Effectiveness of insulin degludec/liraglutide versus insulin degludec/insulin aspart in Japanese patients with type 2 diabetes.

Aims: To evaluate and compare the effectiveness of once-daily insulin degludec/liraglutide (IDegLira) to that of once-daily insulin degludec/insulin aspart (IDegAsp) after switching from basal insulin therapy at 6 months by assessing changes in hemoglobin A1c (HbA1c), body weight, and insulin doses in patients with type 2 diabetes (T2D). Materials and methods: A total of 91 patients with T2D with HbA1c levels exceeding 7.0% were included in this study. Adjusted least square mean changes in HbA1c, body weight, and total insulin doses were compared between the IDegLira group and IDegAsp group. Subgroup analyses were performed, stratified by median values of HbA1c (< 8.5 and ≥ 8.5%), obesity (body mass index < 25 and ≥ 25 kg/m2), and basal insulin doses (< 14 and ≥ 14 units) at baseline to assess treatment interaction by subgroup. Results: The IDegLira group showed a greater reduction in HbA1c levels than the IDegAsp group (- 0.17 vs - 0.79%, p = 0.003) with comparable body weight changes. The analyses of adjusted mean changes of total insulin doses showed that the IDegAsp group had a larger increase than the IDegLira group (3.64 vs 1.30 unis, p = 0.016). The effect of IDegLira on HbA1c levels was superior to that of IDegAsp in patients with high HbA1c. There were no inter-group differences in the rate of hypoglycemic episodes. Conclusions: Once-daily IDegLira had greater effects on HbA1c and a lesser increase in insulin doses than IDegAsp when patients are switched from basal insulin therapy. Moreover, the effect on HbA1c was enhanced in patients with high HbA1c levels at baseline.

Association between changes in bodyweight and cardiovascular disease risk factors among obese Japanese patients with type 2 diabetes.

AIMS/INTRODUCTION: We aimed to assess the association between bodyweight reduction and cardiovascular disease risk factors, and to identify the minimum bodyweight reduction associated with significant improvement in cardiovascular disease risk factors among obese Japanese patients with type 2 diabetes. MATERIALS AND METHODS: The cohort comprised 1,753 patients with type 2 diabetes and body mass index ≥25 kg/m2 , who visited our clinic between 2013 and 2016. Multivariable linear regression analysis was carried out to assess the relationship between bodyweight changes and glycated hemoglobin A1c, serum lipids and blood pressure. Analyses of covariance were carried out to compare mean changes in cardiovascular disease risk factors across six groups of bodyweight change, <-5%, -5% to <-3%, -3% to <-1%, -1% to <1% (reference), 1% to <3% and ≥3%. RESULTS: Log-transformed bodyweight change had a significantly positive relationship with log-transformed glycated hemoglobin A1c, triglycerides, low-density lipoprotein cholesterol and systolic blood pressure changes, and a negative relationship with high-density lipoprotein cholesterol, after adjusting for sex, age, duration of diabetes, body mass index, use of glucose-lowering, lipid-lowering and antihypertensive agents, and changes in the use of these medications. A mean change in glycated hemoglobin A1c was significantly improved only in the <-5% group compared with the reference. Mean changes in triglycerides were improved in all groups, and significantly in the <-5% group. CONCLUSIONS: Bodyweight change was significantly associated with cardiovascular disease risk factor changes, and >5% bodyweight reduction was associated with improved glycated hemoglobin A1c.

Comparative clinical outcomes of insulin degludec and insulin glargine 300 U/mL after switching from other basal insulins in real-world patients with type 1 and type 2 diabetes.

AIMS/INTRODUCTION: To evaluate and compare the efficacy of insulin degludec (IDeg) and insulin glargine 300 U/mL (Gla300) 6 months after switching from other basal insulins by assessing the changes in glycated hemoglobin (HbA1c), body mass index (BMI), and insulin doses in patients with type 1 and type 2 diabetes in a real-world clinical setting. MATERIALS AND METHODS: A total of 307 patients with type 1 diabetes and 294 patients with type 2 diabetes with HbA1c >7.0% were studied. Adjusted mean changes in HbA1c, BMI, and insulin doses were compared between IDeg (IDeg group) and Gla300 (Gla300 group) switchers. Multivariable logistic regression analyses were carried out to examine whether the IDeg or Gla300 group was associated with HbA1c or insulin dose reduction and BMI gain. RESULTS: HbA1c was significantly decreased in both the IDeg and Gla300 groups. Adjusted mean changes in HbA1c (approximately -0.3% and -0.5% in type 1 diabetes and type 2 diabetes patients, respectively) and BMI were similar between both groups. The mean change in insulin dose was slightly larger for dose reduction in the IDeg group than in the Gla300 group. Multivariable logistic regression models showed that the IDeg group was significantly associated with insulin dose reduction after adjusting for basal insulin type, insulin dose, and number of basal insulin injections at baseline and other confounding factors. CONCLUSIONS: The current study suggested that IDeg and Gla300 have similar effects in reducing HbA1c and gaining BMI after switching from other basal insulins in Japanese patients with type 1 diabetes and type 2 diabetes. IDeg selection was associated with insulin dose reduction.

Impact of body mass index and age on the relative accuracy of self-reported energy intakes among Japanese patients with type 2 diabetes.

Dietary questionnaires have been used to ascertain food or nutritional intakes in many studies; however, the extent and characteristics of measurement errors in patients with diabetes have not been examined. This study examined the measurement errors from self-reported dietary history questionnaires (DHQ) in Japanese patients with type 2 diabetes (T2D). Fifty-nine patients with T2D underwent a 24-h urine collection and 3-day dietary record (DR), and completed the DHQ. Intakes of energy, protein, sodium, and potassium were calculated from the DHQ. The estimated energy intake was calculated from the DR, and estimated intakes of protein, sodium, and potassium were determined from the 24-h urine samples. Energy intake values from the DHQ were lower than those from the DR by 12.5% in men and by 14.6% in women, which was significant only in men. In women, protein intake values from the DHQ were 19% higher than those from the 24-h urine. Multivariable linear regression analysis showed that energy intake ratio (DHQ/DR) was significantly negatively associated with body mass index (BMI) in both sexes and significantly positively associated with age only in women (all p < 0.05). Protein intake ratio (DHQ/24-h urine) was positively associated with duration of diabetes only in men (p < 0.05); however, this relation disappeared in the multivariable model. No factors showed association with sodium or potassium intake ratio. The DHQ showed under-reporting of energy intake by approximately 15% in Japanese patients with T2D. This was associated with obesity in both sexes and with younger age in women.

Body Weight Reduction of 5% Improved Blood Pressure and Lipid Profiles in Obese Men and Blood Glucose in Obese Women: A Four-Year Follow-up Observational Study.

Background: Body weight reduction (BWR) of at least 3% in obese Japanese individuals through lifestyle interventions has improved the risk factors for cardiovascular disease (CVD). We aimed to assess the relation between body weight change (BWC) and CVD risk change and to identify lifestyle improvement related to BWR in obese Japanese individuals. Methods: Subjects were 2579 health checkup examinees without medicated diabetes, hypertension or dyslipidemia, and a body mass index ≥25 kg/m2 who completed lifestyle questionnaires in 2008 and 2012. The 4-year changes in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipids, and blood pressure (BP) levels were compared across the five groups based on the 4-year BWC, and presented as <-5%, -5% to -3%, -3% to -1%, -1% to 1%, and ≥1%. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for lifestyle improvement related to BWR. Results: Comparing the groups to the reference group (BWC ranging from -1% to +1%), we observed that FPG and HbA1c levels were lower in women in the <-5% group; BP levels were also lower in the <-5% group; triglyceride levels had improved in the <-3% group, and low-density lipoprotein cholesterol levels in the <-5% group; high-density lipoprotein cholesterol levels had improved in men in the <-5% group. In men, the adjusted OR (95% CI) for BWR related to lifestyle improvement pertaining to "over 30 min exercise" was 2.6 (2.0-3.6). In women, the adjusted ORs for BWR related to "walking or physical activity," "drinking alcohol," and "drinking more than a glass of sake" were 1.7 (1.1-2.7), 1.9 (1.1-3.5), and 1.8 (1.1-3.0), respectively. Conclusions: A 5% BWR improved FPG and HbA1c levels in obese women, and BP and lipid levels in obese men. Improvements in exercise and alcohol consumption habits were associated with BWR in this population.

Serum lipid management in patients with type 1 and type 2 diabetes: a hospital-based cohort study.

INTRODUCTION: Serum lipid management is important for patients with diabetes; however, it has not been examined in our specialized diabetes clinic. AIMS: The aim of the study was to assess the percentage of patients who did not achieve management targets (MT) for low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG), and explore factors related to failure to achieve lipid MT in Japanese patients with type 1 (T1D) and type 2 diabetes (T2D). METHODS: This cross-sectional study included 795 patients (35% men) with T1D and 4018 patients (60% men) with T2D attending our diabetes center. MTs for serum lipids were in accordance with the guidelines of the Japan Atherosclerosis Society. Logistic regression analysis was performed to identify factors related to failure to achieve MTs for serum lipids. RESULTS: The percentages of men/women who did not achieve MT for LDL-C were 34.1/31.8% in T1D and 40.5/52.7% in T2D. The corresponding values for TG were 35.1/14.0% in T1D and 50.1/47.9% in T2D, and for HDL-C were 2.5/0% in T1D and 8.6/2.9% in T2D. Increase in body mass index (BMI) and glycated hemoglobin (HbA1c) were significantly and independently associated with failure to achieve lipid MT in patients with T1D and T2D for both sexes. CONCLUSIONS: The percentages of our patients who did not achieve serum lipid MT were relatively high in T1D and T2D, and higher HbA1c and BMI were associated with failure to achieve serum lipid MTs. More attention should be paid to lipid management in patients with diabetes especially who have higher HbA1c and BMI in our facility.

Incidence of diabetic eye disease among migrants: A cohort study of 100,000 adults with diabetes in Denmark.

AIMS: To examine the incidence rates of any and referable diabetic retinopathy (DR) among migrants in Denmark. METHODS: Nationwide clinical data on diabetes patients followed since 2005 were analysed. Patients were classified according to country of origin into six groups: Denmark, other Europe, Sub Saharan Africa, Middle East/North Africa, Asia, and America/Oceania. A total of 93,780 or 110,897 patients without any (including unspecific diagnoses) or referable (proliferative) DR at baseline were analyzed. We estimated event rates and hazard ratios (HRs) for incidence of any and referable DR according to country of origin. RESULTS: After an average follow-up of 3.59 years 6727 had incident any DR and 4747 patients had referable DR. Compared to people of Danish origin, migrants from the Middle East/North Africa and Asia had a higher risk of any and referable DR after adjustment for age, sex, body mass index, smoking status, types and duration of diabetes, clinic type (general practice vs outpatient clinic), HbA1c, blood pressure and lipid levels. The associations remained significant after further adjustment for frequency of eye screening. CONCLUSIONS: Migrants from the Middle East/North Africa and Asia were at increased risk of developing any and referable DR compared to native Danes, and these differences were not fully explained by differences in underlying clinical, diabetic and cardiometabolic risk factors.

Diabetes diagnostic thresholds of the glycated hemoglobin A1c and fasting plasma glucose levels considering the 5-year incidence of retinopathy.

AIMS: As retinopathy is used as a defining threshold of diabetes, we assessed the glycated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) values associated with an increased risk of 5-year incidence of retinopathy. METHODS: We studied HbA1c, FPG, and optic fundus findings of 2605 individuals without previously diagnosed diabetes annually during a 5-year period. Retinopathy was examined using non-mydriatic, 45° digital fundus photography. Baseline levels were stratified as <5.3 [34], 5.3-5.6 [34-38], 5.7-6.0 [39-42], 6.1-6.4 [43-47], and ⩾6.5% [48mmol/mol] for HbA1c and <5.0, 5.0-5.5, 5.6-6.0, 6.1-6.9, and ⩾7.0mmol/L for FPG. Cox proportional hazard models were used to analyze hazard ratios (HRs) associated with HbA1c or FPG for incident retinopathy. RESULTS: During a total of 11845 person-years, we identified 50 (1.9%) cases of incident retinopathy. The adjusted HRs for incident retinopathy associated with a one-standard deviation increase in HbA1c and FPG were 1.2 (95% confidence intervals: 1.1-1.4) and 1.2 (1.1-1.4), respectively. These HRs were significantly higher for a HbA1c level ⩾6.5% (48mmol/mol) (3.4 [1.1-10.2]) or FPG level ⩾7.0mmol/L (3.6 [1.1-11.6]) than for a HbA1c level <5.3% (34mmol/mol) or FPG level <5.0mmol/L. CONCLUSIONS: A HbA1c value of 6.5% (48mmol/mol) and FPG value of 7.0mmol/L might be proper as diabetes diagnostic thresholds that indicate a high risk of future retinopathy.

Associations of HbA1c and fasting plasma glucose with incident diabetes: Implications for pre-diabetes thresholds in a Japanese population.

AIMS: This study assessed pre-diabetes (pre-DM) cutoffs for HbA1c and fasting plasma glucose (FPG) that were associated with an increased risk of incident DM. METHODS: We evaluated 2267 non-diabetic Japanese health-check examinees (HbA1c: <6.5% [<48mmol/mol] and FPG: <7.0mmol/L) who were 30-79 years old and were followed-up for 5 years. Incident DM was defined as HbA1c of ≥6.5% (≥48mmol/mol), FPG of ≥7.0mmol/L, or physician-diagnosed DM. RESULTS: During 11047 person-years, we identified 99 incident DM cases (4.3%). The incidence of DM increased with increasing baseline HbA1c or FPG levels, and the change points (95% confidence intervals) were 5.7% (5.6-5.7%; 39mmol/mol [38-39mmol/mol]) for HbA1c and 5.5mmol/L (5.5-5.6mmol/L) for FPG. The adjusted hazard ratios (HRs) for incident DM per one standard deviation-increase in HbA1c and FPG were 5.5 (4.4-6.8) and 4.0 (3.2-4.8), respectively. The adjusted HRs for incident DM were significantly higher at HbA1c of 5.7-6.4% (39-46mmol/mol) or FPG of 5.5-6.9mmol/L, compared to HbA1c of <5.7% (<39mmol/mol) or FPG of <5.5mmol/L. CONCLUSION: The lower cut-offs for pre-DM may be 5.7% (39mmol/mol) for HbA1c and 5.5mmol/L for FPG in this Japanese population.

Association of birthweight with diabetes and insulin sensitivity or secretion in the Japanese general population.

AIMS/INTRODUCTION: Low birthweight (birthweight <2,500 g) has been considered to be a risk factor for diabetes in data from Western countries, and its percentage is increasing in Japan. The aim of the present study was to assess the association between birth weight and diabetes, as well as both insulin resistance and secretion. MATERIALS AND METHODS: The participants were 847 adults who underwent health check-ups. The participants were divided by birthweight into four groups (low birthweight and tertiles 1-3 above it). We assessed the effect of birthweight on diabetes using a logistic regression model. Multivariable liner regression analyses were carried out to examine whether birthweight is independently associated with homeostasis model assessment of insulin resistance and ß-cell function. RESULTS: The prevalence of diabetes tended to increase with decreasing birthweight. The adjusted odds ratio for diabetes with low birthweight was 3.52 (1.04-11.96) as compared with the reference category, tertile 2. Univariable linear regression analyses showed that homeostasis model assessment of insulin resistance was negatively associated with birthweight, and this association remained after adjusting for age, sex, current body mass index and family history of diabetes. There was no significant association between homeostasis model assessment of ß-cell function and birthweight. CONCLUSIONS: Low birthweight was inversely associated with diabetes and insulin resistance in the Japanese general population. Longitudinal data analyses are required to examine the causal relationship between bodyweight and diabetes or insulin resistance in adulthood.

Hypoglycemia Observed on Continuous Glucose Monitoring Associated With IGF-2-Producing Solitary Fibrous Tumor.

CONTEXT: Tumors producing IGF-2 (IGF-2oma) are a major cause of spontaneous hypoglycemia. The treatment mainstay is surgical resection. Many case reports note resolution of hypoglycemia after IGF-2oma resection; however, outcomes are variable according to tumor type. We report a case of resolving hypoglycemia, observed on continuous glucose monitoring, after resection of an IGF-2-producing solitary fibrous tumor of pleura and review the current literature. CASE REPORT: A 69-year-old woman presented with impaired consciousness because of hypoglycemia. An IGF-2oma was diagnosed as the cause for hypoglycemia because of decreased serum insulin and IGF-1, the presence of a pleural tumor, and a high-molecular-weight form of serum IGF-2 detected by Western immunoblot. Surgical resection was performed; pathological examination demonstrated a solitary fibrous tumor with low-grade malignancy. Continuous glucose monitoring showed reversal of hypoglycemia after tumor resection. Approximately 2 years after resection, the patient has no signs of tumor recurrence or hypoglycemia. CONCLUSIONS: An IGF-2-producing solitary fibrous tumor of pleura in this case caused hypoglycemia. From a search of the literature of 2004-2014, 32 cases of IGF-2oma with hypoglycemia that underwent radical surgery were identified; in 19 (59%) patients, hypoglycemia was reversed, and there was no subsequent recurrence. The remaining 13 (41%) patients experienced tumor recurrence or metastasis an average of 43 months after initial tumor resection. The tumor of the present case was a low-grade malignancy. Regular follow-up with biomarker monitoring of glucose metabolism and assessment of hypoglycemic symptomatology, in conjunction with imaging tests, is important for detecting possible tumor recurrence and metastasis.

Association between lung function and metabolic syndrome independent of insulin in Japanese men and women.

PURPOSE: We examined the cross-sectional association between lung function and metabolic syndrome (MetS), independent of fasting immunoreactive insulin (F-IRI). METHODS: A total of 3,072 middle-aged, apparently healthy subjects who participated in a general health check-up were included. Lung function, which was expressed as forced vital capacity (%FVC predicted) or forced expiratory volume in 1 second (FEV1% predicted) was examined. Multivariable logistic regression analysis was performed to assess the association between lung function and MetS. RESULTS: Men with the lowest quartile of FVC% predicted, or those with the lowest quartile of FEV1% predicted, had a 3.5-fold or 2.6-fold increased risk of MetS, respectively, compared with those with the highest quartile of FVC% predicted or FEV1% predicted. F-IRI had a positive, significant, and independent association with MetS in both sexes. CONCLUSION: Impaired lung function increased the risk of MetS, independent of F-IRI and smoking in men, but not in women.

Effects of age on insulin resistance and secretion in subjects without diabetes.

OBJECTIVE: To examine whether aging itself affects insulin resistance (IR) and insulin secretion in the general Japanese population. METHODS: This study included data for 2,324 men and 1,472 women 30-79 years of age without diabetes who participated in a general health checkup program. The effects of age on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ß-cell function (HOMA-B) were examined using a linear regression model. Logistic regression models were used to identify clinical characteristics related to age. Multiple regression analyses using a stepwise form were performed to examine factors, including age, possibly affecting HOMA-IR and HOMA-B. RESULTS: The fasting plasma glucose (FPG) levels increased with age in both sexes, whereas the body mass index (BMI) and HOMA-B decreased with increasing age in men and the BMI increased with age in women. The HOMA-IR increased with increasing age in postmenopausal women. The proportion of physically active subjects increased in both sexes, and the proportion of current smokers decreased with age in men and postmenopausal women. The proportion of regular drinkers increased, and the proportion of subjects with a family history of diabetes decreased with age in men. The stepwise multiple regression analysis showed that age was inversely associated with the HOMA-B in both sexes and positively associated with the HOMA-IR in men and postmenopausal women. However, the BMI had the largest impact on the HOMA-IR and HOMA-B in both sexes. CONCLUSION: Age-related increases in the glucose levels in Japanese men and women may be associated with impaired insulin secretion. As a result, a sex difference was observed regarding the impact of aging on IR.

Diabetic gangrene in multiple fingers and toes after a dog bite in an elderly patient with type 2 diabetes.

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.

Increase in gamma-glutamyltransferase level and development of established cardiovascular risk factors and diabetes in Japanese adults.

BACKGROUND: We investigated the predictive value of changes in serum gamma-glutamyltransferase (GGT) for the development of cardiovascular disease (CVD) risk factors in Japanese. METHODS: A total of 1514 adult participants in a general health examination program were followed for 3 years until January, 2006. The subjects were divided into two groups according to whether their serum GGT level had decreased (< or =0 U/L) or increased (> or =1 U/L) from the baseline level of GGT during the study period. The logistic regression model was used to analyze the relationship between increases in GGT levels and the incidence of diabetes (DM), impaired fasting glucose (IFG), dyslipidemia, and hypertension (HT). RESULTS: The mean value of GGT level was significantly higher at baseline than the 3-year follow-up point (47 +/- 41 versus 41 +/- 51, P < 0.0001), and the average 3-year GGT change was -5.7 +/- 32.3 U/L. The subjects with an increased GGT over the 3 years had an increased risk of developing DM, IFG, high triglyceride (TG) levels, and HT, in comparison with that of the subjects with a decreased GGT level, with an odds ratios (OR) of 6.13 (95% confidence interval [CI], 2.83-13.25), 2.70 (1.68-4.34), 2.65 (1.76-3.99), and 1.54 (1.12-2.13), respectively, after adjusting for age, sex, and alcohol habits. Further adjustments for baseline GGT, alanine aminotransferase (ALT), body mass index (BMI), and 3-year changes in BMI did not alter these associations. CONCLUSIONS: The increased change in GGT over 3 years was a significant and an independent risk factor for the development of high TG, HT, IFG, and DM in Japanese.

[A case of advanced breast cancer with multiple lung, bone and lymph node metastases successfully treated with 5'-DFUR alone].

A 78-year-old female patient with locally advanced breast cancer, bleeding from a deep ulcer, and with multiple bone, lung and distant lymph node metastases was successfully treated with 5'-DFUR alone. She was at first treated with docetaxel + 5'-deoxy-5-fluorouridine (5'-DFUR) + tamoxifen, but they were discontinued because of deep venous thrombosis. She underwent simple mastectomy due to periodically recurring bleeding and infection. After administration of 5'-DFUR alone, a decrease of abnormal accumulation on a bone scintigram was obtained in 10 months, the lung metastases were diagnosed as being in complete remission (CR) at 11 months and the lymph node metastases were diagnosed as being in CR at 14 months. These states have continued to the present. The administration of 5'-DFUR alone is suitable for tumor dormancy in some cases.

[Weekly administration of low-dose paclitaxel for advanced or metastatic breast cancer].

The activity and toxicity of a weekly infusion of low-dose paclitaxel was studied. Twelve patients with metastatic or advanced breast cancer received paclitaxel (80 mg/m2 over 1 h) every week. Administration was continued for 6 weeks with two weeks rest until disease progression or limiting toxicity. Dexamethasone 20 mg, diphenhydramine 50 mg, and ranitidine 50 mg were given prior to each dose of paclitaxel. Six patients had received prior standard CMF therapy, and four patients had received CMF and docetaxel therapy. Two patients had not received prior therapy. The overall response rate was 58% with 17% complete responses and 42% partial responses. Responses were observed in both patients without prior therapy, and in five of 10 (50%) with prior therapy. Grade 3/4 neutropenia occurred in one patient; febrile neutropenia was not observed. There was no neuropathy or hypersensitivity. Weekly paclitaxel is active and well tolerated in patients with metastatic or advanced breast cancer. This schedule allows a high cumulative dose of paclitaxel without major myelo- or neurotoxicity. This weekly regimen deserves further exploration.