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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

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, The present study shows that postprandial hyperglycemia at clinic visits is associated with the incidence of diabetic retinopathy, independent of glycated hemoglobin levels, in a real‐world setting in patients with type 2 diabetes. The effect of postprandial hyperglycemia on retinopathy is obvious in patients with well‐controlled glycated hemoglobin levels and in patients aged

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., Among 6,140 patients in a diabetes specialist clinic in Japan, the leading causes of death were cancer, heart diseases and cerebrovascular diseases. A life expectancy at 40 years was 39.2 (95% confidence interval 37.9–40.2) in men and 43.6 (95% confidence interval 41.8–45.3) in women. Although our results must be interpreted with caution, because a healthy survivor bias might exist, 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.

A retrospective case–controlled analysis was performed to identify drug candidates in the current use that may prevent colorectal cancer, outside of aspirin. A total of 37,510 patients aged ≥20 years were assessed to identify subjects who had been diagnosed with colorectal cancer by colonoscopy without a previous diagnosis of colorectal cancer, inflammatory bowel disease (IBD), or gastrointestinal symptoms; 1,560 patients were identified who were diagnosed with colorectal cancer by colonoscopy. The patients with colorectal cancer were matched with 1,560 age, gender, family history of colorectal cancer and comorbidity-matched control patients who were not diagnosed with colorectal cancer at colonoscopy. The medication histories were compared between the two groups. Next, candidate drugs that were more frequently used by the control patients were selected and their effects on human colorectal cancer cell lines in vitro and an inflammation-induced mouse model of colorectal cancer were tested. Putative colorectal cancer preventative agents were identified, including aspirin, vitamin D, vitamin B, vitamin C, vitamin E, xanthine oxidase inhibitor, alpha-blockers, angiotensin receptor blocker, nateglinide, probiotics, thienopyridine, folic acid, nitrovasodilators, bisphosphonates, calcium channel blockers, steroids, and statins (P < 0.05). Alpha-blockers and xanthine oxidase inhibitors were selected for further study because these agents have not been analyzed previously as factors that may affect colorectal cancer outcomes. In vitro doxazosin (alpha-blocker), but not febuxostat (xanthine oxidase inhibitor), suppressed the proliferation of human colorectal cancer cells. Doxazosin also decreased tumorigenesis in an AOM/DSS mouse colorectal cancer model. Alpha-blockers may prevent colorectal cancer.

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.

Objective To analyze the changes in the pharmacotherapy and glycemic control trends in elderly patients with type 2 diabetes mellitus (T2DM) in Japan. Methods We extracted the data of 7,590 patients (5,396 men and 2,194 women; median year of birth: 1945) with T2DM registered in the National Center Diabetes Database for the years 2005 to 2013, and conducted age-stratified (

In 169 Japanese patients with type 2 diabetes mellitus with blood glucose levels that were inadequately controlled with diet and exercise therapy alone, or with diet and exercise therapy plus a sulfonylurea (SU) drug, we evaluated the safety and efficacy of global standard dose metformin given up to a maximum daily dose of 2250 mg for 54 weeks. The changes in HbA1c from baseline to the final evaluation visit were -1.32 ± 0.76% for metformin monotherapy and -1.29 ± 0.81% for metformin plus SU, both significantly lower than baseline. The incidences of adverse events and adverse drug reactions were 91.1% (154/169 patients) and 67.5% (114/169 patients), respectively. The most common adverse events were gastrointestinal symptoms, and most of the gastrointestinal symptoms were considered by investigators to be related to metformin treatment. An increased blood lactic acid level was observed in three subjects (1.8%); however, no clinical symptoms were reported, and there was no increase in mean lactic acid concentration throughout the evaluation period. Symptoms of hypoglycemia were reported in 16 patients, all receiving metformin plus SU, but none received metformin monotherapy. There was a decrease in mean body weight. Global standard dose metformin may be useful for maintaining good blood glucose control over the long term in the treatment of type 2 diabetes mellitus in Japanese patients.

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.

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

Aims/Introduction Insulin degludec/insulin aspart (IDegAsp) is a soluble combination of insulin degludec (70%) and insulin aspart (30%). The present exploratory trial investigated the safety of switching unit-to-unit from twice-daily basal or pre-mix insulin to twice-daily IDegAsp in Japanese patients with type 2 diabetes. Materials and Methods In this 6-week, open-label, parallel-group, controlled trial, 66 participants were randomized (1:1) to receive either IDegAsp or biphasic insulin aspart 30 (BIAsp 30) twice daily at the same total daily dose as pre-trial insulin. During the trial, insulin doses were adjusted according to a pre-specified algorithm to achieve pre-breakfast and pre-dinner plasma glucose of 4.4–7.2 mmol/L. Results No severe hypoglycemic episodes occurred. There were no statistically significant differences in rates of confirmed hypoglycemia (rate ratio IDegAsp/BIAsp 30: 0.63, 95% confidence interval: 0.31–1.30) and confirmed nocturnal hypoglycemia (rate ratio: 0.49, 95% confidence interval: 0.10–2.38) for IDegAsp vs BIAsp 30. The hypoglycemia rate for IDegAsp was constant over the 6 weeks of treatment. IDegAsp and BIAsp 30 were both safe and well tolerated. Reduction in fasting plasma glucose was statistically significantly greater for IDegAsp than for BIAsp 30 (estimated treatment difference, IDegAsp-BIAsp 30: −1.6 mmol/L, 95% confidence interval: −2.4 to −0.8). The apparent decrease in mean postprandial plasma glucose increment (IDegAsp: 4.2–3.8 mmol/L; BIAsp 30: 4.5–2.8 mmol/L) was not statistically significantly different between treatments (estimated treatment difference: 1.0 mmol/L, 95% confidence interval: −0.1 to 2.2). Conclusions Switching unit-to-unit from basal or pre-mix insulin to IDegAsp seems not to be associated with any concerns related to hypoglycemia or general safety in Japanese patients with type 2 diabetes.

A retrospective case-controlled analysis was performed to identify drug candidates in the current use that may prevent colorectal cancer, outside of aspirin. A total of 37,510 patients aged ≥20 years were assessed to identify subjects who had been diagnosed with colorectal cancer by colonoscopy without a previous diagnosis of colorectal cancer, inflammatory bowel disease (IBD), or gastrointestinal symptoms; 1,560 patients were identified who were diagnosed with colorectal cancer by colonoscopy. The patients with colorectal cancer were matched with 1,560 age, gender, family history of colorectal cancer and comorbidity-matched control patients who were not diagnosed with colorectal cancer at colonoscopy. The medication histories were compared between the two groups. Next, candidate drugs that were more frequently used by the control patients were selected and their effects on human colorectal cancer cell lines

Glycemic control is important for diabetic retinopathy (DR), but not sufficient for the inhibition after proliferative DR (PDR). Uric acid in the vitreous is reportedly increased in patients with DR, especially in the PDR. Here, the involvement of xanthine oxidoreductase (XO), responsible for uric acid production, in worsening DR was examined in both mouse model and co-cultured angiogenesis model. First, retinal pericytes were abolished by anti-PDGFRβ antibody injection to C57/Bl6 neonatal mouse at P1. Pericyte dropout from endothelial cells is reportedly early histological change in DR, and induces bleeding, abnormal angiogenesis, inflammation, and retinal detachment with rapid progression at P9-11. The expression of XO level in retina was increasing after pericyte breakdown, and was proportional to VEGF, and preceding the increase of TNFalpha. When 3.6mg/kg Febuxostat (Fbx), an XO inhibitor was injected at P7, widespread edema and retinal detachment/funnel-like deformation were dramatically improved by Fbx treatment at P11. ICAM-1+ cells surrounding edema and CD11b+ cells were reduced. Next, we performed a 3D culture sprouting assay using HUVEC spheroids in collagen gel co-cultured with human lung fibroblast (hLF) in fibrin gel. By Fbx treatment within the physiological concentration, the branch sprouting, cellular migration to the distal side and mitosis in branch stems were inhibited. ICAM-1 increase in HUVEC was observed with hLF co-culture but was suppressed by Fbx treatment. Finally, these effects of Fbx were not shown on HUVEC in planar culture. On the other hand, dissolution of fibrin by hLF was delayed directly due to Fbx. VEGF and PAI-1 expression from hLF and MMP-9 activity in medium were decreased by Fbx treatment. In summary, XO inhibition improved retinal inflammation and injury after pericyte loss. These results suggest the role of humoral inflammatory factors from mesenchymal cells surrounding retinal vessels in the hyperpermeable state such as DR. Disclosure A. Kushiyama: Research Support; Self; Teijin Pharma Limited, Sanwa Kagaku Kenkyusho Co., Ltd., Kowa Pharmaceutical Co., Ltd, StaGen. Consultant; Self; RIZAP. T. Kikuchi: None. H. Yamazaki: None. T. Yamamotoya: None. H. Sakoda: None. M. Fujishiro: Research Support; Self; Johnson & Johnson Services, Inc.. Y. Nakatsu: None. A. Uemura: Research Support; Self; Daiichi Sankyo Company, Limited, Boehringer Ingelheim GmbH, KAN Research Institute, Inc. T. Shirakura: Employee; Self; Teijin Pharma Limited. T. Asano: Research Support; Self; Teijin Pharma Limited, Sanwa Kagaku Kenkyusho Co., Ltd., Sanofi K.K. Y. Iwamoto: Board Member; Self; Japan Diabetes Foundation.

Objectives To determine if a discrepancy exists between subjective symptoms and the grade of endoscopic gastroesophageal reflux disease (GERD) in diabetes mellitus (DM) patients. Methods All 2,884 patients who underwent esophagogastroduodenoscopy completed the modified Gastrointestinal Symptom Rating Scale (GSRS), an interview-based rating scale consisting of 16 items including a question on acid regurgitation. Patients were divided into DM and non-DM groups (1,135 and 1,749 patients, respectively). GERD was diagnosed endoscopically and graded according to the Los Angeles classification. Grade B or more severe GERD was defined as severe endoscopic GERD. The intergroup GSRS score was compared statistically. Results In severe endoscopic GERD patients, the prevalence of patients with a positive GSRS score in the acid regurgitation question was statistically lower in DM patients than non-DM patients. Of the 60 non-DM patients with severe endoscopic GERD, 40 patients (67%) had a positive GSRS score for acid regurgitation; however, of the 51 DM patients with severe endoscopic GERD, 23 patients (45%) had a positive GSRS score. Multivariate analysis showed that severe endoscopic GERD (OR: 2.01; 95% CI: 1.21–3.33; p = 0.0066), non-DM (OR: 0.74; 95% CI: 0.54–0.94; p = 0.0157), younger age (OR: 0.98; 95% CI: 0.97–0.99; p = 0.0125), and hiatal hernia (OR: 1.46; 95% CI: 1.12–1.90; p = 0.0042) were associated with acid regurgitation symptoms. Conclusions There is a discrepancy between subjective symptoms and endoscopic GERD grade in DM patients. The ability of DM patients to feel acid regurgitation may be decreased.

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. 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. 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. 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.

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 m 2 and in those with a baseline eGFR of ≥ 60 to < 90 mL/min/1.73 m 2 . Conversely, eGFR tended to increase at 3 and 12 months in patients with a baseline eGFR of ≥ 45 to < 60 mL/min/1.73 m 2 and in those with a baseline eGFR of ≥ 30 to < 45 mL/min/1.73 m 2 . 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. J Clin Med Res. 2018;10(1):32-40 doi: https://doi.org/10.14740/jocmr3225w

To determine the efficacy and safety of sitagliptin when used with some therapeutic drugs to treat elderly patients. 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. 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

To effectively prevent the worsening of hyperglycemia in type 2 diabetes mellitus, it is of interest to see the clinical efficacy of early introduction of pharmacotherapy in addition to lifestyle intervention which is not always easy to continue throughout life. This is a randomized unblinded comparative clinical study on suppressive effects of lifestyle intervention alone and additional monotherapies for mild hyperglycemia at an early stage of treatment-naive type 2 diabetic patients, whose fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) are less than 140 mg/dl and 7.4%, respectively. The control group (group N = arm N) received conventional lifestyle intervention assisted by routine facilities, while the pharmacological intervention group (group D composed of 4 arms) was additionally treated by monotherapy with one of four kinds of oral antihyperglycemic agents i.e., sulfonylurea (SU), α-glucosidase inhibitor, biguanide and dipeptidyl peptidase-4 inhibitor. The participants were scheduled to follow up for 3 years to maintain glycemic control below primary endpoint which was defined as the first occurrence of FPG ≥140 mg/dl and HbA1c ≥7.4% simultaneously even by increasing doses of oral drug in group D, if necessary. The outcomes of occurrences of primary endpoint were not different between group N and group D composed of 4 arms during 3 years by Kaplan-Meyer plots (p = 0.405). On the other hand, ΔFPG (Δ: incremental change from baseline) and ΔHbA1c in group D significantly decreased when compared to those of group N during 3 years (p

Introduction Insulin degludec (IDeg) is an ultra-long-acting basal insulin with a consistent action profile of >42 h. This trial compared the efficacy and safety of IDeg with insulin glargine (IGlar) in insulin-naive Asian patients with type 2 diabetes. Materials and Methods In this multinational, 26-week, open-label, treat-to-target trial, 435 participants (202 females, 233 males; mean age 58.6 years; mean body mass index 25 kg/m2; mean glycated hemoglobin [HbA1c] 8.5%) were randomized (2:1) to IDeg or IGlar, each administered once daily with ≥1 oral antidiabetic drug(s) (OAD). Results After 26 weeks, HbA1c had decreased by 1.24 and 1.35% in the IDeg and IGlar groups, respectively (treatment difference [IDeg – IGlar] 0.11%, 95% confidence interval [CI] −0.03 to 0.24), confirming non-inferiority. Rates of overall confirmed hypoglycemia were similar for IDeg and IGlar during the full trial period (3.0 vs 3.7 episodes/patient-year of exposure [PYE]; rate ratio [RR] 0.82, 95% CI 0.60 to 1.11, P = 0.20), but significantly lower (by 37%) for IDeg during the maintenance period (from week 16 onward; RR 0.63, 95% CI 0.42 to 0.94, P = 0.02). No significant difference in the rate of nocturnal confirmed hypoglycemia was found between IDeg and IGlar in the full trial period (0.8 vs 1.2 episodes/PYE; RR 0.62, 95% CI 0.38 to 1.04, P = 0.07) or maintenance period (RR 0.52, 95% CI 0.27 to 1.00, P = 0.05). Adverse event rates were similar between treatments. Conclusions Initiating insulin therapy with IDeg in Asian patients with type 2 diabetes, inadequately controlled with OADs, provides similar improvements in long-term glycemic control to IGlar, but at a significantly lower rate of overall confirmed hypoglycemia once stable glycemic control and insulin dosing are achieved. This trial was registered with www.clinicaltrials.gov (no. NCT01059799).

The Japan Diabetes Society (JDS) revised diagnostic criteria of diabetes mellitus in 2010 [1]. The major revision was that HbA1c became the first line, that a diagnosis of diabetes was enabled using HbA1c and the plasma glucose level at one time. Early diagnosis and treatment of diabetes are expected by this revision. Prior to it, the American Diabetes Association (ADA) proposed a revision of the diagnostic criteria for diabetes [2]. They also adopted HbA1c in diagnostic criteria to reflect chronic hyperglycemic states better. Revision of the diagnosis is the difficult problem because it is not the simple thing to replace it by something else. It needs the continuity with the previous diagnostic criteria, the scientific validity based on evidence, the consistency with overseas diagnostic criteria, and the clinical feasibility. In this paper, we will define problems of HbA1c and the international challenge in the future, referring to the history of the diagnosis of diabetes.

Objective As a part of the Diabetes Attitudes, Wishes and Needs (DAWN) Japan study, a multi-center, questionnaire-based survey conducted between 2004 and 2005, this analysis aimed to (1) explore patients' attitudes and beliefs contributing to their decision to start insulin therapy, and (2) assess the changes in their attitudes and beliefs after actual initiation. Methods Insulin-naive patients with type 2 diabetes who were recommended to start insulin therapy (n = 149) were invited to answer a 21-item questionnaire consisting of five clusters assessing their attitudes and beliefs toward insulin therapy. The questionnaire was administered twice: first upon insulin recommendation, and then 1 month after insulin initiation for those who started and 4 months after for those who did not. Results Of 130 patients included in the analysis, 74 patients (56.9%) started insulin therapy. 'Negative image of injections' and 'Positive image toward insulin therapy' were significantly associated with patient decision to start insulin therapy (odds ratios [95% CI]: 0.49 [0.32-0.76] and 2.58 [1.51-4.42], respectively). After insulin initiation, 'Negative image of injections', 'Positive image toward insulin therapy', 'Feelings of guilt regarding diabetes self-management', and 'Negative image toward insulin therapy' decreased significantly (P

Aims/Introduction: To reveal whether visit-to-visit variability in HbA1c is associated with higher risk of cardiovascular disease (CVD) in patients with type 2 diabetes. Materials and Methods: The study was conducted on 689 Japanese patients with type 2 diabetes [295 women, 394 men; mean (±standard deviations (SD)) age 65 ± 11 years]. Variability in HbA1c was evaluated as the intrapersonal SD of serial measurements of HbA1c during the follow-up period for at least 12 months. Patients were divided into quartiles according to the SD of HbA1c, and the primary endpoint was defined as incident CVD. Cox’s proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: During a median follow-up period of 3.3 years (range 1.0–6.3 years), 26 ± 14 measurements of HbA1c were obtained per patient and 61 episodes of incident CVD were recorded. The 5-year cumulative incidence of CVD in patients across the first, second, third, and fourth quartiles of SD in HbA1c was 4.9, 8.7, 17.1, and 26.2%, respectively (P

Background The impact of serum lipid abnormalities on the progression of diabetic kidney disease (DKD) remains conflicting. Furthermore, gender differences in the association between dyslipidaemia and outcome of DKD are largely unknown. We therefore conducted this single-centre observational cohort study to clarify gender differences in the association between serum lipid profiles and the progression of DKD. Methods Seven hundred and twenty-three Japanese type 2 diabetes mellitus (T2DM) patients with normoalbuminuria or microalbuminuria, 280 women and 443 men, with a mean (± SD) age of 63 ± 11 years were studied. The endpoint was the progression to a more advanced stage of albuminuria. For statistical analyses, Cox proportional hazard model analyses were conducted. Results During the mean follow-up period of 4.3 years, 62 of 477 patients with normoalbuminuria and 69 of 246 patients with microalbuminuria reached the endpoint. A significant interaction between high-density lipoprotein (HDL) cholesterol and gender was detected (P(interaction) = 0.04); therefore, separate analyses were conducted for men and women. Overall, in men, the univariate Cox proportional hazard model revealed that higher triglycerides and lower HDL cholesterol levels were significantly associated with higher risk of reaching the endpoint. In the multivariate Cox proportional hazard model, only HDL cholesterol levels remained as an independent predictor of the endpoint (hazard ratio 0.391, P = 0.01). In women, no serum lipid parameters were associated with the endpoint. Conclusions Lower HDL cholesterol levels seem to be associated with the progression of DKD in men but not in women.

Background Sirtuin is a member of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, and has been reported to play a pivotal role in energy expenditure, mitochondrial function and pathogenesis of metabolic diseases, including aging kidneys. In this study, we focused on the genes encoding sirtuin families, and examined the association between single nucleotide polymorphisms (SNPs) within genes encoding sirtuin families and diabetic nephropathy. Methods We examined 52 SNPs within the SIRT genes (11 in SIRT1, 7 in SIRT2, 14 in SIRT3, 7 in SIRT4, 9 in SIRT5, and 4 in SIRT6) in 3 independent Japanese populations with type 2 diabetes (study 1: 747 cases (overt proteinuria), 557 controls; study 2: 455 cases (overt proteinuria) and 965 controls; study 3: 300 cases (end-stage renal disease) and 218 controls). The associations between these SNPs were analyzed by the Cochran–Armitage trend test, and results of the 3 studies were combined with a meta-analysis. We further examined an independent cohort (195 proteinuria cases and 264 controls) for validation of the original association. Results We identified 4 SNPs in SIRT1 that were nominally associated with diabetic nephropathy (P

A 78-year-old diabetic woman experienced multiple sites of gangrene not only in fingers that were directly bitten by a dog but also in fingers and toes that had not beenbitten. Her glycemic control was fair and microvascular complications were mild. There were no clinical findings related to angitis, collagenosis or severe infection. The fingers and toes with gangrene were amputated. The pathological diagnosis was diabetic gangrene. This report presents a case of multiple sites of gangrene of the fingers and toes after a dog bite in an elderly patient with type 2 diabetes.

Diabetes mellitus is a group of diseases associated with various metabolic disorders, the main feature of which is chronic hyperglycemia due to insufficient insulin action. Its pathogenesis involves both genetic and environmental factors. The long-term persistence of metabolic disorders can cause susceptibility to specific complications and also foster arteriosclerosis. Diabetes mellitus is associated with a broad range of clinical presentations, from being asymptomatic to ketoacidosis or coma, depending on the degree of metabolic disorder.

Concept of Diabetes Mellitus: Diabetes mellitus is a group of diseases associated with various metabolic disorders, the main feature of which is chronic hyperglycemia due to insufficient insulin action. Its pathogenesis involves both genetic and environmental factors. The long‐term persistence of metabolic disorders can cause susceptibility to specific complications and also foster arteriosclerosis. Diabetes mellitus is associated with a broad range of clinical presentations, from being asymptomatic to ketoacidosis or coma, depending on the degree of metabolic disorder.

As populations with a higher prevalence of HLADRB1*0406 have been found to have a higher risk of developing insulin autoimmune syndrome (IAS), we report here the clinical features of Asian and Japanese IAS. There was female dominance in the 20- to 49-year-old age group at the onset of IAS development. Forty-two percent of Japanese IAS patients had received drugs or α-lipoic acid containing the sulfhydryl group, while 81% of Asian IAS patients outside Japan had received methimazole or carbimazole before the development of IAS.

Diabet. Med. 27, 1017–1023 (2010) Abstract Aims The relationship between type of diabetes and risk of chronic kidney disease has not been studied in detail. We conducted this study to determine the prevalence of chronic kidney disease in Japanese adults with diabetes, with a particular emphasis on the comparison of Type 1 and Type 2 diabetes. Methods We studied 3,575 Japanese patients with diabetes, 504 with Type 1 (mean ± SD age 38 ± 13 years; 350 women and 154 men) and 3071 with Type 2 diabetes (60 ± 13 years; 1187 women and 1884 men). Prevalence rates of albuminuria [urinary albumin/creatinine ratio (≥ 30 mg/g], decreased estimated glomerular filtration rate (eGFR

Organic cation transporter 1 (OCT1; SLC22A1) seems to play a role in the efficacy and disposition of the widely used antidiabetic drug metformin. Genetic variants in OCT1 have been identified largely in European populations. Metformin is increasingly being used in Asian populations where the incidence of type 2 diabetes (T2D) is on the rise. The goal of this study is to identify genetic variants of OCT1 in Chinese and Japanese populations, which may potentially modulate response to metformin. We used recent data from the 1000 Genomes Project (Chinese and Japanese) and direct sequencing of selected amplicons of OCT1 in 66 DNA samples from Japanese patients with T2D. A total of six nonsynonymous variants were identified. Three of them (Q97K, P117L, and R206C) had not been functionally characterized previously and had allele frequencies of 0.017, 0.023 and 0.008, respectively. The uptake of metformin in cells expressing Q97K, P117L, and R206C was significantly reduced relative to the OCT1 reference (62 ± 4.3, 55 ± 6.8, and 22 ± 1.5% for Q97K, P117L, and R206C, respectively). Kinetic studies indicated that P117L and R206C exhibited a reduced V(max), whereas Q97K showed an increased K(m). The green fluorescent protein (GFP)-tagged Q97K and P117L variants localized to the plasma membrane, whereas the GFP-tagged R206C was retained mainly in the endoplasmic reticulum. Replacement of the highly conserved R206 with different amino acids modulated the subcellular localization and function of the transporter. This study suggests that nonsynonymous variants of OCT1 in Chinese and Japanese populations may affect the differential response to metformin.

Objective The data from the Fulminant Type 1 Diabetes Committee suggested that patients with fulminant type 1 diabetes are a subgroup at high risk for diabetic microangiopathy in the first 5 years after diagnosis associated with the lack of endogenous insulin secretion from the onset of diabetes. The aim of this study was to assess the development of microangiopathy in patients with fulminant type 1 diabetes followed in our diabetes center. Methods Sixteen patients with fulminant type 1 diabetes and 60 age-matched patients with non-fulminant type 1 diabetes were recruited as subjects. The existence or lack of diabetic retinopathy and nephropathy, average HbA1C level, serum C-peptide level, average blood pressure, insulin level, whether or not they were taking antihypertensive agents, and smoking history were investigated retrospectively based on medical records. Results The 5-year incidence of microangiopathy was lower in fulminant than in non-fulminant type 1 diabetes patients; retinopathy cases occurred in 0% vs. 8.3% of patients, and nephropathy occurred in 0% vs. 1.7% of patients. The 10-year incidence of retinopathy was 0% vs. 24.1%, and that of nephropathy was 11.1% vs. 3.4%. The cumulative incidence of microangiopathy did not differ between the fulminant and non-fulminant type 1 diabetes patients. Mean HbA1C levels and systolic blood pressure were significantly lower in fulminant type 1 diabetes patients. Conclusion No difference between the patients visiting the center with fulminant type 1 diabetes and those with non-fulminant type 1 diabetes was observed in the development of microangiopathy complications.

OBJECTIVE Genetic factors are believed to contribute to the development and progression of diabetic nephropathy. Recently, a genome-wide association study for diabetic nephropathy revealed four novel candidate loci in European American subjects with type 1 diabetes. In this study, we determined the association of the four loci with diabetic nephropathy in Japanese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS We genotyped 11 singlenucleotide polymorphisms (SNPs) in four distinct loci (rs39059 and rs39075 in the CPVL/CHN2, rs1888747 and rs10868025 in FRMD3, rs739401 and rs451041 in CARS, and rs1041466, rs1411766, rs6492208, rs7989848, and rs9521445 in a chromosome 13q locus) in four independent Japanese populations. RESULTS Six SNPs were nominally associated with diabetic nephropathy in one of the four Japanese populations (P < 0.05; rs451041 in study 1; rs39059 and rs1888747 in study 3; rs1411766 in studies 1 and 4; and rs7989848 and rs9521445 in study 4); however, no significant association was observed for any SNP after correction for multiple testing errors in the individual populations. Nevertheless, a meta-analysis performed for the data obtained from all four populations revealed that one SNP (rs1411766) in chromosome 13q was significantly associated with diabetic nephropathy in the Japanese populations (nominal P = 0.004, corrected P = 0.04, odds ratio 1.26 [95% CI = 1.07–1.47]). CONCLUSIONS Our results suggest that the rs1411766 locus may be commonly involved in conferring susceptibility to diabetic nephropathy among subjects with type 1 or type 2 diabetes across different ethnic groups.

We collated and analysed data from hospital records regarding the cause of death of 18,385 patients with diabetes who died in 282 medical institutions throughout Japan over the 10-year period between 1991 and 2000. Autopsy was carried out in 1750 cases. The most frequent cause of death in all 18,385 cases was malignant neoplasia, accounting for 34.1% of cases, followed by vascular diseases (including diabetic nephropathy, ischemic heart diseases and cerebrovascular diseases) in 26.8%, infections in 14.3%, and then diabetic coma in 1.2%. The most common malignancy was liver cancer, accounting for 8.6% of all the deaths. Of the deaths from vascular diseases, diabetic nephropathy was the cause of death in 6.8% of cases, and the frequency as cause of death for ischemic heart diseases and cerebrovascular diseases were similar at 10.2% and 9.8%, respectively. Myocardial infarction accounted for almost all the deaths from ischemic heart diseases, whereas deaths from cerebral infarction were 2.2-fold as common as those from cerebral hemorrhage. In the analyses of the relationship between age and causes of death in diabetic patients who underwent autopsy, the overall mortality rate as a result of vascular diseases increased with age, although the mortality rates from diabetic nephropathy and cerebrovascular diseases increased little from the fifth decade of life. The mortality rate from ischemic heart diseases increased with age, however, and was higher than the other forms of vascular diseases from the sixth decade of life, accounting for approximately 50% of vascular deaths in the eighth decade. Malignant neoplasia was the most frequent cause of death from the fifth decade of life, and was extremely common in the seventh decade, accounting for 46.3% of all the deaths. The mortality rate from infections varied little between age groups from the fifth decade of life. In the analyses of glycemic control and the age at the time of death, lifespans were 2.5 years shorter in males, and 1.6 years shorter in female diabetics with poor glycemic control than in those with good or fair glycemic control. This difference was greater for deaths as a result of infections and vascular diseases, particularly diabetic nephropathy, than for malignant neoplasia. Analysis of the relationship between glycemic control and the duration of diabetes and deaths as a result of vascular diseases showed no correlation between the level of glycemic control and death from diabetic nephropathy, ischemic heart diseases or cerebrovascular diseases. In diabetics with disease durations of less than 10 years, the mortality rate from macroangiopathy was higher than that as a result of diabetic nephropathy, a form of microangiopathy. Treatment for diabetes comprised of diet alone in 21.5%, oral hypoglycemic agents in 29.5%, and insulin with or without oral hypoglycemic agents in 44.2%, which was the most common. In particular, 683/1170 (58.4%) diabetics who died from diabetic nephropathy were on insulin therapy, a higher proportion than the 661/1687 (39.2%) who died from ischemic heart diseases, or the 659/1622 (40.6%) who died from cerebrovascular diseases. The average age at the time of death in the survey population was, 68 years for males and 71.6 years for females. These were 9.6 and 13 years, respectively, short of the average life expectancy for the Japanese general population. In comparison with the previous survey (1981–1990), the average age at the time of death had increased 1.5 years for males, and 3.2 years for females. The average life expectancy for the Japanese general population had also increased 1.7 and 2.7 years, respectively, over that period, showing that advances in the management and treatment of diabetes have not led to any improvement in patients’ life expectancies. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00019.x, 2010)

Aim: To evaluate carotid intima-media thickness (IMT) in patients with long-term early-onset type 1 diabetes, and investigate the associations between IMT, diabetic retinopathy and clinical characteristics. Methods: We evaluated anthropometric measurements, biochemical parameters and carotid IMT. Ultrasonography was performed on 73 patients diagnosed with type 1 diabetes before 30 years of age, and who have been living with diabetes for 20 years or more. Results: The mean max-IMT (maximal thickness of whole carotid artery) and IMT-Cmax (maximal thickness of common carotid artery) values were 0.94 mm and 0.67 mm; 21 patients had proliferative diabetic retinopathy and 21 patients had plaque (IMT ≥ 1.1 mm). Age, age at diagnosis of diabetes and adolescent HbA1C level (HbA1C at 18 years old or the earliest measurement available) were higher in patients with plaque than in those without. Max-IMT was greater in patients with proliferative retinopathy than in those without. Similarly, there were significant differences in current HbA1C level, and the prevalence of hypertension and dyslipidemia. In multivariate analysis, age and dyslipidemia were independently associated with max-IMT and IMT-Cmax. Conclusions: Age and dyslipidemia were associated with IMT. In contrast, glycemic control was closely associated with diabetic retinopathy, but weakly associated with IMT. J Atheroscler Thromb, 2009; 16:821-828.

We report a case of type 1 diabetes mellitus who was successfully treated with simultaneous pancreas and kidney (SPK) transplantation and both grafts survived for 16 yr. A 30-yr-old woman underwent SPK transplantation from a non-heart-beating donor in January 1992. She was treated with combined immunosuppressive therapy consisting of cyclosporine, azathioprine, methylprednisolone, and anti-lymphocyte globulin. Allograft kidney biopsy was performed 10 yr after transplantation to determine the cause of proteinuria, which revealed no recurrence of diabetic nephropathy, suggesting that long-term normalization of glycemic control achieved by successful pancreas transplantation can prevent recurrence of diabetic nephropathy in the kidney allograft.

Prediction of the disease status is one of the most important objectives of genetic studies. To select the genes with strong evidence of the association with type 2 diabetes mellitus, we validated the associations of the seven candidate loci extracted in our earlier study by genotyping the samples in two independent sample panels. However, except for KCNQ1, the association of none of the remaining seven loci was replicated. We then selected 11 genes, KCNQ1, TCF7L2, CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX, GCKR, HNF1B, KCNJ11 and PPARG, whose associations with diabetes have already been reported and replicated either in the literature or in this study in the Japanese population. As no evidence of the gene-gene interaction for any pair of the 11 loci was shown, we constructed a prediction model for the disease using the logistic regression analysis by incorporating the number of the risk alleles for the 11 genes, as well as age, sex and body mass index as independent variables. Cumulative risk assessment showed that the addition of one risk allele resulted in an average increase in the odds for the disease of 1.29 (95% CI=1.25-1.33, P=5.4 x 10(-53)). The area under the receiver operating characteristic curve, an estimate of the power of the prediction model, was 0.72, thereby indicating that our prediction model for type 2 diabetes may not be so useful but has some value. Incorporation of data from additional risk loci is most likely to increase the predictive power.

Background: In Europeans and populations of European origin, several groups have recently identified novel type 2 diabetes susceptibility genes, including FTO, SLC30A8, HHEX, CDKAL1, CDKN2B, and IGF2BP2, none of which were in the list of functional candidates. Objective and Design: The aim of this study was to replicate in a Japanese population previously identified associations of single nucleotide polymorphisms (SNPs) within 10 candidate loci with type 2 diabetes using a relatively large sample size: 1921 subjects with type 2 diabetes and 1622 normal controls. Results: A total of 15 SNPs were genotyped. Eight SNPs in five loci were found to be associated with type 2 diabetes: rs3802177 [odds ratio (OR) = 1.16 (95% confidence interval (CI) 1.05–1.27); P = 4.5 × 10−3] in SLC30A8; rs1111875 [OR = 1.27 (95% CI 1.14–1.40); P = 1.4 × 10−5] and rs7923837 [OR = 1.27 (95% CI 1.13–1.43); P = 1.0 × 10−4] in HHEX; rs10811661 [OR = 1.27 (95% CI 1.15–1.40); P = 1.9 × 10−6] in CDKN2B; rs4402960 [OR = 1.23 (95% CI 1.11–1.36); P = 8.1 × 10−5] and rs1470579 [OR = 1.18 (95% CI 1.07–1.31); P = 8.3 × 10−4] in IGF2BP2; and rs7754840 [OR = 1.28 (95% CI 1.17–1.41); P = 4.5 × 10−7] and rs7756992 [OR = 1.27 (95% CI 1.15–1.40); P = 9.8 × 10−7] in CDKAL1. The first and second strongest associations were found at variants in CDKAL1 and CDKN2B, both of which are involved in the regenerative capacity of pancreatic β-cells. Conclusion: Some of these variants represent common type 2 diabetes-susceptibility genes in both Japanese and Europeans.

Aim The association between metabolic syndrome (MS) and renal outcomes in diabetic patients remains unclear. We conducted a cross-sectional study to assess the association between MS and albuminuria and decreased glomerular filtration rate (GFR) in type 2 diabetic patients. Methods We studied a total of 1003 adult Japanese patients with type 2 diabetes, 582 men, with a mean (±S.D.) age of 62 ± 12 years. Patients with macroalbuminuria, defined as a urinary albumin-to-creatinine ratio (ACR) ≥300 mg/g Cr, and those with renal insufficiency, defined as serum creatinine ≥2.0 mg/dl, were excluded. MS was assessed according to Japanese definition proposed in 2005. Microalbuminuria and decreased GFR were defined as ACR of 30–299 mg/g Cr and estimated GFR 2 , respectively. Results The prevalence of microalbuminuria was significantly higher in patients with MS than those without. In contrast, the prevalence of decreased GFR was comparable between patients with and without MS. Waist circumference was selected as a significant variable in the logistic regression analysis for microalbuminuria. Conclusion Microalbuminuria, but not decreased GFR, is independently associated with MS and solely with increased waist circumference in Japanese patients with type 2 diabetes.

A mild increase in liver enzyme levels is sometimes observed in patients with diabetic ketosis or ketoacidosis. The aim of the present study was to assess the cause and prevalence of the elevation of liver transaminase levels in fulminant and acute-onset type 1 diabetic patients experiencing diabetic ketosis or ketoacidosis.We analyzed data on the liver transaminase levels of 108 patients over 18 years of age with newly diagnosed type 1 diabetes complicated by ketosis or ketoacidosis. The data were collated from a nationwide survey on fulminant type 1 diabetes and retrospective medical records.Thirty-two (60.4%) out of the 53 patients suffering from fulminant type 1 diabetes were detected with transient elevation of liver transaminase (TELT) levels during the first month after initiation of insulin therapy; in the case of acute-onset type 1 diabetes, such an observation was noted in 16 (29.1%) out of 55 patients. Fatty liver was diagnosed in 20% of the patients, and 65% of these patients exhibited TELT. The dosage of insulin injected in these patients was significantly high.High blood glucose and fatty liver may influence the elevation of liver transaminase levels during the treatment of new-onset type 1 diabetes.

Transcription factor 7-like 2 (TCF7L2) has been shown to be associated with type 2 diabetes mellitus in multiple ethnic groups. Regarding the Asian population, Horikoshi et al. (Diabetologia 50:747-751, 2007) and Hayashi et al. (Diabetologia 50:980-984, 2007) reported that single nucleotide polymorphisms (SNPs) in TCF7L2 were associated with type 2 diabetes in the Japanese population, while contradictory results were reported for Han Chinese populations. The aim of this study was to investigate the associations of the TCF7L2 gene with type 2 diabetes using a relatively large sample size: 2,214 Japanese individuals with type 2 diabetes and 1,873 normal controls. The minor alleles of rs7903146, rs11196205, and rs12255372 showed significant associations with type 2 diabetes (OR=1.48, P=2.7 x 10(-4); OR=1.39, P=4.6 x 10(-4); OR=1.70, P=9.8 x 10(-5), respectively) in the combined sample sets. However, neither rs11196218 nor rs290487 showed a significant association. These results indicate that TCF7L2 is an important susceptibility gene for type 2 diabetes in the Japanese population.

Using a large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese type 2 diabetic patients, we have identified a gene encoding neurocalcin delta (NCALD) as a candidate for a susceptibility gene to diabetic nephropathy; the landmark SNP was found in the 3' UTR of NCALD (rs1131863: exon 4 +1340 A vs. G, P = 0.00004, odds ratio = 1.59, 95% CI 1.27-1.98). We also discovered two other SNPs in exon 4 of this gene (+999 T/A, +1307 A/G) that showed absolute linkage disequilibrium to the landmark SNP. Subsequent in vitro functional analysis revealed that synthetic mRNA corresponding to the disease susceptible haplotype (exon 4 +1340 G, +1307 G, +999 A) was degraded faster than mRNA corresponding to the major haplotype (exon 4 +1340 A, +1307 A, +999 T), and allelic mRNA expression of the disease susceptibility allele was significantly lower than that of the major allele in normal kidney tissues. In an experiment using a short interfering RNA targeting NCALD, we found that silencing of the NCALD led to a considerable enhancement of cell migration, accompanied by a significant reduction in E-cadherin expression, and by an elevation of alpha smooth muscle actin expression in cultured renal proximal tubular epithelial cells. We also identified the association of the landmark SNP with the progression of diabetic nephropathy in a 8-year prospective study (A vs. G, P = 0.03, odds ratio = 1.91, 95% CI 1.07-3.42). These results suggest that the NCALD gene is a likely candidate for conferring susceptibility to diabetic nephropathy.

Background Helicobacter pylori infection is the most important risk factor for gastric cancer, for which eradication therapy is commonly performed. However, gastric cancer is sometimes discovered after successful eradication of H. pylori. Much evidence indicates that diabetes mellitus (DM) is a risk factor for gastric cancer. The incidence and characteristics of gastric cancer diagnosed after H. pylori eradication in DM patients remain to be determined. Methods We followed the clinical course of patients who underwent H. pylori eradication therapy at our institution. Endoscopy was performed before and after eradication. We compared the incidence and clinical characteristics of gastric cancer arising in DM and non-DM patients. Results In total, 965 patients who underwent successful eradication (518 DM and 447 non-DM patients) were followed-up for an average of 4.5 years. During the follow-up period, 21 gastric cancers were diagnosed (12 in DM patients and 9 in non-DM patients). The incidence of gastric cancer after eradication was not significantly different between DM and non-DM patients (0.485 and 0.482 %/year, respectively). There was no significant difference in the pathology, diameter, depth, location, or treatment of gastric cancer between patients with and without DM. Conclusion The incidence and characteristics of gastric cancer occurring after H. pylori eradication were comparable between DM and non-DM patients.

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.