Efficacy of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the activity of the advanced glycation end product (AGE) - receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes.

BACKGROUND: To examine the effects of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose parameters, the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes patients. METHODS: Sixty-one patients whose HbAlc ≥ 6.1% (mean age 64.7 years; 67% men; mean HbAlc 7.4%; 57% were pharmacologically treated) underwent blood and urine sampling and analysis before and after 12 weeks of treatment with alogliptin (25 mg once daily). RESULTS: Alogliptin treatment significantly reduced fasting glucose (160.3 mg/dL at baseline versus 138.0 mg/dL at 12 weeks), glycoalbumin (21.1% at baseline versus 18.9% at 12 weeks), HbAlc (7.4% at baseline versus 6.9% at 12 weeks), circulating soluble form of RAGE concentrations (847.3 pg/mL at baseline versus 791.4 pg/mL at 12 weeks) and urine albumin to creatinine ratio (31.6 mg/g Cr at baseline versus 26.5 mg/g Cr at 12 weeks), whereas 1,5-anhydroglucitol concentrations were significantly increased (7.5 µg/mL at baseline versus 11.6 µg/mL at 12 weeks; all P < 0.05). Circulating AGEs concentrations were reduced only in patients with baseline AGEs ≥7 U/mL (n = 33, from 8.2 U/mL to 7.2U /mL; p < 0.01) after alogliptin treatment. The treatment-induced change of soluble form of sRAGE concentrations was associated with changes of 1,5-anhydroglucitol and HbAlc concentrations (rho = -0.32 and 0.29, respectively). Meanwhile, the treatment-induced change of urine albumin to creatinine ratio was associated with a change in the fasting glucose concentration (rho = 0.25; all p < 0.05). During the intervention, alogliptin treatment was well tolerated without any hypoglycemia or side effects. CONCLUSION: Alogliptin treatment improved the AGE-RAGE axis and reduced albuminuria in Japanese type 2 diabetes patients.

Association of cognitive dysfunction with cardiovascular disease events in elderly hypertensive patients.

OBJECTIVES: This study assesses whether presence of cognitive dysfunction can be a marker associated with the development of cardiovascular disease (CVD) events independent of ambulatory blood pressure (BP) or other indices of target organ damage (TOD) in elderly hypertensive patients. METHODS: We recruited 585 hypertensive patients (mean age, 73 years; 41% men) who were ambulatory, lived independently, and were without clinically overt dementia. Cognitive function was assessed by Mini-Mental State Examination (MMSE) at baseline, and CVD events (coronary artery disease, stroke, congestive heart failure, and sudden death) were prospectively ascertained. Cognitive dysfunction was defined as the lowest quartile of MMSE scores (n = 183, median 24 points). RESULTS: CVD events occurred in 42 people over an average of 2.8 years (1644 person-years). The prevalence of cognitive dysfunction was higher in patients with CVD events than those without (57 vs. 29%; both P <0.001) at baseline. Cognitive dysfunction was associated with CVD events, after adjustment for nocturnal SBP and evidence of TOD [i.e. albuminuria, cardiac hypertrophy, and carotid-artery intima-media thickness (IMT)], hazard ratio 2.5-2.9 (all P <0.01). Incorporation of MMSE in the risk model (including age, estimated glomerular filtration rate, and preexisting CVD) improved the C-statistics (from 0.691 to 0.741) and resulted in a net reclassification improvement of 17.6% (P = 0.02). In contrast, incorporation of albuminuria, cardiac hypertrophy, and high carotid-artery IMT added little further improvement in the risk prediction. CONCLUSION: Cognitive dysfunction is an independent marker associated with increased risk of CVD events in elderly hypertensive patients.

Nighttime blood pressure, nighttime glucose values, and target-organ damages in treated type 2 diabetes patients.

OBJECTIVE: The associations between nighttime blood pressure (BP) and cardiovascular risk are well established. However, the associations between nighttime glucose values, including nocturnal hypoglycemia, and cardiovascular risk in diabetes remain unclear. METHODS: In this cross-sectional study of 49 treated type 2 diabetes patients (mean, 67.3 years; 61.0% men; mean treatment duration, 9.4 years), we performed 24-h continuous glucose monitoring simultaneously with BP monitoring, and evaluated several target-organ damages (echocardiographic left ventricular mass index [LVMI], urinary albumin excretion [UAE], carotid-artery intima-media thickness [IMT], and brachial-ankle pulse wave velocity [baPWV]). RESULTS: Nighttime average systolic BP values were independently associated with the extent of LVMI, log-transformed UAE, or baPWV (all P < 0.05). In contrast, nighttime average glucose values, rather than daytime glucose values or glucose variability, were independently associated with the extent of common carotid-artery IMT (CCA-IMT) or baPWV (all P < 0.05). We divided the study participants into 3 groups according to the nighttime glucose values (a group with nighttime average glucose values <161 mg/dl [reference], a group with nocturnal hypoglycemia [<70 mg/dl at least one point during sleep], and a group with nighttime average glucose values ≥161 mg/dl), and compared the extent of target-organ damages among them. Patients with nighttime average glucose values ≥161 mg/dl, but not those with nocturnal hypoglycemia, had the highest values of CCA-IMT or baPWV among the 3 groups, and the differences remained significant even after adjustment for covariates (both trend P < 0.05 by ANCOVA). CONCLUSIONS: Among treated type 2 diabetes, high nighttime BP and/or glucose values were associated with a high degree of cardiovascular remodeling.