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Volume 43(2); April 2019
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Reviews
Clinical Diabetes & Therapeutics
Nonalcoholic Fatty Liver Disease and Diabetes: Part II: Treatment
Kyung-Soo Kim, Byung-Wan Lee, Yong Jin Kim, Dae Ho Lee, Bong-Soo Cha, Cheol-Young Park
Diabetes Metab J. 2019;43(2):127-143.   Published online April 15, 2019
DOI: https://doi.org/10.4093/dmj.2019.0034
  • 8,915 View
  • 164 Download
  • 28 Web of Science
  • 37 Crossref
AbstractAbstract PDFPubReader   

Nonalcoholic fatty liver disease (NAFLD) and diabetes are common metabolic disorders that are often comorbid conditions. Among many proposed treatments, weight reduction is the only approved option for NAFLD to date. However, it is not easy to maintain weight loss by lifestyle modification alone; pharmacological treatments are helpful in this regard. Although many drugs have been investigated, pioglitazone could be a first-line therapy in patients with NAFLD and diabetes. Many more drugs are currently being developed and investigated, and it is likely that combination strategies will be used for future treatment of NAFLD and diabetes. Attention should be paid to the management of NAFLD and diabetes and efforts should be made to intervene early and individualize treatment of NAFLD in patients with diabetes.

Citations

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  • Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
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  • Diabetes and Metabolism Journal in 2020: Good to Great
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  • Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association
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  • Effects of sodium–glucose cotransporter 2 inhibitors on non‐alcoholic fatty liver disease in patients with type 2 diabetes: A meta‐analysis of randomized controlled trials
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  • Empaglifozin mitigates NAFLD in high-fat-fed mice by alleviating insulin resistance, lipogenesis and ER stress
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Obesity and Metabolic Syndrome
Metabolic Consequences of Obstructive Sleep Apnea Especially Pertaining to Diabetes Mellitus and Insulin Sensitivity
Sun Ok Song, Ken He, Radhika R. Narla, Hyun Goo Kang, Han Uk Ryu, Edward J. Boyko
Diabetes Metab J. 2019;43(2):144-155.   Published online April 15, 2019
DOI: https://doi.org/10.4093/dmj.2018.0256
  • 8,775 View
  • 171 Download
  • 51 Web of Science
  • 52 Crossref
AbstractAbstract PDFPubReader   

Obstructive sleep apnea (OSA) and diabetes has been known to be closely related to each other and both diseases impact highly on the public health. There are many evidence of reports that OSA is associated with diabetes with a bidirectional correlation. A possible causal mechanism of OSA to diabetes is intermittent hypoxemia and diabetes to OSA is microvascular complication. However, OSA and diabetes have a high prevalence rate in public and shares the common overlap characteristic and risk factors such as age, obesity, and metabolic syndrome that make it difficult to establish the exact pathophysiologic mechanism between them. In addition, studies demonstrating that treatment of OSA may help prevent diabetes or improve glycemic control have not shown convincing result but have become a great field of interest research. This review outlines the bidirectional correlation between OSA and diabetes and explore the pathophysiologic mechanisms by approaching their basic etiologies.

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Editorial
Obesity and Metabolic Syndrome
Simply the Best: Anthropometric Indices for Predicting Cardiovascular Disease
Jie-Eun Lee
Diabetes Metab J. 2019;43(2):156-157.   Published online April 15, 2019
DOI: https://doi.org/10.4093/dmj.2019.0057
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    Qingqing Zhan, Qinyu An, Fuyan Zhang, Tianlin Zhang, Tao Liu, Yiying Wang
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  • Physical performance and glycemic control under SGLT-2-inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular diseases or high cardiovascular risk (PUSH): Design of a 4-week prospective observational study
    Devine S. Frundi, Eva Kettig, Lena Luise Popp, Melanie Hoffman, Marine Dumartin, Magali Hughes, Edgar Lamy, Yvonne Joko Walburga Fru, Arjola Bano, Taulant Muka, Matthias Wilhelm
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Original Articles
Clinical Diabetes & Therapeutics
Predictors of the Therapeutic Efficacy and Consideration of the Best Combination Therapy of Sodium-Glucose Co-transporter 2 Inhibitors
Ji-Yeon Lee, Yongin Cho, Minyoung Lee, You Jin Kim, Yong-ho Lee, Byung-Wan Lee, Bong-Soo Cha, Eun Seok Kang
Diabetes Metab J. 2019;43(2):158-173.   Published online January 25, 2019
DOI: https://doi.org/10.4093/dmj.2018.0057
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We investigated the predictive markers for the therapeutic efficacy and the best combination of sodium-glucose co-transporter 2 (SGLT2) inhibitors (empagliflozin, dapagliflozin, and ipragliflozin) therapy in patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 804 patients with T2DM who had taken SGLT2 inhibitor as monotherapy or an add-on therapy were analyzed. Multivariate regression analyses were performed to identify the predictors of SGLT2 inhibitor response including the classes of baseline anti-diabetic medications.

Results

After adjusting for age, sex, baseline body mass index (BMI), diabetes duration, duration of SGLT2 inhibitor use, initial glycosylated hemoglobin (HbA1c) level, estimated glomerular filtration rate (eGFR), and other anti-diabetic agent usage, multivariate analysis revealed that shorter diabetes duration, higher initial HbA1c and eGFR were associated with better glycemic response. However, baseline BMI was inversely correlated with glycemic status; lean subjects with well-controlled diabetes and obese subjects with inadequately controlled diabetes received more benefit from SGLT2 inhibitor treatment. In addition, dipeptidyl peptidase 4 (DPP4) inhibitor use was related to a greater reduction in HbA1c in patients with higher baseline HbA1c ≥7%. Sulfonylurea users experienced a larger change from baseline HbA1c but the significance was lost after adjustment for covariates and metformin and thiazolidinedione use did not affect the glycemic outcome.

Conclusion

A better response to SGLT2 inhibitors is expected in Korean T2DM patients who have higher baseline HbA1c and eGFR with a shorter diabetes duration. Moreover, the add-on of an SGLT2 inhibitor to a DPP4 inhibitor is likely to show the greatest glycemic response.

Citations

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  • Predictors of efficacy of Sodium‐GLucose Transporter‐2 inhibitors and Glucagon‐Like Peptide 1 receptor agonists: A retrospective cohort study
    Daniele Scoccimarro, Giacomo Cipani, Ilaria Dicembrini, Edoardo Mannucci
    Diabetes/Metabolism Research and Reviews.2024;[Epub]     CrossRef
  • Short-term effectiveness of dapagliflozin versus DPP-4 inhibitors in elderly patients with type 2 diabetes: a multicentre retrospective study
    M. L. Morieri, I. Raz, A. Consoli, M. Rigato, A. Lapolla, F. Broglio, E. Bonora, A. Avogaro, G. P. Fadini, Federica Ginestra, Gloria Formoso, Agostino Consoli, Francesco Andreozzi, Giorgio Sesti, Salvatore Turco, Luigi Lucibelli, Adriano Gatti, Raffaella
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  • Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review
    Katherine G. Young, Eram Haider McInnes, Robert J. Massey, Anna R. Kahkoska, Scott J. Pilla, Sridharan Raghavan, Maggie A. Stanislawski, Deirdre K. Tobias, Andrew P. McGovern, Adem Y. Dawed, Angus G. Jones, Ewan R. Pearson, John M. Dennis, Deirdre K. Tobi
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  • Angiotensin II up-regulates sodium-glucose co-transporter 2 expression and SGLT2 inhibitor attenuates Ang II-induced hypertensive renal injury in mice
    Kana N. Miyata, Chao-Sheng Lo, Shuiling Zhao, Min-Chun Liao, Yuchao Pang, Shiao-Ying Chang, Junzheng Peng, Matthias Kretzler, Janos G. Filep, Julie R. Ingelfinger, Shao-Ling Zhang, John S.D. Chan
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  • Sodium-Glucose Cotransporter-2 Inhibitor for Renal Function Preservation in Patients with Type 2 Diabetes Mellitus: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement
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Epidemiology
Discrepancies between Glycosylated Hemoglobin and Fasting Plasma Glucose for Diagnosing Impaired Fasting Glucose and Diabetes Mellitus in Korean Youth and Young Adults
Jieun Lee, Young Ah Lee, Jae Hyun Kim, Seong Yong Lee, Choong Ho Shin, Sei Won Yang
Diabetes Metab J. 2019;43(2):174-182.   Published online November 2, 2018
DOI: https://doi.org/10.4093/dmj.2018.0046
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Glycosylated hemoglobin (HbA1c) has been recommended as a diagnostic test for prediabetes and diabetes. Here, we evaluated the level of agreement between diagnoses based on fasting plasma glucose (FPG) versus HbA1c levels and determined optimal HbA1c cutoff values for these diseases in youth and young adults.

Methods

The study included 7,332 subjects (n=4,129, aged 10 to 19 years in youth group; and n=3,203 aged 20 to 29 years in young adult group) from the 2011 to 2016 Korea National Health and Nutrition Examination Survey. Prediabetes and diabetes were defined as 100 to 125 mg/dL (impaired fasting glucose [IFG]) and ≥126 mg/dL for FPG (diabetes mellitus [DM] by FPG [DMFPG]), and 5.7% to 6.4% and ≥6.5% for HbA1c, respectively.

Results

In the youth group, 32.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 72.2% with DMFPG had an HbA1c ≥6.5%. In the young adult group, 27.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 66.6% with DMFPG had an HbA1c ≥6.5%. Kappa coefficients for agreement between the FPG and HbA1c results were 0.12 for the youth group and 0.19 for the young adult group. In receiver operating characteristic curve analysis, the optimal HbA1c cutoff for IFG and DMFPG were 5.6% and 5.9% in youths and 5.5% and 5.8% in young adults, respectively.

Conclusion

Usefulness of HbA1c for diagnosis of IFG and DMFPG in Koreans aged <30 years remains to be determined due to discrepancies between the results of glucose- and HbA1c-based tests. Additional testing might be warranted at lower HbA1c levels to detect IFG and DMFPG in this age group.

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Epidemiology
Association between Changes in Anthropometric Indices and in Fasting Insulin Levels among Healthy Korean Adolescents: The JS High School Study
Ji Hye Park, Seyeon Mun, Dong Phil Choi, Joo Young Lee, Hyeon Chang Kim
Diabetes Metab J. 2019;43(2):183-191.   Published online January 22, 2019
DOI: https://doi.org/10.4093/dmj.2018.0034
Correction in: Diabetes Metab J 2022;46(1):164
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

This study investigated the association between changes in anthropometric indices and fasting insulin levels among healthy adolescents and whether the association differed by baseline obesity status.

Methods

This analysis was based on data collected for the JS High School study; 884 healthy adolescents aged 15 to 16 years followed up for 24 to 30 months were included. Changes in anthropometric indices and fasting insulin levels were computed as the difference between baseline and follow-up values. Multivariate linear regression models were used to determine the association between changes in anthropometric indices and fasting insulin levels. Based on body mass index (BMI)-for-age and waist circumference (WC)-for-age percentiles, participants were classified as normal weight (<85th percentile), overweight (85th percentile to <95th percentile), or obese (≥95th percentile).

Results

Changes in BMI, WC, waist-hip ratio, and waist-height ratio were significantly associated with changes in fasting insulin levels in both sexes (P<0.05). In analyses stratified by baseline obesity status, the association between change in BMI and change in fasting insulin was significantly stronger in overweight (males: standardized β=1.136; females: standardized β=1.262) and obese (males: standardized β=1.817; females: standardized β=2.290) participants than in those with normal weight (males: standardized β=0.957; females: standardized β=0.976) at baseline. Results were similar for changes in WC.

Conclusion

Changes in anthropometric indices were positively associated with fasting insulin level increases. Moreover, those who were overweight or obese at baseline had a higher absolute increase in fasting insulin levels per one standard deviation unit increase in anthropometric indices than adolescents with normal weight.

Citations

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  • Rice-based breakfast improves fasting glucose and HOMA-IR in Korean adolescents who skip breakfast, but breakfast skipping increases aromatic amino acids associated with diabetes prediction in Korean adolescents who skip breakfast: a randomized, parallel-
    Hyun Suk Kim, Su-Jin Jung, Soyoung Jang, Min Jung Kim, Youn-Soo Cha
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Islet Studies and Transplantation
Myricetin Protects Against High Glucose-Induced β-Cell Apoptosis by Attenuating Endoplasmic Reticulum Stress via Inactivation of Cyclin-Dependent Kinase 5
Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Jae-Han Jeon, Nam Doo Kim, Keun-Gyu Park, Kyu Chang Won, Jaechan Leem, In-Kyu Lee
Diabetes Metab J. 2019;43(2):192-205.   Published online January 16, 2019
DOI: https://doi.org/10.4093/dmj.2018.0052
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Chronic hyperglycemia has deleterious effects on pancreatic β-cell function and turnover. Recent studies support the view that cyclin-dependent kinase 5 (CDK5) plays a role in β-cell failure under hyperglycemic conditions. However, little is known about how CDK5 impair β-cell function. Myricetin, a natural flavonoid, has therapeutic potential for the treatment of type 2 diabetes mellitus. In this study, we examined the effect of myricetin on high glucose (HG)-induced β-cell apoptosis and explored the relationship between myricetin and CDK5.

Methods

To address this question, we subjected INS-1 cells and isolated rat islets to HG conditions (30 mM) in the presence or absence of myricetin. Docking studies were conducted to validate the interaction between myricetin and CDK5. Gene expression and protein levels of endoplasmic reticulum (ER) stress markers were measured by real-time reverse transcription polymerase chain reaction and Western blot analysis.

Results

Activation of CDK5 in response to HG coupled with the induction of ER stress via the down regulation of sarcoendoplasmic reticulum calcium ATPase 2b (SERCA2b) gene expression and reduced the nuclear accumulation of pancreatic duodenal homeobox 1 (PDX1) leads to β-cell apoptosis. Docking study predicts that myricetin inhibit CDK5 activation by direct binding in the ATP-binding pocket. Myricetin counteracted the decrease in the levels of PDX1 and SERCA2b by HG. Moreover, myricetin attenuated HG-induced apoptosis in INS-1 cells and rat islets and reduce the mitochondrial dysfunction by decreasing reactive oxygen species production and mitochondrial membrane potential (Δψm) loss.

Conclusion

Myricetin protects the β-cells against HG-induced apoptosis by inhibiting ER stress, possibly through inactivation of CDK5 and consequent upregulation of PDX1 and SERCA2b.

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Obesity and Metabolic Syndrome
The Risk of Myocardial Infarction and Ischemic Stroke According to Waist Circumference in 21,749,261 Korean Adults: A Nationwide Population-Based Study
Jung-Hwan Cho, Eun-Jung Rhee, Se-Eun Park, Hyemi Kwon, Jin-Hyung Jung, Kyung-Do Han, Yong-Gyu Park, Hye Soon Park, Yang-Hyun Kim, Soon-Jib Yoo, Won-Young Lee
Diabetes Metab J. 2019;43(2):206-221.   Published online December 27, 2018
DOI: https://doi.org/10.4093/dmj.2018.0039
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  • 24 Web of Science
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

Waist circumference (WC) is a well-known obesity index that predicts cardiovascular disease (CVD). We studied the relationship between baseline WC and development of incident myocardial infarction (MI) and ischemic stroke (IS) using a nationwide population-based cohort, and evaluated if its predictability is better than body mass index (BMI).

Methods

Our study included 21,749,261 Koreans over 20 years of age who underwent the Korean National Health Screening between 2009 and 2012. The occurrence of MI or IS was investigated until the end of 2015 using National Health Insurance Service data.

Results

A total of 127,289 and 181,637 subjects were newly diagnosed with MI and IS. The incidence rate and hazard ratio of MI and IS increased linearly as the WC level increased, regardless of adjustment for BMI. When the analyses were performed according to 11 groups of WC, the lowest risk of MI was found in subjects with WC of 70 to 74.9 and 65 to 69.9 cm in male and female, and the lowest risk of IS in subjects with WC of 65 to 69.9 and 60 to 64.9 cm in male and female, respectively. WC showed a better ability to predict CVD than BMI with smaller Akaike information criterion. The optimal WC cutoffs were 84/78 cm for male/female for predicting MI, and 85/78 cm for male/female for predicting IS.

Conclusion

WC had a significant linear relationship with the risk of MI and IS and the risk began to increase from a WC that was lower than expected.

Citations

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Others
Increased Nociceptive Responses in Streptozotocin-Induced Diabetic Rats and the Related Expression of Spinal NR2B Subunit of N-Methyl-D-Aspartate Receptors
Che Aishah Nazariah Ismail, Rapeah Suppian, Che Badariah Abd Aziz, Khalilah Haris, Idris Long
Diabetes Metab J. 2019;43(2):222-235.   Published online November 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0020
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AbstractAbstract PDFPubReader   
Background

This study investigated the role of NR2B in a modulated pain process in the painful diabetic neuropathy (PDN) rat using various pain stimuli.

Methods

Thirty-two Sprague-Dawley male rats were randomly allocated into four groups (n=8): control, diabetes mellitus (DM) rats and diabetic rats treated with ifenprodil at a lower dose (0.5 µg/day) (I 0.5) or higher dose (1.0 µg/day) (I 1.0). DM was induced by a single injection of streptozotocin at 60 mg/kg on day 0 of experimentation. Diabetic status was assessed on day 3 of the experimentation. The responses on both tactile and thermal stimuli were assessed on day 0 (baseline), day 14 (pre-intervention), and day 22 (post-intervention). Ifenprodil was given intrathecally for 7 days from day 15 until day 21. On day 23, 5% formalin was injected into the rats' hind paw and the nociceptive responses were recorded for 1 hour. The rats were sacrificed 72 hours post-formalin injection and an analysis of the spinal NR2B expression was performed.

Results

DM rats showed a significant reduction in pain threshold in response to the tactile and thermal stimuli and higher nociceptive response during the formalin test accompanied by the higher expression of phosphorylated spinal NR2B in both sides of the spinal cord. Ifenprodil treatment for both doses showed anti-allodynic and anti-nociceptive effects with lower expression of phosphorylated and total spinal NR2B.

Conclusion

We suggest that the pain process in the streptozotocin-induced diabetic rat that has been modulated is associated with the higher phosphorylation of the spinal NR2B expression in the development of PDN, which is similar to other models of neuropathic rats.

Citations

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Short Communication
Epidemiology
Associations between Breastfeeding and Type 2 Diabetes Mellitus and Glycemic Control in Parous Women: A Nationwide, Population-Based Study
Ga Eun Nam, Kyungdo Han, Do-Hoon Kim, Youn Huh, Byoungduck Han, Sung Jung Cho, Yong Gyu Park, Yong-Moon Park
Diabetes Metab J. 2019;43(2):236-241.   Published online December 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0044
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AbstractAbstract PDFPubReader   

We investigated associations between breastfeeding duration and number of children breastfed and type 2 diabetes mellitus (T2DM) and glycemic control among parous women. We performed a cross-sectional analysis of data for 9,960 parous women from the Korea National Health and Nutritional Examination Survey (2010 to 2013). Having ever breastfed was inversely associated with prevalent T2DM (adjusted odds ratio [OR], 0.60; 95% confidence interval [CI], 0.42 to 0.87). All ranges of total and average breastfeeding duration showed inverse associations with T2DM. Even short periods of breastfeeding were inversely associated with T2DM (adjusted OR, 0.61; 95% CI, 0.38 to 0.99 for a total breastfeeding duration ≤12 months; adjusted OR, 0.65; 95% CI, 0.42 to 0.99 for an average breastfeeding duration per child ≤6 months). A longer duration of breastfeeding was associated with better glycemic control in parous women with T2DM (P trend=0.004 for total breastfeeding duration; P trend <0.001 for average breastfeeding duration per child). Breastfeeding may be associated with a lower risk of T2DM and good glycemic control in parous women with T2DM. Breastfeeding may be a feasible method to prevent T2DM and improve glycemic control.

Citations

Citations to this article as recorded by  
  • Association of Childbirth and Breastfeeding with Diabetes Mellitus in Korean Women
    Seulkee Kim, So Yeon Ryu
    Journal of Health Informatics and Statistics.2024; 49(2): 109.     CrossRef
  • Integration of nutrigenomics, melatonin, serotonin and inflammatory cytokines in the pathophysiology of pregnancy-specific urinary incontinence in women with gestational diabetes mellitus
    Danielle Cristina Honorio França, Eduardo Luzía França, Luis Sobrevia, Angélica Mércia Pascon Barbosa, Adenilda Cristina Honorio-França, Marilza Vieira Cunha Rudge
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  • Association of lactation with maternal risk of type 2 diabetes: A systematic review and meta‐analysis of observational studies
    Ana‐Catarina Pinho‐Gomes, Georgia Morelli, Alexandra Jones, Mark Woodward
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    Laura T. Dickens, Celeste C. Thomas
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Letter
Response
Response: Projection of Diabetes Prevalence in Korean Adults for the Year 2030 Using Risk Factors Identified from National Data (Diabetes Metab J 2019;43:90–6)
Inkyung Baik
Diabetes Metab J. 2019;43(2):244-245.   Published online April 15, 2019
DOI: https://doi.org/10.4093/dmj.2019.0060
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  • 41 Download
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PDFPubReader   

Citations

Citations to this article as recorded by  
  • Machine Learning Based Diabetes Classification and Prediction for Healthcare Applications
    Umair Muneer Butt, Sukumar Letchmunan, Mubashir Ali, Fadratul Hafinaz Hassan, Anees Baqir, Hafiz Husnain Raza Sherazi, Daniel Espino
    Journal of Healthcare Engineering.2021; 2021: 1.     CrossRef

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