lifestyle changes (diet and
exercise) with or without medication (oral or injectable
drugs or insulin) are needed to control blood glucose.

Beta cells continue to fail and more medications
and/or insulin are needed to control blood glucose.

Learn More About Your Meds

Find a list of oral type 2 medications here and a list of available insulins here.

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