Abstracts / Can J Diabetes 37 (2013) S2eS4S4

Vascular CognitiveImpairment VC1 ORAL PRESENTATION

Association Between Newly Diagnosed Diabetes and DementiaDiagnosis in Older Adults: A Population-Based StudyNISHA NIGIL HAROON*, JIANBAO WU, SUDEEP S. GILL,PETER C. AUSTIN, BAIJU R. SHAH, GILLIAN L. BOOTHToronto, ON; Kingston, ONBackground: There is increasing evidence linking diabetes anddementia; however, large population-based studies in this area arelacking.Methods: We used administrative health databases to identify amatched cohort of Ontario seniors (age 66 years) with (n¼225 045)and without newly diagnosed diabetes (n¼668 070) between April1995 and March 2007. Individuals were followed until March 2012for a new diagnosis of dementia based on a validated algorithmusing hospitalization records and physician services claims. Coxproportional hazards modelling was used to compare the incidenceof dementia between groups after adjusting for a number ofbaseline risk factors.Results: From baseline until March 31, 2012, there were 169 114new cases of dementia diagnosed among members of our cohort.Individuals with diabetes experienced a significantly higher inci-dence of dementia (156.5 vs. 150.4 per 1000 person years) thanthose without diabetes; even after adjusting for baseline cardio-vascular disease, chronic kidney disease (CKD) and hypertension(adjusted HR 1.20 [1.17 to 1.22] and 1.14 [1.12 to 1.16] among menand women, respectively). Individuals with diabetes who had priorcerebrovascular disease (HR 2.04 [1.89 to 2.21]), peripheral vasculardisease (HR 1.46 [1.18 to 1.81]), CKD (HR 1.41 [1.35 to 1.48]) orhospitalizations/emergency department visits for hypoglycemia(HR 1.53 [1.41 to 1.67]) were at greatest risk for dementia (Table 1).Conclusions: Seniors with newly diagnosed diabetes experiencean approximately 20% higher risk of developing dementia. Pre-existing vascular disease and other comorbidities increase the riskof dementia in the setting of diabetes.

Table 1Risk factors for dementia among individuals with diabetes (n¼225 045)

HR (95% CI) p value

Age (per year) 1.11 (1.11e1.12) <.0001Sex (male vs. female) 0.97 (0.95e0.99) 0.0014Income quintile (lowest vs. highest) 1.17 (1.14e1.21) <.0001Baseline coronary artery disease 1.10 (1.05e1.15) <.0001Baseline cerebrovascular disease 1.91 (1.82e2.00) <.0001Baseline chronic kidney disease 1.40 (1.36e1.45) <.0001Baseline peripheral vascular disease 1.35 (1.18e1.54) <.0001Baseline hypertension 1.05 (1.03e1.08) <.0001Hospitalization or emergency department

visit for hypoglycemia1.53 (1.41e1.67) <.0001

Health Systems HS3 ORAL PRESENTATION

Canadian Practice Assessment in Type 2 DiabetesPIERRE FILTEAU*, RONNIE ARONSON, KEITH BOWERINGSaint-Marc-des-Carrières, QC; Toronto, ON; Edmonton, ABIntroduction: Mesenchymal progenitor cells (MPCs) are multi-potent cells that play an essential role in maintaining stem cell nichesand endogenous repair. We have recently shown that high levels ofglucose lead to enhanced adipogenic differentiation of MPCs, whilesuppressing the differentiation to other lineages. This suggests thatdiabetes may lead to impaired repair mechanisms through alteringMPCs and the stem cell niche. We herein investigated the molecularmechanisms underlying these cellular alterations.Methods: Freshly isolated human bone marrow MPCs weretreated with either 5 mmol/L glucose (control) or 25 mmol/Lglucose (high glucose; HG) for 7 days prior to adipogenic differ-

entiation. We then performed a large-scale screen to identify thepathways involved in HG-mediated differentiation. This screenidentified Wnt pathway as the predominant mechanism. We thenconfirmed the involvement of Wnt pathway by recombinant pro-teins, pharmacological inhibitors and modulation of beta-cateninthrough overexpression and RNA interference.Results: Our results show that HG causes suppression of specificWnt ligands (Wnt4, Wnt5a, Wnt5b) while upregulating others(Wnt11, Wnt 16). Exogenous Wnt5a and 5b caused a decrease inadipogenic differentiation while Wnt11 increased the process.Interestingly, blocking beta-catenin-mediated transcription of Wnttarget genes had no effect on HG-induced adipogenesis. Conversely,increasing the degradation of beta-catenin sufficiently blocked theincrease in HG-induced adipogenesis.Conclusions: We found that HG exacerbates adipogenesis throughselective modification of the Wnt signalling pathway, and bymechanisms other than beta-catenin mediated transcription. Thesenovel findings may lead to exciting new therapeutic targets toreverse MPC dysfunction and diabetic complications.

Highlighted PosterPresentation HO17 HIGHLIGHTED POSTER PRESENTATION

Interaction Between Maternal Obesity and Gestational DiabetesMellitus and Long-Term Development of Diabetes,Hypertension and Cardiovascular Disease: A Population-LevelAnalysisPADMA KAUL*, ANAMARIA SAVU, KARA A. NERENBERG,LOIS E. DONOVAN, CONSTANCE L. CHIK, EDMOND RYAN,JEFFREY A. JOHNSONEdmonton, AB; Ottawa, ON; Calgary, ABObjective: To examine how maternal obesity modulates the long-term risk of developing diabetic and vascular complications amongwomen with and without GDM.Methods and Results: We linked data from a population-levelclinical registry (the Alberta Perinatal Health Program) for 253 970deliveries between April 1999 and March 2010 with administrativehealth claims. Women were grouped as: 1) no GDM, not obese(n¼225 145, reference group); 2) obese only (n¼19 051); 3) GDMonly (n¼8135); and 4) GDM and obese (n¼1639). Maternal obesitywas defined as pre-pregnancy weight >91 kg. During a medianfollow-up of 4.7 years, diabetes incidence was 35.1% in the GDMand obese, 18.5% in the GDM only, 5.2% in the obese only, and 1.2%in the reference groups, respectively (Figure, left panel, p<0.01).With respect to hypertension and cardiovascular disease, womenwith GDM who were obese had the highest rates (25.8% and 3.2%,respectively) and the reference group had the lowest rates (5.6%and 0.8%, respectively). However, the rates were similar amongwomen with GDM only (15.6% and 1.2%, respectively) and womenwhowere obese only (15.2% and 1.3%, respectivelye Figure, middleand right panel). These findings remained after multivariableadjustment for baseline differences.Conclusion: The presence of both obesity and GDM compoundsthe risk of developing diabetes. However, the association betweenobesity alone and GDM alone and hypertension and cardiovasculardisease appears equivalent suggesting a need for interventions thattarget effective management of both these factors to improve thehealth of this patient population.