By Max Bingham, PhD

A Lactobacillus reuteri strain termed SD5865 may have the ability to increase insulin secretion, possibly via increased incretin release, in humans, according to the outcomes of a small proof-of-concept trial published in this issue of Diabetes Care (p. 1827). Although the study focused on lean and obese subjects without diabetes, Simon et al. suggest that oral ingestion of the strain might be the starting point for a novel therapeutic approach toward modifying insulin production particularly via incretin-mediated β-cell function. The authors stress that the strain has not yet been tested in individuals with diabetes. The randomized controlled trial looked at 21 glucose-tolerant lean or obese individuals who ingested 1010L. reuteri or placebo for 4 weeks. Measurements then included oral glucose tolerance tests to assess effects on incretin and GLP-1/GLP-2 secretion. Peripheral insulin sensitivity, glucose production, lipid content, various immune parameters, and gut microbiota composition were also assessed. Significant effects resulting from L. reuteri ingestion included increases in glucose-stimulated GLP-1 and GLP-2 release (76% and 43%, respectively), insulin (49%), and C-peptide secretion (55%) in comparison with placebo. No changes were reported for the variety of other measurements. The authors suggest that increases in GLP-1 explain the increased glucose-stimulated insulin secretion. The increase in GLP-2, meanwhile, may be indicative of effects on tight junctions in the intestinal wall and suggest decreased gut permeability and consequently less endotoxin translocation and low-grade inflammation. Lactobacilli have previously been shown to modulate gut permeability (at least in rodents) and may in theory at least offer some protection against the low-grade inflammation that is characteristic of obesity. Commenting more widely on the study, Drs. Schloot and Roden stated: “We view this pilot study as evidence for a link between dietary intake of one specific probiotic and incretin-mediated insulin secretion that will possibly pave the way for novel therapeutic concepts for people with or at risk of type 2 diabetes.”

Simon et al. Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept. Diabetes Care 2015;38:1827–1834

Skipping breakfast may result in an increased postprandial hyperglycemia response after both lunch and dinner in individuals with type 2 diabetes, according to the outcome of a small trial in humans by Jakubowicz et al. published in this issue of Diabetes Care (p. 1820). The trial, which used a randomized crossover design, explored the effects of consuming breakfast or not on plasma glucose levels, insulin, and variety of other common blood markers. When breakfast was skipped, much larger spikes in blood glucose were observed after both lunch and dinner in comparison with when breakfast was consumed. Insulin response was also dented in terms of magnitude and peaked 30 min later after both lunch and dinner when breakfast was missed. Dr. Jakubowicz suggested that by skipping breakfast, the absence of glucose elevation because of fasting until noon may diminish “β-cell memory” and β-cell responsiveness, leading to a reduced and delayed insulin response after lunch and dinner on the no-breakfast day. The authors also found that a lack of breakfast resulted in increases in plasma free fatty acids and glucagon and reduced levels of insulin, C-peptide, and GLP-1 levels following lunch and to a lesser extent dinner. In turn, this may block sensitization and activation of the β-cells and further serves to blunt insulin response and increase postprandial hyperglycemia after these meals. The authors suggest that the effects of skipping breakfast long term could be considerable as glycemic peaks and postprandial hyperglycemia are strongly linked to cardiovascular complications in type 2 diabetes. Their recommendation for patients with type 2 diabetes: eat breakfast.

Jakubowicz et al. Fasting until noon triggers increased postprandial hyperglycemia and impaired insulin response after lunch and dinner in individuals with type 2 diabetes: a randomized clinical trial. Diabetes Care 2015;38:1820–1826

The frequency and risk of diabetic ketoacidosis events remain high for certain individuals with type 1 diabetes and particularly so when simple diabetes care management is not followed, according to an international comparison of data from 50,000 patients with type 1 diabetes from England, Wales, the U.S., Austria, and Germany (p. 1876). It also reveals a number of risk factors for diabetic ketoacidosis events. Maahs et al. combined and analyzed data from the three registries of patients with type 1 diabetes (covering the U.S., England and Wales [combined], and Austria and Germany [combined]) with the aim of identifying factors associated with diabetic ketoacidosis admissions to hospital. Specifically, they examined the data of pediatric patients who had their diabetes under medical supervision (diabetes duration >1 year). The frequencies of episodes were 5.0% in Germany and Austria, 6.4% in England and Wales, and 7.1% in the U.S. As the authors note, these rates were high despite the existence of advanced health care systems and the rates were quite variable between the countries. Following multivariate analyses, higher odds for diabetic ketoacidosis events were associated with being female, being from an ethnic minority, or having HbA1c above target. Compared to receiving insulin via injections, insulin pump use was associated with lower risk only in the U.S. When all data were combined, pump use was still associated with increased odds of an event in younger patients but decreased risk in older pediatric patients. However, patterns of usage of pumps differed between countries. For example, use by patients aged <6 years was highest in Germany and Austria, but in the U.S. the highest use was in patients aged >13 years. The authors are clear in terms of conclusions: “These analyses highlight the high annual rates of [diabetic ketoacidosis] … in these developed Western nations that already have sophisticated and advanced health care systems. These data should serve as a call to action to develop programs to reduce pediatric [diabetic ketoacidosis].” Elaborating further, author Nicole C. Foster stated: “Diabetic ketoacidosis rates continue to be much too high in the pediatric population with type 1 diabetes. Our collaboration between the T1D Exchange, the DPV in Germany/Austria, and the NPDA in England/Wales demonstrates how large patient registries can identify targets to improve diabetes care. Next steps require intervention programs to reduce diabetic ketoacidosis in this population.”

Maahs et al. Rates of diabetic ketoacidosis: international comparison with 49,859 pediatric patients with type 1 diabetes from England, Wales, the U.S., Austria, and Germany. Diabetes Care 2015;38:1876–1882