The Serum Creatinine Level Might Be Associated with the Onset of Impaired Fasting Glucose: A Community-based Longitudinal Cohort Health Checkup Study.

Objective Skeletal muscle is the main target organ for glycemic control, and the serum creatinine level is a convenient indicator of the skeletal muscle mass. This study aimed to assess the potential relationship between the serum creatinine level and the onset of impaired fasting glucose (IFG). Methods In this large, community-based, retrospective longitudinal cohort study, we examined the records of 7,905 Japanese participants (3,863 men, 4,042 women) of 18-80 years of age who underwent annual health checkups at a single center between April 2003 and August 2013. After applying the exclusion criteria, 6,490 participants were reviewed to identify those with the onset of IFG, defined as a fasting plasma glucose ≥6.11 mM. Among the participants, 278 met the criterion for the onset of IFG during the observation period. Results Creatinine levels were higher in male subjects who exercised periodically and were exercise conscious in comparison to those who did not exercise, and were higher in female subjects who exercised periodically in comparison to female subjects who did not exercise and who were not exercise conscious. Additionally, the serum creatinine level was negatively associated with the onset of IFG in both men [adjusted hazard ratio, 0.98; 95% confidence interval (CI), 0.96-0.99; p=0.008] and women (adjusted hazard ratio, 0.94; 95% CI, 0.91-0.97; p<0.001) after adjustment for variables previously reported to be risk factors for the onset of glucose intolerance and factors associated with chronic kidney disease. Conclusion A low creatinine level might be associated with the onset of IFG. Moreover, the fact that serum creatinine levels increase with exercise might demonstrate the importance of exercise therapy.

A male patient with ferroportin disease B and a female patient with iron overload similar to ferroportin disease B.

Reticuloendothelial iron overload is associated with secondary hemochromatosis including repeated transfusions and iron over-supplementation. Ferroportin disease B is a severe subtype of hereditary iron overload syndrome with an activated reticuloendothelial system. The iron exporter ferroportin may be insensitive to hepcidin 25 in this subtype. However, the interactions between the hepcidin-ferroportin system and modifiers of reticuloendothelial iron overload have not yet been elucidated. We describe two patients with iron overload conditions that were compatible with ferroportin disease B, but their genetic backgrounds and habitual states differed. Both patients had diabetes, periportal fibrosis with severe iron deposits in their hepatocytes and Kupffer cells, and adequate levels of circulating hepcidin 25. However, the first patient was heterozygous for a mutation in the FP gene and free from the acquired factors of iron overload, while the second patient was a heavy drinker with a heterozygous mutation in the TFR2 gene and no mutations in the FP gene. The first patient was the second reported case of ferroportin disease B in Japan. Our study on these 2 patients suggests that liver fibrosis associated with compound iron overload of reticuloendothelial cells and hepatocytes may occur via multi-etiological backgrounds.