A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or β-cell mass in NZO mice

An LCHFD is unlikely to be of benefit for preventing the decline in β-cell function associated with the progression of hyperglycemia in type 2 diabetes.

NZO mice were maintained on either standard rodent chow or an LCHFD from 6 to 15 weeks of age. Body weight, food intake and blood glucose were assessed weekly. Blood glucose and insulin levels were also assessed after fasting and re-feeding and during an oral glucose tolerance test. The capacity of pancreatic β-cells to secrete insulin was assessed in vivo with an intravenous glucose tolerance test. β-Cell mass was assessed in histological sections of pancreata collected at the end of the study.

In NZO mice, an LCHFD reduced plasma triglycerides (P=0.001) but increased weight gain (P<0.0001), adipose tissue mass (P=0.0015), high-density lipoprotein cholesterol (P=0.044) and exacerbated glucose intolerance (P=0.013). Although fasting insulin levels tended to be higher (P=0.08), insulin secretory function in LCHFD-fed mice was not improved (P=0.93) nor was β-cell mass (P=0.75). Conclusions: An LCHFD is unlikely to be of benefit for preventing the decline in β-cell function associated with the progression of hyperglycemia in type 2 diabetes.