Optimal home SBP targets for preventing the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

OBJECTIVES: Home blood pressure control can reduce the risk of increased urinary albumin excretion in patients with diabetes mellitus. However, the optimal home blood pressure targets to prevent the onset or progression of diabetic nephropathy are not well defined. METHODS: We performed a retrospective cohort study of 851 patients with type 2 diabetes mellitus. Logistic regression models were used to evaluate the correlations of home SBP levels with progression of diabetic nephropathy. RESULTS: During the follow-up of 2 years, 86 patients had progression of diabetic nephropathy. Adjusted odds ratios (95% confidence interval) for progression of diabetic nephropathy in patients with morning SBP of 120-129  mmHg [2.725 (1.074-6.917), P = 0.035], 130-139  mmHg [3.703 (1.519-9.031), P = 0.004] and in those with morning SBP equal or more than 140  mmHg [2.994 (1.182-7.581), P = 0.021] were significantly higher than that in those with morning SBP less than 120  mmHg in multiple logistic analyses. CONCLUSION: The preferable morning SBP targets might be less than 120  mmHg for preventing the onset or progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

Maximum home systolic blood pressure is a useful indicator of arterial stiffness in patients with type 2 diabetes mellitus: post hoc analysis of a cross-sectional multicenter study.

AIMS: Maximum (max) home systolic blood pressure (HSBP) as well as mean HSBP or HSBP variability was reported to increase the predictive value of target organ damage. Yet, the association between max HSBP and target organ damage in patients with type 2 diabetes has never been reported. The aim of this study was to investigate the association between max HSBP and pulse wave velocity (PWV), a marker of arterial stiffness which in turn is a marker of target organ damage, in patients with type 2 diabetes. METHODS: We assessed the relationship of mean HSBP or max HSBP to PWV, and compared area under the receiver-operating characteristic curve (AUC) of mean HSBP or max HSBP for arterial stiffness in 758 patients with type 2 diabetes. RESULTS: In the univariate analyses, age, duration of diabetes mellitus, body mass index, mean clinic systolic blood pressure (SBP), mean HSBP and max HSBP were associated with PWV. Multivariate linear regression analyses indicated that mean morning SBP (ß=0.156, P=0.001) or max morning SBP (ß=0.146, P=0.001) were significantly associated with PWV. AUC (95% CI) for arterial stiffness, defined as PWV equal to or more than 1800 cm per second, in mean morning SBP and max morning SBP were 0.622 (0.582-0.662; P<0.001) and 0.631 (0.591-0.670; P<0.001), respectively. CONCLUSIONS: Our findings implicate that max HSBP as well as mean HSBP was significantly associated with arterial stiffness in patients with type 2 diabetes.

Five-item version of the international index of erectile function correlated with albuminuria and subclinical atherosclerosis in men with type 2 diabetes.

AIM: There is increasing evidence of a strong link between erectile dysfunction and atherosclerosis. The aim of this study was to evaluate the relationships between the 5-item version of the International Index of Erectile Function (IIEF-5) score and albuminuria as well as markers of subclinical atherosclerosis in men with type 2 diabetes. METHODS: We evaluated the relationship of the IIEF-5 score with the degree of urinary albumin excretion, pulse wave velocity, ankle-brachial index or toe-brachial index (n = 125) as well as with major cardiovascular risk factors, including age, blood pressure, serum lipid concentration and hemoglobin A1c, body mass index, severity of diabetic retinopathy or nephropathy, and presence of neuropathy or cardiovascular disease in 197 men with type 2 diabetes. RESULTS: The mean IIEF-5 score was 10.0 ± 6.9. The IIEF-5 score was inversely correlated with age or duration of diabetes, and positively correlated with diastolic blood pressure or serum total cholesterol concentration. The IIEF-5 score inversely correlated with log (urinary albumin excretion; r =-0.190, p =0.0078) or pulse wave velocity (r =-0.255, p =0.0003), and positively correlated with the toe-brachial index (r = 0.379, p < 0.0001). The IIEF-5 score was lower in patients with proliferative diabetic retinopathy than in patients with no diabetic retinopathy, and in patients with macroalbuminuria than in patients with normoalbuminuria. The IIEF-5 score was also lower in patients with neuropathy or cardiovascular disease than without. CONCLUSIONS: The IIEF-5 score correlated with diabetic micro- and macroangiopathy in men with type 2 diabetes.

Uncontrolled home blood pressure in the morning is associated with nephropathy in Japanese type 2 diabetes.

The purposes of this study were to investigate the state of blood pressure control level and to investigate the relationship between blood pressure control level and nephropathy in Japanese type 2 diabetes. We measured clinic and home blood pressure in 923 type 2 diabetic patients. According to the criteria for hypertension in the Japanese Society of Hypertension Guidelines 2009, patients were classified into four groups by clinic systolic blood pressure (130 mmHg) and morning systolic blood pressure (125 mmHg), as follows: controlled hypertension (CH), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH). Of all patients, 13.9, 12.6, 13.3, and 60.2% were identified as having CH, WCH, MH, and SH, respectively. The average number of drugs prescribed was 1.8. We assessed the association between blood pressure control level and nephropathy in diabetic patients. The degree of urinary albumin excretion and the prevalence of nephropathy in diabetic patients were higher in MH and SH groups than those in the CH group. The majority of patients had poor blood pressure control, regardless of ongoing conventional antihypertensive therapy, and diabetic patients with MH and SH were associated with nephropathy. It is suggested that more aggressive antihypertensive treatment is recommended to prevent nephropathy in diabetic patients.

Association between serum testosterone concentration and collagen degradation fragments in men with type 2 diabetes mellitus.

The aim of the present study was to evaluate relationships between serum endogenous androgens and urinary concentration of cross-linked N-telopeptides of type I collagen (NTx), a bone resorption marker, in men with type 2 diabetes mellitus because low androgen concentrations are associated with both osteoporosis and cardiovascular disease. Relationships between serum free testosterone and urinary NTx concentrations were investigated in 246 consecutive men with type 2 diabetes mellitus. In addition, relationships between urinary NTx concentration and other variables including age, duration of diabetes, blood pressure, serum lipid concentration, hemoglobin A(1c), and body mass index were evaluated. Urinary NTx concentrations were 27.8 (26.4-29.3) nmol of bone collagen equivalent per millimole of creatinine, correlating inversely with serum free testosterone (r = -0.263, P < .0001). Multiple regression analysis identified serum free testosterone (beta = -.292, P < .0001), hemoglobin A(1c) (beta = .144, P = .0404), and smoking status (beta = .143, P = .0402) as independent determinants of urinary NTx. In conclusion, serum free testosterone concentration correlated inversely with urinary NTx concentration, which may partly account for an observed link between osteoporosis and cardiovascular disease in men with type 2 diabetes mellitus.

Integrin-linked kinase acts as a pro-survival factor against high glucose-associated osmotic stress in human mesangial cells.

BACKGROUND: Integrin-linked kinase (ILK) is a protein that plays an important role in extracellular matrix-mediated signalling. Recent studies implicated ILK dysregulation in the development of diabetic nephropathy. However, little is known about the significance of ILK up-regulation in response to high glucose in mesangial cells. METHODS: The ILK messenger (m)RNA and protein expression in human mesangial cells were analysed with quantitative real-time polymerase chain reaction (PCR) and western blotting after exposure to either 100, 200, or 500 mg/dl glucose, or 100 mg/dl glucose + 400 mg/dl mannitol. Activation of protein Kinase B (PKB)/Akt was also determined by western blot analysis. Cells were transfected with ILK siRNA to determine the effects of ILK knockdown on PKB/Akt activation and cell death following treatment with high glucose or mannitol. RESULTS: High concentrations of glucose or mannitol for three days significantly up-regulated ILK mRNA and protein expression (P < 0.05 vs 100 mg/dl glucose). In contrast, ILK expression in cells exposed to the same conditions for seven days was unaffected. The time course of PKB/Akt phosphorylation was similar to that of ILK protein expression. The siRNA-mediated down-regulation of ILK expression inhibited the elevation of PKB/Akt phosphorylation induced by high glucose treatment. Furthermore, the inhibition of ILK expression promoted high glucose- or mannitol-induced apoptosis. CONCLUSION: The ILK may act as a pro-survival factor and play a role in protecting mesangial cells from hyperglycaemic osmotic stress.

Efficacy of glimepiride in patients with poorly controlled insulin-treated type 2 diabetes mellitus.

We retrospectively investigated the effects of adding glimepiride in patients with type 2 diabetes showing suboptimal control by insulin therapy. Of 63 patients with poorly controlled insulin-treated type 2 diabetes (baseline HbA1c, 8.4 +/- 0.6%), 32 were treated with insulin alone and 31 were given glimepiride in addition to insulin. HbA1c values, daily insulin dose, body weight, blood pressure, plasma lipid concentrations, and the number of hypoglycemic events were recorded at weeks 0, 12, 24, 36, 48, 60, and 72. HbA1c decreased by 1.1%, from 8.5 +/- 0.6% to 7.4 +/- 0.8% (P<0.0001) in patients treated with insulin plus glimepiride at 12 weeks, and improved glycemic control continued throughout the study. Required insulin dose was reduced significantly in patients treated with insulin plus glimepiride (from 29.4 +/- 14.5 to 22.3 +/- 12.1 units/day, P = 0.0187). Body weight increased significantly in patients treated with insulin plus glimepiride (from 57.0 +/- 8.7 to 59.5 +/- 9.2 kg, P = 0.0232). Adding glimepiride showed little effect on blood pressure, plasma total cholesterol, triglyceride, or HDL-cholesterol. Serum C peptide concentrations increased significantly in patients treated with insulin plus glimepiride (from 1.01 +/- 0.71 to 1.28 +/- 0.65 ng/ml, P = 0.0367). The number of hypoglycemic events did not differ between groups. Adding glimepiride to insulin therapy resulted in sustained improvement of glycemic control in patients with poorly controlled type 2 diabetes.

Idiopathic sudden hearing loss in patients with type 2 diabetes.

The aim of the present study was to identify clinical and audiologic characteristics of idiopathic sudden hearing loss (ISHL) in patients with type 2 diabetes. We retrospectively investigated 148 cases of ISHL, whose age was more than 40 years, comparing clinical and audiologic valuables between diabetic and non-diabetic patients. Twenty-four patients (16.2%) had type 2 diabetes (16 male, 8 female). Prevalence of hypertension and hyperlipidemia were significantly greater in diabetic patients. Hearing in the affected ear was more impaired in diabetic than non-diabetic patients, although hearing in the unaffected ear and degree of recovery did not differ significantly. Mean BMI, duration of diabetes, HbA1c values, and ultrasonographically determined carotid intima-media thickness (IMT) and plaque scores in diabetic patients with ISHL were 24.0+/-3.7 kg/m(2), 9.8+/-7.8 years, 7.8+/-1.5%, 0.83+/-0.16 mm, and 3.8+/-2.8, respectively. Of 17 diabetic patients whose ISHL was treated with steroids, 12 required insulin for glycemic control during treatment. Compared with diabetic patients without ISHL, HbA1c value was significantly higher in diabetic patients with ISHL (7.2+/-1.2% versus 7.8+/-1.5%, P=0.0202). In conclusion, nearly 16% of our patients with ISHL had type 2 diabetes, and this subgroup was associated with more severe hearing loss. Further studies are needed to determine which subgroups of diabetic patients are most likely to develop ISHL, which patients are predisposed to more severe hearing loss, and how various factors and treatments influence outcome.