Background Epidemiological as well as animal studies have shown that environmental factors such as nutrition contribute to the development of diabetes. In this study we investigated whether the early introduction of a gluten‐free diet can influence the onset and/or incidence of diabetes, as well as insulitis and the number of gut mucosal lymphocytes, in non‐obese diabetic (NOD) mice. Methods Gluten‐free and standard Altromin diets (with the same milk protein and vitamin content) were given to breeding pairs of NOD mice as well as to the first generation of NOD female mice, which were then observed for 320 days. Results A substantially lower diabetes incidence (χ2=15.8, p=0.00007) was observed in NOD mice on the gluten‐free diet (15%, n=27) compared to mice on the standard diet (64%, n=28). In addition, mice on the gluten‐free diet developed diabetes significantly later (244±24 days SEM) compared to those on the standard diet (197±8 days, p=0.03). No differences in the number of CD3+, TCR‐γδ+, IgA+, and IgM+ cells in the small intestine were observed. Conclusion We showed that gluten‐free diet both delayed and to a large extent prevented diabetes in NOD mice that have never been exposed to gluten. Copyright © 1999 John Wiley & Sons, Ltd.

Background: This observational study investigated whether the connected NovoPen Ò 6 could influence insulin regimen management and glycemic control in people with type 1 diabetes (T1D) using a basal-bolus insulin regimen and continuous glucose monitoring in a real-world setting. Methods: Participants from 12 Swedish diabetes clinics downloaded pen data at each visit (final cohort: n = 94). Outcomes included time in range (TIR; sensor glucose 3.9-10.0 mmol/L), time in hyperglycemia (>10 mmol/L), and hypoglycemia (L1: 3.0-<3.9 mmol/L; L2: <3.0 mmol/L). Missed bolus dose (MBD) injections were meals without bolus injection within -15 and +60 min from the start of a meal. Outcomes were compared between the baseline and follow-up periods ( ‡5 health care professional visits). Data were analyzed from the first 14 days following each visit. For the TIR and total insulin dose analyses (n = 94), a linear mixed model was used, and for the MBD analysis (n = 81), a mixed Poisson model was used. Results: TIR significantly increased (+1.9 [0.8; 3.0] 95% CI h/day; P < 0.001) from baseline to follow-up period, with a corresponding reduction in time in hyperglycemia (-1.8 [-3.0; -0.6] 95% CI h/day; P = 0.003) and L2 hypoglycemia (-0.3 [-0.6; -0.1] 95% CI h/day; P = 0.005), and no change in time in L1 hypoglycemia. MBD injections decreased by 43% over the study (P = 0.002). Change in MBD injections corresponded to a decrease from 25% to 14% based on the assumption that participants had three main meals per day. Conclusions: Our study highlights the potential benefit on glycemic control and dosing behavior when reliable insulin dose data from a connected pen contribute to insulin management in people with T1D.

Gluten+ diet prevents diabetes in NOD mice at the level found with the non-purified gluten-free diet. Possible mechanisms of the enigmatic, dual effect of dietary gluten on the development of T1D are discussed.

The gluten-free diet compared to the standard diet both qualitatively and quantitatively substantially altered the composition of the caecal bacterial flora in NOD mice. Although Gram-positive bacteria might influence the beta cells through certain digestive products, it is more likely to assume that any effect on diabetes incidence is immunological.

Sulfatide is a glycolipid that has been associated with insulin-dependent diabetes mellitus. It is present in the islets of Langerhans and follows the same intracellular route as insulin. However, the role of sulfatide in the beta cell has been unclear. Here we present evidence suggesting that sulfatide promotes the folding of reduced proinsulin, indicating that sulfatide possesses molecular chaperone activity. Sulfatide associates with insulin by binding to the insulin domain A8--A10 and most likely by interacting with the hydrophobic side chains of the dimer-forming part of the insulin B-chain. Sulfatide has a dual effect on insulin. It substantially reduces deterioration of insulin hexamer crystals at pH 5.5, conferring stability comparable to those in beta cell granules. Sulfatide also mediates the conversion of insulin hexamers to the biological active monomers at neutral pH, the pH at the beta-cell surface. Finally, we report that inhibition of sulfatide synthesis with chloroquine and fumonisine B1 leads to inhibition of insulin granule formation in vivo. Our observations suggest that sulfatide plays a key role in the folding of proinsulin, in the maintenance of insulin structure, and in the monomerization process.