scholarly journals Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia

2021 ◽  
Vol 9 (1) ◽  
pp. e002211
Author(s):  
Abu Saleh Md Moin ◽  
Hassan Kahal ◽  
Ahmed Al-Qaissi ◽  
Nitya Kumar ◽  
Thozhukat Sathyapalan ◽  
...  
Keyword(s):  
Percentage Change ◽  
Related Protein ◽  
Control Subjects ◽  
Link Type ◽  
Increase Risk ◽  
Serum Amyloid A1 ◽  
Acute Hypoglycemia ◽  
Related Proteins ◽  
Design And Methods

IntroductionHypoglycemia in type 2 diabetes (T2D) may increase risk for Alzheimer’s disease (AD), but no data on changes in AD-related proteins with differing degrees of hypoglycemia exist. We hypothesized that milder prolonged hypoglycemia would cause greater AD-related protein changes versus severe transient hypoglycemia.Research design and methodsTwo prospective case-control induced hypoglycemia studies were compared: study 1, hypoglycemic clamp to 2.8 mmol/L (50 mg/dL) for 1 hour in 17 subjects (T2D (n=10), controls (n=7)); study 2, hypoglycemic clamp to 2.0 mmol/L (36 mg/dL) undertaken transiently and reversed in 46 subjects (T2D (n=23), controls (n=23)). Blood sampling at baseline, hypoglycemia and 24-hour post-hypoglycemia, with proteomic analysis of amyloid-related proteins performed.ResultsIn control subjects, the percentage change from baseline to hypoglycemia differed between study 1 and study 2 for 5 of 11 proteins in the AD-related panel: serum amyloid A1 (SAA1) (p=0.009), pappalysin (PAPPA) (p=0.002), apolipoprotein E2 (p=0.02), apolipoprotein E3 (p=0.03) and apolipoprotein E4 (p=0.02). In controls, the percentage change from baseline to 24 hours differed between studies for two proteins: SAA1 (p=0.003) and PAPPA (p=0.004); however, after Bonferroni correction only SAA1 and PAPPA remain significant. In T2D, there were no differential protein changes between the studies.ConclusionsThe differential changes in AD-related proteins were seen only in control subjects in response to iatrogenic induction of hypoglycemic insults of differing length and severity and may reflect a protective response that was absent in subjects with T2D. Milder prolonged hypoglycemia caused greater AD-related protein changes than severe acute hypoglycemia in control subjects.Trial registration numbersNCT02205996, NCT03102801.

scholarly journals Secreted Frizzled Related Proteins in Cardiovascular and Metabolic Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Guan ◽  
Jin Zhang ◽  
Jing Luan ◽  
Hao Xu ◽  
Zhenghao Huang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Structural Characteristics ◽  
Wnt Signaling Pathway ◽  
Secreted Protein ◽  
Related Protein ◽  
Disease Biomarkers ◽  
Protein Levels ◽  
Related Proteins

Abnormal gene expression and secreted protein levels are accompanied by extensive pathological changes. Secreted frizzled related protein (SFRP) family members are antagonistic inhibitors of the Wnt signaling pathway, and they were recently found to be involved in the pathogenesis of a variety of metabolic diseases, which has led to extensive interest in SFRPs. Previous reports highlighted the importance of SFRPs in lipid metabolism, obesity, type 2 diabetes mellitus and cardiovascular diseases. In this review, we provide a detailed introduction of SFRPs, including their structural characteristics, receptors, inhibitors, signaling pathways and metabolic disease impacts. In addition to summarizing the pathologies and potential molecular mechanisms associated with SFRPs, this review further suggests the potential future use of SFRPs as disease biomarkers therapeutic targets.

scholarly journals Polygenic Prediction of Type 2 Diabetes in Africa

Diabetes Care ◽  
2022 ◽  
Author(s):  
Tinashe Chikowore ◽  
Kenneth Ekoru ◽  
Marijana Vujkovi ◽  
Dipender Gill ◽  
Fraser Pirie ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
African American ◽  
Association Studies ◽  
Meta Analysis ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Data Set ◽  
Control Subjects ◽  
Design And Methods

OBJECTIVE Polygenic prediction of type 2 diabetes (T2D) in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of T2D from Africa and the poor transferability of European-derived polygenic risk scores (PRSs) in diverse ethnicities. We set out to evaluate if African American–, European-, or multiethnic-derived PRSs would improve polygenic prediction in continental Africans. RESEARCH DESIGN AND METHODS Using the PRSice software, ethnic-specific PRSs were computed with weights from the T2D GWAS multiancestry meta-analysis of 228,499 case and 1,178,783 control subjects. The South African Zulu study (n = 1,602 case and 981 control subjects) was used as the target data set. Validation and assessment of the best predictive PRS association with age at diagnosis were conducted in the Africa America Diabetes Mellitus (AADM) study (n = 2,148 case and 2,161 control subjects). RESULTS The discriminatory ability of the African American and multiethnic PRSs was similar. However, the African American–derived PRS was more transferable in all the countries represented in the AADM cohort and predictive of T2D in the country combined analysis compared with the European- and multiethnic-derived scores. Notably, participants in the 10th decile of this PRS had a 3.63-fold greater risk (odds ratio 3.63; 95% CI 2.19–4.03; P = 2.79 × 10−17) per risk allele of developing diabetes and were diagnosed 2.6 years earlier than those in the first decile. CONCLUSIONS African American–derived PRS enhances polygenic prediction of T2D in continental Africans. Improved representation of non-European populations (including Africans) in GWAS promises to provide better tools for precision medicine interventions in T2D.

386-P: Acute Hypoglycemia Does Not Alter Serum Levels of Amyloid-Related Proteins Associated with Dementia

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 386-P
Author(s):  
ABU MOIN ◽  
THOZHUKAT SATHYAPALAN ◽  
STEPHEN ATKIN ◽  
ALEXANDRA E. BUTLER
Keyword(s):  
Serum Levels ◽  
Acute Hypoglycemia ◽  
Related Proteins

scholarly journals Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Carol H Wysham ◽  
Julio Rosenstock ◽  
Marion L Vetter ◽  
Hui Wang ◽  
Elise Hardy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Registration Number ◽  
Efficacy Measures ◽  
Design And Methods ◽  
To Receive

IntroductionInvestigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.Research design and methodsIn this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.ResultsIn total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28–52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of –1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of –1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.ConclusionsSwitching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.Trial registration numberNCT01652716.

scholarly journals Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic

2021 ◽  
Vol 9 (1) ◽  
pp. e002035
Author(s):  
Merel M Ruissen ◽  
Hannah Regeer ◽  
Cyril P Landstra ◽  
Marielle Schroijen ◽  
Ingrid Jazet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Weight Gain ◽  
Glycemic Control ◽  
Perceived Stress ◽  
Medical Center ◽  
Short Term ◽  
Design And Methods

IntroductionLockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes.Research design and methodsWe performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown.ResultsIn total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: −0.39% (−4.3 mmol/mol) (p<0.0001 and type 2 diabetes: −0.62% (−6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p<0.0001).ConclusionsAn increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations.

scholarly journals Glucose excursions in type 2 diabetes modulate amyloid-related proteins associated with dementia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abu Saleh Md Moin ◽  
Ahmed Al-Qaissi ◽  
Thozhukat Sathyapalan ◽  
Stephen L. Atkin ◽  
Alexandra E. Butler
Keyword(s):  
Type 2 Diabetes ◽  
Related Proteins

scholarly journals Plasma heat shock protein response to euglycemia in type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002057
Author(s):  
Alexander S Atkin ◽  
Abu Saleh Md Moin ◽  
Ahmed Al-Qaissi ◽  
Thozhukat Sathyapalan ◽  
Stephen L Atkin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Heat Shock ◽  
Protein Interactions ◽  
Glucose Variability ◽  
Interacting Protein ◽  
Ubiquitin Conjugating Enzyme ◽  
Shock Proteins ◽  
Protein Response ◽  
Design And Methods

IntroductionGlucose variability is associated with mortality and macrovascular diabetes complications. The mechanisms through which glucose variability mediates tissue damage are not well understood, although cellular oxidative stress is likely involved. As heat shock proteins (HSPs) play a role in the pathogenesis of type 2 diabetes (T2D) complications and are rapidly responsive, we hypothesized that HSP-related proteins (HSPRPs) would differ in diabetes and may respond to glucose normalization.Research design and methodsA prospective, parallel study in T2D (n=23) and controls (n=23) was undertaken. T2D subjects underwent insulin-induced blood glucose normalization from baseline 7.6±0.4 mmol/L (136.8±7.2 mg/dL) to 4.5±0.07 mmol/L (81±1.2 mg/dL) for 1 hour. Control subjects were maintained at 4.9±0.1 mmol/L (88.2±1.8 mg/dL). Slow Off-rate Modified Aptamer-scan plasma protein measurement determined a panel of HSPRPs.ResultsAt baseline, E3-ubiquitin-protein ligase (carboxyl-terminus of Hsc70 interacting protein (CHIP) or HSPABP2) was lower (p=0.03) and ubiquitin-conjugating enzyme E2G2 higher (p=0.003) in T2D versus controls. Following glucose normalization, DnaJ homolog subfamily B member 1 (DNAJB1 or HSP40) was reduced (p=0.02) in T2D, with HSP beta-1 (HSPB1) and HSP-70-1A (HSP70-1A) (p=0.07 and p=0.09, respectively) also approaching significance relative to T2D baseline levels.ConclusionsKey HSPRPs involved in critical protein interactions, CHIP and UBE2G2, were altered in diabetes at baseline. DNAJB1 fell in response to euglycemia, suggesting that HSPs are reacting to basal stress that could be mitigated by tight glucose control with reduction of glucose variability.

scholarly journals Distinct non-ischemic myocardial late gadolinium enhancement lesions in patients with type 2 diabetes

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Annemie Stege Bojer ◽  
Martin Heyn Sørensen ◽  
Niels Vejlstrup ◽  
Jens P. Goetze ◽  
Peter Gæde ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Late Gadolinium Enhancement ◽  
Left Ventricle ◽  
Stress Perfusion ◽  
Gadolinium Enhancement ◽  
Unique Identifier ◽  
Maximal Volume ◽  
Ischemic Lesion ◽  
Control Subjects

Abstract Background Cardiovascular magnetic resonance imaging (CMR) have described localised non-ischemic late gadolinium enhancement (LGE) lesions of prognostic importance in various non-ischemic cardiomyopathies. Ischemic LGE lesions are prevalent in diabetes (DM), but non-ischemic LGE lesions have not previously been described or systematically studied in DM. Methods 296 patients with type 2 DM (T2DM) and 25 sex-matched control subjects underwent echocardiography and CMR including adenosine-stress perfusion, T1-mapping and LGE. Results 264 patients and all control subjects completed the CMR protocol. 78.4% of patients with T2DM had no LGE lesions; 11.0% had ischemic LGE lesions only; 9.5% had non-ischemic LGE lesions only; and 1.1% had both one ischemic and one non-ischemic lesion. The non-ischemic LGE lesions were situated mid-myocardial in the basal lateral or the basal inferolateral part of the left ventricle and the affected segments showed normal to high wall thickness and normal contraction. Patients with non-ischemic LGE lesions in comparison with patients without LGE lesions had increased myocardial mass (150 ± 34 vs. 133 ± 33 g, P = 0.02), average E/e’(9.9 IQR8.7–12.6 vs. 8.8 IQR7.4–10.7, P = 0.04), left atrial maximal volume (102 IQR84.6–115.2 vs. 91 IQR75.2–100.0 mL, P = 0.049), NT-proBNP (8.9 IQR5.9–19.7 vs. 5.9 IQR5.9–10.1 µmol/L, P = 0.02) and high-sensitive troponin (15.6 IQR13.0–26.1 vs. 13.0 IQR13.0–14.6 ng/L, P = 0.007) and a higher prevalence of retinopathy (48 vs. 25%, P = 0.009) and autonomic neuropathy (52 vs. 30.5%, P = 0.005). Conclusion A specific LGE pattern with lesions in the basal lateral or the basal inferolateral part of the left ventricle was found in patients with type 2 diabetes. Trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT02684331.

scholarly journals Prevalence of Prediabetes and Type 2 Diabetes Mellitus in Football Players: A Novel Multi Football Clubs Cross Sectional Study

2021 ◽  
Vol 18 (4) ◽  
pp. 1763
Author(s):  
Sultan Ayoub Meo ◽  
Abdulelah Adnan Abukhalaf ◽  
Ali Abdullah Alomar ◽  
Omar Mohammed Alessa ◽  
Omar Yassin Sumaya ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Elite Athlete ◽  
Population Based ◽  
Football Players ◽  
Preventive Strategy ◽  
Control Subjects ◽  
The Mean

Sports offer great benefits, improving health and reducing the risk of illnesses. This study’s aim was to investigate the prevalence of prediabetes and type 2 diabetes mellitus in football players compared to population based non-elite athlete control subjects. Initially 1100 male volunteers, (550) football players, and (550) population based non-elite athlete control subjects were interviewed. After socio-demographic and medical history analysis, 756 (378) nonsmoker male football players and (378) nonsmoker male control subjects were recruited. The control subjects were not involved in regular sports activities such as football, volleyball, badminton, cricket, hockey, and swimming. Participants with a known history of anemia, blood diseases, diabetes mellitus, and malignancy were excluded from the study. The mean age of football players was 31.80 ± 5.46 years, Body Mass Index (BMI) was 26.40 ± 2.08 (kg/m2), and the mean age of control subjects was 32.32 ± 4.37 years, and BMI was 26.66 ± 1.87 (kg/m2). The selected football players have been playing football for about 2 h a day, 3 days per week, and so the total mean duration of playing football was 1.08 years. American Diabetes Association (ADA) based criteria on Glycated Hemoglobin (HbA1c) was used to investigate prediabetes and type 2 diabetes mellitus. In football players the prevalence of prediabetes was 30 (7.93%) and type 2 diabetes mellitus (T2DM) was 6 (1.59%) compared to population based matched non-elite athlete control subjects where the prediabetes was 71 (18.78%) and T2DM was 89 (23.54%) (p = 0.001). Among football players there was a 7-fold decrease in T2DM compared to control subjects. Football recreational activities markedly reduce the prevalence of prediabetes and T2DM. The study findings demonstrate the benefits of football and other such sport activities and emphasize the urgent need for promoting football based physical activities as a physiological preventive strategy against the globally growing diabetes epidemic.

scholarly journals Inflammatory Osteolysis in Diabetic Neuropathic (Charcot) Arthropathies of the Foot

2008 ◽  
Vol 88 (11) ◽  
pp. 1399-1407 ◽  
Author(s):  
David R Sinacore ◽  
Mary K Hastings ◽  
Kathryn L Bohnert ◽  
Faye A Fielder ◽  
Dennis T Villareal ◽  
...  
Keyword(s):  
Skin Temperature ◽  
Acute Inflammation ◽  
Mineral Density ◽  
Rapid Loss ◽  
Cast Immobilization ◽  
Recent Onset ◽  
Control Subjects ◽  
Quantitative Ultrasonometry ◽  
Design And Methods ◽  
Control Study

ObjectiveOsteolysis and low bone mineral density (BMD) are underappreciated consequences of several chronic diseases that may elevate the risk for fracture. The purpose of this study was to assess tarsal BMD associated with acute inflammation (ie, inflammatory osteolysis) in individuals with chronic diabetes mellitus (DM), peripheral neuropathy (PN), and recent-onset neuropathic (Charcot) arthropathy (NCA) of the foot.Research Design and MethodsThis was a case-control study of 32 people (11 men, 21 women) with DM, PN, and NCA of the foot or ankle. The subjects with DM, PN, and NCA were compared with 64 age-, sex-, and race-matched control subjects (24 men, 40 women) without DM, PN or NCA. Within the first 3 weeks of cast immobilization, BMD was estimated in both calcanei using quantitative ultrasonometry. Acute inflammation was confirmed by comparing skin temperature differences between the feet of the subjects with DM, PN, and NCA and the feet of the control subjects.ResultsSkin temperature differences averaged 6.7°F (SD=4.0°F) (involved foot minus noninvolved foot) in the feet of the subjects with DM, PN, and NCA compared with 0.0°F (SD=1.3°F) in the feet of the control subjects. Calcaneal BMD averaged 384 mg/cm2 (SD=110) in the involved feet and 467 mg/cm2 (SD=123) in the noninvolved feet of the subjects with DM, PN, and NCA and 545 mg/cm2 (SD=121) in combined right and left feet of the control subjects.ConclusionsInflammation in individuals with DM, PN, and NCA may contribute to or exacerbate a rapid loss of BMD. Inflammatory osteolysis may be a prominent factor responsible for both the spontaneous onset of neuropathic fracture and the insidious and progressive foot deformity that is the hallmark of the chronic Charcot foot.

Sign in / Sign up

Export Citation Format

Share Document