Lower aldosterone-renin ratio is a risk factor for total and cancer death in Japanese individuals: the Takahata study.

OBJECTIVE: A higher plasma aldosterone-renin ratio (ARR) is an established marker for screening for primary aldosteronism (PA). The association between higher ARR and mortality in a general population has not been fully explored. We here examined whether higher ARR is a risk factor for total and cause-specific mortality in a Japanese population. SUBJECTS AND METHODS: A population-based, longitudinal study of 1,310 Japanese individuals (age: 63·9 ± 9·8 years) enrolled in the Takahata study between 2004 and 2006 and followed for up to 8 years. The incidence and causes of death were monitored annually until 10 January 2012 (median follow-up: 2691 days). RESULTS: During the follow-up period, 64 subjects died. Kaplan-Meier analysis showed a significantly increased risk for total and cancer mortality in subjects with lower ARR (log-rank P < 0·001). Cox's proportional hazard model analyses with adjustment for age and gender showed that lower ARR was associated with increased total and cancer mortality in subjects with low (≦72) vs high (>72) ARR (hazard ratios and 95% confidential intervals: 2·56, 1·44-4·56 and 2·78, 1·16-6·65, respectively). CONCLUSIONS: Lower ARR was a significant and independent risk factor for increased total and cancer mortality in this Japanese population. Subjects with higher ARR were not-at-risk for total death in general. These findings increase the necessity for identifying people with PA from those with higher ARR. People with higher ARR without PA may be at very low risk for total and cancer death.

Multivariate meta-analysis of the association of G-protein beta 3 gene (GNB3) haplotypes with cardiovascular phenotypes.

The objective of the present study was to review previous investigations on the association of haplotypes in the G-protein ß3 subunit (GNB3) gene with representative cardiovascular risk factors/phenotypes: hypertension, overweight, and variation in the systolic and diastolic blood pressures (SBP and DBP, respectively) and as well as body mass index (BMI). A comprehensive literature search was undertaken in Pubmed, Web of Science, EMBASE, Biological Abstracts, LILACS and Google Scholar to identify potentially relevant articles published up to April 2011. Six genetic association studies encompassing 16,068 participants were identified. Individual participant data were obtained for all studies. The three most investigated GNB3 polymorphisms (G-350A, C825T and C1429T) were considered. Expectation-maximization and generalized linear models were employed to estimate haplotypic effects from data with uncertain phase while adjusting for covariates. Study-specific results were combined through a random-effects multivariate meta-analysis. After carefully adjustments for relevant confounding factors, our analysis failed to support a role for GNB3 haplotypes in any of the investigated phenotypes. Sensitivity analyses excluding studies violating Hardy-Weinberg expectations, considering gender-specific effects or more extreme phenotypes (e.g. obesity only) as well as a fixed-effects "pooled" analysis also did not disclose a significant influence of GNB3 haplotypes on cardiovascular phenotypes. We conclude that the previous cumulative evidence does not support the proposal that haplotypes formed by common GNB3 polymorphisms might contribute either to the development of hypertension and obesity, or to the variation in the SBP, DBP and BMI.

Lower physical activity is a risk factor for a clustering of metabolic risk factors in non-obese and obese Japanese subjects: the Takahata study.

In several countries including Japan, people without obesity but with a clustering of metabolic risk factors (MetRFs) were not considered to have the metabolic syndrome (MetS). Here, we examined whether lifestyle characteristics differed between non-obese and obese subjects with or without a clustering of MetRFs. From a population-based cross-sectional study of Japanese subjects aged ≥ 40 years, 1,601 subjects (age: 61.9 ± 10.3 years; 710/891 men/women) were recruited. Physical activity status and daily nutritional intake were estimated using questionnaires. A clustering of MetRFs was defined based on the presence of at least two non-essential risk factors for the diagnosis of the MetS in Japan. Energy intake was not higher in subjects with a clustering of MetRFs compared with those without. Among men, energy expenditure at work was significantly lower in non-obese (9.0 ± 8.2 vs. 11.3 ± 9.3 metabolic equivalents (METs), P = 0.025) and obese (9.0 ± 7.9 vs. 11.6 ± 9.4 METs, P = 0.017) subjects with a clustering of MetRFs than in those without. Multiple logistic regression analysis showed that energy expenditure at work was significantly associated with a clustering of MetRFs after adjusting for possible confounding factors including total energy intake. The ORs (per 1 METs) were 0.970 (95% CI, 0.944-0.997; P = 0.032) in non-obese men and 0.962 (0.926- 0.999; P = 0.043) in obese men. Similar associations were not observed in women. In Japanese males, lower physical activity, but not excessive energy intake, is a risk factor for a clustering of MetRFs independent of their obesity status.

Thyroid dysfunction in patients treated with tyrosine kinase inhibitors, sunitinib, sorafenib and axitinib, for metastatic renal cell carcinoma.

OBJECTIVE: Targeted drugs are generally associated with a lower toxicity than conventional systemic cytotoxic drugs and, thus, are administered for long periods. As a result, unusual adverse effects, including thyroid dysfunction, have become important clinical issues. METHODS: We retrospectively collected the data and compared the incidence and the time of onset of thyroid dysfunction in 33 patients (M/F: 26/7, age: 34-77) with metastatic renal cell carcinoma treated with the small-molecule tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib and axitinib in Yamagata University Hospital, Japan, from 2005 to 2010. RESULTS: The incidence of thyroid dysfunction tended to be higher in patients treated with axitinib (6 of 6: 100%) than in those treated with sunitinib (9 of 15: 60%) or sorafenib (6 of 12: 50%) (P= 0.1113). The median thyroid dysfunction-free survival evaluated using the Kaplan-Meier product-limit method with the log-rank test was significantly shorter in patients treated with axitinib than in those treated with sunitinib/sorafenib (3 vs. 16 weeks, P=0.0198). A multivariate Cox regression model for thyroid dysfunction-free survival with several probable confounding factors as co-variables showed that patients treated with axitinib were more likely to have thyroid dysfunction than the others (hazard ratio: 4.53, 95% confidence interval: 1.40-14.63, P=0.0116). CONCLUSIONS: Patients treated with the tyrosine kinase inhibitors developed thyroid dysfunction frequently. Furthermore, those treated with axitinib developed thyroid dysfunction significantly more and at a faster rate than the others. Therefore, when the tyrosine kinase inhibitors, especially axitinib, are used, close monitoring of thyroid function is recommended, at least for the initial 1-2 months, to avoid clinical symptoms derived from thyroid dysfunction.

Retinal arteriolar narrowing predicts 5-year risk of hypertension in Japanese people: the Funagata study.

OBJECTIVE: To determine whether retinal arteriolar narrowing, possibly reflecting peripheral arteriolar vasoconstriction, predicts risk of hypertension in Japanese persons. METHODS: The Funagata study is a population-based cohort study of Japanese aged 35+ years. Baseline examinations were conducted in 2000-2002 among 1058 persons without hypertension. Of these, 581 persons (55%) returned for a 5-year follow-up examination, with data on 563 available for analyses. Retinal photographs taken at the baseline visits were assessed for retinal arteriolar or venular diameter and retinal vessel wall signs using standardized protocols. Hypertension was defined if systolic blood pressure > or =140 mmHg, diastolic blood pressure > or =90 mmHg or from self-reported clinical diagnosis, including the use of antihypertensive medications. Incident hypertension was defined as an absence of hypertension at baseline but presence of hypertension at the follow-up visit. RESULTS: One hundred ninety-three subjects (34.3%) had developed hypertension at 5-year follow-up. After adjusting for age, gender, baseline blood pressure and other risk factors, narrower retinal arterioles at baseline was significantly associated with an increased risk of incident hypertension (odds ratio per standard deviation decrease in arteriolar diameter: 1.53, 95% confidence interval: 1.08-2.18). CONCLUSIONS: Our findings support the concept that arteriolar narrowing, evident in the retina, signals an increased risk of developing hypertension in Japanese persons.

Association of the common fat mass and obesity associated (FTO) gene polymorphism with obesity in a Japanese population.

The association of the FTO gene polymorphism, rs9939609, with obesity was examined using the population of the Takahata study (n (M/F): 2,639 (1,168 / 1,470); age: 63.0 +/- 10.2 years), a Japanese community-based study. The effects of lifestyle-related factors, including nutritional intake and physical activities, on the association were also examined. Body mass index (BMI) was significantly associated with the FTO gene polymorphism (p<0.001). A case-control association study of the FTO gene polymorphism with obesity using multiple logistic regression analysis showed a significant association of the genotype AA (odds ratio, 1.53 [95% confidential interval, 1.04-2.24]) after adjustment for age and gender. Analysis to examine the differences in lifestyle-related factors among the genotype groups showed a significant difference in the energy expenditure for moderate to high-intensity physical activity (PA) (> or = 3.0 METs) (p=0.012) with a significant decrease toward the genotype AA (p=0.027). The effect of energy expenditure for moderate to high-intensity PA on the association of the polymorphism with obesity was then examined using study groups stratified based on the energy expenditure for moderate to high-intensity PA (Low-PA and High-PA). The BMI was significantly higher in the genotype AA in the Low-PA group (p=0.016) but not in the High-PA group (p=0.103). Furthermore, the genotype AA was significantly associated with obesity (odds ratio, 2.39 [95% confidential interval, 1.19-4.80]) in the Low-PA group but not in the High- PA group (p=0.650). The FTO gene, rs9939609, was associated with obesity, and the association was evident in subjects with low-PA, suggesting a PA-dependent association.

[The Funagata study--impaired glucose tolerance is a risk factor for stroke in a Japanese sample].

We investigated whether impaired glucose tolerance (IGT) is a risk factor for stroke. The incidence of stroke and coronary heart disease (CHD) in a cohort population (n = 2,938) consisting of participants of the 1990-97 Funagata study was assessed through 2002. During the 147-months (mean 116.5 months) follow-up, 158(normal glucose tolerance (NGT), IGT, and diabetes: 94, 35, and 29, respectively) participants experienced a stroke, and 94 (54, 16, and 24, respectively) experienced CHD. By the person-year method, IGT was shown to be significant risk factors for stroke(odds ratio: 1.87, 95% CI: 1.73-2.03) and CHD(1.53, 1.31-1.78). Cox's proportional hazard analysis showed that IGT was a risk factor for stroke (age-, sex-, and hypertension-adjusted hazard ratio: 1.51, 95 % CI: 1.02-2.24, p = 0.039).

Association of the Ser326Cys polymorphism in the OGG1 gene with type 2 DM.

The association of the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene with type 2 diabetes was examined using a Japanese population (n (M/W): 4585 (2085/2500); age: 62.6 +/- 10.9 years). HbA1c levels and frequency of diabetic subjects were significantly higher in subjects with genotypes with Cys allele than in those without (p = 0.032 and 0.037, respectively). Multiple logistic regression analysis showed that genotypes with Cys allele were significantly associated with diabetes (OR: 1.32, p = 0.0289). In subjects whose glucose tolerance was classified by FPG and 2-h PG (n = 1.634), the association was more substantial (genotypes with Cys allele vs. without, OR: 1.70, p = 0.0059; genotypes Cys/Cys vs. Ser/Ser, OR: 2.19, p = 0.0008). In subjects with genotype Ser/Ser, the insulin secretion index, HOMA-beta, increased in the subjects with glucose intolerance and decreased in the subjects with diabetes, while, in subjects with genotypes Ser/Cys + Cys/Cys, HOMA-beta decreased as the glucose tolerance progressed (p for trend = 0.010).

A functional polymorphism of the TNF-alpha gene that is associated with type 2 DM.

To examine the association of the tumor necrosis factor-alpha (TNF-alpha) gene region with type 2 diabetes (DM), 11 single-nucleotide polymorphisms (SNPs) of the region were analyzed. The initial study using a sample set (148 cases vs. 227 controls) showed a significant association of the SNP IVS1G+123A of the TNF-alpha gene with DM (p=0.0056). Multiple logistic regression analysis using an enlarged sample set (225 vs. 716) revealed the significant association of the SNP with DM independently of any clinical traits examined (OR: 1.49, p=0.014). The functional relevance of the SNP were examined by the electrophoretic mobility shift assays using nuclear extracts from the U937 and NIH3T3 cells and luciferase assays in these cells with Simian virus 40 promoter- and TNF-alpha promoter-reporter gene constructs. The functional analyses showed that YY1 transcription factor bound allele-specifically to the SNP region and, the IVS1+123A allele had an increase in luciferase expression compared with the G allele.

Salt consumption-dependent association of the GNB3 gene polymorphism with type 2 DM.

The associations of the C825T polymorphism (rs5443) of the G-protein beta3 subunit (GNB3) gene and eight adjacent single nucleotide polymorphisms (SNPs) with diabetes were examined using a Japanese population (n (M/W): 2956 (1335/1621); age: 63.0+/-10.2 years). Fasting plasma glucose (FPG) levels were significantly associated with the C825T polymorphism and two flanking SNPs (rs2301339 and rs5446) (p=0.002, 0.001, and 0.008, respectively). A case-control association study of the C825T polymorphism with diabetes using multiple logistic regression analysis showed a significant association of the genotypes TT+TC with an odds ratio of 0.62 (p=0.008) independent of age, gender, and BMI. The effects of salt consumption on the association were then examined (n=1635). The FPG levels were significantly associated with the C825T polymorphism only in subjects with low salt consumption (<12.44 g/day) (p=0.002). A case-control association study also showed a significant association with diabetes only in subjects with low salt consumption (p=0.006).

Association of the PIK3C2G gene polymorphisms with type 2 DM in a Japanese population.

The associations of five SNPs (SNPs1-5: A-5468G, A-3333G, C-1794T, C437T and T9148C) of the class II phosphoinositide 3-kinase gamma-subunit (PIK3C2G) gene with type 2 diabetes were examined using a population of the Takahata Study (n (M/W): 2930 (1328/1602); age: 63.3+/-10.2 years), a Japanese community-based study. Quantitative association study of the SNPs with HbA1c levels showed significant association for SNPs 2 and 4 (p=0.018 and 0.004, respectively). A case-control association study of SNP 4 with diabetes by multiple logistic regression analysis showed a significant association of the genotype TT of the SNP with an odds ratio of 2.21 (p=0.001) independently of age, gender and BMI. In the NGT subjects, serum fasting insulin levels in the at-risk genotype group of SNP 4 were significantly lower than those in the others (TT, TC, and CC, 4.9+/-2.6, 5.4+/-3.0, and 5.6+/-3.4muU/ml, respectively; p=0.029).

Prevalence and risk factors for age-related macular degeneration in an adult Japanese population: the Funagata study.

OBJECTIVE: To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a Japanese population and to compare these with data from a white population. DESIGN: Population-based cross-sectional epidemiologic study. PARTICIPANTS: A population-based sample of Japanese persons 35 years or older from Funagata, Japan. METHODS: The Funagata study is a population-based study of 1758 (43% of eligible) Japanese persons 35 years or older from Funagata, Japan. In 2000 to 2002, 1625 (92.4%) participants had a nonmydriatic fundus photograph of one eye with sufficient quality for grading of AMD lesions, using the Wisconsin protocol. Age-standardized prevalence rates compared with the Blue Mountains Eye Study (BMES) population, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Risk factors were assessed by logistic regression. MAIN OUTCOME MEASURES: Early and late AMD. RESULTS: Of 1625 participants, early AMD and late AMD were present in 3.5% and 0.5%, respectively. Age-standardized early AMD prevalence in right eyes was 4.1%, similar to the corresponding prevalence of 4.4% in the BMES. For men, age-standardized prevalences of late AMD in right eyes were 1.1% and 1.2% in the BMES; for women, the corresponding prevalences were 0.3% and 2.1%, respectively. Increasing age (per 10 years; gender-adjusted OR, 2.27; 95% CI, 1.10-4.67) and current cigarette smoking (age- and gender-adjusted OR, 5.03; 95% CI, 1.00-25.47) were associated with late AMD. CONCLUSIONS: In this Japanese population, prevalence of early AMD was similar to that for whites in the BMES. Although the late AMD prevalence was lower in Japanese women, in Japanese men it was similar to that in whites. This could have resulted from the substantially high proportion of Japanese men who are smokers. Cigarette smoking and increasing age were the 2 principal factors found associated with late AMD.

Impaired glucose tolerance is a risk factor for stroke in a Japanese sample--the Funagata study.

Impaired glucose tolerance (IGT) is a known risk factor for cardiovascular disease, which includes stroke as well as coronary heart disease (CHD). We investigated whether IGT is a risk factor for stroke. The incidence of stroke and CHD in a cohort population (n = 2938) consisting of participants of the 1990-1997 Funagata study was assessed through interviews with the participants and their family members and reviews of death certificates and residence transfer documents through 2002. Glucose tolerance at the baseline was classified according to the criteria of the 1998 World Health Organization (normal glucose tolerance, n = 2189; IGT, n = 320; and diabetes, n = 286). The cumulative incidences among the groups were compared using the Kaplan-Meier product-limit method, and the risks of these conditions were evaluated by person-year and Cox proportional hazard methods. During the 147-month (mean, 116.5 months) follow-up, 158 (normal glucose tolerance, IGT, and diabetes: 94, 35, and 29, respectively) participants experienced a stroke and 94 (54, 16, and 24, respectively) experienced CHD. By the person-year method, IGT and diabetes were shown to be significant risk factors for stroke and CHD (odds ratio, 1.87 [95% confidence interval, 1.73-2.03] and 3.57 [3.21-3.98] for stroke; 1.53 [1.31-1.78] and 3.47 [2.91-4.14] for CHD, respectively). Cox proportional hazard analysis showed that IGT was a risk factor for stroke (age-, sex-, and hypertension-adjusted hazard ratio: 1.51 [95% confidence interval, 1.02-2.24], P = .039) but not for CHD (1.21 [0.69-2.313], .509). Impaired glucose tolerance is a risk factor for future stroke in a Japanese population.

Ghrelin infused into the portal vein inhibits glucose-stimulated insulin secretion in Wistar rats.

Although accumulating evidence has shown crucial roles of ghrelin and insulin in food intake and energy metabolism, the exact relationship between these hormones remains unclear. In this study, we determined the in vivo effect of ghrelin on insulin secretion. We demonstrated that ghrelin inhibited the glucose-stimulated release of insulin when infused into the portal vein of Wistar rats. However, ghrelin infusion into the femoral vein did not induce such an inhibitory effect. Hepatic vagotomy or coinfusion with atropine methyl bromide diminished the inhibitory effect of ghrelin on glucose-stimulated insulin secretion. In conclusion, ghrelin exerts an inhibitory effect on glucose-stimulated insulin secretion via the hepatic portal system and the vagus nerve. The decrease in ghrelin level after a meal is important for the occurrence of the incretin effect in rats.

Is the measurement of glycated hemoglobin A1c alone an efficient screening test for undiagnosed diabetes? Japan National Diabetes Survey.

The aim of the study was to assess the screening test properties of HbA1c for undiagnosed diabetes (DM) according to the 1999-WHO criteria and its relevance of the Japan National Diabetes Survey Cut-off points for possible and probable DM: HbA1c >or=5.6 and 6.1%. Screening properties of HbA1c predicting undiagnosed DM was examined and compared with that of fasting plasma glucose (FPG) in 1904 Funagata-town inhabitants aged 35-89 years old. The prevalence of previous DM, undiagnosed DM, and impaired glucose regulation (IGR) were 5.5, 6.0, and 18.6%, while the prevalence of probable and possible DM were 7.7 and 5.4%. The area under the receiver operating characteristic curve for undiagnosed DM was similar between HbA1c (0.856 [95% CI: 0.812-0.899]) and FPG (0.902 [0.869-0.936]). HbA1c of 5.6% gave a sensitivity of 56.5%, a specificity of 95.1%, positive and negative predictive values of 44.2 and 97.0%, and a proportion of people above the cut-off point of 8.2%. True positive tests were significantly higher with mean levels of BMI, fasting, and 2-h plasma glucose, and HbA1c, but lower with mean levels of high-density-lipoprotein cholesterol than in false negative tests. The measurement of HbA1c alone may be efficient to screen undiagnosed DM and the cut-off point of 5.6% might be proper with respect to screening tests properties for undiagnosed DM, and prediction of vascular complications in Japan.

Cardiovascular risk factors and retinal microvascular signs in an adult Japanese population: the Funagata Study.

OBJECTIVE: To describe the prevalence of retinal vascular signs and their association with cardiovascular risk factors in a Japanese population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Adult persons aged 35 years or older from Funagata, Yamagata Prefecture, Japan (n = 1481). METHODS: The Funagata Study is a Japanese population-based study of persons aged 35 years or older, and included 1961 nondiabetic participants (53.3% of 3676 eligible subjects). A nonmydriatic retinal photograph was taken of 1 eye to assess retinal microvascular signs. Retinal arteriolar wall signs (focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex) and retinopathy were assessed in 1481 participants without diabetes (40.3% of eligible persons) using a standardized protocol. Using a computer-assisted method, retinal vessel diameters were measured in 921 participants with gradable retinal image (25.1% of eligible persons). MAIN OUTCOME MEASURES: Prevalence of retinal microvascular signs and their association with cardiovascular risk factors. RESULTS: Moderate or severe focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex, and retinopathy were found in 8.3%, 15.2%, 18.7%, and 9.0%, respectively, of the study population. Mean (+/-standard error) values for retinal arteriolar diameter were 178.6+/-21.0 mum, and mean values (+/-standard error) for venular diameter were 214.9+/-20.6 mum. Older persons were more likely to have retinal arteriolar wall signs, retinopathy, and narrower retinal vessel diameters. After adjusting for multiple factors, each 10-mmHg increase in mean arterial blood pressure was associated with a 20% to 40% increased likelihood of retinal arteriolar signs and a 2.8-mum reduction in arteriolar diameter. Retinopathy was associated with higher body mass index and both impaired glucose tolerance and impaired fasting glucose. CONCLUSIONS: In nondiabetic Japanese adults, retinal arteriolar wall signs were associated with older age and increased blood pressure, whereas retinopathy was associated with older age, higher body mass index, impaired glucose tolerance, and impaired fasting glucose. These findings are comparable with data from white populations.

Correlation between change in body weight rather than current body weight and change in serum adiponectin levels in a Japanese population -- the Funagata study.

Serum adiponectin levels are decreased in obese subjects. We examined the association of current body weight (BW) and its change with a change in serum adiponectin levels. Serum adiponectin levels at the baseline (from 1995 to 1997) and the 5-year follow-up (from 2000 to 2002) examinations were evaluated in 1003 (M/F, 425/578; age at the baseline examinations, 58.3 +/- 11.7/57.5 +/- 11.0 years) Japanese subjects from a cohort population (N = 2013) of the Funagata study. Correlations and associations of BW at the baseline examinations and changes in BW between the baseline and the follow-up examinations (deltaBW) with changes in the serum adiponectin levels in the study period (deltaAdiponectin) were examined. Stepwise regression analyses revealed a significant correlation of the deltaBW (r = -0.233 and -0.204 for men and women, respectively; r = -0.324 for the upper tertile group divided based on their body mass index in women) with the deltaAdiponectin. However, the BW at the baseline examinations was not significantly correlated in both sexes. Multiple logistic regression analyses revealed that subjects who reduced their BW by 2 kg or more were 2.56 (95% confidence interval, 1.21-5.42; P = .014) and 8.24 times (95% confidence interval, 3.59-18.9; P < .001) more likely to be in the upper tertile of the deltaAdiponectin than those who increased their BW by 2 kg or more in men and women, respectively, independent of their BW at the baseline examinations. In conclusion, we showed here that the deltaBW was strongly associated with the deltaAdiponectin in both sexes, whereas the BW at the baseline examinations was not associated with the deltaAdiponectin, at least in women.

Transient Worsening of Photosensitivity due to Cholelithiasis in a Variegate Porphyria Patient.

Variegate porphyria (VP) is an autosomal dominant disease caused by mutations of the protoporphyrinogen oxidase (PPOX) gene. This porphyria has unique characteristics which can induce acute neurovisceral attacks and cutaneous lesions that may occur separately or together. We herin report a 58-years-old VP patient complicated with cholelithiasis. A sequencing analysis indicated a novel c.40G>C mutation (p.G14R) in the PPOX gene. His cutaneous photosensitivity had been worsening for 3 years before the emergence of cholecystitis and it then gradually improved after cholecystectomy and ursodeoxycholic acid treatment with a slight decline in the porphyrin levels in his blood, urine and stool. In VP patients, a worsening of photosensitivity can thus be induced due to complications associated with some other disease, thereby affecting their porphyrin-heme biosynthesis.

Association of decrease in serum dehydroepiandrosterone sulfate levels with the progression to type 2 diabetes in men of a Japanese population: the Funagata Study.

Association of serum dehydroepiandrosterone sulfate (DHEAS) levels with insulin resistance and impairment of insulin secretion have been reported. We here examined the association of serum DHEAS levels with type 2 diabetes mellitus (DM) and the progression to DM. The serum DHEAS levels at baseline (from 1995 to 1997) were evaluated in 1709 individuals (998 women and 711 men) from a cohort population (n = 3706) of the Funagata Study. Glucose tolerance was evaluated at baseline as well as at 5-year follow-up examinations (n = 970, follow-up rate, 56.8%) according to the 1985 World Health Organization criteria. The statistical significance of the difference between any 2 groups was determined by the Student t test. Multiple logistic regression analysis determined the association of the traits with the progression to DM at the 5-year follow-up examinations. P < .05 was accepted as statistically significant. The serum DHEAS levels were significantly lower in DM than in normal glucose tolerance. However, this difference was not significant when adjusted for age. In men, the decrease in serum DHEAS levels by the 5-year follow-up examinations was significantly larger in the subjects who became diabetic than in the subjects who remained normal glucose tolerance, even when adjusted for age ( P = .0003). Multiple logistic regression analysis revealed a significant association of the decrease in serum DHEAS levels with the progression to DM, with an odds ratio (per 0.1 log ng/mL) of 1.410 (95% confidence interval [CI], 1.020-1.948, P = .038), independently from age, height, and 2-hour plasma glucose in men. A decrease in serum DHEAS levels seems to be associated with the progression to DM in Japanese men.