scholarly journals GDF-15 Is Associated with Cancer Incidence in Patients with Type 2 Diabetes

2016 ◽  
Vol 62 (12) ◽  
pp. 1612-1620 ◽  
Author(s):  
Noemi Pavo ◽  
Raphael Wurm ◽  
Stephanie Neuhold ◽  
Christopher Adlbrecht ◽  
Greisa Vila ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cancer Incidence ◽  
Troponin T ◽  
Increased Risk ◽  
Incidence And Mortality ◽  
Patients With Diabetes ◽  
History Of ◽  
Cardiovascular Biomarkers

Abstract BACKGROUND Diabetes has been linked epidemiologically to increased cancer incidence and mortality. Growth differentiation factor 15 (GDF-15) is increased in patients with diabetes and has recently been linked to the occurrence of cancer. We investigated whether circulating GDF-15 concentrations can predict the incidence of malignant diseases in a diabetic patient cohort already facing increased risk for cancer. METHODS We prospectively enrolled a total of 919 patients with type 2 diabetes and no history of malignant disease, who were clinically followed up for 60 months. GDF-15, N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline; an additional 4 cardiovascular biomarkers were determined for a subpopulation (n = 259). Study end point was defined as the first diagnosis of any type of cancer during the follow-up period. RESULTS During a median follow-up of 60 months, 66 patients (7.2%) were diagnosed with cancer. Baseline circulating GDF-15 concentrations were higher in patients that developed cancer over the follow-up period when compared to cancer-free patients. Increased GDF-15 concentrations were significantly associated with cancer incidence [crude hazard ratio (HR) per 1-IQR (interquartile range) increase 2.13, 95% CI 1.53–2.97, P < 0.001]. This effect persisted after multivariate adjustment with an adjusted HR of 1.86 (95% CI 1.22–2.84; P = 0.004). Among the 4 additionally tested cardiovascular markers in the subpopulation, only troponin T and C-terminal proendothelin-1 showed a significant association with future cancer incidence with unadjusted HRs of 1.71 (95% CI 1.28–2.28, P < 0.001) and 1.68 (95% CI 1.02–2.76, P = 0.042), respectively. CONCLUSIONS Increased circulating concentrations of GDF-15 are associated with increased cancer incidence in patients with type 2 diabetes.

scholarly journals Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

2021 ◽  
Vol 9 (1) ◽  
pp. e001948
Author(s):  
Marion Denos ◽  
Xiao-Mei Mai ◽  
Bjørn Olav Åsvold ◽  
Elin Pettersen Sørgjerd ◽  
Yue Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Family History ◽  
Genetic Predisposition ◽  
Effect Modification ◽  
P Value ◽  
Family History Of Diabetes ◽  
Increased Risk ◽  
History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

Pharmacogenetics of sulfonylurea-induced hypoglycemia in Type 2 diabetes patients: the SUCLINGEN study

2021 ◽  
Author(s):  
Navin Kumar Loganadan ◽  
Hasniza Zaman Huri ◽  
Shireene Ratna Vethakkan ◽  
Zanariah Hussein
Keyword(s):  
Type 2 Diabetes ◽  
Odds Ratio ◽  
Gene Polymorphisms ◽  
Prospective Observational Study ◽  
Severe Hypoglycemia ◽  
Prior History ◽  
Increased Risk ◽  
History Of

Aim: This study investigated the incidence of sulfonylurea-induced hypoglycemia and its predictors in Type 2 diabetes (T2D) patients. Patients & methods: In this prospective, observational study, T2D patients on maximal sulfonylurea-metformin therapy >1 year were enrolled. Hypoglycemia was defined as having symptoms or a blood glucose level <3.9 mmol/l. Results: Of the 401 patients, 120 (29.9%) developed sulfonylurea-induced hypoglycemia during the 12-month follow-up. The ABCC8 rs757110, KCNJ11 rs5219, CDKAL1 rs7756992 and KCNQ1 rs2237892 gene polymorphisms were not associated with sulfonylurea-induced hypoglycemia (p > 0.05). Prior history of hypoglycemia admission (odds ratio = 16.44; 95% CI: 1.74–154.33, p = 0.014) independently predicted its risk. Conclusion: Sulfonylurea-treated T2D patients who experienced severe hypoglycemia are at increased risk of future hypoglycemia episodes.

scholarly journals Weight change and risk of cardiovascular disease among adults with type 2 diabetes: more than 14 years of follow-up in the Tehran Lipid and Glucose Study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Seyyed Saeed Moazzeni ◽  
Reyhane Hizomi Arani ◽  
Niloofar Deravi ◽  
Mitra Hasheminia ◽  
Davood Khalili ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Weight Gain ◽  
Weight Change ◽  
P Value ◽  
Increased Risk ◽  
History Of ◽  
The Impact

Abstract Background To examine the impact of weight change on incident cardiovascular disease and coronary heart disease (CVD/CHD) among an Iranian population with type 2 diabetes mellitus (T2DM). Methods The study population included 763 participants with T2DM aged ≥ 30 years without a history of CVD and cancer at baseline. Two weight measurements done at baseline and about 3 years later. Based on their weight change, they categorized into: > 5% loss, 3–5% loss, stable (± < 3%), 3–5% gain, > 5% gain. Participants were then followed for incident CVD/CHD annually up to 20 March 2018. Multivariable Cox proportional hazard models, adjusted for age, sex, body mass index, educational level, current smoking, glucose-lowering drug use, family history of CVD, hypertension, hypercholesterolemia, chronic kidney disease, and fasting plasma glucose (FPG) were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of weight change categories for incident CVD/CHD, considering stable weight as reference. Results After the weight change measurement, during a median follow-up of 14.4 years, 258 CVD and 214 CHD occurred. Over 5% weight gain was associated with reduced risks of CVD and CHD development by the HRs of 0.70 [95% CI 0.48–1.01; P-value: 0.058] and 0.61 [0.40–0.93], respectively, in multivariable analysis. After further adjustment for FPG change, the HRs of weight gain > 5% were attenuated to 0.75 [0.51–1.10; P-value: 0.138] and 0.66 [043–1.01; P-value: 0.053] for incident CVD and CHD, respectively. The effect of weight loss > 5% was in opposite direction among those older versus younger than 60 years; with suggestive increased risk (not statistically significant) of incident CHD/CVD for the older group. Moreover, weight gain > 5% significantly reduced the risk of CHD only among those older than 60 years (P-value for interaction < 0.2). Furthermore, weight gain > 5% had an association with lower risk of CVD and CHD among sulfonylurea users (0.56 [0.32–0.98] for CVD and 0.54 [0.29–0.99] for CHD). Conclusions Our results with a long-term follow-up showed that weight gain > 5% was associated with better CVD/CHD outcomes among Iranian participants with T2DM, especially older ones. Moreover, we did not find an unfavorable impact on incident CVD/CHD for sulfonylurea-induced weight gain.

scholarly journals Rationale and design of a type 2 diabetes prevention intervention for at-risk mothers and children at a Federally Qualified Healthcare Center: EPIC El Rio Families Study Protocol

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
David G. Marrero ◽  
Robert M. Blew ◽  
Kelly N. B. Palmer ◽  
Kyla James ◽  
Denise J. Roe ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
At Risk ◽  
Cardiovascular Health ◽  
Excess Body Weight ◽  
Lifestyle Behaviors ◽  
Increased Risk ◽  
Group Randomized Trial ◽  
Prevention Model ◽  
History Of

Abstract Background Exposure to gestational diabetes mellitus (GDM) is associated with increased risk for type 2 diabetes (T2DM) in mothers, and poor cardiovascular health among offspring. Identifying effective methods to mitigate T2DM risk has the potential to improve health outcomes for mothers with a history of GDM and their children. The goal of the EPIC El Rio Families Study is to implement and evaluate the effects of a 13-week behavioral lifestyle intervention on T2DM risk factors in at-risk mothers and their 8- to 12-year-old children. We describe herein the rationale for our specific approach, the adaption of the DPP-based curriculum for delivery to patients of a Federally Qualified Health Center (FQHC), and the study design and methodology. Methods The effects of the intervention on reduction in excess body weight (primary outcome), hemoglobin A1c, blood pressure, and changes in lifestyle behaviors associated with weight trajectory and T2DM risk in mother-child dyads will be evaluated during a 13-week, group randomized trial wherein 60 mothers and their children will be recruited to the intervention or wait-listed control conditions at one of two FQHC locations. Intervention participants (n = 30) will begin the group program immediately, whereas the wait-listed controls (n = 30) will receive a booklet describing self-guided strategies for behavior change. Associated program delivery costs, acceptability of the program to participants and FQHC staff, and potential for long-term sustainability will also be evaluated. Discussion Successful completion in our aims will produce a scalable program with high potential for replication and dissemination, and estimated intervention effects to inform T2DM prevention efforts on families who use the FQHC system. The results from this study will be critical in developing a T2DM prevention model that can be implemented and scaled across FQHCs serving populations disproportionately burdened by T2DM. Trial registration ClinicalTrials.gov NCT03781102; Date of registration: 19 December 2018.

scholarly journals Glycemic variability and cardiovascular disease in patients with type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002032
Author(s):  
Marcela Martinez ◽  
Jimena Santamarina ◽  
Adrian Pavesi ◽  
Carla Musso ◽  
Guillermo E Umpierrez
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glycated Hemoglobin ◽  
Glucose Monitoring ◽  
Glycemic Variability ◽  
Cardiovascular Complications ◽  
Glucose Levels ◽  
Increased Risk ◽  
Patients With Diabetes

Glycated hemoglobin is currently the gold standard for assessment of long-term glycemic control and response to medical treatment in patients with diabetes. Glycated hemoglobin, however, does not address fluctuations in blood glucose. Glycemic variability (GV) refers to fluctuations in blood glucose levels. Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level. The use of continuous glucose monitoring devices has markedly improved the assessment of GV in clinical practice and facilitated the assessment of GV as well as hypoglycemia and hyperglycemia events in patients with diabetes. We review current concepts on the definition and assessment of GV and its association with cardiovascular complications in patients with type 2 diabetes.

scholarly journals Type 2 Diabetes Mellitus. From the start – combination therapy

2018 ◽  
Vol 21 (5) ◽  
pp. 386-394 ◽  
Author(s):  
Francesco Indovina ◽  
Pierpaolo Falcetta ◽  
Stefano Del Prato
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Diabetes Diagnosis ◽  
Good Glycemic Control ◽  
Chronic Hyperglycemia ◽  
Increased Risk ◽  
History Of ◽  
First Time ◽  
Early Combination Therapy

Modern treatment of T2DM requires a shift in paradigm with appropriate intensification of therapy from the very first time of diabetes diagnosis. This is supported by data showing how even a moderate delay in achieving good glycemic control can translate into a later increased risk of developing diabetic complications. The recognition of the complexity of the pathogenesis of T2DM leads to the appreciation of the importance of attacking the disease from different angles, i.e. simultaneous tackling of multiple mechanisms contributing to hyperglycemia. From the turn of century a growing number of new anti-hyperglycemic agents have been made available. As compared to the older ones, these new medicines have a more targeted mechanism of action as they act at the level of the specific pathophysiologic disturbances accounting the development and progression of hyperglycemia. Because of that drugs can be use in combination taking advantage of their complementary mechanisms of action and synergistic. If introduced earlier in the natural history of the disease combination therapy may contribute avoiding undesirable exposure to even mild chronic hyperglycemia and provide early benefits. With respect to that in this review we will discuss advantages, disadvantages and still unanswered questions related to the use of early combination therapy in type 2 diabetes.

scholarly journals Elevated circulating follistatin associates with an increased risk of type 2 diabetes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chuanyan Wu ◽  
Yan Borné ◽  
Rui Gao ◽  
Maykel López Rodriguez ◽  
William C. Roell ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Genome Wide Association Study ◽  
Regulatory Protein ◽  
Alcoholic Fatty Liver ◽  
Increased Risk

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.

scholarly journals Association of Bariatric Surgery With Cancer Incidence in Patients With Obesity and Diabetes: Long-term Results From the Swedish Obese Subjects Study

2021 ◽  
Author(s):  
Kajsa Sjöholm ◽  
Lena MS Carlsson ◽  
Per-Arne Svensson ◽  
Johanna C. Andersson-Assarsson ◽  
Felipe Kristensson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bariatric Surgery ◽  
Cancer Risk ◽  
Cancer Incidence ◽  
Diabetes Remission ◽  
Obesity And Diabetes ◽  
Obese Subjects

<b>OBJECTIVE</b> <p>Obesity and type 2 diabetes are associated with serious, adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study. </p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of which underwent bariatric surgery, and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years). </p> <p><b>RESULTS</b></p> <p>During follow-up, the incidence rate for first-time cancer was 9.1 per 1000-person-years (95% CI, 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1000-person-years (95% CI, 11.2-17.7) in patients treated with usual obesity care (HRadj=0.63; 95% CI 0.44-0.89, p=0.008). Moreover, surgery was associated with reduced cancer incidence in women (HRadj=0.58; 0.38-0.90, p=0.016), although the sex-treatment interaction was non-significant (p=0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (HRadj=0.40; 95% CI 0.22-0.74, p=0.003).</p> <p><b>CONCLUSIONS</b></p> <p>These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes, and that durable diabetes remission is associated with reduced cancer risk. </p>

scholarly journals Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)

2021 ◽  
Vol 8 ◽  
Author(s):  
Koki Mise ◽  
Mariko Imamura ◽  
Satoshi Yamaguchi ◽  
Mayu Watanabe ◽  
Chigusa Higuchi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Medical Information ◽  
Information Criterion ◽  
Cox Proportional Hazards ◽  
University Hospital ◽  
Net Reclassification Improvement ◽  
Patients With Diabetes ◽  
High Mannose

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease.Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, P = 0.002) and Calsepa [High-Man (Man2–6)]: 1.56 (1.19–2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001–0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045–0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively].Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE.Trial Registration: This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).

THE EMERGENCE OF FRAILTY MAY LEAD TO A STATE OF BURNT OUT TYPE 2 DIABETES

2016 ◽  
pp. 1-6
Author(s):  
A.H. ABDELHAFIZ ◽  
L. KOAY ◽  
A.J. SINCLAIR
Keyword(s):  
Type 2 Diabetes ◽  
Β Cells ◽  
Risk Of Mortality ◽  
Vulnerable Patients ◽  
Increased Risk ◽  
History Of ◽  
The One ◽  
And Function ◽  
Glucose Dynamics

Ageing is associated with hyperglycaemic tendency due to the change in body composition leading to accumulation of visceral fat and increased insulin resistance on the one hand and reduced insulin secretion due to decreased number and function of the β-cells of the pancreas on the other. However, with the emergence of frailty there may be a tendency towards normoglycaemia or even hypoglycaemia due to malnutrition, weight loss and reduced physiologic reserve. This shift in glucose metabolism induced by frailty may change the natural history of type 2 diabetes from a progressive to a regressive course. Studies which showed increased risk of mortality with low HbA1c included frail patients in the lower HbA1c categories and healthier patients in the higher HbA1c categories suggesting that frailty is a possible confounding factor. Therefore, hypoglycemia may be a prognostic tool to identify vulnerable patients who may be at increased risk of mortality. The metabolic changes of insulin/glucose dynamics associated with frailty need further research.

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