Short-Term Treatment with Metformin Improves the Cardiovascular Risk Profile in First-Degree Relatives of Subjects with Type 2 Diabetes Mellitus who have a Metabolic Syndrome and Normal Glucose Tolerance without Changes in C-Reactive Protein or Fibrinogen

OBJECTIVE:

To study if metformin, when administered to first-degree relatives of type 2 diabetes mellitus subjects who have metabolic syndrome and normal glucose tolerance, could improve the cardiovascular risk profile and reduce the levels of both C-reactive protein and fibrinogen.

INTRODUCTION:

Metabolic syndrome is associated with higher cardiovascular morbidity and mortality. Metformin has vasculo-protective effects even in normoglycemic subjects, and C-reactive protein and fibrinogen are considered markers of endothelial injury and inflammation.

METHODS:

Thirty-one non-diabetic first-degree relatives of type 2 diabetes mellitus subjects with metabolic syndrome were randomized (1:1) and double-blinded for placement in the placebo and metformin groups (850mg bid/±90days); 16 subjects were administered metformin (mean age 40.0 [33.5–50] years; 13 females) and 15 subjects were in the placebo group (mean age 37.0 [32–42] years; 9 females). Blood samples were collected at baseline and at the end of treatment for biochemical analyses, including an assessment of C-reactive protein and fibrinogen levels.

RESULTS:

Metformin improved the lipid profile and decreased fasting plasma glucose, systolic blood pressure, weight and body mass index without changing body composition. For those in the placebo we identified no changes in fibrinogen (282.2 [220.4–323.7] mg/L vs. 286.7 [249.6–295.1] mg/L; NS) or in C-reactive protein levels (0.68 [0.3–1.2] vs. 0.64 [0.3–1.0] mg/L; NS). The same was also observed for the levels of fibrinogen (303.9 [217.6–347.6] mg/L vs. 290.9 [251.5–301.9] mg/L; NS) and C-reactive proteins (0.78 [0.3–1.1] vs. 0.80 [0.4–0.9] mg/L; NS) in the metformin group.

CONCLUSIONS:

Metformin treatment in first-degree relatives of type 2 diabetes mellitus sufferers who have metabolic syndrome and normal glucose tolerance improved the cardiovascular risk profile without changing the levels of C-reactive protein and fibrinogen.     

Comparison of leptin protein levels in Prader-Willi syndrome and control individuals

Prader-Willi syndrome (PWS) is characterized by early childhood obesity, mental deficiency, hypogonadism, hypotonia, hypopigmentation, short stature, small hands and feet, and a characteristic face. It is the most common genetic cause of obesity and obesity is the most significant health problem for PWS patients. Ob protein (leptin), which is produced by adipose tissue, is thought to play a significant role in obesity; thus, unusually low plasma leptin levels, or relative loss of sensitivity to leptin in PWS subjects, could be an important factor in their obesity. We measured plasma leptin levels in 19 obese and 14 non-obese PWS patients [mean body mass index (BMI) 37.2 and 22.0, respectively] and compared these levels to those of 28 obese controls (mean BMI 35.5) and 16 non-obese control individuals (mean BMI 21.6). The mean plasma leptin concentration (ng/ml) for obese PWS subjects was 33.4 and 23.6 for non-obese PWS subjects. Obese control leptin was 36.2 ng/ml and non-obese control was 9.9. Among the control groups, leptin levels in females were significantly higher than those in males; the obese males and females had significantly higher leptin than their respective non-obese counterparts. These differences did not hold true for the PWS subjects. Leptin levels in obese PWS males and females were similar, and the same was true of the non-obese PWS males and females. The differences between obese and non-obese PWS subjects of both sexes were small and not significant. Comparing control groups with their PWS counterparts revealed no significant differences, with one exception: circulating plasma leptin levels in non-obese PWS males were nearly five times higher than in non-obese control males with similar BMI. This difference may reflect a more female pattern of fat distribution and hypogonadism, which are characteristic of PWS males. Leptin levels in PWS patients were not obviously correlated with the chromosome 15 finding seen in the patients. Am. J. Med. Genet. 75:7–12, 1998. © 1998 Wiley-Liss, Inc.     

CSF versus serum leptin in narcolepsy: is there an effect of hypocretin deficiency?

STUDY OBJECTIVE: To determine if hypocretin deficiency is associated with abnormally low serum leptin levels, a putative cause of increased body mass index in narcoleptics. DESIGN: Cross-sectional controlled study. PARTICIPANTS: Three hundred seventy subjects, including 111 healthy controls, 93 narcoleptic subjects with hypocretin deficiency (cerebrospinal fluid [CSF] hypocretin-1 levels < 110 pg/mL), 72 narcoleptic subjects with normal hypocretin levels, and 89 subjects with other sleep disorders INTERVENTION: After completing the Stanford Sleepiness Inventory, participants underwent spinal taps and blood sampling for measurement of CSF leptin and hypocretin-1 levels, HLA DQB1*0602 phenotyping, and serum leptin and C-reactive protein levels. RESULTS: Serum leptin levels were similar in narcoleptic subjects, whether hypocretin-deficient (13.2 +/- 1.7 ng/mL, mean +/- SEM) or not (13.0 +/- 1.8 ng/mL), controls (10.1 +/- 1.1 ng/mL) and subjects with other sleep disorders (11.5 +/- 1.6 ng/mL). Similarly, the CSF leptin levels and the CSF: serum leptin ratios (an indicator of brain leptin uptake) were not different between groups. Serum and CSF leptin levels were higher in women and in subjects with higher body mass indexes. Leptin brain uptake decreased in women, in the aged, and in more-obese subjects. In contrast with a presumed inhibitory effect of leptin on hypocretin-containing cells, CSF leptin levels tended to correlate positively with CSF hypocretin-1 levels. C-reactive protein was higher (4.2 +/- 0.9 mg/L) in narcoleptic subjects with hypocretin deficiency than in controls (1.4 +/- 0.3 mg/L, p = .0055), a difference still significant after adjustment on confounding factors. DISCUSSION: Our data do not support a role for leptin in mediating increased body mass index in narcolepsy. A moderate but selective increase in C-reactive protein in hypocretin-1 deficient subjects should prompt research on inflammation in narcolepsy.     

Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects

The cardinal feature of individuals with Prader-Willi syndrome (PWS) is severe hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (CCK) is a 33-amino-acid peptide found in high levels in the gut and brain involved in mediating the satiety response to meals. Free fatty acids (FFA) are responsible for the stimulation of CCK release after a fatty meal, and CCK and plasma FFA levels rise in tandem in normal individuals. Fasting plasma CCK levels were measured by radio-immunoassay in 33 PWS subjects with a mean age of 22.2 years +/- 8.1 years and 24 obese control subjects without a known cause of their obesity with a mean age of 28.7 years +/- 12.9 years. Consistent with previous findings, neither fasting plasma FFA levels (617.5 versus 486.8 microm/mL) or CCK levels (21.0 versus 19.1 pg/mL) were significantly different in PWS or control subjects, respectively. However, there was a significant correlation between fasting plasma FFA and CCK levels in obese subjects (r = 0. 64, P < 0.01), this correlation was completely lacking in PWS subjects (r = -0.06, P = 0.79). This difference in correlation coefficients constitutes a large effect. There were no significant effects observed for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucagon or leptin, age, or gender on CCK levels in our PWS subjects. These results suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects.     

Relations of plasma high-sensitivity C-reactive protein to various cardiovascular risk factors

This study was performed to evaluate the relation of high-sensitivity C-reactive protein (hsCRP) with several cardiovascular risk factors such as age, blood pressure, smoking habit and serum lipids, body mass index, blood glucose, regular exercise, alcohol drinking, white blood cell counts in a cross-sectional survey. Plasma hsCRP was measured by immunoturbidimetry in 202 subjects, aged over 50 yr, who participated in health-check survey in a rural area of Jeollanamdo, Korea. Plasma hsCRP level was 1.9 +/- 3.0 mg/dL. There were significant associations between hsCRP levels and age, white blood cell counts, blood glucose, diastolic blood pressure, HDL-cholesterol, body mass index and smoking status. In stepwise multivariate regression analysis, white blood cell counts, age, blood glucose, smoking status and body mass index were independent correlates of hsCRP levels. In conclusion, plasma hsCRP levels were associated with several cardiovascular risk factors, and these data are compatible with the hypothesis that CRP levels may be a marker for preclinical cardiovascular disease. Further what we need now are prospective studies to evaluate the association of C-reactive protein concentrations with subsequent cardiac events.     

Increased cardiovascular disease risk indices in HIV-infected women

Little is known regarding cardiovascular disease risk indices in HIV-infected women. This study investigated cardiovascular disease risk indices in 100 consecutively recruited HIV-infected women and 75 healthy female control subjects. Subjects were recruited from hospital- and community-based health care providers. C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, lipid, and glucose levels were the main outcome measures. CT scan, dual-energy x-ray absorptiometry (DXA), and anthropometry were used to assess body composition. Although similar in age, weight, and racial composition, HIV-infected women demonstrated higher CRP (4.6 +/- 0.7 vs. 2.3 +/- 0.4 mg/L, P = 0.007), IL-6 (2.7 +/- 0.2 vs. 1.8 +/- 0.1 pg/mL, P = 0.02), triglyceride (1.84 +/- 0.21 vs. 0.85 +/- 0.05 mM, P = 0.0002), 2-hour glucose after oral glucose challenge (6.88 +/- 0.22 vs. 5.72 +/- 0.17 mM, P = 0.0003), and fasting insulin (81 +/- 8 vs. 45 +/- 2 pM, P = 0.0002) and lower high-density lipoprotein cholesterol (1.17 +/- 0.03 vs. 1.45 +/- 0.05 mM, P < 0.0001) and adiponectin (5.4 +/- 0.3 vs. 7.6 +/- 0.5 mg/L, P = 0.0001) levels compared with the control population. HIV-infected women had more abdominal visceral fat and less extremity fat by CT and DXA scan and demonstrated a higher waist-to-hip ratio (WHR) than the control population. Within the HIV group, CRP and other indices were significantly related to body composition in stepwise regression models. Among all subjects, WHR, but not HIV status, was significantly related to CRP and other cardiovascular disease risk indices. HIV-infected women demonstrate significantly increased risk factors for cardiovascular disease in association with abnormal fat distribution.     

A useful predictor of early atherosclerosis in obese children: serum high-sensitivity C-reactive protein

Childhood obesity seems to contribute to the development of vascular inflammation and the progression of arterial wall changes. High-sensitivity C-reactive protein (hs-CRP) has recently emerged as a useful biomarker for vascular inflammation associated with atherosclerosis. The objectives of this study were to evaluate the association of the serum hs-CRP level with ultrasonic findings of early atherosclerosis, carotid intima-media wall thickness (IMT) and brachial flow-mediated dilation (FMD), in obese children. Thirty eight obese children and 45 sex/age-matched healthy control children were recruited. Serum CRP levels were measured by the high-sensitive latex turbidimetric immunoassay, and we measured carotid IMT and brachial FMD using high-resolution B-mode ultrasonography. Obese children had significantly higher hs-CRP levels (1.40+/-0.74 mg/L vs. 0.55+/-0.49 mg/L, p<0.01), as well as increased IMT (0.52+/-0.09 mm vs. 0.41+/-0.07 mm, p<0.01) and impaired FMD (7.35+/-7.78% vs. 20.34+/-16.81%, p<0.01) compared to healthy controls. Serum hs-CRP correlated positively with IMT (r=0.413, p<0.05) and inversely with FMD (r=-0.350, p<0.05) in the obesity group. Measurement of the serum hs-CRP level is a simple, cheap, and highly reproducible assay and correlates with IMT and FMD in obese children. Thus, it would be a useful marker for evaluating and estimating the degree of atherosclerosis in children.     

Coenzyme Q10 levels in Prader-Willi syndrome: comparison with obese and non-obese subjects

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial respiratory chain and an important scavenger of reactive oxygen species. Low levels are found in individuals with reduced energy expenditure, cardiac and skeletal muscle dysfunction, and mitochondrial disorders, many of these manifestations are seen in individuals with Prader-Willi syndrome (PWS). In addition, CoQ10 supplementation frequently is given to individuals with this syndrome. To determine if CoQ10 levels are decreased in PWS, we studied plasma CoQ10 levels in 16 subjects with PWS, 13 with obesity of unknown cause, and 15 subjects without obesity but of similar age and compared with body composition. Plasma CoQ10 levels were significantly decreased (P < 0.05), using several statistical approaches in subjects with PWS (0.45 +/- 0.16 microg/ml), compared to subjects without obesity (0.93 +/- 0.56 microg/ml), but not different from subjects with obesity (0.73 +/- 0.53 microg/ml). When plasma CoQ10 was normalized relative to cholesterol, triglyceride, and creatinine levels and fat and lean mass [determined by dual energy X-ray absorptiometry (DEXA)] in the subjects with either PWS or obesity, no significant differences were observed. However, a lower muscle mass was found in the PWS subjects.     

The relationship between sleep-disordered breathing and high-sensitivity C-reactive protein in Japanese men

STUDY OBJECTIVES: Elevated C-reactive protein (CRP), an inflammatory marker and emerging risk factor for atherosclerosis and coronary heart disease, has been reported in overweight patients with sleep-disordered breathing (SDB). However, the contribution of C-reactive protein to this disease among non-overweight individuals is uncertain. We thus examined the relationship between serum C-reactive protein levels and nocturnal arterial oxygen desaturation, stratified by category of body mass index (BMI). DESIGN: Cross-sectional study. PARTICIPANTS: Subjects were 316 men with a mean BMI of 25.4 kg/m2, aged 20-79 years, who attended a sleep clinic at Osaka, Japan. MEASUREMENTS AND RESULTS: SDB was assessed by oxygen desaturation index (ODI) measured by pulse oximetry during sleep. We used 3% oxygen desaturations per hour (3% ODI), as the indicator of SDB. We also measured serum levels of C-reactive protein (CRP). After adjustment for age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking status, alcohol consumption, and daily sleep duration, mean high-sensitivity CRP levels were 0.63, 0.65, and 0.96 mg/L for SDB severity levels of 3%ODI<5, 5 to 19.9, and >=20, respectively (p for trend=0.015). This association with SDB tended to be stronger in non-overweight men (BMI<25 kg/m2) (0.47, 0.48 and 1.02 mg/L, p for trend=0.017) than in overweight men (BMI > or = 25 kg/m2) (0.92, 0.87 and 1.21 mg/L, p for trend=0.11). CONCLUSION: SDB is associated with increased levels of CRP, especially in non-overweight men. Our results suggest the importance of follow-up and control of SDB in the prevention of cardiovascular disease even in non-overweight SDB patients.     

Relation Between C-Reactive Protein and Impaired Fasting Glucose in Obese Subjects

Chronic systemic inflammation, characterized by elevated levels of the acute phase proteins, such as C-reactive protein (CRP), plays an important role in the pathogenesis of glucose metabolic disturbances and diabetes. The aim of this study was to determine if the elevated levels of CRP are associated with impaired fasting glucose (IFG) in obese subjects. Healthy obese men and nonpregnant obese women were enrolled in a case-control study. Individuals with new diagnosis of IFG were considered as cases and compared with a control group without IFG. Elevated CRP was defined by high-sensitivity C-reactive protein (hsCRP) levels between 3.0 and 10.0?mg/L and new diagnosis of IFG by the presence of fasting plasma glucose levels of 100 to 126?mg/dL. A total of 74 subjects were allocated into the case group and compared with 74 subjects in the control group. Elevated hsCRP was identified in 61 (41.2?%) and 34 (23.0?%) individuals in the case and control groups, respectively (p?相似文献   

Low sex hormone-binding globulin is associated with low high-density lipoprotein cholesterol and metabolic syndrome in women with PCOS

BACKGROUND: Decreased high-density lipoprotein cholesterol (HDL-C) and sex hormone-binding globulin (SHBG) levels, and the metabolic syndrome, are all closely associated with a higher prevalence of atherosclerotic cardiovascular disease. We investigated the association between HDL-C, SHBG and the metabolic syndrome in women with polycystic ovary syndrome (PCOS). METHODS AND RESULTS: Among 106 young Taiwanese women (mean age +/- SD, 24.9 +/- 4.8 years) with PCOS, 69 (65.1%) women had an HDL-C level <50 mg dl(-1). The level of HDL-C was highly correlated with that of serum SHBG (gamma = 0.6034, P < 0.0001). The SHBG level was significantly lower in subjects with an HDL-C <50 mg dl(-1) than that in subjects with an HDL-C > or =50 mg dl(-1). Using multiple linear regression models with adjustment for age, BMI and other anthropometric, metabolic, liver function and hormonal variables, we showed serum SHBG to be independently correlated with HDL-C. Based on logistic regression analysis with adjustment for age, the SHBG level was significantly lower in women with PCOS with the metabolic syndrome (odds ratio = 0.92, P = 0.003). CONCLUSIONS: Low levels of SHBG in women with PCOS were associated with low levels of HDL-C, independent of insulin resistance and obesity. The SHBG level was inversely related to the occurrence of metabolic syndrome, further strengthening the potential link between SHBG levels and cardiovascular disease in women with PCOS.     

Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have been reported to have subclinical cardiovascular disease (CVD) and increased abdominal fat. The aim of this study was to evaluate the relationship between visceral fat (VF) and early markers of CVD in PCOS women. METHODS: Two hundred overweight PCOS women [(mean +/- SD) age 24.6 +/- 3.2 years, body mass index (BMI) 28.5 +/- 2.8 kg/m2] and 100 healthy age- and BMI-matched volunteer controls entered this cross-sectional study. In all subjects, the amount of VF was measured by ultrasonography. Anthropometric measurements [BMI and waist circumference (WC)], complete hormonal and metabolic pattern, carotid intima-media thickness (IMT), brachial arterial flow-mediated dilation (FMD) and inflammatory biomarkers [C-reactive protein (CRP), fibrinogen, white blood cells count and plasminogen activated inhibitor-1] were also obtained from all subjects. A stepwise linear regression model was used in PCOS patients to verify if IMT or FMD as dependent variables are affected by other independent variables. RESULTS: VF amount was significantly (P < 0.001) higher in PCOS subjects than in healthy controls [31.4 +/- 7.3 versus 28.0 +/- 6.1 (mean+/-SD) mm, respectively] and directly related to insulin resistance: HOMA (r = 0.918, P < 0.001) and AUC(INS) (r = 0.879, P < 0.001), and to WC (r = 0.658; P < 0.001). In PCOS, the two linear regression analyses showed that IMT is positively affected by VF and CRP, whereas FMD is positively affected by IMT and negatively by VF and CRP. CONCLUSIONS: VF amount is associated with subclinical CVD in PCOS patients.     

Association between hepatitis B surface antibody seropositivity and coronary artery disease

BACKGROUND: Specific infectious agents have been found to be related to the pathogenesis of coronary atherosclerosis. AIMS: We assessed the possible association between angiographically proven coronary artery disease (CAD) and hepatitis B surface antibody (HBS Ab) seropositivity in a population with relatively high prevalence of hepatitis B virus (HBV) infection. SETTING AND DESIGN: This was a cross-sectional study. MATERIALS AND METHODS: We analyzed data from 830 consecutive subjects undergoing coronary angiography, including angiographic results reported by two cardiologists for inter-observer reliability and assessment of HBS Ab status determined by enzyme-linked immunosorbent assay (ELISA). STATISTICAL ANALYSIS USED: Chi-square test or Fisher's exact test, independent two-sample t test and the Pearson's Correlation Coefficient test were used, as required. Statistics were performed using SPSS software version 13 (SPSS, Chicago, IL). RESULTS: Two hundred forty-nine (30%) subjects had normal angiogram or minimal CAD, and 581 (70%) had significant CAD in at least one major coronary artery. In patients with CAD and in patients without angiographic evidence of significant atherosclerosis, 28.7% and 28.9% respectively were positive for HBV (P=0.954). Mean C-reactive protein levels in subjects with positive and negative HBS Ab were 10.77+/-8.37 mg/L versus 10.33+/-7.64 mg/L respectively (P=0.465). However, C-reactive protein levels in CAD group were significantly higher (P<0.001). CONCLUSIONS: Our results suggested hepatitis B surface antibody seropositivity has no relationship with coronary artery disease. Moreover, no significant linear correlation exists between HBS Ab and C-reactive protein levels. However, as previously shown, C-reactive protein level in patients with coronary artery disease is significantly higher than in patients with normal coronary arteries.     

Plasma obestatin and ghrelin levels in subjects with Prader-Willi syndrome

Prader-Willi syndrome (PWS) is an obesity syndrome characterized by rapid weight gain and excessive food intake. Food intake is regulated by the hypothalamus but directly influenced by gastrointestinal peptides responding to the nutritional status and body composition of an individual. Ghrelin, derived from preproghrelin, is secreted by the stomach and increases appetite while obestatin, a recently identified peptide derived post-translationally from preproghrelin, works in opposition to ghrelin by decreasing appetite. The objective of this study was to measure fasting obestatin and ghrelin levels in peripheral blood of subjects with PWS and compare to age and gender matched control subjects. Plasma obestatin and ghrelin levels were measured in subjects with PWS (n = 16, mean age = 16.0 +/- 13.3 years; age range 1-44 years) and age and gender matched control subjects (n = 16). Significantly higher obestatin levels were seen in the 16 PWS subjects (398 +/- 102 pg/ml) compared with 16 controls (325 +/- 109 pg/ml; matched t-test, P = 0.04), particularly in 5 young (< or =3 years old) PWS subjects (460 +/- 49 pg/ml) compared with 5 young controls (369 +/- 96 pg/ml; matched t-test, P = 0.03). No significant difference in ghrelin levels was seen between the PWS and comparison groups. No significant correlation was observed for either peptide when compared with body mass index but a significant negative correlation was seen for ghrelin and age in PWS subjects. Our observations suggest that obestatin may be higher in infants with PWS compared to comparison infants. The possibility that obestatin may contribute to the failure to thrive which is common in infants with PWS warrants further investigation.     

β3-肾上腺素能受体基因及解偶联蛋白2基因复合变异与中国人肥胖症的关系

目的　探讨 β3-肾上腺素能受体 ( β3- adrenergic receptor,ADRβ3)基因 Trp6 4 Arg和解偶联蛋白 2 ( uncoupling protein 2 ,UCP2 )基因 Ala5 5 Val复合变异对中国汉族人群肥胖症发生的影响。方法　采用聚合酶链反应 -限制性片段长度多态性 ( PCR- RFL P)技术 ,对 ADRβ3基因 Trp6 4 Arg和 UCP2基因Ala5 5 Val变异进行检测。 119例肥胖症患者 ,平均体重指数 ( body mass index,BMI)为 ( 2 7.9± 2 .98) kg/m2 ,177名正常对照组 ,平均 BMI为 ( 2 1.9± 1.9) kg/ m2 。结果　 ( 1)肥胖患者的 ADRβ3基因 Trp6 4 Arg突变携带者的频率与正常对照组的差异无显著性 ( P>0 .0 5 ) ;正常人携带 Trp6 4 Arg基因变异者有较高的空腹和口服葡萄糖耐量试验 ( oral glucose tolerance test,OGTT) 2小时血糖水平。 ( 2 )肥胖患者携带 UCP2基因 Ala5 5 Val纯合子变异的基因频率明显高于正常对照组的 ( OR=3.71,P=0 .0 0 1) ;正常人携带 Ala5 5 Val基因变异者有较高的 BMI水平。 ( 3)单一的 UCP2或 ADRβ3基因变异时 ,肥胖组的变异基因频率与正常人的分布差异无显著性 ( P>0 .0 5 ) ;但 UCP2和ADRβ3两基因同时发生变异时 ,肥胖组的变异基因频率则明显高于正常组 ( OR=2 .5 7,P=0 .0 0 9)。 ( 4 )携带 Val/ Val Trp/ A     

Genetic variants of the human obesity (OB) gene in subjects with and without Prader—Willi syndrome: comparison with body mass index and weight

We investigated whether an association exists between genetic variants of the human obesity ( OB or leptin) gene and body mass index (BMI) or weight in subjects with Prader-Willi syndrome (PWS) and in age-and gender-matched lean and obese subjects without PWS. The study included 51 subjects with PWS (mean age = 17.7 ± 9.5 years, BMI = 29.7 ± 8.3 kg/m²); 50 non-PWS obese subjects (mean age = 18.2 ± 10.8 years, BMI = 33.3 ± 9.5 kg/m²); and 53 non-PWS lean subjects (mean age = 17.8 ± 9.5 years, BMI = 19.5 ± 2.9 kg/m²). Allele sizes were determined via standard polymerase chain reaction of the D7S1875 locus, a dinucleotide repeat polymorphism close to the OB gene and classified as trichotomous (homozygous < 208 bp, heterozygous < 208/≥ 208 bp, homozygous < 208 bp) or dichotomous (homozygous < 208 bp or not). Non-PWS males showed a marked decrease in weight with larger alleles while females did not (interaction effect, p < 0.05). Comparable effects were not observed among the PWS subjects. Associations between BMI and genotype were statistically significant (r = 0.22, one-tailed p < 0.05) and comparable to previous research among the non-PWS subjects < 18 years, but not the adults (r = 0.05, one-tailed p = 0.38). Correlations were not statistically significant among either the adult or non-adult PWS subjects.     

Uric acid: a surrogate of insulin resistance in older women

OBJECTIVES: The relationship between serum uric acid (UA) and cardiovascular disease has been debated extensively and no conclusion has been reached yet. The main purpose of this study was to explore the sex-different relationship among insulin resistance, metabolic syndrome (MS) and hyperuricemia. METHODS: A community-based prospective study was conducted among people aged over 40 years in I-Lan County, Taiwan. A complete history taking, physical examination and laboratory tests were performed for each subject by the well-trained research staff. Insulin resistance was determined by the homeostasis model assessment (HOMA-IR). Serial comparisons were performed to evaluate the associations between MS, insulin resistance and hyperuricemia in both sexes. RESULTS: A total of 852 subjects (mean age=64.6+/-11.3 years, 56.7% female) were enrolled. The prevalence of obesity, hyperuricemia, chronic kidney disease (CKD), insulin resistance and MS was 42.2, 31.2, 30.9, 36.0 and 47.5%, respectively. Subjects with MS were significantly older (63.4+/-10.0 years versus 60.4+/-12.4 years, P=0.019), higher in body mass index (BMI) (26.3+/-3.5 kg/m(2) versus 23.6+/-3.0 kg/m(2), P<0.001), serum UA (6.1+/-2.1mg/dl versus 5.5+/-1.7 mg/dl, P=0.003), HOMA-IR (2.7+/-3.4 versus 1.0+/-0.8, P<0.001) and lower in glomerular filtration rate (GFR) (66.3+/-17.7 ml/min/1.73 m(2) versus 72.0+/-15.2 ml/min/1.73 m(2), P=0.001). Male gender, CKD, BMI>23 kg/m(2) and insulin resistance were all independent risk factor for hyperuricemia with the covariate of age. When age and BMI were controlled, females had significantly higher prevalence of CKD and insulin resistance, but less hyperuricemia than males (P all<0.05). Adjusted for age, BMI and GFR, hyperuricemia and MS were both independent risk factors for insulin resistance in females (P=0.006, <0.001, respectively). In males, MS remained significantly associated with insulin resistance (P=0.002) but not hyperuricemia (P=0.813). When age, BMI and GFR were controlled, serum UA was positively related to HOMA-IR in females (gamma=0.117, P=0.012), but not in males (P=0.93). CONCLUSION: A positive association was identified between serum UA and insulin resistance in older women but not in men. Studies related to insulin resistance may be needed when hyperuricemia was identified in older women.     

Obstructive sleep apnea is associated with increased arterial stiffness in severe obesity

Obstructive sleep apnea is associated with obesity and metabolic syndrome, leading to greater cardiovascular risk. Severely obese patients with obstructive sleep apnea may still be at risk of adverse health outcomes, even without previous cardiovascular disease. Pulse wave analysis non‐invasively measures peripheral pulse waveforms and derives measures of haemodynamic status, including arterial stiffness, augmentation pressure and subendocardial viability ratio. We hypothesized that the presence of obstructive sleep apnea in severe obesity, even in the absence of an antecedent history of cardiovascular disease, would affect measurements derived from pulse wave analysis. Seventy‐two severely obese adult subjects [obstructive sleep apnea 47 (body mass index 42 ± 7 kg m^?2), without obstructive sleep apnea (non‐OSA) 25 (body mass index 40 ± 5 kg m^?2)] were characterised using anthropometric, respiratory and cardio‐metabolic parameters. Groups were similar in age, body mass index and gender. More subjects with obstructive sleep apnea had metabolic syndrome [obstructive sleep apnea 60%, without obstructive sleep apnea (non‐OSA) 12%]. Those with obstructive sleep apnea had greater arterial stiffness, augmentation pressure and decreased subendocardial viability ratio (all P < 0.001), with significantly higher systolic (P = 0.003), diastolic (P = 0.04) and mean arterial pressures (P = 0.004) than patients without obstructive sleep apnea (non‐OSA). Arterial stiffness correlated with mean arterial blood pressure (P = 0.003) and obstructive sleep apnea severity (apnea–hypopnea index; P < 0.001). apnea–hypopnea index significantly predicted arterial stiffness in multiple regression analysis, but components of the metabolic syndrome did not. Thus, patients with obstructive sleep apnea with severe obesity have increased arterial stiffness that may potentially influence cardiovascular risk independently of metabolic abnormalities. The presence of obstructive sleep apnea in severe obesity identifies a group at high cardiovascular risk; clinicians should ensure that risk factors are managed appropriately in this group whether or not treatment of obstructive sleep apnea is offered or accepted by patients.     

Metabolic syndrome in subjects with type-2 diabetes mellitus

BACKGROUND: Each component of metabolic syndrome (MS) conveys increased cardiovascular disease risk, but as a combination they become much more powerful. Vigorous early management of the syndrome may have a significant impact on the prevention of both diabetes and cardiovascular disease. AIM: This study aims to determine the frequency of occurrence of MS and its relation to cardiovascular events among patients with type-2 diabetic mellitus. METHODS: The study group consisted of 218 type-2 diabetic patients. These were screened for hypertension, hyperlipidemia, obesity, microalbuminuria, and cardiovascular events. RESULTS: There were 128 (58.7%) males and 90 (41.3%) females. The mean age was 53.4 +/- 6.3 years and a mean body mass index (BMI) of 25.5 +/- 5.4 (males-23.4 +/- 4.2; females-26.2 +/- 5.7). MS was present in 55 (25.2%) of the study population. Systemic hypertension was the most common component of MS seen in 84 (38.5%) patients. The mean serum total cholesterol was 168.6 +/- 25.8 mg% (men 153 +/- 23; women 169 +/- 19; p > 0.05). Eight female and 12 male patients had serum total cholesterol > or = 200 mg%. Dyslipidemia occurs more commonly in males than females. Obesity was more common in female patients than in males. Out of 128 male type-2 patients with diabetes seen, 111 (86.7%) were without microalbuminuria. The corresponding figure among the females was 90% (81 out of 90 patients). CONCLUSIONS: The study demonstrated that MS was present in 25.2% of the study population. The syndrome and its different components were positively associated with a higher risk of stroke, peripheral vascular disease, and occurrence of microalbuminuria, p < 0.001. Ischemic heart disease occurs rarely in the population. A long-term, targeted, intensive intervention involving multiple cardiovascular risk factors is recommended to reduce the risk of both cardiovascular and microvascular events among patients with type-2 diabetic mellitus.     

Two years of growth hormone therapy in young children with Prader-Willi syndrome: physical and neurodevelopmental benefits

Infants with Prader-Willi syndrome (PWS) typically display failure to thrive and decreased muscle mass with excess body fat for age. Growth hormone (GH) therapy in children with PWS improves, but does not normalize, body composition and muscle strength and agility. The objective of this study was to determine the effects of earlier GH therapy on anthropometric measurements, body composition, and psychomotor development in affected PWS infants and toddlers. Twenty-five subjects, ages 4-37 months, were randomized to 2 years of GH therapy (1 mg/m(2)/day) or 1 year of observation without GH treatment and then placed on GH (1.5 mg/m(2).day) for 1 year only. Anthropometric measurements were obtained by standard methods: percent body fat, lean body mass, and total body bone mineral density by dual x-ray absorptiometry; motor constructs of mobility and stability by the Toddler Infant Motor Evaluation; and cognitive and language function by the Capute Scales of Infant Language and Cognitive Development. GH-treated PWS subjects demonstrated normalization of length/height standard deviation scores (SDS), faster head growth, increased lean body mass accrual, and decreased percent body fat (P < 0.005 for all parameters), as well as improved language (P = 0.05) and cognitive (P = 0.02) quotient Z-scores compared with similarly aged untreated PWS subjects after 1 year into the study. PWS subjects treated before their first birthday spoke their first words at a mean age of 14.4 +/- 2.8 months and walked independently at 23.3 +/- 4.8 months. GH therapy was well-tolerated; however, one PWS subject experienced scoliosis progression. As greater benefits were seen in our study with early treatment, prompt referral to a pediatric endocrinologist for consideration of GH therapy is recommended for PWS at an early age.