Relationship between dietary patterns and risk factors for cardiovascular disease in patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: While some dietary patterns are associated with the incidence of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), the relationship between dietary pattern and risk factors for CVD in patients with T2DM remains to be clarified. The aim of this study was to identify dietary patterns and investigate the relationship between dietary patterns and potential risk factors for CVD in patients with T2DM. METHODS: The study participants comprised 726 Japanese T2DM outpatients free of history of CVD. Life styles were analyzed using self-reported questionnaires. The relationship between dietary patterns, identified by factor analysis, and potential risk factors for CVD was investigated by linear and logistic regression analyses. RESULTS: Six dietary patterns were identified by factor analysis. Especially, three dietary patterns were associated with risk factors for CVD. The "Seaweeds, Vegetables, Soy products and Mushrooms" pattern, characterized by high consumption of seaweeds, soy products and mushrooms, was associated with lower use of diabetes medication and healthier lifestyles. The "Noodle and Soup" pattern, characterized by high consumption of noodle and soup was associated with higher body mass index, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase and triglyceride levels. The "Fruit, Dairy products and Sweets" pattern was associated with lower γ-glutamyl transpeptidase levels, blood pressure, albuminuria and brachial-ankle pulse wave velocity. CONCLUSIONS: The findings suggested that dietary patterns correlated with risk factors for CVD in T2DM patients.

Poor sleep quality is associated with increased arterial stiffness in Japanese patients with type 2 diabetes mellitus.

BACKGROUND: While poor sleep quality can worsen cardiovascular risk factors such as glucose and lipid profiles in patients with type 2 diabetes mellitus (T2DM), the relationship between sleep quality and atherosclerosis remains largely unknown. The aim of this study was to examine this relationship. METHODS: The study participants comprised 724 Japanese T2DM outpatients free of history of cardiovascular diseases. The relationships between sleep quality (assessed by the Pittsburgh Sleep Quality Index (PSQI)) and various clinical and laboratory parameters were investigated. RESULTS: The mean PSQI was 5.1 ± 3.0 (±SD). Patients were divided into three groups based on the total PSQI score; subjects with good sleep quality (n = 462), average sleep quality (n = 185), and poor sleep quality (n = 77). In the age/gender-adjusted model, patients with poor sleep quality tended to be obese, evening type and depressed. However, other lifestyles showed no significant trends. Alanine aminotransferase, fasting blood glucose, HbA1c, systolic blood pressure, urinary albumin excretion, and brachial-ankle pulse wave velocity (baPWV) tended to be higher in patients with poor sleep quality. High baPWV was the only parameter that correlated with poor sleep in a model adjusted for several other lifestyle factors. CONCLUSIONS: Our study indicates that poor sleep quality in T2DM patients correlates with increased arterial wall stiffness, a marker of atherosclerosis and a risk factor for cardiovascular diseases.

Home blood pressure-lowering effect of a non-steroidal mineralocorticoid receptor blocker, esaxerenone, versus trichlormethiazide for uncontrolled hypertension: the EXCITE-HT randomized controlled study.

The EXCITE-HT study aimed to evaluate the efficacy and safety of esaxerenone versus thiazide diuretics (trichlormethiazide) as second-line treatment for Japanese patients with uncontrolled essential hypertension. This was a 12-week, multicenter, randomized, open-label, parallel-group study. The non-inferiority of esaxerenone to trichlormethiazide was confirmed if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic blood pressure (SBP)/diastolic blood pressure (DBP) change between groups was below 3.9/2.1 mmHg. A total of 295 and 290 patients were included in the esaxerenone and trichlormethiazide groups, respectively. The non-inferiority of esaxerenone to trichlormethiazide was demonstrated: least squares mean change differences in morning home SBP/DBP at end of treatment (EOT) were -2.2 (95% CI, -3.6, -0.8) mmHg for SBP/-0.6 (-1.4, 0.2) mmHg for DBP. Morning home, bedtime home, and office BP significantly decreased (all p < 0.001) from baseline to EOT in both groups. The urinary albumin-to-creatinine ratio and N-terminal pro-brain natriuretic peptide level decreased from baseline to Week 12 in both groups, with no notable intergroup difference. Serum potassium elevations occurred more frequently with esaxerenone, while serum potassium reductions occurred more with trichlormethiazide. Uric acid elevations were observed in both groups, but more frequently with trichlormethiazide than esaxerenone. No cases of gout occurred in this study. Reductions in estimated glomerular filtration rate were similarly observed in both groups. EXCITE-HT is the first randomized controlled study to demonstrate evidence that esaxerenone is non-inferior to trichlormethiazide as second-line treatment for Japanese patients with uncontrolled essential hypertension, with no new safety concerns. The EXCITE-HT study demonstrated the non-inferiority of esaxerenone to trichlormethiazide in its morning home blood pressure lowering effect and safety profile in Japanese patients with uncontrolled essential hypertension who were previously treated with an angiotensin II receptor blocker or calcium channel blocker.

Lower intake of saturated fatty acids is associated with persistently higher arterial stiffness in patients with type 2 diabetes.

AIMS/INTRODUCTION: There are few studies to investigate the relationship between macronutrients and longitudinal changes in arterial stiffness in patients with type 2 diabetes mellitus. This exploratory study sought to determine whether macronutrients were correlated with increased arterial stiffness independently of conventional atherosclerotic risk factors. MATERIALS AND METHODS: The study participants comprised 733 type 2 diabetes outpatients who had no apparent history of cardiovascular diseases. The dietary schedule was assessed with a validated, brief, self-administered diet history questionnaire. At baseline and at years 2 and 5, brachial-ankle pulse wave velocity was measured. A multivariable linear mixed-effects model was used to determine the predictive values of macronutrients and atherosclerotic risk factors for longitudinal changes in brachial-ankle pulse wave velocity. RESULTS: There was a significant increase in brachial-ankle pulse wave velocity values over the 5-year follow-up period. In a multivariable linear mixed-effects model that adjusted for age and sex, lower saturated fatty acid intake was significantly correlated with persistently higher brachial-ankle pulse wave velocity, independently of other atherosclerotic risk factors. Lower intake of dairy products in particular showed this correlation. CONCLUSIONS: Our data showed that lower saturated fatty acids intake was correlated with persistently higher brachial-ankle pulse wave velocity in type 2 diabetes patients. Among food sources of saturated fatty acids, lower dairy products specifically were correlated with elevated brachial-ankle pulse wave velocity. This might be because the consumption of dairy products in Japan is much lower than in Western countries.

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.

Breakfast skipping is associated with persistently increased arterial stiffness in patients with type 2 diabetes.

OBJECTIVE: While certain lifestyle habits may be associated with arterial stiffness, there is limited literature investigating the relationship between lifestyle habits and longitudinal changes in arterial stiffness in patients with type 2 diabetes mellitus (T2DM). This is an exploratory study to determine whether lifestyle habits, in addition to conventional atherosclerotic risk factors, are associated with increased arterial stiffness. RESEARCH DESIGN AND METHODS: The study participants comprised 734 Japanese outpatients with T2DM and no history of apparent cardiovascular diseases. Lifestyle habits were analyzed using self-reported questionnaires, and brachial-ankle pulse wave velocity (baPWV) was measured at baseline, and at years 2 and 5. A multivariable linear mixed-effects model was used to determine the predictive value of lifestyle habits and possible atherosclerotic risk factors for longitudinal change in baPWV. RESULTS: Over 5 years of follow-up, baPWV values significantly increased. In a multivariable linear mixed-effects model that adjusted for age and gender, a low frequency of breakfast intake was significantly associated with persistently high baPWV, independently of other lifestyle habits. Furthermore, in a multivariable linear mixed-effects model that included both lifestyle habits and possible atherosclerotic risk factors, a low frequency of breakfast intake remained the only independent predictive factor for persistently high baPWV. Subjects who ate breakfast less frequently tended to have additional unhealthy lifestyle habits and atherosclerotic risk factors. CONCLUSIONS: Our analyses suggest that breakfast skipping is an independent lifestyle habit that is associated with persistently increased arterial stiffness in patients with T2DM. TRIAL REGISTRATION NUMBER: UMIN000010932.

Efficacy of ipragliflozin as monotherapy or as add-on therapy with other oral antidiabetic medications for treating type 2 diabetes in Japanese patients with inadequate glycemic control: A subgroup analysis based on patient characteristics.

AIMS/INTRODUCTION: The aim of the present study was to evaluate the efficacy and safety of ipragliflozin in treating Japanese type 2 diabetes patients with inadequate glycemic control by investigating diurnal variations of blood glucose and body composition. MATERIALS AND METHODS: This was an investigator-initiated, multicenter, prospective study with a 6-month treatment period. The primary outcome investigated was change in hemoglobin A1c levels from baseline. Secondary outcomes included changes in fasting plasma glucose, insulin resistance, variations in 24-h glucose levels detected by continuous glucose monitoring, bodyweight, body composition, waist circumference and serum lipids. Adverse events were evaluated throughout the study. RESULTS: A total of 98 patients completed the study. Over the 6-month period, ipragliflozin-treated patients showed reduction in hemoglobin A1c levels by 0.3%, fasting plasma glucose levels by 13.0 mg/dL, bodyweight by 2.1 kg, body fat mass by 1.5 kg and extracellular water by 0.3 kg, as well as a decrease in systolic/diastolic blood pressures. Significant reductions from baseline in mean amplitude of glucose excursions and standard deviation, and the reduced frequency of hyperglycemia were confirmed. High-density lipoprotein cholesterol was also significantly improved. Notably, the subgroup analysis of hemoglobin A1c levels, bodyweight, waist circumference, and body composition based on age, sex and body mass index showed similar reductions within each subgroup. The incidences of adverse events and adverse drug reactions were 20.0% and 1.0%, respectively, over the 6-month period. CONCLUSIONS: Ipragliflozin is a useful oral antidiabetic medication for patients with a wide range of background characteristics.

Relationships between lifestyle patterns and cardio-renal-metabolic parameters in patients with type 2 diabetes mellitus: A cross-sectional study.

INTRODUCTION: While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal-metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. PARTICIPANTS AND METHODS: The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. RESULTS: Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. CONCLUSIONS: The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. TRIAL REGISTRATION: UMIN000010932.

Relationships Among Conventional Cardiovascular Risk Factors and Lifestyle Habits With Arterial Stiffness in Type 2 Diabetic Patients.

BACKGROUND: While conventional cardiovascular risk factors and certain lifestyle habits are associated with arterial stiffness in patients with type 2 diabetes mellitus (T2DM), it is still unknown whether they are actually associated with arterial stiffness even after adjustment for conventional cardiovascular risk factors and lifestyle habits. The aim of this study was to identify variables that are associated with brachial-ankle pulse wave velocity (baPWV). METHODS: The study participants comprised 724 Japanese T2DM outpatients free of history of cardiovascular diseases. Lifestyle habits were analyzed using self-reported questionnaires. The associations among conventional cardiovascular risk factors and lifestyle habits with baPWV were investigated by multivariable linear regression analysis. RESULTS: The mean age of the study subjects was 57.8 ± 8.6 years, and 62.8% of those were males. The mean HbA1c was 7.0±1.0%, and the estimated duration of T2DM was 9.9 ± 7.2 years. Multiple linear regression analysis that included age and gender demonstrated that age and male sex were positively associated with baPWV. In a model adjusted for numerous conventional cardiovascular risk factors and lifestyle habits, age, duration of T2DM, systolic blood pressure, serum uric acid, urinary albumin excretion and poor sleep quality were positively associated with baPWV, while body mass index was negatively associated with baPWV. CONCLUSIONS: In Japanese T2DM, in addition to several conventional cardiovascular risk factors, poor sleep quality was associated with baPWV even after adjustment for numerous conventional cardiovascular risk factors and lifestyle habits.

Hydrogen gas production is associated with reduced interleukin-1ß mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients.

Acarbose, an α-glucosidase inhibitor, leads to the production of hydrogen gas, which reduces oxidative stress. In this study, we examined the effects of a single dose of acarbose immediately before a test meal on postprandial hydrogen gas in breath and peripheral blood interleukin (IL)-1ß mRNA expression in Japanese type 2 diabetic patients. Sixteen Japanese patients (14 men, 2 women) participated in this study. The mean±standard deviation age, hemoglobin A1c and body mass index were 52.1±15.4 years, 10.2±2.0%, and 27.7±8.0kg/m(2), respectively. The patients were admitted into our hospital for 2 days and underwent test meals at breakfast without (day 1) or with acarbose (day 2). We performed continuous glucose monitoring and measured hydrogen gas levels in breath, and peripheral blood IL-1ß mRNA levels before (0min) and after the test meal (hydrogen gas: 60, 120, 180, and 300min; IL-1ß: 180min). The induction of hydrogen gas production and the reduction in peripheral blood IL-1ß mRNA after the test meal were not significant between days 1 (without acarbose) and 2 (with acarbose). However, the changes in total hydrogen gas production from day 1 to day 2 were closely and inversely associated with the changes in peripheral blood IL-1ß mRNA levels. Our results suggest that an increase in hydrogen gas production is inversely associated with a reduction of the peripheral blood IL-1ß mRNA level after a single dose of acarbose in Japanese type 2 diabetic patients.

Effects of sitagliptin or mitiglinide as an add-on to acarbose on daily blood glucose fluctuations measured by 72 h subcutaneous continuous glucose monitoring in Japanese patients with type 2 diabetes: a prospective randomized study.

OBJECTIVE: Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life. METHODS: Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7 days in week 3 of each treatment period. RESULTS: The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period. CONCLUSION: Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.

Effect of hemodialysis on plasma glucose profile and plasma level of liraglutide in patients with type 2 diabetes mellitus and end-stage renal disease: a pilot study.

The effect of hemodialysis on the plasma glucose profile and liraglutide level after liraglutide injection was investigated in patients with diabetes and end-stage renal disease (ESRD). Either 0.6 mg or 0.9 mg liraglutide was subcutaneously administered daily to 10 Japanese type 2 diabetic patients with ESRD. Hemodialysis was conducted on days 1 and 3. Plasma liraglutide and glucose concentrations were measured by enzyme-linked immunosorbent assay and a continuous glucose monitoring system, respectively. The safety profile of liraglutide was also assessed. Hemodialysis had no effect on the pharmacokinetic parameters of liraglutide in patients with diabetes and ESRD; the maximum plasma concentration (Cmax), tmax, area under the concentration-time curve (AUC), and CL/f were unaltered. Similarly, hemodialysis did not affect the mean or minimum glucose levels, AUC, or duration of hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) following liraglutide administration. However, significant increases in mean amplitude of glycemic excursions (MAGE) and standard deviation (SD) as markers of glucose fluctuation, and the maximum glucose level were observed during hemodialysis. No adverse events, including hypoglycemia, were observed after liraglutide injection, either off-hemodialysis (day 2) or on-hemodialysis (day 3). Liraglutide was well tolerated in patients with type 2 diabetes and ESRD undergoing hemodialysis. The present results suggested that hemodialysis did not affect the pharmacokinetic profile of liraglutide or most glycemic indices, with the exception of MAGE, SD, and the maximum glucose level. These results suggested that it may be possible to use liraglutide during hemodialysis for diabetes with ESRD, without dose adjustment. Trial Registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000010159.

Morningness-eveningness questionnaire score and metabolic parameters in patients with type 2 diabetes mellitus.

"Morningness" and "Eveningness" represent lifestyle patterns including sleep-wake patterns. Although previous studies described a relationship between the morningness-eveningness trait and glycemic control in patients with type 2 diabetes mellitus (T2DM), the mechanism underlying this association remains unknown. The study participants comprised 725 Japanese T2DM outpatients free of history of cardiovascular diseases. Various lifestyles were analyzed using self-reported questionnaires, including morningness-eveningness questionnaire (MEQ). The relationships between morningness-eveningness trait and various biochemical parameters were investigated by linear regression analysis and logistic regression analysis. We classified the study patients into three groups, morning type (n=117), neither type (n=424) and evening type (n=184). Subjects of the evening type had high levels of alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low high-density lipoprotein-cholesterol level in a model adjusted for age and gender. Furthermore, multivariate analysis showed that the evening type was associated with high HbA1c and estimated glomerular filtration rate even after adjustment for other lifestyle factors known to affect metabolic control. The results suggest that T2DM patients with eveningness trait are under inadequate metabolic control independent of other lifestyle factors. Thus, the evening trait of T2DM patients represents an important target for intervention to ensure appropriate metabolic function.

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.

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).