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Several factors increase the risk of fragility fracture, including low bone mineral density, falls, and poor physical performance. The associations among these factors have been investigated; however, most of the subjects of previous studies were either elderly men or elderly women, and the associations were controversial. The aim of this study was to evaluate the associations between physical performance and bone mineral density, and the history of falls and fractures, stratified by gender and age group. We analyzed 5368 subjects who were aged 50 years or older, including 1288 younger men (younger than 70 years), 1615 younger women (younger than 70 years), 1087 older men (70 years or older), and 1378 older women (70 years or older). We used the one-leg standing time (OLST) for assessing static balance and the timed up-and-go test (TUGT) for assessing dynamic balance. The subjects in the worst performance quartile for the OLST were more likely to have osteoporosis than those in the best performance quartile. Additionally, women who had experienced a fracture during the past 2 years were 1.68 times more likely to be in the worst performance quartile for the OLST than women without a previous fracture. Although the TUGT time was not associated with either the incidence of osteoporosis or the fracture history, the odds ratios for falling were 1.51 and 1.28 as the TUGT time increased by one standard deviation in younger men and younger women, respectively. The findings of the present study show that the OLST was associated with the incidence of osteoporosis and previous fracture and that the TUGT time was associated with the incidence of falling.

Background Transfusional iron overload primarily results in reticuloendothelial iron accumulation, which is considered to be less harmful than parenchymal iron accumulation. However, systematic and comprehensive data on endocrine function in transfusion-associated haemochromatosis are limited. Methods We examined 25 aplastic anaemia patients (11 men and 14 women) diagnosed with transfusion-associated haemochromatosis at a single institution. Pituitary function was determined with a combined pituitary function test. On a different day, a 75-g oral glucose tolerance test was performed. The bone mineral density (BMD) of the lumbar spine and total hip was assessed with dual-energy X-ray absorptiometry. Results Twenty-two (88%) of these 25 patients had at least one endocrine abnormality, and 12 had more than one abnormality. The most common pituitary hormonal deficiency involved the pituitary–gonadal axis; 54% of the total subjects had hypogonadotropic hypogonadism. Two patients had an insufficient cortisol response to corticotrophin-releasing hormone stimulation. No patient had a deficiency of growth hormone or thyroid-stimulating hormone. Twelve (48%) had diabetes mellitus, and these patients tended to have higher concentrations of ferritin, alanine aminotransferase and γ-glutamyl transferase. Osteoporosis (T-score

Purpose: The purpose of this study was to investigate body composition, blood pressure, blood lipids, and glucose according to obesity degree by body fat percentage in female university students. Methods: A total of 231 subjects were participated between July and December 2010. The anthropometric measures and blood analyzer were used. Data were analyzed using descriptive statistics, ANOVA, and Pearson’s correlation coefficient with SPSS 18.0. Results: Percentage of body fat (PBF)-defined obesity had higher preva lence than body mass index (BMI)-defined obesity. Weight, BMI, PBF, fat mass, Waist to hip ratio (WHR), Systolic blood pressure (SBP), Diastolic blood pressure (DBP) in obesity group were higher than normal group and Soft lean mass and Low density lipoprotein (LDL) in obesity group were lower than normal group. There were significant correlations between PFB, SBP, DBP, Triglyceride (TC), High density lipoprotein (HDL), and LDL. Conclusion: In conclusion, when screening for obesity in female university students, body fat should be considered. It is needed to develop obesity management program according to obesity degree and to identify the effec tiveness.

Aims Basal insulin requirement in patients with type 2 diabetes is difficult to determine because of individual variability in insulin sensitivity and secretion. We aimed to identify factors that influence basal insulin requirement in insulin-naive patients with type 2 diabetes. Methods We studied 50 insulin-naive patients with type 2 diabetes. Their basal insulin requirement was calculated by 8h overnight intravenous insulin infusion. Patients underwent abdominal computed tomography; subcutaneous and visceral fat areas were measured. Results The basal insulin requirement was 31.3±16.9units/day, and it varied widely from 0.2 to 1.4units/kg. It was positively correlated with visceral fat area ( γ =0.485, P γ =0.339, P =0.008), glycated hemoglobin (HbA1C, γ =0.327, P =0.019), alanine aminotransferase (ALT, γ =0.310, P =0.027), and triglyceride ( γ =0.305, P =0.032). However, body weight, waist circumference and total fat mass were not related to basal insulin requirement. Multiple linear regression analysis showed that visceral fat area, HbA1C, and ALT are independent predictors of basal insulin requirement. Conclusions Visceral obesity was a better predictor than generalized obesity for basal insulin requirement at the initiation of insulin therapy in patients with type 2 diabetes.

Aims Hepatic endoplasmic reticulum (ER) stress plays a key role in the development of obesity-induced insulin resistance. This study evaluated the effects of peptides from black soybean (BSP) on ER stress and insulin signaling in vitro and in vivo. Main methods Using C2C12 myotubes or HepG2 cells, we evaluated the effects of BSP on the expression of proteins involved in insulin signaling and in the ER stress response in insulin-sensitive or insulin-resistant cells. BSP was given orally to db/db mice for 5 weeks to investigate its antidiabetic effects in vivo and the underlying mechanisms. Key findings BSP increased GLUT4 translocation and glucose transport in myotubes and stimulated Akt-mediated glycogen synthase kinase-3β (GSK-3β) and Foxo1 phosphorylation in HepG2 cells. BSP significantly restored the suppression of insulin-mediated Akt phosphorylation in insulin-resistant cells. BSP significantly inhibited the activation of ER stress-responsive proteins by thapsigargin. BSP also significantly reduced blood glucose and improved glucose tolerance in db/db mice. The serum lipid profile (triglyceride and high-density lipoprotein concentrations) improved concomitantly with the BSP-induced downregulation of hepatic fatty acid synthase expression in db/db mice. Consistent with the results observed in HepG2 cells, BSP downregulated the elevated hepatic ER stress response in diabetic mice concomitantly with an increased expression of phospho-Foxo1. Significance A peptide mixture, BSP, showed beneficial effects through multiple mechanisms involving the suppression of hepatic ER stress and restoration of insulin resistance, suggesting that it has potential as an antidiabetic agent.

We studied 65 adult patients without a history of diabetes who were diagnosed with diabetic ketoacidosis. Ketosis-prone type 2 diabetes was common (42%) among this group of Korean patients with new-onset diabetes presenting with diabetic ketoacidosis. These patients were younger, showed a greater defect in insulin secretion.

The mechanisms of leptin resistance observed in most cases of human obesity are poorly understood. Therefore, we evaluated the effects of nitric oxide (NO) on the leptin-induced activation of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathways and on the leptin receptor (LEPR) expression using SH-SY5Y cells. Here, we show that the NO donor spermine/NONOate inhibited leptin-induced activation of STAT3 in vitro. The inhibition of leptin-mediated STAT3 phosphorylation caused by excessive NO was partially prevented by a sulfhydryl reducing agent, ascorbic acid. Cellular experiments show that reduced expression of long form leptin receptor (LEPR-b) and STAT3 protein instability induced by NO may be mechanisms of the NO-mediated inhibition of leptin-STAT3 signaling. We also present data showing that the hypothalamic NO content of high-fat (HF)-diet-induced obese mice was higher than that of control mice; this is likely caused by decreased caveolin-1 expression and increased nNOS expression induced by HF diet over 19 weeks. Concurrently with the overproduction of NO, the decrease of hypothalamic LEPR-b in obese mice also supports these in vitro data. Combined results suggest that excess of NO can induce the attenuation of leptin-mediated STAT3 activation through reduced expression of LEPR-b mRNA and instability of STAT3 protein at least in part. Furthermore, our in vivo data indicate that long-term HF diet induces hypothalamic overproduction of NO, which may be related with leptin insensitivity. However, further study is required to warrant direct in vivo evidence of a causal relationship between endogenous excess of hypothalamic NO and central leptin resistance.

Currently, obesity is considered a systemic inflammation; however, the effects of obesity on the vulnerability of dopaminergic neurons to oxidative stress are not fully defined. We evaluated the effects of high-fat diet-induced obesity (HF DIO) on neurotoxicity in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Eight weeks after a HF or matched normal diet, a severe decrease in the levels of striatal dopamine and of nigral microtubule-associated protein 2, manganese superoxide dismutase, and tyrosine hydroxylase was observed in obese mice treated with subtoxic doses of MPTP (20 mg/kg) compared with the matched lean group. In addition, the levels of nitrate/nitrite and thiobarbituric acid-malondialdehyde adducts in the substantia nigra of obese mice were reciprocally elevated or suppressed by MPTP. Interestingly, striatal nNOS phosphorylation and dopamine turnover were elevated in obese mice after MPTP treatment, but were not observed in lean mice. The nitrotyrosine immunoreactivity for evaluation of nigral nitrogenous stress in obese mice with MPTP was higher than that in matched lean mice. At higher doses of MPTP (60 mg/kg), the mortality was higher in obese mice than in lean mice. These results suggest that DIO may increase the vulnerability of dopaminergic neurons to MPTP via increased levels of reactive oxygen and nitrogen species, and the role of nNOS phosphorylation in the MPTP toxicities and dopamine homeostasis should be further evaluated.

Aim As serum beta-2-microglobulin (B2M) levels are usually elevated in patients with renal failure, they have been suggested as a surrogate marker of cardiovascular mortality for patients with chronic kidney disease. Glycation of B2M is cytotoxic and may contribute to the risk of diabetic complications in patients with diabetes. Our objective was to evaluate the relationship between B2M and diabetic complications in patients with type 2 diabetes (T2D) and normal kidney function. Methods A total of 366 patients with T2D and preserved renal function with no clinical evidence of cardiovascular disease were enrolled consecutively into this study. High B2M was defined as a median serum B2M level ≥ 1.8mg/L. Subclinical atherosclerosis was defined as a carotid artery intima–media thickness (C-IMT) ≥ 0.9mm or the presence of carotid plaque. The definition of diabetic nephropathy was based on the presence of albuminuria (≥ 30mg/g creatinine). Results Patients with high B2M were older, and had diabetes of longer duration, higher serum creatinine, microalbuminuria, and increased vascular stiffness and C-IMT compared with patients with low B2M. B2M levels were positively correlated with C-IMT and vascular stiffness, and these associations remained constant after adjusting for age. In addition, after adjusting for age, gender, body mass index, serum creatinine, hypertension, smoking and alcohol consumption, the adjusted odds ratio (OR) for atherosclerosis was 2.01 [95% confidence interval (CI): 1.02–3.94] per 1mg/L increase in B2M. The prevalences of diabetic retinopathy and nephropathy were significantly higher with a high B2M than with a low B2M. The multiple adjusted OR for diabetic nephropathy was 2.29 (95% CI: 1.11–4.72) per 1mg/L increase of B2M. Conclusion Higher serum B2M was an independent risk factor for subclinical atherosclerosis and diabetic nephropathy in patients with T2D without renal impairment.

Serum bone morphogenic protein- (BMP-) 4 levels are associated with human adiposity. The aim of this study was to investigate changes in serum levels of BMP-4 and inflammatory cytokines after Roux-en-Y gastric bypass (RYGB). Fifty-seven patients with type 2 diabetes underwent RYGB. Serum levels of BMP-4 and various inflammatory markers, including high-sensitivity C-reactive protein (hsCRP), free fatty acids (FFAs), and plasminogen activator inhibitor- (PAI-) 1, were measured before and 12 months after RYGB. Remission was defined as glycated hemoglobin P=0.024). Of the 57 patients, 40 (70%) had diabetes remission at 1 year after surgery (remission group). Compared with patients in the nonremission group, patients in the remission group had lower PAI-1 levels and smaller visceral fat areas at baseline. There was a difference in the change in the BMP-4 level according to remission status. Our data demonstrate a significant beneficial effect of bariatric surgery on established cardiovascular risk factors and a reduction in chronic nonspecific inflammation after surgery.

Aim To investigate the relationship between small dense LDL cholesterol and cardiac autonomic neuropathy among patients with Type 2 diabetes. Methods A total of 175 patients who had not taken lipid-lowering agents previously were enrolled consecutively in this study. Small dense LDL cholesterol level was measured using polyacrylamide tube gel electrophoresis, which fractionates LDL cholesterol into seven components according to particle size and charge. We analysed the mean LDL cholesterol particle size and the proportion of small dense LDL cholesterol. Results The mean (± sd) patient age was 56 (± 14) years, the mean (± sd) duration of diabetes was 10.3 (± 8.3) years, the mean (± sd) proportion of small dense LDL cholesterol was 21.3 (± 17.6)% and the mean (± sd) LDL cholesterol size was 26.33 (± 0.8) nm. Men with cardiac autonomic neuropathy had a longer duration of diabetes compared with those without cardiac autonomic neuropathy. Women with cardiac autonomic neuropathy had a larger waist circumference, higher plasma triglyceride levels, smaller mean (± sd) LDL cholesterol size [26.8 (± 4.3) nm vs 26.4 (± 6.9) nm; P

Objectives Many chronic kidney disease (CKD) patients have persistent overt proteinuria despite angiotensin receptor blocker (ARB) treatment. This study investigated whether the initial difference in intrarenal renin–angiotensin system activity measured with urinary angiotensinogen would affect the antiproteinuric effects of ARB. Methods Between September 2005 and September 2008, in 50 non-diabetic proteinuric CKD patients not taking renin–angiotensin system inhibitors, the urinary protein/creatinine ratio (P/Cr), angiotensinogen/creatinine ratio (AGT/Cr), plasma renin and aldosterone were measured before starting valsartan, and were followed for 18 months. Results Patients were divided into three groups according to their initial urinary AGT/Cr. The urinary P/Cr was lower in the low angiotensinogen group, but similar in the high and extremely high angiotensinogen groups (1.3±0.38 vs 2.0±0.92 vs 2.2±0.78). In all groups, the urinary P/Cr was decreased most for the first 6 months. The urinary P/Cr reduction at 6 months was greatest in the high angiotensinogen group (−24.2% vs −46.2% vs −16.4%). The urinary AGT/Cr was decreased most in the high angiotensinogen group. Renal functional deterioration was attenuated in the high angiotensinogen group compared with the extremely high angiotensinogen group. Conclusions The antiproteinuric effects of ARB were different according to the initial urinary angiotensinogen levels. These results suggest the potential value of the initial urinary AGT/Cr for predicting the therapeutic effect of ARB in proteinuric non-diabetic CKD patients.

Bupropion is an atypical antidepressant that is currently used as a smoking cessation aid. Bupropion interferes with monoamine reuptake and is potentially neurotoxic, although this is yet to be confirmed. In this study, we evaluated the cytotoxicity of bupropion using SH-SY5Y human catecholaminergic cells as the in vitro model. Exposure of the cells to bupropion for 24h reduced their viability in a concentration-dependent manner. Treatment of the cells with a toxic concentration of bupropion (100μg/mL) induced the phosphorylation of eukaryotic initiation factor alpha (EIF-2α), c-JUN N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) within 1h, which later declined to baseline levels. However, bupropion failed to splice X-box binding protein 1 (XBP1) mRNA. Bupropion caused mitochondrial cytochrome c release and activated caspases 9, 8, and 3 in a time-dependent manner. The reduction in cell viability was significantly inhibited by a caspase 3 inhibitor. Bupropion also induced the mRNA expression of the death receptors DR4 (TRAILR1) and DR5 (TRAILR2). However, bupropion did not increase the level of cellular oxidative stress. Taken together, our data indicate that bupropion activates caspase 3 through the induction of endoplasmic reticulum stress responses and activation of JNK, and consequently induces apoptotic cell death in SH-SY5Y cells.

Although the effect of obesity on drug disposition remains an important issue for clinicians, little is known about the effects of obesity on organic cation transporter 1 (OCT1) expression and activity. Here, we show that hepatic OCT1 expression was higher in mice fed a high-fat (HF) diet for 19 weeks compared with mice fed a control diet. Since HF diet-induced obese mice exhibited elevation of plasma proinflammatory cytokines, leptin, and insulin levels, we evaluated the effect of leptin, insulin, and tumor necrosis factor-alpha (TNF-alpha) on OCT1 mRNA expression in HepG2 cells. Both leptin and insulin significantly increased OCT1 mRNA expression in HepG2 cells, but TNF-alpha did not. This finding was consistent with in vivo results. Using the OCT1 substrate metformin, we further measured the extent of hepatic uptake of metformin in obese and lean mice using the ratio of hepatic concentration to plasma concentration of metformin at 1 h after administration. The hepatic uptake of metformin was significantly higher in mice fed a HF diet compared with lean mice. In conclusion, our results suggest, at least in part, that obesity might have an effect on the absorption or distribution pharmacokinetics of metformin through an increase in hepatic OCT1 expression.

Aims We aimed to evaluate the association between diabetic microangiopathy and subclinical atherosclerosis as a marker of cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes. Methods A total of 142 newly diagnosed type 2 diabetics who were free from CVD underwent evaluation of diabetic microangiopathy. Subclinical atherosclerosis was assessed by measuring carotid intima-media thickness (IMT), and the 10-year absolute risk of CVD was estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine. Results Subclinical atherosclerosis was found in 27 subjects (19.0%). The rates of hypertension and diabetic retinopathy were significantly higher among patients with subclinical atherosclerosis. The UKPDS 10-year risk for CVD was significantly increased in subjects with subclinical atherosclerosis. Old age, hypertension and the presence of diabetic retinopathy showed a significant association to subclinical atherosclerosis after further adjustments for gender, body mass index, smoking status, HbA1c, HDL cholesterol, LDL cholesterol and the presence of diabetic nephropathy. Conclusions This study shows that diabetic retinopathy is an independent risk marker for subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. We suggest that a diagnosis of diabetic retinopathy may warrant a more careful cardiovascular assessment even in the early stages of diabetes.

To clarify the association of serum calcium level with metabolic syndrome (MetS) and diabetes in middle-aged and elderly Korean subjects.We conducted a population-based, cross-sectional survey of 1329 participants aged over 40 years (median age 65.8) in a rural area of Chungju, Korea, in 2007.Serum level of albumin, calcium, 25-hydroxy-vitamin D and intact parathyroid hormone were measured in a central laboratory.The prevalence of MetS increased progressively with elevated serum albumin-corrected calcium levels (P0.001 for trend). After adjusting for various covariates, subjects in the highest quintile group (2.45-2.99 mmol/L) compared with the lowest quintile group (2.05-2.24 mmol/L) of serum calcium levels had an odds ratio (OR) for having MetS of 3.11 (95% confidence intervals, CI, 1.95-4.97; P for trend0.001). Excluding the subjects with hypocalcemia and hypercalcemia (n=1064) did not alter this significant association. After multiple adjustment, subjects with serum calcium levels in the fourth to fifth quintiles had a 2.0- to 3.0-fold increased OR of having diabetes (first quintile reference, fourth quintiles OR 2.38; 95% CI 1.32-4.28, fifth quintiles OR 3.32; 95% CI 1.87-5.88; P for trend0.001).The associations of serum calcium levels with the incidences of MetS or diabetes were unchanged after adjustment for 25(OH)D and PTH levels.Altered calcium homeostasis was associated with an increased risk of having MetS and diabetes in this demographic group.

Recent surveys show that 18% of adults in the United States use prescription drugs concurrently with herbal or vitamin dietary products. Despite possible dietary supplement–drug interactions through modulation of cytochrome P450s (CYPs), dietary supplements have not been studied at a screening scale to assess their effects on CYPs. In this study, 116 herbal dietary supplements, commercially available for nutrient supply and weight management, were administered to rats to test whether they modulate the expressions of CYP1A2, 2C11, 2D1, 2E1 and 3A1 proteins. Seventy-five percent of the 116 dietary supplements modulated at least one CYP, while 25% had no effect. CYP2C11 protein expression was the most inhibited by supplements (51%), whereas CYP1A2, 2D1, 2E1 and 3A1 were the least inhibited (12–18%). CYP1A2 was the most induced, modulated by 21% supplements, while CYP2E1 and 3A1 were moderately induced (7–8%). CYP2C11 and 2D1 were not induced by any supplement tested in this study. Thus, this study suggests that dietary supplement–drug interactions may occur through modulation of CYPs in humans when they are taken simultaneously.

가톨릭대학교 가톨릭 의료원 내과, 안산 안도병원 내과 김수정, 전현지, 장은희, 이준섭, 김미경, 백기현, 송기호, 권혁상 Original Articles & Case Reports http://dx.doi.org/10.4093/jkd.2014.15.2.116

See Article on Page 306-313 Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy. Therefore, one cannot exclude the possibility that undiagnosed glucose intolerance antedated or began concomitantly with the pregnancy. Recently, the International Association of Diabetes and Pregnancy Study Groups recommended that high-risk women found to have diabetes based on standard criteria at their initial prenatal visit should be considered to have overt, not gestational, diabetes mellitus [1]. Moreover, they recommended new criteria for diagnosing GDM using a 75-g oral glucose tolerance test (OGTT). The new criteria require only one abnormal value to make the diagnosis of GDM compared with the two abnormal values required in the criteria using a 100-g OGTT. In 2011, the American College of Obstetricians and Gynecologists announced that they continue to recommend use of the old diagnostic criteria for GDM. Although several countries and international organizations have adopted the new criteria, the World Health Organization has not released its report on this topic. The United States National Institutes of Health plan to hold a conference in 2013 to develop consensus on this topic. The Korean Diabetes Association suggested both old and new criteria for the diagnosis of GDM, depending on the decision of clinicians. GDM is associated with increased risks of maternal, fetal, and neonatal adverse outcomes, depending on the degree of hyperglycemia. Furthermore, GDM has long-term sequelae for both the mother and offspring after delivery. Several studies have reported postpartum type 2 diabetes mellitus (T2DM) rates ranging from 3% to 38% within 1 year after delivery, depending on ethnicity and the proportion of participants with severe hyperglycemia during pregnancy. Cho et al. [2] found that the incidence of T2DM was approximately 41% in Korean women with previous GDM. Like prediabetes, gestational impaired glucose tolerance (GIGT) can be diagnosed when only one abnormal glucose value is seen on the 100-g OGTT. GIGT was thought to be an intermediate phenotype between normal glucose tolerance (NGT) and GDM. However, recent studies showed that the maternal and fetal outcomes are poorer if GIGT is not treated [3,4]. In this issue of The Korean Journal of Internal Medicine, Yang et al. [5] analyzed various indices of insulin resistance and insulin secretion in 1,163 pregnant Korean women undergoing 100-g OGTT. Based on the OGTT results, the study subjects were subdivided into three groups: NGT, GIGT (only one abnormal value based on the criteria of Carpenter and Coustan), and GDM. The subjects with GDM were older than the subjects with NGT and had a higher prepregnancy body mass index (BMI). In addition, the GDM group had higher insulin resistance indexes and lower insulin secretion indexes, as compared to the NGT group. These findings are similar to those of previous reports. It was thought that GDM develops when β-cells fail to adapt to the increasing demand for insulin release during the second half of pregnancy, when insulin resistance is greatest. Buchanan et al. [6] showed that insulin secretion during pregnancy increases in parallel in women with and without GDM, but from a lower starting point in women with GDM. This means that the β-cell defect in GDM is somewhat chronic, rather than acquired during pregnancy. Consequently, the β-cell dysfunction in GDM may worsen over time, which results in overt diabetes mellitus postpartum. Yang et al. [5] found that the insulin resistance indices were significantly worse in the GDM group than in the GIGT group, as expected. However, the insulin levels at each time point in the 100-g OGTT and the area under the curve for insulin were significantly higher in the GIGT group than in the GDM group. This suggests that compensation for insulin secretion occurs in the GIGT group. Insulin secretion indices were significantly lower in subjects with GDM compared with the other two groups. Among the subjects with GIGT, the 1-hour abnormal group had a significantly greater weight gain during pregnancy, and the values from the 50-g OGTT were higher than in the other two groups. Although the insulin resistance indices among the three groups were not different, HOMA-β as an index of insulin secretion capacity was lowest in the 1-hour abnormal group, which means that an insulin secretion defect is prominent in that group. This finding is similar to that of Retnakaran et al. [7]. However, recent studies suggest that women with a single abnormal glucose value at 1 hour on the OGTT had a metabolic phenotype similar to GDM, whereas GIGT at 2 or 3 hours on the OGTT is similar to NGT. Retnakaran et al. [7] reported that the caesarian section rate was higher in women with an abnormal glucose value at 1 hour on the OGTT, and this was associated with postpartum glycemia, insulin resistance, and β-cell dysfunction. Compared with Caucasians, Asians have a smaller β-cell mass with a lower insulin secretion capacity, whereas visceral adiposity with greater insulin resistance is common in Asians, even with a lower BMI. These pathophysiological differences between Caucasians and Asians could explain the recent abrupt increase in the prevalence of type 2 diabetes in Asian countries. In a study that assessed the changes in insulin resistance and β-cell function in a multiethnic population-based cohort of pregnant women [8], the increase in insulin resistance was similar across the ethnic groups. However, the increase in β-cell function was significantly lower for East and South Asians compared with Western Europeans. This suggests that there are similar pathophysiological differences between Asians and Caucasians in pregnancy. Gestational diabetes is a very interesting disease entity because it has a natural course similar to that of type 2 diabetes, which is characterized by two main pathogenic factors: insulin resistance and an insulin secretion defect. Furthermore, most GDM disappears after delivery, which provides a clue to the mechanisms for reversing type 2 diabetes to NGT. Recently, Kwak et al. [9] reported that obesity was a risk factor for both early (2 months postpartum) and late (more than 1 year after delivery) type 2 diabetes converters in women with a history of GDM. In addition, early converters had more pronounced defects in β-cell function. If there is a genetic component of the insulin secretory defect in Asian women, a reduction in insulin resistance after delivery might be the only way to prevent future type 2 diabetes in women with previous GDM.

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.

Hypercalcemia is often observed in cancer patients secondary to parathyroid hormone (PTH) related peptide production. However, primary hyperparathyroidism and colon cancer rarely present simultaneously. Calcium is believed to have a chemopreventive effect against colorectal cancer because it reduces crypt cell hyperproliferation in both humans and in animals. There is evidence to suggest that the incidence of colorectal cancer in humans is reduced by high calcium intake. In patients with primary hyperparathyroidism, increased PTH activates 1,25(OH)2D and enhances calcium absorption in the gut. Consequently, the calcium level in the lumen is decreased, leading to an elevated risk of colorectal cancer. We report two patients with colon cancer and hypercalcemia secondary to primary hyperparathyroidism, along with a brief review of the literature. (J Korean Endocr Soc 23:204~209, 2008)