Gestational diabetes mellitus (GDM), which is defined as carbohydrate intolerance of variable severity with onset or first recognition during the present pregnancy [1], is associated with adverse outcomes of pregnancy including macrosomia, birth trauma and metabolic complications of the newborn [2±4]. Although most women with GDM have a normal glucose tolerance when tested several weeks postpartum, impairment of insulin secretory capacity or increased insulin resistance or both have been reported in these women [5,6], and a substantial proportion of the women with previous GDM will eventually develop Type II diabetes mellitus [7±9]. The reported prevalence of GDM has ranged widely from less than 1 % to more than 10 % [10]. To some extent, this wide variation is thought to reflect a lack of a standardization of screening test procedures and diagnostic criteria of GDM. However, it may also be attributed to the heterogeneous nature of GDM with respect to ethnic or racial influence or both, genetic factors, admixture Diabetologia (1998) Summary We examined the associations between demographic characteristics including short stature and the prevalence of gestational diabetes mellitus (GDM) in Korean women. In this study, a total of 9005 pregnant women underwent universal screening for GDM. Oral glucose tolerance tests (100 g OGTT) were performed in positive screenees (1 h plasma glucose ³ 7.2 mmol/l) and GDM was diagnosed using National Diabetes Data Group criteria. Women with GDM were older and heavier than those with a positive screen and normal OGTT, as well as those with a negative screen. However, height of women with GDM was significantly shorter than those with a positive screen and normal OGTT, and a negative screen. When the study subjects were stratified according to height quartiles, the plasma glucose at the screening test decreased as height increased. Furthermore, the prevalence of GDM was highest in the shortest quartile ( £ 157 cm) group; the odds ratio for GDM was two times greater compared with the highest quartile ( ³ 163 cm) group, even after controlling for age and body mass index (BMI). In addition, multiple logistic regression analysis revealed that greater prepregnancy BMI, age, weight gain, a parental history of diabetes mellitus, and shorter maternal height were directly and independently associated with the prevalence of GDM. We have found that short stature is an independent risk factor for GDM in the racially homogenous population of Seoul, Korea. It is suggested that this propensity may be conveyed primarily by environmental influences. However, genetic factors may also modify the response to the environmental insult. Our findings also emphasize the heterogeneity of factors which predispose to GDM. [Diabetologia (1998) 41: 778±783]

Solar ultra-violet (UV) radiation and the ensuing photo-damage are adverse factors affecting human skin directly exposed to the sun. Stress responses induced by UV radiation (UVR) elicit premature skin ageing (photoageing), resulting in extensive damage to dermal connective tissue. Disruption of the normal dermal structure of skin connective tissue, primarily collagen, impairs a variety of skin functions and is considered to be the main cause of wrinkle formation. Matrix metalloproteases (MMPs) may be responsible for the degradation of collagen and other extracellular matrix proteins, which are major targets for relieving skin photoageing. Herein, we demonstrated that Sirt1, a putative anti-ageing enzyme, reduced MMP-9 transcriptional expression in skin. The known agonists of Sirt1, resveratrol and metformin, also significantly inhibited MMP-9 expression and appeared to protect collagen from degradation after UVR. These studies suggest that the Sirt1 activator could be used as a novel therapeutic agent to delay skin photoageing.

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Estrogen is known to play a critical role in both skeletal maturity and the rate of bone loss. This suggests the possibility that the estrogen receptor (ER) gene is one of the candidate genes that determines peak bone density and/or bone turnover rate. We investigated two established restriction fragment length polymorphisms (RFLPs) in intron 1 at the ER gene, represented as PvuII and XbaI. In 598 healthy Korean women aged 20-74 years, we examined the association of these ER genotypes with bone mineral density (BMD) and bone turnover status. The distribution of the PvuII and XbaI RFLPs was as follows: pp 205 (34.3%), Pp 308 (51.5%), PP 85 (14.2%) and xx 384 (64.2%), Xx 180 (30.1%), XX 34 (5.7%), respectively (where capital letters signify the absence of, and lower-case letters signify the presence of, the restriction site of each RFLP). No significant genotypic differences were found in BMD and bone markers. We grouped the subjects into three categories according to their menstrual status: 104 premenopausal women with regular menstruation, 182 perimenopausal women who had amenorrhea of not less than 3 months and not more than 12 months' duration, and 312 postmenopausal women whose last menstruation was at least 12 months previously. No significant genotypic difference in either BMD or bone markers was found in any of these three groups. Furthermore we categorized women in peri- and postmenopause into a high loser group and a normal loser group according to the level of bone resorption markers. There was no difference in genotypic proportions between the high and normal loser groups. Our data suggest that these ER polymorphisms are not associated with BMD or bone turnover in Korean women.

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Introduction: Thyroid function is evaluated by thyroid stimulating hormone (TSH) and free thyroxine (fT4). Although many studies have indicated an intimate relationship between thyroid hormones and kidney functions, reports about the simultaneous evaluation of TSH and fT4 are rare. Objective: We aimed to analyze the association between TSH and kidney function, with emphasis on a potential nonlinear relationship, and identify an independent relationship between fT4 and kidney function. Methods: We reviewed the data of 7,061 subjects in the Korea National Health and Nutrition Examination Surveys who were randomly subsampled for thyroid function evaluation between 2013 and 2015. A total of 5,578 subjects were included in the final analysis, after excluding people < 18 years old, and those with a short fasting time, abnormal fT4 levels, and thyroid disease or related medications. Creatininebased estimated glomerular filtration rate (eGFR) was used to define kidney function. Results: A 1 mmol/L increase of logarithmic TSH was associated with decreased eGFR (β: -1.8; 95% CI -2.3 to -1.2; p < 0.001), according to multivariate linear regression analysis. On the multivariate generalized additive model plot, TSH demonstrated an L-shaped relationship with eGFR, showing a steeper slope for 0-4 mIU/L of TSH. A 1 µg/dL increase of fT4 was also associated with decreased eGFR (β: -7.0; 95% CI -0.94 to -4.7; p < 0.001) on the multivariate linear regression analysis; this association was reversed after adjusting for age. On the mediation analysis, the indirect effect via age and direct effect per 1 µg/dL increase of fT4 on eGFR was 9.9 (8.1 to 11.7, p < 0.001) and -7.1 (-9.3 to -4.8, p < 0.001), respectively. Conclusions: Increased TSH was associated with decreased eGFR, particularly in the reference range. The direct effect of increased fT4 was decreased eGFR, which may be affected indirectly by age.

We aimed to identify a novel flavonoid from the in-house natural products to suppress matrix metalloproteases (MMPs), which is responsible for degradation of collagen and other extracellular matrix proteins. Total eight natural products were screened for identification of a novel MMP-9 suppressor using MMP-9 reporter system, where the prompt initial screening with multiple samples is readily examined. Among the extracts used in the present study, one extract (Citrus unshiu) was found active in this assay system. Furthermore, three representative flavonoids in this active extract of Citrus unshiu peel were tested in MMP-9 reporter system. Nobiletin (NB) of the tested flavonoids suppressed MMP-9 expression without cytotoxicity, which was validated by both real-time polymerase chain reaction (PCR) and zymography analyses. Sustained p38 mitogen activated protein kinase (MAPK) activity, closely associated with induction of MMP-9 under stress condition, was markedly reduced by NB treatment, which implies that modulation of p38MAPK by nobiletin is responsible for reduction of MMP9 expression. Hence, nobiletin, identified from MMP-9 reporter system based screening, may be further applied for the purpose of delaying collagen degradation in skin fibroblasts.Key words Citrus unshiu; nobiletin; flavonoid; matrix metalloprotease 9; p38 mitogen activated protein kinase (MAPK)The integrity of skin connective tissue, which is important for the elasticity of the skin, relies on the levels of dermal extracellular matrix (ECM) proteins, such as collagen type I and III, elastin, and fibronectin. Aging or chronic exposure to ultra violet (UV) causes loss of ECM and the consequent decreased resilience of skin, which are strongly associated with various phenotypes of aged skin (e.g. wrinkle formation). 1)Matrix metalloproteinases (MMPs), members of the zincdependent endoprotease family, serve as important enzyme in degrading dermal ECM.2) Of note, excess expression of MMPs in keratinocytes and dermal fibroblasts, under a variety of stress conditions such as UV radiation (UVR), and heat-shock, 3) which both are closely associated to the aged skin phenotypes, 4,5) contributes to the degradation of ECM proteins, leading to wrinkle formation in photo-aged skin. 6)Therefore, MMPs, induced by a variety of external stresses and capable of degrading collagen and other ECM proteins, have been widely studied as a target for relieving the appearance of aged skin. 7)Among them, gelatinase A (MMP-2) and gelatinase B (MMP-9) were increased by UV radiation in human dermal fibroblasts (hDFs) 8,9) and are responsible for degrading collagens, which are components of the epidermal basement membranes.10) Thereby, the increased activity or expression of gelatinases induced by UV radiation to cause disruption of the basement membrane is considered to be a main cause of skin photoaging, 11,12) which can provide a rationale to target the gelatinases to prevent UV induced wrinkle formation. 7,12) In special, MMP-9 expression is dependent upon activator protei...

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