Effects of alpha-glucosidase-inhibiting drugs on acute postprandial glucose and insulin responses: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. METHODS: We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. RESULTS: The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (-1.5 mmol/l mean PPG [95% CI -1.9, -1.1] by acarbose, and -1.6 [-1.9, -1.4] by miglitol) as compared to individuals without diabetes (-0.4 [95% CI -0.5, -0.3] by acarbose, and -0.6 [-0.8, -0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43-54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. CONCLUSIONS: The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.

Metabolic cross talk between the colon and the periphery: implications for insulin sensitivity.

Until recently, a glance at a standard undergraduate textbook would have given the impression that the colon was merely a storage organ for faeces and maybe something about the absorption of electrolytes and water. In reality, the colon is a highly-metabolically-active organ, the function of which has implications not only for the remainder of the digestive tract, but also for peripheral organs such as adipose tissue (AT), liver and skeletal muscle. The present review focuses on two distinct but complementary areas: (1) the metabolic adaptation that occurs following surgical removal of colonic tissue; (2) the effect of modulating the colon in situ in terms of postprandial metabolism, insulin sensitivity and disease risk. Work in these two areas points to the colon being important in modulating normal tissue insulin sensitivity. The role of fatty acids is central to the insulin sensitivity hypothesis. AT acts as a daily 'buffer' for fatty acids. However, following colonic resection there is an apparent change in AT function. There is an increase in the AT lipolysis rate, resulting in the release of excess fatty acids into the circulation and consequently the take up of excess fatty acids into skeletal muscle. This resultant increase in either storage of lipid or its oxidation would result in a reduction in insulin sensitivity. The insulin-sensitising effects of high-fibre diets are also related to changes in AT function and fatty acid metabolism, but manipulating colonic tissue in situ allows the mechanisms to be elucidated. This research area is an exciting one, involving the potential role of SCFA (the absorbed by-products of colonic bacterial fermentation) acting directly on peripheral tissues, following the recent identification of G-protein-coupled receptors specific for these ligands.