Hypoglycaemia in type <scp>2</scp> diabetes exacerbates amyloid‐related proteins associated with dementia

Moin, Abu Saleh Md; Al-Qaissi, Ahmed; Sathyapalan, Thozhukat; Atkin, Stephen L.; Butler, Alexandra E.

doi:10.1111/dom.14220

Cited by 18 publications

(28 citation statements)

References 61 publications

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“…It must be emphasized that the absolute changes in protein levels we reported previously in severe acute hypoglycemia (study 2) 13 are not contradictory to the differential relative changes we report here. Specifically, in absolute values at baseline in study 2, APP was elevated in T2D; at hypoglycemia, APCS was elevated in T2D while APP and noggin were elevated in controls; and at 24-hours, noggin had normalized in both cohorts, APP and MAPT normalized in controls but showed a below-baseline decrease in T2D.…”

Section: Discussioncontrasting

confidence: 53%

“…At baseline, only APP differed between T2D and controls, being elevated in T2D in study 2 (p=0.02) as previously reported. 13 …”

Section: Resultsmentioning

confidence: 99%

“…As previously described, 13 the SOMAscan assay used to quantify proteins was performed on an in-house Tecan Freedom EVO liquid handling system (Tecan Group, Maennedorf, Switzerland) using buffers and SOMAmers from the SOMAscan HTS Assay 1.3K plasma kit (SomaLogic, Boulder, Colorado, USA) according to manufacturer’s instructions and as described previously. 15 16 …”

Section: Methodsmentioning

confidence: 99%

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

Moin¹,

Kahal

Al-Qaissi

et al. 2021

BMJ Open Diab Res Care

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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.

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Section: Discussioncontrasting

confidence: 53%

“…At baseline, only APP differed between T2D and controls, being elevated in T2D in study 2 (p=0.02) as previously reported. 13 …”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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

Moin¹,

Kahal

Al-Qaissi

et al. 2021

BMJ Open Diab Res Care

Self Cite

View full text Add to dashboard Cite

show abstract

“…The SOMAscan assay used to quantify proteins was performed on an in-house Tecan Freedom EVO liquid handling system (Tecan Group, Maennedorf, Switzerland) utilizing buffers and SOMAmers from the SOMAscan HTS Assay 1.3K plasma kit (SomaLogic, Boulder, CO) according to manufacturer's instructions and as described previously (15)(16)(17). Initial Relative Fluorescent Units (RFUs) were obtained from microarray intensity images using the Agilent Feature Extraction Software (Agilent, Santa Clara, CA).…”

Section: Soma-scan Assaymentioning

confidence: 99%

Soluble Neuropilin-1 Response to Hypoglycemia in Type 2 Diabetes: Increased Risk or Protection in SARS-CoV-2 Infection?

et al. 2021

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IntroductionNeuropilin-1(NRP1) is a cofactor that enhances SARS-CoV-2 coronavirus cell infectivity when co-expressed with angiotensin-converting enzyme 2(ACE2). The Renin-Angiotensin System (RAS) is activated in type 2 diabetes (T2D); therefore, the aim of this study was to determine if hypoglycaemia-induced stress in T2D would potentiate serum NRP1(sNRP1) levels, reflecting an increased risk for SARS-CoV-2 infection.MethodsA case-control study of aged-matched T2D (n = 23) and control (n = 23) subjects who underwent a hyperinsulinemic clamp over 1-hour to hypoglycemia(<40mg/dl) with subsequent timecourse of 4-hours and 24-hours. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement determined RAS-related proteins: renin (REN), angiotensinogen (AGT), ACE2, soluble NRP1(sNRP1), NRP1 ligands (Vascular endothelial growth factor, VEGF and Class 3 Semaphorins, SEM3A) and NRP1 proteolytic enzyme (A Disintegrin and Metalloproteinase 9, ADAM9).ResultsBaseline RAS overactivity was present with REN elevated and AGT decreased in T2D (p<0.05); ACE2 was unchanged. Baseline sNRP1, VEGF and ADAM9 did not differ between T2D and controls and remained unchanged in response to hypoglycaemia. However, 4-hours post-hypoglycemia, sNRP1, VEGF and ADAM9 were elevated in T2D(p<0.05). SEMA3A was not different at baseline; at hypoglycemia, SEMA3A decreased in controls only. Post-hypoglycemia, SEMA3A levels were higher in T2D versus controls. sNRP1 did not correlate with ACE2, REN or AGT. T2D subjects stratified according to ACE inhibitor (ACEi) therapies showed no difference in sNRP1 levels at either glucose normalization or hypoglycaemia.ConclusionHypoglycemia potentiated both plasma sNRP1 level elevation and its ligands VEGF and SEMA3A, likely through an ADAM9-mediated mechanism that was not associated with RAS overactivity or ACEi therapy; however, whether this is protective or promotes increased risk for SARS-CoV-2 infection in T2D is unclear.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT03102801.

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“…Comparison between groups was performed using Student’s t-test where a p-value <0.05 was taken as significant. Statistical analysis was performed using Graphpad Prism (San Diego, CA, USA)” [ 21 ].…”

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confidence: 99%

The relationship of soluble neuropilin-1 to severe COVID-19 risk factors in polycystic ovary syndrome

et al. 2021

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Hypoglycaemia in type 2 diabetes exacerbates amyloid‐related proteins associated with dementia

Cited by 18 publications

References 61 publications

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

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

Soluble Neuropilin-1 Response to Hypoglycemia in Type 2 Diabetes: Increased Risk or Protection in SARS-CoV-2 Infection?

The relationship of soluble neuropilin-1 to severe COVID-19 risk factors in polycystic ovary syndrome

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