• Cancer incidence
• Lifestyle
• Metabolic syndrome

• Humans
• Female
• Male
• United Kingdom/epidemiology
• Neoplasms/epidemiology
• Neoplasms/etiology
• Middle Aged
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/complications
• Incidence
• Biological Specimen Banks/statistics & numerical data
• Aged
• Risk Factors
• Life Style
• Healthy Lifestyle
• Adult
• Exercise
• Follow-Up Studies
• UK Biobank

• 82273148 National Natural Science Foundation of China
• 82403798 National Natural Science Foundation of China
• 82172673 National Natural Science Foundation of China
• 2023A1515012396 Natural Science Foundation of Guangdong Province
• 2024A04J5202 Science and Technology Projects in Guangzhou

• esophageal squamous cell carcinoma
• machine learning
• metabolism score
• nomogram
• overall survival

• Humans
• Machine Learning
• Esophageal Squamous Cell Carcinoma/pathology
• Esophageal Squamous Cell Carcinoma/metabolism
• Esophageal Squamous Cell Carcinoma/mortality
• Male
• Female
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/mortality
• Esophageal Neoplasms/metabolism
• Esophageal Neoplasms/blood
• Middle Aged
• Nomograms
• Prognosis
• Disease Progression
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/metabolism
• Aged
• Adult

• 20204Y0445 Scientific Research Project of Shanghai Health and Family Planning Commission
• 20234Y0006 Scientific Research Project of Shanghai Health and Family Planning Commission
• shslczdzk06502 Shanghai Key Clinical Specialty Projects-Clinical Pharmacy
• 81901399 National Natural Science Foundation of China
• 81973399 National Natural Science Foundation of China
• 82001399 National Natural Science Foundation of China
• National Natural Science Foundation of China

• Antidiabetic drugs
• Cancer
• Diabetes

• Humans
• Hypoglycemic Agents/therapeutic use
• Neoplasms/drug therapy
• Diabetes Mellitus, Type 2/drug therapy
• Animals

• Japan Diabetes Society
• 22K08330 Japan Society for the Promotion of Science
• 23K14567 Japan Society for the Promotion of Science
• 202112004A Ministry of Health Labour and Welfare
• Japan Diabetes Society
• Japan Society for the Promotion of Science

• acid stress
• growth
• hormone
• lipolysis
• proteolysis
• renal function

• Diabetes
• LDH
• Melanoma
• Nivolumab + relatlimab

• Humans
• Nivolumab/therapeutic use
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/drug therapy
• Melanoma/complications
• Melanoma/drug therapy
• Melanoma/pathology
• Glucose
• Ipilimumab/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/adverse effects

• head and neck melanoma
• metformin
• outcome
• recurrence
• survival
• type 2 diabetes

• cancer
• health disparities
• metabolic syndrome
• sleep duration
• smoking

• T34 GM136494 NIGMS NIH HHS
• U54 CA221704 NCI NIH HHS
• P30 DK111022 NIDDK NIH HHS
• U54 CA221705 NCI NIH HHS
• CA221704 (5) NCI NIH HHS

• Humans
• Esophageal Neoplasms/epidemiology
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/epidemiology
• Diabetes Mellitus, Type 2/prevention & control
• Esophageal Squamous Cell Carcinoma
• Adenocarcinoma/epidemiology
• Adenocarcinoma/complications
• Risk Factors

• alleviation
• inflammatory cytokine
• intervention
• overweight/obesity
• oxidative stress
• panel study
• vitamin C
• walking

Metabolic syndrome (MS) is the simultaneous occurrence of a cluster of predefined cardiovascular risk factors. Although individual MS components are associated with increased risk of cancer, it is still unclear whether the association between MS and cancer differs from the association between individual MS components and cancer. The aim of this matched case-control study was to estimate the association of 13 types of cancer with (1) MS and (2) the diagnosis of 0, 1 or 2 individual MS components.

Cases included 183,248 patients ≥40 years from the SIDIAP database with incident cancer diagnosed between January 2008-December 2017. Each case was matched to four controls by inclusion date, sex and age. Adjusted conditional logistic regression models were used to evaluate the association between MS and cancer risk, comparing the effect of global MS versus having one or two individual components of MS.

MS was associated with an increased risk of the following cancers: colorectal (OR: 1.28, 95%CI: 1.23–1.32), liver (OR: 1.93, 95%CI: 1.74–2.14), pancreas (OR: 1.79, 95%CI: 1.63–1.98), post-menopausal breast (OR: 1.10, 95%CI: 1.06–1.15), pre-menopausal endometrial (OR: 2.14, 95%CI: 1.74–2.65), post-menopausal endometrial (OR: 2.46, 95%CI: 2.20–2.74), bladder (OR: 1.41, 95%CI: 1.34–1.48), kidney (OR: 1.84, 95%CI: 1.69–2.00), non-Hodgkin lymphoma (OR: 1.23, 95%CI: 1.10–1.38), leukaemia (OR: 1.42, 95%CI: 1.31–1.54), lung (OR: 1.11, 95%CI: 1.05–1.16) and thyroid (OR: 1.71, 95%CI: 1.50–1.95). Except for prostate, pre-menopause breast cancer and Hodgkin and non-Hodgkin lymphoma, MS is associated with a higher risk of cancer than 1 or 2 individual MS components. Estimates were significantly higher in men than in women for colorectal and lung cancer, and in smokers than in non-smokers for lung cancer.

MS is associated with a higher risk of developing 11 types of common cancer, with a positive correlation between number of MS components and risk of cancer.

• Breast Neoplasms
• Case-Control Studies
• Colorectal Neoplasms
• Female
• Humans
• Lung Neoplasms
• Lymphoma, Non-Hodgkin
• Male
• Metabolic Syndrome/complications
• Metabolic Syndrome/epidemiology
• Risk Factors
• Spain/epidemiology

• Instituto de Salud Carlos III
• Wereld Kanker Onderzoek Fonds

α-Glucosidase (AGS) is a therapeutic target for Type 2 diabetes mellitus (T2DM) that tends to complicate with other diseases. Some medications for the treatment of T2DM complications have the risk of inducing severe adverse reactions such as diarrhea via the metabolism of intestinal bacterial β-glucuronidase (BGUS). The development of new AGS and/or BGUS inhibitors may improve the therapeutic effects of T2DM and its complications. The present work focused on the isolation and characterization of AGS and/or BGUS inhibitors from the medicinal plant Schisandra sphaerandra. A total of eight compounds were isolated and identified. Sphaerandralide A (1) was obtained as a previously undescribed triterpenoid, which may have chemotaxonomy significance in the authentication of the genus Schisandra and Kadsura. 2′-acetyl-4′,4-dimethoxybiphenyl-2-carbaldehyde (8) was obtained from a plant source for the first time, while compounds 2–7 were isolated from S. sphaerandra for the first time. In the in vitro assay, compounds 1–5 showed potent to moderate activity against AGS. Interestingly, compound 3 also exhibited significant BGUS inhibitory activity, demonstrating the potential of being developed as a bifunctional inhibitor that may find application in the therapy of T2DM and/or the diarrhea induced by medications for the treatment of T2DM complications.

Metabolic syndrome is a cluster of biological irregularities that is a known risk factor for cardiovascular disease, stroke, and diabetes. In a case-control study of 555 West African women, we observed that metabolic syndrome was strongly associated with breast cancer and the aggressive triple-negative molecular subtype, highlighting a need for clinical and lifestyle interventions targeting metabolic syndrome to reduce breast cancer risk in this population.

• Cholesterol
• Diabetes
• Hypertension
• Nigeria
• Triple-negative breast cancer

Conflicting results exist between the potential protective effects of metformin and the prognosis of urologic cancers. This meta-analysis summarized the effects of metformin exposure on the recurrence, progression, cancer-specific survival (CSS), and overall survival (OS) of the three main urologic cancers (kidney cancer, bladder cancer, and prostate cancer).

We systematically searched PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases (January 2010 to December 2019), which identified studies regarding metformin users and nonusers with urologic cancers and extracted patient data. A random effect model or fixed effect model was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs).

Among the 1883 confirmed studies, 27 eligible studies were identified, including 123,212 participants. In prostate cancer, patients using metformin have significant benefits for recurrence (HR = 0.74; 95% CI: 0.61-0.90; P = 0.007; I² = 56%), CSS (HR = 0.74; 95% CI: 0.61-0.91; P = 0.002; I² = 79%), and OS (HR = 0.76; 95% CI: 0.65-0.90; P < 0.001; I² = 86%). Moreover, further subgroup analysis showed that the beneficial effects of metformin may be more significant for patients receiving radical radiotherapy. For kidney cancer, metformin was beneficial for progression (HR = 0.80; 95% CI: 0.65-0.98; P = 0.14; I² = 46%). Analysis revealed that the effect of metformin on the overall survival of kidney cancer patients may be related to nationality (American: HR = 0.76; 95% CI: 0.59-0.98; P = 0.88; I² = 0%). For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a median follow-up time of more than 4 years (HR = 0.43; 95% CI: 0.28-0.67; P = 0.61; I² = 0%).

• Experimental diabetes
• MAT-Lylu
• kidney
• metformin
• oxidative stress

• 1,3,4-Thiadiazole
• 2,5-Disubstituted furan derivatives
• CPT-11-Induced toxicity
• Diabetes
• E. coli β-glucuronidase
• α-Glucosidase

• Binding Sites
• Catalytic Domain
• Cell Line
• Cell Survival
• Escherichia coli/enzymology
• Escherichia coli Proteins/antagonists & inhibitors
• Escherichia coli Proteins/metabolism
• Furans/chemistry
• Furans/pharmacology
• Glucuronidase/antagonists & inhibitors
• Glucuronidase/metabolism
• Glycoproteins/chemistry
• Glycoproteins/pharmacology
• Glycoside Hydrolase Inhibitors/chemistry
• Glycoside Hydrolase Inhibitors/pharmacology
• Humans
• Kinetics
• Molecular Docking Simulation
• Structure-Activity Relationship
• Thiadiazoles/chemistry

• C1632
• LIN28
• Metformin
• Oral squamous cell carcinoma
• Tumor glucose metabolism

• AMP-Activated Protein Kinases/metabolism
• Animals
• Antineoplastic Combined Chemotherapy Protocols/pharmacology
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Dose-Response Relationship, Drug
• Drug Synergism
• Humans
• Male
• Metformin/pharmacology
• Mice, Inbred BALB C
• Mice, Nude
• Mouth Neoplasms/drug therapy
• Mouth Neoplasms/metabolism
• Mouth Neoplasms/pathology
• Neoplasm Invasiveness
• RNA-Binding Proteins/antagonists & inhibitors
• RNA-Binding Proteins/metabolism
• Signal Transduction
• Squamous Cell Carcinoma of Head and Neck/drug therapy
• Squamous Cell Carcinoma of Head and Neck/metabolism
• Squamous Cell Carcinoma of Head and Neck/pathology
• Tumor Burden/drug effects
• Xenograft Model Antitumor Assays
• Mice

• biglycan
• colorectal cancer
• diabetes
• liver metastasis
• mesenchymal stem cell

• Diabetes
• Global
• Mortality
• Primary liver cancer

• Adolescent
• Adult
• Aged
• Databases, Factual
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/mortality
• Diabetes Mellitus, Type 2/pathology
• Female
• Global Burden of Disease
• Humans
• Liver Neoplasms/mortality
• Male
• Middle Aged
• Socioeconomic Factors
• United States/epidemiology
• Young Adult

• cancer
• everolimus
• metformin
• panNETs
• pancreatic neuroendocrine tumors
• review

• Nested case–control sampling
• Oracle property
• PNPMLE
• SCAD

• Algorithms
• Female
• Humans
• Likelihood Functions
• Male
• Proportional Hazards Models
• Sampling Studies
• Statistics, Nonparametric

• Adolescent
• Adult
• Aged
• Cuba/epidemiology
• Female
• Follow-Up Studies
• Humans
• Incidence
• Metabolic Syndrome/complications
• Middle Aged
• Prognosis
• Squamous Intraepithelial Lesions/epidemiology
• Squamous Intraepithelial Lesions/etiology
• Squamous Intraepithelial Lesions/pathology
• Uterine Cervical Neoplasms/epidemiology
• Uterine Cervical Neoplasms/etiology
• Uterine Cervical Neoplasms/pathology
• Young Adult
• Uterine Cervical Dysplasia/epidemiology
• Uterine Cervical Dysplasia/etiology
• Uterine Cervical Dysplasia/pathology

• Breast cancer mortality
• Hormone-receptor subtypes
• Menopause
• Metabolic syndrome
• Obesity

• Aged
• Breast Neoplasms/complications
• Breast Neoplasms/mortality
• Breast Neoplasms/pathology
• Female
• Humans
• Menopause
• Metabolic Syndrome/complications
• Middle Aged
• Obesity/complications
• Risk Factors

• K01 TW010271 FIC NIH HHS

The objective of this study was to investigate the association of metabolic syndrome (MetS) with the risk of invasive breast cancer and molecular subtypes across race, menopause, and body mass index (BMI) groups. We examined the association of metabolic syndrome and its components with risk of invasive breast cancer among 94,555 female participants of the National Institute of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, accounting for ductal carcinoma in situ as a competing risk. Cox proportional hazard regression with the Fine and Gray method was used to generate hazard ratios (HR) and 95% confidence intervals (CI) adjusting for baseline sociodemographic, behavioral, and clinical covariates. During a mean follow-up of 14 years, 5380 (5.7%) women developed breast cancer. Overall, MetS at baseline was associated with a 13% increased risk of breast cancer compared to women without MetS (HR: 1.13, 95% CI: 1.00, 1.27); similar estimates were obtained among postmenopausal women (HR: 1.14, 95% CI: 1.01, 1.29). MetS was associated with a slight but non-significantly increased risk of breast cancer among those with both normal weight and overweight/obesity, and those with estrogen receptor positive breast cancer subtype. In the NIH-AARP cohort, MetS was associated with an increased risk of breast cancer. Further studies are needed to definitively evaluate the association of MetS with triple negative breast cancer subtypes across all levels of BMI.

• NIH-AARP
• breast cancer incidence
• metabolic health
• metabolic syndrome
• obesity

• Epidemiology
• Gastrointestinal cancer
• Incidence
• Incidence rates
• Type 2 diabetes mellitus

• Aged
• Cohort Studies
• Colorectal Neoplasms/epidemiology
• Diabetes Mellitus, Type 2/epidemiology
• Esophageal Neoplasms/epidemiology
• Female
• Gastrointestinal Neoplasms/epidemiology
• Humans
• Hypoglycemic Agents/therapeutic use
• Incidence
• Male
• Middle Aged
• Risk Factors
• United Kingdom/epidemiology

• Anticancer
• Hypoglycemic
• Insulin resistance
• Metabolomics
• Metformin
• NMR

Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ² test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (p< 0.001 for rs1111875, p=0.001 for rs7923837). For rs1111875, increased risk of CRC was observed in TC or TC/CC than CC individuals (p<0.001, OR= 1.780, 95%CI= 1.385-2.287; p<0.001, OR= 1.695, 95%CI= 1.335-2.152). For rs7923837, increased CRC risk was observed in AG, GG, and AG/GG than AA individuals (p< 0.001, OR= 1.520, 95%CI= 1.200-1.924; p=0.036, OR= 1.739, 95%CI= 0.989-3.058; p< 0.001, OR= 1.540, 95%CI= 1.225-1.936). This finding highlights the potentially functional alteration with HHEX rs1111875 and rs7923837 polymorphisms may increase CRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation.

• HHEX
• colorectal cancer
• genetic variants
• type 2 diabetes mellitus

We examined the association between metabolic dysregulation and cancer mortality in a prospective cohort of Black and White adults.

A total of 25,038 Black and White adults were included in the analysis. Metabolic dysregulation was defined in two ways: 1) using the joint harmonized criteria for metabolic syndrome (MetS) and 2) based on factor analysis of 15 variables characterizing metabolic dysregulation. We estimated hazards ratios (HRs) and 95% confidence intervals (CIs) for the association of MetS and metabolic dysregulation with cancer mortality during follow-up using Cox proportional hazards models.

About 46% of Black and 39% of White participants met the criteria for MetS. Overall, participants with MetS (HR: 1.22, 95% CI: 1.03–1.45) were at increased risk of cancer-related death. In race-stratified analysis, Black participants with MetS had significantly increased risk of cancer mortality compared with those without MetS (HR: 1.32, 95% CI: 1.01–1.72), increasing to more than a 2-fold risk of cancer mortality among those with five metabolic syndrome components (HR: 2.35, 95% CI: 1.01–5.51).

There are marked racial differences in the prevalence of metabolic dysregulation defined as MetS based on the harmonized criteria. The strong positive associations between MetS and cancer mortality suggests that efforts to improve cancer outcomes in general, and racial disparities in cancer outcomes specifically, may benefit from prevention and management of MetS and its components.

The online version of this article (10.1186/s12885-017-3807-2) contains supplementary material, which is available to authorized users.

• Cancer
• Cancer mortality
• Metabolic syndrome
• Racial disparities
• Survival

The relationship between Type 2 Diabetes Mellitus(T2DM) and cancer risk has been investigated for more than a decade. Many types of cancer were confirmed to be related with T2DM. The aim of this study is to identify the relationship between T2DM and the prevalence and long-term survivals of Thyroid Carcinoma(TC) using propensity score matching. In present study, 1658 thyroid nodule patients who were diagnosis in Beijing Shijitan hospital were divided into two groups: the TC group (N = 455, 27.4%), and the benign thyroid nodule(BTN) group (N = 1203, 73.6%). Propensity scores analyses were used to compare the overall survival (OS) and recurrence-free survival (RFS) between patients with or without T2DM. After propensity scores analyses, the prevalance of T2DM was significantly increased in the TC group compared with BTN group. Of the 455 TC patients, with T2DM in thyroid carcinoma was associated with increasing 1-, 3-, 5-year OS rates from 98.8, 76.5, and 70.9% to 99.7, 92.2, and 82.7%, respectively (P=0.017). While the 1-, 3-, and 5-year RFS rates in the group with T2DM were 92.3, 69.5, and 58.3%, which were significantly lower than those in the group without T2DM (97.6, 82.7, and 72.4%, P=0.009). After propensity scores analyses, with T2DM was significantly associated with increased risks of OS and RFS in the entire TC cohort.

• PSM
• T2DM
• TC
• overall survival

• Thiazolidinedione
• adverse effects
• bone fracture
• cancer
• diabetes
• drug safety
• heart failure
• hepatotoxicity
• mechanism
• myocardial infarction

Metformin has been reported to have anticancer effect and can affect patient survival in several malignancies. However, the results are inconclusive for endometrial cancer. Hence, we conducted a systematic review and meta-analysis to investigate the prognostic role of metformin in patients with endometrial cancer. Studies were identified from Pubmed and Embase database through March 2017. Observational studies reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were selected. Data were abstracted and summarised using random-effects models. From 250 unique citations, we identified ten studies including 6242 patients with nine studies examining OS and five studies examining PFS. Meta-analysis demonstrated that metformin users had better OS (HR, 0.58; 95% CI, 0.45 to 0.76; P = 0.207, I² = 26.6%) and PFS (HR, 0.61; 95% CI, 0.49 to 0.76; P =0.768, I² = 0%) than non-users for endometrial cancer patients. Similar findings were observed using sensitivity analysis adjusted by trim and filled methods (HR, 0.47; 95% CI, 0.37 to 0.58) and subgroup analyses. Based on the current evidence, we find that metformin use is associated with better OS and PFS in patients with endometrial cancer. However, further large-scale prospective studies are needed to establish its validity.

• endometrial cancer
• metformin
• observational study
• quantitative synthesis
• survival

• Diabetes
• cancer
• hepatocellular carcinoma (HCC)
• nonalcoholic fatty liver disease (NAFLD)

Several studies have shown that anti-diabetic medications may modify the risk of cancer. We performed a systematic review and meta-analysis to evaluate the effect of alpha-glucosidase inhibitors (AGIs) on the risk of cancer in patients with diabetes mellitus. We conducted a systematic search of Medline, EMBASE, and Web of Science databases, up to September 30, 2016. Random-effects model was used to estimate the summary odds ratios (ORs) with 95% CI. Twenty-five studies (14 cohort, 7 case-control, and 4 randomized controlled trials) involving 1,285,433 patients with diabetes were included. Meta-analysis of observational studies showed that the use of AGIs was associated with a lower risk of developing cancer (OR = 0.86, 95% CI 0.78-0.96), especially gastrointestinal cancer (OR = 0.83, 95% CI 0.71-0.97). There was considerable heterogeneity across the studies introduced partly by the quality of included studies and adjustment for potential confounders. Meta-analysis of randomized controlled trials did not reveal any significant association between AGIs and cancer risk. Meta-analysis of observational studies indicated that AGIs may decrease the risk of cancer in individuals with diabetes.

• alpha-glucosidase inhibitor
• cancer risk
• diabetes mellitus
• meta-analysis
• systematic review

• Carcinoma, Hepatocellular/chemically induced
• Carcinoma, Hepatocellular/prevention & control
• Female
• Humans
• Hypoglycemic Agents/adverse effects
• Hypoglycemic Agents/therapeutic use
• Liver Neoplasms/chemically induced
• Liver Neoplasms/prevention & control
• Male
• Metformin/therapeutic use
• Risk Factors

Background: Evidence from epidemiologic investigation indicates that people with type 2 diabetes (T2DM) are at a significantly higher risk of many types of cancer and mortality. The aim of this study was to investigate the incidence and mortality risks of cancer in patients with T2DM compared with the general population in Shanghai, China. Methods: Based on the Shanghai Diabetes Registry (SDR) database linking to the Shanghai Cancer Registry and Surveillance System (SCRSS), a total of 12,276 T2DM patients without cancer were defined and followed up from 1 December 2001 to 31 July 2011. Standardized incidence ratio (SIR) and standardized mortality ratio (SMR) with 95% confidence interval (CI) were calculated using the whole gender and age-matched general population of Shanghai as a reference during the same period. Results: The overall cancer risk was found higher in both males and females T2DM patients, with the SIR of 3.14 (95% CI 2.73–3.56) and 4.29 (95% CI 3.64–4.94), respectively. The overall mortality risk of cancer also significantly increased with the SMR of 2.27 (95% CI 1.86–2.68) and 1.86 (95% CI 1.46–2.26), respectively. Pancreatic cancer was with the highest SIR and SMR in both genders. Conclusions: Compared with the general population, patients with T2DM were associated with higher incidence and mortality risks of cancer, especially pancreatic cancer.

• cancer
• mortality
• standardized incidence ratio
• standardized mortality ratio
• type 2 diabetes

• type 2 diabetes mellitus
• insulin therapy
• insulin glargine
• long-acting insulin analog

• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/epidemiology
• Drug Therapy, Combination
• Glycated Hemoglobin/analysis
• Humans
• Hypoglycemia/chemically induced
• Hypoglycemia/epidemiology
• Hypoglycemic Agents/administration & dosage
• Hypoglycemic Agents/adverse effects
• Insulin/administration & dosage
• Insulin/adverse effects
• Insulin Detemir/administration & dosage
• Insulin Detemir/adverse effects
• Insulin Glargine/administration & dosage
• Insulin Glargine/adverse effects
• Insulin, Isophane/administration & dosage
• Insulin, Isophane/adverse effects
• Insulin, Long-Acting/administration & dosage
• Insulin, Long-Acting/adverse effects
• Randomized Controlled Trials as Topic/statistics & numerical data
• Treatment Outcome

Different anti-diabetic medications (ADMs) may modify cancer risk and mortality in patients with diabetes. We conducted a systematic review and meta-analysis to estimate the magnitude of association and quality of supporting evidence for each ADM. A total of 265 studies (44 cohort studies, 39 case-control studies, and 182 randomized controlled trials (RCT)) were identified, involving approximately 7.6 million and 137,540 patients with diabetes for observational studies and RCTs, respectively. The risk of bias overall was moderate. Meta-analysis demonstrated that the use of metformin or thiazolidinediones was associated with a lower risk of cancer incidence (RR = 0.86, 95% CI 0.83-0.90, I² = 88.61%; RR = 0.93, 95% CI 0.91-0.96, I² = 0.00% respectively). On the other hand, insulin, sulfonylureas and alpha glucosidase inhibitor use was associated with an increased risk of cancer incidence (RR = 1.21, 95% CI 1.08-1.36, I² = 96.31%; RR = 1.20, 95% CI 1.13-1.27, I² = 95.02%; RR = 1.10, 95% CI 1.05-1.15, I² = 0.00% respectively). Use of other types of ADMs was not significantly associated with cancer risk. This study indicates that some ADMs may modify the risk of cancer in individuals with diabetes. Knowledge of this risk may affect the choice of ADM in individuals concerned about cancer or at increased risk for cancer.

Cancer cells often depend on altered metabolism compared with their normal counterparts.1234 As observed in 1924 by Otto Warburg, cancer cells show preferential glucose consumption by way of aerobic glycolysis while normal cells generally assume mitochondrial oxidative phosphorylation.4 Another metabolic hallmark of carcinogenesis is altered lipid metabolism, whereby cancer cells may adopt enhanced de novo lipid production (lipogenesis).123 Enhanced lipid metabolism is also observed in individuals with metabolic syndromes potentially a consequence of increasing popularity of the Standard American Diet, composed of high levels of saturated fats and carbohydrates.5 A growing body of epidemiological data indicates a positive correlation between the occurrence of metabolic syndromes, such as cardiovascular disease, obesity, type-2 diabetes and associated hyperinsulemia, with the aggressiveness of cancer.6789 Remarkably, it is estimated that for every 1% reduction in saturated fats, replaced by polyunsaturated, there would be a 2%–3% reduction in cardiovascular disease.10 Thus, it is conceivable that an equally remarkable attenuation in cancer progression might be achieved with such a reduction in lipid accumulation.