DiRECT: Effects on insulin and liver fat revealed
medwireNews: Researchers from the DiRECT trial have reported large positive effects on liver fat and insulin secretion among people who achieved type 2 diabetes remission in response to a very-low-calorie diet.
Among patients recruited from the Tyneside geographic area, the average weight loss in the 57 patients who undertook a low-energy formula diet (825–853 kcal/day) for at least 3 months was 15.4 kg, compared with just 1.4 kg among the 25 who continued with usual care.
In the intervention group, liver fat, measured on magnetic resonance imaging, decreased from an average of 16.2% to 3.0%, which was no different from levels in 25 people without diabetes. Intrapancreatic fat decreased from 8.4% to 7.5%, but remained above normal levels.
The intervention group also achieved an improved first-phase insulin response, from 0.04 to 0.10 nmol/min per m2, and the 40 patients who achieved remission of type 2 diabetes (glycated hemoglobin <6.5%; 48 mmol/mol) had a still larger improvement, from 0.05 to 0.14 nmol/min per m2. The researchers noted, however, that this only brought patients to around the lower limit of the normal range; controls without diabetes had an average insulin response of 0.38 nmol/min per m2, which was significantly higher.
The DiRECT trial was designed to test the “twin cycle” hypothesis, in which chronic excess calorie intake leads to fatty liver, most particularly in people who are susceptible to insulin resistance, and this is further exacerbated by the increased insulin secretion needed to control plasma glucose. The increased export of very-low-density-lipoprotein (VLDL)-triglyceride from the liver then results in the accumulation of triglycerides in the pancreatic islet cells, impairing their function.
In line with this, the team reported that patients in the intervention group had a significant decrease in hepatic VLDL-triglyceride production, which was greatest in those who achieved remission, and in their triglyceride pool size.
Furthermore, patients who achieved a greater than 10% reduction in VLDL-triglyceride production had a significantly larger improvement in first-phase insulin response than those who had a smaller reduction, from 0.03 to 0.14 nmol/min per m2 compared with 0.07 to 0.10 nmol/min per m2.
The findings were reported in three presentations at the Diabetes UK Professional Conference in London, UK.
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