Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state. MATERIALS AND METHODS: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: Compared with the non-progressor group (fasting C-peptide [F-CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F-CPR levels and a higher prevalence of insulinoma-associated antigen-2 autoantibodies (IA-2A). The PPV of RIA-GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2 , F-CPR <1.41 ng/mL and IA-2A positivity, respectively. In contrast, the PPV of ELISA-GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F-CPR level, respectively. CONCLUSIONS: Our findings show that, unlike RIA-GADA, ELISA-GADA shows no association between GADA titers and the risk of progression to an insulin-dependent state. The PPV improves when age at diagnosis, BMI and F-CPR levels are considered in combination.

Decreased cognitive function is associated with preceding severe hypoglycemia and impaired blood glucose control in the elderly individuals with type 1 diabetes.

Aim/Introduction: This investigation aimed to clarify the relationship between cognitive function and blood glucose control in the elderly individuals with type 1 diabetes. Materials and methods: In total, 45 patients with type 1 diabetes, age 74.9 ± 6.7 years, and HbA1c levels of 7.9 ± 0.9% were studied. Severe hypoglycemia occurred in 33% of patients, and the number of severe hypoglycemia episodes was 0.6 ± 1.2 in the past 5 years before the time of the cognitive function tests. We analyzed clinical data and dementia scores on the Revised Hasegawa's Dementia Scale (HDS-R), Mini-Mental State Examination (MMSE), and Dementia Assessment Sheet for Community-based Integrated Care System, and 21 items (DASC-21). Results: There was a significant correlation between HbA1c and HDS-R, MMSE, respectively. There was a significant correlation between the number of severe hypoglycemic episodes and HDS-R, MMSE, and DASC-21, respectively. When the group with experience of severe hypoglycemia was compared to the control group, HDS-R, MMSE, and DASC-21 were meaningfully different after adjusting for age modeling analysis of covariance. Conclusions: In elderly individuals with type 1 diabetes, our results suggest that high HbA1c for the past 5 years from the cognitive function test and a history of severe hypoglycemic episodes from the time of disease diagnosis are related to decreased cognitive function.

Benefit of Early Add-on of Linagliptin to Insulin in Japanese Patients With Type 2 Diabetes Mellitus: Randomized-Controlled Open-Label Trial (TRUST2).

INTRODUCTION: This trial was conducted to assess the long-term safety, efficacy, and benefit of early add-on of linagliptin to insulin in patients with type 2 diabetes mellitus (T2DM). METHODS: This trial enrolled 246 subjects. The subjects were randomized to the linagliptin group or the control group and were observed for 156 weeks. After week 16, subjects in the control group were also allowed to add linagliptin to evaluate the benefit of early add-on of linagliptin to insulin. The primary end point was a change in HbA1c from baseline to week 16. Secondary end points included fasting plasma glucose, daily insulin dose, and frequency of adverse events. RESULTS: HbA1c and fasting plasma glucose levels significantly decreased from baseline to week 16 in the linagliptin group compared with the control group. The significant improvement in HbA1c continued until week 52. The daily insulin dose significantly decreased in the linagliptin group compared with the control group. The frequency of hypoglycemia and adverse events was comparable in both groups. CONCLUSIONS: Add-on of linagliptin to insulin was tolerated, improved glycemic control, and reduced the daily insulin dose. This study demonstrates the long-term safety, efficacy and benefit of early add-on of linagliptin to insulin in Japanese T2DM patients.

Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8.

AIMS/INTRODUCTION: This study aimed to investigate the dynamics associated with autoantibodies to insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes. METHODS: Using bridging-type enzyme-linked immunosorbent assay, IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies were evaluated in 269 patients with type 1 diabetes (median onset age 18.2 years, range 0.8-86 years; median diabetes duration 7 years, range 0-58 years). We then compared the prevalence of these autoantibodies among the different age groups, along with the duration of diabetes using the Cochran-Armitage trend test and multivariate logistic regression analysis. RESULTS: The prevalence of IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies in patients with duration of ≤3 years was 41.1, 36.7 and 72.2%, respectively, with 80.0% expressing one or more of these autoantibodies. This prevalence declined according to the disease duration (P < 0.005). Both IA-2A and ZnT8A were more frequently observed in younger patients, whereas glutamic acid decarboxylase autoantibodies was more common in older patients. Multivariate logistic regression analysis showed that there was a significant interaction between the onset age and duration of diabetes in patients diagnosed when aged ≤10 years regarding all anti-islet autoantibodies (P < 0.05). However, for patients diagnosed in the middle tertile (aged 11-30 years), the interaction was significant only for ZnT8A, and for those with late-onset diabetes (aged ≥31 years) only for IA-2A. CONCLUSIONS: The current study showed that the rate of disappearance of anti-islet autoantibodies is faster in patients aged ≤10 years, and that even though both proteins are localized in the insulin granule membrane, humoral autoimmunity to IA-2 and ZnT8 differs according to the age of onset.

Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma-associated antigen-2 autoantibodies in the identification and characterization of Japanese type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to investigate the significance of zinc transporter 8 autoantibody (ZnT8A) in identifying and characterizing autoimmune-mediated type 1 diabetes in Japanese individuals. METHODS: ZnT8A were determined in 324 patients with type 1 diabetes, 191 phenotypic type 2 diabetes and 288 healthy control individuals using bridging-type enzyme-linked immunosorbent assay in addition to autoantibodies to glutamic acid decarboxylase and insulinoma-associated antigen-2. RESULTS: We set a cut-off value of 10.0 U/mL, and 25% of the type 1 diabetic patients had ZnT8A levels exceeding this level. The prevalence of ZnT8A was significantly higher in patients with acute-onset type 1 diabetes than in those with slowly progressive and fulminant type 1 diabetes (P < 0.05). ZnT8A were more frequent in patients aged ≤10 years, but less frequent in patients with duration ≥5 years (P < 0.05). ZnT8A were detected in 5.2% of phenotypic type 2 diabetic patients, with 90% of these being ZnT8A-single-positive. Furthermore, the ZnT8A levels in the phenotypic type 2 diabetes cohort (143.8 ± 194.9 U/mL) were significantly higher than those in the type 1 diabetes cohort (22.9 ± 8.3 U/mL, P < 0.05). In the acute-onset and slowly progressive type 1 diabetic patients with duration ≤5 years, additional measurement of glutamic acid decarboxylase autoantibodies significantly increased the disease sensitivity in patients aged ≤10 years, but not in patients aged ≥11 years (11.7 vs 3.6%, P < 0.05). Multivariate analysis showed that ZnT8A positivity was independently associated with age at sampling and insulinoma-associated antigen-2 autoantibody positivity. CONCLUSIONS: These results suggest that the bridging-type ZnT8A enzyme-linked immunosorbent assay might provide a valuable additional marker for Japanese patients with type 1 diabetes, which could, in turn, allow for an increase in the number of identifiable cases and differentiate clinical phenotypes.

"Benifuuki" Extract Reduces Serum Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Ligands Containing Apolipoprotein B: A Double-Blind Placebo-Controlled Randomized Trial.

(1) Background: Arteriosclerosis is associated with high levels of low-density lipoprotein (LDL) cholesterol. O-methylated catechins in "Benifuuki" green tea are expected to reduce cholesterol levels, although there is limited research regarding this topic; (2) Methods: This trial evaluated 159 healthy volunteers who were randomized to receive ice cream containing a high-dose of "Benifuuki" extract including 676 mg of catechins (group H), a low-dose of "Benifuuki" extract including 322 mg of catechins (group L), or no "Benifuuki" extract (group C). Each group consumed ice cream (with or without extract) daily for 12 weeks, and their lipid-related parameters were compared; (3) Results: A significant reduction in the level of lectin-like oxidized LDL receptor-1 ligand containing ApoB (LAB) was detected in group H, compared to groups L and C. No significant differences between the three groups were detected in their levels of total cholesterol, triglycerides, and LDL cholesterol; (4) Conclusions: "Benifuuki" extract containing O-methylated catechins may help prevent arteriosclerosis.

Effects of L-carnitine supplementation on the quality of life in diabetic patients with muscle cramps.

Diabetic patients often suffer from muscle cramps. This study aimed to compare the quality of life (QOL) of diabetic patients with and without muscle cramps and to investigate the effect of L-carnitine supplementation in diabetic patients with muscle cramps. A total of 91 patients with diabetes were enrolled in this study: 69 patients with muscle cramps and 22 patients without muscle cramps. Muscle cramps and QOL were evaluated using the muscle cramp questionnaire and the Short Form 36 health survey version 2 (SF-36), respectively. Clinical characteristics were compared between diabetic patients with and without muscle cramps. In the prospective portion of the study, 25 diabetic patients with muscle cramps received L-carnitine supplementation (600 mg/day orally) for 4 months. The questionnaires were administered before and after supplementation. The SF-36 scores in diabetic patients with muscle cramps were lower than those in patients without muscle cramps on the subscales of physical function, role physical, bodily pain, vitality, general health, and social function. In the 25 patients with muscle cramps who received L-carnitine supplementation, the monthly frequency of muscle cramps and Wong-Baker FACES® Pain Rating Scale scores were significantly decreased. Scores on the following SF-36 subscales improved after L-carnitine supplementation: body pain, vitality, social function, and role emotional. This study demonstrated that muscle cramps decrease the QOL in patients with diabetes, and L-carnitine supplementation may improve the QOL by reducing the frequency and severity of muscle cramps in these patients.

Impact of glycemic variability on the levels of endothelial progenitor cells in patients with type 1 diabetes.

OBJECTIVE: A reduction in endothelial progenitor cell (EPC) count is considered to correlate with cumulative cardiovascular risk factors including hyperglycemia. This study was conducted to elucidate the influence of glycemic variability on EPC count in patients with diabetes. METHODS: In study 1, we examined the number of EPCs in 57 patients with type 1 diabetes and 43 patients with type 2 diabetes. The number of EPCs (CD34+, CD34+CD133+, CD34+CD309+, and CD34+CD133+CD309+) was counted as the number of cells per 106 events. In study 2, we examined 37 outpatients with type 1 diabetes without macrovascular complications. We assessed associations between EPC count and seven parameters of glycemic variability (blood glucose standard deviation, mean amplitude of glycemic excursion, J index, M value, mean of daily differences, low blood glucose index, and high blood glucose index), as measured by continuous glucose monitoring. We further analyzed the correlation between EPC count and the carotid intima-media thickness (IMT) in 24 patients. RESULTS: In study 1, the number of circulating CD34+ and CD34+CD133+ cells was significantly decreased in patients with type 1 diabetes relative to that in patients with type 2 diabetes (p = 0.020 and 0.036, respectively). In study 2, a univariate analysis showed that the J index was negatively correlated with logCD34+ (r = -0.342, p = 0.039). LogCD34+ was significantly negatively associated with the max IMT (r = -0.486, p = 0.012) and the mean IMT (r = -0.503, p = 0.016). CONCLUSIONS: An increase in the J index, which reflects both hyperglycemia and glycemic variability, is associated with a reduction in the EPC count, which might result in the progression of diabetic vascular complications.

Taurine improves glucose tolerance in STZ-induced insulin-deficient diabetic mice.

Blood glucose levels fluctuate considerably in diabetic patients with reduced secretion of endogenous insulin. We previously reported that glucagon is secreted excessively in these patients and that taurine increases glucagon secretion in vitro. Therefore, we hypothesized that glucose tolerance would further deteriorate when taurine was administered to diabetic mice incapable of insulin secretion. We generated four groups of streptozotocin (STZ)-treated C57BL/6J mice (STZ-mice): STZ-mice without taurine treatment (STZ-Con), STZ-mice treated with 0.5% (w/v) taurine (STZ-0.5% Tau), STZ-mice treated with 1% (w/v) taurine (STZ-1% Tau), and STZ-mice treated with 2% (w/v) taurine (STZ-2% Tau). Mice were treated for 4 weeks, and then, we evaluated glucose tolerance, pancreatic ß-cell area and α-cell area, pancreatic insulin and glucagon content, and daily blood glucose variability. As a result, following the administration of taurine, glucose tolerance improved, both pancreatic ß- and α-cell area increased, and both insulin and glucagon content increased. In the 1% taurine administration group, blood glucose variability decreased. These unexpected results suggest that taurine improves glucose tolerance, in spite of its subsequent increased glucagon production, partly by increasing pancreatic ß-cells and insulin production in vivo.

Decreased ß-Cell Function Is Associated with Reduced Skeletal Muscle Mass in Japanese Subjects without Diabetes.

BACKGROUND: Decreased insulin secretion has a great impact on the incidence of type 2 diabetes in Japanese subjects. It is not clear whether ß-cell function is related to muscle mass in subjects without diabetes. We investigated the relationship between ß-cell function and skeletal muscle mass in Japanese subjects without diabetes. METHODS: The study included 1098 subjects (538 men and 560 women) aged 40 to 79 years, without diabetes (fasting glucose lower than 126 mg/dL and glycosylated hemoglobin lower than 6.5%), who consulted Osaka Medical College Health Science Clinic for a medical examination. Appendicular muscle mass was measured by bioelectrical impedance analysis. Appendicular muscle mass index was calculated as appendicular muscle mass divided by height squared (kg/m2). The homeostatic model assessment of ß-cell function was used to assess ß-cell function. The homeostatic model assessment of insulin resistance was used as a measure of insulin resistance. The association between appendicular muscle mass index and clinical parameters of ß-cell function and insulin resistance was examined. RESULTS: Log-transformed homeostatic model assessment of ß-cell function and Log-transformed homeostatic model assessment of insulin resistance showed a normal distribution. In both men and women, there was a significant positive correlation between appendicular muscle mass index and clinical parameters of ß-cell function and insulin resistance. Tertile analysis, following stratification according to appendicular muscle mass index, found that low appendicular muscle mass index was significantly associated with the Log homeostatic model assessment of ß-cell function and Log-transformed homeostatic model assessment of insulin resistance. CONCLUSION: This study shows that decreased ß cell function is associated with reduced skeletal muscle mass in Japanese subjects without diabetes.

Antibody to CMRF35-Like Molecule 2, CD300e A Novel Biomarker Detected in Patients with Fulminant Type 1 Diabetes.

AIMS/HYPOTHESIS: Fulminant type 1 diabetes (FT1D) is a distinct subtype of type 1 diabetes and is fatal without immediate diagnosis and treatment. At present, there are no biomarkers for early and predictive detection of FT1D. METHODS: First, we analyzed a total of 6 serum samples from 3 patients with FT1D (1 sample in the acute and 1 in the sub-acute phases from each patient) by seromic analysis. Second, titres of the antibody were measured by ELISA in sera from 30 patients with FT1D (both in the acute and sub-acute phases), 13 patients with FT1D in the chronic phase, 32 patients with autoimmune type 1 (type 1A) diabetes (T1AD), 30 patients with type 2 diabetes (T2D), 23 patients with autoimmune thyroid disease (AITD) and 31 healthy control subjects (HC). RESULTS: Seromic analysis revealed 9 antibodies which showed high signals from all 3 patients with FT1D in the acute phase. Among them, the titre of anti-CD300e antibody was significantly higher in FT1D patients in the acute phase than that in T1AD, T2D, AITD patients and HC, as determined by ELISA (P<0.01, respectively). The titre of anti-CD300e antibody was also higher in FT1D in the acute phase than that in the sub-acute phase (P = 0.0018, Wilcoxon signed-rank test). The titre of anti-LGALS3 antibody in FT1D patients in the acute phase did not differ from that in patients with FT1D in the sub-acute phase, T1AD, T2D, AITD and HC. CONCLUSION/INTERPRETATION: The titre of a novel antibody, anti-CD300e, was high in sera from patients with FT1D. This antibody might be a diagnostic marker and provide new insight into the pathogenesis of FT1D.

Reversible hypopituitarism with pituitary tuberculoma.

A 50-year-old woman presented with a headache and nausea. A sellar and suprasellar mass was detected on MRI; the tumor was heterogeneously enhanced with gadolinium, and the pituitary stalk was slightly thickened. Laboratory tests revealed severe growth hormone, luteinizing hormone, follicle-stimulating hormone and thyroid-stimulating hormone deficiencies. A pathological examination of the tumor showed scattered granulomas with central necrosis and Langhans giant cells. Tuberculin skin and QuantiFERON TB-Gold tests (QFT-2G) were positive. Accordingly, we diagnosed the patient with pituitary tuberculoma presenting with pituitary dysfunction. Following treatment with antituberculous drugs, the pituitary hormone function normalized and the pituitary tuberculoma disappeared.

Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes.

Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s) involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus.

BACKGROUND: The serum cytokeratin-18 fragment (CK-18) concentration has been suggested to be a biomarker of nonalcoholic fatty liver disease (NAFLD), although its usefulness in patients with type 2 diabetes mellitus (T2DM) is unknown. METHODS: The study was divided into two parts. In the first cross-sectional study, a total of 200 patients with T2DM and 58 healthy control subjects were recruited. NAFLD was diagnosed using ultrasonography. In the subsequent longitudinal study, we evaluated the three-month change (Δ) in the CK-18 concentration and other parameters in 40 T2DM patients with NAFLD. RESULTS: The serum CK-18 values were significantly higher in the NAFLD group than in the nonNAFLD group among both diabetic and nondiabetic subjects. The CK-18 concentration was found to be an independent determinant of NAFLD and was positively correlated with the ultrasonography score and AST and ALT concentrations in the T2DM patients. Positive correlations were also identified between the CK-18 and transaminase concentrations in the T2DM and NAFLD cohorts. ΔCK-18 was found to be significantly associated with ΔBMI in the T2DM patients with NAFLD. CONCLUSIONS: A dose effect between the CK-18 concentration and the severity of NAFLD was found in the T2DM patients; thus, the CK-18 concentration is a potentially useful biomarker for assessing the efficacy of treatment and the improvement in NAFLD in patients with T2DM.

Association between skeletal muscle mass and insulin secretion in patients with type 2 diabetes mellitus.

Recent research has indicated a relationship between skeletal muscle mass and insulin resistance in patients with type 2 diabetes mellitus (T2DM). However, no study has examined the relationship between skeletal muscle mass and insulin secretion in patients with Japanese T2DM. This study aimed to fill this research gap by investigating the relationship between skeletal muscle mass and clinical parameters of T2DM with special reference to the effect of sex or age on the relationship. We examined 138 consecutive T2DM patients who presented at a single center. Anthropomorphic measurement was conducted and skeletal muscle mass was determined by bioelectrical impedance analysis for calculating skeletal muscle index (SMI) as the ratio of appendicular muscle mass (AMM) to total body weight. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) were levels, and values of stimulated C-peptide immunoreactivity (CPR) were determined by glucagon stimulation testing. Statistical analysis showed that AMM was negatively correlated with age in T2DM patients, whereas SMI had no correlation with either FPG or HbA1c levels. On the other hand, SMI was found to be negatively correlated with the log-transformed stimulated CPR values in male patients <65 years (r = -0.40, p < 0.05) and in female patients <65 years (r = -0.40, p < 0.05). The results of multivariate analysis suggest a strong association between the log-transformed stimulated CPR value and SMI. These findings indicate that increased endogenous insulin secretion is associated with lower skeletal muscle mass in T2DM patients who are <65 years of age.

Glycaemic instability correlates with a hyperglucagonaemic response in patients with type 1 diabetes without residual beta-cell function.

We investigated the association between arginine-stimulated glucagon secretion (AUCIRG) and several parameters of glycaemic variability in 12 patients with type 1 diabetes without residual beta-cell function. AUCIRG positively correlated with the SD and mean amplitude of glycaemic excursions, thus glucagon might contribute to glycaemic instability, independent of endogenous insulin.

Use of color Doppler ultrasonography to measure thyroid blood flow and differentiate graves' disease from painless thyroiditis.

BACKGROUNDS: Color Doppler ultrasonography (CDU) has not yet been established as a method to investigate the pathogenesis of thyrotoxicosis. OBJECTIVES: Our first objective was to determine whether the measurement of peak systolic blood-flow velocity in the superior thyroid artery (STV) and thyroid tissue blood flow (TBF) using CDU could differentiate Graves' disease (GD) from painless thyroiditis (PT). The second objective was to examine the factors mediating increased blood flow to the thyroid gland in GD. METHODS: Recruited patients had untreated GD or PT and visited the Department of Internal Medicine (I), Osaka Medical College, between April 1, 2006 and May 31, 2010. Age, gender, blood pressure, pulse rate, thyroid-stimulating hormone, free thyroxine, tri-iodothyronine, TSH receptor antibody and thyroid volume were evaluated in patients. In addition, bilateral measurements of STV, TBF and peak systolic velocity in the common carotid artery (CCV) were also performed. TBF was quantified by calculating the ratio of blood-flow pixels to total pixels in the region of interest using sagittal section images of the thyroid gland. Receiver-operating characteristic curve analysis was performed to determine the ability of STV and TBF measurements to differentiate GD from PT. RESULTS: For the average of STV measured on both sides, the area under the receiver-operating characteristic curve (AUC) was 0.956. For the average of TBF measured on both sides, the AUC was 0.920. At an average STV cut-off value of 43 cm/s, the sensitivity to discriminate GD from PT was 0.87 and the specificity was 1.00. At an average TBF cut-off value of 3.8%, the sensitivity was 0.71 and the specificity was 1.00. In the GD group, neither blood pressure nor pulse rate correlated with the average STV or TBF. Moreover, there was no correlation between STV and CCV or between TBF and CCV on either side. However, STV was correlated with TBF (right side: R = 0.47; left side: R = 0.52). CONCLUSIONS: The results demonstrate that STV and TBF are useful for differentiating GD from PT. Furthermore, the increased STV and TBF found in GD are not related to hyperthyroidism-induced increases in systolic blood pressure, pulse rate or CCV.

Glycated albumin to glycated hemoglobin ratio is a sensitive indicator of blood glucose variability in patients with fulminant type 1 diabetes.

BACKGROUND: Since serum albumin is glycosylated more rapidly than hemoglobin, it is possible that the glycated albumin (GA) to HbA1c ratio (GA: HbA1c ratio) is potentially a more sensitive indicator of blood glucose excursion than HbA1c. The aim of the present study was to assess the clinical usefulness of GA: HbA1c ratio as a marker of daily glucose excursions in patients with type 1 diabetes according to the subtypes; acute onset type 1A, fulminant and slowly progressive type 1 diabetes. METHODS: Fifty-six outpatients with type 1 diabetes [16 fulminant, 20 acute-onset type 1A and 20 slowly progressive (SPIDDM)] were recruited consecutively. Each patient performed self-monitoring of blood glucose at seven points a day. The associations among the daily profile of glucose and GA, HbA1c, GA: HbA1c ratio were examined across and within the subtypes of type 1 diabetes. RESULTS: GA and GA: HbA1c ratio were each independently correlated with mean amplitude of glucose excursion (MAGE) in patients with type 1 diabetes (F=27.53, p<0.001 and F=13.02, p<0.001, respectively). GA: HbA1c ratio was significantly higher in fulminant type 1 diabetic patients than in SPIDDM patients (3.5 ± 0.2 vs. 3.2 ± 0.5, p=0.015) and it was independently associated with MAGE within fulminant type 1 diabetes (F=21.2, p<0.001). CONCLUSION: In conclusion, the present study demonstrated that GA: HbA1c ratio could be a better marker for glycemic variability than HbA1c in type 1 diabetes, especially in fulminant type 1 diabetes.