Reduced incidence of cardiovascular disease in patients with type 2 diabetes through the integrated improvement of diabetes care by comparing two prospective observational cohorts in real-world clinical practice (JDDM 72).

AIM: To investigate whether any reduction in all-cause mortality and cardiovascular disease morbidity was found over the decade in type 2 diabetes on real-world practice. METHODS: A prospective observational study was performed by following two independent cohorts recruited in 2004 (n = 3286, Cohort 1) and 2014 (n = 3919, Cohort 2). The primary outcome was a composite of onset of cardiovascular disease and death. Cox proportional hazards analysis was used to explore any difference between Cohort 2 and Cohort 1 for the composite endpoints and cardiovascular disease after adjustment for covariates and accumulation of five risks (smoking, HbA1c, blood pressure, lipids, and albuminuria) outside target ranges. RESULTS: During the 8-year follow-up, 391 (11.9%) and 270 (6.9%) primary outcomes, and 270 (8.2%) and 161 (4.1%) cardiovascular diseases occurred in Cohort 1 and Cohort 2, respectively. Cohort 2 (vs. Cohort 1) exhibited a significant risk reduction for composite endpoints (HR 0.73, 95% CI 0.62 to 0.86) and cardiovascular disease (HR 0.64, 95% CI 0.52 to 0.79), and similarly exhibited a significant reduction independent of the accumulation of the five risks. CONCLUSIONS: The significant reduction of Cohort 2 for cardiovascular disease independent of the baseline covariates suggests an integrated effect delivered by the recent treatment advances.

DAPagliflozin for the attenuation of albuminuria in Patients with hEaRt failure and type 2 diabetes (DAPPER study): a multicentre, randomised, open-label, parallel-group, standard treatment-controlled trial.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the urinary albumin-to-creatinine ratio (UACR) in patients with elevated levels of albuminuria in the presence or absence of heart failure (HF) or type 2 diabetes mellitus (T2D). However, these effects have not yet been reported in the presence of both HF and T2D. This lack of evidence prompted us to conduct a clinical trial on the effects of dapagliflozin on UACR in patients with HF and T2D. Methods: DAPPER is a multicentre, randomised, open-labeled, parallel-group, standard treatment-controlled trial that enrolled patients at 18 medical facilities in Japan. Eligible participants with both HF and T2D and aged between 20 and 85 years were randomly assigned to a dapagliflozin or control (anti-diabetic drugs other than SGLT 2 inhibitors) group with a 1:1 allocation. The primary outcome was changes in UACR from baseline after a two-year observation, and secondary endpoints were cardiovascular (CV) events and parameters related to HF. This trial was registered with the UMIN-CTR registry, UMIN000025102 and the Japan Registry of Clinical Trials, jRCTs051180135. Findings: Between 12 May 2017 and 31 March 2020, 294 patients were randomly assigned to the dapagliflozin group (n = 146) or control group (n = 148). The mean age of patients was 72.1 years and 29% were female. The mean glycated hemoglobin value was 6.9%, mean NT-proBNP was 429.1 pg/mL, mean estimated GFR was 65.7 mL/min/1.73 m2, and median UACR was 25.0 (8.8-74.6) mg/g Cr in the dapagliflozin group and 25.6 (8.2-95.0) mg/g Cr in the control group. Of the 146 patients in the dapagliflozin group, 122 completed the study, and 107 (87.7%) were taking 5 mg of dapagliflozin daily at the end of the observation period. The primary outcome did not significantly differ between the dapagliflozin and control groups. Among the secondary endpoints, the mean decrease in left ventricular end-diastolic dimensions as one of the echocardiographic parameters was larger in the dapagliflozin group than in the control group. The composite endpoint, defined as CV death or hospitalisation for CV events, hospitalisation for HF events, hospitalisation for all causes, and an additional change in prescriptions for heart failure in a two-year observation, was less frequent in the dapagliflozin group than in the control group. Interpretation: Although dapagliflozin at a dose of 5 mg daily did not reduce urinary albumin excretion in patients with HF and T2D from that in the controls, our findings suggest that dapagliflozin decreased CV events and suppressed left ventricular remodeling. Funding: AstraZeneca KK, Ono Pharmaceutical Co., Ltd.

Study on the effects of changes in lifestyle of patients with diabetes on glycaemic control before and after the declaration of the state of emergency in Japan.

Objective: To investigate the actual conditions of changes in lifestyle and treatment status of patients with diabetes before and after the declaration of the state of emergency issued in response to the novel coronavirus. Methods: This study was a collaborative study in two diabetes clinics. A total of 1000 subjects responded to the questionnaire. In addition, data on HbA1c and body weight before and after the declaration of the state of emergency were collected. Results: HbA1c levels significantly decreased from 7.28 ± 0.97% before the declaration of the state of emergency to 7.07 ± 0.86% after the declaration (p < 0.001). A significant decrease in HbA1c levels was also noted in both T2DM and T1DM. A factorial analysis of the change in HbA1c levels found that a high HbA1c level before the declaration was the most influential factor that made the HbA1c level more likely to decrease, with such factors including a good amount of exercise. A positive correlation with change in body weight was noted. Factors that made the HbA1c level less likely to decrease included stress felt about school closures for children, increased opportunities to eat out, increased food consumption, and refraining from exercise to avoid the "Three Cs" (crowded places, close-contact settings, and confined and enclosed spaces). Conclusion: In the absence of serious economic stagnation or completely disrupted distribution, patients are allowed time to do what they like and can probably improve their glycaemic control status if they see this time as an opportunity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00505-6.

The Effects of Stress on Glycemic Control Brought on by Changes in Social Conditions Due to COVID-19.

Objective The stress brought on by changes in social conditions due to COVID-19 is diverse. However, there have been no studies examining the relationship between the type of stress felt by an individual due to such changes in social conditions and the degree of change in HbA1c, prompting us to conduct this study. Methods We conducted a collaborative study at two diabetes clinics. A total of 1,000 subjects responded to the questionnaire. Data on HbA1c and body weight before and after the declaration of the state of emergency were collected. Results We conducted a questionnaire on some stressors, but when comparing the two groups with respect to whether or not they felt stress from each item, only "school closures for children," seemed to be associated with a significant difference in the amount of change in HbA1c. In the stressed group, i.e. the group of parents who experienced stress due to their children's schools being closed, the HbA1c value changed from 7.30±0.78 to 7.30±1.13 (p=0.985). By contrast, in the unstressed group, the HbA1c value significantly decreased from 7.28±0.98 to 7.06±0.85 (p<0.001). In addition, as a result of comparing the amount of change between the 2 groups, a significant decrease was observed in the unstressed group compared with the stressed group (p=0.032). There was no significant difference in body weight change between the two groups. Conclusion Stress that cannot be avoided by one's own will, such as school closures for children, may affect glycemic control.

Efficacy and safety of dapagliflozin in Japanese patients with inadequately controlled type 1 diabetes (DEPICT-5): 52-week results from a randomized, open-label, phase III clinical trial.

AIMS: To investigate the safety and tolerability of 5 and 10 mg dapagliflozin added to insulin therapy over 52 weeks in Japanese patients with inadequately controlled type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This randomized, open-label, parallel-group, multicentre phase III clinical trial was conducted from October 26, 2015 to June 15, 2017. The primary endpoint was the occurrence of adverse events such as hypoglycaemia and diabetic ketoacidosis. Secondary endpoints included changes in glycaemic parameters, total daily insulin dosage and body weight over time. The efficacy of dapagliflozin in patients stratified by body mass index (BMI) <25.0 and ≥25.0 kg/m2 was evaluated in a subgroup analysis. RESULTS: In total, 151 patients received 5 mg (n = 76) or 10 mg (n = 75) dapagliflozin once daily for 52 weeks. Adverse events were observed in 88.2% and 73.3% of patients in the 5 and 10 mg dapagliflozin groups, respectively. Severe hypoglycaemia was reported in 2.6% (n = 2) and 6.7% (n = 5) of patients, and diabetic ketoacidosis in 2.6% (n = 2) and 1.3% (n = 1) of patients in the 5 and 10 mg dapagliflozin groups, respectively. The adjusted mean (95% confidence interval) changes in glycated haemoglobin at week 52 were -0.33% (-0.50, -0.15) and -0.36% (-0.53, -0.18) in the 5 and 10 mg dapagliflozin groups, respectively. There were no differences in efficacy parameters when stratified by BMI. CONCLUSIONS: This study demonstrated the long-term safety and tolerability of dapagliflozin added to insulin therapy in Japanese patients with inadequately controlled T1DM.

Evaluation of health utility values for diabetic complications, treatment regimens, glycemic control and other subjective symptoms in diabetic patients using the EQ-5D-5L.

AIMS: This study aimed to reveal health utility values for diabetic complications and treatment regimens with adjustment for glycemic control and other clinical manifestations in a diabetic population. METHODS: The EuroQol 5-Dimension 5-Level (EQ-5D-5L) health utility values for 4963 Japanese diabetic patients were analyzed using a multivariate regression model including major complications and treatment regiments (minimally adjusted model), and that additionally included glycemic control and other subjective symptoms (musculoskeletal, dental, respiratory, gastrointestinal, urinary, and cutaneous symptoms, and hearing impairment) (further adjusted model). RESULTS: The mean utility value was 0.901 ± 0.137. In the minimally adjusted model, blindness, overt nephropathy, regular dialysis, cardiac symptom, sequelae of stroke, symptomatic peripheral neuropathy, decreased sensation, claudication, foot ulcer/gangrene, major amputation, and complex treatment regimens were significantly associated with lower utility values, whereas proliferative retinopathy without blindness, coronary artery disease without cardiac symptom, sequela-free cerebrovascular disease, asymptomatic peripheral artery disease, and minor amputation were not. Major complications and treatment regimens that showed significant association in the minimally adjusted model still presented significant impact on the utility decrement in the further adjusted model. However, most of their regression coefficients were lower in absolute value compared to those in the minimally adjusted model. CONCLUSIONS: The utility decrement related to each diabetic complication varied with its severity and accompanying symptoms. Complex treatment regimens were independently associated with lower utility values. The utility decrement associated with diabetic complication and complex treatment regimens would be overestimated in the analysis without adjustment for glycemic control or other subjective symptoms.

Declining trends of diabetic nephropathy, retinopathy and neuropathy with improving diabetes care indicators in Japanese patients with type 2 and type 1 diabetes (JDDM 46).

OBJECTIVE: We examined changes in prevalence of diabetic microvascular/macrovascular complications and diabetes care indicators for adults in Japan with type 2 and type 1 diabetes over one decade. RESEARCH DESIGN AND METHODS: Two independent cohorts were recruited with the same inclusion criteria in 2004 (cohort 1: 3319 with type 2 and 286 with type 1 diabetes) and in 2014 (cohort 2: 3932 with type 2 and 308 with type 1 diabetes). Prevalence of complications and care indicators including achieving treatment targets for glycemia, blood pressure, lipid control, body mass index (BMI), and smoking were compared. In addition, patients in cohort 1 were re-examined in 2014 and their data were compared with the baseline data of each cohort. RESULTS: In type 2 diabetes, the prevalence of nephropathy, retinopathy, neuropathy, chronic kidney disease, current smoking and stroke significantly decreased, with improvements in achieving treatment target rates in cohort 2 two as compared with cohort 1. In type 1 diabetes, the prevalence of nephropathy, retinopathy, chronic kidney disease, and hemoglobin A1Cvalues significantly decreased. Decreases in prevalence of microvascular complications in type 2 diabetes were similarly found in each age-matched and sex-matched group, whereas younger patients exhibited marked increase in BMI and lower treatment target achieving rates compared with elderly patients. Regarding normoalbuminuric renal impairment, only a slight increase in the prevalence was observed both in type 2 and type 1 diabetes. In cohort 1, re-examined in 2014, care indicators were significantly improved from 2004, while complications increased with getting 10 years older. CONCLUSIONS: We observed declining trends of diabetic microvascular complications with improvement in diabetes care indicators in type 2 and type 1 diabetes. Younger patients with type 2 diabetes exhibited marked increase in BMI and lower rates of achieving treatment targets compared with elderly patients, which remains a concern.

Analysis of the effect of seasonal administration on the efficacy of sitagliptin: Subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes Study.

AIMS/INTRODUCTION: Hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus fluctuate throughout the year. However, there are few studies that have evaluated the therapeutic effect of hypoglycemic agents while considering such fluctuations. In a multicenter study (Januvia Multicenter Prospective Trial in Type 2 Diabetes Study), pretreatment patients with type 2 diabetes mellitus were divided into seven groups and given sitagliptin for 1 year. The aim of the present study was to evaluate the differences in the therapeutic effect, and the efficacy of sitagliptin in patients with type 2 diabetes mellitus based on the month the administration of the drug began as a subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes Study. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus were divided into four groups according to the month of initiation of sitagliptin. Changes in HbA1c in each group were compared at 3 and 12 months after administration of sitagliptin. As a negative correlation has been reported between baseline HbA1c and the degree of change after administration of sitagliptin, an analysis using the residual error from the approximate line was carried out. RESULTS: In the analysis of the degree of change in HbA1c, patients in the group in which administration of sitagliptin was started between August and October had the lowest degree of improvement at 3 months after starting sitagliptin. However, there was no significant intergroup difference in improvement at 12 months after the start of sitagliptin. The same result was also obtained in residual analysis. CONCLUSIONS: The present study suggested that the season of administration of sitagliptin influenced the subsequent hypoglycemic effect even after analysis excluding the influence of HbA1c value at the start of treatment. This study provides possibility, showing that seasonal fluctuations have an effect on the efficacy of antidiabetic drugs.

Erratum to: Efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus and comparison of hypoglycemic action of concomitant medications: a subanalysis of the JAMP study.

[This corrects the article DOI: 10.1007/s13340-017-0330-2.].

Renal Function During an Open-Label Prospective Observational Trial of Sitagliptin in Patients With Diabetes: A Sub-Analysis of the JAMP Study.

BACKGROUND: The aim of the study was to determine the effects of sitagliptin on renal function in a diabetic population including patients with normal renal function. METHODS: We analyzed the association between 12-month, 50 mg/day sitagliptin and renal function in outpatients with type 2 diabetes mellitus and poor blood glucose control in a subset of patients in the larger Januvia Multicenter Prospective Trial in Type 2 Diabetes observational study. Stratified analyses of changes in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were performed. Factors associated with changes in eGFR at 3 months were examined by multivariate regression analysis. RESULTS: Of the 779 patients enrolled, 585 were followed up for 12 months. eGFR decreased significantly from baseline at 3 and 12 months in patients with a baseline eGFR of ≥ 90 mL/min/1.73 m2 and in those with a baseline eGFR of ≥ 60 to < 90 mL/min/1.73 m2. Conversely, eGFR tended to increase at 3 and 12 months in patients with a baseline eGFR of ≥ 45 to < 60 mL/min/1.73 m2 and in those with a baseline eGFR of ≥ 30 to < 45 mL/min/1.73 m2. UACR decreased significantly (-21.6 (-46.8, 7.8)) at 3 months in patients with a baseline UACR of ≥ 30 mg/g Cre. Multivariate regression analysis of factors associated with changes in eGFR at 3 months revealed that higher baseline eGFR and greater decline in UACR were associated with more conspicuous decreases in eGFR. CONCLUSIONS: In this group of diabetic patients receiving sitagliptin, eGFR declined in patients with high baseline eGFR, but not in those with a low baseline eGFR.

Efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus and comparison of hypoglycemic action of concomitant medications: a subanalysis of the JAMP study.

PURPOSE: To determine the efficacy and safety of sitagliptin when used with some therapeutic drugs to treat elderly patients. METHODS: Sitagliptin (50 mg/day) was added to the pre-existing therapy for type 2 diabetes. Changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline, and exploratory analysis was performed. These analyses were conducted as subanalyses of the JAMP study, which was an open-label observational study. RESULTS: For patients who were ≥65 years of age, the change in HbA1c level from baseline ranged from -0.50 to -0.87% at 3 months after starting treatment. There was no significant difference in the change in HbA1c level between the patients treated with different concomitant drugs. No significant difference in HbA1c variations at 3 and 12 months from baseline was noted among the three age groups (≥75, 65-74, and <65 years). Multiple regression analysis was performed, and it revealed that patients with higher HbA1c levels at baseline were likely to show decreased HbA1c levels, while those with higher triglyceride (TG) levels were unlikely to show decreased HbA1c levels. CONCLUSION: Sitagliptin has the potential to both improve glycemic control and prevent hypoglycemia, and can be considered a potent alternative drug.

Factors involved in decreasing the therapeutic effect of sitagliptin: a subanalysis of the JAMP study.

OBJECTIVE: As a subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes (JAMP study), we examined factors that decreased blood glucose control effect of sitagliptin after 3 months and patients requiring an addition or increase of diabetes treatment. METHODS: We selected patients in whom glycated hemoglobin (HbA1c) levels decreased by month 3 after initiation of sitagliptin treatment and conducted two analyses: (1) in patients who did not change drugs until month 12, we compared changes in HbA1c levels between concomitant drugs and examined factors that decreased blood glucose control effect of sitagliptin; (2) compared changes in HbA1c levels and backgrounds between patients who did and did not require an addition to or increased dose of the antidiabetic agent. RESULTS: Four hundred and ninety-eight patients were chosen. In 369 patients without drug change until month 12, changes in HbA1c levels during months 3-12 were not significantly different among concomitant drugs; factors causing rebound HbA1c were smoking and weight gain. Patient characteristics were compared between those who did and did not require an additional drug or a dose increase (n = 114) (n = 384). Drug changes were associated with longer disease duration, younger age, higher rate of smoking, and higher degree of insulin resistance but not with concomitantly administered drugs. CONCLUSION: Smoking and weight gain were factors that decreased the effect of sitagliptin on reducing blood glucose levels. Differences in concomitant drugs did not affect sitagliptin's effects on glycemic control. A dose increase or the addition of the antidiabetic drug was not associated with concomitant drugs.

Sodium-glucose co-transporter type 2 inhibitors reduce evening home blood pressure in type 2 diabetes with nephropathy.

BACKGROUND: The effects of sodium-glucose co-transporter type 2 inhibitors on home blood pressure were examined in type 2 diabetes with nephropathy. METHODS: The patients with diabetic nephropathy were screened from medical records in our hospitals. Among them, 52 patients who measured home blood pressure and started to take sodium-glucose co-transporter type 2 inhibitors were selected. Clinical parameters including estimated glomerular filtration rate, albuminuria and home blood pressure for 6 months were analysed. RESULTS: Sodium-glucose co-transporter type 2 inhibitors (luseogliflozin 5 mg/day or canagliflozin 100 mg/day) reduced body weight, HbA1c, albuminuria, estimated glomerular filtration rate and office blood pressure. Although sodium-glucose co-transporter type 2 inhibitors did not alter morning blood pressure, it reduced evening systolic blood pressure. Regression analyses revealed that decreases in evening blood pressure predicted decrements in albuminuria. CONCLUSION: The present data suggest that sodium-glucose co-transporter type 2 inhibitors suppress sodium overload during daytime to reduce evening blood pressure and albuminuria.

Effect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: the JAMP study.

BACKGROUND: To investigate the ameliorating effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood glucose control in patients with type 2 diabetes mellitus who were previously untreated with or who have a poor responsive to existing antidiabetic drugs. METHODS: Sitagliptin (50 mg/day) was added on to the pre-existing therapy for type 2 diabetes and changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline and performed exploratory analysis. RESULTS: HbA1c levels were significantly decreased after 1 month of treatment compared to baseline, with a mean change in HbA1c level from baseline of -0.73% (range, -0.80 to -0.67) in the entire study population at 3 months. Patients who received a medium dose of glimepiride showed the least improvement in HbA1c levels. The percentage of patients who achieved an HbA1c level of <7.0% significantly increased after 1 month of treatment, reaching 53.1% at 3 months. The percentage of patients who achieved a fasting blood glucose level of <130 mg/dL significantly increased after 1 month of treatment, reaching 50.9% at 3 months. CONCLUSIONS: Sitagliptin improved the HbA1c level and rate of achieving the target control levels in patients with type 2 diabetes mellitus who were previously untreated with, or poorly responsive to, existing antidiabetic drugs. Thus, sitagliptin is expected to be useful in this patient group. However, the additional administration of sitagliptin in patients treated with medium-dose glimepiride only slightly improved blood glucose control when corrected for baseline HbA1c level.

Antihypertensive and metabolic effects of hydrochlorothiazide versus amlodipine when added to losartan in patients with type 2 diabetes.

We performed a prospective, randomized, multicenter, parallel-group, per-protocol study to compare the effects of hydrochlorothiazide (HCTZ) and amlodipine as add-on to losartan treatment in hypertensive type 2 diabetic patients. A total of 49 Japanese type 2 diabetic patients with inadequate control of blood pressure while receiving losartan 50 mg were randomly allocated to receive a fixed-dose single-pill combination of HCTZ 12.5 mg plus losartan (N = 26) or a free combination of amlodipine 5 mg plus losartan (N = 23). During 8 weeks of follow-up, changes in blood pressure and laboratory data including HbA1c, uric acid, and potassium were compared between the groups using analysis of covariance. Systolic and diastolic blood pressure decreased in both groups, the reductions of which were greater in the amlodipine group. However, the least square mean (95 % CI) differences between groups were not statistically significant [2.3 (-6.8 to 11.4) mmHg, p = 0.618 and 2.7 (-2.4-7.9) mmHg, p = 0.293, respectively]. HbA1c increased in patients receiving HCTZ but not in the amlodipine group. Uric acid also increased in patients receiving HCTZ but decreased in patients receiving amlodipine, yielding a significant between-group difference of 1.0 (0.5-1.5) mg/dl (p < 0.001). No intra- or intergroup change was observed in serum potassium levels. This pilot study suggests that HCTZ and amlodipine result in nonsignificant effects on systolic and diastolic blood pressure reduction when administrated as add-on therapy to losartan in hypertensive patients with type 2 diabetes; however, addition of HCTZ may be associated with less favorable effects on metabolic profiles than amlodipine.

Variations in the associations of taste-related words with foods in diabetic patients in Japan according to gender, age, and geographical region: a multicenter study conducted in seven regions of Japan.

Although expressions such as "sweet foods" and "fatty foods" are often used without hesitation when communicating with diabetic patients, little is known about what kinds of food items patients associate these expressions with. We therefore investigated these associations by conducting a questionnaire-based survey in seven outpatient clinics in Japan. Patients were asked which food items came into their mind when they heard the following taste-related words: sweet, fatty, salty, sour, hot, and bitter. Multiple answers were allowed. A total of 6,770 diabetic outpatients were analyzed in the current study. The three food items that were most popularly mentioned as sweet foods were Japanese confectionery, cakes, and chocolates. Although a majority of the population (86 %) mentioned at least one of these three food items, the percentage of patients that mentioned a particular food item was at the most 58 %, indicating that patients did not always mention the same food items in association with each taste-related word. The associations varied significantly with gender and age (all p < 0.05); sweet foods were more likely to be associated with Japanese confectionery by old patients but with cakes and chocolates by young patients, whereas males less commonly mentioned these food items than females. Furthermore, there were significant geographic variations in the foods associated with a sweet taste. Such variations in taste-to-food association according to gender, age, and geographical region were also observed for the other taste-related words. In conclusion, the likelihood that a specific food item would be associated with a particular taste-related word varied among the diabetic patients, and there were significant gender, age, and region variations in the taste-to-food associations. These variations would be worth considering during nutrition counseling in clinical practice.

Association between plasma oxidized low-density lipoprotein and diabetic nephropathy.

To investigate the association of oxidized low-density lipoprotein (ox-LDL) with the development of diabetic nephropathy, plasma levels of ox-LDL were measured in 70 patients with type 2 diabetes mellitus. A sandwich enzyme-linked immunoadsorbent assay (ELISA) using the mouse monoclonal antibody FOH1a/DLH3, which specifically recognizes oxidized phosphatidylcholine, and a horseradish peroxidase (HRP)-labeled goat anti-human apolipoprotein B IgG was used to measure ox-LDL levels. The mean age of the patients was 57.0+/-1 3.4 years, and the mean duration of diabetes was 13.4+/-8.5 years. Plasma ox-LDL levels were similar in patients with normoalbuminuria (13.7+/-3.9 U/ml), patients with microalbuminuria (12.8+/-3.9 U/ml), and normal controls (12.5+/-4.2 U/ml). However, the plasma ox-LDL level in patients with macroalbuminuria (16.8+/-7.5 U/ml) was significantly higher than those in the other groups (P<0.05). Hemoglobin A1c (HbA1c) levels were similar in diabetic patients with normoalbuminuria (8.2+/-2.2%), microalbuminuria (7.8+/-1.3%), or macroalbuminuria (7.2+/-1.4%). There was no significant correlation between the ox-LDL level and the HbA1c level. The significantly elevated plasma ox-LDL levels in patients with macroalbuminuria suggest that ox-LDL may play an important role in the progression of diabetic nephropathy.