Correlation between renal function and common risk factors for chronic kidney disease in a healthy middle-aged population: a prospective observational 2-year study.

BACKGROUND/AIMS: Age, proteinuria, metabolic syndrome, and hyperuricemia are the reported risk factors for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the best predictor of changes in renal function in the early stages of renal disease in a healthy middle-aged population is still unknown. Our study evaluated the correlation between changes in renal function and common risk factors to determine such a predictor. METHODS: In total, 2,853 healthy persons aged ≤50 years participated in the study. They had no proteinuria and were not on medications for hypertension, diabetes mellitus, hyperlipidemia, or hyperuricemia. Over 2 years, participants underwent annual health screening. The relationship between changes in estimated glomerular filtration rate (eGFR) and changes in risk factors for CKD was evaluated using univariate and multivariate linear regression analyses. RESULTS: Over 2 years, eGFR showed a significant decrease. Univariate regression analysis revealed that changes in fasting plasma glucose (FPG), total cholesterol, LDL-cholesterol, serum uric acid levels, and hemoglobin showed a significant negative correlation with changes in eGFR. Multiple regression analysis confirmed that changes in FPG, serum uric acid levels, in particular, and hemoglobin had a significant negative correlation with changes in eGFR. CONCLUSION: The changes in eGFR and other variables over 2 years were small and could be within expected biologic variation. A longer observational study is needed to elucidate whether FPG, serum uric acid and hemoglobin represent the earliest markers of eGFR decline.

Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome.

AIM: To clarify the efficiency of the criterion of metabolic syndrome to detecting non-alcoholic fatty liver disease (NAFLD). METHODS: Authors performed a cross-sectional study involving participants of a medical health checkup program including abdominal ultrasonography. This study involved 11 714 apparently healthy Japanese men and women, 18 to 83 years of age. NAFLD was defined by abdominal ultrasonography without an alcohol intake of more than 20 g/d, known liver disease, or current use of medication. The revised criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to characterize the metabolic syndrome. RESULTS: NAFLD was detected in 32.2% (95% CI: 31.0%-33.5%) of men (n = 1874 of 5811) and in 8.7% (95% CI: 8.0%-9.5%) of women (n = 514 of 5903). Among obese people, the prevalence of NAFLD was as high as 67.3% (95% CI: 64.8%-69.7%) in men and 45.8% (95% CI: 41.7%-50.0%) in women. Although NAFLD was thought of as being the liver phenotype of metabolic syndrome, the prevalence of the metabolic syndrome among subjects with NAFLD was low both in men and women. 66.8% of men and 70.4% of women with NAFLD were not diagnosed with the metabolic syndrome. 48.2% of men with NAFLD and 49.8% of women with NAFLD weren't overweight [body mass index (BMI) ≥ 25 kg/m(2)]. In the same way, 68.6% of men with NAFLD and 37.9% of women with NAFLD weren't satisfied with abdominal classification (≥ 90 cm for men and ≥ 80 cm for women). Next, authors defined it as positive at screening for NAFLD when participants satisfied at least one criterion of metabolic syndrome. The sensitivity of the definition "at least 1 criterion" was as good as 84.8% in men and 86.6% in women. Separating subjects by BMI, the sensitivity was higher in obese men and women than in non-obese men and women (92.3% vs 76.8% in men, 96.1% vs 77.0% in women, respectively). CONCLUSION: Authors could determine NAFLD effectively in epidemiological study by modifying the usage of the criteria for metabolic syndrome.

Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease.

AIM: To clarify whether nonalcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular disease. METHODS: We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program. NAFLD was diagnosed by abdominal ultrasonography. The metabolic syndrome (MS) was defined according to the modified National Cholesterol Education Program (NCEP) ATP III criteria. Five years after the baseline evaluations, the incidence of cardiovascular disease was assessed by a self-administered questionnaire. RESULTS: Among 1221 participants available for outcome analyses, the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline (5 coronary heart disease, 6 ischemic stroke, and 1 cerebral hemorrhage) than 990 subjects without NAFLD (3 coronary heart disease, 6 ischemic stroke, and 1 cerebral hemorrhage). Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors (odds ratio 4.12, 95% CI, 1.58 to 10.75, P = 0.004). MS was also independently associated with cardiovascular events. But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease. CONCLUSION: Although both of them were predictors of cardiovascular disease, NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model. NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.

The metabolic syndrome as a predictor of nonalcoholic fatty liver disease.

BACKGROUND: The frequent association of nonalcoholic fatty liver disease with components of the metabolic syndrome such as obesity, hyperglycemia, dyslipidemia, and hypertension is well known. However, no prospective study has examined the role of the metabolic syndrome in the development of this disease. OBJECTIVE: To characterize the longitudinal relationship between the metabolic syndrome and nonalcoholic fatty liver disease. DESIGN: A prospective observational study. SETTING: A medical health checkup program in a general hospital. PARTICIPANTS: 4401 apparently healthy Japanese men and women, 21 to 80 years of age, with a mean body mass index (BMI) of 22.6 kg/m2 (SD, 3.0). MEASUREMENTS: Alcohol intake was assessed by using a questionnaire. Biochemical tests for liver and metabolic function and abdominal ultrasonography were done. Modified criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to characterize the metabolic syndrome. RESULTS: At baseline, 812 of 4401 (18%) participants had nonalcoholic fatty liver disease. During the mean follow-up period of 414 days (SD, 128), the authors observed 308 new cases (10%) of nonalcoholic fatty liver disease among 3147 participants who were disease-free at baseline and who completed a second examination. Regression of nonalcoholic fatty liver disease was found in 113 (16%) of 704 participants who had the disease at baseline and who completed a second examination. Men and women who met the criteria for the metabolic syndrome at baseline were more likely to develop the disease during follow-up (adjusted odds ratio, 4.00 [95% CI, 2.63 to 6.08] and 11.20 [CI, 4.85 to 25.87], respectively). Nonalcoholic fatty liver disease was less likely to regress in those participants with the metabolic syndrome at baseline. LIMITATIONS: Ultrasonography may lead to an incorrect diagnosis of nonalcoholic fatty liver disease in 10% to 30% of cases and cannot distinguish steatohepatitis from simple steatosis. Self-reported alcohol intake may cause bias. Because all of the participants were Japanese, generalizability to non-Japanese populations is uncertain. CONCLUSIONS: The metabolic syndrome is a strong predictor of nonalcoholic fatty liver disease.

Circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 are associated with early carotid atherosclerosis.

OBJECTIVE: Growth hormone (GH)-insulin-like growth factor (IGF)-1 axis regulates growth and survival of vascular cells and cardiomyocytes. The role of GH-IGF-1 axis in cardiovascular disease is controversial. METHODS AND RESULTS: We assessed the association of circulating levels of IGF-1 and IGF binding protein-3 (IGFBP-3) with early carotid atherosclerosis and atherosclerotic risk factors in 330 Japanese men (age 51.6+/-8.6 years, range 29 to 77, body mass index [BMI] 23.6+/-2.9 kg/m2). Intima-media thickness (IMT) of the common carotid artery was measured by ultrasound. Abdominal visceral adipose and subcutaneous adipose tissue area by computer-assisted tomographic scan were determined. Correlation coefficients were calculated by partial correlation analysis. BMI and plasma insulin showed positive associations with circulating IGF-1 and IGFBP-3. Subcutaneous adipose tissue was correlated with IGF-1. High-density lipoprotein cholesterol was inversely associated with IGF-1. Blood pressure, total cholesterol, triglyceride, and visceral adipose tissue were positively associated with IGFBP-3. IGF-1 and IGFBP-3 were associated with carotid IMT independent of age, BMI, blood pressure, and insulin. Insulin was associated with carotid IMT in univariate analysis. However, it was not correlated with carotid IMT in the multivariate analyses which included IGF-1 or IGFBP-3 as a covariate. CONCLUSIONS: Increased circulating IGF-1 and IGFBP-3 may be stimulators of atherosclerosis.

Depressive state and paresthesia dramatically improved by intravenous MgSO4 in Gitelman's syndrome.

A 69-year-old woman was referred to our department for evaluation of hypokalemia, which had been treated by oral potassium for more than ten years. She complained of headache, knee joint pain, sleeplessness and paresthesia in extremities and, most prominently, depression. Laboratory data suggested Gitelman's syndrome, which is caused by mutations in the gene encoding the thiazide-sensitive Na-Cl cotransporter. Direct sequencing of the gene in this patient revealed homozygous mutation R964Q in exon 25. Intravenous supplement of MgSO4 dramatically improved both the depression and the paresthesia, suggesting that hypomagnesemia played a role in the clinical manifestations.

Decrease of beta-cells and increase of alpha-cells in a diabetic patient with mitochondrial DNA 3243 (A-->G) mutation.

We report here a case of a 53-year-old woman with mitochondrial 3243 (A-->G) mutation diabetes. Diabetes mellitus was diagnosed at 39 years of age. At 50 years of age, cardiomyopathy and hypothyroidism were noted. At 53 years of age, the patient was admitted to our hospital for treatment of necrotic ulceration of toes. However, she died of massive heart failure. Pathological examination at autopsy showed a decrease in size, number, and acidophilicity of islets in the pancreas. Immunohistochemical stain revealed a decrease in the beta-cell population to 20.5+/-9.2% and a relative increase in alpha-cell population to 48.6+/-11.5%.

Severe graves ophthalmopathy accompanied by HTLV-1-associated uveitis (HAU) and anti-neutrophil cytoplasmic antibody-related vasculitis: a case report and a review of the literature of HAU with Graves disease.

A 50-year-old woman was admitted because of severe exophthalmos associated with Graves disease. She underwent methimazole (MMI) and methylprednisolone pulse therapy against exophthalmos. She noticed photophobia and blurred vision 3 weeks after the start of pulse therapy and she was diagnosed as having uveitis. Methylprednisolone pulse therapy was performed again for both exophthalmos and uveitis, followed by daily administration of 20 mg of prednisolone and instillation of betamethasone for 2 weeks and the uveitis was improved. Western blot analysis confirmed that human T lymphotropic virus type 1 (HTLV-1) antibody was present in her serum. Propylthiouracil was substituted for MMI and HTLV-1-associated uveitis (HAU) has not recurred. Six months after the beginning of administration of PTU, anti-neutrophil cytoplasmic antibody-related vasculitis developed in the patient. We review 43 cases of HAU with Graves disease, including the present case, in the literature. Only 2 of 27 cases (except unknown cases) (7.4%) had Graves ophthalmopathy. To the best of our knowledge, there has been no investigation of HAU and Graves ophthalmopathy.

Transient Graves disease developing after surgery for Cushing disease.

A 49-year-old man, diagnosed as having Cushing disease in 1976 at the age of 26, underwent a Hardy operation 13 years after treatment with reserpine combined with pituitary radiation. In laboratory examinations before and 2 weeks after the successful surgery, the patient's serum thyroid hormones were found to be normal except for suppressed serum thyroid-stimulating hormone (TSH), and his serum anti-TSH receptor (TRAb) and anti-TSH receptor-stimulating antibodies (TSAb) were negative. Glucocorticoid supplemental treatment was withdrawn on the 15th day after surgery and was restarted on the 48th day, during which time there were no signs of an adrenal crisis. Sinus tachycardia, fine finger tremor, and enlarged thyroid gland, approximately the size of a thumb head, were observed on the 140th day after surgery. Thyrotoxicosis with increased serum TSAb and TRAb and high 24-h thyroid uptake of 123I was noted, indicating a diagnosis of Graves disease. No special treatment was prescribed, but his serum thyroid hormone levels started to decrease on the 140th day after the operation and returned to normal on the 520th day. Serum TRAb also spontaneously decreased, but the timing of the peak of serum TRAb was delayed 230 days from that of the thyroid hormones. This is the first reported case of Graves disease after successful surgery for Cushing disease. We presume that a latent autoimmune process in the thyroid, suppressed by hypercortisolism, developed into overt Graves disease after the abrupt reduction of plasma glucocorticoid levels induced by surgery.