Association between chronic kidney disease and the cognitive function in subjects without overt dementia
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AIM: The association between cognitive function and clinical parameters of chronic kidney disease (CKD) was investigated in Japanese patients without overt dementia in a cross-sectional study. MATERIALS AND METHODS: A population of 497 patients whose cognitive function had been examined using the mini-mental state examination (MMSE) were screened for this study. After the exclusion of 306 subjects who showed overt dementia, the association between the MMSE score and clinical characteristics was investigated in 191 subjects (male: 55%, age: 69 ± 12 years). RESULTS: The mean MMSE score of the study subjects was 26.7 ± 2.0. The MMSE score was negatively correlated with the patients' age and positively with the estimated glomerular filtration rate. It was significantly associated with age and proteinuria based on a multivariate analysis. The scores of "temporal orientation", "attention and calculation", and "remote memory" subitems of MMSE were significantly lower in the subjects ≥ 70 years of age than in those < 70 years of age. The scores of "temporal orientation" (4.3 ± 0.8 vs. 4.7 ± 0.6), "attention and calculation" (2.9 ± 1.6 vs. 3.9 ± 1.5), and "stage command" (2.7 ± 0.5 vs. 2.9 ± 0.3) were significantly lower in the subjects with proteinuria than in those without. CONCLUSION: Cognitive function was disturbed even in CKD patients without overt dementia. Intervention in patients with risk factors is deemed important for preventing future reductions in cognitive and renal functions in CKD patients without dementia.
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Current Metabolic Status Affects Urinary Liver-Type Fatty-Acid Binding Protein in Normoalbuminuric Patients With Type 2 Diabetes.

BACKGROUND: We aimed to study the association between urinary liver-type fatty acid-binding protein (L-FABP), a biomarker of tubulointerstitial injury, and the clinical characteristics of normoalbuminuric and albuminuric patients with type 2 diabetes in order to detect the factors affecting urinary L-FABP. METHODS: Urinary L-FABP levels were measured in 788 patients with type 2 diabetes and again in 666 patients at 6 months after the initial measurement. The association between the urinary L-FABP level and the clinical parameters was investigated in a retrospective cross-sectional study and a subsequent observation. RESULTS: The HbA1c (odds ratio (OR): 1.42; 95% confidence interval (CI): 1.11 - 1.79; P < 0.01), systolic blood pressure (OR: 1.03; 95% CI: 1.01 - 1.05; P < 0.01) levels and estimated glomerular filtration rate (OR: 0.98; 95% CI: 0.96 - 1.00; P = 0.01) were significantly associated with the high levels of urinary L-FABP (> 8.4 µg/gCr) in normoalbuminuric patients. However, a logistic regression analysis revealed that use of renin-angiotensin system (RAS) inhibitors (OR: 2.22; 95% CI: 1.16 - 4.89; P = 0.02), urinary albumin-to-creatinine ratio (ACR) (OR: 1.01; 95% CI: 1.00 - 1.01; P < 0.01) and serum HDL-cholesterol concentration (OR: 0.33; 95% CI: 0.11 - 0.89; P = 0.03) were significantly associated in albuminuric patients. In the follow-up observation, the change in urinary L-FABP was found to be significantly (P < 0.01) influenced by the change in the HbA1c level in both the normoalbuminuric and albuminuric patients. CONCLUSIONS: High urinary L-FABP is associated with part of the current metabolic abnormalities, including high levels of HbA1c and systolic blood pressure among normoalbuminuric patients with type 2 diabetes.

Relationships between the duration of illness and the current status of diabetes in elderly patients with type 2 diabetes mellitus.

AIMS: The aim of the present study was to clarify the relationships between the duration of diabetes and the current statuses of diabetes in elderly (aged ≥65 years) patients with type 2 diabetes. METHODS: Clinical characteristics were cross-sectionally examined in 1436 patients (684 elderly and 752 non-elderly) with type 2 diabetes. RESULTS: As the duration of diabetes increased, the patients' age, frequency of receiving insulin therapy and glycated hemoglobin value increased in both the elderly and non-elderly groups, whereas the urinary C-peptide immunoreactivity and glomerular filtration rate decreased. The duration of diabetes (years) was significantly associated with the prevalence of diabetic retinopathy (OR 1.05, 95% CI 1.03-1.07, P < 0.01), nephropathy (OR 1.03, 95% CI 1.01-1.05, P < 0.01) and neuropathy (OR 1.08, 95% CI 1.05-1.12, P < 0.01), but not with cerebrovascular disease (OR 1.01, 95% CI 0.99-1.03, P = 0.38), coronary heart disease (OR 1.02, 95% CI 1.00-1.04, P = 0.09) or peripheral artery disease (OR 1.02, 95%CI 0.99-1.05, P = 0.12) in the elderly patients after adjusting for the traditional risk factors of diabetic angiopathies. In contrast, the duration of diabetes showed a significant association with the prevalence of both diabetic micro- and macroangiopathies in the non-elderly patients. CONCLUSIONS: It should be noted that atherosclerotic diseases are present in the clinical setting for the management of elderly diabetic patients independent of the duration of diabetes. Geriatr Gerontol Int 2017; 17: 24-30.

Comparison of the Renoprotective Effect of Febuxostat for the Treatment of Hyperuricemia between Patients with and without Type 2 Diabetes Mellitus: A Retrospective Observational Study.

Objective The effects of febuxostat therapy on hyperuricemia in patients with and without type 2 diabetes were compared in this retrospective observational study after pair-matching using the propensity scores. Methods In total, 160 patients with hyperuricemia were studied as the treated set, and the 155 subjects in whom the administration of febuxostat was not discontinued during the observation period were investigated in the full analysis. The study subjects were divided into two groups based on the style of initiation of febuxostat: initial and switching therapy from allopurinol administration. Results The reduction in the serum uric acid (sUA) levels at six months after the initiation of febuxostat administration did not significantly differ between the patients with and without diabetes in both the initial (206±114 and 226±113 µmol/L in patients with and without diabetes, respectively) and switching (154±91 and 129±90 µmol/L in patients with and without diabetes, respectively) therapy groups. The eGFR values were significantly increased compared to the baseline levels only in the patients without diabetes. The changes in the eGFR values were significantly associated with the presence of diabetes and sUA at baseline in a multivariate analysis. The frequency of adverse events was not significantly different between the patients with and without diabetes. Conclusion Although febuxostat exerted a similar sUA-lowering effect against hyperuricemia in patients with type 2 diabetes compared to those without, the renoprotective effect was attenuated in those with diabetes compared to nondiabetic subjects.

Secular Trends in the Clinical Characteristics of Type 2 Diabetic Patients With Severe Hypoglycemia Between 2008 and 2013.

BACKGROUND: We investigated the trends in the clinical characteristics and prescriptions of type 2 diabetic patients with severe hypoglycemia because the prescription rate of antidiabetic agents has significantly changed recently. METHODS: A total of 193 patients with type 2 diabetes with severe hypoglycemia induced by antidiabetic agents between 2008 and 2013 were divided into three groups based on the period of visit: 2008 - 2009, 2010 - 2011 and 2012 - 2013. RESULTS: While the proportion of patients with severe hypoglycemia using insulin (from 55% to 74%), biguanides (from 6% to 20%), glinides, and dipeptidyl peptidase-4 inhibitors significantly increased, those using sulfonylureas (from 45% to 20%) significantly decreased. Errors of drug use significantly increased as a trigger of hypoglycemia in recent years. The number of antidiabetic agents (from 1.9 ± 0.6 to 2.3 ± 0.7), non-diabetic agents (from 2.3 ± 2.4 to 4.3 ± 3.3), and total drugs prescribed were significantly higher in recent years among patients receiving insulin therapy. CONCLUSIONS: Polypharmacy especially in patients receiving insulin therapy and errors of drug use have increased in type 2 diabetic patients with severe hypoglycemia in recent years. Intensive education in the usage rule of drugs is considered to be important in order to prevent severe hypoglycemia.

Flow Mediated Dilatation Is Reduced with the Progressive Stages of Glomerular Filtration Rate and Albuminuria in Type 2 Diabetic Patients without Coronary Heart Disease.

We aimed to clarify the usefulness of measuring the flow mediated dilatation (FMD) in patients with type 2 diabetes mellitus without and with coronary heart disease (CHD). The FMD was measured in 480 patients with type 2 diabetes and in 240 nondiabetic subjects. The FMD was significantly lower in the subjects with CHD (n = 145, 5.4 ± 3.2%) than in those without CHD (n = 95, 6.9 ± 3.5%) among the nondiabetic subjects. The FMD was also lower in the subjects both with CHD (n = 161, 5.6 ± 2.8%) and without CHD (n = 319, 6.1 ± 3.3%) among the patients with diabetes compared to those without both diabetes and CHD. The FMD showed a significant positive correlation with the estimated glomerular filtration rate (eGFR) in the diabetic patients without CHD, while there was no significant association in those with CHD. The FMD was significantly lower with the progressive stages of the GFR or albuminuria in the patients without CHD among those with diabetes, although the FMD was not different in those with CHD. In conclusion, the FMD is considered to be useful for the detection of atherosclerosis in patients with type 2 diabetes, even if overt macroangiopathy is not diagnosed.

Comparison of the antidiabetic effects of linagliptin among groups with a normal renal function and a mild or severe renal impairment - retrospective observation study of Japanese patients with type 2 diabetes mellitus.

OBJECTIVE: The clinical course > 6 months after the initiation of linagliptin in patients with type 2 diabetes was compared among the groups divided by their renal function. METHODS: Two hundred and sixteen Japanese patients with type 2 diabetes treated with 5 mg once daily linagliptin were studied as the treated set. One hundred and forty-five subjects whose medications were not changed during the observation period were investigated as the full analysis set to assess the effectiveness. The subjects were divided into three groups based on an eGFR: eGFR ≥ 60, 59 - 45 and < 45 ml/min/1.73 m(2). The parameters were analyzed separately in the patients receiving monotherapy and additional therapy of linagliptin. RESULTS: The HbA1c (NGSP) levels significantly improved in both the patients receiving monotherapy and additional therapy. The changes in the HbA1c levels at 6 months were not significantly different between the groups with an eGFR ≥ 60, 59 - 45 and < 45 ml/min/1.73 m(2) receiving monotherapy (-1.0, -0.8 and -0.8%, respectively). Similarly, those were not significantly different between the different groups receiving additional therapy (-0.6, -0.5 and -0.7%, respectively). CONCLUSIONS: Linagliptin is considered to be effective for patients with type 2 diabetes and renal impairment in the present analysis performed at our institution.

Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus.

BACKGROUND: The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus. METHODS: The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study. RESULTS: The glycated hemoglobin (HbA1c) level (8.3% ± 1.8% to 8.2% ± 1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤ 8.0% (-0.9 ± 2.0 versus 0.3 ± 0.6, respectively, P = 0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7 ± 3.6 versus -0.8 ± 3.5, P = 0.04). CONCLUSION: B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.

The Prevalence of the Risk Factors for Atherosclerosis among Type 2 Diabetic Patients Is Greater in the Progressive Stages of Chronic Kidney Disease.

BACKGROUND/AIMS: The prevalence of the risk factors for atherosclerosis, other than diabetes mellitus, among type 2 diabetic patients with different stages of chronic kidney disease (CKD) determined by glomerular filtration rate (GFR) was investigated. METHODS: The prevalence of ten risk factors (age ≥65 years, history of smoking, male gender, obesity, albuminuria, hypertension, hypercholesterolemia, hypo-HDL-cholesterolemia, hyperuricemia and anemia) was determined in 2,107 Japanese type 2 diabetic patients with different stages of CKD (six stages according to GFR). RESULTS: The risk factors for age ≥65 years and male gender were found in 49 and 62% of the study subjects, respectively. The percentages of subjects with a current history of smoking, obesity, albuminuria, hypertension, hypercholesterolemia, hypo-HDL-cholesterolemia, hyperuricemia and anemia were 35, 44, 47, 70, 61, 13, 21 and 26%, respectively. The prevalence of age ≥65 years, male gender, albuminuria, hypertension, hypo-HDL-cholesterolemia, hyperuricemia and anemia was greater in the later stages of GFR, whereas the prevalence of hypercholesterolemia and obesity did not differ between stages. The prevalence of a current history of smoking was lower in the later stages of GFR. The cumulative number of risk factors increased from 3.1 to 6.8 in the later stages of GFR. CONCLUSION: Among type 2 diabetic patients with CKD, the total number of risk factors increases with the progression of renal dysfunction. It is important to pay attention to newly recognized risk factors for hyperuricemia and anemia, in addition to hypertension, albuminuria and hypo-HDL-cholesterolemia, in monitoring diabetic patients with later stages of CKD.

Vildagliptin is Effective for Glycemic Control in Diabetic Patients Undergoing either Hemodialysis or Peritoneal Dialysis.

INTRODUCTION: Vildagliptin can be used in patients with type 2 diabetes mellitus and renal impairment. However, there have been few reports investigating the clinical effectiveness of vildagliptin in diabetic patients undergoing hemodialysis. No previous studies have evaluated the use of vildagliptin in patients undergoing peritoneal dialysis. The authors determined the usefulness of vildagliptin for treating type 2 diabetic patients receiving chronic dialysis, including peritoneal dialysis. METHODS: A retrospective study of ten diabetic patients undergoing peritoneal dialysis and five diabetic patients undergoing hemodialysis who were treated with 50 mg/day of vildagliptin was performed. Clinical parameters were investigated for a period of 6 months starting from the vildagliptin therapy. RESULTS: The hemoglobin A1c (HbA1c) levels were significantly reduced after baseline in both the peritoneal dialysis and hemodialysis groups, whereas the hemoglobin levels did not change during the follow-up period. The mean change in the HbA1c level (ΔHbA1c) was -0.6 ± 0.9% and -0.5 ± 0.7% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. The glycated albumin (GA) levels were also significantly reduced compared with baseline in the peritoneal dialysis group, although the serum albumin levels did not change. The mean change in the GA level (ΔGA) was -3.4 ± 3.1% and -2.1 ± 2.5% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. Stepwise multivariate analyses demonstrated the level of HbA1c at baseline to be significantly associated with the ΔHbA1c and that the level of GA at baseline was significantly associated with the ΔGA. CONCLUSION: Vildagliptin exhibits effectiveness in patients with type 2 diabetes mellitus undergoing peritoneal dialysis or hemodialysis. The degree of improvement in the HbA1c and GA levels was dependent on these levels at baseline, similar to the findings of previous reports of subjects without end-stage kidney disease.

Hypoglycemia observed during continuous glucose monitoring in patients with type 2 diabetes mellitus treated by subcutaneous insulin injection.

BACKGROUND: The relationship between hypoglycemia and the dose of insulin used in patients with type 2 diabetes mellitus was investigated by continuous glucose monitoring (CGM). PATIENTS AND METHODS: In total, 83 CGM studies were performed in 70 outpatients with type 2 diabetes receiving treatment by subcutaneous insulin injection. RESULTS: The total dose of insulin, bolus insulin dose, and basal insulin dose used in the subjects were 32±18 units, 19±13 units, and 13±8 units, respectively. The proportion of time in the hypoglycemic range (blood glucose<3.9 mmol/L) during CGM was positively correlated with the bolus insulin ratio (bolus/total insulin dose, r=0.22, P=0.04), although it was not associated with the total dose of insulin or the hemoglobin A1c (HbA1c) level. It was negatively correlated with the mean blood glucose (r=-0.38, P<0.01), whereas it was not associated with the SD or the mean amplitude of glycemic excursions (MAGE). The proportion of time in the hypoglycemic range was significantly greater in the subjects with a bolus insulin ratio of ≥0.6 (3.2±4.4%, n=42) than a ratio of <0.6 (1.2±3.0%, n=41), although the HbA1c level, total dose of insulin, mean blood glucose, SD, and MAGE were not significantly different between the two groups. CONCLUSIONS: An excessive dose of bolus insulin might increase the duration of hypoglycemia, independently from the HbA1c levels, in patients with type 2 diabetes mellitus receiving subcutaneous insulin injection.

Non-alcoholic fatty liver disease is an independent predictor for macroangiopathy in Japanese type 2 diabetic patients: a cross-sectional study.

OBJECTIVE: To clarify the clinical characteristics of type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD) and to assess whether NAFLD is related to angiopathy. METHODS: The study included 388 Japanese type 2 diabetic outpatients without viral hepatitis. The main outcome measures were angiopathy and NAFLD. RESULTS: The 388 subjects were divided into two subgroups based on alcohol consumption. Fatty liver was recognized in 36 of the 142 drinking patients (25%). There was no association of fatty liver disease with diabetic macro- or microangiopathy in these patients. Fatty liver disease (namely, NAFLD) was recognized in 77 of the 246 non-drinking patients (31%). Type 2 diabetic patients with NAFLD had a significantly younger age, higher body mass index level, higher levels of HbA1c, total cholesterol and triglyceride, lower HDL-C level, higher prevalence rates of hypercholesterolemia and obesity than counterparts without NAFLD. In addition, individuals in the elderly (≥65 years) non-drinking group with NAFLD had a significantly higher prevalence rates of diabetic macroangiopathy, coronary heart disease and thicker intima-media thickness level than their counterparts without NAFLD. The logistic regression analysis showed that NAFLD is an independent predictor of diabetic macroangiopathy. CONCLUSION: NAFLD was associated with an increased prevalence of diabetic macroangiopathy and coronary heart disease in elderly patients. In addition, NAFLD is an independent predictor for diabetic macroangiopathy. These findings suggest that type 2 diabetic patients with NAFLD should be considered as a high risk group for developing macroangiopathy, even if macroangiopathy is not clinically detected.

Hypertension resistant to antihypertensive agents commonly occurs with the progression of diabetic nephropathy in Japanese patients with type 2 diabetes mellitus: a prospective observational study.

BACKGROUND: We investigated 1) the frequency of hypertension in patients with type 2 diabetes graded by the new classification of chronic kidney disease (CKD) reported by the Kidney Disease: Improving Global Outcomes (KDIGO) and 2) the number of antihypertensive agents needed to achieve treatment goals using a prospective observational study. METHODS: A population of 2018 patients with type 2 diabetes mellitus was recruited for the study. The CKD stage was classified according to the eGFR and the urinary albumin excretion levels. RESULTS: Hypertension was found in 1420 (70%) of the patients, and the proportion of subjects showing a blood pressure<130/80 mmHg was 31% at the baseline. Although the mean blood pressure was approximately 130/75 mmHg, the rate of patients with a blood pressure of <130/80 mmHg became limited to 41-50% during the observation period. The number of antihypertensive agents required for treatment was significantly higher at the endpoint (2.0±1.3) than at the baseline (1.6±1.2). Furthermore, it increased with the progression of the CKD stage at both the baseline and the endpoint of the observation. However, the frequency of subjects who did not achieve the blood pressure target was found to increase in the group demonstrating the later stage of CKD. CONCLUSIONS: Hypertension resistant to antihypertensive agents was common in the patients with type 2 diabetes mellitus and increased with the progression of CKD. Although powerful combination therapy using antihypertensive agents is considered necessary for the strict control of blood pressure, this became difficult in individuals who were in advanced stages as graded based on the eGFR and the urinary albumin excretion levels.

The usefulness of the revised classification for chronic kidney disease by the KDIGO for determining the frequency of diabetic micro- and macroangiopathies in Japanese patients with type 2 diabetes mellitus.

AIMS: A new classification of chronic kidney disease (CKD) was proposed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2011. The major point of revision of this classification was the introduction of a two-dimensional staging of the CKD according to the level of albuminuria in addition to the GFR level. Furthermore, the previous CKD stage 3 was subdivided into two stages (G3a and G3b). We examined the prevalence of diabetic micro- and macroangiopathies in patients with type 2 diabetes mellitus based on the new classification. METHODS: A cross-sectional study was performed in 2018 patients with type 2 diabetes mellitus. RESULTS: All of the diabetic micro- and macroangiopathies significantly more common in the later stages of both the GFR and albuminuria. The proportion of subjects with diabetic retinopathy, neuropathy, cerebrovascular disease and coronary heart disease was significantly higher in the G3b group than in the G3a group. The brachial-ankle pulse wave velocity, which is one of the surrogate markers for atherosclerosis, was also significantly greater in the G3b group compared to the G3a group. CONCLUSION: The subdivision of the G3 stage in the revised classification proposed by the KDIGO is useful to evaluate the risk for diabetic vascular complications.

Hyperuricemia is independently associated with coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus.

AIMS: To investigate the relationship between hyperuricemia (HUA) and the clinical backgrounds in Japanese patients with type 2 diabetes mellitus. METHODS: After a cross-sectional study evaluating the association of HUA with the clinical characteristics in 1,213 patients with type 2 diabetes mellitus, the estimated glomerular filtration rate (eGFR) and the incidence of diabetic macroangiopathies was investigated in a prospective observational study in 1,073 patients during a 3.5 year period. HUA was defined by serum uric acid levels >327 µmol/L or as patients using allopurinol. RESULTS: The frequency of HUA was significantly higher in the diabetic patients (32% in men and 15% in women) than in the normal controls (14% in men and 1% in women). In total, HUA was found in 299 (25%) of the patients during the cross-sectional study. Even after adjusting for sex, drinking status, treatment for diabetes mellitus, body mass index, hypertension, use of diuretics, hyperlipidemia, HbA1c and/or the eGFR, the HUA was independently associated with some diabetic complications. The eGFR was significantly reduced in HUA patients compared to those with normouricemia in the 12 months after observation was started. HUA was also an independent risk factor for coronary heart disease even after adjustment in the Cox proportional hazard model. CONCLUSIONS: HUA is a associated with diabetic micro- and macroangiopathies. HUA is a predictor of coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus. However, the influence of HUA is considered to be limited.

Long-term effect of metformin on blood glucose control in non-obese patients with type 2 diabetes mellitus.

BACKGROUND: We aimed to investigate the long-term effect of metformin on the blood glucose control in non-obese patients with type 2 diabetes mellitus. METHODS: A retrospective study was performed in 213 patients with type 2 diabetes mellitus under the administration of metformin for more than one year. The clinical parameters were investigated for 3 years. The obese and non-obese individuals were defined as a body mass index (BMI) of 25 kg/m2 or over (n = 105) and a BMI of less than 25 kg/m2 (n = 108), respectively. RESULTS: HbA1c levels were significantly decreased compared with those at the baseline time. The course of HbA1c was similar between the non-obese and the obese groups, while the dose of metformin required to control blood glucose was significantly lower in the non-obese group than in the obese group. The reductions in HbA1c were 1.2% and 1.1% at 12 months, 0.9% and 0.9% at 24 months, and 0.8% and 1.0% at 36 months in the non-obese and obese groups, respectively. BMI did not change during the observation periods. Approximately half of all patients required no additional antidiabetic agents or a reduction in other treatments after the initiation of metformin in either of the two groups. CONCLUSIONS: The present study demonstrated the long-term beneficial effect of metformin in non-obese (BMI < 25 kg/m2) diabetic patients. This effect appears to be maintained even after the observation period of this study, because metformin was limited to a relatively low dose in the non-obese group and the observed worsening in glycemic control over time can probably be attenuated by increasing the dose of metformin.

The estimated GFR, but not the stage of diabetic nephropathy graded by the urinary albumin excretion, is associated with the carotid intima-media thickness in patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: To study the relationship between the intima-media thickness (IMT) of the carotid artery and the stage of chronic kidney disease (CKD) based on the estimated glomerular filtration rate (eGFR) and diabetic nephropathy graded by the urinary albumin excretion (UAE) in the patients with type 2 diabetes mellitus. METHODS: A cross-sectional study was performed in 338 patients with type 2 diabetes mellitus. The carotid IMT was measured using an ultrasonographic examination. RESULTS: The mean carotid IMT was 1.06 +/- 0.27 mm, and 42% of the subjects showed IMT thickening (>or= 1.1 mm). Cerebrovascular disease and coronary heart disease were frequent in the patients with IMT thickening. The carotid IMT elevated significantly with the stage progression of CKD (0.87 +/- 0.19 mm in stage 1, 1.02 +/- 0.26 mm in stage 2, 1.11 +/- 0.26 mm in stage 3, and 1.11 +/- 0.27 mm in stage 4+5). However, the IMT was not significantly different among the various stages of diabetic nephropathy. The IMT was significantly greater in the diabetic patients with hypertension compared to those without hypertension. The IMT positively correlated with the age, the duration of diabetes mellitus, and the brachial-ankle pulse wave velocities (baPWV), and negatively correlated with the eGFR. In a stepwise multivariate regression analysis, the eGFR and the baPWV were independently associated with the carotid IMT. CONCLUSIONS: Our study is the first report showing a relationship between the carotid IMT and the renal parameters including eGFR and the stages of diabetic nephropathy with a confirmed association between the IMT and diabetic macroangiopathy. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis and positive treatments for hypertension, dyslipidaemia, obesity, as well as hyperglycaemia are necessary when a reduced eGFR is found in diabetic patients.

High frequencies of diabetic micro- and macroangiopathies in patients with type 2 diabetes mellitus with decreased estimated glomerular filtration rate and normoalbuminuria.

BACKGROUND: The clinical characteristics of diabetic patients presenting with normoalbuminuria with decreased kidney functions were investigated. METHODS: A cross-sectional study was performed in 1197 patients with type 2 diabetes mellitus. The estimated glomerular filtration rate (eGFR) was calculated using the formula recommended by the Japanese Society of Nephrology. RESULTS: The groups with normoalbuminuria, microalbuminuria, macroalbuminuria and renal failure consisted of 696 (58%), 229 (19%), 196 (16%) and 76 (6%) subjects, respectively. The frequencies of all diabetic micro- and macroangiopathies increased with progression of diabetic nephropathy stage. However, in the groups with chronic kidney disease (CKD) stage 3+4 (60 > eGFR > or = 15 mL/min/1.73 m(2)), the frequencies of diabetic neuropathy and macroangiopathies were not different among the groups staged by urinary albumin excretion. In the normoalbuminuria group, 223 (32%) cases showed CKD stage 3+4. Diabetic neuropathy and macroangiopathies were significantly more frequent in the groups presenting with normoalbuminuria with CKD stage 3+4 than in those with CKD stage 1+2 (eGFR > or = 60 mL/min/1.73 m(2)). The patients' age, duration of diabetes mellitus and frequency of hypertension were significantly higher in the groups presenting with normoalbuminuria with CKD stage 3+4. After adjustment by age, grade of albuminuria or both, CKD stage 3+4 was an independent risk factor for some diabetic complications. CONCLUSIONS: The combination of urinary albumin excretion and eGFR is useful for earlier detection of kidney and vascular damage in patients with diabetes mellitus. Evaluation of eGFR should be performed for all diabetic patients even if they show normoalbuminuria.

Mild anemia is frequent and associated with micro- and macroangiopathies in patients with type 2 diabetes mellitus.

UNLABELLED: Aims/Introduction: The present study investigated the frequency of mild anemia, which is not an indication of intensive therapy using drugs, in Japanese patients with type 2 diabetes mellitus and the association of mild anemia with diabetic complications. MATERIALS AND METHODS: This is a cross-sectional study of 1189 patients with type 2 diabetes mellitus. Anemia was defined as a hemoglobin level <13.5 g/dL in men and <12.0 g/dL in women. The patients with anemia were divided into two groups: (i) grade 1 anemia with a hemoglobin level ≥11.0 g/dL; and (ii) grade 2 anemia with a hemoglobin level <11.0 g/dL. RESULTS: The prevalence of anemia increased with the progression of the stage of diabetic nephropathy and chronic kidney disease. The frequencies of diabetic micro- and macroangiopathies increased with the progression of anemia among 798 patients without anemia, 300 with grade 1 anemia and 91 with grade 2 anemia. Both grade 1 and grade 2 anemia were associated with diabetic micro- and macroangiopathies. They remained independently associated with diabetic retinopathy, coronary heart disease and peripheral arterial disease after adjustment by age, sex, body mass index, use of angiotensin II receptor blocker, estimated glomerular filtration rate and stage of diabetic nephropathy. CONCLUSIONS: Mild anemia is frequent and associated with micro- and macroangiopathies in patients with type 2 diabetes mellitus. It is important to carry out intensive examinations for the detection of diabetic micro- and macroangiopathies in addition to evaluating the causes of anemia when mild anemia is found in patients with diabetes mellitus. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00060.x, 2010).