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Volume 35(2); April 2011
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The Importance of Global Studies of the Genetics of Type 2 Diabetes
Mark I. McCarthy
Diabetes Metab J. 2011;35(2):91-100.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.91
  • 4,429 View
  • 29 Download
  • 11 Crossref
AbstractAbstract PDFPubReader   

Genome wide association analyses have revealed large numbers of common variants influencing predisposition to type 2 diabetes and related phenotypes. These studies have predominantly featured European populations, but are now being extended to samples from a wider range of ethnic groups. The transethnic analysis of association data is already providing insights into the genetic, molecular and biological causes of diabetes, and the relevance of such studies will increase as human discovery genetics increasingly moves towards sequencing-based approaches and a focus on low frequency and rare variants.

Citations

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  • Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21
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  • A replication study of 19 GWAS-validated type 2 diabetes at-risk variants in the Lebanese population
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  • Single nucleotide polymorphisms in JAZF1 and BCL11A gene are nominally associated with type 2 diabetes in African-American families from the GENNID study
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  • Genomweite Assoziationsstudien (GWAS) — Möglichkeiten und Grenzen
    Jennifer Kriebel, Thomas Illig, Harald Grallert
    BIOspektrum.2012; 18(5): 508.     CrossRef
  • T2DM: Why Epigenetics?
    Delphine Fradin, Pierre Bougnères
    Journal of Nutrition and Metabolism.2011; 2011: 1.     CrossRef
The Causes and Consequences of Low Levels of High Density Lipoproteins in Patients with Diabetes
Philip J. Barter
Diabetes Metab J. 2011;35(2):101-106.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.101
  • 4,345 View
  • 38 Download
  • 43 Crossref
AbstractAbstract PDFPubReader   

Type 2 diabetes is commonly accompanied by a low level of high density lipoprotein cholesterol (HDL-C) that contributes to the increased cardiovascular risk associated with this condition. Given that HDLs have the ability to improve increase the uptake of glucose by skeletal muscle and to stimulate the secretion of insulin from pancreatic beta cells the possibility arises that a low HDL concentration in type 2 diabetes may also contribute to a worsening of diabetic control. Thus, there is a double case for raising the level of HDL-C in patients with type 2 diabetes: to reduce cardiovascular risk and to improve glycemic control. Approaches to raising HDL-C include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. Of currently available drugs, the most effective is niacin. Newer formulations of niacin are reasonably well tolerated and have the ability to increase HDL-C by up to 30%. The effect of niacin on cardiovascular events in type 2 diabetes is currently being tested in a large-scale clinical outcome trial.

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The Prediabetic Period: Review of Clinical Aspects
Sang Youl Rhee, Jeong-Taek Woo
Diabetes Metab J. 2011;35(2):107-116.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.107
  • 4,150 View
  • 38 Download
  • 54 Crossref
AbstractAbstract PDFPubReader   

Hyperglycemia that does not satisfy the diagnostic criteria for diabetes mellitus (DM) is generally called prediabetes (preDM). The global prevalence of preDM has been increasing progressively in the past few decades, and it has been established that preDM status is a strong risk factor for DM and cardiovascular disease. Currently, preDM status is classified into two subtypes: impaired fasting glucose and impaired glucose tolerance. Currently, preDM is not regarded as an independent clinical entity, but only as a risk factor for others. In this article, we review various clinical aspects of preDM in terms of the working definition, changes in criteria over the years, epidemiology, and pathophysiological characteristics, and its clinical significance in current medicine.

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Editorial
Candidate Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Type 2 Diabetes
Yun-Mi Jang, Dong-Lim Kim
Diabetes Metab J. 2011;35(2):117-118.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.117
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PDFPubReader   
Original Articles
Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells
Young-Hye You, Dong-Sik Ham, Heon-Seok Park, Marie Rhee, Ji-Won Kim, Kun-Ho Yoon
Diabetes Metab J. 2011;35(2):119-129.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.119
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AbstractAbstract PDFPubReader   
Background

A limitation in the number of insulin-producing pancreatic beta-cells is a special feature of diabetes. The identification of alternative sources for the induction of insulin-producing surrogate beta-cells is a matter of profound importance. PDX-1/VP16, BETA2/NeuroD, and MafA overexpression have been shown to influence the differentiation and proliferation of pancreatic stem cells. However, few studies have been conducted using adult animal pancreatic stem cells.

Methods

Adult pig pancreatic cells were prepared from the non-endocrine fraction of adult pig pancreata. Porcine neonatal pancreas cell clusters (NPCCs) were prepared from neonatal pigs aged 1-2 days. The dispersed pancreatic cells were infected with PDX-1/VP16, BETA2/NeuroD, and MafA adenoviruses. After infection, these cells were transplanted under the kidney capsules of normoglycemic nude mice.

Results

The adenovirus-mediated overexpression of PDX-1, BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in adult pig pancreatic cells. Immunocytochemistry revealed that the number of insulin-positive cells in NPCCs and adult pig pancreatic cells was approximately 2.6- and 1.1-fold greater than those in the green fluorescent protein control group, respectively. At four weeks after transplantation, the relative volume of insulin-positive cells in the grafts increased in the NPCCs, but not in the adult porcine pancreatic cells.

Conclusion

These data indicate that PDX-1, BETA2/NeuroD, and MafA facilitate the beta-cell differentiation of NPCCs, but not adult pig pancreatic cells. Therefore PDX-1, BETA2/NeuroD, and MafA-induced NPCCs can be considered good sources for the induction of pancreatic beta-cells, and may also have some utility in the treatment of diabetes.

Citations

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Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model
Mi Young Lee, Myoung Sook Shim, Bo Hwan Kim, Soon Won Hong, Ran Choi, Eun Young Lee, Soo Min Nam, Gun Woo Kim, Jang Yel Shin, Young Goo Shin, Choon Hee Chung
Diabetes Metab J. 2011;35(2):130-137.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.130
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AbstractAbstract PDFPubReader   
Background

While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.

Methods

Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9).

Results

At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.

Conclusion

These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

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The Association of Unintentional Changes in Weight, Body Composition, and Homeostasis Model Assessment Index with Glycemic Progression in Non-Diabetic Healthy Subjects
Eun-Jung Rhee, Ji-Hun Choi, Seung-Hyun Yoo, Ji-Cheol Bae, Won-Jun Kim, Eun-Suk Choi, Se Eun Park, Cheol-Young Park, Seok Won Park, Ki-Won Oh, Sung-Woo Park, Sun-Woo Kim, Won-Young Lee
Diabetes Metab J. 2011;35(2):138-148.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.138
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AbstractAbstract PDFPubReader   
Background

We performed a retrospective longitudinal study on the effects of changes in weight, body composition, and homeostasis model assessment (HOMA) indices on glycemic progression in subjects without diabetes during a four-year follow-up period in a community cohort without intentional intervention.

Methods

From 28,440 non-diabetic subjects who participated in a medical check-up program in 2004, data on anthropometric and metabolic parameters were obtained after four years in 2008. Body composition analyses were performed with a bioelectrical impedance analyzer. Skeletal muscle index (SMI, %) was calculated with lean mass/weight×100. Subjects were divided into three groups according to weight change status in four years: weight loss (≤-5.0%), stable weight (-5.0 to 5.0%), weight gain (≥5.0%). Progressors were defined as the subjects who progressed to impaired fasting glucose or diabetes.

Results

Progressors showed worse baseline metabolic profiles compared with non-progressors. In logistic regression analyses, the increase in changes of HOMA-insulin resistance (HOMA-IR) in four years presented higher odds ratios for glycemic progression compared with other changes during that period. Among the components of body composition, a change in waist-hip ratio was the strongest predictor, and SMI change in four years was a significant negative predictor for glycemic progression. Changes in HOMA β-cell function in four years was a negative predictor for glycemic progression.

Conclusion

Increased interval changes in HOMA-IR, weight gain and waist-hip ratio was associated with glycemic progression during a four-year period without intentional intervention in non-diabetic Korean subjects.

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Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity
Jae-Geun Lee, Dong Gu Kang, Jung Re Yu, Youngree Kim, Jinsoek Kim, Gwanpyo Koh, Daeho Lee
Diabetes Metab J. 2011;35(2):149-158.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.149
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AbstractAbstract PDFPubReader   
Background

Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents.

Methods

Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects.

Results

ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; P<0.05). ADA activity was correlated with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248, P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy.

Conclusion

Our results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect.

Citations

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Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus
Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim
Diabetes Metab J. 2011;35(2):159-165.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.159
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AbstractAbstract PDFPubReader   
Background

Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.

Methods

We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.

Results

We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group.

Conclusion

In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.

Citations

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  • Letter: Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus (Diabetes Metab J 2011;35:159-65)
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Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea
Jin Taek Kim, Tae Jung Oh, Ye An Lee, Jun Ho Bae, Hyo Jeong Kim, Hye Seung Jung, Young Min Cho, Kyong Soo Park, Soo Lim, Hak Chul Jang, Hong Kyu Lee
Diabetes Metab J. 2011;35(2):166-172.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.166
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AbstractAbstract PDFPubReader   
Background

To investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects.

Methods

We analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009.

Results

A total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users.

Conclusion

We identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.

Citations

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A Survey of Diabetic Educators and Patients for the Revision of Korean Food Exchange Lists
Jae Won Cho, Mee Ra Kweon, Young Mi Park, Mi Hye Woo, Hye Sook Yoo, Jeong Hyun Lim, Bo Kyung Koo, Chong Hwa Kim, Hae Jin Kim, Tae Sun Park, Choong Ho Shin, Kyu Chang Won, Soo Lim, Hak Chul Jang
Diabetes Metab J. 2011;35(2):173-181.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.173
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AbstractAbstract PDFPubReader   
Background

Food exchange lists are one of the main methods of nutritional education. However, Korean food exchange lists have not been revised since 1994. Therefore, we surveyed the opinions of diabetes educators and patients with diabetes regarding the need for revision of the current food exchange lists.

Methods

For two weeks beginning on 10 March 2008, a 12-item questionnaire regarding the opinion and need for revision of the current food exchange lists was e-mailed to diabetes educators nationwide. Another 15-question survey was administered to patients with diabetes in 13 hospitals located in the Seoul and Gyeonggi regions of Korea.

Results

We obtained survey responses from 101 diabetes educators and 209 patients; 65 (64.3%) of the educators answered that the current food exchange lists should be revised. The items that needed revision were the glycemic index, addition of new foods and reaffirmation of exchange standard amounts. The patients demanded specific education about choosing appropriate foods, a balanced meal plan, proper snacks, and dining intake.

Conclusion

Our survey results demonstrate the need to revise the Korean food exchange lists. This process should focus on glycemic index, the addition of new foods and reconfirmation of one exchange reference unit.

Citations

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  • Mediterranean Diet and Naltrexone/Bupropion Treatment for Weight Loss in Overweight and Obese Breast Cancer Survivors and Non-Cancer Participants: A Pilot Randomized Controlled Trial


    A-Ra Cho, Won-Jun Choi, Yu-Jin Kwon, Hye Sun Lee, Sung Gwe Ahn, Ji-Won Lee
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    Jeong Hyun Lim
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    Dal Lae Ju, Hak Chul Jang, Young Yun Cho, Jae Won Cho, Hye Sook Yoo, Kyung Suk Choi, Mi Hye Woo, Cheong Min Sohn, Yoo Kyoung Park, Ryo Won Choue
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  • Korean Food Exchange Lists for Diabetes: Revised 2010
    Dal Lae Ju, Hak Chul Jang, Young Yun Cho, Jae Won Cho, Hye Sook Yoo, Kyung Suk Choi, Mi Hye Woo, Cheong Min Sohn, Yoo Kyoung Park, Ryowon Choue
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Evaluation of Stress in Korean Patients with Diabetes Mellitus Using the Problem Areas in Diabetes-Korea Questionnaire
Young Sil Eom, Hwa Sun Park, Sei-Hyun Kim, Sun Mee Yang, Moon Suk Nam, Hyoung Woo Lee, Ki Young Lee, Sihoon Lee, Yeun Sun Kim, Ie Byung Park
Diabetes Metab J. 2011;35(2):182-187.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.182
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AbstractAbstract PDFPubReader   
Background

It is known that diabetes and stress are directly or indirectly related, and that it is important to evaluate stress in patients with diabetes. The relationship between Korean diabetics and diabetes-related stress has never been reported. The objective of this study was to develop a stress questionnaire suitable for use with Korean diabetics and to evaluate its utility.

Methods

This study subjects were 307 Korean diabetics, aged 40 to 74 years old, who visited the Department of Endocrinology and Metabolism at Gachon University Gil Hospital, Yeungnam University Medical Center, and Inha University Hospital in Korea between March 2006 and February 2008. We developed a Korean version of Polonsky's Problem Areas in Diabetes (PAID) stress questionnaire (PAID-K) and used it to assess degrees of stress in our sample of Korean patients. We evaluated the utility of the questionnaire and analyzed the relationships between clinical characteristics of the study subjects and degrees of stress.

Results

Cronbach's alpha for PAID-K was 0.95, and PAID-K scores were significantly correlated with Hypoglycemia Fear Survey scores (r=0.44, P<0.05) and State Trait Anxiety Inventory-6 scores (r=0.21, P<0.05). PAID-K scores were significantly higher in patients with longer durations of diabetes, patients using insulin, and female patients (P=0.02, P=0.038, and P=0.001, respectively). The score also tended to increase as HbA1c levels increased, except for very high HbA1c levels (above 11%) (P for trend<0.05).

Conclusion

We developed the PAID-K questionnaire and demonstrated its utility to evaluate levels of stress in diabetic patients in Korea.

Citations

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    Carlos Vasconcelos, António Almeida, Maria Cabral, Elisabete Ramos, Romeu Mendes
    International Journal of Environmental Research and Public Health.2019; 16(13): 2403.     CrossRef
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    Jin Hee Jung, Jung Hwa Lee
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    Sebahat Atalikoğlu Başkan, Mehtap Tan
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Letter
Letter: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetes Patients (Diabetes Metab J 2011;35:41-9)
Min Suk Lee, Hae Jin Kim
Diabetes Metab J. 2011;35(2):188-189.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.188
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Response
Response: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:41-9)
Sung-Tae Kim, Byung-Joon Kim, Dong-Mee Lim, In-Geol Song, Jang-Han Jung, Kang-Woo Lee, Keun-Young Park, Youn-Zoo Cho, Dae-Ho Lee, Gwan-Pyo Koh
Diabetes Metab J. 2011;35(2):190-191.   Published online April 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.2.190
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