Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia
Introduction Hypoglycemia 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 seve...
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BMJ Publishing Group
2021-03-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/9/1/e002211.full |
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| author | Stephen L Atkin Thozhukat Sathyapalan Alexandra E Butler Abu Saleh Md Moin Ahmed Al-Qaissi Hassan Kahal Nitya Kumar |
| author_facet | Stephen L Atkin Thozhukat Sathyapalan Alexandra E Butler Abu Saleh Md Moin Ahmed Al-Qaissi Hassan Kahal Nitya Kumar |
| author_sort | Stephen L Atkin |
| collection | DOAJ |
| description | Introduction Hypoglycemia 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 methods Two 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.Results In 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.Conclusions The 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 numbers NCT02205996, NCT03102801. |
| format | Article |
| id | doaj-art-46f0ef3877d34048bd18507c0add45b5 |
| institution | Kabale University |
| issn | 2052-4897 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-46f0ef3877d34048bd18507c0add45b52024-12-12T14:15:13ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972021-03-019110.1136/bmjdrc-2021-002211Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemiaStephen L Atkin0Thozhukat Sathyapalan1Alexandra E Butler2Abu Saleh Md Moin3Ahmed Al-Qaissi4Hassan Kahal5Nitya Kumar6Royal College of Surgeons in Ireland and Medical University of Bahrain, Busaiteen, BahrainDiabetes and Endocrinology, Hull University Teaching Hospitals NHS Trust, Hull, UKDiabetes Research Center, Qatar Biomedical Research Institute, Doha, QatarDiabetes Research Center, Qatar Biomedical Research Institute, Doha, QatarDiabetes and Metabolism, Hull York Medical School, Hull, UKDepartment of Diabetes and Endocrinology, Southmead Hospital, Bristol, UKRoyal College of Surgeons in Ireland and Medical University of Bahrain, Busaiteen, BahrainIntroduction Hypoglycemia 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 methods Two 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.Results In 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.Conclusions The 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 numbers NCT02205996, NCT03102801.https://drc.bmj.com/content/9/1/e002211.full |
| spellingShingle | Stephen L Atkin Thozhukat Sathyapalan Alexandra E Butler Abu Saleh Md Moin Ahmed Al-Qaissi Hassan Kahal Nitya Kumar Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia BMJ Open Diabetes Research & Care |
| title | Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia |
| title_full | Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia |
| title_fullStr | Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia |
| title_full_unstemmed | Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia |
| title_short | Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia |
| title_sort | amyloid related protein changes associated with dementia differ according to severity of hypoglycemia |
| url | https://drc.bmj.com/content/9/1/e002211.full |
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