Improved insulin sensitivity with sodium-glucose cotransporter 2 inhibitor treatment in a patient with slowly progressive type 1 diabetes mellitus with metabolic syndrome: a case report.

We herein report the clinical course of a 56-year-old Japanese patient with slowly progressive type 1 diabetes mellitus, metabolic syndrome, non-alcoholic fatty liver disease, and severe insulin resistance. The patient's intravenous glucose tolerance test indicated marked reductions in insulin sensitivity and endogenous insulin secretion. Accordingly, administration of ipragliflozin l-proline, a sodium-glucose cotransporter 2 inhibitor, promoted improvements in insulin sensitivity and blood glucose levels, as well as a decrease in visceral fat, improvement in dyslipidemia, and decrease in hepatic lipid content, suggesting the potential efficacy of sodium-glucose cotransporter 2 inhibitors for obese patients with type 1 diabetes mellitus exhibiting insulin resistance.

Relationship between kidney function decline and initial risk factors for the progression of diabetic kidney disease: a retrospective analysis of 91 Japanese patients with type 2 diabetes.

BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in Japan. The clinical course and factors related to the progression of DKD to ESRD are important issues when treating patients with DKD. METHODS: Ninety-one type 2 diabetic patients with DKD that had progressed from chronic kidney disease (CKD) stages G1-3 on their initial clinical visit to ESRD were enrolled. The decline in the estimated glomerular filtration rate (eGFR) was analyzed and the initial clinical factors that influenced the decline rate were explored. RESULTS: There was a linear decline in eGFR before progression to ESRD, with a median annual decline rate (∆eGFR) of 9.2 mL/min/1.73 m2. In all patients, a history of coronary artery disease and increased levels of initial eGFR and high-density lipoprotein cholesterol (HDL-C) were positive predictors of log ∆eGFR, whereas age, history of cerebral infarction (CI), and an increased level of serum albumin were negative predictors of log ∆eGFR. In patients with CKD stages G1-2 on their first visit, male sex and increased diastolic blood pressure were positive predictors. In patients with CKD stage G3 on their first visit, an increased level of LDL-C was a positive predictor, whereas a history of CI and an increased level of serum total bilirubin (TBil) were negative predictors. CONCLUSION: In addition to the common risk factors, initial eGFR, HDL-C, and TBil were identified as novel risk factors for ESRD. These risk factors may differ between patients with early and advanced stages of CKD.

A patient with Werner syndrome and adiponectin gene mutation.

Werner syndrome is a premature aging disease characterized by genomic instability and increased cancer risk. Here, we report a 45-year-old diabetic man as the first Werner syndrome patient found to have an adiponectin gene mutation. Showing graying and loss of hair, skin atrophy, and juvenile cataract, he was diagnosed with Werner syndrome type 4 by molecular analysis. His serum adiponectin concentration was low. In the globular domain of the adiponectin gene, I164T in exon 3 was detected. When we examined effects of pioglitazone (15 mg/day) on serum adiponectin multimer and monomer concentrations using selective assays, the patient's relative percentage increased in adiponectin concentration was almost same as that in the 18 diabetic patients without an adiponectin mutation, but the absolute adiponectin concentration was half of those seen in diabetic patients treated with the same pioglitazone dose who had no adiponectin mutation. The response suggested that pioglitazone treatment might help to prevent future Werner syndrome-related acceleration of atherosclerosis. Present and further clinical relevant to atherosclerosis in this patient should be imformative concerning the pathogenesis and treatment of atherosclerosis in the presence of hypoadiponectinemia and insulin resistance.

Association of hypoadiponectinemia in men with early onset of coronary heart disease and multiple coronary artery stenoses.

Adiponectin influences insulin sensitivity and lipid oxidation. Because low plasma adiponectin concentrations are suspected to promote atherosclerosis, we retrospectively assessed relationships of plasma adiponectin concentration to characteristics of coronary heart disease (CHD). Japanese men undergoing coronary angiography for CHD (n = 139) were grouped according to serum adiponectin concentration by enzyme-linked immunosorbent assay (low, <4.0; medium, 4.0-8; high, >8.0 microg/mL). Numbers of coronary arteries with at least 50% stenosis were determined. Serum adiponectin concentration correlated positively with age at onset of CHD (r = 0.285, P = .003). Age at CHD onset in the low-adiponectin group was younger than in the medium or high groups. Adiponectin was protective against CHD onset at ages younger than 58 years (relative risk, 0.778; P = .0047). Significantly more arteries were affected in low-adiponectin patients than in the medium or high group (each P < .01). Adiponectin concentration correlated positively with high-density lipoprotein cholesterol concentration and negatively with triglyceride concentration. Only in diabetic patients did serum adiponectin concentration correlate negatively with body mass index. Low plasma adiponectin concentrations were associated with early CHD onset and multiple atherosclerotic lesions in coronary arteries. Thus, adiponectin concentrations may influence risk of CHD and might serve as one of the screening tests facilitating early intervention.

[Contributions of certified diabetes educator (CDE) on the improvement of medical services for diabetes in the Sanbu area].

The age-adjusted mortality rate by diabetes mellitus in Chiba prefecture is significantly higher than that of the national average. In the Sanbu medical service area where our hospital is located, there are many patients who are suffering from diabetic complications due to low recognition of diabetes. On the other hand, the number of doctors in the Sanbu area is lower than a half of the national average. In this report, we introduce the activity of medical services provided by a member of the lifestyle-related disease control team, which mainly consist with CDEs. The lifestyle-related disease control team was established in June 2003 for providing improved medical services for lifestyle related diseases and for the primary and secondary prevention of diabetes. The member of the medical team is required to accumulate experience in teaching patients and to continuously improve the quality of medical treatment.

Generation of a monoclonal antibody against the mouse Sf3b1 (SAP155) gene product for U2 snRNP component of spliceosome.

SAP155 is a subunit of the U2 snRNP, and plays an important role for prespliceosome assembly and splicing catalysis of the major spliceosome. Recently, it was reported that SAP155 was also a subunit of the minor spliceosome. These suggest that SAP155 is essential for the removal of any type of intron. More recently, a homolog of SAP155 cDNA, designated Sf3b1, was isolated from mouse. In this study, we report the generation of a monoclonal antibody (MAb) against murine Sf3b1 protein. This MAb recognizes endogenous Sf3b1 gene product by Western blotting, but less efficiently by immunoprecipitation.