Abstract
Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and α-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.
Highlights
The mechanisms underlying the increasing prevalence of obesity and type 2 diabetes (T2D) are poorly understood
glucagon-like peptide (GLP)-1 levels were almost doubled at 30 min (21.66 ± 2.24 vs. 13.28 ± 1.34, p = 0.0151) following the high-fat diet (HFD) compared to the high-carbohydrate diet (HCD) during the MTT (Figure 1C)
We suggested that the HFD, via increased intestinal ketone body production and inhibition of enteroendocrine cells in the jejunum, could inhibit GLP-1 and explain the decreased levels seen in obese subjects [17]
Summary
The mechanisms underlying the increasing prevalence of obesity and type 2 diabetes (T2D) are poorly understood. There is an unresolved debate on the role of the interaction between the diet and the gut for the development of T2D [1,2,3]. In order to be absorbed, carbohydrates are chemically degraded into smaller mono- or disaccharides before being absorbed in the upper part of the small intestine (mainly the duodenum and jejunum) [4]. Triglycerides are degraded to free fatty acids and glycerol before being absorbed. On their way through the intestinal epithelium, carbohydrates and fatty acids stimulate enteroendocrine cells to release gut peptides, e.g., glucagon-like peptide (GLP)-1 and gastric inhibitory peptide (GIP), that enhance insulin release from the pancreas and thereby prepare whole-body metabolism for the incoming nutrient load
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