Long-term observation of estimated fluid volume reduction after the initiation of ipragliflozin in patients with type 2 diabetes mellitus: a sub-analysis from a randomized controlled trial (PROTECT).

BACKGROUNDS/AIM: Recent studies have shown that the addition of sodium-glucose co-transporter 2 (SGLT2) inhibitors gradually reduces the estimated fluid volume parameters in a broad range of patient populations, suggesting that this mediates the clinical benefits of SGLT2 inhibitors in preventing heart failure. Here, we sought to examine the long-term (24 months) effect of the SGLT2 inhibitor ipragliflozin on the estimated fluid volume parameters in patients with type 2 diabetes mellitus (T2DM). METHODS: In this prespecified sub-analysis of the PROTECT (Prevention of Atherosclerosis by SGLT2 Inhibitor: Multicenter, Randomized Controlled Study) trial, which was an investigator-initiated, multicenter, prospective, randomized, open-label, clinical trial primarily designed to evaluate the effect of ipragliflozin treatment administered for 24 months on carotid atherosclerosis in patients with T2DM, we evaluated serial changes in estimated plasma volume (ePV, %) calculated using the Straus formula and estimated extracellular volume (eEV, mL) calculated by the body surface area by 24 months following the initiation of 50-mg ipragliflozin once daily and compared them with those following standard care for T2DM (non-SGLT2 inhibitor use). RESULTS: This sub-analysis included 464 patients (ipragliflozin, n = 232; control, n = 232), a full analysis set of the PROTECT trial. In an analysis using mixed-effects models for repeated measures, relative to the control group, ipragliflozin significantly reduced ePV by - 10.29% (95% confidence interval [CI] - 12.47% to - 8.11%; P < 0.001) at 12 months and - 10.76% (95% CI - 12.86% to - 8.67%; P < 0.001) at 24 months. Additionally, ipragliflozin significantly reduced eEV by - 190.44 mL (95% CI - 249.09 to - 131.79 mL; P < 0.001) at 12 months and - 176.90 mL (95% CI - 233.36 to - 120.44 mL; P < 0.001) at 24 months. The effects of ipragliflozin on these parameters over 24 months were mostly consistent across various patient clinical characteristics. CONCLUSIONS: This prespecified sub-analysis from the PROTECT trial demonstrated that ipragliflozin treatment, compared with the standard care for T2DM, reduced two types of estimated fluid volume parameters in patients with T2DM, and the effect was maintained for 24 months. Our findings suggest that SGLT2 inhibitor treatment regulates clinical parameters incorporated into the calculating formulas analyzed and consequently fluid volume status for the long-term, and this may be at least partly associated with clinical benefits from chronic use of SGLT2 inhibitors. Trial registration Japan Registry of Clinical Trials, ID jRCT1071220089.

Prevention of CaCl2-induced aortic inflammation and subsequent aneurysm formation by the CCL3-CCR5 axis.

Inflammatory mediators such as cytokines and chemokines are crucially involved in the development of abdominal aortic aneurysm (AAA). Here we report that CaCl2 application into abdominal aorta induces AAA with intra-aortic infiltration of macrophages as well as enhanced expression of chemokine (C-C motif) ligand 3 (CCL3) and MMP-9. Moreover, infiltrating macrophages express C-C chemokine receptor 5 (CCR5, a specific receptor for CCL3) and MMP-9. Both Ccl3-/- mice and Ccr5-/- but not Ccr1-/- mice exhibit exaggerated CaCl2-inducced AAA with augmented macrophage infiltration and MMP-9 expression. Similar observations are also obtained on an angiotensin II-induced AAA model. Immunoneutralization of CCL3 mimics the phenotypes observed in CaCl2-treated Ccl3-/- mice. On the contrary, CCL3 treatment attenuates CaCl2-induced AAA in both wild-type and Ccl3-/- mice. Consistently, we find that the CCL3-CCR5 axis suppresses PMA-induced enhancement of MMP-9 expression in macrophages. Thus, CCL3 can be effective to prevent the development of CaCl2-induced AAA by suppressing MMP-9 expression.

Neonatal diabetes caused by the heterozygous Pro1198Leu mutation in the ABCC8 gene in a male infant: 6-year clinical course.

Neonatal diabetes is a rare disease, often caused by a monogenic abnormality. A male infant patient developed diabetic ketoacidosis at 2 months-of-age due to the heterozygous ABCC8 gene mutation (p.Pro1198Leu). After genetic diagnosis, insulin therapy was successfully transitioned to oral sulfonylurea therapy. For >6 years, oral sulfonylurea therapy has been safe and effective, and the required amount of sulfonylureas has progressively decreased. The mutation was transmitted in an autosomal-dominant fashion across three generations of his family, but the severity of diabetes varied among members from neonatal diabetes to mild diabetes. One family member had normal glucose tolerance despite having the mutation. This case presentation could help in the understanding of neonatal diabetes caused by the ABCC8 gene mutation.

Identification of a compound heterozygous inactivating ABCC8 gene mutation responsible for young-onset diabetes with exome sequencing.

Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years-of-age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes.

CCL2-Mediated Reversal of Impaired Skin Wound Healing in Diabetic Mice by Normalization of Neovascularization and Collagen Accumulation.

Patients with diabetes frequently present with complications such as impaired skin wound healing. Skin wound sites display a markedly enhanced expression of CCL2, a potent macrophage chemoattractant, together with macrophage infiltration during the early inflammatory phase in skin wound healing of healthy individuals, but the association of CCL2 with delayed skin wound healing in patients with diabetes remains elusive. In this study, we showed that, compared with control mice, mice with streptozotocin-induced diabetes displayed impaired healing after excisional skin injury, with decreased neovascularization, CCL2 expression, and macrophage infiltration. Compromised skin wound healing in mice with diabetes was reversed by the administration of topical CCL2 immediately after the injury, as evidenced by normalization of wound closure rates, neovascularization, collagen accumulation, and infiltration of macrophages expressing vascular endothelial growth factor, a potent angiogenic factor, and transforming growth factor-ß. CCL2 treatment further increased the accumulation of endothelial progenitor cells at the wound sites of mice with diabetes and eventually accelerated neovascularization. Thus, the topical application of CCL2 can be an effective therapeutic option for the treatment of patients with diabetes with defective wound repair, promoting neovascularization and collagen accumulation at skin wound sites.

Identification of a variant associated with early-onset diabetes in the intron of the insulin gene with exome sequencing.

Whole-exome sequencing is a new technology. We used it to explore the gene responsible for early-onset diabetes as a result of impaired insulin secretion in a family. In the INS gene, we identified the heterozygous c.188-31G>A mutation in the proband - a 43-year-old woman. The mutation was also identified in her two daughters with diabetes, but not in her son or her parents, all of whom did not have diabetes. The substitution was located 31 bp proximal to exon 3 in intron 2. It was predicted to create an ectopic splice site leading to inserting 29 nucleotides of intron 2 as an exonic sequence in the transcript. The mutation has been reported in White families, and the present case is the first report in an Asian person. The present results would help in understanding the role of the mutation in developing diabetes.

Contribution of the TNF-α (Tumor Necrosis Factor-α)-TNF-Rp55 (Tumor Necrosis Factor Receptor p55) Axis in the Resolution of Venous Thrombus.

Objective- Deep vein thrombosis results from a combination of risk factors including genetic conditions, obesity, drugs, pregnancy, aging, and malignancy. We examined pathophysiological roles of the TNF-α (tumor necrosis factor-α)-TNF-Rp55 (tumor necrosis factor receptor p55) axis in thrombus resolution using Tnfrp55-/- (TNF-Rp55-deficient) mice. Approach and Results- On ligating the inferior vena cava of wild-type (WT) mice, venous thrombi formed and grew progressively until 5 days but shrunk to <50% of the thrombus weight at day 14. Concomitantly, inferior vena cava ligation enhanced intrathrombotic gene expression of Tnfa and Tnfrp55, and intrathrombotic macrophages expressed both TNF-α and TNF-Rp55 proteins. In Tnfrp55-/- mice treated with the same manner, thrombus formed at a similar rate for 5 days, but shrinking was delayed compared with WT mice. Moreover, the blood flow recovery in thrombosed inferior vena cava was suspended in Tnfrp55-/- mice compared with WT mice. Intrathrombotic Plau (urokinase-type plasminogen activator), Mmp2 (matrix metalloproteinase 2), and Mmp9 (matrix metalloproteinase 9) mRNA expression was significantly reduced in Tnfrp55-/- mice, compared with WT ones. Supportingly, the administration of anti-TNF-α antibody or TNF-α inhibitor (etanercept) delayed the thrombus resolution in WT mice. Furthermore, TNF-α treatment enhanced gene expression of Plau, Mmp2, and Mmp9 in WT macrophages but not Tnfrp55-/- macrophages. These effects were significantly suppressed by ERK (extracellular signal regulated kinase) and NF-κB (nuclear factor-kappa B) inhibitors. Therefore, the lack of TNF-Rp55 has detrimental roles in the thrombus resolution by suppressing PLAU, MMP-2, and MMP-9 expression. In contrast, TNF-α administration accelerated thrombus resolution in WT but not Tnfrp55-/- mice. Conclusions- The TNF-α-TNF-Rp55 axis may have essential roles in the resolution of venous thrombus in mice.

Predominant Improvement of Alpha Cell Function after Steroid Therapy in a Patient with Autoimmune Pancreatitis: Case Report.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a subset of inflammatory pancreatic disease, responsive to corticosteroid therapy. It is prone to being affected by diabetes mellitus, but the effectiveness of steroid therapy on pancreatic endocrine function is still controversial. We present a case of AIP, focusing on pancreatic endocrine function after steroid therapy. CASE REPORT: The patient was referred to our hospital with exacerbation of diabetic control and pancreatic swelling. By admission, the insulin secretory capacity was severely impaired. The patient was diagnosed with AIP and treated with prednisolone, resulting in marked improvement of the pancreatic swelling. Glycemic control worsened transiently after initiation of steroid therapy, but insulin requirements decreased along with tapering prednisolone dosage. Pancreatic cytology showed that the acinar structure had been destroyed, and the islets had disappeared. Insulin and glucagon immunostaining revealed slightly scattered alpha and beta cells within the fibrotic stroma. The patient notably showed improved pancreatic alpha cell function predominantly after steroid therapy, despite partial improvement of beta cell function. CONCLUSION: An imbalance between alpha and beta cell function may contribute to insufficient diabetic control in some patients with AIP. The pancreatic endocrine function test in combination with pancreatic cytology could be helpful when considering the treatment strategy for diabetic control in patients with AIP.

Protective Roles of Interferon-γ in Cardiac Hypertrophy Induced by Sustained Pressure Overload.

BACKGROUND: A clear understanding of the molecular mechanisms underlying hemodynamic stress-initiated cardiac hypertrophy is important for preventing heart failure. Interferon-γ (IFN-γ) has been suggested to play crucial roles in various diseases other than immunological disorders by modulating the expression of myriad genes. However, the involvement of IFN-γ in the pathogenesis of cardiac hypertrophy still remains unclear. METHODS AND RESULTS: In order to elucidate the roles of IFN-γ in pressure overload-induced cardiac pathology, we subjected Balb/c wild-type (WT) or IFN-γ-deficient (Ifng-/-) mice to transverse aortic constriction (TAC). Three weeks after TAC, Ifng-/- mice developed more severe cardiac hypertrophy, fibrosis, and dysfunction than WT mice. Bone marrow-derived immune cells including macrophages were a source of IFN-γ in hearts after TAC. The activation of PI3K/Akt signaling, a key signaling pathway in compensatory hypertrophy, was detected 3 days after TAC in the left ventricles of WT mice and was markedly attenuated in Ifng-/- mice. The administration of a neutralizing anti-IFN-γ antibody abrogated PI3K/Akt signal activation in WT mice during compensatory hypertrophy, while that of IFN-γ activated PI3K/Akt signaling in Ifng-/- mice. TAC also induced the phosphorylation of Stat5, but not Stat1 in the left ventricles of WT mice 3 days after TAC. Furthermore, IFN-γ induced Stat5 and Akt phosphorylation in rat cardiomyocytes cultured under stretch conditions. A Stat5 inhibitor significantly suppressed PI3K/Akt signaling activation in the left ventricles of WT mice, and aggravated pressure overload-induced cardiac hypertrophy. CONCLUSIONS: The IFN-γ/Stat5 axis may be protective against persistent pressure overload-induced cardiac hypertrophy by activating the PI3K/Akt pathway.

Combined examination of glyceryl trinitrate-mediated vascular dilation with flow-mediated vascular dilation is essential for assessment of vascular function in type 2 diabetes.

AIMS/INTRODUCTION: In order to characterize the impaired vascular function in type 2 diabetes (DM) patients, we evaluated the flow-mediated vascular dilation (FMD) with glyceryl trinitrate-mediated vascular dilation (NMD) using ultrasonography. MATERIALS AND METHODS: A total of 111 DM patients and 42 healthy control participants were studied. The maximal dilatation of FMD and NMD (%FMD and %NMD, respectively), the beginning time (T) of dilatation after stimulation and the velocity (V) of the vascular dilatation were also measured. RESULTS: Among DM patients, 49% had impaired %NMD, which affects the results of %FMD. In DM patients with normal %NMD, the %FMD was also significantly lower than that in control participants, although the T and the V were not impaired. In contrast, both the T and the V were disturbed in the DM patients with low %NMD. Multiple linear regression analysis showed that %NMD was independently correlated with albuminuria. Our results indicate that the impaired FMD in DM is be affected by low NMD, and impaired endothelial function already exists even in DM patients whose vascular smooth muscle function is still retained, and also albuminuria is the clinical feature of DM with low %NMD. CONCLUSIONS: Examination of NMD, not only FMD, should be carried out as it offers the possibility of clarifying vascular function in DM patients.

Protective role of human insulin against the cytotoxicity associated with human mutant S20G islet amyloid polypeptide.

AIMS/INTRODUCTION: Islet amyloid polypeptide (IAPP) is a main component of islet amyloid in type 2 diabetes and cosecreted from ß-cell with insulin. Clinical evidence from the patients with S20G mutation of the IAPP gene, as well as experimental evidence that insulin could inhibit amyloid formation of IAPP, suggests that a gradual reduction of insulin could be related to the cytotoxicity associated with S20G-IAPP through long-term deterioration of ß-cells in type 2 diabetes. Our objective was to show an effect of human insulin on S20G-IAPP associated cytotoxicity. MATERIALS AND METHODS: We analyzed the cytotoxicity associated with S20G-IAPP by controlling human insulin expression using adenovirus vectors with micro ribonucleic acid specifically against human insulin in endocrine AtT-20ins cells, which express human insulin permanently. Additionally, we carried out a follow-up study of circulating IAPP and insulin in type 2 diabetic patients. RESULTS: S20G-IAPP expression was associated with a decrease in viability and an increase in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling-positive cells in AtT-20ins cells. Furthermore, downregulation of human insulin enhanced the cytotoxicity associated with S20G-IAPP, and induced the cytotoxicity associated with wild-type (WT)-IAPP. Reduction of ubiquitin carboxy-terminal hydrolase L1 activity enhanced cytotoxicity under the downregulation of human insulin expression in both S20G- and WT-IAPP transduced cells. A 5-year follow up of type 2 diabetic patients showed a disproportionate increase of serum fasting IAPP-to-insulin ratio from baseline. CONCLUSIONS: Human insulin plays a protective role against the cytotoxicity associated with S20G-IAPP, as well as WT-IAPP. The findings could suggest long-term deterioration of insulin secretion associates with IAPP linked cytotoxicity in type 2 diabetes.

Kir6.2 E23K polymorphism is related to secondary failure of sulfonylureas in non-obese patients with type 2 diabetes.

AIMS/INTRODUCTION: The Kir6.2 E23K polymorphism was studied with a special reference to secondary sulfonylurea (SU) failure in non-obese patients with type 2 diabetes. MATERIALS AND METHODS: We recruited 278 non-obese (body mass index ≤30.0 kg/m(2)) Japanese patients with type 2 diabetes who had a history of SU treatment (for 11.2 ± 6.3 years) and compared the frequency of the secondary SU failure among the genotypes of the polymorphism. Genotyping of the Kir6.2 E23K was carried out by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The genotype frequencies of the polymorphism were similar to those previously reported in Japanese patients with type 2 diabetes. The frequency with which patients deteriorated into secondary SU failure was significantly higher in those with the KK genotype than those with EE or EK genotypes. Among 214 patients who eventually received insulin therapy because of secondary SU failure, the period of SU treatment in those with the KK genotype was significantly shorter than those with the EE or EK genotype, although the period from diagnosis to the start of SU treatment was not significantly different. CONCLUSIONS: These data suggest that the Kir6.2 E23K polymorphism is related to the acceleration of secondary SU failure in non-obese Japanese patients with type 2 diabetes.

[Evaluation of seasonal changes in hemoglobin A1c in diabetic patients].

In order to evaluate seasonal changes in hemoglobin A1c (HbA1c) values, we examined HbA1c values among 34,590 patients in 2010, and calculated the monthly average of HbA1c values through the year. HbA1c values were the highest in March and the lowest in October with a difference of 0.30%. The similar annual pattern was observed in HbA1c values from 2006 to 2009. Then we selected 453 diabetic patients whose treatment did not change through the year, and calculated average HbA1c values in four seasons each. There were also significant seasonal changes in diabetic patients, which were the highest in the spring and the lowest in the autumn, especially found in patients with insulin therapy. These effects may be caused by cold climate, decreased physical activity, over food intake and body weight gain in the winter. These seasonal changes in HbA1c should be concerned in the case of health service research, clinical trials and evaluation of the effects of medical treatment.

[Clinical evaluation of insulin measuring kit not cross-react with insulin analogue preparations].

Clinical evaluation of insulin assay system reacting with only human insulin molecule (kit B) was performed by comparing it with conventional insulin assay system (kit A) cross-reacting with insulin analogue as well as human insulin preparation. In vitro, the kit B was confirmed to cross-react with only human insulin, not with insulin analogue preparations such as insulin aspart, lyspro and glargine. In non-insulin treated diabetic patients, postprandial and post-insulin injected serum immunoreactive insulin (IRI) concentrations measured by kit B were almost the same as those measured by the kit A. On the other hand, in diabetic patients treated with insulin analogue preparations, postprandial and post-insulin injected serum IRI levels measured by kit B were obviously low compared with those by kit A. After intravenous injection of insulin analogue preparations (0.1 unit/kg), insulin lyspro or insulin aspart, serum IRI levels measured by the kit B were not increased but gradually decreased in contrast to the obviously increased serum IRI level measured by the kit A. From these results, the kit B was confirmed not to measure the insulin analogue preparations in vitro and in vivo.

Progressive deterioration of insulin secretion in Japanese type 2 diabetic patients in comparison with those who carry the S20G mutation of the islet amyloid polypeptide gene: A long-term follow-up study.

UNLABELLED: Aims/Introduction: In order to clarify the enhanced ß-cell dysfunction in type 2 diabetic patients carrying the S20G mutation of the islet amyloid polypeptide gene (S20G-patients), we first estimated the decline of insulin secretion in Japanese type 2 diabetic patients without the S20G mutation (non-S20G-T2D-patients) by long-term observation, and then compared it with that of the S20G-patients. MATERIALS AND METHODS: We followed 70 non-S20G-T2D-patients (body mass index <30 kg/m(2)) for more than 10 years and six S20G-patients for more than 5 years. We measured fasting C-peptide (F-CP) every 1-2 years and carried out a glucagon test at least once during the follow-up period. F-CP and a 5-min value of C-peptide after glucagon injection (5'-CP) were used as the indices of insulin secretion. We excluded patients who had renal dysfunction and/or anti-insulin antibodies in the insulin-treated patients. The individual annual declines were calculated from the slopes of the regression lines between C-peptide levels and duration (years after diagnosis). RESULTS: The mean individual annual declines of both F-CP and 5'-CP were significantly greater in the S20G-patients than the non-S20G-T2D-patients (F-CP; 0.047 ± 0.026 vs 0.011 ± 0.037 nmol/L/year, P = 0.025, 5'-CP; 0.139 ± 0.055 vs 0.022 ± 0.012 nmol/L/year, P = 0.008). CONCLUSIONS: We established the annual decline of insulin secretion in the Japanese type 2 diabetic patients by the long-term observation. The results show that the decline of insulin secretion is more rapid in the S20G-patients than the non-S20G-T2D-patients. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00102.x, 2011).

Chronic kidney disease has a more powerful impact on peripheral arterial disease than metabolic syndrome in Japanese type 2 diabetic patients.

BACKGROUND: Chronic kidney disease (CKD) and metabolic syndrome have been recognized as risk factors for cardiovascular disease. However, there is no information comparing their impact on macroangiopathy in diabetic patients. Thus, we studied the prevalence of CKD and metabolic syndrome in Japanese type 2 diabetic patients and then compared their impact on peripheral arterial disease (PAD) in type 2 diabetic patients. METHODS: This study focused on Japanese type 2 diabetic patients without hemodialysis (n = 1014). Patients with albuminuria, including microalbuminuria and/or an estimated glomerular filtration rate less than 60 mL/min/1.73(2), were diagnosed as having CKD. PAD was defined as ankle-brachial blood pressure index less than 0.9. RESULTS: The prevalence of CKD and metabolic syndrome was 47.1% and 39.6%, respectively. In four age- and duration-matched groups classified by the presence or absence of CKD and metabolic syndrome, the prevalence of PAD was significantly higher in groups with CKD alone than those with metabolic syndrome alone, and the high prevalence in the groups with CKD was not influenced by the coexistence with metabolic syndrome. CONCLUSIONS: This study indicates that CKD has more powerful impact on PAD than metabolic syndrome in type 2 diabetic patients.

[Clinical usefulness of measurement of urine type IV collagen for detection of early phase of nephropathy in type 2 diabetic patients].

Urine type IV collagen concentrations in type 2 diabetic patients were measured by enzyme immunoassay which has crossreactivity with only intact type IV collagen, and the clinical usefulness for estimating the early phase of diabetic nephropathy was evaluated. Precision of the measurement system was satisfactory for clinical use and the value did not influenced by the presence of sediments in urine. In whole type 2 diabetic patients (N=132), urine type IV collagen concentration (microg/g of creatinine) increased with development of nephropathy and showed significantly increase even in normoalbuminuria when compared with that in normal control subjects (N=117). In type 2 diabetic patients (N=100) with mild microalbuminuria (less than 100 mg/g of creatinine), multiple regression analysis revealed that HbA1C was extracted as a significant valuable for urine type IV collagen, while body mass index was extracted as a significant valuable for urine albumin. In these subjects, urine type IV collagen was significantly lower in the patients with good metabolic control (HbA1C<8.0%) than those with poor control (HbA1> or =8.0%), while the urine albumin was not significantly different between those two groups. These results suggest that measurement of urine type IV collagen in type 2 diabetic patients is useful for detection of early phase of diabetic nephropathy.

The angiotensin II receptor blocker telmisartan improves insulin resistance and has beneficial effects in hypertensive patients with type 2 diabetes and poor glycemic control.

The angiotensin II receptor blocker (ARB) telmisartan has a molecular structure that confers it partial agonist properties similar to those of peroxisome proliferators-activated receptor-gamma molecule, which is thought to modulate tissue response to insulin. In order to investigate the effects of telmisartan on insulin sensitivity and glucose metabolism, we enrolled 14 hypertensive patients under treatment with ARB other than telmisartan who had insulin resistance [homeostasis model for insulin resistance (HOMA-IR)>2.0] but no severe glucose tolerance (HbA1c<6.5%), and HOMA-IR was compared before and after the displacement by telmisartan. We also enrolled 27 obese (body mass index>25kg/m(2)) and hypertensive patients with type 2 diabetes under treatment with ARB other than telmisartan, and HbA1c was assessed before and after the displacement by telmisartan. The telmisartan significantly improved HOMA-IR in hypertensive patients and also significantly decreased HbA1c in type 2 diabetic patients especially in the patients with poor glycemic control (HbA1c>==8.0%). These results indicate that telmisartan improves insulin resistance and gives beneficial effects in hypertensive patients with type 2 diabetes and a poor glycemic control.

Prevalence of metabolic syndrome in Japanese type 2 diabetic patients and its significance for chronic vascular complications.

Prevalence of metabolic syndrome (MetS) in type 2 diabetes and its association with vascular complications were studied in 637 Japanese type 2 diabetic patients. MetS was diagnosed using criteria proposed by the Japanese study group for the definition of MetS in 2005. The prevalence of MetS in patients studied was higher in males (45.9%) than females (28.0%). The prevalence of MetS was 53.0% in males and 35.4% in females in patients with duration of less than 10 years, and decreased with an increase in duration. Upon comparing patients groups complicated with and without MetS, we determined the MetS group had significantly higher levels of fasting serum C-peptide and high-sensitivity C-reactive protein, and a significantly lower level of serum adiponectin. However, the prevalence of coronary heart disease, brain infarction, or peripheral arterial disease was not significantly different between these groups. On the other hand, the prevalence of microangiopathy in the group with MetS was significantly higher than in that without MetS, and became significantly higher along with an increase in duration. This study clarifies the prevalence of MetS in Japanese type 2 diabetic patients, and suggests that MetS is associated with microangiopathy rather than macroangiopathy in Japanese type 2 diabetic patients.