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Objective Diet-related quality of life has not been explored previously in patients with type 2 diabetes using sodium glucose cotransporter 2 (SGLT-2) inhibitors, the latest class of diabetes medications. In this study, we sought to describe the patient experience on SGLT-2 inhibitors and examine whether there have been improvements in dietary perception and satisfaction with these drugs. Methods Adults ≥40 years of age with type 2 diabetes and using SGLT-2 inhibitors for at least 1 month were recruited to take part in one-time 1-on-1 interviews. An interpretive descriptive methodology was used. Data collection and analysis occurred concurrently and a constant comparative analysis was used. Results An overall positive response to SGLT-2 inhibitor use was observed. Interviews revealed 3 themes: Recognizing, Reckoning and Realizing. In Recognizing, all patients reported a significant relationship with food that was typically negative and included feelings of food restriction and deprivation. Positive side effects of the drug in Reckoning included better glycemic control, weight loss and improved energy. Some participants were motivated in Realizing to pursue additional behavioural changes to improve their diabetes management. Conclusions An improved dietary-related quality of life was described by some participants. Although not all individuals were seen to move into the Realizing phase after initiating an SGLT-2 inhibitor, there appeared to be an opportunity to create a behaviour change after positive Reckoning experiences.

Understanding the molecular mechanisms that underpin the pleiotropic effects of IL6 in disease are critical to better inform when this cytokine should be therapeutically targeted to provide the most benefit to patients. This is particularly important for cancer and other pathologic conditions strongly linked to chronic inflammation. Shriki and colleagues provide mechanistic evidence that IL6 protects against chronic liver injury and its ensuing tumor development, thereby challenging the prevailing paradigm that IL6 always acts as a tumor-promoting cytokine. These observations contribute to an emerging view of dichotomous and complex activities of IL6 in solid malignancies and will help understand which patients under which circumstances receive the most benefit from therapies that interfere with IL6 signaling. See related article by Shriki et al., p. 4766

OBJECTIVE The aim of the study was to evaluate remission of type 2 diabetes following a short-term intervention with insulin glargine, sitagliptin/metformin, and lifestyle approaches. RESEARCH DESIGN AND METHODS In this open multicenter trial, 102 patients with type 2 diabetes were randomized to 1) a 12-week intervention with sitagliptin/metformin, insulin glargine, and lifestyle therapy or 2) control group. Participants with HbA1c 10 mmol/L over 1 week, and reinitiation of diabetes medications with or without abnormal fasting plasma glucose (FPG) or 2-h plasma glucose on an oral glucose tolerance test (OGTT). Time-to-relapse analysis was conducted to compare the treatment groups with (primary analysis) and without (supplementary analysis) FPG/OGTT relapse criteria. RESULTS With the FPG/OGTT relapse criteria included, the hazard ratio (HR) of relapse was 0.72 (95% CI 0.47–1.10) in the intervention group compared with the control group (primary analysis), and the number of participants remaining in remission was not significantly different between treatment groups at 24, 36, 48, and 64 weeks. In the supplementary analyses without these criteria, HR of relapse was 0.60 (95% CI 0.39–0.95), and the number of participants remaining in remission was significantly higher (26 vs. 10%) in the intervention group at 36 weeks. CONCLUSIONS Although our primary outcome was not statistically significant, the tested approach deserves further study with further optimization of its components.

Assessment of myocardial strain using cardiac magnetic resonance (CMR) tissue tracking provides prognostic information incremental to left ventricular ejection fraction and allows for detailed analysis of regional myocardial deformation. This study sought to evaluate the effect of percutaneous

AIMS: This study aimed to evaluate associations between coronary collaterals and myocardial viability as assessed by quantitative cardiac magnetic resonance (CMR) imaging in patients with a chronic coronary total occlusion (CTO). METHODS AND RESULTS: A total of 218 patients with a CTO who underwent CMR between 2013 and 2018 were included. A concomitant collateral connection (CC) score 2 and Rentrop grade 3 defined well-developed collaterals in 146 (67%) patients, whereas lower CC scores or Rentrop grades characterised poorly developed collaterals. Dysfunctional myocardium (50%) was observed in only 5% of CTO segments. In the CTO territory, SWT was greater (3.72±1.51 vs 3.05±1.60 mm, p

Excessive signaling through gp130, the shared receptor for the interleukin (IL)6 family of cytokines, is a common hallmark in solid malignancies and promotes their progression. Here, we established the in vivo utility of bazedoxifene, a steroid analog clinically approved for the treatment of osteoporosis, to suppress gp130‐dependent tumor growth of the gastrointestinal epithelium. Bazedoxifene administration reduced gastric tumor burden in gp130 Y757F mice, where tumors arise exclusively through excessive gp130/STAT3 signaling in response to the IL6 family cytokine IL11. Likewise, in mouse models of sporadic colon and intestinal cancers, which arise from oncogenic mutations in the tumor suppressor gene Apc and the associated β‐catenin/canonical WNT pathway, bazedoxifene treatment reduces tumor burden. Consistent with the proposed orthogonal tumor‐promoting activity of IL11‐dependent gp130/STAT3 signaling, tumors of bazedoxifene‐treated Apc‐mutant mice retain excessive nuclear accumulation of β‐catenin and aberrant WNT pathway activation. Likewise, bazedoxifene treatment of human colon cancer cells harboring mutant APC did not reduce aberrant canonical WNT signaling, but suppressed IL11‐dependent STAT3 signaling. Our findings provide compelling proof of concept to support the repurposing of bazedoxifene for the treatment of gastrointestinal cancers in which IL11 plays a tumor‐promoting role.

Current guidelines advocate viability assessment before revascularization of chronic coronary total occlusions (CTO). The present study evaluated associations between coronary collaterals and myocardial viability assessed by cardiac magnetic resonance (CMR) imaging in patients with a CTO. Patients

Gestational diabetes mellitus is associated with an increased risk of type 2 diabetes mellitus and hypertension. Additionally, gestational dysglycemia has been associated with an increased risk of type 2 diabetes mellitus but not yet associated with hypertension subsequent to pregnancy in long-term follow-up. Therefore, we set out to examine this relationship as well as the role of race/ethnicity in modifying this relationship. We analyzed a prospective observational cohort followed between 1998 and 2007. There were 17 655 women with self-reported race/ethnicity and full-term, live births. A 1-hour 50 g oral glucose-load test and a 3-hour 100 g oral glucose-tolerance test enabled third trimester stratification of women into 1 of 4 glucose-tolerance groups: (1) normal (n=15 056); (2) abnormal glucose-load test (n=1558); (3) abnormal glucose-load and -tolerance tests (n=520); and (4) gestational diabetes mellitus (n=521). Women were then followed for a mean±standard deviation of 4.1±2.9 years after delivery for the development of hypertension. Although gestational diabetes mellitus was associated with an increased risk of hypertension after pregnancy (odds ratio [95% confidence interval]: 1.58 [1.02, 2.45]; P =0.04), dysglycemia defined by an abnormal glucose-load test predicted hypertension only among black women (4.52 [1.24, 16.52]; P =0.02). The risk of hypertension after pregnancy among dysglycemia groups not meeting criteria for gestational diabetes mellitus varied based on the race/ethnicity of the population. Further research on the implications of the intersection of race/ethnicity and gestational dysglycemia on subsequent hypertension is warranted.

Introduction The relationship between gestational diabetes mellitus (GDM) and postpregnancy mental health disorders has been inconsistently reported. Additionally, race/ethnicity data are limited. We sought to elucidate the intersection of these relationships. Methods We analyzed 18,109 women aged 18–40 with self-reported race/ethnicity. Women with (n = 659) and without (n = 14,461) GDM were followed for a median of 4.4 (interquartile range 1.4–6.8) and 4.0 (1.5–6.4) years, respectively, for incident mental health disorders. Multivariable repeated measures analyses were conducted to examine associations between GDM and postpregnancy mental health disorders, race/ethnicity, and the interaction of these factors. Results Women with compared to women without GDM were older (mean ± standard deviation, 32 ± 5 vs. 30 ± 5 years; P < .001) and had higher body mass index (29.0 ± 7.2 vs. 25.3 ± 5.2 kg/m2; P < .001). GDM was associated with increased risk for depression and anxiety after adjusting for age and pregnancy complications; however, loss of significance in the fully adjusted model for depression (odds ratio [95% CI]: 1.29 [0.98, 1.70]; P = .064) and anxiety (1.14 [0.83, 1.57], P = .421) suggested that clinical and socioeconomic factors influence this relationship. Hispanic compared to white women had a greater risk for depression (1.40 [1.15, 1.72]; P = .001), even after multivariable adjustment. The interaction between GDM and race was evident in complication-adjusted but not fully adjusted models. Conclusions The incidence of mental health disorders subsequent to GDM was attenuated after adjustment for clinical and socioeconomic factors. Moreover, race/ethnicity influenced this relationship. Further investigation is warranted to clarify potential underlying mechanisms.

Introduction During a pregnancy complicated by diabetes, the human placenta undergoes a number of functional and structural pathologic changes, such as increased placental weight and increased incidence of placental lesions including villous maturational defects and fibrinoid necrosis. The pathologic findings reported have differed among studies, potentially reflecting differences in type of diabetes, study methodology, or glycemic control of study participants. Alternatively, these discrepancies may represent different biologic adaptations to distinct metabolic diseases. Methods We conducted a comprehensive review of English language citations in Pubmed and Embase using the keywords “diabetes”, “placenta”, AND “pathology”. Abstracts were reviewed for relevance then full-text articles were reviewed in order to extract a comprehensive summary of current pathological findings associated with pregestational and gestational diabetes mellitus, as well as an understanding of the impact of glycemic control on placental pathology. Results Placental abnormalities most consistently associated with maternal diabetes are an increased incidence of villous immaturity, increased measures of angiogenesis, and increased placental weight. Conclusions The literature suggests that, despite similarities in placental abnormalities, differences in placental pathology may reflect differences in pathophysiology among different types of diabetes. Consequently, standardization of terminology used to define placental lesions is warranted. Moreover, further research is needed to investigate the impact of pathophysiology, glycemic control and clinical factors, such as infant sex, weight and race, on placental structure and function.

Introduction: Gestational diabetes mellitus (GDM) is associated with increased maternal cardiovascular disease (CVD) risk manifest as hypertension subsequent to pregnancy. The impacts of dysglycemia and race/ethnicity on hypertension risk have been examined; however, the study of putative risk factors has been limited. Hypothesis: We hypothesize that GDM and gestational dysglycemia are sufficiently predictive of hypertension subsequent to pregnancy and that a risk score based on degree of dysglycemia can be used to identify at-risk patients. Methods: We examined a cohort of 23,223 women who presented for prenatal care to the Massachusetts General Hospital Obstetrical Department between September 1998 and January 2007. We selected women, ages 18 to 40 years, free of CVD or pre-GDM, with complete glycemic and demographic data who delivered a singleton, live birth. Each woman’s initial pregnancy was selected in order to not violate the independence assumption. The population was stratified by incident hypertension subsequent to pregnancy. Logistic regression models (with and without stepwise selection) were used to identify significant maternal risk factors based on their predictive performance. Finally, the risk prediction score was developed from β-coefficients in multivariable Weibull models. Results: The study sample comprised of 11,161 women, 547 (4.9%) of whom developed hypertension during 4.2 years (median) follow-up. Significant predictors of hypertension included age, body mass index, systolic and diastolic blood pressures, parity, dysglycemia, and race/ethnicity. These factors were used to develop a risk score for subsequent hypertension risk. The final risk score achieved a c-statistic of 0.76, indicating moderate discriminative ability (Figure 1). Conclusions: We developed a risk score that may be used to identify patients with an elevated risk of hypertension subsequent to a pregnancy complicated by dysglycemia. Further external validation is warranted to determine clinical effectiveness.

To systematically review literature on women's acceptance, preference, willingness, and attitudes toward human papillomavirus DNA vaginal self-sampling and assess study validity using the STROBE statement.From September to October 2008, Ovid MEDLINE, EMBASE, and CINAHL databases were searched systematically over all years available. Participants were women who either completed vaginal self-sampling or were described the procedure. Studies were required to report women's acceptance, preference, willingness or attitudes toward self-sampling. Two independent reviewers assessed abstracts and articles for inclusion and collected study data. Disagreements were resolved by consensus.Twenty studies were included. Of 8 studies, 7 reported that women found self-sampling acceptable. Of the 13 studies, 8 found that more women (63%-94%) preferred self-sampling to clinician-collected sampling. Most women were also receptive to self-sampling as part of future screening. Common opinions expressed by women included an uncertainty if they had or could perform the self-test properly and greater confidence in clinician sampling. Only 2 studies used questionnaires that had been validated, and selection bias favoring self-sampling could not be ruled out in most studies.Vaginal human papillomavirus DNA self-sampling is generally well received among women. However, the possibility of selection bias and survey instrument measurement error may have led to an overestimate of women's favorable opinions for self-sampling. A self-sampling option may increase screening coverage, but concerns of women must also be addressed.

Introduction Colorectal cancer is a pressing health concern and there is a demand to develop novel therapeutics and improve current therapies to treat this disease. Immune checkpoint inhibitors (i.e. anti-PD-1 treatment) have been highly successful for the treatment of solid malignancies however, the majority of colorectal cancers do not typically respond to immunotherapy. Accumulating evidence alludes to a role for IL-11 signaling in tumor development although the mechanisms underlying IL-11 biology in colorectal cancer remain largely unknown. We postulate that IL-11 could be a mode of immunosuppression which can be targeted to overcome the poor responses of colorectal cancer to immunotherapy. Here we aim to investigate IL-11 signaling as a therapeutic strategy which can also be targeted in combination with anti-PD-1 treatment. Moreover, we present data that indicates an immunological function for IL-11 in modulating T cell anti-tumor activity. Method To assess the therapeutic potential for targeting IL-11 signaling in colon cancer in vivo, wild type and Il11r-/- C57BL/6 mice were injected subcutaneously in the flank on Day 0 with 1 x 106 MC38 colon cancer cells. The mice were then treated with an anti-PD-1 antibody i.p. dose once every 3 days. Mice were euthanised at Day 18. Harvested tumors were analysed by FACs and immunohistochemistry. To ascertain a role for IL-11 signaling in T cell activity, CD8+ and CD4+ T cells were FACs-sorted from wild type and il11r-/- mice, and activated with PMA/ionomycin for 24h. T cell activation was assessed by measuring mRNA levels of granzyme B and perforin by qPCR, and IFNγ production by ELISA. Results MC38 growth was attenuated in il11r-/- mice compared to wild type hosts. Lower tumor burden corresponded with a modest increase in tumor-infiltrating CD8+ T cells however we observed no differences in other immune cell subtypes (i.e. CD4+ T cells, MDSCs and macrophages). In addition, lower tumor burden corresponded with a marked reduction in Ki67 as assessed by immunohistochemistry. In addition, T cells harvested from il11r-/- hosts expressed lower levels of granzyme B, perforin and IFNγ under both basal conditions and following PMA/ionomycin stimulation. Conclusion Here we report that IL-11 signaling supports tumorigenesis using the MC38 colon cancer mouse model. For the first time, we have characterized a functional role for IL-11 in modulating T cell function. Overall, the findings from this study indicate IL-11R as a potential therapeutic target to improve the efficacy of immune checkpoint inhibitors for the treatment of colorectal cancer. Citation Format: Jennifer Huynh, Ashwini Chand, Matthias Ernst. IL-11 as a therapeutic target to treat colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5733.

During a pregnancy complicated by diabetes, the placenta undergoes a number of functional and structural pathologic changes. However, differences across studies may reflect pathophysiologic differences of diabetes types under investigation.We examined placental pathology from women ages 18-40 years with self-identified race/ethnicity; singleton, live births; and type 1 (T1DM; n = 36), type 2 (T2DM; n = 37), or gestational diabetes mellitus (GDM; n = 126). Clinical data were abstracted from medical records. Placental diagnoses were independently re-reviewed by a perinatal pathologist. Multivariable analyses adjusting for race, gestational weight gain, gestational age, and systolic blood pressure were conducted.Women with T1DM compared with either T2DM or GDM had higher gestational weight gain (mean ± SD, T1DM vs. T2DM: 28.5 ± 12.4 vs. 20.5 ± 13.4 kg, p = 0.03; or GDM: 21.3 ± 12.7 kg, p = 0.009) and insulin use (T2DM: 100.0% vs. 85.3%, p = 0.02; or GDM: 4.0%, p0.001). Women with T1DM compared with either T2DM or GDM also had a similarly lower prevalence of placental infarcts in univariate analyses; however, these findings did not remain significant after multivariable adjustment. Also, placentas from women with T2DM compared to GDM had higher rates of decidual vasculopathy when excluding women with preeclampsia (10.3 vs. 1.6%, p = 0.049) and diffuse chorangiosis (62.2 vs. 32.5%, p0.001) but a lower rate of villous immaturity (10.8 vs. 90.5%, p = 0.007) after full adjustment.Placental vasculopathic abnormalities differ by maternal diabetes type, potentially reflecting underlying pathophysiologic mechanisms. Further research on placental pathology and metabolic derangements is warranted.

Metabolomic profiling in populations with impaired glucose tolerance has revealed that branched chain and aromatic amino acids (BCAAs) are predictive of type 2 diabetes. Because gestational diabetes mellitus (GDM) shares pathophysiological similarities with type 2 diabetes, the metabolite profile predictive of type 2 diabetes could potentially identify women who will develop GDM.We conducted a nested case-control study of 18- to 40-year-old women who participated in the Massachusetts General Hospital Obstetrical Maternal Study between 1998 and 2007. Participants were enrolled during their first trimester of a singleton pregnancy and fasting serum samples were collected. The women were followed throughout pregnancy and identified as having GDM or normal glucose tolerance (NGT) in the third trimester. Women with GDM (n = 96) were matched to women with NGT (n = 96) by age, BMI, gravidity and parity. Liquid chromatography-mass spectrometry was used to measure the levels of 91 metabolites.Data analyses revealed the following characteristics (mean ± SD): age 32.8 ± 4.4 years, BMI 28.3 ± 5.6 kg/m(2), gravidity 2 ± 1 and parity 1 ± 1. Six metabolites (anthranilic acid, alanine, glutamate, creatinine, allantoin and serine) were identified as having significantly different levels between the two groups in conditional logistic regression analyses (p 0.05). The levels of the BCAAs did not differ significantly between GDM and NGT.Metabolic markers identified as being predictive of type 2 diabetes may not have the same predictive power for GDM. However, further study in a racially/ethnically diverse population-based cohort is necessary.

Gestational diabetes mellitus is associated with adverse maternal and fetal outcomes during, as well as subsequent to, pregnancy, including increased risk of type 2 diabetes and cardiovascular disease. Because of the importance of early risk stratification in preventing these complications, improved first-trimester biomarker determination for diagnosing gestational diabetes would enhance our ability to optimise both maternal and fetal health. Metabolomic profiling, the systematic study of small molecule products of biochemical pathways, has shown promise in the identification of key metabolites associated with the pathogenesis of several metabolic diseases, including gestational diabetes. This article provides a systematic review of the current state of research on biomarkers and gestational diabetes and discusses the clinical relevance of metabolomics in the prediction, diagnosis and management of gestational diabetes.We conducted a systematic search of MEDLINE (PubMed) up to the end of February 2014 using the key term combinations of 'metabolomics,' 'metabonomics,' 'nuclear magnetic spectroscopy,' 'mass spectrometry,' 'metabolic profiling' and 'amino acid profile' combined (AND) with 'gestational diabetes'. Additional articles were identified through searching the reference lists from included studies. Quality assessment of included articles was conducted through the use of QUADOMICS.This systematic review included 17 articles. The biomarkers most consistently associated with gestational diabetes were asymmetric dimethylarginine and NEFAs. After QUADOMICS analysis, 13 of the 17 included studies were classified as 'high quality'.Existing metabolomic studies of gestational diabetes present inconsistent findings regarding metabolite profile characteristics. Further studies are needed in larger, more racially/ethnically diverse populations.

Background: μ opioid receptors (μORs) are expressed by neurons and inflammatory cells, and mediate immune response. We tested whether activation of peripheral μORs ameliorates the acute and delayed phase of colitis. Methods: C57BL/6J mice were treated with 3% dextran sodium sulfate (DSS) in water, 5 days with or without the peripherally acting μOR agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) or with DAMGO+μOR antagonist at day 2-5, then euthanized. Other mice received DSS followed by water for 4 weeks, or DSS with DAMGO starting at day 2 of DSS for 2 or 3 weeks followed by water, then euthanized at 4 weeks. Disease activity index (DAI), histological damage, and myeloperoxidase assay (MPO), as index of neutrophil infiltration, were evaluated. Cytokines and μOR mRNAs were measured with RT-PCR, and nuclear factor-kB (NF-kB), the antiapoptotic factor Bcl-xL, and caspase 3 and 7 with Western blot. Key Results: DSS induced acute colitis with elevated DAI, tissue damage, apoptosis and increased MPO, cytokines, μOR mRNA, and NF-kB. DAMGO significantly reduced DAI, inflammatory indexes, cytokines, caspases, and NF-kB, and upregulated Bcl-xL, effects prevented by μOR antagonist. In DSS mice plus 4 weeks of water, DAI, NF-kB, and μOR were normal, whereas MPO, histological damage, and cytokines were still elevated; DAMGO did not reduce inflammation, and did not upregulate Bcl-xL. Conclusions & Inferences: μOR activation ameliorated the acute but not the delayed phase of DSS colitis by reducing cytokines, likely through activation of the antiapoptotic factor, Bcl-xL, and suppression of NF-kB, a potentiator of inflammation. μ opioid receptors (μORs) mediate a variety of biological processes, including gastrointestinal functions and immune response. This study showed that activation of peripheral μOR with DAMGO, a selective μOR agonist, reduces the inflammatory response and disease activity index in acute experimental colitis through a mechanism involving the activation of the antiapoptotic factor, Bcl-xL, a member of the Bcl-2 family of apoptosis regulator proteins, and the suppression of the transcription nuclear factor-kB (shown here), which in turns reduces the release of pro-inflammatory cytokines and immune cells infiltration. By contrast, the delayed phase of colitis, which is characterized by lower level of inflammation, does not appear to benefit for additional treatment with peripherally acting μOR agonists as indicated by the lack of effect of DAMGO on the expression of Bcl-xL and NF-kB.

The purpose of the present study was to compare the effects of methylnaltrexone (MNTX), a peripherally acting μ opioid receptor (μOR) antagonist, on gastrointestinal (GI) motility in naïve vs. opiate chronically treated guinea pigs in vitro and in vivo. We have used the electrically stimulated muscle twitch contractions of longitudinal muscle-myenteric plexus (LMMP) preparations and total GI transit as measure of GI motility. In LMMP preparations of naïve guinea pigs, MNTX (1-30 μM) induced a significant, dose-response reduction of morphine-induced inhibition of electrically stimulated muscle twitch contractions, with an IC50 of 9.4 10(-8)M. By contrast, MNTX abolished the inhibitory effect of acute morphine at any concentrations tested (1-30 μM) in the guinea pigs chronically treated with opiates. In vivo, MNTX (10-50 mg s.c.) did not affect GI transit in naïve guinea pigs when administered acutely or for five consecutive days, but reversed the GI transit delay induced by chronic morphine treatment. These findings show that MNTX is effective in reversing opiate-induced inhibition of GI motility acting at peripheral μ opioid receptors, but does not exert a pharmacologic effect on GI transit in the absence of opiate stimulation.

Objectives. To evaluate the clinical management of type 2 diabetes in the Eeyou Istchee communities of northern Quebec. Study design. Retrospective quality assurance audit. Methods. Patients with diabetes were identified using the Cree Diabetes Information System. Charts of eligible patients were audited for healthcare visits, glycemic control, blood pressure, lipid profile, pharmacological treatment and complications for the 2006 calendar year. Analyses were performed to assess the association of disease duration, age, target glycemic and blood pressure control with diabetes complications. Results. Half of the patients (49.7%) achieved target HbA1c, 53.6% had a blood pressure of ≤130/80 and 58.7% had an LDL of ≤2.5 mmol/L. The proportion of patients meeting all 3 targets was low at 17.1%. The mean number of diabetes-related clinic visits was high, with an average of 3.9 visits to a physician and an average of 8.7 visits to a registered nurse. Of patients with a documented diabetic complication, 39.4% of patients were not being managed with an ACE/ARB and 48.2% of patients were not prescribed a statin. Conclusions. These findings suggest a possible treatment gap for risk factors and complications management. To circumvent further increases in diabetes-related complications, emphasis should be placed on improved healthcare worker training, greater use of clinical management and patient education tools and improved communication during the diabetes-related clinical visits. Development of a culturally appropriate multidisciplinary approach towards improved understanding of diabetes and multifactorial risk management for diabetic patients is essential for the prevention of diabetic complications. Keywords: Aboriginal; Canada; diabetes; First Nations; clinical management; epidemiology (Published: 25 April 2012) Citation: Int J Circumpolar Health 2012, 71 : 18418 - http://dx.doi.org/10.3402/ijch.v71i0.18418