Association of time in range with hemoglobin A1c, glycated albumin and 1,5-anhydro-d-glucitol.

AIMS/INTRODUCTION: Hemoglobin A1c (HbA1c), glycated albumin (GA) and 1,5-anhydro-d-glucitol (1,5-AG) are used as indicators of glycemic control, whereas continuous glucose monitoring (CGM) is used to assess daily glucose profiles. The aim of this study was to investigate the relationships between CGM metrics, such as time in range (TIR), and glycemic control indicators. MATERIALS AND METHODS: We carried out retrospective CGM and blood tests on 189 outpatients with impaired glucose tolerance (n = 22), type 1 diabetes mellitus (n = 67) or type 2 diabetes mellitus (n = 100). RESULTS: In type 1 diabetes mellitus and type 2 diabetes mellitus patients, HbA1c and GA were negatively correlated with TIR, whereas 1,5-AG was positively correlated with TIR. In type 1 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5-AG of 6.9% (95% confidence interval [CI] 6.5-7.2%), 20.3% (95% CI 19.0-21.7%) and 6.0 µg/mL (95% CI 5.1-6.9 µg/mL), respectively. In type 2 diabetes mellitus patients, a TIR of 70% corresponded to HbA1c, GA and 1,5-AG of 7.1% (95% CI 7.0-7.3%), 19.3% (95% CI 18.7-19.9%) and 10.0 µg/mL (95% CI 9.0-11.0 µg/mL), respectively. TIR values corresponding to HbA1c levels of 7.0% were 56.1% (95% CI 52.3-59.8%) and 74.2% (95% CI 71.3-77.2%) in type 1 diabetes mellitus and type 2 diabetes mellitus patients, respectively. CONCLUSIONS: The results of this study showed that the estimated HbA1c corresponding to a TIR of 70% was approximately 7.0% for both type 1 diabetes mellitus and type 2 diabetes mellitus patients, and that the estimated 1,5-AG calculated from the TIR of 70% might be different between type 1 diabetes mellitus and type 2 diabetes mellitus patients.

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus.

Cardiovascular (CV) complications are an essential causal element of prospect in diabetes mellitus (DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine (ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM (T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin (U-Alb), mean intimal-medial thickness (IMT) and ankle brachial index (ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA (standardized ß = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.

Hepatocyte growth factor, a biomarker of macroangiopathy in diabetes mellitus.

Atherosclerotic involvements are an essential causal element of prospect in diabetes mellitus (DM), with carotid atherosclerosis (CA) being a common risk-factor for prospective crisis of coronary artery diseases (CAD) and/or cerebral infarction (CI) in DM subjects. From another point of view, several reports have supplied augmenting proof that hepatocyte growth factor (HGF) has a physiopathological part in DM involvements. HGF has been a mesenchymal-derived polyphenic factor which modulates development, motion, and morphosis of diverse cells, and has been regarded as a humor intermediator of epithelial-mesenchymal interplays. The serum concentrations of HGF have been elevated in subjects with CAD and CI, especially during the acute phase of both disturbances. In our study with 89 type 2 DM patients, the association between serum concentrations of HGF and risk-factors for macrovascular complications inclusive of CA were examined. The average of serum HGF levels in the subjects was more elevated than the reference interval. The serum HGF concentrations associated positively with both intimal-media thickness (IMT) (r = 0.24, P = 0.0248) and plaque score (r = 0.27, P = 0.0126), indicating a relationship between the elevated HGF concentrations and advancement of CA involvements. Multivariate statistical analysis accentuated that serum concentrations of HGF would be associated independently with IMT (standardized = 0.28, P = 0.0499). The review indicates what is presently known regarding serum HGF might be a new and meaningful biomarker of macroangiopathy in DM subjects.

Profile of saxagliptin in the treatment of type 2 diabetes: focus on Japanese patients.

Saxagliptin is a selective and potent dipeptidyl peptidase (DPP)-4 inhibitor, approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus (T2DM) in the USA on July 2009, and had been launched globally in over 86 countries by September 2013. In patients with T2DM, once-daily administration of saxagliptin before breakfast achieves sustained inhibition of plasma DPP-4 activity and reduction of postprandial hyperglycemia, including after dinner, associated with an increase in plasma glucagon-like peptide-1 levels. This paper reviews the safety and efficacy of saxagliptin in Japanese patients with T2DM. The clinical development study in Japan supported its usefulness for the disease. Saxagliptin 1, 2.5, and 5 mg led to significant improvements in glycated hemoglobin (HbA1c), and was generally well tolerated. Treatment with saxagliptin 5 mg induced a sustained reduction in HbA1c over 52 weeks. Long-term combination therapy with saxagliptin and other oral hypoglycemic agents also provided sustained glycemic control and was well tolerated for up to 52 weeks. Saxagliptin as add-on to sulfonylureas or glinides has a tendency to increase hypoglycemia, but not with other oral antidiabetic agents, such as α-glucosidase inhibitors, metformin, or thiazolidinediones. The results of clinical trials have confirmed the long-term efficacy and safety of saxagliptin monotherapy as well as its use as add-on combination therapy, and support its usefulness as a therapeutic agent for T2DM. Saxagliptin has less concern for hypoglycemia and weight gain, which often becomes problematic in routine care of T2DM. Meta-analysis of clinical trials in the USA showed no evidence of increased risk of cardiovascular events associated with saxagliptin, suggesting the superior of saxagliptin in terms of safety. Recently, investigators in the SAVOR-TIMI (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction) 53 study suggested that DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, although the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. Saxagliptin is applicable for various pathological conditions, and is considered to be clinically significant as a new therapeutic option for Japanese patients with T2DM.