• YAKHAK HOEJI
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• v.52 no.5
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• pp.331-344
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• 2008

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

• Journal of Cancer Prevention
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• v.23 no.4
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• pp.191-196
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• 2018

Background: Type 2 diabetes mellitus (T2DM) and cancer are serious health problems worldwide, and their prevalences have been on the rise in recent years. It has been reported that adropin plays an important role in the development of T2DM, oxidative stress, inflammation, and obesity. However, there is limited information available on T2DM from human studies, especially for the Korean population. In this study, we aimed to investigate the correlation between adropin levels and obesity of Korean T2DM patients. Methods: Thirty-six T2DM patients were recruited for this study. The participants were further classified into female (n = 12) and male (n = 24). Their body composition, metabolic parameters, inflammatory factors, and oxidative stress were measured. Results: The severity of obesity is more manifested in male than in female. Plasma triglyceride (TG) and high-sensitivity C-reactive protein (hs-CRP) levels of male were significantly higher than female. The plasma adropin and adiponectin level of female was significantly higher than male. The body weight, body mass index (BMI), body fat mass were negatively correlated with the plasma adropin level in female, whereas adropin has positive correlation with adiponectin in female. The hs-CRP was negatively correlated with the plasma adropin level in female and male. malondialdehyde, reactive oxidative species, and $TNF-{\alpha}$ was not significantly correlated with adropin in patients with T2DM. Conclusions: These findings suggest that adropin may be more used as a biomarker for predicting the risk of obesity and inflammation in Korean patients with T2DM, especially women.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.1
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• pp.81-87
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• 2021

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is one of the most common types of diabetes and is caused by increased insulin resistance and reduced insulin secretion. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is a master modulator of mitochondrial biogenesis and of gluconeogenesis in liver. In this study, we analyzed genetic polymorphisms of PPARGC1A gene in a middle-aged Korean population with T2DM. Using the genotype data of 736 T2DM cases and 4544 healthy controls obtained from the Korean Association Resource (KARE), we analyzed genetic correlations between single nucleotide polymorphisms (SNPs) of PPARGC1A and T2DM. Fifteen SNPs of PPARGC1A demonstrated a statistically significant association with T2DM. Of these, rs10212638 exhibited the strongest correlation with T2DM (P-value=0.015, OR=1.29, CI=1.05~1.59), and the minor G allele of PPARGC1A increased the risk of T2DM. This is the first study to report a significant association between genetic polymorphisms in PPARGC1A and T2DM and suggests that SNPs of PPARGC1A display genetic correlations to the etiology of T2DM.

• Journal of Acupuncture Research
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• v.25 no.3
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• pp.115-125
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• 2008

Diabetes mellitus is a worldwide epidemic. Global projections suggest that most nations will have a doubling of the incidence of Diabetes mellitus(DM) within 20years. The Herb-Combined Remedy(HCR) of DM was known as one of anti-hyperglycaemic agents. But it is unclear whether HCR can be used to treat patients with Diabetic nephropathy or not. The present study was designed to investigate the anti-hyperglycaemic and preventive effects from diabetic nephropathy of HCR in STZ-induced diabetic rats. Treatment with HCR regulated blood glucose levels, but did not affect body weights. In addition, HCR was able to decrease blood glucose levels after 120min. Serum BUN levels were not effective but, serum Creatinine levels were lowered by treatment with HCR or MF. In histopathological observation of renal tissue, both HCR and MF groups showed decreased tendency of inflammation and renal injury. In conclusion, these results demonstrate that HCR is effective to treat patients with DM and also has preventive activity on diabetic nephropathy.

• Journal of Korean Academy of Nursing
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• v.41 no.2
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• pp.182-190
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• 2011

Purpose: This study was done to identify correlates and variables predicting daily activity among elders with Diabetes Mellitus (DM). Methods: Seventy-six elders registered in the Department of Endocrine Medicine at C university hospital participated in data collection. Data on daily activity and biochemical variables were collected via actigraph accelerator (Actical) and blood tests between September 2009 and July 2010. Data analysis was done using SPSS WIN 15.0 program and included one-way ANOVA, independent t-test, Pearson correlation coefficients, and stepwise multiple regression. Results: This study showed a positive correlation between daily activity and High Density Lipoprotein Cholesterol (HDL-C) and a negative correlation among Total Cholesterol (TC), Triglyceride (TG), and Low Density Lipoprotein Cholesterol (LDL-C). The variables predicting daily activity were frequency of exercise, HDL-C, and TC. These factors accounted for 40.0% of the variance of daily activity in elders with DM. Conclusion: The results indicate that it is necessary to improve daily activity to reduce Fasting Blood Glucose (FBG), TC, and TG in elders with DM.

• Korean Journal of Adult Nursing
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• v.29 no.1
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• pp.1-11
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• 2017

Purpose: The purpose of this study was to identify the factors and the relative risk associated with admission of patients with diabetes mellitus (DM). Methods: The sample included one hundred twenty-eight patients with type II DM. Seventy-seven patients who were admitted within six months of a hospitalization to one hospital from the first of February to the 31st of August 2014, were compared with fifty-one patients who regularly attended an outpatient clinic and had no hospitalizations. Results: Hospitalization probabilities among patients who had only diet and exercise or took oral diabetic medication were 0.03 (p=.004) and 0.21 (p=.007) times independently lower than the ones with insulin injection. The risks for hospitalization increases 6.33 times if there is absence of a spouse (p=.027) whereas the presence of a spouse seems to make hospitalization less likely. The risk among the ones having diabetic complications was 5.15 times higher than ones having no recognition of the complications (p=.040). For every one point increase in self-efficacy and every 1 mg/dL increase in high density lipoprotein (HDL) cholesterol, there was a 0.84 (p=.005) and a 0.96 (p=.036) decrease in hospitalization risk, respectively. Conclusion: Nurses should be sensitive to the risk groups of hospital admission among patients with DM including no spouse, insulin injection, diabetic complications, low self-efficacy, and low HDL cholesterol.

• Journal of Korean Biological Nursing Science
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• v.23 no.2
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• pp.119-126
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• 2021

Purpose: This study confirmed the effects of body mass index (BMI) and waist circumference (WC) on fasting blood glucose (FBS) and hemoglobin A1c (HbA1c) in adults without diabetes mellitus (DM). Methods: The subjects were 4,659 adults (≥ 20 years), and data were extracted from the 6th National Health and Nutrition Survey 2015 (KNHANES VI-3). The subject's data were analyzed using a complex sample t-test, χ²-test, and multiple logistic regression analysis (SPSS 24.0). Results: The incidence of the high FBS group was increased 1.60 times in males with a WC ≥ 90 cm and 1.78 times in females with a WC ≥ 85 cm. The incidence of the high HbA1c group was increased 1.54 times in those who were overweight and 2.22 times in those who were obese. The incidence of the high HbA1c group was increased 1.99 times in males with a WC ≥ 90 cm and 1.87 times in females with a WC ≥ 85 cm. Conclusion: This study presented evidence that interventions for BMI and WC should be included in DM prevention programs. It also suggested that these findings can be utilized for early detection of DM.

• Journal of Veterinary Clinics
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• v.36 no.1
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• pp.74-77
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• 2019

A 10-year-old, 8.28 kg, intact female Cocker Spaniel was presented with continuous polyuria and polydipsia. The dog had proestrus bleeding 5 weeks earlier, and hyperglycemia, glucosuria, ketouria, and high level of serum fructosamine in laboratory findings. Based on hyperglycemia, glucosuria, ketouria, and ketosis, the patient was tentatively diagnosed as diabetes mellitus (DM) with ketouria. After diagnosis, 5 to 7 U/body porcine lente insulin was administered during 11 days from initial presentation as the remission of DM for the dog. But, blood glucose was still high level. Because there was no reaction to porcine lente insulin, it was replaced by 4-10 U/body neutral protamine Hagedorn (NPH) during 3 days. But, NPH also did not regulate blood glucose level. Because insulin therapy failed to regulate blood glucose level, the dog was considering insulin-resistant diabetes. The dog was tentatively diagnosed with progesterone-resistant DM on the basis of the history that had revealed proestrus bleeding 5 weeks earlier. Progesterone level was moderate high (43.7 ng/ml; reference range, 15.0-90.0 ng/ml). Ovariohysterectomy (OHE) was performed to remove the cause of the dog's diabetes. After OHE 11 days, blood glucose was gradually declined by insulin treatment. Consequently, blood glucose was well controlled in reference range without insulin treatment after 2 months. This case is a report on progesterone-induced DM treated with OHE and insulin treatment during the diestrus.

• Journal of Preventive Medicine and Public Health
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• v.32 no.4
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• pp.526-537
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• 1999

Objectives : It is known that the prevalence of diabetes mellitus(DM) appears to be rapidly increasing in recent times in Korea, presumably due to a westernized diet and change of life style followed by rapid economic growth. Based on the Seoul male cohort which was constructed in 1993, this study was conducted to estimate the annual incidence rates of DM through 4 years' follow up and to determine which factors are associated with DM risk in Korean middle-aged men. Methods : Among 14,533 men recruited at baseline, 559 were excluded because they reported a history of diabetes or were found to be diabetes at 1992 routine health examination. During 4 years' follow-up, 237 incident DM cases were ascertained through chart reviews and telephone contacts for those who have ever visited hospitals or clinics under suspicion of DM during 1993-1996 and the biennial routine health examinations in 1994 and 1996. Results : In this study the annual incidence of DM among the study population was estimated to be 0.5 per 100. This study showed that fasting glucose level at initial baseline examination was a powerful predictor of risk for diabetes several years later(fasting blood glucose of $\geq$ 110 mg/dl compared with $\leq$ 80 mg/dl, Hazard Ratio[HR]:15.6, 95% Confidence interval[CI]=9.1-26.6) after considering potential covariates such as age, family history, smoking and alcohol history, body mass index, physical activity, total energy intake, and total fiber intake. Adjusted hazard ratios of family history of diabetes was 1.95(95% CI=1.38-2.75); of obesity as measured by BMI(BMI $\geq$ 25.3 compared with $\leq$ 21.3) was 7.19(95% CI=3,75-13.8); of weight change during middle life(>10kg compared with $\leq$ 5) was 1.77(95% CI=1.16-2.69); of smoking(current vs none) was 1.93(95% CI=1.06-3.51); and fat intake(upper fertile compared with lower fertile) was 1.88(95% CI=1.01-3.49), while fiber intake was associated with the reduced risk(HR=0.36, 95% CI=0.19-0.67). Conclusion : The factors identified in this study indicate that the greatest reduction in risk of diabetes might be achieved through population-based efforts that promote fiber intake and reduce obesity, smoking, and fat intake.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5675-5680
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• 2013

Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.