{"title":"Do SGLT2 inhibitors and GLP-1 receptor agonists modulate differently the risk of stroke ? Discordance between randomised controlled trials and observational studies","authors":"André J. Scheen","doi":"10.1016/j.diabet.2023.101474","DOIUrl":"10.1016/j.diabet.2023.101474","url":null,"abstract":"<div><p>Stroke represents a major burden in patients with type 2 diabetes, yet this cerebrovascular complication has been less carefully investigated than the risk of cardiovascular mortality, heart failure and renal disease. Some data suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert a better protection against stroke than sodium-glucose cotransporter 2 inhibitors (SGLT2is). However, this conclusion was derived from indirect comparisons in absence of any head-to-head randomised controlled trial (RCT). The present comprehensive review compares the effects of SGLT2is versus GLP-1RAs on nonfatal and fatal/nonfatal strokes in network meta-analyses of RCTs (mostly cardiovascular outcome trials) versus placebo, on the one hand, and in real-life observational cohort studies, on the other hand. Whereas network meta-analyses of placebo-controlled RCTs confirm a slight but significant (in 11 out of 13 meta-analyses) higher incidence of stroke in patients treated with SGLT2is compared with those treated with GLP-1RAs, a large majority of retrospective observational cohort studies (19 out of 21) failed to find any significant difference in the risk of stroke between the two pharmacological classes. Available, yet limited, findings suggest that SGLT2is may be more efficacious against haemorrhagic than ischaemic strokes, in patients at risk for atrial fibrillation and in patients with chronic kidney disease.</p></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10251267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zi-Yang Peng , Yao-Tseng Wang , Chin-Sung Chang , Chih-Hsing Wu , Huang-Tz Ou
{"title":"Effect of SGLT2 inhibitors versus DPP4 inhibitors on major and non-major osteoporotic fracture risks among general and high-risk type 2 diabetes patients: A nationwide retrospective cohort study","authors":"Zi-Yang Peng , Yao-Tseng Wang , Chin-Sung Chang , Chih-Hsing Wu , Huang-Tz Ou","doi":"10.1016/j.diabet.2023.101465","DOIUrl":"10.1016/j.diabet.2023.101465","url":null,"abstract":"<div><h3>Aims</h3><p>To retrospectively analyze the association of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) with a range of major and non-major fracture events, and explore heterogeneous treatment effect among high-risk patient subgroups.</p></div><div><h3>Methods</h3><p>Newly stable SGLT2i or DPP4i users in 2017 were identified in Taiwan's National Health Insurance Research Database and followed up until a fracture occurred, loss of follow-up, death, or December 31, 2018, whichever came first. Outcomes included composite major and non-major fractures and individual components in major fractures. Cox model and restricted mean survival time (RMST) analyses were utilized to assess the treatment effect on fractures.</p></div><div><h3>Results</h3><p>21,155 propensity-score-matched SGLT2i and DPP4i users were obtained. Over 2 years, the hazard ratio and RMST difference for major fracture with SGLT2i versus DPP4i use were 0.89 (95% CI, 0.80, 1.00) and 1.51 (-0.17, 3.17) days, respectively, and those for non-major fracture with SGLT2i versus DPP4i use were 0.89 (0.81, 0.98) and 2.44 (0.47, 4.37) days, respectively. A 180-day lag time analysis for fracture outcomes showed consistent results with primary findings. A SGLT2is-associated harmful effect on major fractures (but not on non-major fractures) was observed among female patients and those with a diabetes duration of ≥ 8 years, prior fractures, and established osteoporosis.</p></div><div><h3>Conclusion</h3><p>This study adds supporting real-world evidence for SGLT2is-associated bone safety for a wide range of fractures, which promotes the rational use of SGLT2is in routine care and highlights the importance of the close monitoring of patients with high fracture risks to maximize treatment benefits while reducing undesirable effects.</p></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10297211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang-Wei Cai , Hai-Feng Zhang , Jing-Wei Gao , Zhao-Xi Cai , Jie-Wen Cai , Qing-Yuan Gao , Zhi-Teng Chen , Guang-Hong Liao , Chuan-Rui Zeng , Nuo Chen , Pin-Ming Liu , Jing-Feng Wang , Yang-Xin Chen
{"title":"Serum albumin and risk of incident diabetes and diabetic microvascular complications in the UK Biobank cohort","authors":"Yang-Wei Cai , Hai-Feng Zhang , Jing-Wei Gao , Zhao-Xi Cai , Jie-Wen Cai , Qing-Yuan Gao , Zhi-Teng Chen , Guang-Hong Liao , Chuan-Rui Zeng , Nuo Chen , Pin-Ming Liu , Jing-Feng Wang , Yang-Xin Chen","doi":"10.1016/j.diabet.2023.101472","DOIUrl":"10.1016/j.diabet.2023.101472","url":null,"abstract":"<div><h3>Aim</h3><p>To examine the associations between serum albumin and the incidences of diabetes and diabetic microvascular complications in participants of the UK Biobank cohort.</p></div><div><h3>Methods</h3><p>There were 398,146 participants without diabetes and 30,952 patients with diabetes from the UK Biobank cohort included in this study. Multivariate-adjusted Cox proportional hazard models were used to analyze the association of albumin with the incidences of diabetes and diabetic microvascular complications. Mendelian randomization (MR) analysis was used to determine the genetic relationships between serum albumin and diabetes.</p></div><div><h3>Results</h3><p>After a median 12.90 years follow-up, 14,710 participants developed incident diabetes (58.83 ± 7.52 years, 56.10% male). After multivariate adjustment, serum albumin was inversely associated with incident diabetes: hazard ratio (HR) [95% confidence interval] per 10 g/l increase 0.88 [0.82;0.94]. MR analyses suggested a potential genetic influence of serum albumin on diabetes in both the UK Biobank and the FinnGen consortium: odds ratios (ORs) [95% confidence interval per 1 g/l increase 0.99 [0.98;1.00] and 0.78 [0.67;0.92], respectively. In patients with diabetes, higher serum albumin levels were significantly associated with lower risk for diabetic microvascular complications. Specifically, per 10 g/l increase in serum albumin, the HRs for diabetic nephropathy, ophthalmopathy, and neuropathy were 0.42 [0.30;0.58], 0.61 [0.52;0.72], and 0.67 [0.51;0.88], respectively.</p></div><div><h3>Conclusion</h3><p>In this large prospective study, serum levels of albumin were inversely associated with the incidences of diabetes and diabetic microvascular complications. These findings underscore the importance of maintaining optimal nutrient status in reducing the risk of diabetes and its complications.</p></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10251265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexandra Katz , Aidan Shulkin , Meryem K. Talbo , Asmaa Housni , Jane Yardley , Anne-Sophie Brazeau , Rémi Rabasa-Lhoret
{"title":"Hyperglycemia-related anxiety during competition in an elite athlete with type 1 diabetes: A case report","authors":"Alexandra Katz , Aidan Shulkin , Meryem K. Talbo , Asmaa Housni , Jane Yardley , Anne-Sophie Brazeau , Rémi Rabasa-Lhoret","doi":"10.1016/j.diabet.2023.101476","DOIUrl":"10.1016/j.diabet.2023.101476","url":null,"abstract":"<div><h3>Aim</h3><p>Managing blood glucose (BG) levels during intense physical activity is challenging for elite athletes with type 1 diabetes (T1D), as it can lead to unpredictable hyper- or hypoglycemia, which can affect performance. This case study presents an 18-year-old male hockey goalie with hyperglycemia-related anxiety during competition and its impact on his T1D management.</p></div><div><h3>Methods</h3><p>Mixed-methods approach, incorporating qualitative data from an unstructured interview and responses from the <em>Hyperglycemia Avoidance Scale</em> along with quantitative data retrieved from Diasend and laboratory results.</p></div><div><h3>Results</h3><p>The athlete experiences physical and cognitive symptoms during hyperglycemia, affecting his performance. Hyperglycemia-related anxiety influences insulin dosage adjustments and eating habits on game days. Glycemic variability analysis reveals lower BG levels during game time.</p></div><div><h3>Conclusion</h3><p>Hyperglycemia-related anxiety leads to modified therapeutic and lifestyle regimens on competition day. Tailored treatment programs are needed for elite athletes with T1D and hyperglycemia-related anxiety.</p></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10251672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valeria Grancini , Andrea Gramegna , Laura Zazzeron , Gianfranco Alicandro , Laura L Porcaro , Federica Piedepalumbo , Chiara Lanfranchi , Valeria Daccò , Emanuela Orsi , Francesco Blasi
{"title":"Effects of elexacaftor / tezacaftor / ivacaftor triple combination therapy on glycaemic control and body composition in patients with cystic fibrosis-related diabetes","authors":"Valeria Grancini , Andrea Gramegna , Laura Zazzeron , Gianfranco Alicandro , Laura L Porcaro , Federica Piedepalumbo , Chiara Lanfranchi , Valeria Daccò , Emanuela Orsi , Francesco Blasi","doi":"10.1016/j.diabet.2023.101466","DOIUrl":"10.1016/j.diabet.2023.101466","url":null,"abstract":"<div><p>Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are a group of new drugs for the treatment of cystic fibrosis (CF) and elexacaftor + tezacaftor + ivacaftor (ETI) triple combination therapy has been approved as first choice therapy in the treatment of patients with at least 1 copy of F508del variation. Data on the effects of CFTR modulators on glucose metabolism are limited to small studies with conflicting results.</p><p>We conducted a prospective observational study on 24 CF patients with CF-related diabetes requiring insulin therapy, with the aim to evaluate the effectiveness of ETI on glucose metabolism, glucose variability and body composition. After six months of treatment, HbA1c and coefficient of variation, measured through flash or continuous glucose monitoring, significantly decreased (median changes: -0.5, <em>P</em> = 0.029 and -6.3, <em>P</em> = 0.008, respectively), despite unchanged insulin requirements.</p><p>Over the treatment period, percent of fat mass increased by a median value of 3% (<em>p</em> = 0.029).</p></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9962063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marine Monney , François R Jornayvaz , Karim Gariani
{"title":"GLP-1 receptor agonists effect on cognitive function in patients with and without type 2 diabetes","authors":"Marine Monney , François R Jornayvaz , Karim Gariani","doi":"10.1016/j.diabet.2023.101470","DOIUrl":"10.1016/j.diabet.2023.101470","url":null,"abstract":"<div><p>Glucagon-like peptide 1 (GLP-1) is a hormone of the incretin family, secreted in response to nutrient ingestion, and plays a role in metabolic homeostasis. GLP-1 receptor agonist has a peripheral and a central action, including stimulation of glucose-dependent insulin secretion and insulin biosynthesis, inhibition of glucagon secretion and gastric emptying, and inhibition of food intake. Through their mechanism, their use in the treatment of type 2 diabetes has been extended to the management of obesity, and numerous trials are being conducted to assess their cardiovascular effect. Type 2 diabetes appears to share common pathophysiological mechanisms with the development of cognitive disorders, such as Alzheimer's and Parkinson's disease, related to insulin resistance. In this review, we aim to examine the pathological features between type 2 diabetes and dementia, GLP-1 central effects, and analyze the relevant literature about the effect of GLP-1 analogs on cognitive function of patients with type 2 diabetes but also without. Results tends to show an improvement in some brain markers (e.g. hippocampal connections, cerebral glucose metabolism, hippocampal activation on functional magnetic resonance imaging), but without being able to demonstrate a strong correlation to cognitive scores. Some epidemiological studies suggest that GLP-1 receptor agonists may offer a protective effect, by delaying progression to dementia when diabetic patients are treated with GLP-1 receptor agonists. Ongoing trials are in progress and may provide disease-modifying care for Alzheimer's disease and Parkinson's disease patients in the future.</p></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10188806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shen Chen , Hongliang Xue , Rong Huang , Ke Chen , Haoyang Zhang , Xu Chen
{"title":"Associations of MAFLD and MAFLD subtypes with the risk of the incident myocardial infarction and stroke","authors":"Shen Chen , Hongliang Xue , Rong Huang , Ke Chen , Haoyang Zhang , Xu Chen","doi":"10.1016/j.diabet.2023.101468","DOIUrl":"10.1016/j.diabet.2023.101468","url":null,"abstract":"<div><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a condition characterized by liver fat accumulation and metabolic abnormalities. Given the potential impact of MAFLD on patient health, it is important to understand its association with major adverse cardiovascular events (MACE) such as myocardial infarction (MI) and stroke. In the prospective UK Biobank cohort, we sought to elucidate the association of MAFLD and its subtypes with incident MI and stroke. In this study, we analyzed the data of 325,129 participants in the UK Biobank and calculated relative risks for MI and stroke using Cox regression analysis. Among 325,129 participants over a median duration of 12.8 years follow-up, participants with MAFLD were significantly more likely to experience a MI (hazard ratio [HR] = 1.35, 95% confidence interval [CI: 1.29;1.41] <em>P</em> < 0.001) or a stroke (HR = 1.26 [1.18–1.33] <em>P</em> < 0.001) compared to those without MAFLD. In addition, diabetic, overweight with metabolic dysfunction (MD), and lean MAFLD subtypes were significantly associated with an increased risk for MI and stroke, whereas overweight without MD subtype did not appear to be associated with this risk. Our findings also revealed graded associations between liver fibrosis scores and risk of MI and stroke in MAFLD patients. However, only diabetic, and overweight patients with MD subtypes exhibited graded associations between liver fibrosis score and the risk of MI and stroke among the MAFLD subtypes. Furthermore, the risk alleles traits of fatty liver did not enhance the effect of MAFLD on the risk of MI and stroke. In conclusion, a diagnosis of MAFLD is associated with an increased risk of MI or stroke, and the assessment of MAFLD and its subtypes should be a component of the cardiovascular risk assessment.</p></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alicia Nevriana, Marios Rossides, Kyriaki Kosidou, Matthias Pierce, Christina Dalman, Susanne Wicks, Kathryn M. Abel
{"title":"Correspondence for “Parental history of psychiatric disorders and risk of type 1 diabetes in the offspring”","authors":"Alicia Nevriana, Marios Rossides, Kyriaki Kosidou, Matthias Pierce, Christina Dalman, Susanne Wicks, Kathryn M. Abel","doi":"10.1016/j.diabet.2023.101434","DOIUrl":"10.1016/j.diabet.2023.101434","url":null,"abstract":"","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9838630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}