Cellular β function in type 2 prediabetes. Therapeutic efficacy in prediabetes: beta cell preservation options

Abstract

Islets of Langerhans' evolution, and within it, β cellular pool from normality to T2D undergoes several stages. Among them, it can be observed initial adaptative hyperplasia to insulin resistance and a later claudication with cellular mass reduction greater than 50%, α cells increase, fibrosis and amyloid deposits appearance.   Between these two stages, one additional stage, corresponding to the one clinically manifested as prediabetes, can be observed. During this stage, alterations in the dynamic of normal insulin secretions, with losses of its first peak, are already present. 

In order to prevent progression from prediabetes to T2D, several therapeutic strategies are proposed:

• Annually monitoring people before T2D development (E*),

• Integrating them to lifestyle behavior change programs to achieve and maintain a minimum weight loss of 7% (A),

• Incorporating them to a minimum of 150 minutes brisk walking physical activity routine per week,

• Establishing proper meal planning (B),

• Using support programs through Apps (B).

Given the cost – effectiveness (A), all these programs should be covered by the health system. 

It was found out that, even without weight loss, 150 minutes of physical activity per week (700 kcal/week) reduced T2D incidence by 44%; it was also discovered, that even though 7% weight loss is enough to reduce T2D incidence, there are better results by reducing it to a 10%. It was deemed necessary a weight loss of about 0,5 and 1 kg/week with caloric restriction between 500 and 1000 calories/day without being a defined pattern about diet composition to achieve this goal. 

Given that lifestyle behavior changes are hard to achieve or maintain, additional pharmacotherapeutic options may be considered. The ones having proven their effectiveness on prospective randomized studies are the following: acarbose, liraglutide, rosiglitazone, pioglitazone, insulin glargine, orlistat, phentermine plus topiramate and metformin.

The use of metformin is recommended by the American Diabetes Association 3. Acarbose and metformin are recommended by the American Association of Clinical Endocrinologist and American College of Endocrinology along with TZD and/or GLP1 in case of diagnosed prediabetes with more than one criterion. Additional pharmacotherapeutic options or other therapies, such as bariatric surgery, can be added to lifestyle modifications to benefit patients attempting to achieve weight loss. 

*Level of evidence