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":null,"pages":null},"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}
João Carlos Locatelli, Juliene Gonçalves Costa, Andrew Haynes, Louise H. Naylor, P. Gerry Fegan, Bu B. Yeap, Daniel J. Green
This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15–24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin. However, these agents also cause rapid and significant loss of lean mass (∼10% or ∼6 kg), comparable to a decade or more of aging. Maintaining muscle mass and function as humans age is crucial to avoiding sarcopenia and frailty, which are strongly linked to morbidity and mortality. Studies indicate that supervised resistance exercise training interventions with a duration >10 weeks can elicit large increases in lean mass (∼3 kg) and strength (∼25%) in men and women. After a low-calorie diet, combining aerobic exercise with liraglutide improved weight loss maintenance compared with either alone. Retaining lean mass during incretin therapy could blunt body weight (and fat) regain on cessation of weight loss pharmacotherapy. We propose that tailored resistance exercise training be recommended as an adjunct to incretin therapy to optimize changes in body composition by preserving lean mass while achieving fat loss.
{"title":"Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?","authors":"João Carlos Locatelli, Juliene Gonçalves Costa, Andrew Haynes, Louise H. Naylor, P. Gerry Fegan, Bu B. Yeap, Daniel J. Green","doi":"10.2337/dci23-0100","DOIUrl":"https://doi.org/10.2337/dci23-0100","url":null,"abstract":"This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15–24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin. However, these agents also cause rapid and significant loss of lean mass (∼10% or ∼6 kg), comparable to a decade or more of aging. Maintaining muscle mass and function as humans age is crucial to avoiding sarcopenia and frailty, which are strongly linked to morbidity and mortality. Studies indicate that supervised resistance exercise training interventions with a duration >10 weeks can elicit large increases in lean mass (∼3 kg) and strength (∼25%) in men and women. After a low-calorie diet, combining aerobic exercise with liraglutide improved weight loss maintenance compared with either alone. Retaining lean mass during incretin therapy could blunt body weight (and fat) regain on cessation of weight loss pharmacotherapy. We propose that tailored resistance exercise training be recommended as an adjunct to incretin therapy to optimize changes in body composition by preserving lean mass while achieving fat loss.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817610","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}
Angelica Cristello Sarteau, Gabriella Ercolino, Rashmi Muthukkumar, Angela Fruik, Elizabeth J. Mayer-Davis, Anna R. Kahkoska
There is an emerging population of older adults (≥65 years) living with type 1 diabetes. Optimizing health through nutrition during this life stage is challenged by multiple and ongoing changes in diabetes management, comorbidities, and lifestyle factors. There is a need to understand nutritional status, dietary intake, and nutrition-related interventions that may maximize well-being throughout the life span in type 1 diabetes, in addition to nutrition recommendations from clinical guidelines and consensus reports. Three reviewers used Cochrane guidelines to screen original research (January 1993–2023) and guidelines (2012–2023) in two databases (MEDLINE and CENTRAL) to characterize nutrition evidence in this population. We found limited original research explicitly focused on nutrition and diet in adults ≥65 years of age with type 1 diabetes (six experimental studies, five observational studies) and meta-analyses/reviews (one scoping review), since in the majority of analyses individuals ≥65 years of age were combined with those age ≥18 years, with diverse diabetes durations, and also individuals with type 1 and type 2 diabetes were combined. Further, existing clinical guidelines (n = 10) lacked specificity and evidence to guide clinical practice and self-management behaviors in this population. From a scientific perspective, little is known about nutrition and diet among older adults with type 1 diabetes, including baseline nutrition status, dietary intake and eating behaviors, and the impact of nutrition interventions on key clinical and patient-oriented outcomes. This likely reflects the population’s recent emergence and unique considerations. Addressing these gaps is foundational to developing evidence-based nutrition practices and guidelines for older adults living with type 1 diabetes.
{"title":"Nutritional Status, Dietary Intake, and Nutrition-Related Interventions Among Older Adults With Type 1 Diabetes: A Systematic Review and Call for More Evidence Toward Clinical Guidelines","authors":"Angelica Cristello Sarteau, Gabriella Ercolino, Rashmi Muthukkumar, Angela Fruik, Elizabeth J. Mayer-Davis, Anna R. Kahkoska","doi":"10.2337/dci23-0099","DOIUrl":"https://doi.org/10.2337/dci23-0099","url":null,"abstract":"There is an emerging population of older adults (≥65 years) living with type 1 diabetes. Optimizing health through nutrition during this life stage is challenged by multiple and ongoing changes in diabetes management, comorbidities, and lifestyle factors. There is a need to understand nutritional status, dietary intake, and nutrition-related interventions that may maximize well-being throughout the life span in type 1 diabetes, in addition to nutrition recommendations from clinical guidelines and consensus reports. Three reviewers used Cochrane guidelines to screen original research (January 1993–2023) and guidelines (2012–2023) in two databases (MEDLINE and CENTRAL) to characterize nutrition evidence in this population. We found limited original research explicitly focused on nutrition and diet in adults ≥65 years of age with type 1 diabetes (six experimental studies, five observational studies) and meta-analyses/reviews (one scoping review), since in the majority of analyses individuals ≥65 years of age were combined with those age ≥18 years, with diverse diabetes durations, and also individuals with type 1 and type 2 diabetes were combined. Further, existing clinical guidelines (n = 10) lacked specificity and evidence to guide clinical practice and self-management behaviors in this population. From a scientific perspective, little is known about nutrition and diet among older adults with type 1 diabetes, including baseline nutrition status, dietary intake and eating behaviors, and the impact of nutrition interventions on key clinical and patient-oriented outcomes. This likely reflects the population’s recent emergence and unique considerations. Addressing these gaps is foundational to developing evidence-based nutrition practices and guidelines for older adults living with type 1 diabetes.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817583","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}
Hector M. González, Wassim Tarraf, Ariana M. Stickel, Alejandra Morlett, Kevin A. González, Alberto R. Ramos, Tatjana Rundek, Linda C. Gallo, Gregory A. Talavera, Martha L. Daviglus, Richard B. Lipton, Carmen Isasi, Melissa Lamar, Donglin Zeng, Charles DeCarli
OBJECTIVE Hispanics/Latinos in the United States have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanics/Latinos of diverse heritages. RESEARCH DESIGN AND METHODS Study of Latinos–Investigation of Neurocognitive Aging (SOL-INCA) is a Hispanic Community Health Study/Study of Latinos (HCHS/SOL) ancillary study. HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability sampled prospective cohort study. SOL-INCA enrolled 6,377 diverse Hispanics/Latinos age 50 years and older (2016–2018). The primary outcomes were cognitive function, 7-year cognitive decline and mild cognitive impairment (MCI). The primary glycemia exposure variables were measured from fasting blood samples collected at HCHS/SOL visit 1 (2008–2011). RESULTS Visit 1 mean age was 56.5 years ± 8.2 SD, and the average glycosylated hemoglobin A1C (HbA1c) was 6.12% (43.5 ± 14.6 mmol/mol). After covariates adjustment, higher HbA1c was associated with accelerated 7-year global (b = −0.045; 95% CI = −0.070; −0.021; in z-score units) and executive cognitive decline, and a higher prevalence of MCI (odds ratio = 1.20; 95% CI = 1.11;1.29). CONCLUSIONS Elevated HbA1c levels were associated with 7-year executive cognitive decline and increased MCI risk among diverse middle-aged and older Hispanics/Latinos. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanics/Latinos of diverse heritages.
{"title":"Glycemic Control, Cognitive Aging, and Impairment Among Diverse Hispanics/Latinos: Study of Latinos–Investigation of Neurocognitive Aging (Hispanic Community Health Study/Study of Latinos)","authors":"Hector M. González, Wassim Tarraf, Ariana M. Stickel, Alejandra Morlett, Kevin A. González, Alberto R. Ramos, Tatjana Rundek, Linda C. Gallo, Gregory A. Talavera, Martha L. Daviglus, Richard B. Lipton, Carmen Isasi, Melissa Lamar, Donglin Zeng, Charles DeCarli","doi":"10.2337/dc23-2003","DOIUrl":"https://doi.org/10.2337/dc23-2003","url":null,"abstract":"OBJECTIVE Hispanics/Latinos in the United States have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanics/Latinos of diverse heritages. RESEARCH DESIGN AND METHODS Study of Latinos–Investigation of Neurocognitive Aging (SOL-INCA) is a Hispanic Community Health Study/Study of Latinos (HCHS/SOL) ancillary study. HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability sampled prospective cohort study. SOL-INCA enrolled 6,377 diverse Hispanics/Latinos age 50 years and older (2016–2018). The primary outcomes were cognitive function, 7-year cognitive decline and mild cognitive impairment (MCI). The primary glycemia exposure variables were measured from fasting blood samples collected at HCHS/SOL visit 1 (2008–2011). RESULTS Visit 1 mean age was 56.5 years ± 8.2 SD, and the average glycosylated hemoglobin A1C (HbA1c) was 6.12% (43.5 ± 14.6 mmol/mol). After covariates adjustment, higher HbA1c was associated with accelerated 7-year global (b = −0.045; 95% CI = −0.070; −0.021; in z-score units) and executive cognitive decline, and a higher prevalence of MCI (odds ratio = 1.20; 95% CI = 1.11;1.29). CONCLUSIONS Elevated HbA1c levels were associated with 7-year executive cognitive decline and increased MCI risk among diverse middle-aged and older Hispanics/Latinos. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanics/Latinos of diverse heritages.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817580","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}
Maya Spaur, Marta Galvez-Fernandez, Qixuan Chen, Melissa A. Lombard, Benjamin C. Bostick, Pam Factor-Litvak, Amanda M. Fretts, Steven J. Shea, Ana Navas-Acien, Anne E. Nigra
OBJECTIVE We examined the association of arsenic in federally regulated community water systems (CWSs) and unregulated private wells with type 2 diabetes (T2D) incidence in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially and ethnically diverse urban U.S. communities. RESEARCH DESIGN AND METHODS We evaluated 1,791 participants from SHFS and 5,777 participants from MESA who had water arsenic estimates available and were free of T2D at baseline (2001–2003 and 2000–2002, respectively). Participants were followed for incident T2D until 2010 (SHFS cohort) or 2019 (MESA cohort). We used Cox proportional hazards mixed-effects models to account for clustering by family and residential zip code, with adjustment for sex, baseline age, BMI, smoking status, and education. RESULTS T2D incidence was 24.4 cases per 1,000 person-years (mean follow-up, 5.6 years) in SHFS and 11.2 per 1,000 person-years (mean follow-up, 14.0 years) in MESA. In a meta-analysis across the SHFS and MESA cohorts, the hazard ratio (95% CI) per doubling in CWS arsenic was 1.10 (1.02, 1.18). The corresponding hazard ratio was 1.09 (0.95, 1.26) in the SHFS group and 1.10 (1.01, 1.20) in the MESA group. The corresponding hazard ratio (95% CI) for arsenic in private wells and incident T2D in SHFS was 1.05 (0.95, 1.16). We observed statistical interaction and larger magnitude hazard ratios for participants with BMI <25 kg/m2 and female participants. CONCLUSIONS Low to moderate water arsenic levels (<10 µg/L) were associated with T2D incidence in the SHFS and MESA cohorts.
{"title":"Association of Water Arsenic With Incident Diabetes in U.S. Adults: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study","authors":"Maya Spaur, Marta Galvez-Fernandez, Qixuan Chen, Melissa A. Lombard, Benjamin C. Bostick, Pam Factor-Litvak, Amanda M. Fretts, Steven J. Shea, Ana Navas-Acien, Anne E. Nigra","doi":"10.2337/dc23-2231","DOIUrl":"https://doi.org/10.2337/dc23-2231","url":null,"abstract":"OBJECTIVE We examined the association of arsenic in federally regulated community water systems (CWSs) and unregulated private wells with type 2 diabetes (T2D) incidence in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially and ethnically diverse urban U.S. communities. RESEARCH DESIGN AND METHODS We evaluated 1,791 participants from SHFS and 5,777 participants from MESA who had water arsenic estimates available and were free of T2D at baseline (2001–2003 and 2000–2002, respectively). Participants were followed for incident T2D until 2010 (SHFS cohort) or 2019 (MESA cohort). We used Cox proportional hazards mixed-effects models to account for clustering by family and residential zip code, with adjustment for sex, baseline age, BMI, smoking status, and education. RESULTS T2D incidence was 24.4 cases per 1,000 person-years (mean follow-up, 5.6 years) in SHFS and 11.2 per 1,000 person-years (mean follow-up, 14.0 years) in MESA. In a meta-analysis across the SHFS and MESA cohorts, the hazard ratio (95% CI) per doubling in CWS arsenic was 1.10 (1.02, 1.18). The corresponding hazard ratio was 1.09 (0.95, 1.26) in the SHFS group and 1.10 (1.01, 1.20) in the MESA group. The corresponding hazard ratio (95% CI) for arsenic in private wells and incident T2D in SHFS was 1.05 (0.95, 1.16). We observed statistical interaction and larger magnitude hazard ratios for participants with BMI &lt;25 kg/m2 and female participants. CONCLUSIONS Low to moderate water arsenic levels (&lt;10 µg/L) were associated with T2D incidence in the SHFS and MESA cohorts.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642181","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}
Hongwei Ji, Joseph E. Ebinger, Alan C. Kwan, Karen Reue, Jennifer C. Sullivan, John Shyy, Susan Cheng
OBJECTIVE To investigate whether the sex disparities in type 2 diabetes–associated cardiovascular disease (CVD) risks may be related to early-onset hypertension that could benefit from intensive blood pressure (BP) control. RESEARCH DESIGN AND METHODS We analyzed intensive versus standard BP control in relation to incident CVD events in women and men with type 2 diabetes, based on their age of hypertension diagnosis. RESULTS Among 3,792 adults with type 2 diabetes (49% women), multivariable-adjusted CVD risk was increased per decade earlier age at hypertension diagnosis (hazard ratio 1.11 [1.03–1.21], P = 0.006). Excess risk associated with early-diagnosed hypertension was attenuated in the presence of intensive versus standard antihypertensive therapy in women (P = 0.036) but not men (P = 0.76). CONCLUSIONS Women with type 2 diabetes and early-onset hypertension may represent a higher-risk subpopulation that not only contributes to the female excess in diabetes-related CVD risk but may benefit from intensive BP control.
{"title":"Early-Onset Hypertension and Sex-Specific Residual Risk for Cardiovascular Disease in Type 2 Diabetes","authors":"Hongwei Ji, Joseph E. Ebinger, Alan C. Kwan, Karen Reue, Jennifer C. Sullivan, John Shyy, Susan Cheng","doi":"10.2337/dc23-2275","DOIUrl":"https://doi.org/10.2337/dc23-2275","url":null,"abstract":"OBJECTIVE To investigate whether the sex disparities in type 2 diabetes–associated cardiovascular disease (CVD) risks may be related to early-onset hypertension that could benefit from intensive blood pressure (BP) control. RESEARCH DESIGN AND METHODS We analyzed intensive versus standard BP control in relation to incident CVD events in women and men with type 2 diabetes, based on their age of hypertension diagnosis. RESULTS Among 3,792 adults with type 2 diabetes (49% women), multivariable-adjusted CVD risk was increased per decade earlier age at hypertension diagnosis (hazard ratio 1.11 [1.03–1.21], P = 0.006). Excess risk associated with early-diagnosed hypertension was attenuated in the presence of intensive versus standard antihypertensive therapy in women (P = 0.036) but not men (P = 0.76). CONCLUSIONS Women with type 2 diabetes and early-onset hypertension may represent a higher-risk subpopulation that not only contributes to the female excess in diabetes-related CVD risk but may benefit from intensive BP control.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642247","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}
Giuseppe Daniele, Andrea Tura, Alex Brocchi, Alessandro Saba, Beatrice Campi, Veronica Sancho-Bornez, Angela Dardano, Stefano Del Prato
OBJECTIVE To explore the complementary effects of a combination of dipeptidyl peptidase 4 and sodium–glucose cotransporter 2 inhibitors added to metformin on hormonal and metabolic responses to meal ingestion. RESEARCH DESIGN AND METHODS Forty-five patients (age 58 ± 8 years; HbA1c 58 ± 6 mmol/mol; BMI 30.7 ± 3.2 kg/m2) with type 2 diabetes uncontrolled with metformin were evaluated at baseline and 3 and 28 days after 5 mg saxagliptin (SAXA), 10 mg dapagliflozin (DAPA), or 5 mg saxagliptin plus 10 mg dapagliflozin (SAXA+DAPA) using a mixed-meal tolerance test (MMTT) spiked with dual-tracer glucose to assess glucose metabolism, insulin secretion, and sensitivity. RESULTS At day 3, fasting and mean MMTT glucose levels were lower with SAXA+DAPA (−31.1 ± 1.6 and −91.5 ± 12.4 mg/dL) than with SAXA (−7.1 ± 2.1 and −53 ± 10.5 mg/dL) or DAPA (−17.0 ± 1.1 and −42.6 ± 10.0 mg/dL, respectively; P < 0.001). Insulin secretion rate (SAXA+DAPA +75%; SAXA +11%; DAPA 3%) and insulin sensitivity (+2.2 ± 1.7, +0.4 ± 0.7, and +0.4 ± 0.4 mg ⋅ kg−1⋅ min−1, respectively) improved with SAXA+DAPA (P < 0.007). Mean glucagon-like peptide 1 (GLP-1) was higher with SAXA+DAPA than with SAXA or DAPA. Fasting glucagon increased with DAPA and SAXA+DAPA but not with SAXA. Fasting endogenous glucose production (EGP) increased with SAXA+DAPA and DAPA. During MMTT, EGP suppression was greater (48%) with SAXA+DAPA (vs. SAXA 44%; P = 0.02 or DAPA 34%; P = 0.2). Metabolic clearance rate of glucose (MCRglu) increased more with SAXA+DAPA. At week 4, insulin secretion rate, β-cell glucose sensitivity, and insulin sensitivity had further increased in the SAXA+DAPA group (P = 0.02), with no additional changes in GLP-1, glucagon, fasting or MMTT EGP, or MCRglu. CONCLUSIONS SAXA+DAPA provided superior glycemic control compared with DAPA or SAXA, with improved β-cell function, insulin sensitivity, GLP-1 availability, and glucose clearance.
{"title":"β-Cell Function, Incretin Effect, and Glucose Kinetics in Response to a Mixed Meal in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin","authors":"Giuseppe Daniele, Andrea Tura, Alex Brocchi, Alessandro Saba, Beatrice Campi, Veronica Sancho-Bornez, Angela Dardano, Stefano Del Prato","doi":"10.2337/dc23-2051","DOIUrl":"https://doi.org/10.2337/dc23-2051","url":null,"abstract":"OBJECTIVE To explore the complementary effects of a combination of dipeptidyl peptidase 4 and sodium–glucose cotransporter 2 inhibitors added to metformin on hormonal and metabolic responses to meal ingestion. RESEARCH DESIGN AND METHODS Forty-five patients (age 58 ± 8 years; HbA1c 58 ± 6 mmol/mol; BMI 30.7 ± 3.2 kg/m2) with type 2 diabetes uncontrolled with metformin were evaluated at baseline and 3 and 28 days after 5 mg saxagliptin (SAXA), 10 mg dapagliflozin (DAPA), or 5 mg saxagliptin plus 10 mg dapagliflozin (SAXA+DAPA) using a mixed-meal tolerance test (MMTT) spiked with dual-tracer glucose to assess glucose metabolism, insulin secretion, and sensitivity. RESULTS At day 3, fasting and mean MMTT glucose levels were lower with SAXA+DAPA (−31.1 ± 1.6 and −91.5 ± 12.4 mg/dL) than with SAXA (−7.1 ± 2.1 and −53 ± 10.5 mg/dL) or DAPA (−17.0 ± 1.1 and −42.6 ± 10.0 mg/dL, respectively; P &lt; 0.001). Insulin secretion rate (SAXA+DAPA +75%; SAXA +11%; DAPA 3%) and insulin sensitivity (+2.2 ± 1.7, +0.4 ± 0.7, and +0.4 ± 0.4 mg ⋅ kg−1⋅ min−1, respectively) improved with SAXA+DAPA (P &lt; 0.007). Mean glucagon-like peptide 1 (GLP-1) was higher with SAXA+DAPA than with SAXA or DAPA. Fasting glucagon increased with DAPA and SAXA+DAPA but not with SAXA. Fasting endogenous glucose production (EGP) increased with SAXA+DAPA and DAPA. During MMTT, EGP suppression was greater (48%) with SAXA+DAPA (vs. SAXA 44%; P = 0.02 or DAPA 34%; P = 0.2). Metabolic clearance rate of glucose (MCRglu) increased more with SAXA+DAPA. At week 4, insulin secretion rate, β-cell glucose sensitivity, and insulin sensitivity had further increased in the SAXA+DAPA group (P = 0.02), with no additional changes in GLP-1, glucagon, fasting or MMTT EGP, or MCRglu. CONCLUSIONS SAXA+DAPA provided superior glycemic control compared with DAPA or SAXA, with improved β-cell function, insulin sensitivity, GLP-1 availability, and glucose clearance.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640255","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}
Heiko Bratke, Eva Biringer, Anastasia Ushakova, Hanna D. Margeirsdottir, Siv Janne Kummernes, Pål R. Njølstad, Torild Skrivarhaug
OBJECTIVE To evaluate, from 2013 to 2022, how HbA1c, the incidence of acute complications, and use of diabetes technology changed at the national level in Norway and how glycemic control was associated with use of diabetes technology, carbohydrate counting, or participation in a quality improvement project. RESEARCH DESIGN AND METHODS This longitudinal observational study was based on 27,214 annual registrations of 6,775 children from the Norwegian Childhood Diabetes Registry from 2013 to 2022. Individuals aged >18 years, those with diabetes other than type 1, and those without HbA1c measurements were excluded. The outcome measure was HbA1c. The predictor variables in the adjusted linear mixed-effects model were 1) the use of diabetes technology, 2) the use of carbohydrate counting for meal bolusing, and 3) whether the patient’s diabetes team participated in a quality improvement project. RESULTS Mean HbA1c decreased from 8.2% (2013) to 7.2% (2021), and the proportion of youth reaching an HbA1c <7.0% increased from 13% (2013) to 43% (2022). Insulin pump use increased from 65% (2013) to 91% (2022). Continuous glucose monitoring (CGM) use increased from 34% (first recorded in 2016) to 97% (2022). Insulin pump, CGM, and carbohydrate counting were associated with lower HbA1c and higher achievement of glycemic targets. Girls had a higher mean HbA1c than boys. Mean HbA1c levels were lower in clinics that participated in a quality improvement project for the following 4 years after the project. CONCLUSIONS Diabetes technology, carbohydrate counting, and systematic quality improvement in pediatric departments led to improved glycemic control.
{"title":"Ten Years of Improving Glycemic Control in Pediatric Diabetes Care: Data From the Norwegian Childhood Diabetes Registry","authors":"Heiko Bratke, Eva Biringer, Anastasia Ushakova, Hanna D. Margeirsdottir, Siv Janne Kummernes, Pål R. Njølstad, Torild Skrivarhaug","doi":"10.2337/dc24-0086","DOIUrl":"https://doi.org/10.2337/dc24-0086","url":null,"abstract":"OBJECTIVE To evaluate, from 2013 to 2022, how HbA1c, the incidence of acute complications, and use of diabetes technology changed at the national level in Norway and how glycemic control was associated with use of diabetes technology, carbohydrate counting, or participation in a quality improvement project. RESEARCH DESIGN AND METHODS This longitudinal observational study was based on 27,214 annual registrations of 6,775 children from the Norwegian Childhood Diabetes Registry from 2013 to 2022. Individuals aged &gt;18 years, those with diabetes other than type 1, and those without HbA1c measurements were excluded. The outcome measure was HbA1c. The predictor variables in the adjusted linear mixed-effects model were 1) the use of diabetes technology, 2) the use of carbohydrate counting for meal bolusing, and 3) whether the patient’s diabetes team participated in a quality improvement project. RESULTS Mean HbA1c decreased from 8.2% (2013) to 7.2% (2021), and the proportion of youth reaching an HbA1c &lt;7.0% increased from 13% (2013) to 43% (2022). Insulin pump use increased from 65% (2013) to 91% (2022). Continuous glucose monitoring (CGM) use increased from 34% (first recorded in 2016) to 97% (2022). Insulin pump, CGM, and carbohydrate counting were associated with lower HbA1c and higher achievement of glycemic targets. Girls had a higher mean HbA1c than boys. Mean HbA1c levels were lower in clinics that participated in a quality improvement project for the following 4 years after the project. CONCLUSIONS Diabetes technology, carbohydrate counting, and systematic quality improvement in pediatric departments led to improved glycemic control.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636154","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}
Philip Zeitler, Rodolfo J. Galindo, Melanie J. Davies, Brandon K. Bergman, Vivian T. Thieu, Claudia Nicolay, Sheryl Allen, Robert J. Heine, Clare J. Lee
OBJECTIVE We evaluated baseline characteristics of participants with early-onset type 2 diabetes (T2D) from the SURPASS program and tirzepatide’s effects on glycemic control, body weight (BW), and cardiometabolic markers. RESEARCH DESIGN AND METHODS This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in 3,792 participants with early-onset versus later-onset T2D at week 40 (A Study of Tirzepatide [LY3298176] in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone [SURPASS-1], A Study of Tirzepatide [LY3298176] Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes [SURPASS-2]) or week 52 (A Study of Tirzepatide [LY3298176] Versus Insulin Degludec in Participants With Type 2 Diabetes [SURPASS-3]). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. RESULTS At baseline in SURPASS-2, participants with early-onset versus later-onset T2D were younger with longer diabetes duration (9 vs. 7 years, P < 0.001) higher glycemic levels (8.5% vs. 8.2%, P < 0.001), higher BW (97 vs. 93 kg, P < 0.001) and BMI (35 vs. 34 kg/m2, P < 0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs. 156 mg/dL). At week 40, similar improvements in HbA1c (−2.6% vs. −2.4%), BW (−14 vs. −13 kg), WC (−10 vs. −10 cm), triglycerides (−26% vs. −24%), HDL (7% vs. 7%), and systolic BP (−6 vs. −7 mmHg) were observed in both subgroups with tirzepatide. CONCLUSIONS Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline versus those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW, and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D.
目的 我们评估了 SURPASS 计划中早发 2 型糖尿病 (T2D) 参与者的基线特征以及替扎帕肽对血糖控制、体重 (BW) 和心脏代谢指标的影响。研究设计与方法 本项事后分析比较了 3792 名早发与晚发 T2D 参与者在第 40 周时的基线特征以及平均 HbA1c、体重、腰围 (WC)、血脂和血压 (BP) 的变化（单靠饮食和运动无法控制血糖的 2 型糖尿病患者服用替扎帕肽 [LY3298176] 的研究 [SURPASS-1]）、2型糖尿病患者二甲双胍附加疗法中替唑帕肽[LY3298176]与塞马鲁肽每周一次的比较研究[SURPASS-2]）或第52周（2型糖尿病患者中替唑帕肽[LY3298176]与德格鲁德胰岛素的比较研究[SURPASS-3]）。研究分析了参与者在接受指定治疗期间的数据，在出现持续高血糖时未使用抢救药物。结果 在 SURPASS-2 的基线研究中，早发与晚发 T2D 患者的年龄更小，糖尿病病程更长（9 年 vs. 7 年，P < 0.001），血糖水平更高（8.5% vs. 8.2%，P < 0.001）。5% vs. 8.2%，Pamp;lt; 0.001），体重（97 kg vs. 93 kg，Pamp;lt; 0.001）和体重指数（35 kg/m2 vs. 34 kg/m2，Pamp;lt; 0.001）较高，血脂也同样异常（如甘油三酯 167 vs. 甘油三酯 167 vs. 甘油三酯 34 kg/m2，Pamp;lt; 0.001）、甘油三酯 167 vs. 156 mg/dL）。第 40 周时，观察到两个亚组的 HbA1c（-2.6% vs. -2.4%）、体重（-14 kg vs. -13kg）、腹围（-10 cm vs. -10cm）、甘油三酯（-26% vs. -24%）、高密度脂蛋白（7% vs. 7%）和收缩压（-6 mmHg vs. -7mmHg）在使用替扎帕肽后均有类似改善。结论 尽管 SURPASS 计划的早发性 T2D 参与者年龄较小，但与晚发性 T2D 参与者相比，他们的血糖水平较高，整体代谢健康状况较差。在这项事后分析中，无论确诊 T2D 时的年龄如何，使用替扎帕肽对 HbA1c、体重和心脏代谢指标都有类似的改善。未来还需要进行研究，以确定替扎帕肽对早发性 T2D 的长期疗效。
{"title":"Early-Onset Type 2 Diabetes and Tirzepatide Treatment: A Post Hoc Analysis From the SURPASS Clinical Trial Program","authors":"Philip Zeitler, Rodolfo J. Galindo, Melanie J. Davies, Brandon K. Bergman, Vivian T. Thieu, Claudia Nicolay, Sheryl Allen, Robert J. Heine, Clare J. Lee","doi":"10.2337/dc23-2356","DOIUrl":"https://doi.org/10.2337/dc23-2356","url":null,"abstract":"OBJECTIVE We evaluated baseline characteristics of participants with early-onset type 2 diabetes (T2D) from the SURPASS program and tirzepatide’s effects on glycemic control, body weight (BW), and cardiometabolic markers. RESEARCH DESIGN AND METHODS This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in 3,792 participants with early-onset versus later-onset T2D at week 40 (A Study of Tirzepatide [LY3298176] in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone [SURPASS-1], A Study of Tirzepatide [LY3298176] Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes [SURPASS-2]) or week 52 (A Study of Tirzepatide [LY3298176] Versus Insulin Degludec in Participants With Type 2 Diabetes [SURPASS-3]). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. RESULTS At baseline in SURPASS-2, participants with early-onset versus later-onset T2D were younger with longer diabetes duration (9 vs. 7 years, P &lt; 0.001) higher glycemic levels (8.5% vs. 8.2%, P &lt; 0.001), higher BW (97 vs. 93 kg, P &lt; 0.001) and BMI (35 vs. 34 kg/m2, P &lt; 0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs. 156 mg/dL). At week 40, similar improvements in HbA1c (−2.6% vs. −2.4%), BW (−14 vs. −13 kg), WC (−10 vs. −10 cm), triglycerides (−26% vs. −24%), HDL (7% vs. 7%), and systolic BP (−6 vs. −7 mmHg) were observed in both subgroups with tirzepatide. CONCLUSIONS Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline versus those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW, and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621612","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}
Stine H. Scheuer, Gregers S. Andersen, Bendix Carstensen, Lars Diaz, Vanja Kosjerina, Nanna Lindekilde, Sarah H. Wild, Caroline A. Jackson, Frans Pouwer, Michael E. Benros, Marit E. Jørgensen
OBJECTIVE To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year. RESEARCH DESIGN AND METHODS We conducted a cohort study using nationwide registers from 1996 to 2020 to identify individuals with diabetes, ascertain SMI status (namely, schizophrenia, bipolar disorder, or major depression) and identify the outcomes: hospitalization for hypoglycemia and diabetic ketoacidosis (DKA). We used Poisson regression to estimate incidence rates (IRs) and incidence rate ratios (IRRs) of recurrent hypoglycemia and DKA events by SMI, age, and calendar year, accounting for sex, diabetes duration, education, and country of origin. RESULTS Among 433,609 individuals with diabetes, 8% had SMI. Risk of (first and subsequent) hypoglycemia events was higher for individuals with SMI than for those without SMI (for first hypoglycemia event, IRR: type 1 diabetes, 1.77 [95% CI 1.56–2.00]; type 2 diabetes, 1.64 [95% CI 1.55–1.74]). Individuals with schizophrenia were particularly at risk for recurrent hypoglycemia events. The risk of first DKA event was higher in individuals with SMI (for first DKA event, IRR: type 1 diabetes, 1.78 [95% CI 1.50–2.11]; type 2 diabetes, 1.85 [95% CI 1.64–2.09]). Except for DKA in the type 2 diabetes group, IR differences between individuals with and without SMI were highest in younger individuals (<50 years old) but stable across the calendar year. CONCLUSIONS SMI is an important risk factor for acute diabetes complication and effective prevention is needed in this population, especially among the younger population and those with schizophrenia.
{"title":"Trends in Incidence of Hospitalization for Hypoglycemia and Diabetic Ketoacidosis in Individuals With Type 1 or Type 2 Diabetes With and Without Severe Mental Illness in Denmark From 1996 to 2020: A Nationwide Study","authors":"Stine H. Scheuer, Gregers S. Andersen, Bendix Carstensen, Lars Diaz, Vanja Kosjerina, Nanna Lindekilde, Sarah H. Wild, Caroline A. Jackson, Frans Pouwer, Michael E. Benros, Marit E. Jørgensen","doi":"10.2337/dc23-2394","DOIUrl":"https://doi.org/10.2337/dc23-2394","url":null,"abstract":"OBJECTIVE To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year. RESEARCH DESIGN AND METHODS We conducted a cohort study using nationwide registers from 1996 to 2020 to identify individuals with diabetes, ascertain SMI status (namely, schizophrenia, bipolar disorder, or major depression) and identify the outcomes: hospitalization for hypoglycemia and diabetic ketoacidosis (DKA). We used Poisson regression to estimate incidence rates (IRs) and incidence rate ratios (IRRs) of recurrent hypoglycemia and DKA events by SMI, age, and calendar year, accounting for sex, diabetes duration, education, and country of origin. RESULTS Among 433,609 individuals with diabetes, 8% had SMI. Risk of (first and subsequent) hypoglycemia events was higher for individuals with SMI than for those without SMI (for first hypoglycemia event, IRR: type 1 diabetes, 1.77 [95% CI 1.56–2.00]; type 2 diabetes, 1.64 [95% CI 1.55–1.74]). Individuals with schizophrenia were particularly at risk for recurrent hypoglycemia events. The risk of first DKA event was higher in individuals with SMI (for first DKA event, IRR: type 1 diabetes, 1.78 [95% CI 1.50–2.11]; type 2 diabetes, 1.85 [95% CI 1.64–2.09]). Except for DKA in the type 2 diabetes group, IR differences between individuals with and without SMI were highest in younger individuals (&lt;50 years old) but stable across the calendar year. CONCLUSIONS SMI is an important risk factor for acute diabetes complication and effective prevention is needed in this population, especially among the younger population and those with schizophrenia.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":16.2,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621587","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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