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Volume 39(2); April 2015
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Reviews
New Drugs for Treating Dyslipidemia: Beyond Statins
Chang Ho Ahn, Sung Hee Choi
Diabetes Metab J. 2015;39(2):87-94.   Published online April 20, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.87
  • 5,652 View
  • 82 Download
  • 41 Web of Science
  • 37 Crossref
AbstractAbstract PDFPubReader   

Statins have been shown to be very effective and safe in numerous randomized clinical trials, and became the implacable first-line treatment against atherogenic dyslipidemia. However, even with optimal statin treatment, 60% to 80% of residual cardiovascular risk still exists. The patients with familial hypercholesterolemia which results in extremely high level of low density lipoprotein cholesterol (LDL-C) level and the patients who are intolerant or unresponsive to statins are the other hurdles of statin treatment. Recently, new classes of lipid-lowering drugs have been developed and some of them are available for the clinical practice. The pro-protein convertase subtilisin/kexintype 9 (PCSK9) inhibitor increases the expression of low density lipoprotein (LDL) receptor in hepatocytes by enhancing LDL receptor recycling. The microsomal triglyceride transport protein (MTP) inhibitor and antisense oligonucleotide against apolipoprotein B (ApoB) reduce the ApoB containing lipoprotein by blocking the hepatic very low density lipoprotein synthesis pathway. The apolipoprotein A1 (ApoA1) mimetics pursuing the beneficial effect of high density lipoprotein cholesterol and can reverse the course of atherosclerosis. ApoA1 mimetics had many controversial clinical data and need more validation in humans. The PCSK9 inhibitor recently showed promising results of significant LDL-C lowering in familial hypercholesterolemia (FH) patients from the long-term phase III trials. The MTP inhibitor and antisesnse oligonucleotide against ApoB were approved for the treatment of homozygous FH but still needs more consolidated evidences about hepatic safety such as hepatosteatosis. We would discuss the benefits and concerns of these new lipid-lowering drugs anticipating additional benefits beyond statin treatment.

Citations

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Current Antiplatelet Treatment Strategy in Patients with Diabetes Mellitus
Jung Hwa Jung, Udaya S. Tantry, Paul A. Gurbel, Young-Hoon Jeong
Diabetes Metab J. 2015;39(2):95-113.   Published online April 20, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.95
  • 6,525 View
  • 92 Download
  • 31 Web of Science
  • 25 Crossref
AbstractAbstract PDFPubReader   

Patients with diabetes mellitus (DM) have accelerated atherosclerosis with an increased risk for atherothrombotic cardiovascular complications. A state of high platelet reactivity and activation, hypercoagulability (prothrombotic state) and a subdued response to standard antiplatelet agents may explain high rate of adverse cardiovascular events in patients with DM. Several antithrombotic treatment strategies have been developed to control the prothrombotic state in patients with DM: dose modification of commonly used agents; use of potent agents; and addition of a third antithrombotic drug (triple therapy) to commonly prescribed dual antiplatelet therapy of aspirin and a P2Y12 inhibitor. The present review aims to provide an overview of the current knowledge on platelet abnormalities in patients with DM, focusing on the challenges and perspectives of antiplatelet treatment strategies in this population.

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Editorial
How Can We Easily Measure Glycemic Variability in Diabetes Mellitus?
Suk Chon
Diabetes Metab J. 2015;39(2):114-116.   Published online April 20, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.114
  • 2,905 View
  • 30 Download
  • 4 Web of Science
  • 4 Crossref
PDFPubReader   

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Original Articles
The Insulin Resistance but Not the Insulin Secretion Parameters Have Changed in the Korean Population during the Last Decade
Hae Kyung Yang, Jin Hee Lee, In-Young Choi, Hyuk Sang Kwon, Jeong Ah Shin, Seung Hee Jeong, Seung-Hwan Lee, Jae Hyoung Cho, Ho Young Son, Kun Ho Yoon
Diabetes Metab J. 2015;39(2):117-125.   Published online April 20, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.117
  • 4,797 View
  • 47 Download
  • 8 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   
Background

This study aimed to compare the patterns of insulin secretion and resistance between Korean subjects in the 1990s and 2000s.

Methods

Insulin secretion and resistance indices were calculated from subjects who underwent 75-g oral glucose tolerance tests in the year 1997 to 1999 and 2007 to 2011 at the Seoul St. Mary's Hospital, Korea.

Results

A total of 578 subjects from the 1990s (mean age, 48.5 years) and 504 subjects from the 2000s (mean age, 50.2 years) were enrolled. Compared with the subjects from the 1990s, those from the 2000s exhibited increased insulin resistance (increased homeostatic model assessment for insulin resistance), and reduced insulin sensitivity (reduced Matsuda index and quantitative insulin sensitivity check index), regardless of their glucose tolerance status. However, insulinogenic index did not reveal significant differences between the 2 decades in subjects with or without diabetes. A distinct relationship was confirmed between Matsuda index and total area under the curve (insulin/glucose) in each glucose tolerance group. The mean product of the Matsuda index and the total area under the curve (insulin/glucose) as well as the oral disposition index, was lower in subjects with normal glucose tolerance from the 2000s than in those from the 1990s.

Conclusion

After rapid economic growth and changes in lifestyle patterns, insulin resistance has worsened across the glucose tolerance status; however, the insulin secretory function remained unchanged, which resulted in an increase in the susceptibility to the development of type 2 diabetes mellitus among Korean subjects without diabetes. We could not rule out the potential selection bias and therefore, further studies in general Korean population are needed.

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Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea
Chang-Yun Woo, Ji Yun Jeong, Jung Eun Jang, Jaechan Leem, Chang Hee Jung, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Jung Bok Lee, Ki-Up Lee
Diabetes Metab J. 2015;39(2):126-131.   Published online March 9, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.126
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AbstractAbstract PDFPubReader   
Background

Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.

Methods

To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.

Results

Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.

Conclusion

The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

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Selective Immunoglobulin A Deficiency in Type 1 Diabetes Mellitus: A Prevalence Study in Western Sicily (Italy)
Domenico Greco, Filippo Maggio
Diabetes Metab J. 2015;39(2):132-136.   Published online March 10, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.132
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AbstractAbstract PDFPubReader   
Background

The association between type 1 diabetes and immunoglobulin A deficiency (IgA-D) has long been recognized in many populations. The aim of this study was to assess the prevalence of IgA-D in patients with type 1 diabetes mellitus all coming from a defined geographical area and to investigate the clinical features of these subjects.

Methods

The records of 150 consecutive patients with type 1 diabetes mellitus referred in a period of one year were analyzed. A detailed history was obtained for each patient. Information was collected concerning age, gender, time of onset of diabetes, and presence of other autoimmune diseases.

Results

Out of 150 patients with type 1 diabetes, eight (5.3%) had a diagnosis of IgA-D. There were one female and seven male; all these patients were diagnosed by screening: none of them had history of recurrent infections. Autoimmune thyroiditis was coexisting in five patients (62%). Although other associated autoimmune disorders were found in a number of patients, there was no different prevalence rate in IgA deficient patients.

Conclusion

This study shows the prevalence of IgA-D in Sicilian patients with type 1 diabetes as 5.3% which is much higher than reported in other Italian studies. Moreover, our data show a high prevalence of IgA-D in male gender and describe thyroiditis as the most frequent autoimmune disease present in these patients. Finally, in our case report, IgA-D diagnosis always followed routine IgA measurement when case finding for celiac disease with no history of recurrent infections in each patient.

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Low Economic Status Is Identified as an Emerging Risk Factor for Diabetes Mellitus in Korean Men Aged 30 to 59 Years in Korean National Health and Nutrition Examination Survey 2008 to 2010
Bo Kyung Koo, Sang Wan Kim, Ka Hee Yi, Min Kyong Moon
Diabetes Metab J. 2015;39(2):137-146.   Published online March 11, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.137
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AbstractAbstract PDFPubReader   
Background

We compared the association between economic status and the prevalence of diabetes mellitus (DM) using large nationwide datasets covering the previous 10 years in Korea.

Methods

We analyzed the association between economic status and DM using Korean National Health and Nutrition Examination Survey (KNHANES) data from 2001 to 2010 weighted to represent the Korean population between 30 and 59 years of age. The economic status of participants was classified into quartiles according to monthly family income with an equivalence scale.

Results

In men, the prevalence of diabetes in the lowest income quartile (Q1) was significantly higher than that in the other quartiles in 2008 (age and body mass index-adjusted odds ratio [OR], 1.846; 95% confidence interval [CI], 1.126 to 3.027; P=0.015), 2009 (OR, 1.706; 95% CI, 1.094 to 2.661; P=0.019), and 2010 (OR, 1.560; 95% CI, 1.024 to 2.377; P=0.039) but not in 2001 or 2005. The data indicated that classification in the lowest economic status was an independent risk factor for diabetes even after adjusting for abdominal obesity, dyslipidemia, hypertension and education level in men of KNHANES 2008 to 2010. Although economic status was significantly associated with abdominal obesity, hypertriglyceridemia, and hypertension in women (P<0.001), there was no significant association between economic status and DM in women.

Conclusion

Korean men between 30 and 59 years of age with the lowest economic status had a significantly higher prevalence of DM in 2008 to 2010 even after adjusting for other risk factors.

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Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance
Tae Jung Oh, Se Hee Min, Chang Ho Ahn, Eun Ky Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho
Diabetes Metab J. 2015;39(2):147-153.   Published online March 9, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.147
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AbstractAbstract PDFPubReader   
Background

Subjects with normal glucose tolerance (NGT) who have a high 1-hour postload plasma glucose level (≥155 mg/dL; NGT 1 hour-high) have been shown to be at higher risk for type 2 diabetes than subjects with NGT 1 hour-low postload plasma glucose level (<155 mg/dL). We compared β-cell function in subjects with NGT 1 hour-high, NGT 1 hour-low, and impaired glucose tolerance (IGT).

Methods

We classified subjects into NGT 1 hour-low (n=149), NGT 1 hour-high (n=43), and IGT (n=52). The β-cell function was assessed based on insulinogenic index (IGI), oral disposition index (DI), and insulin secretion-sensitivity index-2 (ISSI-2).

Results

Insulin sensitivity was comparable between the subjects with NGT 1 hour-high and NGT 1 hour-low. The β-cell function with/without adjusting insulin sensitivity was significantly different among the three groups. The IGI (pmol/mmol) was 116.8±107.3 vs. 64.8±47.8 vs. 65.8±80.6 (P=0.141), oral DI was 3.5±4.2 vs. 1.8±1.4 vs. 1.8±3.1 (P<0.001), and ISSI-2 was 301.2±113.7 vs. 213.2±67.3 vs. 172.5±87.5 (P<0.001) in NGT 1 hour-low, NGT 1 hour-high, and IGT, respectively. Post hoc analyses revealed that oral DI and ISSI-2 were significantly different between NGT 1 hour-low and NGT 1 hour-high but comparable between NGT 1 hour-high and IGT.

Conclusion

Among Korean subjects with NGT, those who have a higher 1-hour postload glucose level have a compromised insulin-sensitivity adjusted β-cell function to a similar degree as IGT subjects.

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  • Response: Normal Glucose Tolerance with a High 1-Hour Postload Plasma Glucose Level Exhibits Decreased β-Cell Function Similar to Impaired Glucose Tolerance (Diabetes Metab J2015;39:147-53)
    Tae Jung Oh, Se Hee Min, Chang Ho Ahn, Eun Ky Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho
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Intensive Individualized Reinforcement Education Is Important for the Prevention of Hypoglycemia in Patients with Type 2 Diabetes
Yun-Mi Yong, Kyung-Mi Shin, Kang-Min Lee, Jae-Young Cho, Sun-Hye Ko, Min-Hyang Yoon, Tae-Won Kim, Jong-Hyun Jeong, Yong-Moon Park, Seung-Hyun Ko, Yu-Bae Ahn
Diabetes Metab J. 2015;39(2):154-163.   Published online March 10, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.154
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We investigated whether an intensive individualized reinforcement education program could influence the prevention of hypoglycemic events in patients with type 2 diabetes.

Methods

From March 2013 to September 2013, patients aged 35 to 75 years with type 2 diabetes who had not previously participated in diabetes education, and treated with insulin or a sulfonylurea-containing regimen were included in the study. After structured group education, the patients assigned to the intensive individualized education group (IT) were requested to visit for reinforcement. All subjects in the IT were encouraged to self-manage dose adjustments. Participants in both groups (control group [CG, group education only; n=22] and IT [n=24]) attended follow-up visits at 2, 8, 12, and 24 weeks. At each visit, all patients were asked whether they had experienced hypoglycemia.

Results

The total study population consisted of 20 men (43.5%; mean age and diabetic duration of 55.9±11.0 and 5.1±7.3 years, respectively). At 24 weeks, there were no significant differences in hemoglobin A1c values between the CG and IT. The total number of hypoglycemic events per patient was 5.26±6.5 in the CG and 2.58±2.3 times in the IT (P=0.004). Adherence to lifestyle modification including frequency of exercise, self-monitoring of blood glucose, or dietary habit was not significantly different between the groups. However, adherence to hypoglycemia management, especially the dose adjustment of medication, was significantly higher in the IT compared with the CG.

Conclusion

Compared with the structured group education, additional IT resulted in additional benefits in terms of avoidance of hypoglycemia and treating hypoglycemia in patients with type 2 diabetes.

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1,5-Anhydroglucitol as a Useful Marker for Assessing Short-Term Glycemic Excursions in Type 1 Diabetes
Hannah Seok, Ji Hye Huh, Hyun Min Kim, Byung-Wan Lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha
Diabetes Metab J. 2015;39(2):164-170.   Published online March 9, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.164
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AbstractAbstract PDFPubReader   
Background

Type 1 diabetes is associated with more severe glycemic variability and more frequent hypoglycemia than type 2 diabetes. Glycemic variability is associated with poor glycemic control and diabetic complications. In this study, we demonstrate the clinical usefulness of serum 1,5-anhydroglucitol (1,5-AG) for assessing changes in glycemic excursion in type 1 diabetes.

Methods

Seventeen patients with type 1 diabetes were enrolled in this study. A continuous glucose monitoring system (CGMS) was applied twice at a 2-week interval to evaluate changes in glycemic variability. The changes in serum glycemic assays, including 1,5-AG, glycated albumin and hemoglobin A1c (HbA1c), were also evaluated.

Results

Most subjects showed severe glycemic excursions, including hypoglycemia and hyperglycemia. The change in 1,5-AG level was significantly correlated with changes in the glycemic excursion indices of the standard deviation (SD), mean amplitude of glucose excursion (MAGE), lability index, mean postmeal maximum glucose, and area under the curve for glucose above 180 mg/dL (r=-0.576, -0.613, -0.600, -0.630, and -0.500, respectively; all P<0.05). Changes in glycated albumin were correlated with changes in SD and MAGE (r=0.495 and 0.517, respectively; all P<0.05). However, changes in HbA1c were not correlated with any changes in the CGMS variables.

Conclusion

1,5-AG may be a useful marker for the assessment of short-term changes in glycemic variability. Furthermore, 1,5-AG may have clinical implications for the evaluation and treatment of glycemic excursions in type 1 diabetes.

Citations

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Letter
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Erratum
Erratum: Figure Correction. A Gut Feeling to Cure Diabetes: Potential Mechanisms of Diabetes Remission after Bariatric Surgery
Young Min Cho
Diabetes Metab J. 2015;39(2):175-175.   Published online April 20, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.175
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