Non-nutritive sweeteners and type 2 diabetes: Should we ring the bell?

Non-nutritive sweeteners (NNS) were thought to be healthy sugar substitutes used instead of sugar for caloric and glycemic control but evidences blaming them for contributing to type 2 diabetes (T2D) are rising. We aim to investigate whether NNS consumption prevents or causes T2D. Articles of all designs conducted on humans were retrieved from three databases in addition to manually reviewed articles. The literature is highly heterogeneous, and conclusions vary with different studies' types and designs. While some studies highlighted the neutral effect of NNS on T2D or reported inconclusive evidences to make their conclusion, others either found NNS culprit for increasing the risk for T2D or reported their protective effect against it. Those results were changing after adjustment for confounders. Due to the inconsistency in the literature, well-designed studies that take into consideration all types of confounders are needed. RESEARCH IN CONTEXT: Evidence before this study: The epidemic of obesity is the result of many factors and causes several chronic diseases where its association with type 2 diabetes is well established. The first line of treatment for obesity is lifestyle changes including physical activity and dietary intervention where non-nutritive sweeteners have received a high attention; those were thought to be healthy sugar substitutes used instead of sugar for caloric and glycemic control but several evidences have blamed them for having a role in the development of type 2 diabetes. In our paper, we aim to investigate whether non-nutritive sweeteners consumption prevents or causes type 2 diabetes. To respond to this question, an extensive search of the literature was conducted between October and December 2018 using the key terms "non-nutritive sweeteners", "artificial sweeteners", "high-intensity sweeteners", "type 2 diabetes" and "prediabetes" on three databases including Pubmed, Science direct and Scopus. Additional search for relevant articles was carried out manually from the reference list of selected articles. Animal studies, studies involving sugar alcohols or those conducted on children, adolescents, pregnant women, or on participants with diabetes were excluded. Human studies conducted from January 2004 to October 2018 were included and divided into observational, interventional, and systematic review and meta-analysis for discussion and analysis Added value of this study: In the literature, the term high-intensity sweeteners has been used interchangeably with non-nutritive sweeteners, artificial sweeteners or low-calorie sweeteners but few articles, if any, clarified the difference between them. In our review, we gathered the different definitions and classifications and summarized them to help the reader understand the difference. Since artificial sweeteners are nowadays widely used and prescribed for caloric and glycemic control, and are unintentionally consumed because they enter in the manufacturing process of thousands of products and due to their potential side effects reported in several studies, we found it interesting to gather, summarize and discuss the available results assessing the role of non-nutritive sweeteners in the development of type 2 diabetes. Those results showed the heterogeneity of the literature and the difficulty in having a firm conclusion; this helps researchers to profit from our study and to conduct well-designed studies leading to firm conclusions and recommendations. Implications of all the available evidence: Despite the absence of strong conclusion that confirms the fact that non-nutritive sweeteners consumption increases the risk for diabetes, no firm conclusion rejects this statement. In result, the existing evidences in addition to our study should ring the bell for clinicians and practitioners who are prescribing those sugar-alternatives as "healthy substitute" to white sugar. Moreover, this encourages the manufacturers to search for a healthy natural alternative to artificial sweeteners to be used in the manufacturing process.