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Background: The changes in the estimated glomerular filtration rate (eGFR) and predictors of the renal prognosis were retrospectively assessed over the 12 months after the initiation of tofogliflozin, which has the shortest half-life among sodium-glucose cotransporter 2 (SGLT2) inhibitors, in Japanese patients with type 2 diabetes and renal impairment., Methods: In total, 158 patients treated with tofogliflozin between 2019 and 2021 were studied as the safety analysis set. One hundred and thirty subjects whose medication was continued over 12 months were investigated as the full analysis set. The subjects were divided into two groups based on the eGFR: normal- (eGFR ≥60 mL/min/1.73 m2, n = 87) and low- (eGFR <60 mL/min/1.73 m2, n = 43) eGFR groups., Results: The body weight, blood pressure, urinary protein excretion, and serum uric acid concentration decreased from baseline in both eGFR groups while the hemoglobin level increased. The eGFR did not significantly differ over time, except for the initial dip (-4.3±9.6 mL/min/1.73 m2 in the normal-eGFR group and -1.5±5.3 mL/min/1.73 m2 in the low-eGFR group). The change in the eGFR at 12 months after the initiation of tofogliflozin was -1.9±9.0 mL/min/1.73 m2 and 0.2±6.0 mL/min/1.73 m2 in the normal- and low-eGFR group, respectively. In the normal-eGFR group, the change in the eGFR showed a significant negative correlation with the HbA1c and eGFR at baseline, according to a multiple regression analysis. In the low-eGFR group, the change in the eGFR showed a significant negative correlation with urate-lowering agent use. The frequencies of adverse events specific for SGLT2 inhibitors were not significantly different between the normal- and low-eGFR groups., Conclusions: Tofogliflozin may preserve renal function in the medium term in patients with type 2 diabetes and kidney impairment without an increase in specific adverse events., Competing Interests: H Ito has received funding support and lecture fees from Kowa Company, Ltd. and Taisho Pharmaceutical Co., Ltd., and lecture fees from Eli Lilly Japan KK, Novo Nordisk Pharma Ltd., Sumitomo Pharma Co., Ltd., Boehringer Ingelheim, Sanofi KK, Daiichi Sankyo Company, Novartis Pharma KK, Takeda Pharmaceutical Company Ltd., MSD KK, Astellas Pharma, Terumo Corporation, Mochida Pharmaceuticals, Teijin Pharma, Kissei Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation, Sanwa Kagaku Kenkyusho, AstraZeneca KK, Kyowa Kirin Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., EA Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., Viatris Inc., and has received consulting fee from Becton, Dickinson and Company. H Inoue has received lecture fees from AstraZeneca KK. T Izutsu has received lecture fees from Boehringer Ingelheim, Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd., Kowa Company, Ltd. and Asahi Kasei Pharma Corporation. S Matsumoto has received lecture fees from Eli Lilly Japan KK, Novo Nordisk Pharma Ltd., Astellas Pharma, Kyowa Kirin Co., Ltd. and AstraZeneca KK. S Antoku has received lecture fees from Kyowa Kirin Co. Ltd., Sanofi KK, Taisho Pharmaceutical Co., Ltd., Daiichi Sankyo Company, and Otsuka Pharmaceutical Co., Ltd. T Yamasaki, T Mori and M Togane have no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Ito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective Diabetes is recognized as an underlying disease of constipation. However, the prevalence of constipation varies according to the diagnostic criteria applied. We investigated the prevalence of constipation based on the new guideline for constipation in Japanese patients with type 2 diabetes and examined the relationship with the clinical background, including diabetic vascular complications. Methods Questionnaire surveys including items concerning the diagnosis and treatment status of constipation were administered to 410 patients with type 2 diabetes. Results Although 29% of the patients considered that they had experienced constipation (self-judged), only 14% had consulted a physician about constipation. The prevalence of chronic constipation based on the guideline was 26%. After including laxative users, constipation was finally found in 36%. Despite the use of laxatives (n=81), 51% of the patients were still diagnosed with chronic constipation. Patients with constipation (chronic constipation or laxative use) were significantly older and had a longer duration of diabetes than those without constipation. The body mass index (BMI) of patients with constipation (24.9±3.8 kg/m 2 ) was significantly lower than that of those without constipation (26.3±4.6 kg/m 2 ). Diabetic neuropathy (49% vs. 32%) and coronary heart disease (CHD) (27% vs. 13%) were significantly more frequent in the patients with constipation than in those without constipation. A multivariate logistic regression analysis revealed that gender, BMI, diabetic neuropathy, insulin use, and CHD were significantly associated with constipation. Conclusion An accurate diagnosis of constipation is desirable in patients with type 2 diabetes because constipation is independently associated with CHD.

A 77-year-old man was treated with a DPP-4 inhibitor for type 2 diabetes. Hypoglycemia occurred frequently, and an examination revealed a tumor with a maximum diameter of 140 mm in both lobes of the liver. Western immunoblotting detected a high-molecular-weight form of insulin-like growth factor-II, and non-islet cell tumor hypoglycemia was diagnosed. Although prednisolone 40 mg was started, hypoglycemia continued to occur frequently. Surgical tumor removal was not indicated, so lenvatinib was initiated. Hypoglycemia improved quickly, and the tumor shrank until it had partially disappeared. His condition continued to improve, and he was discharged.

Aims: The safety and efficacy, particularly, the factors associated with the renal prognosis, were assessed over 12 months after the initiation of luseogliflozin therapy in Japanese patients with type 2 diabetes and renal impairment., Methods: In total, 238 patients treated with luseogliflozin (2.5 mg, once daily) were studied as the safety analysis set. Two hundred and two subjects whose medication was continued over 12 months were investigated as the full analysis set. The subjects were divided into 3 groups based on the estimated glomerular filtration rate (eGFR): high eGFR (n = 49), normal eGFR (n = 116) and low eGFR (n = 37) groups., Results: The body weight, systolic blood pressure, HbA1c and urinary protein excretion gradually decreased from baseline in all eGFR groups. While the eGFR was significantly reduced from baseline in the high and normal eGFR groups, the eGFR did not significantly differ over time in the low eGFR group. There was no marked difference in the frequency of adverse events that were specific for SGLT2 inhibitors among the 3 groups in the safety analysis set., Conclusions: Luseogliflozin can preserve the renal function in the medium term in patients with type 2 diabetes and renal impairment without an increase in specific adverse events., Competing Interests: H Ito has received funding support and lecture fees from Taisho Pharmaceutical Co., Ltd., and lecture fees from Eli Lilly Japan KK, Boehringer Ingelheim, Takeda Pharmaceutical Company Ltd., Sanofi KK, Novo Nordisk Pharma Ltd., MSD KK, Novartis Pharma KK, Astellas Pharma, Daiichi Sankyo Company, Terumo Corporation, Mochida Pharmaceuticals, Teijin Pharma, Kissei Pharmaceuticals, Kowa Pharmaceuticals, Mitsubishi Tanabe Pharma Corporation, Sanwa Kagaku Kenkyusho, Dainippon Sumitomo Pharma, AstraZeneca KK, Kyowa Hakko Kirin, Shionogi and Co, Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., and Santen Pharmaceutical Co., Ltd., and has received consulting fee from Becton, Dickinson and Company. S Matsumoto has received lecture fees from Novo Nordisk Pharma Ltd., Astellas Pharma, and AstraZeneca KK. T Izutsu has received lecture fees from Sanofi KK, Taisho Pharmaceutical Co., Ltd., Kyowa Hakko Kirin, Bayer Yakuhin, Ltd., and Mitsubishi Tanabe Pharma Corporation. S Antoku has received lecture fees from Kyowa Hakko Kirin, Sanofi KK, Kyowa Hakko Kirin, Taisho Pharmaceutical Co., Ltd., Daiichi Sankyo Company, and Otsuka Pharmaceutical Co., Ltd. E Kusano, J Kondo, H Inoue, T Yamasaki, T Mori and M Togane have no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: To determine the renal and cardiovascular prognosis and all-cause mortality of Japanese patients with type 2 diabetes showing a reduced estimated glomerular filtration rate (eGFR) without albuminuria., Methods: A population of 675 patients with type 2 diabetes was prospectively observed for 4 years to determine the renal and cardiovascular outcomes and mortality. The subjects were divided into the four groups: those with a preserved eGFR and no albuminuria (n = 306), a preserved eGFR and albuminuria (n = 151), a reduced eGFR and no albuminuria (n = 96), and a reduced eGFR and albuminuria (n = 122). The Cox proportional hazard model and Fine and Gray method were used to assess between-group differences in the risk of mortality and cardiovascular events., Results: In the group with a reduced eGFR, the eGFR value did not significantly change in the subjects without albuminuria (0 ± 8 mL/min/1.73 m 2 ), whereas it decreased continuously in those with albuminuria (-6 ± 12 mL/min/1.73 m 2 ). The incidence of cardiovascular events was significantly (P = 0.03) higher in the subjects with albuminuria (17%) than those without albuminuria (7%) in the group with a reduced eGFR. Cardiovascular events were significantly (P < 0.01) more frequent in the group with a reduced eGFR than in those with a preserved eGFR in both subjects with and without albuminuria., Conclusions: The risk of end-stage kidney disease in non-albuminuric subjects with a reduced eGFR is considered to be low. We should focus on cardiovascular prognosis, because these patients are still at high risk of cardiovascular events, even though the prognosis is better in comparison to albuminuric patients.

Aims: The changes in patients' satisfaction with the treatment, medication adherence and unused drugs before and after switching from daily DPP-4 inhibitors to once-weekly trelagliptin administration were prospectively investigated in patients with type 2 diabetes., Methods: After excluding 46 patients who declined to switch from daily DPP-4 inhibitors, 79 subjects were included in the present study. The clinical parameters and results of questionnaire surveys regarding satisfaction with treatment as well as impressions of the amount of medicine/number of doses, medication adherence, and unused drug were examined at the baseline and 3 months after switching from daily DPP-4 inhibitors to trelagliptin in 75 patients with type 2 diabetes., Results: Although the value of HbA1c did not change (7.0% ± 0.5% to 7.0% ± 0.6%), the scores representing satisfaction with the treatment (25.2 ± 6.4 to 26.4 ± 6.0), impression of the amount of medicine (-0.3 ± 1.0 to 0.3 ± 1.0) and number of doses (0.3 ± 1.0 to 0.8 ± 0.6), and medication adherence (0.8 ± 0.4 to 0.9 ± 0.3) as assessed by the questionnaire surveys were significantly improved after switching from DPP-4 inhibitors. The self-reported amount of unused drugs was significantly reduced after switching., Conclusions: Switching from daily DPP-4 inhibitors to once-weekly trelagliptin improved the satisfaction with the treatment, impression of the prescribed medicine and medication adherence in the type 2 diabetic patients who expresses a desire to reduce their prescription medicines. In such patients, improvements in the glycemic control and long-term prognosis might be expected through the reduction of unused drugs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (© 2015 Japan Geriatrics Society.)

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.

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.

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.

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.

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.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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.