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Volume 35(3); June 2011
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Diabetes and Cancer: Is Diabetes Causally Related to Cancer?
Sunghwan Suh, Kwang-Won Kim
Diabetes Metab J. 2011;35(3):193-198.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.193
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  • 39 Download
  • 82 Crossref
AbstractAbstract PDFPubReader   

Diabetes mellitus is a serious and growing health problem worldwide and is associated with severe acute and chronic complications. Moreover, epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer. Several studies indicate an association between diabetes and the risk of liver, pancreas, endometrium, colon/rectum, breast, and bladder cancer. Mortality is also moderately increased in subjects with diabetes. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in diabetic patients. Hyperinsulinemia most likely favors cancer in diabetic patients as insulin is a growth factor with pre-eminent metabolic as well as mitogenic effects, and its action in malignant cells is favored by mechanisms acting at both the receptor and post-receptor level. The effect of diabetes treatment drugs, aside from metformin, on cancer is not conclusive. In order to fight the perfect storm of diabetes and cancer, strategies to promote primary prevention and early detection of these conditions are urgently needed.

Citations

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Clinical Allogeneic and Autologous Islet Cell Transplantation: Update
Shinichi Matsumoto
Diabetes Metab J. 2011;35(3):199-206.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.199
  • 11,103 View
  • 43 Download
  • 17 Crossref
AbstractAbstract PDFPubReader   

Islet cell transplantation is categorized as a β-cell replacement therapy for diabetic patients who lack the ability to secrete insulin. Allogeneic islet cell transplantation is for the treatment of type 1 diabetes, and autologous islet cell transplantation is for the prevention of surgical diabetes after a total pancreatectomy. The issues of allogeneic islet cell transplantation include poor efficacy of islet isolation, the need for multiple donor pancreata, difficulty maintaining insulin independence and undesirable side effects of immunosuppressive drugs. Those issues have been solved step by step and allogeneic islet cell transplantation is almost ready to be the standard therapy. The donor shortage will be the next issue and marginal and/or living donor islet cell transplantation might alleviate the issue. Xeno-islet cell transplantation, β-cell regeneration from human stem cells and gene induction of the naïve pancreas represent the next generation of β-cell replacement therapy. Autologous islet cell transplantation after total pancreatectomy for the treatment of chronic pancreatitis with severe abdominal pain is the standard therapy, even though only limited centers are able to perform this treatment. Remote center autologous islet cell transplantation is an attractive option for hospitals performing total pancreatectomies without the proper islet isolation facilities.

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Sulwon Lecture 2010
Mitochondrial Dysfunction and Insulin Resistance: The Contribution of Dioxin-Like Substances
Hong Kyu Lee
Diabetes Metab J. 2011;35(3):207-215.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.207
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AbstractAbstract PDFPubReader   

Persistent organic pollutants (POPs) are known to cause mitochondrial dysfunction and this in turn is linked to insulin resistance, a key biochemical abnormality underlying the metabolic syndrome. To establish the cause and effect relationship between exposure to POPs and the development of the metabolic syndrome, Koch's postulates were considered. Problems arising from this approach were discussed and possible solutions were suggested. In particular, the difficulty of establishing a cause and effect relationship due to the vagueness of the metabolic syndrome as a disease entity was discussed. Recently a bioassay, aryl-hydrocarbon receptor (AhR) trans-activation activity using a cell line expressing AhR-luciferase, showed that its activity is linearly related with the parameters of the metabolic syndrome in a population. This finding suggests the possible role of bioassays in the analysis of multiple pollutants of similar kinds in the pathogenesis of several closely related diseases, such as type 2 diabetes and the metabolic syndrome. Understanding the effects of POPs on mitochondrial function will be very useful in understanding the integration of various factors involved in this process, such as genes, fetal malnutrition and environmental toxins and their protectors, as mitochondria act as a unit according to the metabolic scaling law.

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Editorial
Chemerin: A Novel Link between Inflammation and Atherosclerosis?
Eun-Jung Rhee
Diabetes Metab J. 2011;35(3):216-218.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.216
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PDFPubReader   

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Original Articles
ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity
Yeul Bum Park, Yun Jung Choi, So Young Park, Jong Yeon Kim, Seong Ho Kim, Dae Kyu Song, Kyu Chang Won, Yong Woon Kim
Diabetes Metab J. 2011;35(3):219-225.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.219
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AbstractAbstract PDFPubReader   
Background

The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (KATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight.

Methods

To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the KATP channel.

Results

The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice.

Conclusion

These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.

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Comparison of EGF with VEGF Non-Viral Gene Therapy for Cutaneous Wound Healing of Streptozotocin Diabetic Mice
Junghae Ko, Haejung Jun, Hyesook Chung, Changshin Yoon, Taekyoon Kim, Minjeong Kwon, Soonhee Lee, Soojin Jung, Mikyung Kim, Jeong Hyun Park
Diabetes Metab J. 2011;35(3):226-235.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.226
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AbstractAbstract PDFPubReader   
Background

To accelerate the healing of diabetic wounds, various kinds of growth factors have been employed. It is the short half-life of administered growth factors in hostile wound beds that have limited wide-spread clinical usage. To overcome this limitation, growth factor gene therapy could be an attractive alternative rather than direct application of factors onto the wound beds. We administered two growth factor DNAs, epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) into a cutaneous wound on diabetic mice. We compared the different characteristics of the healing wounds.

Methods

Streptozotocin was injected intraperitoneally to induce diabetes into C57BL/6J mice. The ultrasound micro-bubble destruction method with SonoVue as a bubbling agent was used for non-viral gene delivery of EGF828 and VEGF165 DNAs. Each gene was modified for increasing efficacy as FRM-EGF828 or minicircle VEGF165. The degree of neoangiogenesis was assessed using qualitative laser Doppler flowmetry. We compared wound size and histological findings of the skin wounds in each group.

Results

In both groups, accelerated wound closure was observed in the mice receiving gene therapy compared with non treated diabetic control mice. Blood flow detected by laser doppler flowmetry was better in the VEGF group than in the EGF group. Wound healing rates and histological findings were more accelerated in the EGF gene therapy group than the VEGF group, but were not statistically significant.

Conclusion

Both non-viral EGF and VEGF gene therapy administrations could improve the speed and quality of skin wound healing. However, the detailed histological characteristics of the healing wounds were different.

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The Effect of an Angiotensin Receptor Blocker on Arterial Stiffness in Type 2 Diabetes Mellitus Patients with Hypertension
Ji Hyun Kim, Su Jin Oh, Jung Min Lee, Eun Gyoung Hong, Jae Myung Yu, Kyung Ah Han, Kyung Wan Min, Hyun Shik Son, Sang Ah Chang
Diabetes Metab J. 2011;35(3):236-242.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.236
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AbstractAbstract PDFPubReader   
Background

Hypertension and type 2 diabetes mellitus are major risk factors for cardiovascular disease. This study analyzed the changes in central aortic waveforms and pulse wave velocity as well as related parameters after treatment with valsartan, an angiotensin II type 1 receptor blocker, in patients with type 2 diabetes and hypertension.

Methods

We used pulse wave analysis to measure central aortic waveform in a total of 98 subjects. In 47 of these patients, pulse wave velocity measurements were obtained before and after 12 weeks of treatment with valsartan.

Results

In the central aortic waveform analysis, the aortic pulse pressure and augmentation index were significantly decreased after valsartan treatment, as was the aortic pulse wave velocity. Factors contributing to the improvement in pulse wave velocity were the fasting blood glucose and haemoglobin A1c levels.

Conclusion

Short-term treatment with valsartan improves arterial stiffness in patients with type 2 diabetes and hypertension, and the glucose status at baseline was associated with this effect.

Citations

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  • Letter: The Effect of an Angiotensin Receptor Blocker on Arterial Stiffness in Type 2 Diabetes Mellitus Patients with Hypertension (Diabetes Metab J 2011;35:236-42)
    Chul-Hee Kim
    Diabetes & Metabolism Journal.2011; 35(4): 427.     CrossRef
Angiotensin II Inhibits Insulin Binding to Endothelial Cells
Su-Jin Oh, Won-Chul Ha, Jee-In Lee, Tae-Seo Sohn, Ji-Hyun Kim, Jung-Min Lee, Sang-Ah Chang, Oak-Kee Hong, Hyun-Shik Son
Diabetes Metab J. 2011;35(3):243-247.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.243
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AbstractAbstract PDFPubReader   
Background

Insulin-mediated glucose uptake in insulin target tissues is correlated with interstitial insulin concentration, rather than plasma insulin concentration. Therefore, insulin delivery to the interstitium of target tissues is very important, and the endothelium may also play an important role in the development of insulin resistance.

Methods

After treating bovine aortic endothelial cells with angiotensin II (ATII), we observed the changes in insulin binding capacity and the amounts of insulin receptor (IR) on the cell membranes and in the cytosol.

Results

After treatment of 10-7M ATII, insulin binding was decreased progressively, up to 60% at 60 minutes (P<0.05). ATII receptor blocker (eprosartan) dose dependently improved the insulin binding capacity which was reduced by ATII (P<0.05). At 200 µM, eprosartan fully restored insulin binding capacity, althogh it resulted in only a 20% to 30% restoration at the therapeutic concentration. ATII did not affect the total amount of IR, but it did reduce the amount of IR on the plasma membrane and increased that in the cytosol.

Conclusion

ATII decreased the insulin binding capacity of the tested cells. ATII did not affect the total amount of IR but did decrease the amount of IR on the plasma membrane. Our data indicate that ATII decreases insulin binding by translocating IR from the plasma membrane to the cytosol. The binding of insulin to IR is important for insulin-induced vasodilation and transendothelial insulin transport. Therefore, ATII may cause insulin resistance through this endothelium-based mechanism.

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Relationship between Chemerin Levels and Cardiometabolic Parameters and Degree of Coronary Stenosis in Korean Patients with Coronary Artery Disease
Yu-Jin Hah, Nam-Keong Kim, Mi-Kyung Kim, Hye-Soon Kim, Seung-Ho Hur, Hyuck-Jun Yoon, Yoon-Nyun Kim, Keun-Gyu Park
Diabetes Metab J. 2011;35(3):248-254.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.248
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AbstractAbstract PDFPubReader   
Background

Chemerin is a novel adipokine that is associated with inflammation and adipogenesis. However, it remains unclear whether chemerin is involved in patients with cardiovascular disease. We investigated whether the serum chemerin levels of Korean patients with coronary artery disease correlated with specific cardiometabolic parameters.

Methods

In total, 131 patients, all of whom had coronary artery stenosis exceeding 50%, participated in this study. Their serum chemerin levels and cardiometabolic parameters were measured. The serum chemerin levels of two groups of patients were compared; those with one stenotic vessel (n=68) and those with multiple stenotic vessels, including left main coronary artery disease (n=63).

Results

Serum chemerin levels correlated positively with the degree of coronary artery stenosis and fasting glucose, triglyceride, total cholesterol, low density lipoprotein cholesterol, and high sensitive C-reactive protein levels. The group with multiple stenotic vessels, including left main disease, had higher chemerin levels than the group with one stenotic vessel (t=-2.129, P=0.035). Multiple binary logistic regression showed chemerin was not an independent risk factor of multiple vessel disease (odds ratio, 1.018; confidence interval, 0.997 to 1.040; P=0.091).

Conclusion

Serum chemerin levels have a significant correlation with several cardiometabolic risk factors and the degree of coronary artery stenosis in Korean patients with coronary artery disease. However, multiple binary logistic regression showed chemerin was not an independent risk factor of multiple vessel disease. Additional investigations are necessary to fully elucidate the role of chemerin in cardiovascular disease.

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Prevalence of Diabetes Mellitus and Prediabetes in Dalseong-gun, Daegu City, Korea
Jung-Eun Lee, Sung-Chang Jung, Gui-Hwa Jung, Sung-Woo Ha, Bo-Wan Kim, Shung-Chull Chae, Wee-Hyun Park, Ji-Sun Lim, Jin-Hoon Yang, Sin Kam, Byung-Yeol Chun, Jong-Yeon Kim, Jung-Jeung Lee, Kyeong-Soo Lee, Moon-Young Ahn, Young-Ae Kim, Jung-Guk Kim
Diabetes Metab J. 2011;35(3):255-263.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.255
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AbstractAbstract PDFPubReader   
Background

The aim of the present study was to determine the population-based prevalence of diabetes mellitus (DM) and prediabetes in a rural district of Daegu City, Korea.

Methods

Between August and November 2003, a community-based health survey of adults aged 20 years and older was performed in the rural district of Dalseong-gun in Daegu City. A total of 1,806 of all eligible individuals agreed to participate. Fasting plasma glucose was measured in all participants. Two hour oral glucose tolerance was measured in the 1,773 participants for whom there was neither an established diagnosis of DM nor evidence of DM according to fasting glucose levels. The prevalence of DM and prediabetes was determined according to the 2003 criteria of the American Diabetes Association. Subjects with prediabetes were classified into one of three categories of glucose intolerance: isolated impaired fasting glucose (IFG); isolated impaired glucose tolerance (IGT); or combined IFG and IGT.

Results

The prevalence of DM was 12.2%. The highest prevalence rates were observed in subjects in their seventies. A total of 34.7% of all subjects who were assigned a diagnosis of DM in the present study had not been diagnosed previously. The prevalence of prediabetes was 22.7%. The highest prevalence rates were observed in subjects in their fifties.

Conclusion

The present study identified prevalence rates of 12.2% for DM (age-standardized prevalence rate [ASR], 6.8%), and 22.7% for prediabetes (ASR 18.5%). These results emphasize the need for community health promotion strategies to prevent or delay the onset of DM in individuals with prediabetes.

Citations

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    Rong Liu, Wendy J. Brickman, Katherine K. Christoffel, Xin Liu, Guoying Wang, Lester Arguelles, Shanchun Zhang, Donald Zimmerman, Binyan Wang, Xiping Xu, Zhiping Li, Houxun Xing, Xiaobin Wang
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Therapeutic Target Achievement in Type 2 Diabetic Patients after Hyperglycemia, Hypertension, Dyslipidemia Management
Ah Young Kang, Su Kyung Park, So Young Park, Hye Jeong Lee, Ying Han, Sa Ra Lee, Sung Hwan Suh, Duk Kyu Kim, Mi Kyoung Park
Diabetes Metab J. 2011;35(3):264-272.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.264
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AbstractAbstract PDFPubReader   
Background

Our study group established "3H care" in 2002. The meaning of "3H care" attain and maintain adequate controls over hypertension, hyperlipidemia, and hyperglycemia in type 2 diabetic patients. This study evaluated the achievement of target goals after one year or more of "3H care" by specialists in our diabetic clinic.

Methods

This was a retrospective study of 200 type 2 diabetic patients who received "3H care" for one year or more in our diabetic clinic. We evaluated achievement of target goals for metabolic controls as suggested by the American Diabetes Association.

Results

Overall, 200 type 2 diabetes patients were enrolled, of whom 106 were males (53%) and 94 were females (47%). After one year of "3H care," the mean HbA1c was 7.2±1.5% and the percentage of patients achieving glycemic control (HbA1c <7%) was 51.8%. However only 32.2% of hypertensive patients achieved the recommended target. After one year of "3H care," the percentages of those who achieved the target value for dyslipidemia were 80.0% for total cholesterol, 66.3% for low density lipoprotein cholesterol, 57.9% for triglyceride, and 51.8% for high density lipoprotein cholesterol. The percentage that achieved all three targets level was only 4.4% after one year and 14.8% after two years.

Conclusion

The results of this study demonstrate that only a minor proportion of patients with type 2 diabetes achieved the recommended goals despite the implementation of "3H care." It is our suggestion that better treatment strategies and methods should be used to control hypertension, hyperlipidemia and hyperglycemia.

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Small Rice Bowl-Based Meal Plan for Energy and Marcronutrient Intake in Korean Men with Type 2 Diabetes: A Pilot Study
Hee Jung Ahn, Kyung Ah Han, Jin Young Jang, Jae Hyuk Lee, Kang Seo Park, Kyung Wan Min
Diabetes Metab J. 2011;35(3):273-281.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.273
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AbstractAbstract PDFPubReader   
Background

Koreans eat rice, which is usually served in a rice bowl. We investigated the effect of a meal plan using small rice bowls on the total energy intake (TEI) and the marcronutrient intake in Korean men with type 2 diabetes.

Methods

A total of 62 men with type 2 diabetes were divided by body mass index (BMI) (normal weight [NW], BMI<23 kg/m2; overweight [OW], 23≤BMI<25 kg/m2; obese [OB], BMI≥25 kg/m2) and proportions of carbohydrate intake to TEI (PCI) (low carbohydrate intake [LC], <55%; recommended carbohydrate intake [RC], ≥55% and ≤60%; high carbohydrate intake [HC], >60%). The 3-day dietary records were analyzed for TEI and proportions of macronutrients, before and 2 weeks after a small-sized (300 mL) rice bowl based education was given.

Results

There were no significant differences in the age and BMI within the sub-groups by BMI and PCI groups. In baseline, the ratio of TEI to recommended total energy intake (RTR) of OW and OB were higher than that of NW. The PCI of HC was higher than that of LC and alcohol intake of HC was lower than that of LC. After education, the reduction of RTREI in OB was higher than that in OW and NW. The reduction of PCI in HC was higher than that of LC.

Conclusion

A small rice bowl based meal plan was effective for the reduction of energy intake and control of marcronutrient intake in Korean obese men with type 2 diabetes consuming a high carbohydrate diet.

Citations

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  • Comprehensive Understanding for Application in Korean Patients with Type 2 Diabetes Mellitus of the Consensus Statement on Carbohydrate-Restricted Diets by Korean Diabetes Association, Korean Society for the Study of Obesity, and Korean Society of Hyperte
    Jong Han Choi, Jee-Hyun Kang, Suk Chon
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Factors Associated with Long-Term Oral Hypoglycemic Agent Responsiveness in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon Kim, Chan-Hee Jung, Ji-Oh Mok, Chul-Hee Kim
Diabetes Metab J. 2011;35(3):282-289.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.282
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AbstractAbstract PDFPubReader   
Background

This study was performed to determine the factors associated with long-term oral hypoglycemic agent (OHA) responsiveness in Korean type 2 diabetic patients.

Methods

Two groups of patients were selected among the type 2 diabetic patients who were followed for more than two years at a university hospital diabetes clinic. The OHA responsive group consisted of 197 patients whose HbA1c levels were maintained at ≤7% with OHA for more than two years. The OHA failure group consisted of 180 patients whose HbA1c levels were >8% in spite of optimal combined OHA therapy or patients who required insulin therapy within the two years of the study.

Results

The OHA failure group had higher baseline values of fasting and postprandial glucose, HbA1c, and lower fasting, postprandial, and delta C-peptide compared to those of the OHA responsive group. The OHA failure group also had a higher proportion of female patients, longer diabetic duration, and more family history of diabetes. There were no significant differences in body mass index (BMI) or insulin resistance index between the two groups. Multiple logistic regression analysis showed that the highest quartile of baseline fasting, postprandial glucose, and HbA1c and the lowest quartile of postprandial and delta C-peptide were associated with an increased odds ratio of OHA failure after adjustment for age, sex, body mass index, and family history of diabetes.

Conclusion

Lower baseline values of postprandial and delta C-peptide and elevated fasting glucose and HbA1c are associated with long-term OHA responsiveness in Korean patients with type 2 diabetes mellitus.

Citations

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  • Therapeutic Effects of Switching to Anagliptin from Other DPP-4 Inhibitors in T2DM Patients with Inadequate Glycemic Control: A Non-interventional, Single-Arm, Open-Label, Multicenter Observational Study
    Sang-Yong Kim, Sungrae Kim
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Retrospective Analysis on the Efficacy, Safety and Treatment Failure Group of Sitagliptin for Mean 10-Month Duration
Won Jun Kim, Cheol-Young Park, Eun Haeng Jeong, Jeong Youn Seo, Ji Soo Seol, Se Eun Park, Eun Jung Rhee, Won Young Lee, Ki Won Oh, Sung Woo Park, Sun Woo Kim
Diabetes Metab J. 2011;35(3):290-297.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.290
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AbstractAbstract PDFPubReader   
Background

To investigate the clinical results of sitagliptin (SITA) and the characteristics of the treatment failure group or of low responders to SITA.

Methods

A retrospective study of type 2 diabetic patients reviewed 99 cases, including 12 treatment failure cases, who stopped SITA because of worsening patients' condition, and 87 cases, who continued treatment over five visits (total 9.9±10.1 months) after receiving the prescription of SITA from December 2008 to June 2009. Subjects were classified as five groups administered SITA as an initial combination with metformin (MET), add-on to metformin or sulfonylurea, and switching from sulfonylurea or thiazolidinedione. The changes in HbA1c level from the first to last visit (ΔHbA1c) in treatment maintenance group were subanalyzed.

Results

The HbA1c level was significantly reduced in four groups, including initial coadministration of SITA with metformin (ΔHbA1c=-1.1%, P<0.001), add-on to MET (ΔHbA1c=-0.6%, P=0.017), add-on to sulfonylurea (ΔHbA1c=-0.5%, P<0.001), and switching from thiazolidinedione (ΔHbA1c=-0.3%, P=0.013). SITA was noninferior to sulfonlyurea (ΔHbA1c=-0.2%, P=0.63). There was no significant adverse effect. The treatment failure group had a longer diabeties duration (P=0.008), higher HbA1c (P=0.001) and fasting plasma glucose (P=0.003) compared to the maintenance group. Subanalysis on the tertiles of ΔHbA1c showed that low-response to SITA (tertile 1) was associated with a longer diabetes duration (P=0.009) and lower HbA1c (P<0.001).

Conclusion

SITA was effective and safe for use in Korean type 2 diabetic patients. However, its clinical responses and long-term benefit-harm profile is yet to be established.

Citations

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Letter

Diabetes Metab J : Diabetes & Metabolism Journal