Endocrinology and Metabolism

Review Article

Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia: Joonyub Lee, Kun-Ho Yoon; Received October 7, 2024 Accepted October 29, 2024 Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2193 [Epub ahead of print]

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Abstract PDF: In East Asians, type 2 diabetes mellitus (T2DM) is primarily characterized by significant defects in insulin secretion and comparatively low insulin resistance. Recently, the prevalence of T2DM has rapidly increased in East Asian countries, including Korea, occurring concurrently with rising obesity rates. This trend has led to an increase in the average body mass index among East Asian T2DM patients, highlighting the influence of insulin resistance in the development of T2DM within this group. Currently, the incidence of T2DM in Korea is declining, which may indicate potential adaptive changes in insulin secretory capacity. This review focuses on the changing epidemiology of T2DM in East Asia, with a particular emphasis on the characteristics of peak functional β-cell mass.

Original Articles

Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis: A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Deep Dutta, Thanikai Sasikanth, Fatema Tuz Zahura Aalpona, Lakshmi Nagendra; Received September 29, 2024 Accepted November 14, 2024 Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2164 [Epub ahead of print]

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Abstract PDF: Background
Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.
Methods
RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.
Results
Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.
Conclusion
Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.

Effectiveness and Safety of Oral Quadruple Combination Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis: Jaehyun Bae, Min Heui Yu, Minyoung Lee, Bong-Soo Cha, Byung-Wan Lee; Received July 29, 2024 Accepted November 5, 2024 Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2120 [Epub ahead of print]

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Abstract PDF: Background
Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
Methods
This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge’s g) and the risk ratio for adverse events in random-effects meta-analyses.
Results
The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist–containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Conclusion
Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.

Brief Report

Metabolic Consequences of Glucagon-Like Peptide-1 Receptor Agonist Shortage: Deterioration of Glycemic Control in Type 2 Diabetes: Hun Jee Choe, Michael A. Nauck, Joon Ho Moon; Received August 19, 2024 Accepted October 7, 2024 Published online November 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.2150 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: In the context of a global shortage of glucagon-like peptide-1 (GLP-1) receptor agonists, we assessed the impact of discontinuing dulaglutide on metabolic control in individuals with type 2 diabetes. Our analysis included data from 69 individuals and revealed a significant deterioration in glycemic control following the discontinuation. Specifically, the average hemoglobin A1c level increased from 7.0%±0.9% to 8.1%±1.4% (P<0.001), and fasting glucose levels rose from 129±31 to 156±50 mg/dL (P<0.001) within 3 months after stopping the medication. Alternative treatments such as dipeptidyl peptidase-4 inhibitors and sodium glucose cotransporter- 2 inhibitors were insufficient substitutes, highlighting the essential role of continuous GLP-1 receptor agonist therapy in maintaining metabolic health.

Original Articles

Risk of Diabetes Mellitus in Adults with Intellectual Disabilities: A Nationwide Cohort Study: Hye Yeon Koo, In Young Cho, Yoo Jin Um, Yong-Moon Mark Park, Kyung Mee Kim, Chung Eun Lee, Kyungdo Han; Received July 31, 2024 Accepted October 15, 2024 Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2126 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations.
Methods
This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID.
Results
Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001).
Conclusion
Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

Diabetes, obesity and metabolism
Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes: Claudia Regina Lopes Cardoso, Nathalie Carvalho Leite, Gil Fernando Salles; Endocrinol Metab. 2024;39(5):732-747. Published online October 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.2001

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Abstract PDF Supplementary Material PubReader ePub: Background
This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c).
Methods
Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence.
Results
During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53).
Conclusion
HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

Review Article

Diabetes, obesity and metabolism
Changes in the Epidemiological Landscape of Diabetes in South Korea: Trends in Prevalence, Incidence, and Healthcare Expenditures: Kyoung Hwa Ha, Dae Jung Kim; Endocrinol Metab. 2024;39(5):669-677. Published online September 25, 2024; DOI: https://doi.org/10.3803/EnM.2024.2073

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Abstract PDF Supplementary Material PubReader ePub

Diabetes is a serious public health concern that significantly contributes to the global burden of disease. In Korea, the prevalence of diabetes is 12.5% among individuals aged 19 and older, and 14.8% among individuals aged 30 and older as of 2022. The total number of people with diabetes among those aged 19 and older is estimated to be 5.4 million. The incidence of diabetes decreased from 8.1 per 1,000 persons in 2006 to 6.3 per 1,000 persons in 2014, before rising again to 7.5 per 1,000 persons in 2019. Meanwhile, the incidence of type 1 diabetes increased significantly, from 1.1 per 100,000 persons in 1995 to 4.8 per 100,000 persons in 2016, with the prevalence reaching 41.0 per 100,000 persons in 2017. Additionally, the prevalence of gestational diabetes saw a substantial rise from 4.1% in 2007 to 22.3% in 2023. These changes have resulted in increases in the total medical costs for diabetes, covering both outpatient and inpatient services. Therefore, effective diabetes prevention strategies are urgently needed.

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Citations to this article as recorded by

Trends in prescribing sodium‐glucose cotransporter 2 inhibitors for individuals with type 2 diabetes with and without cardiovascular‐renal disease in South Korea, 2015–2021
Kyoung Hwa Ha, Soyoung Shin, EunJi Na, Dae Jung Kim
Journal of Diabetes Investigation.2024;[Epub] CrossRef

Original Article

Diabetes, obesity and metabolism
Impact of Chronic Kidney Disease and Gout on End-Stage Renal Disease in Type 2 Diabetes: Population-Based Cohort Study: Inha Jung, Da Young Lee, Seung Min Chung, So Young Park, Ji Hee Yu, Jun Sung Moon, Ji A Seo, Kyungdo Han, Nan Hee Kim; Endocrinol Metab. 2024;39(5):748-757. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.2020

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Abstract PDF Supplementary Material PubReader ePub: Background
We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status.
Methods
Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m²) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD⁻Gout⁻, CKD⁻ Gout⁺, CKD⁺Gout⁻, and CKD⁺Gout⁺. Patients with incident ESRD were followed up until December 2018.
Results
Among 847,884 patients, 11,825 (1.4%) experienced progression to ESRD. ESRD incidence increased in the following order: 0.77 per 1,000 person-years (PY) in the CKD⁻Gout⁻ group, 1.34/1,000 PY in the CKD⁻Gout⁺ group, 8.20/1,000 PY in the CKD⁺Gout⁻ group, and 23.06/1,000 PY in the CKD⁺Gout⁺ group. The presence of gout modified the ESRD risk in a status-dependent manner. Hazard ratios (HR) were 1.49 (95% confidence interval [CI], 1.32 to 1.69) and 2.24 (95% CI, 2.09 to 2.40) in patients without and with CKD, respectively, indicating a significant interaction (P<0.0001). The CKD⁺Gout⁺ group had a markedly higher risk of developing ESRD (HR, 18.9; 95% CI, 17.58 to 20.32) than the reference group (CKD⁻Gout⁻).
Conclusion
Gout substantially enhances the risk of ESRD, even in the absence of CKD. Concurrent CKD and gout synergistically increase the risk of ESRD. Therefore, physicians should carefully screen for hyperuricemia to prevent progression to ESRD.

Brief Report

Diabetes, obesity and metabolism
Impact of Diabetes on COVID-19 Susceptibility: A Nationwide Propensity Score Matching Study: Han Na Jang, Sun Joon Moon, Jin Hyung Jung, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2024;39(5):813-818. Published online August 28, 2024; DOI: https://doi.org/10.3803/EnM.2024.2014

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Abstract PDF Supplementary Material PubReader ePub: Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.

Original Articles

Diabetes, obesity and metabolism
Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE): Nam Hoon Kim, Juneyoung Lee, Suk Chon, Jae Myung Yu, In-Kyung Jeong, Soo Lim, Won Jun Kim, Keeho Song, Ho Chan Cho, Hea Min Yu, Kyoung-Ah Kim, Sang Soo Kim, Soon Hee Lee, Chong Hwa Kim, Soo Heon Kwak, Yong‐ho Lee, Choon Hee Chung, Sihoon Lee, Heung Yong Jin, Jae Hyuk Lee, Gwanpyo Koh, Sang-Yong Kim, Jaetaek Kim, Ju Hee Lee, Tae Nyun Kim, Hyun Jeong Jeon, Ji Hyun Lee, Jae-Han Jeon, Hye Jin Yoo, Hee Kyung Kim, Hyeong-Kyu Park, Il Seong Nam-Goong, Seongbin Hong, Chul Woo Ahn, Ji Hee Yu, Jong Heon Park, Keun-Gyu Park, Chan Ho Park, Kyong Hye Joung, Ohk-Hyun Ryu, Keun Yong Park, Eun-Gyoung Hong, Bong-Soo Cha, Kyu Chang Won, Yoon-Sok Chung, Sin Gon Kim; Endocrinol Metab. 2024;39(5):722-731. Published online August 22, 2024; DOI: https://doi.org/10.3803/EnM.2024.1995

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Abstract PDF PubReader ePub: Background
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Diabetes, obesity and metabolism
Amelioration of Insulin Resistance after Delivery Is Associated with Reduced Risk of Postpartum Diabetes in Women with Gestational Diabetes Mellitus: Heejun Son, Joon Ho Moon, Sung Hee Choi, Nam H. Cho, Soo Heon Kwak, Hak Chul Jang; Endocrinol Metab. 2024;39(5):701-710. Published online August 21, 2024; DOI: https://doi.org/10.3803/EnM.2024.1974

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Background
Identifying risk factors for postpartum type 2 diabetes in women with gestational diabetes mellitus (GDM) is crucial for effective interventions. We examined whether changes in insulin sensitivity after delivery affects the risk of type 2 diabetes in women with GDM.
Methods
This prospective cohort study included 347 women with GDM or gestational impaired glucose tolerance, who attended the follow-up visits at 2 months postpartum and annually thereafter. Changes in insulin sensitivity were calculated using the Matsuda index at GDM diagnosis and at 2 months postpartum (ΔMatsuda index). After excluding women with pregestational diabetes or those followed up only once, we analyzed the risk of postpartum type 2 diabetes based on the ΔMatsuda index tertiles.
Results
The incidence of type 2 diabetes at the two-month postpartum visit decreased with increasing ΔMatsuda index tertiles (16.4%, 9.5%, and 1.8%, P=0.001). During a 4.1-year follow-up, 26 out of 230 women who attended more than two follow-up visits (11.3%) developed type 2 diabetes. Compared to the lowest tertile, subjects in the highest ΔMatsuda index tertile showed a significantly reduced risk of type 2 diabetes (hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.93; P=0.036) after adjusting for confounders.
Conclusion
Improvement in insulin sensitivity after delivery is associated with a reduced risk of postpartum type 2 diabetes in women with GDM. Postpartum changes in insulin sensitivity could be a useful prediction for future type 2 diabetes development in women with GDM.

Citations

Citations to this article as recorded by

Evaluation of Maternal Factors Affecting Postpartum Insulin Resistance Markers in Mothers with Gestational Diabetes—A Case–Control Study
Karolina Karcz, Paulina Gaweł, Barbara Królak-Olejnik
Nutrients.2024; 16(22): 3871. CrossRef

Diabetes, obesity and metabolism
Financial Benefits of Renal Dose-Adjusted Dipeptidyl Peptidase-4 Inhibitors for Patients with Type 2 Diabetes and Chronic Kidney Disease: Hun Jee Choe, Yeh-Hee Ko, Sun Joon Moon, Chang Ho Ahn, Kyoung Hwa Ha, Hyeongsuk Lee, Jae Hyun Bae, Hyung Joon Joo, Hyejin Lee, Jang Wook Son, Dae Jung Kim, Sin Gon Kim, Kwangsoo Kim, Young Min Cho; Endocrinol Metab. 2024;39(4):622-631. Published online August 1, 2024; DOI: https://doi.org/10.3803/EnM.2024.1965

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Abstract PDF Supplementary Material PubReader ePub: Background
Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes.
Methods
This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models.
Results
In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m², respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m² and 30.4% for eGFR <30 mL/min/1.73 m². According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity.
Conclusion
Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

Brief Report

Diabetes, obesity and metabolism
Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment: Hyun Ah Kim, Han Na Jang, Sung Hye Kong, Young Lee, Sung Hee Choi, Young Min Cho, Hak Chul Jang, Tae Jung Oh; Endocrinol Metab. 2024;39(4):653-658. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1919

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We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, –0.02 mL/min/1.73 m² [95% confidence interval (CI), –3.87 to 3.83 mL/min/1.73 m²] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m² [95% CI, 3.16 to 10.46 mL/min/1.73 m²]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications’ substantial renoprotective effects in individuals with ketonuria.

Citations

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Trigger Warning: How Modern Diet, Lifestyle, and Environment Pull the Trigger on Autosomal Dominant Polycystic Kidney Disease Progression
Melina Messing, Jacob A. Torres, Nickolas Holznecht, Thomas Weimbs
Nutrients.2024; 16(19): 3281. CrossRef

Review Articles

Diabetes, obesity and metabolism
Scaling Insulin-Producing Cells by Multiple Strategies: Jinhyuk Choi, Fritz Cayabyab, Harvey Perez, Eiji Yoshihara; Endocrinol Metab. 2024;39(2):191-205. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1910

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In the quest to combat insulin-dependent diabetes mellitus (IDDM), allogenic pancreatic islet cell therapy sourced from deceased donors represents a significant therapeutic advance. However, the applicability of this approach is hampered by donor scarcity and the demand for sustained immunosuppression. Human induced pluripotent stem cells are a game-changing resource for generating synthetic functional insulin-producing β cells. In addition, novel methodologies allow the direct expansion of pancreatic progenitors and mature β cells, thereby circumventing prolonged differentiation. Nevertheless, achieving practical reproducibility and scalability presents a substantial challenge for this technology. As these innovative approaches become more prominent, it is crucial to thoroughly evaluate existing expansion techniques with an emphasis on their optimization and scalability. This manuscript delineates these cutting-edge advancements, offers a critical analysis of the prevailing strategies, and underscores pivotal challenges, including cost-efficiency and logistical issues. Our insights provide a roadmap, elucidating both the promises and the imperatives in harnessing the potential of these cellular therapies for IDDM.

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Citations to this article as recorded by

Insulin evolution: A holistic view of recombinant production advancements
Ansuman Sahoo, Prabir Kumar Das, Veeranki Venkata Dasu, Sanjukta Patra
International Journal of Biological Macromolecules.2024; 277: 133951. CrossRef

Diabetes, obesity and metabolism
Glucocorticoid-Induced Hyperglycemia: A Neglected Problem: Jung-Hwan Cho, Sunghwan Suh; Endocrinol Metab. 2024;39(2):222-238. Published online March 27, 2024; DOI: https://doi.org/10.3803/EnM.2024.1951

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Glucocorticoids provide a potent therapeutic response and are widely used to treat a variety of diseases, including coronavirus disease 2019 (COVID-19) infection. However, the issue of glucocorticoid-induced hyperglycemia (GIH), which is observed in over one-third of patients treated with glucocorticoids, is often neglected. To improve the clinical course and prognosis of diseases that necessitate glucocorticoid therapy, proper management of GIH is essential. The key pathophysiology of GIH includes systemic insulin resistance, which exacerbates hepatic steatosis and visceral obesity, as well as proteolysis and lipolysis of muscle and adipose tissue, coupled with β-cell dysfunction. For patients on glucocorticoid therapy, risk stratification should be conducted through a detailed baseline evaluation, and frequent glucose monitoring is recommended to detect the onset of GIH, particularly in high-risk individuals. Patients with confirmed GIH who require treatment should follow an insulin-centered regimen that varies depending on whether they are inpatients or outpatients, as well as the type and dosage of glucocorticoid used. The ideal strategy to maintain normoglycemia while preventing hypoglycemia is to combine basal-bolus insulin and correction doses with a continuous glucose monitoring system. This review focuses on the current understanding and latest evidence concerning GIH, incorporating insights gained from the COVID-19 pandemic.

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Citations to this article as recorded by

Effect of hypoglycemic events on cognitive function in individuals with type 2 diabetes mellitus: a dose–response meta-analysis
Min Ye, Qiqi Yang, Lele Zhang, Hudie Song, Qin Fu, Jun Qian, Hongyu Xie, Aihong Yuan
Frontiers in Neurology.2024;[Epub] CrossRef
Diabetes and the associated complications: The role of antioxidants in diabetes therapy and care
Lowell Dilworth, Dewayne Stennett, Aldeam Facey, Felix Omoruyi, Shada Mohansingh, Felix O. Omoruyi
Biomedicine & Pharmacotherapy.2024; 181: 117641. CrossRef

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