Relationship between obstructive sleep apnoea during rapid eye movement sleep and metabolic syndrome parameters in patients with type 2 diabetes mellitus.

PURPOSE: Sleep-disordered breathing (SDB) is associated with hypertension, poor glycemic control and dyslipidemia. Usually, apnoea events tend to be more prominent during rapid eye movement (REM) sleep than non-REM (NREM) sleep. We examined which SDB parameters are associated with blood pressure (BP), HbA1c and lipid profile in patients with type 2 diabetes (T2D). METHODS: A total of 185 patients with T2D who underwent polysomnography were analysed. Exclusion criteria were: the presence of pulmonary diseases, central sleep apnoea, treated SDB, or REM sleep < 30 min. To predict BP, HbA1c, and lipid profiles, we performed multiple linear regression analyses adjusted for known risk factors. Subsequently, we performed multivariable logistic regression analyses. RESULTS: Patient characteristics (mean ± standard deviation/median) were as follows: age 58.0 ± 11.8 years, body mass index 26.0 kg/m2 (24.1-28.9 kg/m2 ), systolic BP 134 ± 19 mmHg, mean BP 98 ± 14 mmHg, HbA1c 7.4% (6.8-8.4%), triglyceride 143 mg/dL (97-195 mg/dL), non-high density lipoprotein (non-HDL) cholesterol 143 mg/dL (120-163 mg/dL), REM-apnoea-hypopnea index (AHI) 35.1/h (21.1-53.1/h). The analyses revealed that REM-AHI was independently associated with systolic and mean BP, whereas NREM-AHI was not. A statistically significant association was not observed between REM-AHI and HbA1c or lipid profile. CONCLUSION: In patients with T2D, REM-AHI was associated with systolic and mean BP. The alteration of BP, associated with SDB during REM sleep, may be an important pathophysiological link between SDB and cardiovascular diseases.

Efficacy and safety of repaglinide added to sitagliptin in Japanese patients with type 2 diabetes: A randomized 24-week open-label clinical trial.

Although sitagliptin and repaglinide monotherapies improve postprandial hyperglycemia, the long-term effects and safety of their combination has not been examined. In this randomized 24-week trial of Japanese patients with poor control (HbA1c 7.0-8.5%) by sitagliptin, we divided 40 patients randomly into two equal groups of the repaglinide add-on to sitagliptin (ADD-ON, n=20), or sitagliptin switched to repaglinide (SWITCH, n=20). The meal tolerance test was carried out at weeks 0 and 24. The primary outcomes were changes in HbA1c and area under the curves (AUC) of glucose from the baseline to week 24. The mean change in HbA1c from baseline to week 24 was larger in the ADD-ON (-0.87±0.63%, mean±SD), compared with the SWITCH (0.03±0.65%, p=0.000). Significant improvements were noted in the mean changes in fasting glucose and AUCs of glucose in the ADD-ON vs. SWITCH (p=0.007 and p=0.000). Insulin secretion relative to glucose elevation (ISG; defined as AUC insulin/AUC glucose) increased significantly in the ADD-ON, although the mean change in fasting insulin level was significantly decreased in the ADD-ON (p=0.015 and p=0.026). The AUC of glucagon was significantly lower at 24-week relative to baseline in the ADD-ON, but was not significant in the two groups (p=0.047 and p=0.056, respectively). The combination therapy produced significant reductions in HbA1c, AUC of glucose and fasting glucose compared with switching to repaglinide without weight gain or severe hypoglycemia. The improved glycemic control with this combination therapy may be at least in part due to augmentation of repaglinide-induced insulin secretion by sitagliptin.

Exponential increase of glutamic acid decarboxylase (GAD) antibody titer after initiating and stopping insulin in a patient with slowly progressive type 1 diabetes.

Few articles have described fluctuations in glutamic acid decarboxylase antibody (GADAb) levels after a diagnosis of slowly progressive type 1 diabetes (SPIDDM). Here, we present a case in which GADAb levels exponentially increased after initiating and stopping insulin. A 64-year-old female patient newly diagnosed with SPIDDM was admitted and started multiple daily insulin injections. The patient's GADAb titer was 6.9 U/mL (normal: <1.4 U/mL) and the patient had a type 1 diabetes susceptible HLA class II haplotype known in the Japanese population as: DRB1*04:05-DQB1*04:01. When the patient's "honeymoon period" set in, hypoglycemia was observed and the dose of insulin was reduced. Two months after the diagnosis, 1 unit of insulin glargine/day was being injected and the patient demonstrated good glycemic control. Subsequently, the patient's home doctor recommended that insulin injections be stopped. Three months after the diagnosis, the patient's GADAb titer suddenly increased to 1600 U/mL. The patient's GADAb titer decreased but was still positive (40 U/mL) 36 months after diagnosis. HbA1c levels were maintained below 7%, and oral glucose tolerance tests at 10, 26, and 36 months after diagnosis suggested that the patient had preserved insulin secretion. To the best of our knowledge, this is the first report that describes exponential increases in GADAb after initiating and stopping insulin in a patient with SPIDDM.

Global cognition and executive functions of older adults with type 1 diabetes mellitus without dementia.

AIMS/INTRODUCTION: This study aimed to characterize the global cognition and executive functions of older adults with type 1 diabetes mellitus in comparison with type 2 diabetes mellitus. MATERIALS AND METHODS: This study included 37 patients with type 1 diabetes mellitus aged ≥65 years and 37 age- and sex-matched patients with type 2 diabetes mellitus. Patients with dementia scoring <24 on the Mini-Mental State Examination were excluded. General cognition, memory, classic, and practical executive function were investigated. RESULTS: Patients with type 1 diabetes mellitus demonstrated lower psychomotor speed scores on Trail Making Tests A and B (P < 0.001, P < 0.013) than those with type 2 diabetes mellitus. The dysexecutive syndrome behavioral assessment revealed similar results in patients with types 1 and 2 diabetes mellitus. The Wechsler Memory Scale-Revised verbal episodic memory and Montreal Cognitive Assessment Japanese version were similar in terms of general cognition, but worse delayed recall subset on the latter was associated with type 2 diabetes mellitus (P = 0.038). A worse Trail Making Test-A performance was associated with type 1 diabetes mellitus and age (P < 0.004, P < 0.029). CONCLUSIONS: Executive function of psychomotor speed was worse in older outpatient adults without dementia with type 1 diabetes mellitus than in those with type 2 diabetes mellitus but with no significant differences in the comprehensive and practical behavioral assessment of dysexecutive syndrome. Patients with type 1 diabetes had more severely impaired executive function, whereas those with type 2 had greater impaired memory than executive function.

Factors affecting glycemic control in diabetes mellitus complicated by autoimmune pancreatitis.

AIMS/INTRODUCTION: To investigate factors influencing glycemic control in diabetes mellitus complicated by autoimmune pancreatitis. MATERIALS AND METHODS: This retrospective cohort study investigated 33 patients with diabetes mellitus complicated by autoimmune pancreatitis who had received steroid therapy at Toranomon Hospital between January 1, 2011, and December 31, 2020. The course of glycemic control at 12 months after starting steroids was classified into three groups: Improved, Unchanged, or Worsened. Factors affecting these groups were investigated. Furthermore, we created two scores: (1) time of diabetes mellitus onset and baseline body mass index; (2) time of diabetes mellitus onset and baseline C-peptide index. Diabetes mellitus occurring at the same time as autoimmune pancreatitis, body mass index ≥22 kg/m2 , and C-peptide index ≥1.1 were each worth 1 point. Scores were summed and totals of 0-2 were compared between groups. RESULTS: Ten patients were in the Improved group, 10 were in the Unchanged group, and 13 were in the Worsened group. The baseline body mass index and baseline C-peptide index were lower in the Worsened group than in the Improved group (P < 0.05 each). In addition, the scores were lower in the Worsened group than in the other groups (P < 0.05). CONCLUSIONS: Patients with a lower baseline body mass index and a decreased baseline C-peptide index may experience worse glycemic control on steroid therapy.

Successful treatment of adult-onset nesidioblastosis by continuous subcutaneous octreotide infusion in a patient on hemodialysis.

Octreotide may be useful in noninsulinoma pancreatogenous hypoglycemia syndrome with nesidioblastosis patients who was on hemodialysis. Continuous octreotide subcutaneous infusion can reduce side-effects and stabilize plasma glucose levels.

Obstructive sleep apnea during rapid eye movement sleep in patients with diabetic kidney disease.

STUDY OBJECTIVES: Although recent studies suggest that obstructive sleep apnea during rapid eye movement (REM) is associated with different cardiometabolic and neurocognitive risks compared with non-REM (NREM) sleep, there is no information on whether obstructive sleep apnea during REM and/or NREM sleep is independently associated with diabetic kidney disease (DKD). METHODS: In this cross-sectional study, 303 patients with type 2 diabetes who were followed up at our diabetes outpatient clinic underwent all-night polysomnography. Logistic regression analysis was performed to determine the separate effects of obstructive sleep apnea during REM and/or NREM sleep (REM and/or NREM-apnea-hypopnea index [AHI]) and several other polysomnography parameters on DKD after adjustment for several known risk factors for DKD. RESULTS: The median (interquartile range) AHI, REM-AHI, and NREM-AHI of the patients (age 57.8 ± 11.8 years, male sex 86.8%, hypertension 64.3%, and DKD 35.2%) were 29.8 (18.0-45.4), 35.4 (21.1-53.3), and 29.1 (16.3-45.4) events/h, respectively. REM-AHI quartiles, but not NREM-AHI quartiles, correlated independently and significantly with DKD (P = .03 for linear trend, odds ratio (OR), and 95% confidence interval for Q2: 3.14 (1.10-8.98), Q3: 3.83 (1.26-11.60), Q4: 4.97 (1.60-15.46), compared with Q1). In addition, categorical AHI (P = .01, OR, and 95% confidence interval for ≥ 15 to < 30: 1.54 (0.64-3.71), ≥ 30: 3.08 (1.36-6.94) compared with < 15), quartiles of AHI (P = .01), quartiles of lowest arterial oxyhemoglobin saturation (P < .01), quartiles of percentage of time spent with arterial oxyhemoglobin saturation < 90 (P < .01), and quartiles of mean arterial oxyhemoglobin saturation were independently associated with DKD. CONCLUSIONS: Obstructive sleep apnea, especially during REM sleep, is a potential risk factor for DKD.

Glutest Neo Super--a new handheld blood glucose meter-corrects for the effects of the hematocrit values in both hematocrit-adjusted samples and samples obtained from anemic patients.

BACKGROUND: Handheld blood glucose (BG) meters are convenient tools that are widely used to measure the BG levels. However, the hematocrit (Hct) value has been identified as a confounding factor for accurate BG measurement. Some BG meters are equipped with an Hct-correcting feature, whose effectiveness has been tested previously. Nevertheless, the measurements yielded by many BG meters are confounded by the Hct values. Recently, a new BG meter equipped with an Hct-correcting feature has been developed; however, its effectiveness has not yet been confirmed. STUDY DESIGN: Venous blood samples were collected from two healthy volunteers, and the Hct values in the samples were adjusted to approximately 0%, 10%, 20%, 30%, 40%, 50%, and 60%. Further, venous blood samples were collected from 10 anemic patients (Hct <40%). The whole BG (WBG) levels in the samples were measured using two devices-the new BG meter (Glutest Neo Super [Sanwa Kagaku Kenkyusho Co. Ltd., Nagoya, Japan]) and a standard BG meter (OneTouch Ultra [Life Scan Inc., Milpitas, CA]). For reference, plasma glucose (PG) levels were measured using a machine at our hospital laboratory (GA08 [A&T Co., Kanagawa, Japan]). The bias in the measurements was calculated as follows: bias = ([WBG - PG]/PG) x 100. Further, the correlation between the Hct values and the bias was assessed by performing linear regression analysis. RESULTS: In both the Hct-adjusted samples and the samples obtained from anemic patients, the WBG levels measured using Glutest Neo Super were minimally affected by the Hct values, while those measured using OneTouch Ultra were affected by the Hct values to a statistically significant extent. CONCLUSIONS: The Hct-correcting feature of the new BG meter Glutest Neo Super was effective. The use of this new device for BG measurements may lead to more appropriate treatment selection.

Slowly Progressive Type 1 Diabetes Mellitus: Current Knowledge And Future Perspectives.

Slowly progressive type 1 insulin-dependent diabetes mellitus (SPIDDM), sometimes referred to as latent autoimmune diabetes in adults (LADA), is a heterogeneous disease that is often confused with type 1 and type 2 diabetes. As a result, there were few diagnostic criteria for this disorder until 2012, when the Japan Diabetes Society established criteria that could be used in clinical practice. A primary question is whether pathologic markers for type 1 or type 2 diabetes are present in the pancreas of patients with SPIDDM, because the phenotype of SPIDDM is similar to both type 1 and type 2 diabetes. Recent studies clarified pathologic findings in the pancreas of patients with SPIDDM, which included T-cell-mediated insulitis, a marker of type 1 diabetes; pseudoatrophic islets (islets specifically devoid of beta cells), another hallmark of type 1 diabetes; and a lack of amylin (ie, islet amyloid polypeptide) deposition to the islet cells, a pathologic marker of type 2 diabetes. In terms of preventing the loss of beta-cell function in patients with SPIDDM, several studies have shown that some drugs, including dipeptidyl peptidase-4 inhibitors, are effective. There is an increased need for early diagnosis of SPIDDM to preserve beta-cell function. This review presents updated findings on the pathogenesis and immunologic findings of the affected pancreas, diagnostic markers, risk factors for progression of beta-cell dysfunction, epidemiology, clinical features, diagnostic strategies, prevention strategies, and clinical options for patients with SPIDDM.

Apnea Hypopnea Index During Rapid Eye Movement Sleep With Diabetic Retinopathy in Patients With Type 2 Diabetes.

CONTEXT: Recent studies based on home sleep apnea testing (HSAT) reported the potential association of sleep disordered breathing, such as obstructive sleep apnea (OSA), with diabetic retinopathy (DR). A few studies showed that the apnea-hypopnea index (AHI) during rapid eye movement (REM) sleep (REM-AHI) is associated with glycated hemoglobin and hypertension, two known risk factors for DR. However, there are no studies that have evaluated the association of REM-AHI with DR because previous studies were based on HSAT. OBJECTIVE: To determine the association of REM-AHI with DR. DESIGN, SETTING, AND PATIENTS: The study subjects were 131 patients with type 2 diabetes mellitus who underwent all-night polysomnography with ≥30 minutes of REM sleep and were free of heart failure or active lung disease and had not yet been treated for OSA. Logistic regression analysis was performed to determine the effect of REM-AHI on the prevalence of DR adjusted by several known risk factors for DR. RESULTS: Quartile of REM-AHI was independently associated with DR (P = 0.024) (Q2: OR, 3.887; 95% CI, 0.737 to 20.495; Q3: OR, 9.467; 95% CI, 1.883 to 47.588; Q4: OR, 12.898; 95% CI, 2.008 to 82.823 relative to Q1), whereas quartile of non-REM (NREM)-AHI was not (P = 0.119). Similarly, continuous REM-AHI (OR, 2.875; 95% CI, 1.224 to 6.752; P = 0.015) was independently associated with DR, whereas NREM-AHI was not (P = 0.107). In addition, AHI was independently associated with DR when controlling for several known risk factors for DR (P = 0.043). CONCLUSION: REM-AHI was independently associated with DR. REM-AHI could be a potential risk factor for DR.

Effect of Sleep-Disordered Breathing on Albuminuria in 273 Patients With Type 2 Diabetes.

STUDY OBJECTIVES: Sleep-disordered breathing (SDB) can induce hyperglycemia, hypertension, and oxidative stress, conditions that are known to cause kidney damage. Therefore, SDB may exacerbate albuminuria, which is an established marker of early-stage kidney damage in patients with type 2 diabetes mellitus (T2DM). The association between SDB and albuminuria in patients with T2DM was investigated in this study. METHODS: This cross-sectional study included 273 patients with T2DM who underwent portable sleep testing and measurement of urine albumin to creatinine ratio (UACR). The association between the severity of SDB and albuminuria was investigated. Patients were divided into three groups according to the respiratory event index (REI): the no or mild group (REI < 15 events/h), moderate (REI 15 to < 30 events/h), and severe (REI ≥ 30 events/h). Albuminuria was defined as UACR ≥ 3.4 mg/mmol creatinine. Logistic regression analysis for albuminuria included the categorical REI as the independent variable. RESULTS: The median (interquartile range) REI of all patients (age 57.9 ± 11.9 years, mean ± standard deviation, male sex 81.7%, body mass index 26.7 [24.2-29.5] kg/m2, estimated glomerular filtration rate 82 [65-97] mL/min/1.73 m2) was 13.0 (7.0-24.2) events/h. The REI, as a categorical variable, was significantly associated with albuminuria after adjustment for other risk factors for albuminuria; REI 15 to < 30 events/h: odds ratio (OR) 3.35, 95% confidence interval (95% CI), 1.68-6.67, P < .001; REI ≥ 30: OR 8.52, 95% CI, 3.52-20.63, P < .001). In addition, the natural logarithm-transformed REI of all patients also correlated significantly with albuminuria. CONCLUSIONS: The severity of SDB is associated with albuminuria in patients with T2DM.

Aggravation of diabetes, and incompletely deficient insulin secretion in a case with type 1 diabetes-resistant human leukocyte antigen DRB1*15:02 treated with nivolumab.

Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse effects, especially in the endocrine system. Several cases of acute-onset insulin-dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of these cases have a susceptible human leukocyte antigen (HLA) genotype for type 1 diabetes, possibly suggesting that HLA might be involved in the onset of diabetes with anti-PD-1 therapy. We describe an atypical case of hyperglycemia after anti-PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes and steroid diabetes was given nivolumab three times for chemoresistant adenocarcinoma of the lung. On day 5 after the third infusion of nivolumab, he had hyperglycemia (blood glucose 330 mg/dL and hemoglobin A1c 8.0%) without ketosis and with incompletely deficient insulin secretion. The patient had both type 1 diabetes susceptible (HLA-A*24:02 and -DRB1*09:01) and resistant (HLA-DRB1*15:02) HLA genotypes. These HLA genotypes differ from those previously reported in anti-PD-1 antibody-induced diabetes, and might have influenced the preservation of insulin secretion after nivolumab administration in the present case.

Predictive value of titer of GAD antibodies for further progression of beta cell dysfunction in slowly progressive insulin-dependent (type 1) diabetes (SPIDDM).

AIMS: Whether the titer of glutamic acid decarboxylase antibodies (GADAs), especially a low titer, is a marker of progression of beta cell dysfunction in patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) is unclear. MATERIALS AND METHODS: Patients were subdivided as follows: patients with high GADA titers [≥10 U/ml (≥180 WHO U/ml): high GADA] (group 1, n = 37); those with low GADA titers [<10 U/ml (<180 WHO U/ml): low GADA] (group 2, n = 33); those without GADA and with islet cell antibodies (ICA) (group 3, n = 8); those without both GADA and ICA and with insulinoma-associated antigen 2 antibodies (IA-2A) (group 4, n = 6). We also allocated 198 type 2 diabetic patients without any GADA, ICA or IA-2A as group 5. Serum C-peptide responses to annual oral glucose tolerance tests (OGTTs) were followed up for a mean of 107 months from entry. RESULTS: The proportion of patients progressing to an insulin-dependent state in groups 1, 2, 3 and 4 was significantly higher than in group 5. C-peptide responses in OGTTs of patients in groups 1 and 2 were decreased at a significantly higher rate than in group 5. Multivariate Cox proportional hazard analysis revealed that factors including high GADA, low GADA, onset age <45 years, duration of diabetes <24 months, body mass index (BMI) <22.0 kg/m2, low degree of preserved beta cell function and ICA were independent risk factors for progression to an insulin-dependent state. CONCLUSIONS: SPIDDM patients with low GADA titers have a significantly higher risk of progression to an insulin-dependent state than type 2 diabetic patients, suggesting that the presence of GADA, irrespective of the titer, is a hallmark of beta cell failure. Other risk factors for further progression to an insulin-dependent state in SPIDDM patients were ICA, onset age, duration of diabetes, BMI and residual beta cell function.

Relationship between sleep disordered breathing and diabetic retinopathy: Analysis of 136 patients with diabetes.

AIMS: Sleep disordered breathing (SDB) is associated with poor glycemic control. However, whether SDB contributes to diabetic microangiopathies, especially diabetic retinopathy (DR), is unknown. The aim of this study was to assess the relationship between SDB and DR. METHODS: Between January 2010 and November 2012, 136 patients underwent a sleep test and were divided into two groups according to the presence or absence of DR. Sleep test results and known risk factors for DR were compared between groups. Optic fundi were examined using indirect ophthalmoscope or retinal photographs and diagnosed by experienced ophthalmologists. Multivariate stepwise (backward) logistic regression analysis was performed to assess factors associated with DR. RESULTS: Ninety-nine patients without DR (NDR) and 37 patients with DR were assessed. Patients in the DR group had significantly longer duration of diabetes, were more likely to have hypertension and cardiovascular disease (CVD), and were more likely to be taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers (p=0.000 for each). In the multivariate backward logistic regression analysis, minimum SO2 (odds ratio [OR], 0.89; p=0.001), HbA1c (OR, 1.40; p=0.021), duration of diabetes (OR, 1.23; p<0.001), and history of CVD (OR, 8.96; p=0.008) remained significant. CONCLUSIONS: Minimum SO2 values were associated with DR independent from glycemic control level, duration of diabetes, and history of CVD. This finding suggests that SDB may contribute to the development of DR not through frequency, but due to the degree of intermittent hypoxia.

Ketoacidosis as the initial clinical condition in nine patients with acromegaly: a review of 860 cases at a single institute.

OBJECTIVE: Excess GH causes insulin resistance and impaired glucose metabolism. The objective of this study was to clarify the prevalence of ketoacidosis as the initial presenting symptom of acromegaly. DESIGN AND METHODS: Data were collected from 860 patients with acromegaly who underwent pituitary surgery at Toranomon Hospital over the last 32 years, between 1980 and 2011. RESULTS: Nine cases had ketoacidosis before being diagnosed with acromegaly, including seven males and two females with a mean +/- S.D. age of 38.8 +/- 14.2 years. Serum GH and IGF1 levels were 155 +/- 203 ng/ml and 9.86 +/- 0.68 SDS before pituitary surgery and 3.6 +/- 1.7 ng/ml and 3.72 +/- 3.40 SDS after surgery respectively. The maximum tumor diameter was 28.2 +/- 11.6 mm (ranging from 15 to 47 mm, n=8). None of the patients were diagnosed with diabetes mellitus (DM) nor were they positive for antibodies related to type 1 DM. A possible precipitating factor for ketoacidosis in six cases was excessive ingestion of sugar-containing soft drinks. All the cases had invasive pituitary adenomas. After pituitary surgery, plasma glucose levels were under control without requiring insulin in all cases. Furthermore, six patients did not need oral hypoglycemic agents. CONCLUSIONS: Approximately 1% of patients with acromegaly presented with diabetic ketoacidosis as their first clinical condition.

The best insulin injection pen device for caregivers: results of injection trials using five insulin injection devices.

BACKGROUND: Insulin injection pens have been primarily developed for self-injection among individuals with diabetes. However, an increased elderly population with diabetes has caused an increase in the number of patients who cannot self-inject insulin. Consequently, caregivers inject insulin to the patients ("other-injection"); however, insulin injection devices have not yet been developed for other-injection use. METHODS: We evaluated five devices-OptiClik (Sanofi-aventis, Paris, France), SoloStar (Sanofi-aventis), MirioPen without an antiskid tool (Eli Lilly and Co., Indianapolis, IN), MirioPen with an antiskid tool (Eli Lilly, Hyogo, Japan), and FlexPen (Novo Nordisk A/S, Bagsvaerd, Denmark). In all, 22 respondents (mean +/- SD age, 42.6 +/- 9.3 years [range, 26-57 years]), including 11 men (50.0%) and 11 women (50.0%), injected themselves (self-injection) and others (other-injection). Thereafter, respondents evaluated the ease of use and feel of the pen devices via questionnaires. As a result, we evaluated 220 procedures of insulin injections [22 (respondents) x 5 (devices) x 2 (self and other)] in this study. RESULTS: FlexPen was selected as the best device for self-injection but as the worst device for other-injection. OptiClik was selected as the second worst device for self-injection but as the best device for other-injection. Moreover, for other-injection, FlexPen was too long and less stable, had poor dial visibility, was difficult to recap, and was comprehensively inferior. CONCLUSIONS: We identified problems that were not apparent during studies evaluating conventional self-injection. We conclude that devices meant for other-injection should have different features from those designed for self-injection and that consideration of caregivers' viewpoints is necessary for developing an insulin device specifically meant for other-injection.

The relation of initial methimazole dose to the incidence of methimazole-induced agranulocytosis in patients with Graves' disease.

The relation between the incidence of methimazole (methylmercaptoimidazole; MMI)-induced agranulocytosis and initial MMI dose was evaluated in a group of 514 patients with Graves' disease who were treated between 1995 and 2005. One hundred and forty-six (28.40%) patients had received an initial dose of 30 mg MMI and 277 (53.89%) patients had been treated with 15 mg MMI. Nine patients (1.75%) developed agranulocytosis due to MMI treatment. Six (4.11%) of 146 patients who received an initial dose of 30 mg MMI, two (4.54%) of 44 patients given an initial dose of 20 mg MMI, and one (0.36%) of 277 patients given an initial dose of 15 mg MMI developed agranulocytosis. There was a statistically significant difference in agranulocytosis incidence between patients receiving an initial dose of 30 mg MMI and those who received an initial dose of 15 mg. Although 8 (4.10%) of 195 patients in the high-dose group (20 mg or higher) developed agranulocytosis, only 1 (0.31%) of 319 patients in the low-dose group (15 mg or lower) did. In conclusion, the incidence of agranulocytosis with low-dose MMI therapy was ten times lower than that of the high-dose regimen.