A literature review and meta-analysis of safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus

Abstract We conducted a literature review and meta-analysis of safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies from their inception through to August 2019 and there was no language restriction. Trials were included in the analysis if they were randomized controlled trials (RCTs) (1) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM ≤ 18 years, and (2) reporting HbA1c and at least one adverse event. We calculated risk ratios with 95%CI and used a random-effects model. Twenty-two out of the 765 RCTs retrieved were ultimately included in the present review, and only one RCT included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparisons with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatments with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.

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Safety profiles of sodium-glucose co-transporter 2 inhibitors in Japanese patients with diabetes mellitus: A literature review and meta-analysis

10.21203/rs.3.rs-353578/v2 ◽

2021 ◽

Author(s):

Junichi Mukai ◽

Shinya Kanno ◽

Rie Kubota

Keyword(s):

Diabetes Mellitus ◽

Literature Review ◽

Meta Analysis ◽

Japanese Patients ◽

Sglt2 Inhibitors ◽

Patients With Diabetes ◽

Language Restriction ◽

Calculated Risk ◽

Favorable Safety ◽

Type 1 Dm

Abstract We conducted a literature review and meta-analysis of safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies from their inception through to August 2019 and there was no language restriction. Trials were included in the analysis if they were randomized controlled trials (RCTs) (1) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM ≤ 18 years, and (2) reporting HbA1c and at least one adverse event. We calculated risk ratios with 95%CI and used a random-effects model. Twenty-two out of the 765 RCTs retrieved were ultimately included in the present review, and only one RCT included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparisons with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatments with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.

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Helicobacter pyloriInfection Is Associated with Type 2 Diabetes, Not Type 1 Diabetes: An Updated Meta-Analysis

Gastroenterology Research and Practice ◽

10.1155/2017/5715403 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 16

Author(s):

Jun-Zhen Li ◽

Jie-Yao Li ◽

Ting-Feng Wu ◽

Ji-Hao Xu ◽

Can-Ze Huang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Meta Analysis ◽

Cochrane Library ◽

Knowledge Database ◽

Type 2 Dm ◽

The Difference ◽

H Pylori ◽

Type 1 Dm

Background. Extragastric manifestations ofHelicobacter pylori(H. pylori) infection have been reported in many diseases. However, there are still controversies about whetherH. pyloriinfection is associated with diabetes mellitus (DM). This study was aimed at answering the question.Methods. A systematic search of the literature from January 1996 to January 2016 was conducted in PubMed, Embase databases, Cochrane Library, Google Scholar, Wanfang Data, China national knowledge database, and SinoMed. Published studies reportingH. pyloriinfection in both DM and non-DM individuals were recruited.Results. 79 studies with 57,397 individuals were included in this meta-analysis. The prevalence ofH. pyloriinfection in DM group (54.9%) was significantly higher than that (47.5%) in non-DM group (OR = 1.69,P<0.001). The difference was significant in comparison between type 2 DM group and non-DM group (OR = 2.05), but not in that between type 1 DM group and non-DM group (OR = 1.23, 95% CI: 0.77–1.96,P=0.38).Conclusion. Our meta-analysis suggested that there is significantly higher prevalence ofH. pyloriinfection in DM patients as compared to non-DM individuals. And the difference is associated with type 2 DM but not type 1 DM.

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Novel Molecular Evidence Related to COVID-19 in Patients with Diabetes Mellitus

Journal of Clinical Medicine ◽

10.3390/jcm9123962 ◽

2020 ◽

Vol 9 (12) ◽

pp. 3962

Author(s):

Yu-Huang Liao ◽

Jing-Quan Zheng ◽

Cai-Mei Zheng ◽

Kuo-Cheng Lu ◽

You-Chen Chao

Keyword(s):

Diabetes Mellitus ◽

Viral Entry ◽

Cell Injury ◽

Molecular Evidence ◽

Protective Effects ◽

Cytosolic Ph ◽

S Protein ◽

Patients With Diabetes ◽

Type 1 Dm

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a global pandemic. The hyperglycemia in patients with diabetes mellitus (DM) substantially compromises their innate immune system. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) receptors to enter the affected cell. Uncontrolled hyperglycemia-induced glycosylation of ACE2 and the S protein of SARS-CoV-2 could facilitate the binding of S protein to ACE2, enabling viral entry. Downregulation of ACE2 activity secondary to SARS-CoV-2 infection, with consequent accumulation of angiotensin II and metabolites, eventually leads to poor outcomes. The altered binding of ACE2 with SARS-CoV-2 and the compromised innate immunity of patients with DM increase their susceptibility to COVID-19; COVID-19 induces pancreatic β-cell injury and poor glycemic control, which further compromises the immune response and aggravates hyperglycemia and COVID-19 progression, forming a vicious cycle. Sequential cleavage of viral S protein by furin and transmembrane serine protease 2 (TMPRSS2) triggers viral entry to release the viral genome into the target cell. Hence, TMPRSS2 and furin are possible drug targets. As type 1 DM exhibits a Th1-driven autoimmune process, the relatively lower mortality of COVID-19 in type 1 DM compared to type 2 DM might be attributed to an imbalance between Th1 and Th2 immunity. The anti-inflammatory effects of dipeptidyl peptidase-4 inhibitor may benefit patients with DM and COVID-19. The potential protective effects of sodium–glucose cotransporter-2 inhibitor (SGLT2i), including reduction in lactate level, prevention of lowering of cytosolic pH and reduction in pro-inflammatory cytokine levels may justify the provision of SGLT2i to patients with DM and mild or asymptomatic COVID-19. For patients with DM and COVID-19 who require hospitalization, insulin-based treatment is recommended with cessation of metformin and SGLT2i. Further evidence from randomized or case–control clinical trials is necessary to elucidate the effectiveness and pitfalls of different types of medication for DM.

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Thyroid dysfunction in patients with diabetes mellitus at Puducherry, India: a retrospective study

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20182445 ◽

2018 ◽

Vol 5 (4) ◽

pp. 822

Author(s):

K. Shaik Anwar Hussain

Keyword(s):

Diabetes Mellitus ◽

Retrospective Study ◽

Thyroid Dysfunction ◽

Diabetic Patients ◽

Type Ii ◽

Patients With Diabetes ◽

Study Participants ◽

Type 1 Dm

Background: There is a complex interrelationship in the co-existence of thyroid dysfunction among diabetic patients and may be related to the development of cardiovascular diseases and other complications of long term metabolic derangements. The prevalence of thyroid dysfunction varies from 10 to 24% among diabetic patients. The objective of the present study was to determine the prevalence of thyroid dysfunction among the patients with diabetes mellitus in a tertiary care hospital at Puducherry, India.Methods: This retrospective study was conducted during June 2018 analysing the records of diabetes patients attending to the diabetes OPD, Department of General Medicine in the past one year and their association with thyroid dysfunction was studied.Results: Among the study participants (n=200), 14.5% (n=29) were Type I diabetics and 85.5% (n=171) were type II Diabetes patients. The prevalence of Thyroid Dysfunction (TD) among the study participants was 28.5% (n=57). The proportion of TD was higher among type 1 DM compared to type 2 (p<0.001). The prevalence of subclinical hypothyroidism was more (n=7, 24.1%) among type 1DM compared to type II DM patients (p=0.05).Conclusions: There was a higher prevalence of TD among the diabetics. TD was more frequent among type 1 DM compared to Type 2 DM patients and the most frequent TD associated with diabetes was subclinical hypothyroidism.

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Increased levels of YKL-40 in patients with diabetes mellitus: a systematic review and meta-analysis

10.21203/rs.3.rs-66065/v2 ◽

2020 ◽

Author(s):

Wanwan Luo ◽

Lingmin Zhang ◽

Lingling Sheng ◽

Zhencheng Zhang ◽

Zaixing Yang

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Meta Analysis ◽

Healthy Controls ◽

Patients With Diabetes ◽

Severe Degree ◽

The Relationship

Abstract Background: Diabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according to etiology and pathology. Diabetic nephropathy (DN) is one of the most serious complications of DM. YKL-40 is a marker of inflammation and some studies have indicated that DM was related with inflammation. The objective of our study is to perform a systematic review and meta-analysis to confirm the relationship between YKL-40 and DM as well as DN.Methods: Pubmed, Embase, CNKI and Chinese wanfang databases were searched for eligible studies by two independent authors. Studies were included in this meta-analysis if they fulfilled the following inclusion criteria: (1) a study involving the role of YKL-40 in DM (or DN) designed as a case-control study or cohort study; (2) the data of serum YKL-40 levels were available; (3) studies were published in English or Chinese.Results: Twenty-five studies involving 2498 DM patients and 1424 healthy controls were included. Compared with healthy controls, DM patients had significantly higher levels of YKL-40 (DM: SMD=1.62, 95%CI, 1.08 to 2.25, P=0.000; GDM: SMD=2.85, 95%CI, 1.01 to 4.70, P=0.002). Additionally, DM patients with different degree of albuminuria had significantly higher levels of YKL-40 compared with healthy controls (normoalbuminuria: SMD=1.58, 95%CI, 0.59 to 2.56, P=0.002; microalbuminuria: SMD=2.57, 95%CI, 0.92 to 4.22, P=0.002; macroalbuminuria: SMD=2.69, 95%CI, 1.40 to 3.98, P=0.000) and serum YKL-40 levels increased with increasing severity of albuminuria among DM patients (microalbuminuria vs normoalbuminuria: SMD=1.49, 95%CI, 0.28 to 2.71, P=0.016; macroalbuminuria vs microalbuminuria: SMD=0.93, 95%CI, 0.34 to 1.52, P=0.002).Conclusions: DM patients have higher levels of YKL-40 compared with healthy controls. Additionally, levels of YKL-40 are significantly higher in DM patients with different degree of albuminuria than in the healthy controls and the levels of YKL-40 are positively related with the severe degree of albuminuria. Therefore, our current meta-analysis suggests that their sera should be detected for YKL-40, if DM, especially DN, is suspected in patients.

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Increased Levels of YKL-40 in Patients With Diabetes Mellitus: A Systematic Review and Meta-analysis

10.21203/rs.3.rs-66065/v1 ◽

2020 ◽

Author(s):

Wanwan Luo ◽

Lingmin Zhang ◽

Lingling Sheng ◽

Zhencheng Zhang ◽

Zaixing Yang

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Meta Analysis ◽

Healthy Controls ◽

Patients With Diabetes ◽

Severe Degree ◽

The Relationship

Abstract Background: Diabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according to etiology and pathology. Diabetic nephropathy (DN) is one of the most serious complications of DM. YKL-40 is a marker of inflammation and some studies have indicated that DM was related with inflammation. The objective of our study is to perform a systematic review and meta-analysis to confirm the relationship between YKL-40 and DM as well as DN.Methods: Pubmed, Embase, CNKI and Chinese wanfang databases were searched for eligible studies by two independent authors. Studies were included in this meta-analysis if they fulfilled the following inclusion criteria: (1) a study involving the role of YKL-40 in DM (or DN) designed as a case-control study or cohort study; (2) the data of serum YKL-40 levels were available; (3) studies were published in English or Chinese.Results: Twenty-five studies involving 2498 DM patients and 1424 healthy controls were included. Compared with healthy controls, DM patients had significantly higher levels of YKL-40 (DM: SMD=1.62, 95%CI, 1.08 to 2.25, P=0.000; GDM: SMD=2.85, 95%CI, 1.01 to 4.70, P=0.002). Additionally, DM patients with different degree of albuminuria had significantly higher levels of YKL-40 compared with healthy controls (normoalbuminuria: SMD=1.58, 95%CI, 0.59 to 2.56, P=0.002; microalbuminuria: SMD=2.57, 95%CI, 0.92 to 4.22, P=0.002; macroalbuminuria: SMD=2.69, 95%CI, 1.40 to 3.98, P=0.000) and serum YKL-40 levels increased with increasing severity of albuminuria among DM patients (microalbuminuria vs normoalbuminuria: SMD=1.49, 95%CI, 0.28 to 2.71, P=0.016; macroalbuminuria vs microalbuminuria: SMD=0.93, 95%CI, 0.34 to 1.52, P=0.002).Conclusions: DM patients have higher levels of YKL-40 compared with healthy controls. Additionally, levels of YKL-40 are significantly higher in DM patients with different degree of albuminuria than in the healthy controls and the levels of YKL-40 are positively related with the severe degree of albuminuria.

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MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover – a systematic review and meta-analysis

Acta Endocrinologica ◽

10.1530/eje-16-0652 ◽

2017 ◽

Vol 176 (3) ◽

pp. R137-R157 ◽

Cited By ~ 96

Author(s):

Katrine Hygum ◽

Jakob Starup-Linde ◽

Torben Harsløf ◽

Peter Vestergaard ◽

Bente L Langdahl

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Type 2 Diabetes ◽

Bone Resorption ◽

Bone Turnover ◽

Meta Analysis ◽

Patients With Diabetes ◽

Low Bone Turnover

Objective To investigate the differences in bone turnover between diabetic patients and controls. Design A systematic review and meta-analysis. Methods A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms ‘diabetes mellitus’ and ‘bone turnover’, ‘sclerostin’, ‘RANKL’, ‘osteoprotegerin’, ‘tartrate-resistant acid’ and ‘TRAP’ were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers. Results A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (−0.10 ng/mL (−0.12, −0.08)) and the bone formation markers osteocalcin (−2.51 ng/mL (−3.01, −2.01)) and procollagen type 1 amino terminal propeptide (−10.80 ng/mL (−12.83, −8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (−0.31 U/L (−0.56, −0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)). Conclusions Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.

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Increased levels of YKL-40 in patients with diabetes mellitus: a systematic review and meta-analysis

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00624-9 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Wanwan Luo ◽

Lingmin Zhang ◽

Lingling Sheng ◽

Zhencheng Zhang ◽

Zaixing Yang

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Meta Analysis ◽

Healthy Controls ◽

Patients With Diabetes ◽

Severe Degree ◽

The Relationship

Abstract Background Diabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according to etiology and pathology. Diabetic nephropathy (DN) is one of the most serious complications of DM. YKL-40 is a marker of inflammation and some studies have indicated that DM was related with inflammation. The objective of our study is to perform a systematic review and meta-analysis to confirm the relationship between YKL-40 and DM as well as DN. Methods Pubmed, Embase, CNKI and Chinese wanfang databases were searched for eligible studies by two independent authors. Studies were included in this meta-analysis if they fulfilled the following inclusion criteria: (1) a study involving the role of YKL-40 in DM (or DN) designed as a case–control study or cohort study; (2) the data of serum YKL-40 levels were available; (3) studies were published in English or Chinese. Finally, twenty-five studies were included in this meta-analysis. Results Compared with healthy controls, DM patients had significantly higher levels of YKL-40 (DM: SMD = 1.62, 95% CI 1.08 to 2.25, P = 0.000; GDM: SMD = 2.85, 95% CI 1.01 to 4.70, P = 0.002). Additionally, DM patients with different degree of albuminuria had significantly higher levels of YKL-40 compared with healthy controls (normoalbuminuria: SMD = 1.58, 95% CI 0.59 to 2.56, P = 0.002; microalbuminuria: SMD = 2.57, 95% CI 0.92 to 4.22, P = 0.002; macroalbuminuria: SMD = 2.69, 95% CI 1.40 to 3.98, P = 0.000) and serum YKL-40 levels increased with increasing severity of albuminuria among DM patients (microalbuminuria vs normoalbuminuria: SMD = 1.49, 95% CI 0.28 to 2.71, P = 0.016; macroalbuminuria vs microalbuminuria: SMD = 0.93, 95% CI 0.34 to 1.52, P = 0.002). Conclusions Our current meta-analysis demonstrates that serum level of YKL-40 is increased in DM and positively associated with the severe degree of albuminuria. Therefore, we suggest that YKL-40 could be considered to be detected, along with other inflammatory markers, if DM, especially DN, is suspected.

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Hepatocellular Glycogen Accumulation in the Setting of Poorly Controlled Type 1 Diabetes Mellitus: Case Report and Review of the Literature

Case Reports in Hepatology ◽

10.1155/2020/9368348 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Atinuke Aluko ◽

Ikponmwosa Enofe ◽

Jacob Burch ◽

Julie Yam ◽

Nazia Khan

Keyword(s):

Diabetes Mellitus ◽

Rare Complication ◽

Diagnostic Workup ◽

Review Of Literature ◽

Glycogen Accumulation ◽

Control Regimen ◽

Patients With Diabetes ◽

History Of ◽

Type 1 Dm

Glycogenic hepatopathy (GH) is the accumulation of glycogen in the hepatocytes and represents a rare complication in patients with diabetes mellitus (DM), most commonly type 1 DM. We present a case of a 23-year-old woman with a medical history of poorly controlled type 1 DM and gastroesophageal reflux disease (GERD) who presented with progressively worsening right-sided abdominal pain. Diagnostic workup resulted in a liver biopsy with hepatocytes that stained heavily for glycogen with no evidence of fibrosis or steatohepatitis. A diagnosis of glycogenic hepatopathy was made, and an aggressive glucose control regimen was implemented leading to resolution of symptoms and improvement in AST, ALT, and ALP. In addition to presenting this rare case, we offer a review of literature and draw important distinctions between glycogenic hepatopathy and other differential diagnoses with the aim of assisting providers in the diagnostic workup and treatment of glycogenic hepatopathy.

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