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We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range.This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR;70 mg/dL).The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index 5 was significantly reduced (8.6 % vs 23.7 %, P 0.001).The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM.

A 43-year-old male with type 2 diabetes, under treatment with 5 mg/day of dapagliflozin, was referred to our hospital with upper left abdominal pain and marked hypertriglyceridemia (triglycerides [TGs], 5,960 mg/dl). He was also on a low-carbohydrate diet that promoted ketosis under sodium glucose cotransporter 2 (SGLT2) inhibitor administration. Polyacrylamide gel electrophoresis revealed a remarkable increase in very-low-den-sity lipoprotein, a TG-rich lipoprotein particle synthesized in the liver using free fatty acids derived from adi-pose tissue. Although SGLT2 inhibitors generally improve the lipid profile, under certain conditions such as a low-carbohydrate diet, they may adversely exacerbate the lipid profile via ketosis.

Background: Continuous subcutaneous insulin infusion (CSII) is associated with improved glycemic control, a reduced incidence of hypoglycemia, and improved quality of life (QOL). To date, however, ...

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease.Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, P = 0.002) and Calsepa [High-Man (Man2–6)]: 1.56 (1.19–2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001–0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045–0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively].Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE.Trial Registration: This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).

Aims/introduction The predictive low glucose management (PLGM) system was introduced in March 2018 in Japan. Although there are some reports demonstrating the benefit of PLGM in preventing hypoglycemia, no data are currently available in Japanese patients with type 1 diabetes mellitus (T1DM). The aim of the present study is to evaluate the effect of PLGM with sensor-augmented pump therapy in the prevention of hypoglycemia in Japanese patients. Materials and methods We included 16 patients with T1DM who used the MiniMed®640G system after switching from the MiniMed®620G system. We retrospectively analysed the data of the continuous glucose monitoring system in 1 month after switching to MiniMed®640G. Results The area under the curve (AUC) of hypoglycemia of 180 mg/dL and the duration of hyperglycemia did not change. With the PLGM function, 79.3% of the predicted hypoglycemic events were avoided. Conclusions The hypoglycemia avoidance rate was comparable to those in previous reports. In addition, we demonstrated that PLGM can markedly suppress severe hypoglycemia without deteriorating glycemic control in Japanese T1DM patients. It is necessary to further investigate the effective use of the PLGM feature such as establishing a lower limit and the timing of resumption.

Intermittent-scanning continuous glucose monitoring (isCGM) is widely used in type 1 diabetes (T1D) patients; however, the education required to prevent hypoglycemia by using isCGM is not established. This study examines the combined effect of isCGM device usage and the education to reduce the time in hypoglycemia in comparison to conventional self-monitoring of blood glucose (SMBG).The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study), a randomized, crossover trial, enrolls 104 T1D patients (age, 20-74 years) with T1D. Participants are randomized to use isCGM combined with structured education (Intervention period) or SMBG (Control period) for 84 days, followed by the other for a further 84 days. During the Intervention period, participants have access to the sensor glucose levels and trend arrow of the device. During the Control period, participants conduct SMBG at least three times a day, and retrospective CGM is used to record the blinded sensor glucose levels. The primary endpoint is the decrease of time in hypoglycemia (70 mg/dL) per day (hour/day) during the Intervention period compared with the Control period. The secondary endpoints include other indices of glycemic control, glycoalbumin, accuracy of isCGM, diabetes-related quality of life (QOL), adherence, and cost-effectiveness. The study protocol has received Certified Review Board (CRB) approval from National Hospital Organization Osaka National Hospital (N2018002, Feb 14, 2019). This study is carried out in accordance with the Declaration of Helsinki and the Clinical Trials Act. The findings will be published in peer-reviewed journals.The ISCHIA study will contribute to the standardization of patient education regarding the prevention of hypoglycemia by using isCGM.

Background: Information about factors related to better adherence to continuous glucose monitoring (CGM) sensor adherence is quite limited. Materials and Methods: Forty-six participants with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) without CGM were recruited. The participants’ characteristics and diabetes-related quality of life (QOL) were evaluated at baseline and one year after starting to use CGM. Participants wearing the sensor for ≥60% of the time were considered as adherent. Results: The mean age of the 46 participants was 44.1 ± 15.0 years old and the mean glycohemoglobin (HbA1c) was 7.7 ± 1.0%; 60.9% of the participants were classified as adherent. The duration of using CSII was longer in the adherent group, and the degree of diabetic retinopathy was significantly different. There were no significant differences in age, frequency of self-monitoring of blood glucose, or Hypoglycemia Fear Survey (HFS-B for behavior, HFS-W for worry) score at baseline between the adherent and nonadherent groups. The Problem Areas in Diabetes (PAID) score at baseline was significantly higher and the total CSII-QOL score at baseline was significantly lower in the adherent group. The usage of dual-wave bolus was significantly increased in the adherent group (34.6%-61.5%, P = .016), but not in the nonadherent group (33.3%-33.3%, P > .999). The HbA1c level showed a significant improvement in the adherent group (7.8%-7.3%, P Conclusions: Higher adherence to CGM sensors may be associated with a heavier emotional burden of diabetes and a worse QOL in relation to CSII at baseline.

Supplemental material, Murata_T_PARCS_study_Supplementary_File_rev2 for Predictive Factors of the Adherence to Real-Time Continuous Glucose Monitoring Sensors: A Prospective Observational Study (PARCS STUDY) by Takashi Murata, Akio Kuroda, Munehide Matsuhisa, Masao Toyoda, Moritsugu Kimura, Yushi Hirota, Ken Kato, Hideaki Sawaki, Atsuhito Tone, Satoshi Kawashima, Akira Okada, Tomokazu Watanabe, Shinsuke Nirengi, Akiko Suganuma and Naoki Sakane in Journal of Diabetes Science and Technology

OBJECTIVE Because quantifying glycans with complex structures is technically challenging, little is known about the association of glycosylation profiles with the renal prognosis in diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS In 675 patients with type 2 diabetes, we assessed the baseline urinary glycan signals binding to 45 lectins with different specificities. The end point was a decrease of estimated glomerular filtration rate (eGFR) by ≥30% from baseline or dialysis for end-stage renal disease. RESULTS During a median follow-up of 4.0 years, 63 patients reached the end point. Cox proportional hazards analysis revealed that urinary levels of glycans binding to six lectins were significantly associated with the outcome after adjustment for known indicators of DKD, although these urinary glycans, except that for DBA, were highly correlated with baseline albuminuria and eGFR. Hazard ratios for these lectins were (+1 SD for the glycan index) as follows: SNA (recognizing glycan Siaα2-6Gal/GalNAc), 1.42 (95% CI 1.14–1.76); RCA120 (Galβ4GlcNAc), 1.28 (1.01–1.64); DBA (GalNAcα3GalNAc), 0.80 (0.64–0.997); ABA (Galβ3GalNAc), 1.29 (1.02–1.64); Jacalin (Galβ3GalNAc), 1.30 (1.02–1.67); and ACA (Galβ3GalNAc), 1.32 (1.04–1.67). Adding these glycan indexes to a model containing known indicators of progression improved prediction of the outcome (net reclassification improvement increased by 0.51 [0.22–0.80], relative integrated discrimination improvement increased by 0.18 [0.01–0.35], and the Akaike information criterion decreased from 296 to 287). CONCLUSIONS The urinary glycan profile identified in this study may be useful for predicting renal prognosis in patients with type 2 diabetes. Additional investigation of glycosylation changes and urinary glycan excretion in DKD is needed.

Objective We compared the pain accompanying the injection of high-concentration (300 units/mL) insulin glargine (U300G) with that accompanying the injection of conventional (100 units/mL) insulin glargine (U100G). Methods U100G was switched to U300G at basically the same dosage. Visual analog scales were used to assess the quality of life (QOL). The primary outcome was the change in the pain accompanying injections in those using ≥30 units of U100G compared with those using

Continuous subcutaneous insulin infusion (CSII) is associated with improved glycemic control, reduced incidence of hypoglycemia and improved quality of life (QoL). To date, however, there is no QoL scale specific to CSII. The objective of this study was to develop and validate a scale to measure CSII-QoL for patients with type 1 diabetes (T1D).A total of 50 T1D patients aged ≥15 years who used CSII (28% males; age 47.6±17.0 years, mean±SD; duration of diabetes 14.7±9.7 years; duration of CSII use 6.1±3.3 years; HbA1c 7.4±0.8%) took part in the CSII-QoL study. Twenty-eight potential CSII-QoL items were developed in a combined approach consisting of semi-structured patient interviews, expert input and literature research. The resulting CSII-QoL was tested for factor analysis, validity, reliability and influence factors. The final 25-item questionnaire was found to have a three-domain structure (“convenience,” “social restriction,” and “psychological problems”), high internal consistency (Cronbach’s alpha = 0.851), and substantial test-retest reliability (intraclass correlation coefficient = 0.69). The CSII-QoL score correlated positively with basal insulin ratio, but not with age, sex, HbA1c, or total daily insulin dose. The CSII-QoL score correlated negatively with the Problem Areas in Diabetes (PAID) score. The CSII-QoL is the first CSII-related QoL scale for patients with T1D. This short, validated and reliable instrument can potentially be useful in future clinical studies and in routine clinical patient care. (UMIN-CTR: UMIN000031595). Disclosure M. Toyoda: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Medtronic Japan Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. A. Tone: Speaker's Bureau; Self; Lilly Diabetes, Medtronic Japan Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. K. Kato: None. M. Kimura: None. S. Kawashima: Speaker's Bureau; Self; Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd. H. Sawaki: None. Y. Hirota: Speaker's Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Medtronic Japan Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. A. Okada: None. A. Kuroda: Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi. M. Matsuhisa: Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. T. Watanabe: None. A. Suganuma: None. T. Murata: Research Support; Self; Kowa Company, Ltd. Speaker's Bureau; Self; Kowa Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Sanofi K.K. N. Sakane: Board Member; Spouse/Partner; Kao Corporation.

BACKGROUND The Home Blood Pressure for Diabetic Nephropathy study is a prospective observational study conducted to determine the effect of home blood pressure (HBP) on remission/regression of microalbuminuria in patients with type 2 diabetes mellitus (DM). METHODS Patients with type 2 DM having microalbuminuria were followed-up for 3 years. Remission of microalbuminuria was defined as shift from microalbuminuria to normoalbuminuria. Regression of microalbuminuria was defined as a 50% reduction in urinary albumin–creatinine ratio from baseline. All measurements of morning and evening HBP were averaged every year and defined as all HBP. RESULTS In total, 235 patients were followed up. The 3-year cumulative incidences of remission and regression were 32.3% and 44.7%, respectively. Following analysis of all cases, the degree of decline in all home systolic blood pressure (AHSBP), rather than mean AHSBP, influenced the incidence of remission/regression. There was a strong relationship between the decline in AHSBP during the follow-up period and AHSBP at baseline. Therefore, separate analyses of the patients with AHSBP below 140 mm Hg at baseline were performed, which revealed that mean AHSBP during the follow-up period independently affected the incidence of remission/regression. The hazard ratio for inducing remission/regression was significantly lower in patients with AHSBP during the follow-up period above 130 mm Hg than in those with AHSBP below 120 mm Hg. CONCLUSIONS Optimal AHSBP for the induction of remission/regression of microalbuminuria might be below 130 mm Hg. It is required to confirm whether keeping AHSBP below 130 mm Hg leads to subsequent renoprotection or not. CLINICAL TRIALS REGISTRATION Trial Number UMIN000000804.

Controlling hypertension has been revealed to be as important as controlling hyperglycemia to prevent the progression of diabetic nephropathy. Home blood pressure (HBP) measurement is useful for the treatment of hypertension. This study aimed to determine whether HBP measurement is a stronger predictor of the progression of diabetic nephropathy than clinic blood pressure (CBP) measurement. A multicenter follow-up study was performed at the Japan National Hospital Organization. A database of type 2 diabetic patients was constructed. In addition to CBP measurement patients, those using HBP were included in the database. Fifty-four patients with diabetic nephropathy were extracted from the database and analyzed. The rate of decline of the estimated glomerular filtration rate (eGFR) was calculated as the outcome. Correlations between the rate of eGFR decline and various clinical and laboratory parameters, including HBP and CBP measurement, were analyzed. The white-coat effect and reverse white-coat effect were frequently observed. The rate of eGFR decline correlated significantly with home systolic blood pressure (HSBP) measurement, but not with clinic systolic blood pressure (CSBP) measurement. Stepwise multiple linear regression analysis was performed. The rate of eGFR decline was significantly explained by the morning HSBP reading. The rate of eGFR decline was also significantly explained by the average of the morning HSBP readings during the follow-up period, the eGFR and age at baseline in the model, which included CBP and HBP measurements during the follow-up period instead of those at baseline. Home blood pressure measurement is useful for predicting the prognosis of diabetic nephropathy.

Although persistent proteinuria is characteristic of diabetic nephropathy (DN), it is important to differentiate non-diabetic renal diseases (NDRD) in diabetic patients with proteinuria. In order to re-evaluate the indications for renal biopsy in the diabetic patients, we retrospectively analyzed the relationship between clinical features and histological diagnosis in 97 Japanese patients with type 2 diabetes manifesting overt proteinuria. Renal biopsy was performed because they were clinically suspected to have NDRD. Patients were divided into three groups according to the histological diagnosis: (1) the DN group (n = 35) had only diabetic lesions, (2) the complicated group (n = 16) had histological changes of NDRD superimposed on DN and (3) the non-DN group (n = 46) had NDRD without diabetic lesions. We evaluated the specificity and sensitivity of four clinical parameters (duration of diabetes, presence or absence of diabetic retinopathy, microscopic hematuria and granular casts as urinary sediments) for the prediction of NDRD. Short duration of diabetes (

Mononuclear cells infiltrating the interstitium are involved in renal tubulointerstitial injury. The unilateral ureteral obstruction (UUO) is an established experimental model of renal interstitial inflammation. In our previous study, we postulated that L-selectin on monocytes is involved in their infiltration into the interstitium by UUO and that a sulfated glycolipid, sulfatide, is the physiological L-selectin ligand in the kidney. Here we tested the above hypothesis using sulfatide- and L-selectin-deficient mice. Sulfatide-deficient mice were generated by gene targeting of the cerebroside sulfotransferase (Cst) gene. Although the L-selectin-IgG chimera protein specifically bound to sulfatide fraction in acidic lipids from wild-type kidney, it did not show such binding in fractions of Cst(-/-) mice kidney, indicating that sulfatide is the major L-selectin-binding glycolipid in the kidney. The distribution of L-selectin ligand in wild-type mice changed after UUO; sulfatide was relocated from the distal tubules to the peritubular capillaries where monocytes infiltrate, suggesting that sulfatide relocated to the endothelium after UUO interacted with L-selectin on monocytes. In contrast, L-selectin ligand was not detected in Cst(-/-) mice irrespective of UUO treatment. Compared with wild-type mice, Cst(-/-) mice showed a considerable reduction in the number of monocytes/macrophages that infiltrated the interstitium after UUO. The number of monocytes/macrophages was also reduced to a similar extent in L-selectin(-/-) mice. Our results suggest that sulfatide is a major L-selectin-binding molecule in the kidney and that the interaction between L-selectin and sulfatide plays a critical role in monocyte infiltration into the kidney interstitium.

The Home Blood Pressure for Diabetic Nephropathy (HBP-DN) study is a prospective cohort study to determine the optimal home blood pressure (HBP) required to improve the prognosis of type 2 diabetic patients with microalbuminuria. The glomerular filtration rate (GFR) is heterogeneous in microalbuminuric diabetic patients. The first step of the HBP-DN study explored the significance of estimating GFR for the identification of patients for whom HBP measurement would be more helpful. The patients were divided into two groups based on their estimated GFR (eGFR): a low eGFR group (eGFR

OBJECTIVE An inflammatory process is involved in the mechanism of obesity-related insulin resistance. Recent studies indicate that monocyte chemoattractant protein-1 (MCP-1) is a major chemokine that promotes monocyte infiltration into adipose tissues; however, the adhesion pathway in adipose tissues remains unclear. We aimed to clarify the adhesion molecules that mediate monocyte infiltration into adipose tissue. RESEARCH DESIGN AND METHODS We used a DNA microarray to compare the gene expression profiles in epididymal white adipose tissues (eWAT) between db/db mice and C57/BL6 mice each fed a high-fat diet (HFD) or a low-fat diet (LFD). We investigated the change of insulin resistance and inflammation in eWAT in P-selectin glycoprotein ligand-1 (PSGL-1) homozygous knockout (PSGL-1−/−) mice compared with wild-type (WT) mice fed HFD. RESULTS DNA microarray analysis revealed that PSGL-1, a major ligand for selectins, is upregulated in eWAT from both db/db mice and WT mice fed HFD. Quantitative real-time RT-PCR and immunohistochemistry showed that PSGL-1 is expressed on both endothelial cells and macrophages in eWAT of obese mice. PSGL-1−/− mice fed HFD showed a remarkable reduction of macrophage accumulation and expression of proinflammatory genes, including MCP-1 in eWAT. Moreover, adipocyte hypertrophy, insulin resistance, lipid metabolism, and hepatic fatty change were improved in PSGL-1−/− mice compared with WT mice fed HFD. CONCLUSIONS These results indicate that PSGL-1 is a crucial adhesion molecule for the recruitment of monocytes into adipose tissues in obese mice, making it a candidate for a novel therapeutic target for the prevention of obesity-related insulin resistance.

Localization of insulinomas by preoperative imaging is critical for successful surgical resection. However, the visualization and localization of small insulinomas by recent imaging modalities still remains a challenge. Here, we report a 77-year-old woman with a small insulinoma successfully localized by performing arterial stimulation and venous sampling (ASVS), and subsequent super-selective CTA (SSCTA). It was not visualized by routine non-invasive imaging tests such as digital subtraction angiography (DSA). The small size (1.0 cm) of the surgically removed tumor supports the usefulness of SSCTA for localizing very small insulinomas.

Recent studies have shown the involvement of microinflammation in the pathogenesis of diabetic nephropathy. We previously demonstrated that erythromycin, one of the macrolides, ameliorated renal injury via anti-inflammatory effects in experimental diabetic rats. We conducted an open randomized controlled pilot study to investigate the renoprotective effect of clarithromycin for diabetic nephropathy in type 2 diabetic patients manifesting albuminuria.Sixteen patients were randomly assigned to the control (n = 8) or the CAM group in which they received 200 mg/day of clarithromycin (n = 8). At the beginning of the study and after 3 months of investigation, the following parameters were assessed: urinary albumin creatinine ratio (ACR), the levels of serum MCP-1, soluble ICAM-1, IL-18, IL-6 and hs-CRP, and the levels of urinary MCP-1 and IL-18.The changes in urinary ACR were significantly improved (P = 0.039), and serum creatinine levels showed a decreasing trend (P = 0.053) in the CAM group compared with the control group. Urinary MCP-1 levels were significantly reduced in the clarithromycin-administrated group (P = 0.009). However, there was no significant difference in other proinflammatory markers. A significant positive correlation was obtained between the post-to-pre-urinary ACR and the post-to-pre-urinary MCP-1 ratio(r = 0.526, P = 0.043). In the CAM group, the changes of serum creatinine also showed a significant positive correlation with those of urinary ACR, urinary MCP-1, urinary IL-18 and serum levels of soluble ICAM-1.The results from our study suggest that clarithromycin may attenuate the production of renal MCP-1 in type 2 diabetic patients, resulting in amelioration of urinary ACR via anti-inflammatory effects. Modulation of microinflammation with clarithromycin may provide a new approach for diabetic nephropathy.

The diagnosis of insulinoma is sometimes challenging and the symptoms of hypoglycemia may be overlooked in elderly patients with cerebrovascular diseases and higher cerebral dysfunction. Recently, there have been an increasing number of case reports of insulinoma secreting proinsulin without hyperinsulinemia. We report a case of proinsulinsecreting malignant insulinoma in a 72-year-old man with aphasia due to cerebral infarction. He manifested no apparent symptoms, although he was incidentally found to have recurrent hypoglycemia by plasma glucose measurements. The Fajans, Grunt and Turner indexes were all within normal range and the arterial stimulation and venous sampling (ASVS) test revealed no increase in insulin concentration. However, proinsulin concentration was markedly elevated (2470 pmol/l) and well-differentiated endocrine adenocarcinoma, malignant insulinoma, with 2 cm in size in the tail of the pancreas was surgically removed. The diagnosis of hypoglycemia requires careful attention especially in elderly persons and/or patients with cerebrovascular diseases. Measurement of proinsulin is recommended in the diagnosis of insulinoma without hyperinsulinemia.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease that is also referred to as Berardinelli-Seip syndrome. It is characterized by a lack of adipose tissue throughout the body from birth, muscular hypertrophy, advanced bone age, fatty liver, and insulin resistance. We describe computed tomography (CT) and magnetic resonance findings for a 35-year-old woman with CGL. Multiple nodular, well-defined regions of fatty infiltration of the liver are rare and have never been previously reported in a patient with lipodystrophy. To our knowledge, this is the first report describing CT findings of bone sclerotic changes associated with CGL.

Microinflammation is a common major mechanism in the pathogenesis of diabetic vascular complications, including diabetic nephropathy. Macrophage scavenger receptor-A (SR-A) is a multifunctional receptor expressed on macrophages. This study aimed to determine the role of SR-A in diabetic nephropathy using SR-A-deficient (SR-A(-/-)) mice. Diabetes was induced in SR-A(-/-) and wild-type (SR-A(+/+)) mice by streptozotocin injection. Diabetic SR-A(+/+) mice presented characteristic features of diabetic nephropathy: albuminuria, glomerular hypertrophy, mesangial matrix expansion, and overexpression of transforming growth factor-beta at 6 months after induction of diabetes. These changes were markedly diminished in diabetic SR-A(-/-) mice, without differences in blood glucose and blood pressure levels. Interestingly, macrophage infiltration in the kidneys was dramatically decreased in diabetic SR-A(-/-) mice compared with diabetic SR-A(+/+) mice. DNA microarray revealed that proinflammatory genes were overexpressed in renal cortex of diabetic SR-A(+/+) mice and suppressed in diabetic SR-A(-/-) mice. Moreover, anti-SR-A antibody blocked the attachment of monocytes to type IV collagen substratum but not to endothelial cells. Our results suggest that SR-A promotes macrophage migration into diabetic kidneys by accelerating the attachment to renal extracellular matrices. SR-A may be a key molecule for the inflammatory process in pathogenesis of diabetic nephropathy and a novel therapeutic target for diabetic vascular complications.

We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n = 17) and measured urinary excretion of fetuin-A (n = 85). The increased signals of urine samples were observed in Sia alpha 2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography-tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40 +/- 0.43; A2, 0.60 +/- 0.53; A3 1.57 +/- 1.13 ng/gCr; p = 7.29x10(-8)) and of GFR stages (G1, 0.39 +/- 0.39; G2, 0.49 +/- 0.45; G3, 1.25 +/- 1.18; G4, 1.34 +/- 0.80 ng/gCr; p = 3.89x10(-4)). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR