RESUSCITATING FLAGGING PANCREATIC BETA-CELLS FOR TYPE 2 DIABETES PREVENTION AND REMISSION

Resuscitating flagging pancreatic beta-cells is looking promising for preventing, managing, and potentially putting type 2 diabetes into remission. Recent research shows that beta-cells are not irreversibly lost in early type 2 diabetes and that they can recover their function if metabolic stress is removed.

The pancreas

The pancreas is a small organ located behind the stomach in the upper part of the abdomen. It is surrounded by other organs including the stomach, small intestine (duodenum), liver, and spleen. It is spongy, about 15–25cm (6–10in) long, 2.5cm (1in) thick, and is shaped a bit like a flattened pear or a fish extended horizontally across the abdomen. The bulk (95%) of the pancreas consists of tissues and cells that produce pancreatic secretions for the digestion of carbohydrates, fats and proteins. The remainder consists of little islands of cells called islets of Langerhans. These look a bit like small bunches of grapes and produce hormones that regulate blood glucose and help regulate pancreatic digestive secretions.

Blood glucose hormones

Two of the most important pancreatic hormones are insulin produced by beta cells and glucagon produced by alpha cells in the islets of Langerhans which manufacture and release these hormones directly into the bloodstream.

Insulin

Insulin is a di-peptide (i.e., protein) hormone that maintains normal blood glucose levels by facilitating cellular glucose uptake, regulating carbohydrate, lipid and protein metabolism and promoting cell division and growth. Insulin regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and muscle cells.

Glucagon

Glucagon stimulates the liver to break down glycogen into glucose, which is then released into the blood. It also activates gluconeogenesis, the conversion of certain amino acids from proteins into glucose. Finally, it facilitates the breakdown of stored fat (triglycerides) into fatty acids and glycerol for use as fuel by cells.

Type 2 diabetes

The exact cause of type 2 diabetes is not fully understood but people have a reduced number of pancreatic beta cells, and of those that survive there is a reduced secretory function, and there is also frequently (but not always) peripheral tissue insulin resistance (the insulin that is produced does not work as efficiently in the target cells as it should). Type 2 diabetes is also characterized by high rates of glucagon secretion which is less responsive to the concentration of glucose in the blood, but insulin is still secreted into the blood in response to concomitantly increasing blood glucose concentrations. As a result, insulin levels are typically much higher than they are in people without type 2 diabetes.

Prevention of type 2 diabetes

Over the last few decades, clinical trials have been conducted all around the world to see whether people with pre-diabetes (Impaired Glucose Tolerance or Impaired Fasting Glucose) can prevent or at the very least delay the development of type 2 diabetes. The trials have followed similar designs in that after randomisation, one group of people with pre-diabetes were provided with lifestyle advice focusing on healthy eating and regular moderate physical activity and another group provided common blood glucose lowering medications (e.g., metformin), for several years. As well as returning average blood glucose levels back to the normal range, one of the primary goals of the studies was to reduce body weight modestly – by between 5 and 10% of a person’s starting weight when they first entered the trial.

Weight loss was typically achieved through moderate energy reduction (around 2,000 kJ or 500 Calorie less each day), as part of an overall healthy eating plan that was reduced in fat (25-30% of kilojoules), low in saturated fat (7-10% of kilojoules) and high in dietary fibre (around 30 g for a typical adult). People were also advised to do at least 150 minutes (e.g., 30 minutes, 5 times a week) of moderate intensity (e.g., brisk walking) physical activity each week, to assist with fat loss, decrease muscle loss, and to decrease insulin resistance.

A systematic review of all of the diabetes prevention trials conducted so far was published recently, incorporating over 4,000 people from around the world, and it found that lifestyle interventions could decrease the risk of people with pre-diabetes from developing type 2 diabetes by more than 50% (more than 1 in 2 people).

In addition to this, there is evidence from observational studies (where large groups of healthy free living healthy people are followed up for 5-25 years while their lifestyle habits are measured regularly), that healthy low glycemic index (GI) and glycemic load (GL) diets may decrease the risk of developing diabetes by up to 90%.

Reversing type 2 diabetes

While type 2 diabetes cannot be “cured” as such, it can be put into remission if an individual is able to lose a significant amount of body fat (at least 10% of initial weight) and keep it off, within the first ~5 years of diagnosis. We say “remission” rather than “cure”, because the diabetes may come back years later, either due to slowly regaining fat, losing muscle (sarcopenia), or simply due to advancing age.

An umbrella review of 14 diabetes remission studies was published recently. Perhaps unsurprisingly, success at achieving remission at 12 months varied according to the kind of diet used in the randomised controlled trial:

• Consuming very low energy total diet replacements for several months followed by stepwise food reintroduction, was the most effective at achieving diabetes remission at 1 year, with a median of 54% of participants doing so.
• Mediterranean style diets achieved 15% remission at 1 year.
• Studies using 1-2 meal replacements per day achieved 11% remission at 1 year.
  

While currently popular (again), and showing promising results at 6 months, the evidence for low carbohydrate/ketogenic diets and type 2 diabetes remission is not strong. Another recent systematic review and meta-analysis of 3 RCTs found that there is no compelling evidence to-date that low-carb diets can put type 2 diabetes into remission at 1 year.

Conclusion

It is possible to resuscitate flagging pancreatic beta-cells in people with pre-diabetes or type 2 diabetes through adoption of a healthy lifestyle, including a healthy diet and regular physical activity.

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