The effect of local application of recombinant human basic fibroblast growth factor (rhbFGF) on fracture repair was examined using normal rats and streptozotocin-diabetic rats with impaired repairing ability. Immediately after fracturing the fibula, rhbFGF was applied by a single injection to the fracture site. Application of rhbFGF increased the volume and mineral content of callus in a dose-dependent manner in both normal and diabetic rats, and callus formation of diabetic rats was stimulated to levels similar to those in nontreated normal rats. The marked effect of rhbFGF on fracture repair was associated with an improvement in the mechanical properties of the healing fibula in both normal and diabetic rats. Immunohistochemical staining showed that endogenous bFGF was widely distributed in normal rats 1 and 3 weeks after fracture, especially in the soft callus and periosteum, whereas much less bFGF was detected in diabetic rats. Insulin treatment of diabetic rats restored the immunostaining for bFGF. These results demonstrate that bFGF is expressed during the early stage of fracture repair, and that the impaired fracture-repairing ability in diabetic rats is associated with reduced expression of bFGF at the fracture site. A single application of bFGF immediately after fracture not only facilitates the repair process in normal rats, but also recovers the impaired repairing ability in diabetic rats. These results suggest that local application of bFGF may facilitate bone union in patients with impaired as well as normal repairing ability.

Purpose Extra virgin olive oil (EVOO) and flaxseed oil (FO) contain a variety of constituents beneficial for chronic inflammation and cardio-metabolic derangement. However, little is known about the impact of EVOO and FO on dysbiosis of gut microbiota, intestinal immunity, and barrier. We, therefore, aimed to assess the impact of EVOO and FO on gut microbiota, mucosal immunity, barrier integrity, and metabolic health in mice. Methods C57BL/6 J mice were exposed to a low-fat (LF), lard (HF), high fat-extra virgin olive oil (HF-EVOO), or high fat-flaxseed oil (HF-FO) diet for 10 weeks. Gut microbiota assessment was undertaken using 16S rRNA sequencing. Levels of mRNA for genes involved in intestinal inflammation and barrier maintenance in the intestine and bacterial infiltration in the liver were measured by qPCR. Results HF-EVOO or HF-FO mice showed greater diversity in gut microbiota as well as a lower abundance of the Firmicutes phylum in comparison with HF mice (P < 0.05). The qPCR analyses revealed that mRNA level of FoxP3, a transcription factor, and IL-10, an inducer of regulatory T cells, was significantly elevated in the intestines of mice-fed HF-EVOO in comparison with mice-fed HF (P < 0.05). The mRNA level of the antimicrobial peptide, RegӀӀӀγ, was markedly elevated in the intestines of HF-EVOO and HF-FO compared with HF group (P < 0.05). Conclusions Our data suggest that the consumption of EVOO or FO can beneficially impact gut microbiota, enhance gut immunity, and assist in the preservation of metabolic health in mice.

A 61-year-old woman with multiple metastatic and unresectable gastrointestinal stromal tumors (GISTs) was referred for investigation of refractory hypoglycemia that developed four months before this hospitalization. On admission, her fasting plasma glucose was 38 mg/dL despite 10% glucose infusion. Investigations revealed that her serum C-peptide, insulin and growth hormone levels were suppressed, and big insulin-like growth factor II was observed. She was diagnosed with non-islet cell tumor hypoglycemia, which resolved after glucocorticoid treatment. Clinicians should thus be vigilant to identify hypoglycemia in patients with large metastatic GISTs because glucocorticoid therapy is useful even if the GIST is inoperable.

Although fasting plasma glucose levels <70 mg/dL are associated with a high incidence of cardiovascular disease (CVD), whether there is any risk of new-onset diabetes mellitus owing to fasting plasma glucose at this range has not been clarified. We measured the odds ratio (OR) of new-onset diabetes mellitus relative to fasting plasma glucose levels at various ranges in a nation-wide Japanese population with and without CVD history. Of 186,749 participants without diabetes in 2008, 171,408 had no history of CVD, while 15,341 did. Participants were classified into 8 categories according to their fasting plasma glucose levels. Unadjusted and multivariable-adjusted logistic regression models were used to measure the OR of new-onset diabetes mellitus in the 3-year follow up. In all participants, multivariable-adjusted OR increased when fasting plasma glucose levels were <70 mg/dL or 90–125 mg/dL. Participants without CVD showed increased OR when glucose levels were <70 mg/dL or 90–125 mg/dL. Participants with a history of CVD showed increased OR with glucose levels of 95–125 mg/dL. The risk of new-onset diabetes mellitus is higher when fasting glucose levels are <70 mg/dL, indicating that the paradox of fasting glucose seeks a new risk stratification for new-onset diabetes mellitus.

BackgroundLiraglutide is one of the glucagon-like peptide-1 analogs; there are only a few reports of liraglutide being used for the treatment of insulin allergy. Furthermore, anti-insulin immunoglobulin G antibodies are occasionally detected in patients with diabetes. Hence, we report a case in which switching to liraglutide therapy ameliorated both the symptoms of insulin allergy with hypereosinophilia and the characteristics of insulin antibodies in a patient with type 2 diabetes mellitus.Case presentationWe present the case of a 70-year-old Japanese man with type 2 diabetes who developed insulin allergy with hypereosinophilia. Anti-insulin antibodies, high glycated hemoglobin levels (approximately 12 %), and high serum insulin levels were detected. Because a change in his insulin treatment was inefficient, treatment with liraglutide to protect residual insulin secretion was started, resulting in improvements in his insulin allergy, serum glycated hemoglobin, insulin, and eosinophil levels. Scatchard plots revealed decreased binding capacity and increased affinity constant for high affinity sites of anti-insulin antibodies.ConclusionsLiraglutide might be useful for treating insulin allergy and anti-insulin antibodies in patients with type 2 diabetes.