Sex differences in predictive factors for onset of type 2 diabetes in Japanese individuals: A 15-year follow-up study.

AIMS/INTRODUCTION: The increase in the number of patients with type 2 diabetes mellitus is an important concern worldwide. The goal of this study was to investigate factors involved in the onset of type 2 diabetes mellitus, and sex differences in long-term follow up of people with normal glucose tolerance. MATERIALS AND METHODS: Of 1,309 individuals who underwent screening at our facility in 2004, 748 individuals without diabetes were enrolled. Correlations of metabolic markers including serum adiponectin (APN) with onset of type 2 diabetes mellitus were examined over 15 years in these individuals. RESULTS: The Kaplan-Meier curve for onset of type 2 diabetes mellitus for 15 years in the decreased APN group was examined. Hazard ratios for the APN concentration for onset of diabetes were 1.78 (95% confidence interval [CI] 1.20-2.63, P = 0.004) in all participants, 1.48 (95% CI 0.96-2.29, P = 0.078) for men and 3.01 (95% CI 1.37-6.59, P = 0.006) for women. During the follow-up period of 15 years, body mass index, estimated glomerular filtration rate, fatty liver, C-reactive protein and alanine aminotransferase in men were significant in univariate analysis, but only estimated glomerular filtration rate and fatty liver were significantly related to onset of type 2 diabetes mellitus in multivariate analysis. In women, body mass index, systolic blood pressure, triglyceride, fatty liver and APN were significant in univariate analysis, and APN was the only significant risk factor in multivariate analysis (P < 0.05). CONCLUSIONS: There are differences between men and women with regard to targets for intervention to prevent the onset of type 2 diabetes mellitus. Individuals requiring intensive intervention should be selected with this finding to maximize the use of limited social and economic resources.

Hyperferritinemia Is a Predictor of Onset of Diabetes in Japanese Males Independently of Decreased Renal Function and Fatty Liver: A Fifteen-Year Follow-Up Study.

BACKGROUND: Type 2 diabetes is an important health concern worldwide. The disease etiology may depend on multiple environmental and genetic factors that cause insulin resistance, including dysregulation of iron storage. The goal of this study was to examine the relationship of the serum ferritin concentration with onset of diabetes over a long period. METHODS: Correlations of serum ferritin and metabolic markers with onset of diabetes mellitus were examined over 15 years in 150 males participating in a health screening program. RESULTS: HOMA-ß showed a gradual significant decrease in the first 4 years in subjects with ferritin > 190 ng/mL (group H) compared to those with ferritin ≤ 190 ng/mL, but there was no difference in HOMA-R between these groups. A significant number of cases with onset of diabetes was observed over 15 years (hazard ratio (HR): 3.97), and obesity, fasting blood glucose level, hemoglobin A1c (HbA1c), HOMA-R, fasting immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) were all significant in univariate comparison between non-diabetes and diabetes-onset groups. In multivariate analysis, ferritin in group H (HR: 3.25), fatty liver (HR: 3.38), estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m2 (HR: 3.48) and high-density lipoprotein (HDL) < 40 mg/dL (HR: 2.61) were significant predictive factors for onset of type 2 diabetes mellitus. CONCLUSIONS: These results suggest that the serum ferritin level is an important index for priority intervention in preventive medicine for reduction of onset of diabetes.

Characteristics and prognosis of patients with non-immunoglobulin-M monoclonal gammopathy of undetermined significance: a retrospective study.

Non-immunoglobulin (Ig)-M monoclonal gammopathy of undetermined significance (MGUS) is a precursor lesion with the potential to evolve into a malignant plasma cell neoplasm. The prevalence of MGUS differs by ethnicity and is lower in the Japanese population than in the Western population. However, there is limited evidence about the clinical course of MGUS in Asian races. The present study aims at elucidating the clinical course and prognosis of Japanese patients with non-IgM MGUS in the clinical setting. We retrospectively examined 1009 patients with non-IgM MGUS identified by screening procedures. The median overall survival of these patients was > 20 years, and only one-fifth patients died of plasma cell neoplasms. The cumulative incidence of plasma cell neoplasms requiring treatment was 19%. Multivariate analysis revealed that immunoparesis and female gender were independent factors affecting treatment requirement. Although the characteristics and clinical course of patients with non-IgM MGUS obtained in this study were found to be essentially similar to those of previous studies, we report here for the first time that female gender is a significant independent factor for requiring treatment.

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.

Characteristics and Prognosis of Patients with Immunoglobulin M Monoclonal Gammopathy.

Many patients with immunoglobulin M (IgM) monoclonal gammopathy remain asymptomatic and, consequently, untreated; however, few studies have evaluated the clinical course and prognosis of these patients. Using the screening procedures at our hospital, 74 patients with IgM monoclonal gammopathy were selected. We excluded 11 patients in whom the treatment for lymphoid neoplasms had been initiated at the time of IgM monoclonal protein detection. The remaining 63 patients were considered to be the patient population with IgM MGUS and asymptomatic WM, and were analyzed. In these patients, the median overall survival was longer than 14 years. More than half of these patients died from causes other than lymphoid neoplasm. The cumulative incidence of lymphoid neoplasm requiring treatment was 17.5%. In five of eight patients requiring treatment for lymphoid neoplasms, the causes of death were related with these lymphoid neoplasms. Our study suggests that not all patients with IgM monoclonal gammopathy require uniform treatment for prolonged survival; however, most lymphoid neoplasms requiring treatment are refractory diseases. Our findings may help manage patients with macroglobulinemia.

Impact of Hematopoietic Progenitor Cell Count as an Indicator for Optimal Timing of Peripheral Stem Cell Harvest in Clinical Practice.

For optimizing CD34+ cell collection, appropriately timing peripheral blood stem cell harvest (PBSCH) initiation is crucial. Automatic cell analyzers with the immature myeloid information channel provide hematopoietic progenitor cell (HPC) count, a surrogate marker of CD34+ cells, which can be obtained within a few minutes without requiring monoclonal antibodies. The final decision on PBSCH initiation can be made using the HPC count obtained on the morning of the harvest day. Herein, we evaluated the impact of the HPC count as an indicator for the optimal timing of PBSCH in clinical practice over 9 years. One hundred and eighteen aphereses from 72 cases had a definite number of CD34+ cells/kg in the PBSC yield. A correlation was found between the HPC count in the PB and the CD34+ cell count (R = 0.563, p ＜ 0.001), whereas no correlation existed between the white blood cell and CD34+ cell counts (R = 0.0418, p = 0.65). We defined ＞ 2.0 × 106/kg of CD34+ cells in a single apheresis as good mobilization. Multivariate analysis demonstrated that an HPC count of ＞ 21/µL, myeloblast count of ＞ 12/µL, and age at PBSCH of ＜ 50 years were independently associated with good mobilization (p = 0.001, p ＜ 0.001, and p = 0.005, respectively). Our findings suggest that the HPC count is a good indicator for the optimal timing of PBSCH.

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.