Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients. (65/8027)

OBJECTIVE: To examine the relationships between central obesity, insulin resistance index, plasma insulin, growth hormone (GH), and cortisol concentrations in 90 young Chinese type 2 diabetic patients (aged 33+/-5 years) and 104 age- and sex-matched control subjects (aged 32+/-9 years). RESEARCH DESIGN AND METHODS: Young Chinese diabetic patients (aged <40 years) were recruited from the Prince of Wales Hospital. Blood pressure, height, weight, and waist and hip circumferences were determined. Venous blood was sampled for measurements of fasting plasma glucose, HbA1c, lipids, creatinine, insulin, GH, and cortisol. A 24-h urine was assayed for urinary albumin excretion (UAE). General and central obesity was represented by BMI and waist circumference, respectively. Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations. RESULTS: Compared with control subjects, diabetic patients were more obese, hyperglycemic, and had worse lipid profile, higher blood pressures, UAE, insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.001) but lower GH concentrations (P < 0.05). When analyzed as a whole group (n = 194), increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.01) but a decreasing trend of plasma GH concentration (P < 0.05). Using stepwise multiple regression analysis, waist circumference was only associated with sex variable (being higher in men) in the control subjects. In the diabetic group, 51% of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels. CONCLUSIONS: In young Chinese type 2 diabetic patients, hyperinsulinemia, hypercortisolemia, and reduced plasma GH levels were closely associated with central obesity. Based on these findings, we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients. Alternatively, lifestyle-related obesity may have given rise to these hormonal changes. More studies are required to delineate the nature of these relationships.  (+info)

Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis. (66/8027)

By virtue of its potential effects on rates of energy expenditure, uncoupling protein 3 (UCP3) is an obesity candidate gene. We identified nine sequence variants in UCP3, including Val9Met, Val102Ile, Arg282Cys, and a splice site mutation in the intron between exons 6 and 7. The splice mutation results in an inability to synthesize mRNA for the long isoform (UCP3L) of UCP3. Linkage (sib pair), association, and transmission disequilibrium testing studies on 942 African-Americans did not suggest a significant effect of UCP3 on body composition in this group. In vastus lateralis skeletal muscle of individuals homozygous for the splice mutation, no UCP3L mRNA was detectable; the short isoform (UCP3S) was present in an increased amount. In this muscle, we detected no alterations of in vitro mitochondrial coupling activity, mitochondrial respiratory enzyme activity, or systemic oxygen consumption or respiratory quotient at rest or during exercise. These genetic and physiologic data suggest the following possibilities: UCP3S has uncoupling capabilities equivalent to UCP3L; other UCPs may compensate for a deficiency of bioactive UCP3L; UCP3L does not function primarily as a mitochondrial uncoupling protein.  (+info)

Absence of genetic alteration at codon 531 of the human c-src gene in 479 advanced colorectal cancers from Japanese and Caucasian patients. (67/8027)

Activation of c-src, a cellular human gene homologous in sequence to the v-src gene of Rous sarcoma virus, had been thought to play an important role in the progression of several types of human cancers, without having undergone any genetic changes. However, recently truncating mutations at codon 531 of the c-src gene were reported in 12% of the advanced colon cancers, and it was also demonstrated that this change was activating, transforming, tumorigenic, and metastasis promoting. To investigate whether the codon 531-specific mutation could be involved in the carcinogenesis of colorectal cancer in the Japanese and Caucasian populations, we examined a total of 479 advanced colorectal cancers from 421 Japanese patients (46 of them with liver or lung metastases) and from 58 Caucasian patients (11 of them with liver metastases). Using the PCR-RFLP assay and additional single-strand conformation polymorphism analysis, we detected no genetic alteration in any of the advanced colorectal cancers. Our results suggest that the codon 531-specific mutational activation of c-src is unlikely to play a significant role in the malignant progression of colorectal cancers among most Japanese and Caucasian patients.  (+info)

Decrease in multiple sclerosis with acute transverse myelitis in Japan. (68/8027)

Acute transverse myelitis (ATM) may be a manifestation of multiple sclerosis (MS) and was reported to be more common among Japanese MS patients than in Caucasian MS patients. Recently there are arguments whether clinical manifestations of MS may have changed. Therefore, we studied the frequency of ATM in MS and the clinical subtypes of MS in 86 clinically definite MS patients whose onsets were in 1970-1979, 1980-1989, and 1990-1998 in Sendai City, Japan. Fifty-six of the patients were women and 30 were men. Forty-four patients had the conventional form of MS (C-MS) commonly seen in Western countries, and 42 had optic-spinal or spinal forms of MS (OSS-MS). Twenty MS patients had ATM, and all of them were belong to optic-spinal form of MS. ATM was not seen in any cases of C-MS. The mean onset age (years) of the clinical subtypes was 25.5 in C-MS, 34.1 in OSS-MS without ATM, and 30.9 in OSS-MS with ATM. Among the patients whose onset of the disease was in 1970-1979, 60.0% of them were cases of OSS-MS with ATM, but such cases were markedly decreased to 5.3% in 1990-1998. In contrast, the frequency of C-MS increased to 63.2% in 1990-1998 compared with 20.0% in 1970-1979. Analysis of the data by the year of birth of the patients showed similar results. Our data suggest that the frequency of ATM in MS markedly decreased, and that of C-MS increased during the last 30 years in Sendai, Japan. Since the genetic background of Japanese has not changed, some exogenous factors, such as food, infectious microorganisms, and chemicals in our environment, may be responsible for the change.  (+info)

Association between serotonin transporter gene polymorphism and smoking among Japanese males. (69/8027)

The serotoninergic system may be involved in smoking behavior because nicotine increases brain serotonin secretion, nicotine withdrawal decreases serotonin levels, and a selective serotonin reuptake inhibitor antagonizes the response to nicotine. Compared with the L allele, the S allele of the polymorphism in the upstream regulatory region of the serotonin transporter gene is associated with decreased transcription efficiency of the 5-HTT gene promoter. We examined this polymorphism in a Japanese population consisting of 387 males from two different areas in Japan. The L allele was observed significantly more often in smokers (21%) than in nonsmokers (lifetime nonsmokers + ex-smokers, 14%; P = 0.005). The presence of the L allele (the L/L + L/S genotypes) was also significantly increased in smokers (37%) compared with that in nonsmokers (24%; P = 0.003). The present study suggests that individuals with the S/S genotype are less inclined to smoke and/or can more easily stop smoking than others, supporting a role of the serotoninergic system in smoking behavior.  (+info)

Selective amplification of exons 3 and 8 of the human growth hormone receptor (hGHR) gene based on newly identified intron sequences. (70/8027)

The gene for human growth hormone receptor (hGHR) consists of at least 10 exons, and the corresponding protein is encoded in exons 2-10 which span at least 87 kbp of chromosome 5. Failure to amplify exons 3 and 8 of the hGHR gene from Japanese subjects with the previously reported primers prompted us to determine intron sequences flanking exon 3 and those flanking exon 8 of the hGHR gene, and novel intron sequences flanking exons 3 and 8 of the hGHR gene were identified. We designed new oligonucleotide primers based on these sequences, and successfully amplified DNA fragments encompassing exon 3 and those encompassing exon 8 of the hGHR gene. Since all of the 50 Japanese and the two Caucasians had the very same intron sequences which were different from the previously reported ones, it is more likely that the previously reported sequences were simply wrong than that there exist polymorphic differences in the intron sequences among different ethnic populations.  (+info)

Short-term longitudinal changes in subcutaneous fat distribution and body size among Japanese women in the third decade of life. (71/8027)

This research clarified the changes in body shape among Japanese women aged in their 20's, by measuring the subcutaneous fat distribution over the whole body and its circumference at certain points. The subjects, 13 healthy women, were measured twice, once in their early 20's and 5 years later in their late 20's. Subcutaneous fat thickness was measured at 14 points on the body using the B-mode ultrasound method and the body size was measured directly at 8 points on the body using a steel measure. Subcutaneous fat thickness tends to increase with age, except at the cheek, neck, bust and leg. Significant increases were detected especially at lower parts of the trunk such as the waist and infragluteal region. Meanwhile, despite the significant change in subcutaneous fat thickness, the circumferences measured did not change, and also weight tended to decrease with age. Based on this finding, except for fat, body mass, such as muscle and bone, decreases with age due to decreased exercise and changes in calorie intake. Cluster analysis of the accumulation patterns of subcutaneous fat indicated that there were the following 3 patterns of subcutaneous fat accumulation from the early 20's to the late 20's. I. Accumulation on the whole trunk (bust, abdomen, waist and back) and upper arm--trunk/upper arm accumulation pattern. II. Significant accumulation around waist--waist accumulation pattern. III. Even accumulation at abdomen, side abdomen, hip and lower hip--abdomen/hip accumulation pattern.  (+info)

Temporal trends and ethnic variations in asthma mortality in Singapore, 1976-1995. (72/8027)

BACKGROUND: A study was undertaken to examine temporal trends and ethnic differences in the asthma mortality rate in Singapore. METHODS: Asthma mortality rates in Singapore were estimated from vital data for the years from 1976 to 1995. Trends in sex and age specific (5-14, 15-34, 35-59, 60+ years) rates were obtained for four periods (1976-80, 1981-85, 1986-90, 1991-95) and for Chinese, Malay, and Indian subjects for the years when these data were available (1989-95). RESULTS: An increase in asthma mortality was observed in children aged 5-14 years from 0.21 per 100,000 person years in 1976-80 to 0.72 per 100,000 person years in 1991-95. No increases were noted in the other age groups but a small decrease was observed in the 1991-95 period for the 35-59 year age group. Marked ethnic differences in mortality rates were observed. In the group aged 5-34 years the asthma mortality rates were 0.5 per 100,000 in Chinese subjects, 1.3 per 100,000 in Indians, and 2.5 per 100,000 in Malay subjects. Similar 2-4 fold differences were observed in all other age groups. CONCLUSIONS: Apart from genetic factors, environmental exposures and medical care factors which influence asthma prevalence and severity are most likely to be the causes of the observed temporal trends and ethnic differences in the asthma mortality rate in Singapore, but further studies are needed to elucidate these more fully.  (+info)