Vissa biomarkörer för diabetes kopplas till ökad risk för kognitiv svikt i en svensk studie. Resultaten är en del i att förstå kopplingen mellan diabetes och hjärnan, skriver Petra Hedbpm www.dagensmedicin.se, och fortsätter
 

Det är känt att diabetes ökar risken att drabbas av kognitiv svikt och demens. Risken att drabbas av demens är ungefär dubbelt så stor bland individer med diabetes som de utan sjukdomen.

För att försöka ta reda på vad det är som driver detta, har en grupp forskare från bland annat Lunds universitet mätt en rad biomarkörer som är typiska för diabetes, och tittat på ett tvärsnittssamband mellan dessa och deltagarnas resultat i kognitiva tester.

Elin Dybjer, doktorand vid Lunds universitet, är på plats på diabeteskongressen EASD för att presentera resultaten. Deras slutsats är att höga nivåer av de blodsockersänkande inkretinerna GLP 1 och GIP samt av glukagon hos deltagarna kan kopplas till bättre resultat på de kognitiva testerna.

– Det finns inte så många studier som undersökt kopplingen med hur diabetes påverkar hjärnan så detta är en pusselbit, säger hon.

Deltagarna i studien kommer från kohorten Malmö diet and cancer study och inkluderades när de var i 60-årsåldern. De kognitiva testerna utfördes när de var i snitt 72 år. Testerna som använts är så kallade MMSE som används för att screena för demens samt ett uppmärksamhetstest.

Forskarna har justerat för en rad faktorer som ålder, kön, livsstilsfaktorer och kardiovaskulära riskfaktorer.

Elin Dybjer påpekar att det har hänt mycket inom behandling av diabetes de senaste 10-15 åren och att detta förhoppningsvis kommer att leda till att de kognitiva komplikationerna av diabetes minskar.

– I tidigare forskning har vi sett att kognitionen påverkas redan vid prediabetes så slutsatsen är att detta är ännu ett tecken som visar att det är viktigt att kontrollera sin diabetes. Inte minst då diabetesrelaterad kognitiv svikt är ett problem som väntas öka med en åldrande befolkning och ökad förekomst av övervikt och diabetes, säger hon.

Under EASD presenteras även annan forskning på temat diabetes och hjärnan. Bland annat Carolina cognition, där ingen skillnad i kognitiv svikt sågs i en jämförelse mellan linagliptin och glimepirid, och en mindre rumänsk studie som pekar mot att patienter med diabetes typ 2 som behandlas med inkretiner får en bättre bevarad kognition.

Läs mer i abstract:

  • Elin Dybjer med flera. The interplay between glucometabolic markers, incretins, AGEs and cognition in an elderly population.
    https://www.abstractsonline.com/pp8/#!/7895/presentation/1759
  • AbstractBackground and aims: The mechanisms behind diabetes-related cognitive impairment and dementia are yet unknown. Animal studies have shown that incretins (Glucose-dependent Insulinotropic Peptide, GIP, and Glucagon-like peptide 1, GLP-1) may have neuro-protective potential and there is an ongoing clinical trial evaluating the effect of linagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, on cognition in humans. It has been proposed that both insulin signalling and Advanced Glycation End products (AGEs) can modify pathophysiological processes behind Alzheimer’s Disease (AD), by regulating Β-amyloid plaque and neurofibrillary tangle formation, but the evidence is not clear. The aim of this observational study was to investigate relationships between physiological levels of glucometabolic biomarkers and cognitive test results in a population-based setting.
    Materials and methods: Data were obtained from the population-based, cross-sectional Malmö Diet and Cancer Study Re-examination cohort during 2007-2012, in which 3001 people (mean age 72 years) underwent the OGTT and cognitive tests including the Mini Mental State Examination (MMSE) measuring global cognitive function and A Quick Test of Cognitive Speed (AQT) measuring processing speed and executive functioning. Regression analyses were performed to investigate associations between biomarkers or related indices as exposure variables (serum insulin, plasma glucagon, Insulin Sensitivity Index (ISI), HOMA-IR, serum GIP and plasma GLP-1 measured during the OGTT, and also Skin Autofluorescence (SAF) AGE on a sub-population of 454 individuals) and cognitive test results as outcomes.
    Results: Positive associations after adjustment for demographics and lifestyle factors were found between MMSE results (measured in score points out of 30) and the following variables: ISI (B=0.822, p=0.004), 2-h plasma glucagon (B=0.596, p=0.026), 2-h serum GIP (B=0.581, p=0.040) and 2-h plasma GLP-1 (B=0.585, p=0.038), respectively. Negative associations were found between MMSE and HOMA-IR (B= -0.734, p=0.006), fasting plasma GLP-1 (B= -0.544, p=0.033) and SAF (B= -1.459, p=0.030). Higher levels of fasting plasma GLP-1 were associated with worse AQT scores (longer test time) (B=0.008, p=0.022), and higher ISI was associated with better AQT scores (B= -0.010, p=0.018). No significant associations were found between serum insulin and cognitive test results.
    Conclusion: Higher insulin sensitivity and higher levels of plasma glucagon, serum GIP and plasma GLP-1 measured two hours after glucose administration were cross-sectionally associated with better cognitive test results. Higher insulin resistance, fasting levels of plasma GLP-1 and SAF levels were associated with worse cognitive test results. Longitudinal and interventional studies are needed to confirm these findings and to evaluate possible neuro-modulating effects of these biomarkers.
  • G.J Biessels med flera. Effects of linagliptin (LINA) versus glimepiride (GLIM) on cognitive performance in type 2 diabetes: the CAROLINA COGNITION study.
  • https://www.abstractsonline.com/pp8/#!/7895/presentation/1937
  • AbstractBackground and aims: Cognitive dysfunction is a well-known complication of type 2 diabetes. Experimental, preclinical, and human observational studies suggest that incretin-based therapies like dipeptidyl peptidase 4 inhibitors (DPP4i) and glucagon like petide-1 receptor agonists (GLP1 RA), regardless of their glucose lowering effect, might prevent cognitive decline. The aim of the present study was to examine the effects of incretin-based therapy on cognitive performance in type 2 diabetes patients compared to other glucose lowering medication, and the change of cognitive function in non-diabetic individuals over a 6-month period.
    Materials and methods: A randomized controlled prospective observational study was carried out on 111 subjects. From these 74 patients were with type 2 diabetes (Group 1 37 with incretin-based therapy added to Metformin, mean age 63.4 ± 8.6 years, 46% men; Group 2 37 with Metformin and/or sulfonylurea, mean age 63.7±8.7 years, 46% men) and Group 3 37 healthy subjects (mean age 62.5±8.9 years, 46% men). The three groups were age, and gender matched. The two groups with diabetes were also matched for diabetes duration and HbA1c before inclusion. The incretin-based therapy was started 3 month (± 2 weeks) before inclusion in study. Patients with hypothyreosis, vitamin B deficiencies were excluded. Cognitive status was measured with the help of Mini-Mental State Examination (MMSE) and Montreal-Cognitive Assessment (MOCA) tests at inclusion and after 6 months. For statistical analysis SPSS version 17.0 was used. Groups variables were compared using Mann Whitney test, and Wilcoxon test was used to compare initial and final evaluation; p was considered significant if less than 0.05.
    Results: Cognitive status (according to MMSE and MOCA test results) did not change significantly during the 6 months in the diabetes group with incretin therapy, and the healthy controls, however it declined significantly in the diabetes group without incretin-based therapy (ΔMMSE - 0.45±0.22, p=0.04). There was a significant difference between group 1 and 2 regarding the change of MMSE and MOCCA results (Z = - 3.1, p=0.002, and Z = - 1.8, p = 0.02). The greatest difference between group 1 and 2 were observed related to decline of attention (0.24±0.21 vs. - 0.48±0.12, p=0.03), and memory (0.75±0.31 vs. 0.21±0.11, p=0.04).
    Conclusion: Our data show that type 2 diabetes patients treated with incretin-based therapy had a cognitive function preservation similar to healthy subjects during the 6-month period, compared to type 2 diabetes patients without incretin therapy, who had a cognitive decline. Main benefits were observed regarding attention and memory preservation.
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