Independent risk factors of rapid glomerular filtration rate decline in patients with type 2 diabetes with preserved kidney function and normoalbuminuria: A multicenter cohort study.

AIMS/INTRODUCTION: Research on the incidence and underlying mechanisms of rapid renal function decline in patients with type 2 diabetes mellitus with preserved renal function and normoalbuminuria is limited. This study aimed to investigate the involvement of hemoglobin level as a risk factor for rapid decliners among patients with type 2 diabetes with preserved renal function and normoalbuminuria. MATERIALS AND METHODS: This was a retrospective observational study of 242 patients with type 2 diabetes with a baseline estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 and normoalbuminuria (<30 mg/gCr), followed up for >1 year. The annual rate of estimated glomerular filtration rate decline during the follow-up period was calculated using least square regression analysis; rapid decliners defined at ≥3.3%/year. Risk factors associated with rapid decliners were identified using a logistic regression analysis of variables previously identified as risk factors of rapid decliners. RESULTS: The median follow-up period was 6.7 years, and 34 patients showed rapid decliners. On multivariate analysis, lower baseline hemoglobin level was a risk factor of rapid decliners (odds ratio 0.69, 95% confidence interval 0.47-0.99; P = 0.045). Furthermore, the baseline hemoglobin levels were correlated positively with iron and ferritin levels, implying that an impaired iron metabolism might cause lower hemoglobin levels in rapid decliners. CONCLUSIONS: In patients with type 2 diabetes with preserved renal function and normoalbuminuria, lower hemoglobin levels were a risk factor for rapid decliners, where disturbed iron metabolism might precede the development of diabetic kidney disease.

Urinary afamin levels are associated with the progression of diabetic nephropathy.

AIMS: In this study, we applied quantitative proteomic analysis to identify urinary proteins associated with diabetic nephropathy (DN). METHODS: Two-dimensional image-converted analysis of liquid chromatography and mass spectrometry detected the proteins differentially excreted between normoalbuminuric and macroalbuminuric patients with type 2 diabetes mellitus (T2DM) (n = 6 each). Urinary levels of excreted proteins were measured by multiple reaction monitoring (MRM) analysis using an independent sample set (n = 77). Urinary afamin levels were measured by ELISA in T2DM and DN patients enrolled in this cohort study (n = 203). RESULTS: One-hundred-four proteins displayed significant alterations in excretion. Nine of these candidates were validated by MRM analysis. Among them, the levels of afamin, CD44 antigen, and lysosome-associated membrane glycoprotein 2, which have not previously been implicated in DN, were significantly associated with both the urinary albumin to creatinine ratio (ACR) and eGFR. We further measured afamin levels in urine collected from T2DM patients who did not yet have significant kidney disease (ACR < 300 mg/g or eGFR change rate ≤ 3.3%/year). The urinary afamin to creatinine ratio (Afa/Cre) was significantly higher in patients who progressed to a more severe DN stage or had early renal decline than in patients who did not. CONCLUSIONS: Afa/Cre was significantly increased in T2DM patients who subsequently developed DN. Afa/Cre may be useful to predict patients with T2DM at high risk of nephropathy before the development of macroalbuminuria or reduced kidney function, although further validation studies in a larger population are needed.

Two distinct serotonin receptors co-mediate non-photic signals to the circadian clock.

Several lines of evidence indicate that serotonin type 7 (5-HT7) receptors play a critical role for non-photic resetting of the mammalian circadian clock; however, the contributions of other types of 5-HT receptors to non-photic entrainment are not yet clarified. The present study demonstrates that MKC-242, a selective 5-HT1A receptor agonist, can evoke a non-photic-like phase-response in hamsters in vivo. This phase-shifting response to MKC-242 was antagonized not only by the selective 5-HT1A receptor blocker WAY100635 but also by the selective 5-HT7 receptor blocker DR4004. These suggest that synchronous activation of 5-HT1A and 5-HT7 receptors mediates non-photic signals to the hamster circadian clock.

Effects of Saireito on the ovarian function of patients with polycystic ovary syndrome.

PURPOSES: It is sometimes difficult to restore a regular ovulatory cycle in women with polycystic ovary syndrome (PCOS) using classic agents such as clomiphene citrate or gonadotropins. Saireito, a herbal medicine, is believed to have an effect similar to corticosteroids. We examined the effect of Saireito on ovulatory induction and endocrine status in women with PCOS. METHODS: Twenty-four women with PCOS were treated with Saireito for 3 months. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), testosterone (T), estradiol (E2), adrenocorticotropic hormone (ACTH), and cortisol were measured before and after treatment, and ovulation was assessed. We compared serum LH levels between ovulation (n = 21) and anovulation (n = 3) groups, and compared ovulation rate and serum LH levels between obese (n = 6) and nonobese (n = 18) groups. RESULTS: Ovulation was restored in 21 (87.5%) of the 24 PCOS patients following administration of Saireito for 3 months. LH levels were significantly decreased 1 month after medication in ovulatory group (P < 0.001), but only slightly decreased in anovulatory group. Ovulation rate in the nonobese group (94.4%) was higher than in the obese group (66.7%). Serum LH levels were significantly reduced in the nonobese group, but only slightly reduced in the obese group. CONCLUSIONS: Saireito reduced serum LH levels and increased ovulatory rate, particularly in nonobese women.