Blood glucose variability is known to be associated with increased risk of long-term complications. Reliable indices for predicting hyperglycaemic and hypoglycaemic fluctuations are therefore needed. Glycaemic standard deviation (SD) obtained by continuous glucose monitoring correlates closely with nine previously described glycaemic variability formulas. Here, new indices predictive of glycaemic variability were developed, which can be calculated from laboratory measures based on a single blood draw. The indices included the glycated albumin (GA) to HbA1c ratio (GA/A1c ratio) and the fasting C-peptide immunoreactivity (FCPR) to fasting plasma glucose (FPG) ratio (FCPR index). Predictive values of these indices were assessed in 100 adults with diabetes. GA/A1c ratio and FCPR index showed close associations with glycaemic SD in addition to the nine existing glucose variability formulas. Subjects with a GA/A1c ratio ≥2.8 and FCPR index <3.0 showed the greatest SD and longest durations of hypoglycaemia, while those with a GA/A1c ratio <2.8 and FCPR index ≥3.0 had smaller SDs and little sign of hypoglycaemia. In adults with diabetes, a high GA/A1c ratio and low FCPR index value reflect higher glycaemic excursions, irrespective of diabetes type. Simultaneous measurements of GA, HbA1c, FPG and FCPR may help to identify a group of patients who warrant closer monitoring in relation to glycaemic variability and hypoglycaemia.

α2-Macroglobulin is a highly abundant serum protein involved in the development of atherosclerosis and cardiac hypertrophy. However, its circulating molecular form and exact concentrations in human health/diseases are not known. Blue native-polyacrylamide gel electrophoresis of human serum was used to confirm the native conformation of α2-macroglobulin. We created an enzyme-linked immunosorbent assay suitable for quantifying its circulating molecular form and undertook a cross-sectional study to measure its serum levels in 248 patients with diabetes mellitus and 59 healthy volunteers. The predominant circulating molecular form of α2-macroglobulin was the tetramer, whereas its dimer was detectable in patients with high serum levels of α2-macroglobulin. The serum α2-macroglobulin concentration was not associated with glycated hemoglobin or any other glycemic variable as evaluated from 48-h continuous glucose monitoring, but showed close correlation with left ventricular posterior wall thickness, carotid artery intima-media thickness, urinary albumin:creatinine ratio (ACR) and brachial–ankle pulse wave velocity (baPWV). Multivariate analysis revealed only the ACR and baPWV to be independent variables influencing serum levels of α2-macroglobulin. Thus, an increased ACR and baPWV are associated with higher serum concentrations of α2-macroglobulin, and the latter may contribute to the mechanism by which albuminuria increases the risk of developing cardiovascular diseases.

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The distraction rate of 0.5 mm/day produces good osteogenesis in small rodents; however, the effects of this distraction rate on muscle are not well documented. We evaluated the soleus and the extensor digitorum longus (EDL) after two weeks of lengthening distraction osteogenesis (DO) at 0.5 mm/day in skeletally mature rats. We found a modest but significant local increase of insulin like growth factor-1 (IGF-1) in the EDL, however, muscle growth indicated by developmental forms of myosin heavy chain (MHC) was not detected by mRNA (RT-PCR). To the contrary, the data suggested a decrease in cross-sectional area of the muscle fibers as well as a decrease in mRNA for slow MHC. Immunolabeling of fibronectin in cryosections of the EDL indicated fibrosis of the perimuscular connective tissue while assessment of the passive joint motion did not suggest a lack of excursion on the part of the dorsal flexors. While the literature suggests that IGF-I facilitates muscle growth especially in young animals, excess of IGF-I in muscle from adults may exacerbate DO-induced fibrosis.

Despite the high-risk of asymptomatic hypoglycemia associated with hemodialysis (HD) using glucose-free dialysate, presence of dialysate glucose is believed to prevent intradialytic hypoglycemia. However, exact glycemic fluctuation profiles and frequency of asymptomatic hypoglycemia during HD remain unappreciated. Using continuous glucose monitoring, we evaluated glycemic excursions in 63 type 2 diabetic HD patients (44 male, HbA1c 6.4±1.2%) treated with a dialysate containing either 100, 125 or 150 mg/dL glucose. Average sensor glucose level (SGL) at start of HD after 7.2±5.0 U bolus insulin and breakfast was 187.9±56.2 mg/dL. SGL showed gradual and sustained decrease during HD irrespective of the dialysate glucose levels (Figure). SGL nadir reached below the dialysate glucose levels in 23 of 37 patients treated with dialysate containing 100 mg/dL glucose, in 14 of 17 patients with 125 mg/dL and in all 9 patients with 150 mg/dL. Fourteen of all 63 patients (22%) presented with HD-related hypoglycemia as defined by SGL &lt;63 mg/dL during HD or immediately after HD up until the next meal. All hypoglycemic episodes revealed asymptomatic. In conclusion, type 2 diabetic HD patients present a high-risk of HD-related hypoglycemia unawareness despite the use of dialysate containing 100-150 mg/dL glucose. SGL may fall well below the dialysate glucose level toward the end of HD. Disclosure A. Hayashi: None. A. Momozono: None. S. Kawai: None. T. Masaki: None. S. Yoshino: None. A. Ogawa: None. K. Takano: None. M. Shichiri: None.