Vitamin B6 intake and incidence of diabetic retinopathy in Japanese patients with type 2 diabetes: analysis of data from the Japan Diabetes Complications Study (JDCS).

PURPOSE: Although vitamin B6 has been suspected to prevent the progression of diabetic retinopathy, evidence of this in patients with type 2 diabetes based on longitudinal studies is sparse. This study investigated the relationship between vitamin B6 intake and the incidence of diabetic retinopathy in Japanese patients with type 2 diabetes. METHODS: The study was part of an examination of a nationwide cohort of patients with type 2 diabetes aged 40-70 years with HbA1c ≥ 48 mmol/mol. After excluding nonresponders to a dietary survey using the Food Frequency Questionnaire based on food groups, 978 patients were analyzed. Primary outcome was the 8-year risk of a diabetic retinopathy event, and Cox regression analyses estimated hazard ratios (HRs) for retinopathy according to vitamin B6 intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. RESULTS: Mean vitamin B6 intake in quartiles ranged from 1.1 to 1.6 mg/day, and half of the participants had vitamin B6 intake below the recommended daily dietary allowance according to dietary reference intakes in Japanese adults (men 1.4 mg/day; women 1.2 mg/day). After adjusting for confounders, HRs for diabetic retinopathy in the 2nd, 3rd, and 4th quartile groups of vitamin B6 intake compared with the 1st quartile group were 1.17 (95% confidence interval 0.81-1.69, p = 0.403), 0.88 (0.58-1.34, p = 0.550), and 0.50 (0.30-0.85, p = 0.010), respectively. CONCLUSIONS: Findings suggested that high vitamin B6 intake was associated with a lower incidence of diabetic retinopathy in Japanese with type 2 diabetes.

Meat intake and incidence of cardiovascular disease in Japanese patients with type 2 diabetes: analysis of the Japan Diabetes Complications Study (JDCS).

PURPOSE: Excessive meat intake has been researched as a major cause of cardiovascular disease (CVD) among healthy adults, but data on this topic in Asian patients with diabetes are sparse. The quantity and variety of available meats vary widely between Asian and Western countries. As part of a nationwide cohort study we investigated the relationship between meat intake and incidence of CVD in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c ≥ 6.5%. METHODS: Analyzed were 1353 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 8-year risk of a CVD event, including coronary heart disease (CHD) and stroke. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. RESULTS: Mean meat intake in quartiles ranged from 9.9 to 97.7 g/day. After adjusting for confounders, HRs of CHD in the 2nd, 3rd, and 4th quartiles for meat intake compared with the 1st quartile were 2.84 (95% confidence interval 1.29-6.24, p = 0.01), 3.02 (1.36-6.70, p < 0.01), and 2.99 (1.35-6.65, p = 0.01), respectively. In two groups according to meat intake, patients consuming ≥ 20 g/day of meat had a 2.94-fold higher risk of CHD than those consuming < 20 g/day (p < 0.01). There was no significant association of stroke with meat intake. CONCLUSIONS: An elevated incidence of CHD in Japanese patients with type 2 diabetes was associated with high meat intake.

Fruit intake and incident diabetic retinopathy with type 2 diabetes.

BACKGROUND: Antioxidants and dietary fiber are postulated to have preventive effects on diabetic retinopathy, but evidence is lacking. We investigated this association in a cohort with type 2 diabetes 40-70 years of age with hemoglobin (Hb)A1C ≥6.5%, originally part of the Japan Diabetes Complications Study. METHODS: After excluding people who did not respond to a dietary survey and patients with diabetic retinopathy or a major ocular disease at baseline, we analyzed 978 patients. Baseline dietary intake was assessed by a food frequency questionnaire based on food groups and 24-hour dietary records. Primary outcome was incident diabetic retinopathy determined using international severity scales. RESULTS: Mean fruit intake in quartiles ranged from 23 to 253 g/day, with increasing trends across quartiles of fruit intake for vitamin C, vitamin E, carotene, retinol equivalent, dietary fiber, potassium, and sodium. Mean energy intake ranged from 1644 to 1863 kcal/day, and fat intake was approximately 25%. HbA1C, body mass index, triglycerides, and systolic blood pressure were well controlled. During the 8-year follow-up, the numbers of incident cases of diabetic retinopathy from the first through the fourth quartiles of fruit intake were 83, 74, 69, and 59. Multivariate-adjusted hazard ratios for the second, third, and fourth quartiles of fruit intake compared with the first quartile were 0.66 (95% confidence interval = 0.46-0.92), 0.59 (0.41-0.85), and 0.48 (0.32-0.71) (test for trend, P < 0.01). There was no substantial effect modification by age, sex, HbA1C, diabetes duration, overweight, smoking, and hypertension. Risk for diabetic retinopathy declined with increased intake of fruits and vegetables, vitamin C, and carotene. CONCLUSION: Increased fruit intake in ranges commonly consumed was associated with reduced incident diabetic retinopathy among patients adhering to a low-fat energy-restricted diet.

Risk of cardiovascular diseases is increased even with mild diabetic retinopathy: the Japan Diabetes Complications Study.

OBJECTIVE: Diabetic retinopathy (DR) is linked to cardiovascular risk in diabetic patients. This study examined whether mild-stage DR is associated with risk of coronary heart disease (CHD) and stroke in type 2 diabetic patients of the Japan Diabetes Complications Study (JDCS). DESIGN: Prospective cohort study. PARTICIPANTS: In the JDCS, there were 2033 Japanese persons with type 2 diabetes free of cardiovascular diseases at baseline. METHODS: Diabetic retinopathy was ascertained from clinical and photographic grading (70%) following the international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Incident CHD and stroke were followed up prospectively annually up to 8 years. MAIN OUTCOME MEASURES: Eight-year incidence of CHD and stroke compared between persons with or without DR. RESULTS: After adjusting for traditional cardiovascular risk factors, persons with mild to moderate nonproliferative DR had a higher risk of CHD (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.17-2.97) and stroke (HR, 2.69; 95% CI, 1.03-4.86). Presence of retinal hemorrhages or microaneurysms was associated with risk of CHD (HR, 1.63; 95% CI, 1.04-2.56) but was not associated with stroke (P = 0.06). Presence of cotton-wool spots was associated with risk of incident stroke (HR, 2.39; 95% CI, 1.35-4.24) but was not associated with CHD (P = 0.66). When information about DR was added in the prediction models for CHD and stroke based on traditional cardiovascular risk factors, the area under the receiver operating curve improved from 0.682 to 0.692 and 0.640 to 0.677, and 9% and 13% of persons were reclassified correctly for CHD and stroke, respectively. CONCLUSIONS: Type 2 diabetic patients with even a mild stage of DR, such as dot hemorrhages, are already at higher risk of CHD and stroke independent of traditional risk factors.

The long-term coronary heart disease risk of previously obese patients with type 2 diabetes mellitus.

BACKGROUND: Obesity is associated with insulin resistance, development of diabetes, and coronary heart disease. There is limited information on the contribution of previous obesity on the risk of coronary heart disease. We aimed to examine the effect of previous history of obesity on the occurrence of coronary heart disease in patients with diabetes. METHODS: We carried out a retrospective chart analysis of 315 type 2 diabetic patients without obesity and without atherosclerotic cardiovascular events at their initial hospital visit (men/women 236/79; mean ± standard deviation; age 53.1 ± 6.6 years; maximal body mass index before enrollment (MAXBMI) 26.6 ± 3.4 kg/m2; decrease of the BMI at enrollment from MAXBMI (deltaBMI) 4.23 ± 2.62 kg/m2) to investigate the association of previous obesity (MAXBMI larger than 30 kg/m2) with the long-term incidence of cardiovascular events. Of 315 patients, forty-eight were previously obese. RESULTS: After median follow-up of 13.9 years, 48 patients developed coronary heart disease. The Kaplan-Meier analysis exhibited that coronary heart disease occurred more frequently in previously obese patients than in subjects in the reference category (22 kg/m2 < or = MAXBMI < 25 kg/m2) and that the effect lasted proportionally over follow-up periods. Multivariate Cox regression models showed that hazard ratios and corresponding 95% confidence intervals of coronary heart disease for patients with previous obesity compared with subjects in the reference category were 2.52 and 1.15 to 5.50 (p value = 0.020) after adjustment for age, sex, smoking status, systolic blood pressure, total cholesterol and HDL cholesterol. In this cohort, deltaBMI strongly correlated with MAXBMI and also behaved as a risk factor. The hazard ratios and 95% confidence intervals by the increment of one standard deviation of deltaBMI after adjustment for age, sex, smoking status, systolic blood pressure, total cholesterol and HDL cholesterol were 1.38 and 1.08 to 1.79 (p value = 0.013). CONCLUSIONS: Previous obesity and/or large body weight loss before admission might act as an increased risk for coronary heart disease.

Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice.

The CBP protein (cAMP response element binding protein (CREB) binding protein) is a co-activator for several transcription factors with a wide range of important biological functions, such as sterol regulatory element binding proteins (SREBPs), CCAAT/enhancer-binding proteins (C/EBPs), nuclear receptors (including peroxisome proliferator-activated receptors, PPARs), and signal transducers and activators of transcription (STATs). In contrast to these individual transcription factors, the biological roles of CBP are poorly understood. CBP enhances transcriptional activities via histone acetylation and the recruitment of additional co-activators such as SRC (steroid coactivator)-1 (ref. 9). To identify its physiological functions using a loss-of-function mutant, we analyzed CBP-deficient mice. As Crebbp null mice (Crebbp-/-) died during embryogenesis, we used Crebbp+/- mice. Unexpectedly, Crebbp+/- mice showed markedly reduced weight of white adipose tissue (WAT) but not of other tissues. Despite this lipodystrophy, Crebbp+/- mice showed increased insulin sensitivity and glucose tolerance and were completely protected from body weight gain induced by a high-fat (HF) diet. We observed increased leptin sensitivity and increased serum adiponectin levels in Crebbp+/- mice. These increased effects of insulin-sensitizing hormones secreted from WAT may explain, at least in part, the phenotypes of Crebbp+/- mice. This study demonstrates that CBP may function as a 'master-switch' between energy storage and expenditure.

Association between Low Protein Intake and Mortality in Patients with Type 2 Diabetes.

The aim of this study was to investigate the association between protein intake and mortality risk in patients with type 2 diabetes. We analyzed a pooled data of 2494 diabetic patients from two prospective longitudinal studies. Nutritional intake was assessed using a Food Frequency Questionnaire at baseline. Protein intake per body weight (kg) per day was categorized into quartile groups. Adjusted hazard ratios (HRs) and 95% confidence interval (CI) were calculated using Cox regression analysis. During the six-year follow-up, there were 152 incidents of all-cause mortality. The HR for mortality in the lowest quartile of protein intake per body weight compared with the highest quartile was 2.26 (95% CI: 1.34-3.82, p = 0.002) after adjustment for covariates. Subgroup analyses revealed significant associations between low protein intake and mortality in patients aged over 75 years or under 65 years. After further adjustment of the total energy intake, a significant association between protein intake and mortality remained in patients aged ≥ 75 years, whereas the association was attenuated in those aged < 65 years. Our results suggest that adequate protein intake is necessary in older diabetic patients over 75 years, whereas with diabetes, whereas whole optimal total energy intake is required in younger patients with type 2 diabetes.

Effect of mitiglinide on glycemic control over 52 weeks in Japanese type 2 diabetic patients insufficiently controlled with pioglitazone monotherapy.

This study was performed to examine the efficacy and safety of the rapid- and short-acting insulinotropic SUR ligand mitiglinide given as add-on therapy for 52 weeks in type 2 diabetic patients whose blood glucose was insufficiently controlled by pioglitazone monotherapy. Type 2 diabetic patients aged > or = 20 years with postprandial plasma glucose (PPG1 or 2) > or = 200 mg/dL and glycated hemoglobin (HbA(1C)) 6.5-<9.0% despite receiving pioglitazone 15-45 mg/day were additionally treated with concomitant mitiglinide 10 mg tid p.o. for a total treatment period of 52 weeks. In 171 patients recruited, HbA(1C) was significantly reduced from 7.64 +/- 0.77% at baseline to 6.84 +/- 0.73%, 6.64 +/- 0.64%, 6.67 +/- 0.57% and 6.81 +/- 0.65% at weeks 16, 28, 40, and 52, respectively. Over half the patients achieved HbA(1C) target of <7.0%, and one third <6.5%. Significant reductions in fasting plasma glucose (FPG) and PPG 1 and 2 hours after a meal versus baseline were noted at all time-points evaluated. The most frequently noted adverse reactions were hypoglycemic symptoms, weight gain, and peripheral edema (all mild). In type 2 diabetic patients combination therapy with mitiglinide and pioglitazone exerted significant long-term improvements in HbA(1C), FPG, and PPG and was well tolerated. This drug combination therapy is a promising means of alleviating insufficient pancreatic insulin secretion and insulin resistance.

Addition of mitiglinide to pioglitazone monotherapy improves overall glycemic control in Japanese patients with type 2 diabetes: a randomized double blind trial.

A 16-week, multicenter, randomized, double blind, parallel-group study was performed to examine whether additional administration of mitiglinide improves glycemic control in Japanese type 2 diabetic patients who are insufficiently controlled by pioglitazone monotherapy. Japanese adult type 2 diabetic patients were at first treated with diet plus pioglitazone 15-30 mg/day for 4 weeks then randomized to receive additional mitiglinide 5 or 10 mg or placebo tid for a further 16 weeks. In all, 381 patients were randomized. At final evaluation, glycated hemoglobin (HbA(1C)) was reduced by (mean +/- SD) -0.02 +/- 0.60% in the pioglitazone monotherapy group and by -0.45 +/- 0.77% and -0.67 +/- 0.59% in the mitiglinide 5 and 10 mg combination groups, respectively (both p<0.001 vs. pioglitazone monotherapy group). The percentage of patients who achieved HbA(1C) targets was significantly (p<0.001) higher in the mitiglinide combination groups than in the pioglitazone monotherapy group. Significant improvements in fasting plasma glucose and postprandial plasma glucose were noted in the mitiglinide combination groups versus the pioglitazone monotherapy group. No increase in adverse events was noted when mitiglinide was administered concomitantly with pioglitazone monotherapy. Hypoglycemic adverse events were infrequently and similarly observed in all three groups. Body weight gain and edema presented no clinical problem. HbA(1C) was significantly improved in the mitiglinide combination groups compared with the pioglitazone monotherapy group, and significantly more patients achieved HbA(1C) targets. Therefore mitiglinide effectively improves glycemic control in type 2 diabetic patients who are inadequately controlled by pioglitazone monotherapy.

Distribution of blood glucose and the correlation between blood glucose and hemoglobin A1c levels in diabetic outpatients.

PURPOSE OF THE STUDY: Tight glycemic control is important for the prevention of microvascular complications in diabetic patients. We examined the reliability of using blood glucose levels measured at various time-points relative to a meal as an index of glycemic control in Japanese diabetic outpatients. Basic procedures followed: We examined the correlation between the fasting blood glucose (FBG) level; the one-hour (1-h), two-hour (2-h), and three-hour (3-h) post breakfast blood glucose (PBBG) levels, the 1 h, 2 h, and 3 h post lunch blood glucose (PLBG) levels and the hemoglobin A1c (HbA1c) levels in Japanese diabetic outpatients. A total of 11451 patient-visits to the Marunouchi Hospital between January 2002 and December 2002 were included in the study. The main findings: The blood glucose levels measured at all of the above time-points were significantly correlated with the HbA1c level. As calculated using local polynomial regression fitting, the FPG, 1-h, 2-h, and 3-h PBBG levels that corresponded to an HbA1c level of 6.5% were 132 mg/dL, 174 mg/dL, 170 mg/dL, and 143 mg/dL, respectively. The FPG and 2-h PBBG levels exhibited a good sensitivity and specificity for predicting a glycemic control corresponding to an HbA1c<5.8%, while the FPG and 3-h PBBG levels exhibited fair sensitivity and specificity for predicting glycemic control corresponding to an HbA1c<6.5%. The principal conclusions: The FBG, 2-hPBBG, and 3-hPBBG levels can be used as rough estimates of glycemic control in Japanese diabetic outpatients.

Hepatic safety profile and glycemic control of pioglitazone in more than 20,000 patients with type 2 diabetes mellitus: postmarketing surveillance study in Japan.

The prospective observational study was designed to identify factors affecting glycemic control with pioglitazone and to confirm the hepatic safety of the drug in patients with type 2 diabetes. Baseline patient characteristics, changes in serum hemoglobin A1c (A1c) and alanine aminotransferase (ALT), other treatments for diabetes mellitus, and hepatobiliary adverse reactions were examined. In total, 24,993 patients, representing 28,008 patient-years, were included in the safety evaluation and 20,447 patients in the efficacy evaluation. No case of hepatic failure was reported, and neither temporal nor dose relations were found between pioglitazone and ALT abnormalities. Serum A1c was clearly reduced in patients with baseline body mass index <25 kg/m(2) or baseline fasting immunoreactive insulin <5.0 microU/mL. Among the patients treated for more than 6 months, the change in A1c was -1.0% at 6 months with both monotherapy and combination therapy and remained stable up to 18 months. The overall rate of achievement of A1c<7% in patients with baseline A1c above 7% was 34.1%; notably, the achievement rate of A1c<7% was approximately 30% even in patients with high baseline A1c (mean 8.8%) taking multiple antidiabetic medications, including sulfonylurea, for whom insulin therapy is usually indicated in Japan.

A long-term effect of epalrestat on motor conduction velocity of diabetic patients: ARI-Diabetes Complications Trial (ADCT).

In order to study a long-term effect along with adverse action of epalrestat, an aldose reductase inhibitor, a randomized, prospective study was conducted over the period of 3 years at 112 facilities. Six hundred and three diabetic patients with median motor conduction velocity (MCV)>40 m/s, HbA1c<9% were randomly allocated to epalrestat (50 mg/day p.o. ac, t.i.d.) group (E group: n=289, age: 61+/-9.8 y.o.) and a control group (C group: n=305, age: 61+/-9.1 y.o.). MCV was measured once a year for 3 years. MCV (m/s, M+/-S.D.) on baseline, 1 year and 3 years, was 52.0+/-4.5, 52.2+/-4.9, 52.1+/-4.6 in E group and 53.3+/-4.4, 52.4+/-4.2, 52.0+/-4.6 in C group, respectively. After 3 years, difference from the baseline was significant (p<0.0001, E versus C). Among the subjects with HbA1c<7.0%, C group showed marked deterioration of MCV while in E group, there was no significant deterioration (p<0.001). Although, the subjects with pre-proliferative or proliferative retinopathy, there was no difference between E and C groups for 3 years, in subjects with background retinopathy or without retinopathy, deterioration rate of E group was significantly less than that of C group (p<0.0001). Epalrestat was found to prevent deterioration of MCV especially in well-controlled patients without advanced complications. No remarkable side effects serious enough to discontinue the study was observed.

Cross-sectional association between BMI, glycemic control and energy intake in Japanese patients with type 2 diabetes. Analysis from the Japan Diabetes Complications Study.

Although, weight loss is associated with improved glycemic control in diabetic patients, the relationships between patient weight, daily energy intake (EI), and glycemic or other control status have been poorly investigated. Baseline characteristics of the Japan Diabetes Complications Study, a representative cohort of Japanese diabetic patients, were used for quartile analysis stratified according to patient body mass index (BMI) and EI. Despite a 1.4-fold discrepancy in BMI between the highest and the lowest quartiles, no significant linear trend in HbA(1C) levels or EI between quartiles was seen, although, waist/hip ratio, blood pressure, total cholesterol and triglycerides increased and HDL cholesterol decreased with the increase in BMI. Quartile analysis, according to EI, revealed a 1.8-fold elevation in EI between the lowest and the highest quartile. Nevertheless, the differences in patient BMI between the lowest and the highest quartile were no more than 3% and there were no significant linear trends among the four quartiles in most parameters including HbA(1C), blood pressure, serum lipids. These results revealed only very limited cross-sectional correlations among BMI, EI and other parameters suggesting that it is necessary to consider much wider variations in ideal weight and optimal dietary prescription when making assessments of diabetic patients.

Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial.

OBJECTIVE: We sought to evaluate the long-term efficacy and safety of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: Subjects with diabetic neuropathy, median motor nerve conduction velocity (MNCV) >or=40 m/s, and HbA(1c)

Patients with type 2 diabetes having higher glomerular filtration rate showed rapid renal function decline followed by impaired glomerular filtration rate: Japan Diabetes Complications Study.

AIMS: The Japan Diabetes Complications Study (JDCS), a nation-wide, multicenter, prospective study of patients with type 2 diabetes, reported that hemoglobin A1c (HbA1c), systolic blood pressure, and smoking were risk factors for the onset of macroalbuminuria. This study explored the risk factors for glomerular filtration rate (GFR) decline in the JDCS patients. METHODS: We examined the 1407 JDCS patients (667 women, mean age 59years, 974 normoalbuminuria, 433 microalbuminuria) whose urinary albumin-to-creatinine ratio (UACR) and estimated GFR (eGFR) were determined at baseline with an 8-year follow-up. We divided all the patients into four groups according to baseline eGFR: G1 (120≤eGFR), G2 (90≤eGFR<120), G3 (60≤eGFR<90), G4 (eGFR<60). RESULTS: The eGFRs in groups G1 and G2 decreased at follow-up compared to those at the baseline. The risk of annual eGFR decline rate≥3ml/min/1.73m2 (rapid decliners) increased as the baseline eGFR increased. Advanced age, high HbA1c, and UACR, or diabetic retinopathy at baseline were risk factors for the rapid decliners. Especially the G1 group had a significant risk for the rapid decliners. The frequency of the patients with GFR<60ml/min/1.73m2 at the follow-up amounted to 31.1% in the rapid decliners, which was higher than 12% in the non-rapid decliners. CONCLUSIONS: In normo- and microalbuminuric patients with type 2 diabetes, extra careful attention should be paid to patients with eGFR ≥120ml/min/1.73m2 to detect cases with rapidly decreased GFR under the normal range.

Is the Proportion of Carbohydrate Intake Associated with the Incidence of Diabetes Complications?-An Analysis of the Japan Diabetes Complications Study.

The appropriate proportions of macronutritional intake have been controversial in medical nutritional therapy for diabetes, and evidence of the effects of carbohydrate consumption on diabetes complications in prospective settings is sparse. We investigated the relationships between proportions of carbohydrate intake as the % of total energy and diabetes complications in a nationwide cohort of Japanese patients with type 2 diabetes aged 40-70 years with hemoglobin A1c ≥6.5%. The analysis was of 1516 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to overt nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) after 8 years. Hazard ratios (HRs) for proportions of carbohydrate intake were estimated by Cox regression adjusted for confounders. High carbohydrate intake was significantly related to higher intakes of grain, fruits, and sweets/snacks and lower intakes of soybean and soy products, vegetables, seaweed, meat and processed meat, fish and processed fish, eggs, milk and dairy products, oil, and alcoholic beverages. During the eight-year follow-up, there were 81, 275, and 129 events of overt nephropathy, diabetic retinopathy, and CVD, respectively. After adjustment for confounders, HRs for complications in patients with carbohydrate intake in the second or third tertiles (51.0%-56.4% and ≥56.5%, respectively) compared with carbohydrate intake in the first tertile (<50.9%, referent) were analyzed. No significant associations were shown in the second and third tertiles relative to first tertile (overt nephropathy: 1.05 (95% Confidence Interval, 0.54-2.06) and 0.98 (0.40-2.44); diabetic retinopathy: 1.30 (0.90-1.88) and 1.30 (0.78-2.15); and CVD: 0.95 (0.55-1.63) and 1.37 (0.69-2.72)). By exploring potentially nonlinear relationships, trends for the incidence of diabetes complications according to proportions of carbohydrate intake were not clearly shown. Findings suggested that proportions of carbohydrate intake were not associated with the incidence of diabetes complications among type 2 diabetes patients in Japan.

Association between all-cause mortality and severity of depressive symptoms in patients with type 2 diabetes: Analysis from the Japan Diabetes Complications Study (JDCS).

OBJECTIVE: The aims of this study are to confirm whether the excess mortality caused by depressive symptoms is independent of severe hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and to evaluate the association between all-cause mortality and degrees of severity of depressive symptoms in Japanese patients with T2DM. METHODS: A total of 1160 Japanese patients with T2DM were eligible for this analysis. Participants were followed prospectively for 3years and their depressive states were evaluated at baseline by the Center for Epidemiologic Studies Depression Scale (CES-D). Cox proportional hazards model was used to evaluate the relative risk of all-cause mortality and was adjusted by possible confounding factors, including severe hypoglycemia, all of which are known as risk factors for both depression and mortality. RESULTS: After adjustment for severe hypoglycemia, each 5-point increase in the CES-D score was significantly associated with excess all-cause mortality (hazard ratio 1.69 [95% CI 1.26-2.17]). The spline curve of HRs for mortality according to total CES-D scores showed that mortality risk was slightly increased at lower scores but was sharply elevated at higher scores. CONCLUSION: A high score on the CES-D at baseline was significantly associated with all-cause mortality in patients with T2DM after adjusting for confounders including severe hypoglycemia. However, only a small effect on mortality risk was found at relatively lower levels of depressive symptoms in this population. Further research is needed to confirm this relationship between the severity of depressive symptoms and mortality in patients with T2DM.

Is the diagnosis of metabolic syndrome useful for predicting cardiovascular disease in asian diabetic patients? Analysis from the Japan Diabetes Complications Study.

OBJECTIVE: The metabolic syndrome (MetS) is believed to be associated with an increased risk of cardiovascular disease (CVD). Although its prevalence is extremely high among diabetic patients, its prevalence in those with no history of CVD has not been determined. Moreover, prospective studies published on the association between MetS and cardiovascular events in diabetic populations have used only the World Health Organization (WHO) definition of MetS and included only white European subjects. The aim of this study was to determine the prevalence of MetS, as defined by both the WHO and the National Cholesterol Education Program (NCEP), and its predictive value for CVD in Asian diabetic patients in a long-term, prospective setting. RESEARCH DESIGN AND METHODS: The baseline characteristics and incidence/hazard ratio of cardiovascular events (coronary heart disease and stroke) were determined in 1,424 Japanese type 2 diabetic patients with and without MetS, as defined by WHO (WHO-MetS) or the NCEP. RESULTS: A high prevalence (38-53%, depending on sex and definition) of MetS was found among diabetic patients, even those with no history of CVD. During the 8-year study period, only WHO-MetS was a predictor for CVD in female patients. In male patients, although both definitions of MetS were significant predictors for CVD, individual components of MetS, such as hyperlipidemia or hypertension, were equivalent or better predictors. CONCLUSIONS: We found that MetS is relatively common in diabetic patients with no history of CVD. We suggest that the commonly used definitions of MetS, at least in their present forms, have limited clinical usefulness for Asian diabetic patients and may need some ethnic group-specific modifications for global use.