Diabetes & Metabolism Journal

Original Articles

Cardiovascular Risk/Epidemiology
Glycemic Control and Adverse Clinical Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: Results from KNOW-CKD: Ga Young Heo, Hee Byung Koh, Hyung Woo Kim, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Jayoun Kim, Soo Wan Kim, Yeong Hoon Kim, Su Ah Sung, Kook-Hwan Oh, Seung Hyeok Han; Diabetes Metab J. 2023;47(4):535-546. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0112

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Background
The optimal level of glycosylated hemoglobin (HbA1c) to prevent adverse clinical outcomes is unknown in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).
Methods
We analyzed 707 patients with CKD G1-G5 without kidney replacement therapy and T2DM from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort study. The main predictor was time-varying HbA1c level at each visit. The primary outcome was a composite of development of major adverse cardiovascular events (MACEs) or all-cause mortality. Secondary outcomes included the individual endpoint of MACEs, all-cause mortality, and CKD progression. CKD progression was defined as a ≥50% decline in the estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.
Results
During a median follow-up of 4.8 years, the primary outcome occurred in 129 (18.2%) patients. In time-varying Cox model, the adjusted hazard ratios (aHRs) for the primary outcome were 1.59 (95% confidence interval [CI], 1.01 to 2.49) and 1.99 (95% CI, 1.24 to 3.19) for HbA1c levels of 7.0%–7.9% and ≥8.0%, respectively, compared with <7.0%. Additional analysis of baseline HbA1c levels yielded a similar graded association. In secondary outcome analyses, the aHRs for the corresponding HbA1c categories were 2.17 (95% CI, 1.20 to 3.95) and 2.26 (95% CI, 1.17 to 4.37) for MACE, and 1.36 (95% CI, 0.68 to 2.72) and 2.08 (95% CI, 1.06 to 4.05) for all-cause mortality. However, the risk of CKD progression did not differ between the three groups.
Conclusion
This study showed that higher HbA1c levels were associated with an increased risk of MACE and mortality in patients with CKD and T2DM.

Citations

Citations to this article as recorded by

The Beneficial Effect of Glycemic Control against Adverse Outcomes in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease
Dong-Hwa Lee
Diabetes & Metabolism Journal.2023; 47(4): 484. CrossRef
Prevalence and predictors of chronic kidney disease among type 2 diabetic patients worldwide, systematic review and meta-analysis
Eneyew Talie Fenta, Habitu Birhan Eshetu, Natnael Kebede, Eyob Ketema Bogale, Amare Zewdie, Tadele Derbew Kassie, Tadele Fentabil Anagaw, Elyas Melaku Mazengia, Sintayehu Shiferaw Gelaw
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
Efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus: a Bayesian network meta-analysis
Miao Zhu, Ruifang Guan, Guo Ma
Frontiers in Endocrinology.2023;[Epub] CrossRef

Type 1 Diabetes
Abnormal Responses in Cognitive Impulsivity Circuits Are Associated with Glycosylated Hemoglobin Trajectories in Type 1 Diabetes Mellitus and Impaired Metabolic Control: Helena Jorge, Isabel C. Duarte, Sandra Paiva, Ana Paula Relvas, Miguel Castelo-Branco; Diabetes Metab J. 2022;46(6):866-878. Published online March 22, 2022; DOI: https://doi.org/10.4093/dmj.2021.0307

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Background
Risky health decisions and impulse control profiles may impact on metabolic control in type 1 diabetes mellitus (T1DM). We hypothesize that the neural correlates of cognitive impulsivity and decision-making in T1DM relate to metabolic control trajectories.
Methods
We combined functional magnetic resonance imaging (fMRI), measures of metabolic trajectories (glycosylated hemoglobin [HbA1c] over multiple time points) and behavioral assessment using a cognitive impulsivity paradigm, the Balloon Analogue Risk Task (BART), in 50 participants (25 T1DM and 25 controls).
Results
Behavioral results showed that T1DM participants followed a rigid conservative risk strategy along the iterative game. Imaging group comparisons showed that patients showed larger activation of reward related, limbic regions (nucleus accumbens, amygdala) and insula (interoceptive saliency network) in initial game stages. Upon game completion differences emerged in relation to error monitoring (anterior cingulate cortex [ACC]) and inhibitory control (inferior frontal gyrus). Importantly, activity in the saliency network (ACC and insula), which monitors interoceptive states, was related with metabolic trajectories, which was also found for limbic/reward networks. Parietal and posterior cingulate regions activated both in controls and patients with adaptive decision-making, and positively associated with metabolic trajectories.
Conclusion
We found triple converging evidence when comparing metabolic trajectories, patients versus controls or risk averse (non-learners) versus patients who learned by trial and error. Dopaminergic reward and saliency (interoceptive and error monitoring) circuits show a tight link with impaired metabolic trajectories and cognitive impulsivity in T1DM. Activity in parietal and posterior cingulate are associated with adaptive trajectories. This link between reward-saliency-inhibition circuits suggests novel strategies for patient management.

Citations

Citations to this article as recorded by

Glycated hemoglobin, type 2 diabetes, and poor diabetes control are positively associated with impulsivity changes in aged individuals with overweight or obesity and metabolic syndrome
Carlos Gómez‐Martínez, Nancy Babio, Lucía Camacho‐Barcia, Jordi Júlvez, Stephanie K. Nishi, Zenaida Vázquez, Laura Forcano, Andrea Álvarez‐Sala, Aida Cuenca‐Royo, Rafael de la Torre, Marta Fanlo‐Maresma, Susanna Tello, Dolores Corella, Alejandro Arias Vás
Annals of the New York Academy of Sciences.2024;[Epub] CrossRef
The usefulness of an intervention with a serious video game as a complementary approach to cognitive behavioural therapy in eating disorders: A pilot randomized clinical trial for impulsivity management
Cristina Vintró‐Alcaraz, Núria Mallorquí‐Bagué, María Lozano‐Madrid, Giulia Testa, Roser Granero, Isabel Sánchez, Janet Treasure, Susana Jiménez‐Murcia, Fernando Fernández‐Aranda
European Eating Disorders Review.2023; 31(6): 781. CrossRef
Adaptations of the balloon analog risk task for neuroimaging settings: a systematic review
Charline Compagne, Juliana Teti Mayer, Damien Gabriel, Alexandre Comte, Eloi Magnin, Djamila Bennabi, Thomas Tannou
Frontiers in Neuroscience.2023;[Epub] CrossRef
Trust-based health decision-making recruits the neural interoceptive saliency network which relates to temporal trajectories of Hemoglobin A1C in Diabetes Type 1
Helena Jorge, Isabel C. Duarte, Miguel Melo, Ana Paula Relvas, Miguel Castelo-Branco
Brain Imaging and Behavior.2023; 18(1): 171. CrossRef

Short Communication

Technology/Device
A 4-Week, Two-Center, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of EOPatch in Well-Controlled Type 1 Diabetes Mellitus: Jiyun Park, Nammi Park, Sangjin Han, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Woo Je Lee, Jae Hyeon Kim; Diabetes Metab J. 2022;46(6):941-947. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0299

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This study evaluated the safety and efficacy of tubeless patch pump called EOPatch in patients with well-controlled type 1 diabetes mellitus (T1DM). This 4-week, two-center, open-label, single-arm study enrolled 10 adult patients diagnosed with T1DM with glycosylated hemoglobin less than 7.5%. The co-primary end points were patch pump usage time for one attachment and number of serious adverse events related to the patch pump. The secondary end points were total amount of insulin injected per patch and changes in glycemic parameters including continuous glucose monitoring data compared to those at study entry. The median usage time per patch was 84.00 hours (interquartile range, 64.50 to 92.50). Serious adverse events did not occur during the trial. Four weeks later, time in range 70 to 180 mg/dL was significantly improved (70.71%±17.14 % vs. 82.96%±9.14%, P=0.01). The times spent below range (<54 mg/dL) and above range (>180 mg/dL) also improved (All P<0.05). Four-week treatment with a tubeless patch pump was safe and led to clinical improvement in glycemic control.

Citations

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Multilayer track‐etched membrane‐based electroosmotic pump for drug delivery
Qian Yang, Zebo Zhang, Junshu Lin, Boyu Zhu, Rongying Yu, Xinru Li, Bin Su, Bo Zhao
ELECTROPHORESIS.2024; 45(5-6): 433. CrossRef
Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial
Ji Yoon Kim, Sang-Man Jin, Eun Seok Kang, Soo Heon Kwak, Yeoree Yang, Jee Hee Yoo, Jae Hyun Bae, Jun Sung Moon, Chang Hee Jung, Ji Cheol Bae, Sunghwan Suh, Sun Joon Moon, Sun Ok Song, Suk Chon, Jae Hyeon Kim
Diabetologia.2024; 67(7): 1235. CrossRef
Approaches of wearable and implantable biosensor towards of developing in precision medicine
Elham Ghazizadeh, Zahra Naseri, Hans-Peter Deigner, Hossein Rahimi, Zeynep Altintas
Frontiers in Medicine.2024;[Epub] CrossRef
Advancements in Insulin Pumps: A Comprehensive Exploration of Insulin Pump Systems, Technologies, and Future Directions
Mohammad Towhidul Islam Rimon, Md Wasif Hasan, Mohammad Fuad Hassan, Sevki Cesmeci
Pharmaceutics.2024; 16(7): 944. CrossRef
A true continuous healthcare system for type 1 diabetes
Jiyong Kim, Salman Khan, Eun Kyu Kim, Hye-Jun Kil, Bo Min Kang, Hyo Geon Lee, Jin-Woo Park, Jun Young Yoon, Woochul Kim
Nano Energy.2023; 113: 108553. CrossRef

Original Articles

Drug/Regimen
Effects of Teneligliptin on HbA1c levels, Continuous Glucose Monitoring-Derived Time in Range and Glycemic Variability in Elderly Patients with T2DM (TEDDY Study): Ji Cheol Bae, Soo Heon Kwak, Hyun Jin Kim, Sang-Yong Kim, You-Cheol Hwang, Sunghwan Suh, Bok Jin Hyun, Ji Eun Cha, Jong Chul Won, Jae Hyeon Kim; Diabetes Metab J. 2022;46(1):81-92. Published online June 16, 2021; DOI: https://doi.org/10.4093/dmj.2021.0016

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Background
To evaluate the effects of teneligliptin on glycosylated hemoglobin (HbA1c) levels, continuous glucose monitoring (CGM)-derived time in range, and glycemic variability in elderly type 2 diabetes mellitus patients.
Methods
This randomized, double-blinded, placebo-controlled study was conducted in eight centers in Korea (clinical trial registration number: NCT03508323). Sixty-five participants aged ≥65 years, who were treatment-naïve or had been treated with stable doses of metformin, were randomized at a 1:1 ratio to receive 20 mg of teneligliptin (n=35) or placebo (n=30) for 12 weeks. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability.
Results
After 12 weeks, a significant reduction (by 0.84%) in HbA1c levels was observed in the teneligliptin group compared to that in the placebo group (by 0.08%), with a between-group least squares mean difference of –0.76% (95% confidence interval [CI], –1.08 to –0.44). The coefficient of variation, standard deviation, and mean amplitude of glycemic excursion significantly decreased in participants treated with teneligliptin as compared to those in the placebo group. Teneligliptin treatment significantly decreased the time spent above 180 or 250 mg/dL, respectively, without increasing the time spent below 70 mg/dL. The mean percentage of time for which glucose levels remained in the 70 to 180 mg/dL time in range (TIR70–180) at week 12 was 82.0%±16.0% in the teneligliptin group, and placebo-adjusted change in TIR70–180 from baseline was 13.3% (95% CI, 6.0 to 20.6).
Conclusion
Teneligliptin effectively reduced HbA1c levels, time spent above the target range, and glycemic variability, without increasing hypoglycemia in our study population.

Citations

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Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study
Harmanjit Singh, Ravi Rohilla, Shivani Jaswal, Mandeep Singla
Expert Review of Endocrinology & Metabolism.2024; 19(1): 81. CrossRef
Potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus: current status and future prospects
Harmanjit Singh, Jasbir Singh, Ravneet Kaur Bhangu, Mandeep Singla, Jagjit Singh, Farideh Javid
Expert Review of Clinical Pharmacology.2023; 16(1): 49. CrossRef
Mechanism of molecular interaction of sitagliptin with human DPP4 enzyme - New Insights
Michelangelo Bauwelz Gonzatti, José Edvar Monteiro Júnior, Antônio José Rocha, Jonathas Sales de Oliveira, Antônio José de Jesus Evangelista, Fátima Morgana Pio Fonseca, Vânia Marilande Ceccatto, Ariclécio Cunha de Oliveira, José Ednésio da Cruz Freire
Advances in Medical Sciences.2023; 68(2): 402. CrossRef
A prospective multicentre open label study to assess effect of Teneligliptin on glycemic control through parameters of time in range (TIR) Metric using continuous glucose monitoring (TOP-TIR study)
Banshi Saboo, Suhas Erande, A.G. Unnikrishnan
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2022; 16(2): 102394. CrossRef
Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes
Min Jeong Park, Kyung Mook Choi
Diabetes & Metabolism Journal.2022; 46(1): 49. CrossRef

Drug/Regimen
Increasing Age Associated with Higher Dipeptidyl Peptidase-4 Inhibition Rate Is a Predictive Factor for Efficacy of Dipeptidyl Peptidase-4 Inhibitors: Sangmo Hong, Chang Hee Jung, Song Han, Cheol-Young Park; Diabetes Metab J. 2022;46(1):63-70. Published online April 19, 2021; DOI: https://doi.org/10.4093/dmj.2020.0253

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Graphical Abstract Abstract PDF Supplementary Material PubReader ePub: Background
It is not known which type 2 diabetes mellitus (T2DM) patients would most benefit from dipeptidyl peptidase-4 (DPP-4) inhibitor treatment. We aimed to investigate the predictors of response to DPP-4 inhibitors considering degree of DPP-4 inhibition.
Methods
This study is a post hoc analysis of a 24-week, randomized, double-blind, phase III trial that compared the efficacy and safety of a DPP-4 inhibitor (gemigliptin vs. sitagliptin) in patients with T2DM. Subjects were classified into tertiles of T1 <65.26%, T2=65.26%–76.35%, and T3 ≥76.35% by DPP-4 inhibition. We analyzed the change from baseline in glycosylated hemoglobin (HbA1c) according to DPP-4 inhibition with multiple linear regression adjusting for age, ethnicity, body mass index, baseline HbA1c, and DPP-4 activity at baseline.
Results
The mean age was greater in the high tertile group compared with the low tertile group (T1: 49.8±8.3 vs. T2: 53.1±10.5 vs. T3: 55.3±9.5, P<0.001) of DPP-4 inhibition. Although HbA1c at baseline was not different among tertiles of DPP-4 inhibition (P=0.398), HbA1c after 24-week treatment was lower in the higher tertile compares to the lower tertile (T1: 7.30%±0.88% vs. T2: 7.12%±0.78% vs. T3: 7.00%±0.78%, P=0.021). In multiple regression analysis, DPP-4 enzyme inhibition rate was not a significant determent for HbA1c reduction due to age. In subgroup analysis by tertile of DPP-4 inhibition, age was the only significant predictor and only in the highest tertile (R²=0.281, B=–0.014, P=0.024).
Conclusion
This study showed that HbA1c reduction by DPP-4 inhibitor was associated with increasing age, and this association was linked with higher DPP-4 inhibition.

Review

Type 1 Diabetes
Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control: Jee Hee Yoo, Jae Hyeon Kim; Diabetes Metab J. 2020;44(6):828-839. Published online December 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0257; Correction in: Diabetes Metab J 2021;45(5):795

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Glycosylated hemoglobin (HbA1c) has been the sole surrogate marker for assessing diabetic complications. However, consistently reported limitations of HbA1c are that it lacks detailed information on short-term glycemic control and can be easily interfered with by various clinical conditions such as anemia, pregnancy, or liver disease. Thus, HbA1c alone may not represent the real glycemic status of a patient. The advancement of continuous glucose monitoring (CGM) has enabled both patients and healthcare providers to monitor glucose trends for a whole single day, which is not possible with HbA1c. This has allowed for the development of core metrics such as time spent in time in range (TIR), hyperglycemia, or hypoglycemia, and glycemic variability. Among the 10 core metrics, TIR is reported to represent overall glycemic control better than HbA1c alone. Moreover, various evidence supports TIR as a predictive marker of diabetes complications as well as HbA1c, as the inverse relationship between HbA1c and TIR reveals. However, there are more complex relationships between HbA1c, TIR, and other CGM metrics. This article provides information about 10 core metrics with particular focus on TIR and the relationships between the CGM metrics for comprehensive understanding of glycemic status using CGM.

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Xiaopeng Shao, Jingyi Lu, Rui Tao, Liang Wu, Yaxin Wang, Wei Lu, Hongru Li, Jian Zhou, Xia Yu
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Ji Yoon Kim, Sang-Man Jin, Kang Hee Sim, Bo-Yeon Kim, Jae Hyoung Cho, Jun Sung Moon, Soo Lim, Eun Seok Kang, Cheol-Young Park, Sin Gon Kim, Jae Hyeon Kim
Diabetologia.2024; 67(7): 1223. CrossRef
Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial
Ji Yoon Kim, Sang-Man Jin, Eun Seok Kang, Soo Heon Kwak, Yeoree Yang, Jee Hee Yoo, Jae Hyun Bae, Jun Sung Moon, Chang Hee Jung, Ji Cheol Bae, Sunghwan Suh, Sun Joon Moon, Sun Ok Song, Suk Chon, Jae Hyeon Kim
Diabetologia.2024; 67(7): 1235. CrossRef
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Brief Report

Drug/Regimen
Long-Term Glycaemic Durability of Early Combination Therapy Strategy versus Metformin Monotherapy in Korean Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Soon-Jib Yoo, Sang-Ah Chang, Tae Seo Sohn, Hyuk-Sang Kwon, Jong Min Lee, Sungdae Moon, Pieter Proot, Päivi M Paldánius, Kun Ho Yoon; Diabetes Metab J. 2021;45(6):954-959. Published online November 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0173

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We assessed the glycaemic durability with early combination (EC; vildagliptin+metformin [MET], n=22) versus MET monotherapy (n=17), among newly-diagnosed type 2 diabetes mellitus (T2DM) enrolled (between 2012 and 2014) in the VERIFY study from Korea (n=39). Primary endpoint was time to initial treatment failure (TF) (glycosylated hemoglobin [HbA1c] ≥7.0% at two consecutive scheduled visits after randomization [end of period 1]). Time to second TF was assessed when both groups were receiving and failing on the combination (end of period 2). With EC the risk of initial TF significantly reduced by 78% compared to MET (n=3 [15%] vs. n=10 [58.7%], P=0.0228). No secondary TF occurred in EC group versus five patients (29.4%) in MET. Patients receiving EC treatment achieved consistently lower HbA1c levels. Both treatment approaches were well tolerated with no hypoglycaemic events. In Korean patients with newly diagnosed T2DM, EC treatment significantly and consistently improved the long-term glycaemic durability as compared with MET.

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Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial
Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon
Diabetes & Metabolism Journal.2024; 48(5): 915. CrossRef
2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
Diabetes & Metabolism Journal.2023; 47(5): 575. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim,
Diabetes & Metabolism Journal.2021; 45(4): 461. CrossRef

Original Articles

Complications
Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study: Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2021;45(3):368-378. Published online October 20, 2020; DOI: https://doi.org/10.4093/dmj.2020.0046

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Background
To evaluate the association of time to reach the target glycosylated hemoglobin (HbA1c) level with long-term durable glycemic control and risk of diabetic complications in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
Methods
In a longitudinal observational cohort, 194 patients with T2DM newly diagnosed between January 2011 and March 2013 were followed up over 6 years. Patients were classified according to the time needed to reach the target HbA1c (<7.0%): <3, 3 to 6 (early achievement group), and ≥6 months (late achievement group). Risks of microvascular complications including diabetic retinopathy, nephropathy, and neuropathy as well as macrovascular events including ischemic heart disease, ischemic stroke, and peripheral arterial disease were assessed by multivariable Cox proportional hazards analysis.
Results
During a median follow-up of 6.53 years, 66 microvascular and 14 macrovascular events occurred. Maintenance of durable glycemic control over 6 years was more likely in the early achievement groups than in the late achievement group (34.5%, 30.0%, and 16.1% in <3, 3 to 6, and ≥6 months, respectively, P=0.039). Early target HbA1c achievement was associated with lower risk of composite diabetic complications (adjusted hazard ratio [HR, 0.47; 95% confidence interval [CI], 0.26 to 0.86 in <3 months group) (adjusted HR, 0.50; 95% CI, 0.23 to 1.10 in 3 to 6 months group, in reference to ≥6 months group). Similar trends were maintained for risks of microvascular and macrovascular complications, although statistical significance was not reached for macrovascular complications.
Conclusion
Early target HbA1c achievement was associated with long-term durable glycemic control and reduced risk of diabetic complications in newly diagnosed T2DM.

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Lifestyle
Reducing Carbohydrate from Individual Sources Has Differential Effects on Glycosylated Hemoglobin in Type 2 Diabetes Mellitus Patients on Moderate Low-Carbohydrate Diets: Hajime Haimoto, Shiho Watanabe, Keiko Maeda, Takashi Murase, Kenji Wakai; Diabetes Metab J. 2021;45(3):390-403. Published online July 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0033

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Background

We evaluated decreases in glycosylated hemoglobin (HbA1c) achieved by reducing carbohydrate from various sources in type 2 diabetes mellitus patients.

Methods

We followed up 138 male and 107 female outpatients on a moderate low-carbohydrate diet without diabetic medication for 6 months. Changes in carbohydrate sources (Δcarbohydrate) were assessed from 3-day dietary records at baseline and 6 months, and associations with changes in HbA1c (ΔHbA1c) were examined with Spearman's correlation coefficients (r_s) and multiple regression analysis.

Results

ΔHbA1c was −1.5%±1.6% in men and −0.9%±1.3% in women, while Δtotal carbohydrate was −115.3±103.7 g/day in men and −63.6±71.1 g/day in women. Positive associations with ΔHbA1c were found for Δtotal carbohydrate (r_s=0.584), Δcarbohydrate from soft drinks (0.368), confectionery (0.361), rice (0.325), bread (0.221), Chinese soup noodles (0.199) in men, and Δtotal carbohydrate (0.547) and Δcarbohydrate from rice (0.376) and confectionery (0.195) in women. Reducing carbohydrate sources by 50 g achieved decreases in HbA1c of 0.43% for total carbohydrate, 1.33% for soft drinks, 0.88% for confectionery, 0.63% for bread, 0.82% for Chinese soup noodles and 0.34% for rice in men and 0.45% for total carbohydrate, 0.67% for confectionery and 0.34% for rice in women, although mean reductions in carbohydrate from these sources were much smaller than that from rice.

Conclusion

Decreases in HbA1c achieved by reducing carbohydrate from soft drinks, confectionery, bread and Chinese soup noodles were 2- to 4-fold greater than that for rice. Our results will enable patients to decrease HbA1c efficiently (UMIN000009866).

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Jong Han Choi, Jee-Hyun Kang, Suk Chon
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Associations of Dietary Salt and Its Sources with Hemoglobin A1c in Patients with Type 2 Diabetes Not Taking Anti-Diabetic Medications: Analysis Based on 6-Month Intervention with a Moderate Low-Carbohydrate Diet
Hajime Haimoto, Takashi Murase, Shiho Watanabe, Keiko Maeda, Kenji Wakai
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Complications
Deterioration of Sleep Quality According to Glycemic Status: Myung Haeng Hur, Mi-Kyoung Lee, Kayeon Seong, Jun Hwa Hong; Diabetes Metab J. 2020;44(5):679-686. Published online April 17, 2020; DOI: https://doi.org/10.4093/dmj.2019.0125

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Background

Type 2 diabetes mellitus (T2DM) is a progressive disease with multiple complications. The present study aimed to determine the effects of glycemic status on sleep quality in individuals with T2DM, prediabetes, and normal glucose tolerance (NGT).

Methods

A total of 90 participants were categorized into three groups, T2DM (n=30), prediabetes (n=30), and NGT (n=30). Objective sleep quality was measured with the actigraph wrist-worn device over 3 nights and subjective sleep quality was evaluated with a questionnaire.

Results

The duration of diabetes in the T2DM group was 2.23 years and the glycosylated hemoglobin (HbA1c) levels in the T2DM, prediabetes, and NGT groups were 7.83%, 5.80%, and 5.31%, respectively. Sleep efficiency decreased across the T2DM, prediabetes, and NGT groups (86.25%, 87.99%, and 90.22%, respectively; P=0.047). Additionally, HbA1c levels revealed a significant negative correlation with sleep efficiency (r=−0.348, P=0.001). The sleep quality questionnaire results were similar among the three groups.

Conclusion

Although the participants in the present study were not necessarily conscious of their sleep disturbances, deterioration in sleep quality progressed according to glycemic status.

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Yusra Amin, Sonia Mushtaq, Rukhsana Farooq
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Influence of sleep quality and other associated factors on glycemic control among diabetic patients: A hospital-based study
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Replacing sedentary time with sleep and physical activity: associations with physical function and wellbeing in Type 2 diabetes
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Relation between sleep quality and glycemic control among type 2 diabetic patients
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Heart rate variability in different sleep stages is associated with metabolic function and glycemic control in type 2 diabetes mellitus
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Nutritional Biomarkers and Factors Correlated with Poor Sleep Status among Young Females: A Case-Control Study
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The impact of sleep disorders on microvascular complications in patients with type 2 diabetes (SLEEP T2D): the protocol of a cohort study and feasibility randomised control trial
Christina Antza, Ryan Ottridge, Smitaa Patel, Gemma Slinn, Sarah Tearne, Matthew Nicholls, Brendan Cooper, Asad Ali, Abd A. Tahrani
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Early Development of Bidirectional Associations between Sleep Disturbance and Diabetes
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Short Communication

Epidemiology
Low-Normal Free Thyroxine Levels in Euthyroid Male Are Associated with Prediabetes: Sung Woo Kim, Jae-Han Jeon, Jun Sung Moon, Eon Ju Jeon, Mi-Kyung Kim, In-Kyu Lee, Jung Beom Seo, Keun-Gyu Park; Diabetes Metab J. 2019;43(5):718-726. Published online March 19, 2019; DOI: https://doi.org/10.4093/dmj.2018.0222

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Abstract PDF Supplementary Material PubReader: Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.

Original Article

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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Abstract PDF Supplementary Material PubReader

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.

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Short Communication

Complications
Glycosylated Hemoglobin in Subjects Affected by Iron-Deficiency Anemia: Jari Intra, Giuseppe Limonta, Fabrizio Cappellini, Maria Bertona, Paolo Brambilla; Diabetes Metab J. 2019;43(4):539-544. Published online November 28, 2018; DOI: https://doi.org/10.4093/dmj.2018.0072

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Previous studies have suggested that iron-deficiency anemia affects glycosylated hemoglobin (HbA1c) measurements, but the results were contradictory. We conducted a retrospective case-control study to determine the effects of iron deficiency on HbA1c levels. Starting with the large computerized database of the Italian Hospital of Desio, including data from 2000 to 2016, all non-pregnant individuals older than 12 years of age with at least one measurement of HbA1c, cell blood count, ferritin, and fasting blood glucose on the same date of blood collection were enrolled. A total of 2,831 patients met the study criteria. Eighty-six individuals were diagnosed with iron-deficiency anemia, while 2,745 had a normal iron state. The adjusted means of HbA1c were significantly higher in anemic subjects (5.59% [37.37 mmol/mol]), than those measured in individuals without anemia (5.34% [34.81 mmol/mol]) (P<0.0001). These results suggest that clinicians should be cautious about diagnosing prediabetes and diabetes in individuals with anemia.

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Original Articles

Clinical Diabetes & Therapeutics
Effectiveness of Exercise Intervention in Reducing Body Weight and Glycosylated Hemoglobin Levels in Patients with Type 2 Diabetes Mellitus in Korea: A Systematic Review and Meta-Analysis: Ji-Eun Jang, Yongin Cho, Byung Wan Lee, Ein-Soon Shin, Sun Hee Lee; Diabetes Metab J. 2019;43(3):302-318. Published online November 19, 2018; DOI: https://doi.org/10.4093/dmj.2018.0062

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Background

This study aimed to assess the effectiveness of exercise intervention in reducing body weight and glycosylated hemoglobin (HbA1c) level in patients with type 2 diabetes mellitus (T2DM) in Korea.

Methods

Cochrane, PubMed, Embase, KoreaMed, KMbase, NDSL, KCI, RISS, and DBpia databases were used to search randomized controlled trials and controlled clinical trials that compared exercise with non-exercise intervention among patients with non-insulin-treated T2DM in Korea. The effectiveness of exercise intervention was estimated by the mean difference in body weight changes and HbA1c level. Weighted mean difference (WMD) with its corresponding 95% confidence interval (CI) was used as the effect size. The pooled mean differences of outcomes were calculated using a random-effects model.

Results

We identified 7,692 studies through literature search and selected 23 articles (723 participants). Compared with the control group, exercise intervention (17 studies) was associated with a significant decline in HbA1c level (WMD, −0.58%; 95% CI, −0.89 to −0.27; I²=73%). Although no significant effectiveness on body weight was observed, eight aerobic training studies showed a significant reduction in body weight (WMD, −2.25 kg; 95% CI, −4.36 to −0.13; I²=17%) in the subgroup analysis.

Conclusion

Exercise significantly improves glycemic control; however, it does not significantly reduce body weight. Aerobic training can be beneficial for patients with non-insulin-treated T2DM in Korea.

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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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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 [DM_FPG]), 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 DM_FPG 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 DM_FPG 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 DM_FPG 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 DM_FPG 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 DM_FPG in this age group.

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