INTRODUCTION:To evaluate glycemic changes during caloric restriction with continuous glucose monitoring (CGM)-derived time in range (TIR) in individuals with type 2 diabetes and obesity. MATERIALS AND METHODS:This 12-week single-arm intervention consisted of 6 weeks of home-delivered meals (800-1,200 kcal/day), followed by 6 weeks of self-managed diet (1,500-1,800 kcal/day for men; 1,200-1,500 kcal/day for women). CGM (14-day sensor) was performed at baseline, weeks 5-6, and weeks 11-12. A 75-g oral glucose tolerance test was conducted at baseline, week 6, and week 12 to calculate the C-peptide index (CPI) and Matsuda index. RESULTS:Participants had a median age of 46.0 years [38.0, 53.5], body mass index (BMI) of 29.2 kg/m2 [26.8, 31.2], HbA1c 6.6% [6.0, 7.13], and diabetes duration 2.01 years [0.91, 3.65]. Over 12 weeks, TIR improved from 84.3% to 90.3% (P = 0.041), and BMI decreased from 29.3 to 26.7 kg/m2 (P < 0.001). Weight reduction was associated with improved insulin sensitivity, whereas changes in CPI were not significant. CPI showed a stronger association with TIR than the Matsuda index, underscoring the importance of insulin secretion capacity in glycemic control. The association between CPI and TIR was more pronounced participants with higher insulin sensitivity (P = 0.011), suggesting that adequate peripheral sensitivity is required to influence glycemic outcomes. CONCLUSIONS:In individuals with type 2 diabetes and obesity, caloric restriction was associated with improved glycemic profiles and reduced body weight. Enhanced insulin sensitivity appears to be the predominant contributor to improved TIR, while preserved β-cell function remains essential for achieving optimal glycemic outcomes.

Background/Aims: Parathyroid hormone–related protein (PTHrP) is a major mediator of hypercalcemia in patients with malignancy; however, understanding of PTHrP-mediated hypercalcemia remains limited because available evidence has largely been derived from small case series.Methods: We retrospectively analyzed electronic medical records from eight hospitals affiliated with The Catholic University of Korea. Adult patients (> 20 years) with confirmed malignancy and albumin-corrected hypercalcemia (≥ 10.5 mg/dL) between 2013 and 2022 were identified and classified as having PTHrP-mediated hypercalcemia (PTHrP > 1.1 pmol/L) or hypercalcemia due to other causes (PTHrP ≤ 1.1 pmol/L).Results: Among the 289 patients reported to have PTHrP-mediated hypercalcemia, median age was 66 years (interquartile range [IQR], 59–75) and median plasma PTHrP level was 6.1 pmol/L (IQR, 3.5–11.5). Solid tumors accounted for 86% of cases, while hematologic malignancies accounted for the other 14%. The most common cancer types were lung cancer (30%, n = 87), head and neck cancer (11%, n = 31), and multiple myeloma (8%, n = 24). Median survival after the onset of hypercalcemia was 46 days (95% confidence interval [CI], 36–61) in patients with PTHrP-mediated hypercalcemia. Compared with the 169 patients with hypercalcemia due to other causes, PTHrP-mediated hypercalcemia was associated with a higher risk of mortality after adjustment for age, corrected calcium level, and cancer type (adjusted hazard ratio, 4.0; 95% CI, 2.9–5.4).Conclusions: PTHrP-mediated hypercalcemia occurs across a broad spectrum of malignancies and is associated with worse clinical outcomes.

The effects of psychological resilience and depressive symptoms on bone health have not been well-studied. This work aimed to evaluate the association between psychological resilience and depressive symptoms on bone mineral density (BMD) and osteoporotic fracture in community-dwelling adults in Korea. Data from the Chungju Metabolic Disease Cohort were used. Between May 2007 and March 2011, 4029 participants aged 40 years or older underwent a baseline examination, and approximately four years later, they underwent a second examination. BMD was measured, and resilience and depression scales were completed. Participants in the lowest resilience group had lower BMD Z-scores at the femoral neck (0.04 ± 0.53 vs. 0.22 ± 0.950, p < 0.001) and the total hip (0.17 ± 0.98 vs. 0.34 ± 0.92, p < 0.001) compared to those in the highest resilience group. Individuals with clinical depression also had lower BMD Z-scores than those without it. However, resilience status was not associated with the prevalence of osteoporosis at follow-up or incident fracture. In contrast, the odds of osteoporosis were 1.39 (95% CI 1.12-1.71) in women with clinical depression even after adjusting for covariates. In men, clinical depression was not associated with the odds of osteoporosis. Among non-osteoporotic participants, subjects with clinical depression had a 1.40-fold (95% CI 1.07-1.92) higher fracture incidence than those without depression. In this study, low resilience did not appear to negatively affect the prevalence of osteoporosis at follow-up or fracture. Among non-osteoporotic participants, depressive individuals have a potentially increased risk of fracture compared with those without clinical depression.

Background This study aimed to evaluate the applicability of deep learning technology to thyroid ultrasound images for classification of thyroid nodules. Methods This retrospective analysis included ultrasound images of patients with thyroid nodules investigated by fine-needle aspiration at the thyroid clinic of a single center from April 2010 to September 2012. Thyroid nodules with cytopathologic results of Bethesda category V (suspicious for malignancy) or VI (malignant) were defined as thyroid cancer. Multiple deep learning algorithms based on convolutional neural networks (CNNs) —ResNet, DenseNet, and EfficientNet—were utilized, and Siamese neural networks facilitated multi-view analysis of paired transverse and longitudinal ultrasound images. Results Among 1,048 analyzed thyroid nodules from 943 patients, 306 (29%) were identified as thyroid cancer. In a subgroup analysis of transverse and longitudinal images, longitudinal images showed superior prediction ability. Multi-view modeling, based on paired transverse and longitudinal images, significantly improved the model performance; with an accuracy of 0.82 (95% confidence intervals [CI], 0.80 to 0.86) with ResNet50, 0.83 (95% CI, 0.83 to 0.88) with DenseNet201, and 0.81 (95% CI, 0.79 to 0.84) with EfficientNetv2_ s. Training with high-resolution images obtained using the latest equipment tended to improve model performance in association with increased sensitivity. Conclusion CNN algorithms applied to ultrasound images demonstrated substantial accuracy in thyroid nodule classification, indicating their potential as valuable tools for diagnosing thyroid cancer. However, in real-world clinical settings, it is important to aware that model performance may vary depending on the quality of images acquired by different physicians and imaging devices.

BACKGROUND:Lifestyle-related factors have been studied as a fundamental aspect in the onset and progression of type 2 diabetes mellitus. However, behavioral factors are easily overlooked in clinical practice. This study investigated whether lifestyle changes were associated with diabetes remission in newly diagnosed type 2 diabetes patients. METHODS:We enrolled patients with new-onset type 2 diabetes from 2009 to 2012 using a health examination cohort from the Korean National Health Insurance Service (KNHIS). Remission was defined as a fasting glucose level less than 126 mg/dL at least once during a health examination after stopping medication. A self-administered questionnaire was used to investigate patients' lifestyles. We investigated smoking, alcohol consumption, and regular exercise before and after starting diabetes medication and the odds ratios (ORs) of logistic regression on remission to evaluate the associations. RESULTS:A total of 138,211 patients diagnosed with type 2 diabetes from 2009 to 2012 were analyzed, and 8,192 (6.3%) reported remission during the follow-up period to 2017. Baseline fasting blood glucose level measured before starting diabetes medication was significantly higher in the non-remission group (180 mg/dL vs. 159 mg/dL, P < 0.001). In addition, the use rate of combined oral hypoglycemic agent treatment was higher in the non-remission group (15% vs. 8%, P < 0.001). Consistent smoking and drinking showed negative associations with remission (OR, 0.72; 95% confidence interval [CI], 0.67-0.77 and OR, 0.90; 95% CI, 0.84-0.95, respectively), and initiation of regular exercise presented a positive association with remission (OR, 1.54; 95% CI, 0.46-1.63). Abstinence from alcohol increased the likelihood of remission in the male population (OR, 1.20; 95% CI, 1.10-1.32). The association with smoking history or smoking cessation was not clear, but new smoking behavior interfered with remission in women (OR, 0.48; 95% CI, 0.28-0.81). CONCLUSION:We confirmed associations between a healthy lifestyle and diabetic remission in new-onset type 2 diabetes patients. The results of this study suggest that improving lifestyle after diabetes diagnosis may contribute to disease remission.

AIMS:To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI). MATERIALS AND METHODS:We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching. RESULTS:During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI. CONCLUSIONS:The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI.

OBJECTIVES:Glucagon-like peptide-1(GLP-1) is a hormone often measured in the short-term following Roux-en-Y gastric bypass (RYGB) due to its elevation and association with improvement of glucose metabolism. We examined the durability of this effect in patients with type 2 diabetes mellitus (DM) in the long term after RYGB. METHODS:Obese patients with type 2 DM who had received RYGB 10 years ago (n = 10) were enrolled and a meal tolerance test (MTT) was performed. A matched control group with type 2 DM (n = 5) underwent MTT. RESULTS:Glucose levels during the MTT did not differ between patients with RYGB and the nonsurgical group. Insulin, C-peptide and GLP-1 levels during MTT were significantly higher in patients with RYGB compared with the nonsurgical group (Area under the curve [AUC] of insulin; 57.4 ± 22.9 vs. 27.7 ± 11.1 mIU/L•hr, P = 0.008; AUC of total GLP-1; 189.4 ± 74.72 vs. 52.13 ± 10.23 pM •hr, P = 0.002), and in particular, peak insulin, C-peptide and GLP-1 levels observed 30-45 min after eating were markedly different from those in the nonsurgical group. Bile acids (BAs) and fibroblast growth factor 19 (FGF-19) levels during MTT were higher in patients with RYGB compared with the nonsurgical group. Peak BAs and FGF-19 levels tended to be higher in the RYGB. CONCLUSIONS:An enhanced GLP-1 response was noted 10 years after RYGB, strongly suggesting a durability of this effect. BAs and FGF-19 were increased in the RYGB group, but not as much as the pronounced increase in GLP-1 secretion.

Currently, the supply of beta cells for islet transplantation in the treatment of type 1 diabetes is limited. Enteroendocrine cells (EECs) are believed to have high potential as stem cells because they share significant developmental similarities with beta cells. In a previous study, we derived EEC cells that secrete individual gut hormones from STC-1 cells. This study aimed to examine intestinal hormone secretion and expression, investigate the expression of developmental-related transcription factors, and analyze the effect of MEOX on insulin gene expression in isolated EECs. The expression and secretion of enteroendocrine hormones were evaluated in L6 and K34 cells from STC-1 cells. Expression patterns of beta cell- and development-related genes in L6 and K34 cells were compared with beta cells. Comparisons of the MEOX-induced expression of Ins in beta cells and GLP-1-secreting cells were investigated. Both L6 and K34 cells predominantly expressed Glp1 and Gip, respectively. The secretion pattern of GLP-1 in L6 cells was similar to that of GLUTag cells. Previous microarray analysis confirmed MEOX as developmentally relevant transcription factors expressed in beta cells. Overexpression of MEOX showed a tendency to increase Ins expression in L6 and GLUTag cells, but not in MIN6 cells. However, when PDX1 and MEOX were co-expressed in GLUTag cells, insulin expression was suppressed, similar to that observed in MIN6 cells. These findings suggest a potential role for MEOX in regulating the expression of the Ins gene in both beta cells and GLP-1-secreting cells. Further studies are warranted to elucidate the underlying mechanism.

Aim To determine whether the twice-daily (BID) regimen is superior to the once-daily (QD) regimen for managing glycaemic variability by comparing the effects of anagliptin 100 mg BID versus sitagliptin 100 mg QD.Materials and MethodsA double-blinded, randomized, multicentre study was performed in 89 patients with type 2 diabetes treated with metformin alone (6.5% < HbA1c < 8.5%). Subjects were randomly assigned to anagliptin 100 mg BID or sitagliptin 100 mg QD in a 1:1 ratio for 12 weeks. Continuous glucose monitoring was used to measure the mean amplitude of glycaemic excursion (MAGE) and postprandial time in range (TIR) before and after dipeptidyl peptidase-4 (DPP-4) inhibitor treatment to compare glycaemic variability.Results The decrease from baseline in MAGE at 12 weeks after DPP-4 inhibitor treatment was significantly greater in the anagliptin BID group than in the sitagliptin QD group (P < .05); -30.4 & PLUSMN; 25.6 mg/dl (P < .001) in the anagliptin group versus -9.5 & PLUSMN; 38.0 mg/dl (P = .215) in the sitagliptin group. The TIR after dinner increased by 33.0% & PLUSMN; 22.0% (P < .001) in the anagliptin group and by 14.6% & PLUSMN; 28.2% (P = .014) in the sitagliptin group, with a statistically significant difference (P = .009). No statistically significant differences were observed between the groups in the changes in HbA1c and fasting plasma glucose (FPG).Conclusions The anagliptin BID regimen for the treatment of type 2 diabetes was superior in blood glucose control after dinner to improve glycaemic variability, as indicated by MAGE and TIR, but was equivalent to the QD regimen in terms of HbA1c and FPG.

Background/Aims A re-increasing trend of thyroid cancer since 2015 has been observed despite a similar examination rate, and the incidence of thyroid cancer among young adults continues to rise. Methods This study used data from the Korean National Health Insurance Service. Individuals 20–39 years of age who underwent ≥ 4 health checkups from 2009–2013 were enrolled and followed throughout 2019. To quantify the metabolic burden, groups were divided by the number of diagnoses of metabolic syndrome across four consecutive health examinations. Results Among the study population (n = 1,204,646), 5,929 (0.5%) were diagnosed with thyroid cancer during a follow-up period of 5 years. The hazard ratio (95% confidence interval) values of thyroid cancer occurrence according to the number (1–4) of diagnoses of metabolic syndrome across the four health examinations compared to the group without met-abolic syndrome were significantly greater, as follows: 1.12 (1.02–1.23), 1.25 (1.10–1.42), 1.33 (1.15–1.55), and 1.48 (1.25–1.75) (p for trend < 0.01), respectively. Each component of metabolic syndrome showed a significant increase in hazard ratio according to the number of diagnoses except for impaired fasting glucose criteria. Conclusions Cumulative exposure to metabolic syndrome was associated with thyroid cancer risk in young adults.

This study aimed to investigate the effects of repeated detection of non‐alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults.

The natural history of type 2 diabetes (T2D) is mostly progressive and patients often die from diabetes-related complications. However, T2D can sometimes improve enough to discontinue medications, and this phenomenon remains poorly understood. Using health examination data from the Korean National Health Insurance Service (KNHIS) for a new-onset T2D cohort, we investigated the incidence of diabetes remission and associated clinical factors. Remission was defined as normal fasting blood glucose levels < 126 mg/dL, an alternative criterion for remission based on expert consensus; patients who reached normal fasting blood glucose levels measured at 2-year intervals after discontinuation of treatment were defined as achieving remission. New-onset T2D patients (N=114,874) from 2009 to 2012 were followed until 2017, and 2,429 patients (2.1%) experienced remission during the study period. No significant difference in age was reported between the remission and non-remission groups. Compared to the non-remission group, the remission group had lower baseline body mass index (25.4 kg/m2 vs. 25.7 kg/m2), lower baseline fasting glucose levels (157.7 mg/dL vs. 177.1mg/dL), and a lower prevalence of hypertension (47.7% vs. 52.2%) and hyperlipidemia (44.4% vs. 48.2%). When investigating treatment methods, the remission rate was lower in patients who used more than three oral hypoglycemic agents including sulfonylurea (5.43% vs. 14.4%), while the rate of insulin users was higher in the remission group (10.5% vs. 8.0%). When weight change within 2 years before and after remission was reviewed through health examination results, the group that succeeded in weight loss of 5% or more had a significantly higher rate of remission. In summary, remission was observed at rates as low as 2.1% in patients in standard medical care settings. Weight loss and insulin therapy in early T2D patients are thought to lead a favorable prognosis in terms of remission. Disclosure K. Song: None. J. Kim: None. K. Han: None. H. Kwon: None. Funding National Research Foundation of Korea (2021R1A2C2013890)

AIMS:We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with risk of total and site-specific cancer in the Korean population aged 65 years and above. METHODS:This study included 1,232,173 subjects aged ≥ 65 years who underwent a general health screening program. Diabetes status was categorized as normal glucose tolerance, impaired fasting glucose, new-onset diabetes, diabetes duration of < 5 years, and diabetes duration of ≥ 5 years. Cox proportional hazards models were used to investigate the association of diabetes status with cancer risk. RESULTS:The risk of total cancer increased as diabetes status worsened, as did the risks of liver, biliary, and pancreatic cancer. Risks of liver, biliary, and pancreatic cancer were significantly higher in subjects aged 65-74 years than in those aged ≥ 75 years. The relationship of diabetes status with overall cancer incidence was found to significantly interact with sex. Among subjects with diabetes, the risks of liver and lung cancer were significantly higher in men than in women regardless of diabetes duration. CONCLUSIONS:Diabetes status is associated with increased risk of cancer in the elderly. There are age and sex differences in the risk of total and site-specific cancers, including liver, biliary, and pancreatic cancer. This study highlights the importance of cancer screening for elderly subjects with diabetes.

Hypoxia in pancreatic islets (islet hypoxia) can occur in type 2 diabetes mellitus. Previously, our in vitro experiments demonstrated that pancreatic stellate cells (PSCs) within the islet are activated in hypoxia, promoting pancreatic β-cell death. Here, we aimed to demonstrate the in vivo activation of intra-islet PSCs and investigate the mechanism of PSC-induced β-cell death in hypoxia. A novel in vivo model of islet hypoxia was established by injecting fluorescent microspheres into a carotid artery of Balb/c mice (Microsphere mice). The intraperitoneal glucose tolerance (IPGTT) was performed, and pancreatic tissues were stained for insulin expression after tissue clearing. Pimonidazole staining was also performed in the pancreas to detect the presence of hypoxia in islets. Next, primary PSCs were isolated and cultured from Balb/c mice. Exosomes were isolated from culture media from PSCs cultured in hypoxia (1% oxygen). MicroRNAs (miRNAs) were prepared from exosomes from PSCs, and miRNA expression profiles were analyzed by miRNA sequencing. Several miRNAs were overexpressed in islets using miRNA mimics. Two weeks after injection of microspheres, the Microsphere mice showed worsening of glucose tolerance in IPGTT. Later, cataracts were developed in the eyes of the mice. The pancreas showed that the areas, perimeters, and diameters of insulin-positive cells decreased in Microsphere mice. Pimonidazole adducts were detected in the islets of these mice, indicating the presence of islet hypoxia. In addition, α-smooth muscle actin-positive cell numbers per islet were higher in Microsphere mice, confirming the in vivo activation of intra-islet PSCs in hypoxia. Mouse islets incubated with exosomes isolated from PSCs cultured in hypoxia showed a decrease in cell viability. The exosomes contained a variety of miRNAs, of which miR-23a-3p was found to notably increase β-cell death through apoptosis. Together, our in vivo and in vitro data provide evidence to support that PSCs within the islets are activated in hypoxia and promote β-cell death through exosomal miRNA transfer, which may contribute to the progression of type 2 diabetes mellitus.

Background: Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures.Methods: We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider’s medical specialty, the proximity to the medical center, and financial burdens of treatment.Results: Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over –2.5, and in five (2.3%) patients due to expected dental procedures.Conclusion: Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.

Aims: We aimed to investigate weight change in patients with new-onset type 2 diabetes mellitus and the association of weight loss on diabetes remission in Korean adults.Materials and MethodsWe used the health examination database of the Korean National Health Insurance Service. Patients diagnosed with type 2 diabetes mellitus from 2009 to 2012 were enrolled and followed to 2017. The baseline body weight was measured at the health examination closest to the time the patient was enrolled, and the change was calculated by examining the weight measured at the subsequent examination within 2 years. Remission was defined as fasting blood glucose less than 126 mg/dl at two or more consecutive health examinations after stopping medication.Results: In total, 114, 874 patients with new-onset type 2 diabetes mellitus were analysed. Of these, 23 156 (20.2%) lost more than 5% of their body weight, and 2429 (2.1%) achieved remission. The adjusted odds ratio for remission in the weight loss group was 2.56 (95% confidence interval 2.35-2.79) compared with the group with stable body weight. Sensitivity analysis according to the degree of weight change showed that the greater weight loss, the higher the likelihood of remission. In the subgroup analysis, the effects of weight loss on remission were significantly greater in subgroups of age <65 years, male sex and body mass index >25.Conclusion: Weight loss within the first 2 years of treating type 2 diabetes mellitus was associated with diabetes remission. Physicians should pay more attention to weight management in new-onset type 2 diabetes mellitus, particularly for young and obese individuals.

Metabolic syndrome is associated with type 2 diabetes and its prevalence is increasing worldwide in young adults. We aimed to determine whether cumulative exposure to metabolic syndrome is associated with type 2 diabetes risk in young adults. Data of 1,376,540 participants aged 20–39 years without a history of type 2 diabetes and who underwent four annual health check-ups were collected. In this large-scale prospective cohort study, we evaluated the incidence rates and hazard ratios (HRs) of diabetes according to cumulative frequencies of metabolic syndrome over 4 years of consecutive annual health check-ups (burden score 0–4). Subgroup analyses were performed by sex and age. During 5.18 years of follow-up, 18,155 young adults developed type 2 diabetes. The incidence of type 2 diabetes increased with burden score (P < 0.0001). The multivariable-adjusted HRs for type 2 diabetes were 4.757, 10.511, 18.288, and 31.749 in participants with a burden score of 1 to 4, respectively, compared to those with 0. In subgroup analyses, the risk of incident diabetes was greater in women than men and in the 20–29 years age group than the 30–39 years age group. The HRs were 47.473 in women and 27.852 in men with four burden scores. The risk of type 2 diabetes significantly increased with an increase in the cumulative burden of metabolic syndrome in young adults. Additionally, the association between cumulative burden and diabetes risk was stronger in women and the 20s age group.