Insulin Independence in Newly Diagnosed Type 1 Diabetes Patient following Fenofibrate Treatment

A 19-year-old girl was diagnosed with type 1 diabetes and showing polydipsia and polyuria. She was double autoantibody-positive and had a diabetes-prone tissue type. She was immediately started on insulin. Fenofibrate treatment (160 mg daily) was initiated seven days after diagnosis. The need for insulin quickly declined, and she took her last dose of insulin 19 days after the first dose of fenofibrate, having regained endogenous control of blood glucose concentrations. She has now been insulin independent for one year and 9 months. Unstimulated C-peptide has increased by 51% (317 to 479 pmol/l), and IA-2 autoantibody level has decreased by 65% (49 to 17 × 103 arbitrary units). Fenofibrate is a widely used drug for reducing triglyceride and cholesterol levels. Fenofibrate reverses and prevents autoimmune diabetes in nonobese diabetic (NOD) mice by increasing the amount of the sphingolipid sulfatide in islets. Sphingolipid metabolism is otherwise abnormal in the islets at diagnosis of type 1 diabetes. In conclusion, we describe a 19-year-old patient with classical newly diagnosed type 1 diabetes, which following fenofibrate treatment has been without insulin for 21 months

Possible Prevention of Diabetes with a Gluten-Free Diet

Gluten seems a potentially important determinant in type 1 diabetes (T1D) and type 2 diabetes (T2D). Intake of gluten, a major component of wheat, rye, and barley, affects the microbiota and increases the intestinal permeability. Moreover, studies have demonstrated that gluten peptides, after crossing the intestinal barrier, lead to a more inflammatory milieu. Gluten peptides enter the pancreas where they affect the morphology and might induce beta-cell stress by enhancing glucose- and palmitate-stimulated insulin secretion. Interestingly, animal studies and a human study have demonstrated that a gluten-free (GF) diet during pregnancy reduces the risk of T1D. Evidence regarding the role of a GF diet in T2D is less clear. Some studies have linked intake of a GF diet to reduced obesity and T2D and suggested a role in reducing leptin- and insulin-resistance and increasing beta-cell volume. The current knowledge indicates that gluten, among many environmental factors, may be an aetiopathogenic factors for development of T1D and T2D. However, human intervention trials are needed to confirm this and the proposed mechanisms

PPARs and the Development of Type 1 Diabetes

Peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors with a key role in glucose and lipid metabolism. PPARs are expressed in many cell types including pancreatic beta cells and immune cells, where they regulate insulin secretion and T cell differentiation, respectively. Moreover, various PPAR agonists prevent diabetes in the non-obese diabetic (NOD) mouse model of type 1 diabetes. PPARs are thus of interest in type 1 diabetes (T1D) as they represent a novel approach targeting both the pancreas and the immune system. In this review, we examine the role of PPARs in immune responses and beta cell biology and their potential as targets for treatment of T1D

L-serine supplementation lowers diabetes incidence and improves blood glucose homeostasis in NOD mice

<div><p>Sphingolipids are a diverse group of lipids with important roles in beta-cell biology regulating insulin folding and controlling apoptosis. Sphingolipid biosynthesis begins with the condensation of L-serine and palmitoyl-CoA. Here we tested the effect of L-serine supplementation on autoimmune diabetes development and blood glucose homeostasis in female NOD mice. We found that continuous supplementation of L-serine reduces diabetes incidence and insulitis score. In addition, L-serine treated mice had an improved glucose tolerance test, reduced HOMA-IR, and reduced blood glucose levels. L-serine led to a small reduction in body weight accompanied by reduced food and water intake. L-serine had no effect on pancreatic sphingolipids as measured by mass spectrometry. The data thus suggests that L-serine could be used as a therapeutic supplement in the treatment of Type 1 Diabetes and to improve blood glucose homeostasis.</p></div

L-serine supplementation lowers diabetes incidence and improves blood glucose homeostasis in NOD mice

<div><p>Sphingolipids are a diverse group of lipids with important roles in beta-cell biology regulating insulin folding and controlling apoptosis. Sphingolipid biosynthesis begins with the condensation of L-serine and palmitoyl-CoA. Here we tested the effect of L-serine supplementation on autoimmune diabetes development and blood glucose homeostasis in female NOD mice. We found that continuous supplementation of L-serine reduces diabetes incidence and insulitis score. In addition, L-serine treated mice had an improved glucose tolerance test, reduced HOMA-IR, and reduced blood glucose levels. L-serine led to a small reduction in body weight accompanied by reduced food and water intake. L-serine had no effect on pancreatic sphingolipids as measured by mass spectrometry. The data thus suggests that L-serine could be used as a therapeutic supplement in the treatment of Type 1 Diabetes and to improve blood glucose homeostasis.</p></div

L-serine supplementation improves glucose homeostasis.

<p>(a) Blood glucose levels in healthy NOD mice up to 45 weeks of age, control (n = 46) and L-serine (n = 30), p = 0.047. Homeostasis model assessment of insulin resistance (HOMA-IR) (a) and beta-cell function (HOMA-Beta) (b) was assessed in mice age 13 weeks based on fasting insulin and blood glucose concentration (n = 4) p = 0.03 and p = 0.15, respectively. (d) Glucose tolerance test (GTT) was performed on healthy NOD mice age 45 weeks, which were injected with 1M glucose 0.01ml/g body weight. Blood glucose was measured at the indicated time (n = 5). (e) Area under the curve (AUC) calculation for the GTT, p = 0.04. Control is shown in red and L-serine in blue. Statistical tests: mixed model (a) and unpaired two-tailed Student’s <i>t</i>-test (b, c, and e). Data shown as mean ± SEM. *p<0.05.</p

L-serine supplementation reduces body weight.

<p>(a) Body weight as measured once a week in healthy NOD mice, control (n = 49), and L-serine (n = 30). p = 0.045 (b) Food intake was calculated per cage by weighing the food racks, control (n = 5) and L-serine (n = 4). (c) Area under the curve (AUC) calculation for food intake, p = 0.01. d) Water intake as calculated per cage by weighting of water flasks, control (n = 5) and L-serine (n = 4). AUC calculation for water intake, p = 0.001. (f) Calorie intake was calculated to adjust for the intake of L-serine through water, control (n = 5) and L-serine (n = 4). AUC calculation for calorie intake, p = 0.054. Control is shown in red and L-serine in blue. Statistical tests: mixed model (a) and unpaired two-tailed Student’s t-test (c, e g). Data is shown as mean ± SEM. *p<0.05; **p<0.01; ***p<0.001.</p

Pancreas lipid content.

<p>Pancreas lipid content.</p