Coralie Amadou, Yuxia Wei, Maria Feychting, Sofia Carlsson
OBJECTIVE Childhood-onset type 1 diabetes (T1D) is associated with perinatal factors, but data related to adult-onset T1D are scarce. This study aimed at investigating the association between early-life factors and adult-onset T1D in a Swedish nationwide cohort and family-based study. RESEARCH DESIGN AND METHODS We included 1,813,415 individuals aged ≥18 years, born in Sweden 1983 to 2002, followed until 2020. T1D diagnosis (n = 3,283) was identified from the National Diabetes, Patient and Prescribed Drugs Registers, and perinatal exposures were obtained from the Medical Birth Register. We performed Cox proportional hazard (hazard ratio [95% CI]) regression with mutual adjustment for perinatal exposures, sex, birth year, and parental sociodemographic background and history of diabetes. We also compared T1D risks among siblings’ groups identified from the Multiple Generation Register. RESULTS The incidence rate of adult-onset T1D was 18.8 per 100,000 person-years. Year of birth (1.06 [1.01–1.10], per five additional years) and history of maternal (4.10 [3.09–5.43]) and paternal (6.24 [5.10–7.64]) T1D were associated with a higher incidence of adult-onset T1D, whereas female sex (0.69 [0.64–0.74]) and having parents born outside Sweden were associated with a lower incidence. Regarding perinatal exposures, only non–full-term birth (<39 weeks vs. ≥39 weeks) was associated with a higher incidence of adult-onset T1D (1.12 [1.04–1.22]). The sibling cohort results were consistent with the full cohort analysis. CONCLUSIONS Perinatal factors seem to play a minor role in the development of adult-onset T1D compared with childhood-onset T1D, suggesting that triggers or accelerators of autoimmunity occurring later in life are more significant.
{"title":"Early-Life Factors Associated With Adult-Onset Type 1 Diabetes: A Swedish Nationwide Cohort and Family-Based Study","authors":"Coralie Amadou, Yuxia Wei, Maria Feychting, Sofia Carlsson","doi":"10.2337/dc24-0896","DOIUrl":"https://doi.org/10.2337/dc24-0896","url":null,"abstract":"OBJECTIVE Childhood-onset type 1 diabetes (T1D) is associated with perinatal factors, but data related to adult-onset T1D are scarce. This study aimed at investigating the association between early-life factors and adult-onset T1D in a Swedish nationwide cohort and family-based study. RESEARCH DESIGN AND METHODS We included 1,813,415 individuals aged ≥18 years, born in Sweden 1983 to 2002, followed until 2020. T1D diagnosis (n = 3,283) was identified from the National Diabetes, Patient and Prescribed Drugs Registers, and perinatal exposures were obtained from the Medical Birth Register. We performed Cox proportional hazard (hazard ratio [95% CI]) regression with mutual adjustment for perinatal exposures, sex, birth year, and parental sociodemographic background and history of diabetes. We also compared T1D risks among siblings’ groups identified from the Multiple Generation Register. RESULTS The incidence rate of adult-onset T1D was 18.8 per 100,000 person-years. Year of birth (1.06 [1.01–1.10], per five additional years) and history of maternal (4.10 [3.09–5.43]) and paternal (6.24 [5.10–7.64]) T1D were associated with a higher incidence of adult-onset T1D, whereas female sex (0.69 [0.64–0.74]) and having parents born outside Sweden were associated with a lower incidence. Regarding perinatal exposures, only non–full-term birth (&lt;39 weeks vs. ≥39 weeks) was associated with a higher incidence of adult-onset T1D (1.12 [1.04–1.22]). The sibling cohort results were consistent with the full cohort analysis. CONCLUSIONS Perinatal factors seem to play a minor role in the development of adult-onset T1D compared with childhood-onset T1D, suggesting that triggers or accelerators of autoimmunity occurring later in life are more significant.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"16 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coco M Fuhri Snethlage, Timothy J McDonald, Richard D Oram, Pleun de Groen, Elena Rampanelli, Alinda W M Schimmel, Frits Holleman, Sarah Siegelaar, Joost Hoekstra, Catherine B Brouwer, Filip K Knop, C Bruce Verchere, Daniël H van Raalte, Bart O Roep, Max Nieuwdorp, Nordin M J Hanssen
Objective: Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual β-cell function and metrics of continuous glucose monitoring (CGM) in individuals with T1D.
Research design and methods: In this cross-sectional cohort comprising 489 individuals (64% female, age 41.0 ± 14.0 years), T1D duration was 15.0 (interquartile range [IQR] 6.0-29.0) years. Individuals had a time in range (TIR) of 66% (IQR 52-80%) and a urinary C-peptide-to-creatinine ratio (UCPCR) of 0.01 (IQR 0.00-0.41) nmol/mmol. To assess β-cell function, we measured UCPCR (detectable >0.01 nmol/mmol), and to assess α-cell function, fasting plasma glucagon/glucose ratios were measured. CGM was used to record TIR (3.9-10 mmol/L), time below range (TBR) (<3.9 mmol/L), time above range (TAR) (>10 mmol/L), and glucose coefficient of variance (CV). For CGM, 74.7% used FreeStyle Libre 2, 13.8% Medtronic Guardian, and 11.5% Dexcom G6 as their device.
Results: The percentage of patients with T1D who had a detectable UCPCR was 49.4%. A higher UCPCR correlated with higher TIR (r = 0.330, P < 0.05), lower TBR (r = -0.237, P < 0.05), lower TAR (r = -0.302, P < 0.05), and lower glucose CV (r = -0.356, P < 0.05). A higher UCPCR correlated negatively with HbA1c levels (r = -0.183, P < 0.05) and total daily insulin dose (r = -0.183, P < 0.05). Glucagon/glucose ratios correlated with longer TIR (r = 0.234, P < 0.05).
Conclusions: Significantly longer TIR, shorter TBR and TAR, and lower CV were observed in individuals with greater UCPCR-assessed β-cell function. Therefore, better CGM-derived metrics in individuals with preserved β-cell function may be a contributor to a lower risk of developing long-term complications.
{"title":"Residual β-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes.","authors":"Coco M Fuhri Snethlage, Timothy J McDonald, Richard D Oram, Pleun de Groen, Elena Rampanelli, Alinda W M Schimmel, Frits Holleman, Sarah Siegelaar, Joost Hoekstra, Catherine B Brouwer, Filip K Knop, C Bruce Verchere, Daniël H van Raalte, Bart O Roep, Max Nieuwdorp, Nordin M J Hanssen","doi":"10.2337/dc23-0776","DOIUrl":"10.2337/dc23-0776","url":null,"abstract":"<p><strong>Objective: </strong>Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual β-cell function and metrics of continuous glucose monitoring (CGM) in individuals with T1D.</p><p><strong>Research design and methods: </strong>In this cross-sectional cohort comprising 489 individuals (64% female, age 41.0 ± 14.0 years), T1D duration was 15.0 (interquartile range [IQR] 6.0-29.0) years. Individuals had a time in range (TIR) of 66% (IQR 52-80%) and a urinary C-peptide-to-creatinine ratio (UCPCR) of 0.01 (IQR 0.00-0.41) nmol/mmol. To assess β-cell function, we measured UCPCR (detectable >0.01 nmol/mmol), and to assess α-cell function, fasting plasma glucagon/glucose ratios were measured. CGM was used to record TIR (3.9-10 mmol/L), time below range (TBR) (<3.9 mmol/L), time above range (TAR) (>10 mmol/L), and glucose coefficient of variance (CV). For CGM, 74.7% used FreeStyle Libre 2, 13.8% Medtronic Guardian, and 11.5% Dexcom G6 as their device.</p><p><strong>Results: </strong>The percentage of patients with T1D who had a detectable UCPCR was 49.4%. A higher UCPCR correlated with higher TIR (r = 0.330, P < 0.05), lower TBR (r = -0.237, P < 0.05), lower TAR (r = -0.302, P < 0.05), and lower glucose CV (r = -0.356, P < 0.05). A higher UCPCR correlated negatively with HbA1c levels (r = -0.183, P < 0.05) and total daily insulin dose (r = -0.183, P < 0.05). Glucagon/glucose ratios correlated with longer TIR (r = 0.234, P < 0.05).</p><p><strong>Conclusions: </strong>Significantly longer TIR, shorter TBR and TAR, and lower CV were observed in individuals with greater UCPCR-assessed β-cell function. Therefore, better CGM-derived metrics in individuals with preserved β-cell function may be a contributor to a lower risk of developing long-term complications.</p>","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":" ","pages":"1114-1121"},"PeriodicalIF":14.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aino Latva-Rasku, Eleni Rebelos, Jouni Tuisku, Richard Aarnio, Achol Bhowmik, Helmi Keskinen, Sanna Laurila, Minna Lahesmaa-Hatting, Laura Pekkarinen, Henrik Isackson, Anna K. Kirjavainen, Jukka Koffert, Kerstin Heurling, Lauri Nummenmaa, Ele Ferrannini, Jonas Oldgren, Jan Oscarsson, Pirjo Nuutila
OBJECTIVE The aim of this study was to investigate the impact of the sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET). RESEARCH DESIGN AND METHODS In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups. RESULTS A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] μmol ⋅ 100 g−1 ⋅ min−1; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] μmol ⋅ 100 g−1 ⋅ min−1; P = 0.01), an effect observed in both gray and white matter regions. CONCLUSIONS Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain.
目的 本研究旨在通过正电子发射断层扫描（PET）研究钠-葡萄糖共转运体 2 (SGLT2) 抑制剂达帕格列净对 2 型糖尿病患者骨骼肌、大脑、小肠、皮下和内脏脂肪组织中组织脂肪酸 (FA) 摄取的影响。研究设计与方法 在一项为期 6 周的随机双盲安慰剂对照试验中，53 名接受二甲双胍治疗的 2 型糖尿病患者每天服用 10 毫克达帕格列净或安慰剂。在基线和治疗结束时，使用 PET 和长链 FA 类似物放射性示踪剂 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid 对组织 FA 摄取量进行量化。治疗效果采用方差分析进行评估，结果以最小平方均值和组间差异的 95% CI 报告。结果 共有 38 名患者（达帕格列净 n = 21；安慰剂 n = 17）完成了研究。6 周后，与安慰剂相比，达帕格列净增加了骨骼肌对 FA 的吸收（1.0 [0.07, 2.0] μmol⋅100 g-1 ⋅min-1; P = 0.032），而小肠、内脏或皮下脂肪组织对 FA 的吸收没有显著变化。达帕格列净治疗可显著增加全脑 FA 摄取量（0.10 [0.02, 0.17] μmol⋅100 g-1⋅min-1; P = 0.01），在灰质和白质区域均可观察到这种效应。结论 达帕格列净治疗六周可增加骨骼肌和大脑对 FA 的吸收，部分原因是游离 FA 的增加。这一发现与之前的间接测量结果一致，表明SGLT2抑制剂可促进脂肪酸代谢，并将脂肪酸使用增加的概念延伸至肌肉和大脑。
{"title":"SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study","authors":"Aino Latva-Rasku, Eleni Rebelos, Jouni Tuisku, Richard Aarnio, Achol Bhowmik, Helmi Keskinen, Sanna Laurila, Minna Lahesmaa-Hatting, Laura Pekkarinen, Henrik Isackson, Anna K. Kirjavainen, Jukka Koffert, Kerstin Heurling, Lauri Nummenmaa, Ele Ferrannini, Jonas Oldgren, Jan Oscarsson, Pirjo Nuutila","doi":"10.2337/dc24-0470","DOIUrl":"https://doi.org/10.2337/dc24-0470","url":null,"abstract":"OBJECTIVE The aim of this study was to investigate the impact of the sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET). RESEARCH DESIGN AND METHODS In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups. RESULTS A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] μmol ⋅ 100 g−1 ⋅ min−1; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] μmol ⋅ 100 g−1 ⋅ min−1; P = 0.01), an effect observed in both gray and white matter regions. CONCLUSIONS Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"23 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaqi Hu, James R. Pike, Pamela L. Lutsey, A. Richey Sharrett, Lynne E. Wagenknecht, Timothy M. Hughes, Jesse C. Seegmiller, Rebecca F. Gottesman, Thomas H. Mosley, Elizabeth Selvin, Michael Fang, Josef Coresh
OBJECTIVE The impact of age of diabetes diagnosis on dementia risk across the life course is poorly characterized. We estimated the lifetime risk of dementia by age of diabetes diagnosis. RESEARCH DESIGN AND METHODS We included 13,087 participants from the Atherosclerosis Risk in Communities Study who were free from dementia at age 60 years. We categorized participants as having middle age–onset diabetes (diagnosis <60 years), older-onset diabetes (diagnosis 60–69 years), or no diabetes. Incident dementia was ascertained via adjudication and active surveillance. We used the cumulative incidence function estimator to characterize the lifetime risk of dementia by age of diabetes diagnosis while accounting for the competing risk of mortality. We used restricted mean survival time to calculate years lived without and with dementia. RESULTS Among 13,087 participants, there were 2,982 individuals with dementia and 4,662 deaths without dementia during a median follow-up of 24.1 (percentile 25–percentile 75, 17.4–28.3) years. Individuals with middle age–onset diabetes had a significantly higher lifetime risk of dementia than those with older-onset diabetes (36.0% vs. 31.0%). Compared with those with no diabetes, participants with middle age–onset diabetes also had a higher cumulative incidence of dementia by age 80 years (16.1% vs. 9.4%), but a lower lifetime risk (36.0% vs. 45.6%) due to shorter survival. Individuals with middle age–onset diabetes developed dementia 4 and 1 years earlier than those without diabetes and those with older-onset diabetes, respectively. CONCLUSIONS Preventing or delaying diabetes may be an important approach for reducing dementia risk throughout the life course.
{"title":"Age of Diabetes Diagnosis and Lifetime Risk of Dementia: The Atherosclerosis Risk in Communities (ARIC) Study","authors":"Jiaqi Hu, James R. Pike, Pamela L. Lutsey, A. Richey Sharrett, Lynne E. Wagenknecht, Timothy M. Hughes, Jesse C. Seegmiller, Rebecca F. Gottesman, Thomas H. Mosley, Elizabeth Selvin, Michael Fang, Josef Coresh","doi":"10.2337/dc24-0203","DOIUrl":"https://doi.org/10.2337/dc24-0203","url":null,"abstract":"OBJECTIVE The impact of age of diabetes diagnosis on dementia risk across the life course is poorly characterized. We estimated the lifetime risk of dementia by age of diabetes diagnosis. RESEARCH DESIGN AND METHODS We included 13,087 participants from the Atherosclerosis Risk in Communities Study who were free from dementia at age 60 years. We categorized participants as having middle age–onset diabetes (diagnosis &lt;60 years), older-onset diabetes (diagnosis 60–69 years), or no diabetes. Incident dementia was ascertained via adjudication and active surveillance. We used the cumulative incidence function estimator to characterize the lifetime risk of dementia by age of diabetes diagnosis while accounting for the competing risk of mortality. We used restricted mean survival time to calculate years lived without and with dementia. RESULTS Among 13,087 participants, there were 2,982 individuals with dementia and 4,662 deaths without dementia during a median follow-up of 24.1 (percentile 25–percentile 75, 17.4–28.3) years. Individuals with middle age–onset diabetes had a significantly higher lifetime risk of dementia than those with older-onset diabetes (36.0% vs. 31.0%). Compared with those with no diabetes, participants with middle age–onset diabetes also had a higher cumulative incidence of dementia by age 80 years (16.1% vs. 9.4%), but a lower lifetime risk (36.0% vs. 45.6%) due to shorter survival. Individuals with middle age–onset diabetes developed dementia 4 and 1 years earlier than those without diabetes and those with older-onset diabetes, respectively. CONCLUSIONS Preventing or delaying diabetes may be an important approach for reducing dementia risk throughout the life course.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"36 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zsu-Zsu Chen, Chang Lu, Jonathan M. Dreyfuss, Gaurav Tiwari, Xu Shi, Shuning Zheng, Danielle Wolfs, Laura Pyle, Petter Bjornstad, Laure El Ghormli, Robert E. Gerszten, Elvira Isganaitis
OBJECTIVE We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10–17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0–36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. RESULTS Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function. CONCLUSIONS Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.
{"title":"Circulating Metabolite Biomarkers of Glycemic Control in Youth-Onset Type 2 Diabetes","authors":"Zsu-Zsu Chen, Chang Lu, Jonathan M. Dreyfuss, Gaurav Tiwari, Xu Shi, Shuning Zheng, Danielle Wolfs, Laura Pyle, Petter Bjornstad, Laure El Ghormli, Robert E. Gerszten, Elvira Isganaitis","doi":"10.2337/dc23-2441","DOIUrl":"https://doi.org/10.2337/dc23-2441","url":null,"abstract":"OBJECTIVE We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10–17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0–36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. RESULTS Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q &lt; 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q &lt; 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function. CONCLUSIONS Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"23 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariana Byndloss, Suzanne Devkota, Frank Duca, Jan Hendrik Niess, Max Nieuwdorp, Marju Orho-Melander, Yolanda Sanz, Valentina Tremaroli, Liping Zhao
This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single–time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.
{"title":"The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications—2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum","authors":"Mariana Byndloss, Suzanne Devkota, Frank Duca, Jan Hendrik Niess, Max Nieuwdorp, Marju Orho-Melander, Yolanda Sanz, Valentina Tremaroli, Liping Zhao","doi":"10.2337/dci24-0052","DOIUrl":"https://doi.org/10.2337/dci24-0052","url":null,"abstract":"This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single–time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"62 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guillermo E. Umpierrez, Georgia M. Davis, Nuha A. ElSayed, Gian Paolo Fadini, Rodolfo J. Galindo, Irl B. Hirsch, David C. Klonoff, Rozalina G. McCoy, Shivani Misra, Robert A. Gabbay, Raveendhara R. Bannuru, Ketan K. Dhatariya
The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American Association of Clinical Endocrinology (AACE), and Diabetes Technology Society (DTS) convened a panel of internists and diabetologists to update the ADA consensus statement on hyperglycemic crises in adults with diabetes, published in 2001 and last updated in 2009. The objective of this consensus report is to provide up-to-date knowledge about the epidemiology, pathophysiology, clinical presentation, and recommendations for the diagnosis, treatment, and prevention of diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) in adults. A systematic examination of publications since 2009 informed new recommendations. The target audience is the full spectrum of diabetes health care professionals and individuals with diabetes.
{"title":"Hyperglycemic Crises in Adults With Diabetes: A Consensus Report","authors":"Guillermo E. Umpierrez, Georgia M. Davis, Nuha A. ElSayed, Gian Paolo Fadini, Rodolfo J. Galindo, Irl B. Hirsch, David C. Klonoff, Rozalina G. McCoy, Shivani Misra, Robert A. Gabbay, Raveendhara R. Bannuru, Ketan K. Dhatariya","doi":"10.2337/dci24-0032","DOIUrl":"https://doi.org/10.2337/dci24-0032","url":null,"abstract":"The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American Association of Clinical Endocrinology (AACE), and Diabetes Technology Society (DTS) convened a panel of internists and diabetologists to update the ADA consensus statement on hyperglycemic crises in adults with diabetes, published in 2001 and last updated in 2009. The objective of this consensus report is to provide up-to-date knowledge about the epidemiology, pathophysiology, clinical presentation, and recommendations for the diagnosis, treatment, and prevention of diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) in adults. A systematic examination of publications since 2009 informed new recommendations. The target audience is the full spectrum of diabetes health care professionals and individuals with diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"1 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karl Sebastian Johansson, Espen Jimenez-Solem, Tonny Studsgaard Petersen, Mikkel Bring Christensen
OBJECTIVE Type 2 diabetes often coexists with other conditions that are amenable to pharmacological treatment. We hypothesized that polypharmacy among individuals with type 2 diabetes has increased since 2000. RESEARCH DESIGN AND METHODS Using Danish national registries, we established a cohort of all Danish individuals (aged ≥18 years) with type 2 diabetes between 2000 and 2020. We analyzed their medication use and prevalence of varying degrees of polypharmacy (≥5 or ≥10 medications), stratifying by age, sex, number of chronic diseases, and socioeconomic status. RESULTS The cohort grew from 84,917 patients in 2000 to 307,011 in 2020, totaling 461,849 unique patients. The number of daily medications used per patient increased from (mean ± SD) 3.7 ± 2.8 (in 2000) to 5.3 ± 3.2 (in 2020). The lifetime risk of polypharmacy was substantial, with 89% (n = 409,062 of 461,849) being exposed to ≥5 medications at some point and 47% (n = 217,467of 461,849) to ≥10 medications. The increases were driven by an expanding group of medications, with analgesics, antihypertensives, proton pump inhibitors, and statins having the largest net increase. Advanced age, male sex, lower socioeconomic status, and Danish ethnicity positively correlated with polypharmacy but could not explain the overall increase in polypharmacy. CONCLUSIONS Medication use and polypharmacy have increased among patients with type 2 diabetes. Although the implications and appropriateness of this increased medication use are uncertain, the results stress the increasing need for health care personnel to understand the potential risks associated with polypharmacy, including medication interactions, adverse effects, and over- and underprescribing.
{"title":"Increasing Medication Use and Polypharmacy in Type 2 Diabetes: The Danish Experience From 2000 to 2020","authors":"Karl Sebastian Johansson, Espen Jimenez-Solem, Tonny Studsgaard Petersen, Mikkel Bring Christensen","doi":"10.2337/dc24-0011","DOIUrl":"https://doi.org/10.2337/dc24-0011","url":null,"abstract":"OBJECTIVE Type 2 diabetes often coexists with other conditions that are amenable to pharmacological treatment. We hypothesized that polypharmacy among individuals with type 2 diabetes has increased since 2000. RESEARCH DESIGN AND METHODS Using Danish national registries, we established a cohort of all Danish individuals (aged ≥18 years) with type 2 diabetes between 2000 and 2020. We analyzed their medication use and prevalence of varying degrees of polypharmacy (≥5 or ≥10 medications), stratifying by age, sex, number of chronic diseases, and socioeconomic status. RESULTS The cohort grew from 84,917 patients in 2000 to 307,011 in 2020, totaling 461,849 unique patients. The number of daily medications used per patient increased from (mean ± SD) 3.7 ± 2.8 (in 2000) to 5.3 ± 3.2 (in 2020). The lifetime risk of polypharmacy was substantial, with 89% (n = 409,062 of 461,849) being exposed to ≥5 medications at some point and 47% (n = 217,467of 461,849) to ≥10 medications. The increases were driven by an expanding group of medications, with analgesics, antihypertensives, proton pump inhibitors, and statins having the largest net increase. Advanced age, male sex, lower socioeconomic status, and Danish ethnicity positively correlated with polypharmacy but could not explain the overall increase in polypharmacy. CONCLUSIONS Medication use and polypharmacy have increased among patients with type 2 diabetes. Although the implications and appropriateness of this increased medication use are uncertain, the results stress the increasing need for health care personnel to understand the potential risks associated with polypharmacy, including medication interactions, adverse effects, and over- and underprescribing.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"14 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Celeste Durnwald, Roy W. Beck, Zoey Li, Elizabeth Norton, Richard M. Bergenstal, Mary Johnson, Sean Dunnigan, Matthew Banfield, Katie Krumwiede, Judy Sibayan, Peter Calhoun, Anders L. Carlson
OBJECTIVE To determine whether continuous glucose monitoring (CGM)-derived glycemic patterns can characterize pregnancies with gestational diabetes mellitus (GDM) as diagnosed by standard oral glucose tolerance test at 24–28 weeks’ gestation compared with those without GDM. RESEARCH DESIGN AND METHODS The analysis includes 768 individuals enrolled from two sites prior to 17 weeks’ gestation between June 2020 and December 2021 in a prospective observational study. Participants wore blinded Dexcom G6 CGMs throughout gestation. Main outcome of interest was a diagnosis of GDM by oral glucose tolerance test (OGTT). Glycemic levels in participants with GDM versus without GDM were characterized using CGM-measured glycemic metrics. RESULTS Participants with GDM (n = 58 [8%]) had higher mean glucose (109 ± 13 vs. 100 ± 8 mg/dL [6.0 ± 0.7 vs. 5.6 ± 0.4 mmol/L], P < 0.001), greater glucose SD (23 ± 4 vs. 19 ± 3 mg/dL [1.3 ± 0.2 vs. 1.1 ± 0.2 mmol/L], P < 0.001), less time in range 63–120 mg/dL (3.5–6.7 mmol/L) (70% ± 17% vs. 84% ± 8%, P < 0.001), greater percent time >120 mg/dL (>6.7 mmol/L) (median 23% vs. 12%, P < 0.001), and greater percent time >140 mg/dL (>7.8 mmol/L) (median 7.4% vs. 2.7%, P < 0.001) than those without GDM throughout gestation prior to OGTT. Median percent time >120 mg/dL (>6.7 mmol/L) and time >140 mg/dL (>7.8 mmol/L) were higher as early as 13–14 weeks of gestation (32% vs. 14%, P < 0.001, and 5.2% vs. 2.0%, P < 0.001, respectively) and persisted during the entire study period prior to OGTT. CONCLUSIONS Prior to OGTT at 24–34 weeks’ gestation, pregnant individuals who develop GDM have higher CGM-measured glucose levels and more hyperglycemia compared with those who do not develop GDM.
{"title":"Continuous Glucose Monitoring Profiles in Pregnancies With and Without Gestational Diabetes Mellitus","authors":"Celeste Durnwald, Roy W. Beck, Zoey Li, Elizabeth Norton, Richard M. Bergenstal, Mary Johnson, Sean Dunnigan, Matthew Banfield, Katie Krumwiede, Judy Sibayan, Peter Calhoun, Anders L. Carlson","doi":"10.2337/dc23-2149","DOIUrl":"https://doi.org/10.2337/dc23-2149","url":null,"abstract":"OBJECTIVE To determine whether continuous glucose monitoring (CGM)-derived glycemic patterns can characterize pregnancies with gestational diabetes mellitus (GDM) as diagnosed by standard oral glucose tolerance test at 24–28 weeks’ gestation compared with those without GDM. RESEARCH DESIGN AND METHODS The analysis includes 768 individuals enrolled from two sites prior to 17 weeks’ gestation between June 2020 and December 2021 in a prospective observational study. Participants wore blinded Dexcom G6 CGMs throughout gestation. Main outcome of interest was a diagnosis of GDM by oral glucose tolerance test (OGTT). Glycemic levels in participants with GDM versus without GDM were characterized using CGM-measured glycemic metrics. RESULTS Participants with GDM (n = 58 [8%]) had higher mean glucose (109 ± 13 vs. 100 ± 8 mg/dL [6.0 ± 0.7 vs. 5.6 ± 0.4 mmol/L], P &lt; 0.001), greater glucose SD (23 ± 4 vs. 19 ± 3 mg/dL [1.3 ± 0.2 vs. 1.1 ± 0.2 mmol/L], P &lt; 0.001), less time in range 63–120 mg/dL (3.5–6.7 mmol/L) (70% ± 17% vs. 84% ± 8%, P &lt; 0.001), greater percent time &gt;120 mg/dL (&gt;6.7 mmol/L) (median 23% vs. 12%, P &lt; 0.001), and greater percent time &gt;140 mg/dL (&gt;7.8 mmol/L) (median 7.4% vs. 2.7%, P &lt; 0.001) than those without GDM throughout gestation prior to OGTT. Median percent time &gt;120 mg/dL (&gt;6.7 mmol/L) and time &gt;140 mg/dL (&gt;7.8 mmol/L) were higher as early as 13–14 weeks of gestation (32% vs. 14%, P &lt; 0.001, and 5.2% vs. 2.0%, P &lt; 0.001, respectively) and persisted during the entire study period prior to OGTT. CONCLUSIONS Prior to OGTT at 24–34 weeks’ gestation, pregnant individuals who develop GDM have higher CGM-measured glucose levels and more hyperglycemia compared with those who do not develop GDM.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"52 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVE Metformin, insulin, and insulin secretagogues do not alter HbA1c levels in glucokinase-maturity-onset diabetes of the young (GCK-MODY). However, the efficacy of the new hypoglycemic drugs on GCK-MODY remains unclear. RESEARCH DESIGN AND METHODS We describe a case of GCK-MODY with unchanged blood glucose under different therapies during an 8 years’ follow-up. His HbA1c and biochemical indices under different hypoglycemic treatments were recorded. RESULTS Oral antidiabetic drugs, including thiazolidinediones, dipeptidyl peptidase IV inhibitor, α-glucosidase inhibitor, and sodium-glucose cotransporter 2 inhibitor that had not been evaluated previously, did not improve the HbA1c level in this patient. However, the glucokinase activator dorzagliatin effectively and safely lowered his HbA1c level. CONCLUSIONS Dorzagliatin was effective and safe in this patient with GCK-MODY, providing potential application prospects for precise treatment of GCK-MODY with dorzagliatin.
{"title":"Hypoglycemic Response to Dorzagliatin in a Patient With GCK-MODY","authors":"Yilin Zhao, Yumin Ma, Tianhao Ba, Xueyao Han, Qian Ren, Linong Ji","doi":"10.2337/dc23-2417","DOIUrl":"https://doi.org/10.2337/dc23-2417","url":null,"abstract":"OBJECTIVE Metformin, insulin, and insulin secretagogues do not alter HbA1c levels in glucokinase-maturity-onset diabetes of the young (GCK-MODY). However, the efficacy of the new hypoglycemic drugs on GCK-MODY remains unclear. RESEARCH DESIGN AND METHODS We describe a case of GCK-MODY with unchanged blood glucose under different therapies during an 8 years’ follow-up. His HbA1c and biochemical indices under different hypoglycemic treatments were recorded. RESULTS Oral antidiabetic drugs, including thiazolidinediones, dipeptidyl peptidase IV inhibitor, α-glucosidase inhibitor, and sodium-glucose cotransporter 2 inhibitor that had not been evaluated previously, did not improve the HbA1c level in this patient. However, the glucokinase activator dorzagliatin effectively and safely lowered his HbA1c level. CONCLUSIONS Dorzagliatin was effective and safe in this patient with GCK-MODY, providing potential application prospects for precise treatment of GCK-MODY with dorzagliatin.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":"24 1","pages":""},"PeriodicalIF":16.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140819474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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