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Volume 42(3); June 2018
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Review
Epidemiology
The Evidence for an Obesity Paradox in Type 2 Diabetes Mellitus
Seung Jin Han, Edward J. Boyko
Diabetes Metab J. 2018;42(3):179-187.   Published online May 31, 2018
DOI: https://doi.org/10.4093/dmj.2018.0055
  • 6,664 View
  • 123 Download
  • 62 Web of Science
  • 63 Crossref
AbstractAbstract PDFPubReader   

Although overweight/obesity is a major risk factor for the development of type 2 diabetes mellitus, there is increasing evidence that overweight or obese patients with type 2 diabetes mellitus experience lower mortality compared with patients of normal weight. This paradoxical finding, known as the “obesity paradox,” occurs in other chronic diseases, and in type 2 diabetes mellitus is particularly perplexing given that lifestyle intervention with one goal being weight reduction is an important feature of the management of this condition. We summarize in this review the findings from clinical and epidemiologic studies that have investigated the association between overweight and obesity (usually assessed using body mass index [BMI]) and mortality in type 2 diabetes mellitus and discuss potential causes of the obesity paradox. We conclude that most studies show evidence of an obesity paradox, but important conflicting findings still exist. We also evaluate if potential bias might explain the obesity paradox in diabetes, including, for example, the presence of confounding factors, measurement error due to use of BMI as an index of obesity, and reverse causation.

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Sulwon Lecture 2017
Complications
The Role of Advanced Glycation End Products in Diabetic Vascular Complications
Sang Youl Rhee, Young Seol Kim
Diabetes Metab J. 2018;42(3):188-195.   Published online May 31, 2018
DOI: https://doi.org/10.4093/dmj.2017.0105
  • 9,206 View
  • 158 Download
  • 156 Web of Science
  • 155 Crossref
AbstractAbstract PDFPubReader   

In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are actively produced and accumulated in the circulating blood and various tissues. AGEs also accelerate the expression of receptors for AGEs, and they play an important role in the development of diabetic vascular complications through various mechanisms. Active interventions for glucose and related risk factors may help improve the clinical course of patients by reducing AGEs. This review summarizes recent updates on AGEs that have a significant impact on diabetic vascular complications.

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Editorial
Epidemiology
Hidden Risks behind Normal Fasting Glucose: Is It Significant?
Seung-Hwan Lee
Diabetes Metab J. 2018;42(3):196-197.   Published online June 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0083
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PDFPubReader   
Original Articles
Epidemiology
Predictors of Incident Type 2 Diabetes Mellitus in Japanese Americans with Normal Fasting Glucose Level
You-Cheol Hwang, Wilfred Y. Fujimoto, Steven E. Kahn, Donna L. Leonetti, Edward J. Boyko
Diabetes Metab J. 2018;42(3):198-206.   Published online April 25, 2018
DOI: https://doi.org/10.4093/dmj.2017.0100
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AbstractAbstract PDFPubReader   
Background

Little is known about the natural course of normal fasting glucose (NFG) in Asians and the risk factors for future diabetes.

Methods

A total of 370 Japanese Americans (163 men, 207 women) with NFG levels and no history of diabetes, aged 34 to 75 years, were enrolled. Oral glucose tolerance tests were performed at baseline, 2.5, 5, and 10 years after enrollment.

Results

During 10 years of follow-up, 16.1% of participants met criteria for diabetes diagnosis, and 39.6% of subjects still had NFG levels at the time of diabetes diagnosis. During 5 years of follow-up, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01 to 1.10; P=0.026) and family history of diabetes (OR, 3.24; 95% CI, 1.42 to 7.40; P=0.005) were independently associated with future diabetes diagnosis; however, fasting glucose level was not an independent predictor. During 10 years of follow-up, family history of diabetes (OR, 2.76; 95% CI, 1.37 to 5.54; P=0.004), fasting insulin level (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.037), and fasting glucose level (OR, 3.69; 95% CI, 1.13 to 12.01; P=0.030) were associated with diabetes diagnosis independent of conventional risk factors for diabetes.

Conclusion

A substantial number of subjects with NFG at baseline still remained in the NFG range at the time of diabetes diagnosis. A family history of diabetes and fasting insulin and glucose levels were associated with diabetes diagnosis during 10 years of follow-up; however, fasting glucose level was not associated with diabetes risk within the relatively short-term follow-up period of 5 years in subjects with NFG.

Citations

Citations to this article as recorded by  
  • J-shape relationship between normal fasting plasma glucose and risk of type 2 diabetes in the general population: results from two cohort studies
    Linfeng He, Wenbin Zheng, Zeyu Li, Lu Chen, Wen Kong, Tianshu Zeng
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Complications
Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome
Kwi-Hyun Bae, Sung Woo Kim, Yeon-Kyung Choi, Jung Beom Seo, Namkyun Kim, Chang-Yeon Kim, Won Kee Lee, Sungwoo Lee, Jung Guk Kim, In-Kyu Lee, Jang Hoon Lee, Keun-Gyu Park
Diabetes Metab J. 2018;42(3):207-214.   Published online May 2, 2018
DOI: https://doi.org/10.4093/dmj.2017.0081
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  • 54 Download
  • 25 Web of Science
  • 23 Crossref
AbstractAbstract PDFPubReader   
Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown.

Methods

From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated.

Results

Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores.

Conclusion

Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.

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    Diabetes & Metabolism Journal.2018; 42(4): 348.     CrossRef
  • Response: Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome (Diabetes Metab J 2018;42:207-14)
    Sung Woo Kim, Keun-Gyu Park
    Diabetes & Metabolism Journal.2018; 42(4): 350.     CrossRef
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Complications
Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease
Ji Hye Huh, Minyoung Lee, So Young Park, Jae Hyeon Kim, Byung-Wan Lee
Diabetes Metab J. 2018;42(3):215-223.   Published online May 2, 2018
DOI: https://doi.org/10.4093/dmj.2017.0091
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AbstractAbstract PDFPubReader   
Background

The aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR).

Methods

We classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters.

Results

Subjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213, P=0.016), but not with HbA1c (β=−0.137, P=0.096) or stimulated glucose (β=0.095, P=0.140) after adjusting confounding factors. In receiver operating characteristic analysis, the value of the area under the curve (AUC) for renal tubular injury of GA was significantly higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI, 0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%, specificity 62%).

Conclusion

GA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.

Citations

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  • Glucagon-Like Peptide 1 Receptor Agonist Improves Renal Tubular Damage in Mice with Diabetic Kidney Disease
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Complications
Higher Prevalence and Progression Rate of Chronic Kidney Disease in Elderly Patients with Type 2 Diabetes Mellitus
Kyung-Soo Kim, Seok Won Park, Yong-Wook Cho, Soo-Kyung Kim
Diabetes Metab J. 2018;42(3):224-232.   Published online May 31, 2018
DOI: https://doi.org/10.4093/dmj.2017.0065
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AbstractAbstract PDFPubReader   
Background

To evaluate the prevalence of chronic kidney disease (CKD) and progression rate to CKD in elderly patients with type 2 diabetes mellitus (T2DM).

Methods

We investigated the medical records of 190 elderly patients (65 years or older) with T2DM from 2005 to 2011 in 6-month increments. Mean follow-up duration was 64.5 months. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or the presence of albuminuria.

Results

The mean age was 70.4 years and mean diabetes duration was 10.6 years. Among all the participants, 113 patients (59.5%) had CKD. The eGFR was significantly decreased between baseline (65.7±15.0 mL/min/1.73 m2) and the end of follow-up (52.7±17.5 mL/min/1.73 m2, P<0.001). At the end of follow-up, the prevalence of eGFR <60 mL/min/1.73 m2 had increased by 61.6% (at baseline, 44.2%). Furthermore, in patients with eGFR ≥60 mL/min/1.73 m2, the progression rate to more than CKD stage 3 was 39.6% at the end of follow-up; 30.2% of elderly diabetic patients had progressed to albuminuria from normoalbuminuria. Kaplan-Meier analysis showed that the time interval to worsening nephropathy was significantly shorter in elderly patients with diabetes duration ≥10 years than in those with diabetes duration <5 years (P=0.018).

Conclusion

CKD was commonly observed in older patients with T2DM, and the progression rate to CKD is also high. Consequently, it is important to identify and manage CKD as early as possible in elderly patients with T2DM, especially in those with diabetes duration ≥10 years.

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Obesity and Metabolic Syndrome
Inhibition of Serotonin Synthesis Induces Negative Hepatic Lipid Balance
Jun Namkung, Ko Eun Shong, Hyeongseok Kim, Chang-Myung Oh, Sangkyu Park, Hail Kim
Diabetes Metab J. 2018;42(3):233-243.   Published online April 25, 2018
DOI: https://doi.org/10.4093/dmj.2017.0084
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AbstractAbstract PDFPubReader   
Background

Hepatic steatosis is caused by metabolic stress associated with a positive lipid balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid accumulation. Here, we showed the possibility of direct action of serotonin on hepatic steatosis.

Methods

Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 to inhibit serotonin synthesis and fed with high fat diet (HFD) or high carbohydrate diet (HCD) to induce hepatic steatosis. Hepatic triglyceride content and gene expression profiles were analyzed.

Results

Pharmacological and genetic inhibition of serotonin synthesis reduced HFD-induced hepatic lipid accumulation. Furthermore, short-term PCPA treatment prevented HCD-induced hepatic steatosis without affecting glucose tolerance and browning of subcutaneous adipose tissue. Gene expression analysis revealed that the expressions of genes involved in de novo lipogenesis and triacylglycerol synthesis were downregulated by short-term PCPA treatment as well as long-term PCPA treatment.

Conclusion

Short-term inhibition of serotonin synthesis prevented hepatic lipid accumulation without affecting systemic insulin sensitivity and energy expenditure, suggesting the direct steatogenic effect of serotonin in liver.

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Short Communication
Others
Synthesis of a New Zinc-Mixed Ligand Complex and Evaluation of Its Antidiabetic Properties in High Fat Diet: Low Dose Streptozotocin Induced Diabetic Rats
Muruganantham Koothappan, Roshana Devi Vellai, Iyyam Pillai Subramanian, Sorimuthu Pillai Subramanian
Diabetes Metab J. 2018;42(3):244-248.   Published online April 24, 2018
DOI: https://doi.org/10.4093/dmj.2018.0002
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AbstractAbstract PDFPubReader   

Due to the multifactorial and multisystemic nature of diabetes mellitus, it is often treated with a combination of therapeutic agents having different mode of action. Earlier, we have synthesized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental type 2 diabetes mellitus (T2DM). More recently, we have synthesized a metformin-3-hydroxyflavone complex and studied its antidiabetic efficacy in experimental rats. In the present study, a new zinc-mixed ligand (metformin-3-hydroxyflavone) was synthesized, characterized by spectral studies and its antidiabetic properties was evaluated in HFD fed—low dose streptozotocin induced T2DM in rats. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and by determining the status of important biochemical parameters. Oral administration of the complex at a concentration of 10 mg/kg body weight/rat/day for 30 days significantly improved the glucose homeostasis. The complex possesses significant antidiabetic properties relatively at a less concentration than metformin-3-hydroxyflavone complex in ameliorating hyperglycemia.

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Letter
Letter: Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes between 2015 and 2016: Difference by Age and Body Mass Index (Diabetes Metab J 2018;42:137-46)
Ah Reum Khang
Diabetes Metab J. 2018;42(3):249-250.   Published online June 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0074
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Response
Response: Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes between 2015 and 2016: Difference by Age and Body Mass Index (Diabetes Metab J 2018;42:137-46)
Kyoung Hwa Ha, Dae Jung Kim, Sungrae Kim
Diabetes Metab J. 2018;42(3):251-253.   Published online June 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0099
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Corrigendum
Corrigendum: Hemorheologic Alterations in Patients with Type 2 Diabetes Mellitus Presented with an Acute Myocardial Infarction
Kyu-Hwan Park, Ung Kim, Kang-Un Choi, Jong-Ho Nam, Jung-Hee Lee, Chan-Hee Lee, Jang-Won Son, Jong-Seon Park, Dong-Gu Shin, Kyu-Chang Won, Jun Sung Moon, Yu Kyung Kim, Jang-Soo Suh
Diabetes Metab J. 2018;42(3):254-254.   Published online June 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0096
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Diabetes Metab J : Diabetes & Metabolism Journal