Association of self-stigma with glycated hemoglobin: A single-center, cross-sectional study of adults with type 1 diabetes in Japan.

AIMS/INTRODUCTION: There has been an increase in research on diabetes-related stigma and its association with glycated hemoglobin (HbA1c) over the past years. However, little is known about the association of self-stigma with HbA1c in persons with type 1 diabetes. This study aims to examine the association between self-stigma and HbA1c in Japanese people with type 1 diabetes. MATERIALS AND METHODS: This cross-sectional study was conducted at a clinic in Tokyo. Questionnaires using nine items from the Japanese version of the Self-Stigma Scale was distributed to outpatients with type 1 diabetes, aged ≥18 years. We excluded outpatients with serious mental disorder, those who required urgent medical treatment or received hemodialysis. Adjusted linear regression analyses tested the association between the score of the 9-item Self-Stigma Scale and HbA1c. RESULTS: Questionnaires were distributed to 166 eligible participants. A total of 109 participants were included in the final analysis after excluding participants with incomplete answers and laboratory data. After adjusting for age, sex, employment status, body mass index, duration of diabetes and insulin secretion, there was a significant positive association between self-stigma and HbA1c (ß = 0.05, 95% confidence interval 0.01 to 0.08). CONCLUSIONS: This cross-sectional study showed a significant association between self-stigma and HbA1c in persons with type 1 diabetes. Addressing self-stigma might be as equally essential as measuring HbA1c in evaluating glycemic outcome among individuals with type 1 diabetes.

Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study.

AIMS/INTRODUCTION: We aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes. MATERIALS AND METHODS: A cross-sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin-to-creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of < 60 mL/min/1.73 m2 . Areas under the curves (AUCs), cutoff values, and thresholds for detecting DKD were determined for the Cu/Zn ratio, soluble tumor necrosis factor-α receptor 1 (sTNFαR1), and high-sensitivity C-reactive protein (hsCRP). Patients were categorized by each cutoff value of sTNFαR1 and the Cu/Zn ratio. Odds ratios (ORs) and biological interactions for the prevalence of DKD were determined. RESULTS: DKD was identified in 220 patients. AUC/optimal cutoff values were 0.777/1300 pg/mL for sTNFαR1, 0.603/1.1648 for the Cu/Zn ratio, and 0.582/305 ng/mL for hsCRP. The ORs for DKD were higher, but not significantly, in the sTNFαR1 < 1300 and Cu/Zn ≥ 1.1648 group, significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P < 0.0001), and further synergistically elevated in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group (P < 0.0001) compared with the sTNFαR1 < 1300 and Cu/Zn < 1.1648 group after multivariable adjustment. Levels of sTNFαR1 were significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group than in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P = 0.0006). CONCLUSIONS: Under an inflammatory initiation signal of elevated serum sTNFαR1 levels, an increase in the Cu/Zn ratio may further exacerbate inflammation and is synergistically associated with a high prevalence of DKD in patients with type 2 diabetes.

Diabetes management by either telemedicine or clinic visit improved glycemic control during the coronavirus disease 2019 pandemic state of emergency in Japan.

The purpose of this retrospective cohort study at a Tokyo diabetes clinic was to evaluate the effect of telemedicine and clinic visit on glycated hemoglobin (HbA1c) during the coronavirus disease 2019 state of emergency. The effect of telemedicine and clinic visit during the emergency period on the post-emergency measured HbA1c was evaluated by multiple regression models and logistic regression models adjusted for age, sex, type of diabetes, pre-emergency HbA1c and body mass index, and body mass index change during the emergency period. Among 2,727 patients who visited the clinic before and after the emergency period, the interval between clinic visits during the emergency period was significantly associated with HbA1c improvement. Telemedicine and clinic visit were independently associated with HbA1c improvement when pre-emergency HbA1c was ≥7%. In conclusion, clinic visit and telemedicine during the coronavirus disease 2019 emergency period were both independently effective in HbA1c improvement in Japanese diabetes patients who had insufficient HbA1c control.

Association of insulin treatment with gastric residue during an esophagogastroduodenoscopy.

The purpose of this study was to investigate the association of glycemic control and diabetes treatment to gastric residue observed during an esophagogastroduodenoscopy. Among 6,592 individuals who had esophagogastroduodenoscopy at our clinic between 2003 and 2019, we retrospectively and longitudinally identified those who had gastric residue during an esophagogastroduodenoscopy. Other data collected were age, sex, diagnosis of diabetes, glycated hemoglobin and diabetes medication. Cox proportional hazards models were used to assess the association of these data with the occurrence of gastric residue. To the best of our knowledge, this is the first retrospective cohort study finding that undergoing insulin treatment is a risk factor for gastric residue independent of age, sex and diabetes or glycated hemoglobin.

Thresholds for postprandial hyperglycemia and hypertriglyceridemia associated with increased mortality risk in type 2 diabetes patients: A real-world longitudinal study.

AIMS/INTRODUCTION: To identify thresholds for postprandial hyperglycemia and hypertriglyceridemia predictive of all-cause mortality in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 1,928 patients with type 2 diabetes visited our clinic for the first time from 1995 to 1999 and were followed up for ≥1 year. During the first year, 2-h post-breakfast blood glucose (2h-BG) levels were measured in 1,122 patients (BG cohort) and postprandial serum triglyceride (ppTG) levels were measured in 1,826 patients (TG cohort). Patients were retrospectively followed until 2017 and administered questionnaires. Associations between 2h-BG and ppTG levels and mortality risk were assessed by the multivariate Cox regression analysis. RESULTS: Over of 17,429 person-years, 162 deaths occurred in the BG cohort, and over 28,026 person-years, 253 deaths occurred in the TG cohort. Hazard ratios (HRs) with 95% confidence intervals for all-cause mortality per 1-standard deviation increases in 2h-BG and ppTG were 1.34 (1.08-1.67) and 1.24 (1.06-1.45), respectively. HRs showed increasing trends across quintiles of 2h-BG (P = 0.034) and ppTG (P = 0.007). The HR was significantly elevated (2.37, 1.26-4.47) in the fifth quintile of 2h-BG (≥13.8 mmol/L) compared with the first quintile (<7.0 mmol/L; P = 0.008). The HR was also significantly elevated (1.63, 1.03-2.60) in the fifth quintile of ppTG (≥2.30 mmol/L) compared with the first quintile (<0.91 mmol/L; P = 0.038). CONCLUSIONS: Postprandial hyperglycemia and hypertriglyceridemia were associated with all-cause mortality in patients with type 2 diabetes. We propose thresholds of 13.8 mmol/L 2h-BG and 2.30 mmol/L ppTG to identify patients at increased risk of mortality.

Combined effect of diabetic retinopathy and diabetic kidney disease on all-cause, cancer, vascular and non-cancer non-vascular mortality in patients with type 2 diabetes: A real-world longitudinal study.

AIMS/INTRODUCTION: We assessed the relationship between diabetic retinopathy (DR) and/or diabetic kidney disease (DKD) according to their severity and all-cause, cancer, vascular and non-cancer non-vascular mortality in real-world patients with type 2 diabetes. MATERIALS AND METHODS: A total of 1,902 patients with type 2 diabetes were enrolled from 1995 to 1999 and followed to 2017. At baseline, DR was diagnosed in 374 patients, DKD in 529, vision-threatening DR in 123 and advanced DKD in 287. Patients were classified by the status of DR and DKD. Multivariate Cox regression analysis was carried out. RESULTS: There were 266 deaths during a median follow-up period of 18.6 years. Among these, 92 were from cancer, 78 were from vascular causes and 82 were from non-cancer non-vascular causes. DR and/or DKD predicted all-cause, vascular and non-cancer non-vascular mortality, but not cancer mortality. Similarly, vision-threatening DR and/or advanced DKD predicted all-cause, vascular and non-cancer non-vascular mortality, but not cancer mortality. Hazard ratios for all-cause, vascular and non-cancer non-vascular mortality were highest in the DR(+)DKD(+) group, and higher in the DR(-)DKD(+) and the DR(+)DKD(-) groups than in the DR(-)DKD(-) group. The results for vision-threatening DR and advanced DKD were similar. The interaction for non-cancer non-vascular mortality, but not all-cause and vascular mortality, between DR and DKD and between vision-threatening DR and advanced DKD might be significant. CONCLUSIONS: DR and DKD may be jointly and independently associated with all-cause, vascular and non-cancer non-vascular mortality, but not cancer mortality, according to their severity in real-world patients with type 2 diabetes.

Effect of postprandial hyperglycemia at clinic visits on the incidence of retinopathy in patients with type 2 diabetes: An analysis using real-world long-term follow-up data.

AIMS/INTRODUCTION: There is little evidence on the role of postprandial glycemia in the incidence of diabetic retinopathy (DR) in a real-world setting. We aimed to assess the effect of postprandial hyperglycemia at clinic visits on the incidence of DR in patients with type 2 diabetes, and whether its effect differs depending on glycated hemoglobin (HbA1c) values and age. MATERIALS AND METHODS: Intrapersonal mean blood glucose levels at 1-2 h post-breakfast (1-2h-PBBG), post-lunch (1-2 h-PLBG) and both (1-2h-PBLBG) during 2 years from the first visit were used as baseline data. This retrospective cohort study enrolled 487, 323 and 406 patients who had 1-2h-PBLBG, 1-2h-PBBG and 1-2h-PLBG measurements, respectively. These three groups were followed from 1999 up through 2017. RESULTS: DR occurred in 145, 92 and 126 patients in the 1-2h-PBLBG, 1-2h-PBBG and 1-2h-PLBG groups, respectively. Multivariate Cox regression analysis showed that the mean 1-2h-PBLBG, 1-2h-PBBG and 1-2h-PLBG levels were significant predictors of DR, independent of mean HbA1c. In patients with mean HbA1c <7.0% and those with a baseline age <60 years, the mean 1-2h-PBLBG, 1-2h-PBBG and 1-2h-PLBG levels were significant predictors. CONCLUSIONS: Postprandial hyperglycemia at clinic visits might predict the incidence of DR, independent of HbA1c. The effect of postprandial hyperglycemia on DR is obvious in patients with well-controlled HbA1c and in younger patients. Even with the lower HbA1c level, correcting postprandial hyperglycemia is important for preventing DR, especially in middle-aged adults with type 2 diabetes.

Causes of death and estimated life expectancy among people with diabetes: A retrospective cohort study in a diabetes clinic.

We sought to estimate the exact causes of death, mortality rate and life expectancy of diabetes patients by analyzing death records in a diabetes specialist clinic in Japan. Of the 6,140 participants included in our analysis, the average age was 58.1 years and 77% were men. A total of 261 deaths were recorded during the total follow-up period of 24,079 total person-years. The leading causes of death were cancer, heart diseases and cerebrovascular diseases. Using a life table prepared from the mortality rates estimated with the exponential distribution model, a life expectancy at 40 years was 39.2 years (95% confidence interval 37.9-40.2 years) for men and 43.6 years (95% confidence interval 41.8-45.3 years) for women. Although the present results must be interpreted with caution, compared with populations with diabetes surveyed during similar periods by the Japan Diabetes Society, our diabetes patients had similar ranking of the causes of death.

Analysis of the duration and extent of the legacy effect in patients with type 2 diabetes: A real-world longitudinal study.

AIMS: To analyze the duration and extent of the legacy effect on diabetic complications in real-world patients with type 2 diabetes. METHODS: This was a retrospective cohort study. We included the following three cohorts of patients: diabetic retinopathy (DR) (n = 1107), diabetic kidney disease (DKD) (n = 1486), and cardiovascular disease (CVD) (n = 1485). Patients were enrolled from 1995 to 1999 and followed up to 2017. Endpoints were DR incidence, ≥40% decrease in estimated glomerular filtration rate, and CVD incidence. The relationships between HbA1c as a time-dependent variable and the risk of reaching each endpoint were analyzed using multivariate Cox regression models. RESULTS: A total of 313 patients developed DR, 316 developed DKD, and 177 developed CVD. Hazard ratios as a function of time-dependent HbA1c (moving mean) accumulated over time. This accumulation was largest for DR, followed by DKD and CVD. The hazard ratios for each endpoint reached a plateau during the preceding 14-19 years. CONCLUSIONS: The effect of past glycemic control may continue during 14-19 years, with a greater effect during ≤10 years. Therefore, the end of the legacy effect could be 15-20 years. This effect may be the greatest for DR, followed by DKD, and the smallest for CVD.

Association between postprandial hyperglycemia at clinic visits and all-cause and cancer mortality in patients with type 2 diabetes: A long-term historical cohort study in Japan.

AIMS: To evaluate the effect of postprandial hyperglycemia at clinic visits on all-cause and cancer mortality independent of glycated hemoglobin (HbA1c) levels in a real-world setting in Japanese patients with type 2 diabetes. We also investigated age at death. METHODS: This historical cohort study included 1582 patients with type 2 diabetes who first visited our clinic from 1995 to 1998 and continued visiting for at least 1 year. The patients were followed up through 2017. Blood glucose levels at 2 h ±â€¯30 min post-breakfast (2h-PBBG) were measured in 926 patients during the first year. The first measurements of 2h-PBBG levels were used as a measure of postprandial hyperglycemia. RESULTS: A total of 233 patients died. The average age at death (men/women) was 75.6/80.8 years. A total of 139 patients who had 2h-PBBG levels measured died, including 46 deaths from cancer. Multivariate Cox regression analysis showed that 2h-PBBG levels significantly predicted all-cause and cancer mortality independent of HbA1c levels. CONCLUSIONS: Postprandial hyperglycemia at clinic visits may be associated with all-cause and cancer mortality in patients with type 2 diabetes independent of HbA1c levels. As this is a small observational study, further studies are warranted to confirm our findings.

Optimal cutoff values of fasting plasma glucose (FPG) variability for detecting retinopathy and the threshold of FPG levels for predicting the risk of retinopathy in type 2 diabetes: A longitudinal study over 27 years.

AIMS: To determine the cutoff values of fasting plasma glucose (FPG) variability for detecting retinopathy and examine the threshold of FPG levels for predicting retinopathy incidence in type 2 diabetes. METHODS: Subjects comprised 170 patients with type 2 diabetes who had no retinopathy at their first visit, and continuously visited thereafter for 27 years. Retinopathy was evaluated by ophthalmologists at least annually. RESULTS: 114 patients developed retinopathy. 46 of them had advanced retinopathy. The optimal cutoff values of intrapersonal mean and standard deviation (SD) of FPG over 27 years and intrapersonal mean HbA1c from the initial measurement to the last visit for detecting retinopathy were 7.4 mmol/L, 1.4 mmol/L, and 7.2% (56 mmol/mol), respectively. Similarly, for advanced retinopathy, 7.7 mmol/L, 1.9 mmol/L, and 7.5% (59 mmol/mol), respectively. Hazard ratios of deciles of intrapersonal mean FPG (mmol/L) during the initial 2 years for retinopathy incidence significantly increased from eighth-decile (6.9-7.4), and were sharply elevated from ninth-decile (7.4-8.7). CONCLUSIONS: Our study provides new cutoff values for FPG variability. Cutoff values of FPG and HbA1c were slightly higher than recommended targets of the current guideline. The threshold of FPG levels (6.9 mmol/L) is proposed to predict retinopathy incidence during the subsequent 25 years.

Predictive ability of visit-to-visit variability in HbA1c and systolic blood pressure for the development of microalbuminuria and retinopathy in people with type 2 diabetes.

AIMS: We explored whether visit-to-visit variability in both glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) simultaneously predicted the development of microalbuminuria and retinopathy, and whether the predictive ability of these measurements changed according to mean HbA1c and SBP levels in people with type 2 diabetes. METHODS: A retrospective observational cohort study was conducted on 243 type 2 diabetes patients with normoalbuminuria and 486 without retinopathy at the first visit and within 1year thereafter. The two cohorts were followed up from 1995 until 2012. Multivariate and stratified analyses were performed using Cox proportional hazard models. RESULTS: Microalbuminuria developed in 84 patients and retinopathy in 108. Hazard ratios (HRs) for the development of microalbuminuria associated with the coefficient of variation (CV) and variation independent of mean (VIM) of both HbA1c and SBP significantly increased. In participants with a mean SBP <130mmHg, the HRs for the development of retinopathy associated with CV and VIM of HbA1c were abruptly elevated and significant compared with those with a mean SBP ≥130mmHg. CONCLUSIONS: Visit-to-visit variability in both HbA1c and SBP simultaneously predict the development of microalbuminuria. HbA1c variability may predict the development of retinopathy when the mean SBP is normal (<130mmHg).

Impact of postprandial hyperglycemia at clinic visits on the incidence of cardiovascular events and all-cause mortality in patients with type 2 diabetes.

AIMS/INTRODUCTION: We evaluated the impact of postprandial hyperglycemia at clinic visits on the incidence of cardiovascular diseases (CVD) and all-cause mortality independently of mean glycosylated hemoglobin in type 2 diabetes patients in a real-world setting. MATERIALS AND METHODS: The present retrospective observational cohort study included 646 type 2 diabetes patients. All of the participants had their initial consultations at the Institute for Diabetes Care and Research, Asahi Life Foundation affiliated Marunouchi Hospital, Tokyo, Japan, during the period from 1995 to 1996, visited the clinic ≥4 times, had their 2-h post-breakfast blood glucose (2h-PBBG) levels measured and were followed up for ≥1 year. The 646 patients were followed up for survival. Of the 646 patients, 618 had no history of CVD at the first visit and had measured 2h-PBBG until the first CVD onset or censorings. These two cohorts were followed up through June 2012, and subsequently questionnaires were mailed. Multivariate Cox proportional hazard models were used to evaluate the risk of CVD incidence and death. RESULTS: CVD occurred in 78 patients, and 56 patients died. The median follow-up periods of the CVD cohort and the mortality cohort were 15.6 and 15.9 years, respectively. The mean 2h-PBBG is a significant predictor of the CVD incidence and all-cause mortality after adjusting for the mean glycosylated hemoglobin, the number of 2h-PBBG measurements, age, sex and classical risk factors. CONCLUSIONS: Postprandial hyperglycemia represented by the mean level of 2h-PBBG at clinic visits is associated with CVD incidence and all-cause mortality independently of the mean glycosylated hemoglobin level in type 2 diabetes patients. Prospective interventional trials are warranted to confirm the present findings.

Prediction of the effect on antihyperglycaemic action of sitagliptin by plasma active form glucagon-like peptide-1.

AIM: To investigate whether active glucagon-like peptide-1 (GLP-1) is a prediction Factor of Effect of sitagliptin on patients with type 2 diabetes mellitus (GLP-1 FEST:UMIN000010645). METHODS: Seventy-six patients with type 2 diabetes, who had insufficient glycemic control [Hemoglobin A1c (HbA1c) ≥ 7%] in spite of treatment with metformin and/or sulfonylurea, were included in the investigation. Patients were divided into three groups by tertiles of fasting plasma active GLP-1 level, before the administration of 50 mg sitagliptin. RESULTS: At baseline, body mass index, serum UA, insulin and HOMA-IR were higher in the high active GLP-1 group than in the other two groups. The high active GLP-1 group did not show any decline of HbA1c (7.6% ± 1.4% to 7.5% ± 1.5%), whereas the middle and low groups indicated significant decline of HbA1c (7.4 ± 0.7 to 6.8 ± 0.6 and 7.4 ± 1.2 to 6.9 ± 1.3, respectively) during six months. Only the low and middle groups showed a significant increment of active GLP-1, C-peptide level, a decreased log and proinsulin/insulin ratio after administration. In logistic analysis, the low or middle group is a significant explanatory variable for an HbA1c decrease of ≥ 0.5%, and its odds ratio is 4.5 (1.40-17.6) (P = 0.01) against the high active GLP-1 group. This remains independent when adjusted for HbA1c level before administration, patients' medical history, medications, insulin secretion and insulin resistance. CONCLUSION: Plasma fasting active GLP-1 is an independent predictive marker for the efficacy of dipeptidyl peptidase 4 inhibitor sitagliptin.

C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus.

In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F-CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to ΔCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization.

The combined effect of visit-to-visit variability in HbA1c and systolic blood pressure on the incidence of cardiovascular events in patients with type 2 diabetes.

OBJECTIVE: To investigate the association between long-term visit-to-visit variability in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) and the incidence of cardiovascular disease (CVD) in patients with type 2 diabetes. METHODS: We retrospectively enrolled 632 patients with type 2 diabetes and no history of CVD who first visited our hospital between 1995 and 1996, were followed-up for ≥1 year, attended at least 4 clinic visits and had at least 1 visit per year. Patients were followed until June 2012 at the latest, and mailed questionnaires. RESULTS: During the median follow-up period (15.4 years), 81 patients developed CVD. Multivariate analysis revealed that the coefficient of variation (CV) and the variation independent of mean (VIM) for HbA1c and SBP were significant predictors of CVD incidence independent of mean HbA1c and SBP. Patients were classified into 4 groups by median HbA1cCV and SBPCV values and by median HbA1cVIM and SBPVIM values. Among these groups, the HRs were highest in the high-HbA1cCV/high-SBPCV and high-HbA1cVIM/high-SBPVIM groups and were significantly higher compared with those in the low-HbA1cCV/low-SBPCV and low-HbA1cVIM/low-SBPVIM groups, respectively. Among patients with mean SBP≥130 mm Hg, the HRs associated with HbA1cCV and HbA1cVIM were drastically elevated compared with those with mean SBP<130 mm Hg (interaction p<0.05). CONCLUSIONS: Long-term visit-to-visit variability in HbA1c and SBP represented a combined and additive risk for CVD incidence in patients with type 2 diabetes. It is suggested that a synergistic effect exists between HbA1c variability and mean SBP levels for CVD incidence.

Relationships between the risk of cardiovascular disease in type 2 diabetes patients and both visit-to-visit variability and time-to-effect differences in blood pressure.

AIMS: To determine whether visit-to-visit blood pressure (BP) variability can predict cardiovascular disease (CVD) incidence in type 2 diabetes patients independently of mean BP, and to analyze the time-to-effect relationship between BP and CVD risk. METHODS: We retrospectively enrolled 629 type 2 diabetes patients with no history of CVD who first visited our hospital between 1995 and 1996, made at least one hospital visit per year, were followed-up for at least 1 year, and had undergone four or more BP measurements. The patients were followed until June 2012 at the latest. RESULTS: CVD occurred in 66 patients. Variability in systolic or diastolic BP (SBP and DBP, respectively) was a significant predictor of CVD incidence, independent of mean SBP or DBP. CVD incidence was significantly associated with SBP during the preceding 3-5 years, with the highest risk occurring during the preceding 3 years. CONCLUSIONS: Visit-to-visit BP variability independently predicts CVD incidence in type 2 diabetes patients. Increased SBP over the preceding 3-5 years indicated a significant CVD risk. To prevent CVD, BP management should focus on stable and well-timed control. In particular, BP stabilization at an early phase and BP control during late phases are important.

Time-to-effect relationships between systolic blood pressure and the risks of nephropathy and retinopathy in patients with type 2 diabetes.

AIMS: To analyze time-to-effect relationships between systolic blood pressure (SBP) and the risks of development of nephropathy and retinopathy in patients with type 2 diabetes. METHODS: We retrospectively enrolled 647 patients with type 2 diabetes who first visited our hospital between 1995 and 1996, made ≥1 hospital visit per year, had been followed-up for ≥1year, and had undergone ≥4 SBP measurements. Of these, 352 with normoalbuminuria and 516 without retinopathy were followed through June 2012. RESULTS: Nephropathy developed in 90 patients and retinopathy in 113. Hazard ratios (HRs) for time-dependent SBP-associated nephropathy and retinopathy were the highest during 1year preceding each endpoint or censoring. The HRs for nephropathy had been steadily lower during the preceding 1-17 years, while that for retinopathy had been lower during the preceding 1-5 years and constant during the preceding 5-17 years. CONCLUSIONS: The time-to-effect relationship with SBP differed for the development of nephropathy and retinopathy. The long-term effect was obvious for nephropathy and borderline for retinopathy, while the short-term effect was stronger and evident for both. Continuous SBP lowering is necessary to prevent nephropathy, whereas SBP control during the preceding 5years seems to be important to prevent retinopathy.

Association between HbA1c variability and mortality in patients with type 2 diabetes.

AIMS: We aimed to evaluate the association between HbA1c variability and mortality due to all causes, cancer, and non-cancer in patients with type 2 diabetes independently of mean HbA1c levels. METHODS: We enrolled 754 patients with type 2 diabetes who first visited our hospital between 1995 and 1996, had been followed for at least 2years, and had undergone four or more HbA1c determinations. Patients were followed through June 2012. The standard deviation (SD) or coefficient of variation (CV) was used as a measure of HbA1c variability. Risk of death was evaluated by multivariate Cox proportional hazard models. RESULTS: Through June 2012, 63 patients died. Hazard ratios (HRs) for all-cause mortality and non-cancer mortality including cardiovascular diseases (CVD) increased across tertiles of both HbA1cSD and HbA1cCV. HRs for cancer mortality did not increase across tertiles of either HbA1cSD or HbA1cCV. Using a stepwise regression method, both HbA1cSD and HbA1cCV predicted all-cause mortality, especially non-cancer mortality. In contrast, mean HbA1c predicted cancer mortality. CONCLUSIONS: HbA1c variability is a predictor of all-cause mortality, especially non-cancer mortality including CVD, in patients with type 2 diabetes, independent of mean HbA1c level. In contrast, mean HbA1c, but not HbA1c variability, might predict cancer mortality.

Visit-to-visit variability in systolic blood pressure predicts development and progression of diabetic nephropathy, but not retinopathy, in patients with type 2 diabetes.

OBJECTIVE: To investigate whether visit-to-visit variability in systolic blood pressure (SBP) can predict development and progression of diabetic nephropathy and retinopathy in patients with type 2 diabetes mellitus (T2DM). METHODS: From 1995 through 1996, 664 T2DM patients visited our hospital for the first time and were subsequently examined 4 times or more and at least once annually. At first visit, 326 had normoalbuminuria, 644 had an estimated glomerular filtration rate (eGFR) of ≥ 45 ml/min/1.73 m(2), 526 had no diabetic retinopathy and 609 had no severe non-proliferative diabetic retinopathy (NPDR). They were followed through June 2012, at the latest. RESULTS: Ninety patients developed microalbuminuria, 76 showed decrease of eGFR to <45 ml/min/1.73 m(2), 113 developed mild-moderate NPDR and 50 progression to severe NPDR. The unadjusted, age- and sex-adjusted and multivariate-adjusted hazard ratios for development and progression of nephropathy, but not retinopathy, increased across tertiles of the standard deviation (SD) of SBP. Both the SD and coefficient of variation (CV) of SBP were significant predictors of development and progression of nephropathy, but not retinopathy, independently of mean SBP. CONCLUSION: Visit-to-visit SBP variability is an independent predictor of development and progression of diabetic nephropathy, but not retinopathy, in T2DM patients.