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Abstract Background Aboriginal peoples globally, and First Nations peoples in Canada particularly, suffer from high rates of type 2 diabetes and related complications compared with the general population. Research into the unique barriers faced by healthcare providers working in on-reserve First Nations communities is essential for developing effective quality improvement strategies. Methods In Phase I of this two-phased study, semi-structured interviews and focus groups were held with 24 healthcare providers in the Sioux Lookout Zone in north-western Ontario. A follow-up survey was conducted in Phase II as part of a larger project, the Canadian First Nations Diabetes Clinical Management and Epidemiologic (CIRCLE) study. The survey was completed with 244 healthcare providers in 19 First Nations communities in 7 Canadian provinces, representing three isolation levels (isolated, semi-isolated, non-isolated). Interviews, focus groups and survey questions all related to barriers to providing optimal diabetes care in First Nations communities. Results the key factors emerging from interviews and focus group discussions were at the patient, provider, and systemic level. Survey results indicated that, across three isolation levels, healthcare providers' perceived patient factors as having the largest impact on diabetes care. However, physicians and nurses were more likely to rank patient factors as having a large impact on care than community health representatives (CHRs) and physicians were significantly less likely to rank patient-provider communication as having a large impact than CHRs. Conclusions Addressing patient factors was considered the highest impact strategy for improving diabetes care. While this may reflect "patient blaming," it also suggests that self-management strategies may be well-suited for this context. Program planning should focus on training programs for CHRs, who provide a unique link between patients and clinical services. Research incorporating patient perspectives is needed to complete this picture and inform quality improvement initiatives.

Abstract Background Diabetes is a chronic medical condition accompanied by a considerable health-related quality of life (HRQL) burden. The purpose of this analysis was to use generic measures of HRQL to describe HRQL deficits associated with varying degrees of severity of type 2 diabetes. Methods The RAND-12 physical and mental health composites (PHC and MHC, respectively) and Health Utilities Index Mark 3 (HUI3) were self-completed by 372 subjects enrolled in a prospective, controlled study of an intervention to improve care for individuals with type 2 diabetes in rural communities. Analysis of covariance was used to assess differences in HRQL according to disease severity and control of blood glucose. Disease severity was defined in terms of treatment intensity, emergency room visits and absenteeism from work specifically attributable to diabetes. To control for potential confounding, the analysis was adjusted for important sociodemographic and clinical characteristics. Results The PHC and MHC were significantly lower for individuals treated with insulin as compared to diet alone (PHC: 41.01 vs 45.11, MHC: 43.23 vs 47.00, p < 0.05). Individuals treated with insulin had lower scores on the vision, emotion and pain attributes of the HUI3 than individuals managed with oral medication or diet. The PHC, MHC, pain attribute and overall score on the HUI3 captured substantial decrements in HRQL associated with absenteeism from work due to diabetes, while the burden associated with emergency room utilization for diabetes was seen in the PHC and HUI3 pain attribute. Conclusions We concluded that generic measures of HRQL captured deficits associated with more severe disease in type 2 diabetes.

INTRODUCTION: Populations that are developing (westernizing) are suffering the highest rates of increases in diabetes incidence and prevalence worldwide, with the most notable and documented increases in Canada seen among the First Nations. Less is known about the Métis (mixed blood) or the rural populations in general. To date, no studies have assessed the contributions of ethnicity to diabetes risk-factors. Our objective was to examine diabetes risk factors in First Nations, Métis and non-Aboriginal individuals residing in rural or remote locations, investigating whether ethnicity contributed to any differences. METHODS: From the databases of three separate community-based diabetes screening projects in Alberta we created a unique subject pool of 3148 adults without diabetes (1790 First Nation, 867 Métis, and 491 non-Aboriginals). Age, body mass index (BMI), waist circumference, reported history of gestational diabetes (GDM) or babies over nine pounds (females only), hemoglobin A1c (A1c) fasting plasma glucose (FPG) or random plasma glucose (RPG) were assessed. Chi-square tests and logistic regression analysis were used to identify between-group differences. RESULTS: The highest mean values for waist circumference (104.7 cm) and BMI (31.2) were found in First Nations subjects (p<0.01). First Nations individuals had the highest prevalence of overweight/obesity (84.4%), abnormal waist circumference (76.8%) and history of GDM (9.0%) (p<0.01). The RPG was also higher in First Nations, but there were no differences between groups with respect to mean FPG and A1c levels, and there were no differences with respect to the prevalence of pre-diabetes or undiagnosed diabetes. Métis (OR 0.80; p = 0.01) and non-Aboriginal individuals (OR 0.62; p< 0.01) were less likely to be obese after age/gender adjustment, compared with First Nations. Métis (OR 0.70; p<0.01) and non-Aboriginals (OR 0.35; p<0.01) were also less likely than the First Nations group to have abnormal waist circumferences. Individuals in the non-Aboriginal group had a lower prevalence of pre-diabetes (OR 0.50; p = 0.01) compared with both the Métis and First Nations groups. CONCLUSIONS: First Nations individuals had more risk factors for diabetes than Métis and non-Aboriginal individuals, although Métis rates appeared intermediate. While these risk-factor differences did not translate to more undiagnosed diabetes or pre-diabetes, they are consistent with known rates of diagnosed diabetes in Alberta. [ABSTRACT FROM AUTHOR]

Alterations in renal elimination processes of glomerular filtration and active tubular secretion by renal transporters can result in adverse drug reactions. Nonalcoholic steatohepatitis (NASH) alters hepatic transporter expression and xenobiotic elimination, but until recently, renal transporter alterations in NASH were unknown. This study investigates renal transporter changes in rodent models of NASH to identify a model that recapitulates human alterations. Quantitative protein expression by surrogate peptide liquid chromatography-coupled mass spectrometry (LC-MS/MS) on renal biopsies from NASH patients was used for concordance analysis with rodent models, including methionine/choline deficient (MCD), atherogenic (Athero), or control rats and Lepr db/db MCD ( db/db ), C57BL/6J fast-food thioacetamide (FFDTH), American lifestyle-induced obesity syndrome (ALIOS), or control mice. Demonstrating clinical similarity to NASH patients, db/db, FFDTH, and ALIOS showed decreases in glomerular filtration rate (GFR) by 76%, 28%, and 24%. Organic anion transporter 3 (OAT3) showed an upward trend in all models except the FFDTH (from 3.20 to 2.39 pmol/mg protein), making the latter the only model to represent human OAT3 changes. OAT5, a functional ortholog of human OAT4, significantly decreased in db/db, FFDTH, and ALIOS (from 4.59 to 0.45, 1.59, and 2.83 pmol/mg protein, respectively) but significantly increased for MCD (1.67 to 4.17 pmol/mg protein), suggesting that the mouse models are comparable to human for these specific transport processes. These data suggest that variations in rodent renal transporter expression are elicited by NASH, and the concordance analysis enables appropriate model selection for future pharmacokinetic studies based on transporter specificity. These models provide a valuable resource to extrapolate the consequences of human variability in renal drug elimination. SIGNIFICANCE STATEMENT: Rodent models of nonalcoholic steatohepatitis that recapitulate human renal transporter alterations are identified for future transporter-specific pharmacokinetic studies to facilitate the prevention of adverse drug reactions due to human variability., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Disease-mediated alterations to drug disposition constitute a significant source of adverse drug reactions. Cisplatin (CDDP) elicits nephrotoxicity due to exposure in proximal tubule cells during renal secretion. Alterations to renal drug transporter expression have been discovered during nonalcoholic steatohepatitis (NASH), however, associated changes to substrate toxicity is unknown. To test this, a methionine- and choline-deficient diet-induced rat model was used to evaluate NASH-associated changes to CDDP pharmacokinetics, transporter expression, and toxicity. NASH rats administered CDDP (6 mg/kg, i.p.) displayed 20% less nephrotoxicity than healthy rats. Likewise, CDDP renal clearance decreased in NASH rats from 7.39 to 3.83 mL/min, renal secretion decreased from 6.23 to 2.80 mL/min, and renal CDDP accumulation decreased by 15%, relative to healthy rats. Renal copper transporter-1 expression decreased, and organic cation transporter-2 and ATPase copper transporting protein-7b increased slightly, reducing CDDP secretion. Hepatic CDDP accumulation increased 250% in NASH rats relative to healthy rats. Hepatic organic cation transporter-1 induction and multidrug and toxin extrusion protein-1 and multidrug resistance-associated protein-4 reduction may contribute to hepatic CDDP sequestration in NASH rats, although no drug-related toxicity was observed. These data provide a link between NASH-induced hepatic and renal transporter expression changes and CDDP renal clearance, which may alter nephrotoxicity., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Background: Historical, colonial, and racist policies continue to influence the health of Indigenous people, and they continue to have higher rates of chronic diseases and reduced life expectancy compared with non-Indigenous people. We determined factors accounting for variations in cardiovascular risk factors among First Nations communities in Canada., Methods: Men and women (n=1302) aged 18 years or older from eight First Nations communities participated in a population-based study. Questionnaires, physical measures, blood samples, MRI of preclinical vascular disease, and community audits were collected. In this cross-sectional analysis, the main outcome was the INTERHEART risk score, a measure of cardiovascular risk factor burden. A multivariable model was developed to explain the variations in INTERHEART risk score among communities. The secondary outcome was MRI-detected carotid wall volume, a measure of subclinical atherosclerosis., Findings: The mean INTERHEART risk score of all communities was 17·2 (SE 0·2), and more than 85% of individuals had a risk score in the moderate to high risk range. Subclinical atherosclerosis increased significantly across risk score categories (p<0·0001). Socioeconomic advantage (-1·4 score, 95% CI -2·5 to -0·3; p=0·01), trust between neighbours (-0·7, -1·2 to -0·3; p=0·003), higher education level (-1·9, -2·9 to -0·8, p<0·001), and higher social support (-1·1, -2·0 to -0·2; p=0·02) were independently associated with a lower INTERHEART risk score; difficulty accessing routine health care (2·2, 0·3 to 4·1, p=0·02), taking prescription medication (3·5, 2·8 to 4·3; p<0·001), and inability to afford prescription medications (1·5, 0·5 to 2·6; p=0·003) were associated with a higher INTERHEART risk score. Collectively, these factors explained 28% variation in the cardiac risk score among communities. Communities with higher socioeconomic advantage and greater trust, and individuals with higher education and social support, had a lower INTERHEART risk score. Communities with difficulty accessing health care, and individuals taking or unable to afford prescription medications, had a higher INTERHEART risk score., Interpretation: Cardiac risk factors are lower in communities with high socioeconomic advantage, greater trust, social support and educational opportunities, and higher where it is difficult to access health care or afford prescription medications. Strategies to optimise the protective factors and reduce barriers to health care in First Nations communities might contribute to improved health and wellbeing., Funding: Heart and Stroke Foundation of Canada, Canadian Partnership Against Cancer, Canadian Institutes for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Disease progression to nonalcoholic steatohepatitis (NASH) has profound effects on the expression and function of drug-metabolizing enzymes and transporters, which provide a mechanistic basis for variable drug response. Breast cancer resistance protein (BCRP), a biliary efflux transporter, exhibits increased liver mRNA expression in NASH patients and preclinical NASH models, but the impact on function is unknown. It was shown that the transport capacity of multidrug resistance protein 2 (MRP2) is decreased in NASH. SN-38, the active irinotecan metabolite, is reported to be a substrate for Bcrp, whereas SN-38 glucuronide (SN-38G) is a Mrp2 substrate. The purpose of this study was to determine the function of Bcrp in NASH through alterations in the disposition of SN-38 and SN-38G in a Bcrp knockout (Bcrp -/- KO) and methionine- and choline-deficient (MCD) model of NASH. Sprague Dawley [wild-type (WT)] rats and Bcrp -/- rats were fed either a methionine- and choline-sufficient (control) or MCD diet for 8 weeks to induce NASH. SN-38 (10 mg/kg) was administered i.v., and blood and bile were collected for quantification by liquid chromatography-tandem mass spectrometry. In Bcrp -/- rats on the MCD diet, biliary efflux of SN-38 decreased to 31.9%, and efflux of SN-38G decreased to 38.7% of control, but WT-MCD and KO-Control were unaffected. These data indicate that Bcrp is not solely responsible for SN-38 biliary efflux, but rather implicate a combined role for BCRP and MRP2. Furthermore, the disposition of SN-38 and SN-38G is altered by Bcrp -/- and NASH in a gene-by-environment interaction and may result in variable drug response to irinotecan therapy in polymorphic patients., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Pregnant Indigenous women suffer a disproportionate burden of risk and adverse outcomes relative to non-Indigenous women. Although there has been a call for improved prenatal care, examples are scarce. Therefore, we explored the characteristics of effective care with First Nations women from the perspective of prenatal healthcare providers (HCPs)., Methods: We conducted an ethnographic community-based participatory research study in collaboration with a large Cree First Nations community in Alberta, Canada. We carried out semi-structured interviews with 12 prenatal healthcare providers (HCPs) that were recorded, transcribed, and subjected to qualitative content analysis., Results: According to the participants, relationships and trust, cultural understanding, and context-specific care were key features of effective prenatal care and challenge the typical healthcare model. HCPs that are able to foster sincere, non-judgmental, and enjoyable interactions with patients may be more effective in treating pregnant First Nations women, and better able to express empathy and understanding. Ongoing HCP cultural understanding specific to the community served is crucial to trusting relationships, and arises from real experiences and learning from patients over and above relying only on formal cultural sensitivity training. Consequently, HCPs report being better able to adapt a more flexible, all-inclusive, and accessible approach that meets specific needs of patients., Conclusions: Aligned with the recommendations of the Truth and Reconciliation Commission of Canada, improving prenatal care for First Nations women needs to allow for genuine relationship building with patients, with enhanced and authentic cultural understanding by HCPs, and care approaches tailored to women's needs, culture, and context.

Objective: Using a large administrative dataset we examined stillbirth epidemiology in First Nations and non-First Nations pregnancies in Alberta, focusing on previously unexplored longitudinal trends., Methods: We undertook a retrospective analysis of de-identified data from 426 945 delivery records for the years 2000 to 2009. Age-adjusted prevalence of antepartum and intrapartum stillbirth were calculated and compared by ethnicity, as were longitudinal changes via average annual percent change analyses. Risk factors were explored via multivariable logistic regression analysis., Results: Overall age-adjusted prevalence of antepartum and intrapartum stillbirth was significantly higher (P < 0.001) in First Nations pregnancies than in non-First Nations pregnancies, and prevalence remained stable over time in both groups. Pre-existing diabetes was a strong predictor of stillbirth., Conclusion: Stillbirth prevalence remains higher in First Nations pregnancies than in non-First Nations. Improved awareness of pre-existing diabetes and effective interventions are needed in First Nations women to decrease stillbirth risk.

Introduction: We used an exploratory sequential mixed methods approach to study the association between cultural continuity, self-determination, and diabetes prevalence in First Nations in Alberta, Canada., Methods: We conducted a qualitative description where we interviewed 10 Cree and Blackfoot leaders (members of Chief and Council) from across the province to understand cultural continuity, self-determination, and their relationship to health and diabetes, in the Alberta First Nations context. Based on the qualitative findings, we then conducted a cross-sectional analysis using provincial administrative data and publically available data for 31 First Nations communities to quantitatively examine any relationship between cultural continuity and diabetes prevalence., Results: Cultural continuity, or "being who we are", is foundational to health in successful First Nations. Self-determination, or "being a self-sufficient Nation", stems from cultural continuity and is seriously compromised in today's Alberta Cree and Blackfoot Nations. Unfortunately, First Nations are in a continuous struggle with government policy. The intergenerational effects of colonization continue to impact the culture, which undermines the sense of self-determination, and contributes to diabetes and ill health. Crude diabetes prevalence varied dramatically among First Nations with values as low as 1.2% and as high as 18.3%. Those First Nations that appeared to have more cultural continuity (measured by traditional Indigenous language knowledge) had significantly lower diabetes prevalence after adjustment for socio-economic factors (p =0.007)., Conclusions: First Nations that have been better able to preserve their culture may be relatively protected from diabetes.

Background: In addition to increasing the risk of adverse birth outcomes, diabetes in pregnancy is thought to be an important driver of the epidemic of type 2 diabetes affecting Canada's First Nations population. The relative contributions of gestational diabetes mellitus (GDM) and pre-existing diabetes are not well understood. We generated a comprehensive epidemiological profile of diabetes in pregnancy over a 10-year period among the First Nations population of Alberta, Canada., Methods: De-identified administrative data for 427,058 delivery records were obtained for the years 2000-2009. Pregnancy risk factors and delivery outcomes were described and compared by ethnicity (First Nations vs. non-First Nations) and diabetes status. Age-adjusted prevalence values for GDM and pre-existing diabetes were calculated and were compared by ethnicity. Longitudinal changes over time were also examined. Predictors were explored using logistic regression analysis., Results: First Nations women had more antenatal risk factors and adverse infant outcomes that were compounded by diabetes. First Nations descent was an independent predictor of diabetes in pregnancy (p < 0.001). GDM prevalence was significantly higher among First Nations (6.1%) compared to non-First Nations women (3.8%; p < 0.001), but prevalence values increased significantly over time only in non-First Nations women (4.5 average annual percent change; p < 0.05). The prevalence of pre-existing diabetes was stable over time in both groups, but First Nations women experienced a 2.5-fold higher overall prevalence compared with non-First Nations women (1.5% vs. 0.6%, respectively; p < 0.001)., Conclusions: Although First Nations women experience a higher overall prevalence of diabetes in pregnancy, the lack of increase in the prevalence over time is encouraging. However, because high-risk pregnancies and poor outcomes are more common among First Nations women, particularly those with diabetes, strategies to improve perinatal care must be implemented.

Objectives: To track and compare trends in diabetes rates from 1995 to 2007 for Status Aboriginal and general population youth., Study Design: Longitudinal observational research study (quantitative) using provincial administrative data., Methods: De-identified data was obtained from Alberta Health and Wellness administrative databases for Status Aboriginal (First Nations and Inuit people with Treaty status) and general population youth (<20 years). Diabetes cases were identified using the National Diabetes Surveillance System algorithm. Crude annual diabetes prevalence and incidence rates were calculated. The likelihood of being a prevalent case and incident case of diabetes for the 2 populations was compared for the year 2007. Average Annual Percent Changes (AAPC) in prevalence and incidence from 1995 to 2007 were determined and compared between the 2 groups to examine trends over time., Results: While the prevalence of diabetes was higher in the general population in 1995, by 2007 there were no between group differences, reflected in the significantly higher AAPC of 6.98 for Status Aboriginal youth. Status Aboriginal males had a lower diabetes risk in 1995 compared with females, and experienced a greater increase in prevalence over the 13 years (AAPC 9.18) so that by 2007 their rates were equivalent to those of the females. Differences in diabetes incidence trends were only observed among male youth, where increases in incidence were greater for Status Aboriginal (AAPC 11.65) compared to general population males (AAPC 4.62) (p = 0.03)., Conclusion: Youth-onset diabetes is an increasing problem in Alberta, especially among young Status Aboriginal males.

Background: Little is known about longitudinal trends in diabetes mellitus among Aboriginal people in Canada. We compared the incidence and prevalence of diabetes, and its impact on mortality, among status Aboriginal adults and adults in the general population between 1995 and 2007., Methods: We examined de-identified data from Alberta Health and Wellness administrative databases for status Aboriginal people (First Nations and Inuit people with treaty status) and members of the general public aged 20 years and older who received a diagnosis of diabetes mellitus from Apr. 1, 1995, to Mar. 31, 2007. We calculated the incidence and prevalence of diabetes and mortality rate ratios by sex and ethnicity in 2007. We examined the average relative changes per year for longitudinal trends., Results: The average relative change per year in the prevalence of diabetes showed a smaller increase over time in the Aboriginal population than in the general population (2.39 v. 4.09, p < 0.001). A similar finding was observed for the incidence of diabetes. In the Aboriginal population, we found that the increase in the average relative change per year was greater among men than among women (3.13 v. 1.88 for prevalence, p < 0.001; 2.60 v. 0.02 for incidence, p = 0.001). Mortality among people with diabetes decreased over time to a similar extent in both populations. Among people without diabetes, mortality decreased in the general population but was unchanged in the Aboriginal population (-1.92 v. 0.11, p = 0.04). Overall, mortality was higher in the Aboriginal population than in the general population regardless of diabetes status., Interpretation: The increases in the incidence and prevalence of diabetes over the study period appeared to be slower in the status Aboriginal population than in the general population in Alberta, although the overall rates were higher in the Aboriginal population. Mortality decreased among people with diabetes in both populations but was higher overall in the Aboriginal population regardless of diabetes status.

Background. Geographic isolation, poverty, and loss of culture/tradition contribute to "epidemic" rates of diabetes amongst indigenous Canadians. The Mobile Diabetes Screening Initiative travels to rural indigenous and other remote communities in Alberta to screen for diabetes and cardiovascular risk. We sought to examine risk factors longitudinally. Methods. Clinical and anthropometric measurements were undertaken for 809 adults (aged 20-91) between November 2003 and December 2009. For those who had more than one MDSi visit, trend estimates (actual changes) were calculated for body mass index (BMI), weight, waist circumference, hemoglobin A1c (A1c), total cholesterol, and blood pressure. Results. Among those without diabetes (N = 629), BMI and weight increased (P < .01) and blood pressure decreased (P < .05). For those with diabetes (N = 180), significant improvements (P < .05) were observed for all indicators except waist circumference. Conclusion. Improvements observed suggest that MDSi's model may effectively mediate some barriers and support subjects in managing their health.

Objective: The goal of Screening for Limb, I-Eye, Cardiovascular, and Kidney complications of diabetes (SLICK) is to reduce the burden of diabetes among Alberta First Nations individuals. By analyzing the longitudinal results of SLICK over a six-year time span, our purpose was to examine both baseline diabetes-related health status and whether subsequent improvements occurred., Methods: Diabetes complications screening, diabetes education, and community-based care were provided by mobile clinics which traveled to 43 Alberta First Nations communities biannually. Body mass index (BMI), waist circumference, hemoglobin A1c (HbA1c), total cholesterol and blood pressure, as well as the presence of foot and kidney abnormalities were assessed among 2102 unique subjects with diabetes. Mean values of diabetes health indicators at baseline and subsequent visits for returning subjects were compared. Secular trends were sought by examining trends in mean baseline health indicators per year., Results: High baseline rates of obesity, poor HbAlc concentrations, hypercholesterolemia, hypertension, foot abnormalities and kidney damage were observed. Significant improvements in BMI, blood pressure, total cholesterol and HbA1c concentrations were identified (p < 0.01) in returning subjects. Similarly, significant decreasing secular trends in total cholesterol and HbA1c concentrations were observed (p < 0.01). At baseline, females had a higher prevalence of obesity and abnormal waist circumference (p < 0.05); however, males had more inadequate HbA1c concentrations (>8.4%), hypercholesterolemia, hypertension, foot abnormalities and kidney damage (p < 0.05)., Discussion: Despite worrisome baseline clinical characteristics, diabetes-related health appears to be improving modestly in Alberta First Nations individuals.

Objectives: To determine the prevalence of diabetes (using secondary data analysis), as well as undiagnosed diabetes and pre-diabetes (using primary research methods) among adult Métis Settlement dwellers in northern Alberta. We also sought to identify cardiovascular risk factors., Study Design: Quantitative research study utilizing both population census and community-based diabetes screening data., Methods: Self-reported diabetes was analyzed from the results of the Métis Settlement specific censuses in 1998 and 2006. Mobile clinics travelled into each of the 8 Métis Settlement communities in Alberta recruiting 693 subjects for screening for undiagnosed diabetes, pre-diabetes and metabolic syndrome. Logistic regression analyses (adjusted for age and sex) were used to identify associated factors., Results: According to the censuses, 4,312 Métis individuals were living on Settlements in 1998 and 5,059 in 2006. Self-reported age-adjusted prevalence of diabetes increased significantly from 5.1% in 1998 to 6.9% in 2006 (p < 0.01), with a crude prevalence increase of 66% (p < 0.01). In 2006, diabetes prevalence was higher among females than males, 7.8% vs. 6.1% respectively (p < 0.05). Of the 266 adults screened in the fasting state, 5.3% had undiagnosed diabetes, whereas 20.3% (Canadian Diabetes Association criteria) and 51.9% (American Diabetes Association criteria) had pre-diabetes. Rates of obesity and metabolic syndrome were 49.4% (n = 693) and 46.4% (n = 266), respectively. Hemoglobin A1c > 6.1% was strongly associated with diabetes, pre-diabetes and metabolic syndrome., Conclusions: Our results indicate high rates of diabetes, undiagnosed diabetes, pre-diabetes and metabolic syndrome among adult Alberta Métis Settlement dwellers.

Objective: To compare changes in diagnosed diabetes prevalence and incidence among Status Aboriginal men and women living in urban and rural areas of Alberta., Methods: We compared trends in diabetes prevalence and incidence from 1995 to 2006 based on diagnostic codes from Alberta Health and Wellness (AHW) administrative records for adults aged 20 years and older. The AHW Registry file was used to determine registered Aboriginal status, as well as rural and urban residence (based on postal code). Multivariable logistic regression was used to compare diabetes rates over time, by sex and location of residence., Results: Age- and sex-adjusted diabetes prevalence increased 35% in rural Status Aboriginals, from 10.9 (10.4-11.5) per 100 in 1995 to 14.7 (14.2-15.2) per 100 in 2006. Rates in urban Status Aboriginals increased 22% in the same time period from 9.4 (8.5-10.3) per 100 in 1995 to 11.5 (10.9-12.1) per 100 in 2006. The increases in prevalence were greater (p < 0.001) for men (43% and 40%) compared to women (30% and 12%) in rural and urban settings, respectively. Diabetes incidence increased 45% in Status Aboriginal men, from 7.4 (4.9-10.6) per 1000 in 1995 to 10.7 (8.3-13.5) per 1000 in 2006 in urban locations, compared to a 35% increase among Status Aboriginal men living in rural locations (p = 0.628). Among Status Aboriginal women, incidence increased by 25% for those living in urban locations, but did not change for those in rural locations (p = 0.109)., Conclusions: Prevalence and incidence of diagnosed diabetes were highest in Status Aboriginal women, but these rates have increased faster in men over the past decade, regardless of their location of residence.

Objective: To describe the state of diabetes care among Alberta First Nations individuals with diabetes living on reserves., Design: Survey and screening for diabetes-related complications., Setting: Forty-three Alberta First Nations communities., Participants: A total of 743 self-referred First Nations individuals with known diabetes., Main Outcome Measures: Clinical measurements (glycated hemoglobin A(1c) levels, body mass index, waist circumference, total cholesterol, blood pressure, and the presence of kidney complications or proteinuria, retinopathy, and foot abnormalities), self-reported health services utilization, clinical history, and knowledge of and satisfaction with diabetes services., Results: Female participants tended to be more obese (P < .05) and to have abnormal waist circumferences more often than men (P < .05). Male participants, however, had a higher proportion of proteinuria (P < .05), hypertension (P < .05), limb complications (P < .05), and retinopathy (P < .05). Family physicians were the main diabetes care providers for most participants. Nearly half the participants felt they did not have care from a diabetes team. A total of 38% had never seen dietitians. Diabetes-related concerns were responsible for 24% of all hospitalizations and emergency department visits. Approximately 46% and 21% of participants had recommended hemoglobin A(1c) testing and foot examinations, respectively. Only 24% of participants with kidney complications were receiving treatment. A considerable proportion of participants had undiagnosed complications of diabetes: kidney damage or proteinuria (23%), high cholesterol (22%), foot complications (11%), hypertension (9%), and retinopathy (7%)., Conclusion: Diabetes care is suboptimal in Alberta First Nations communities. Rural physicians caring for First Nations individuals on reserves should be involved, along with other members of diabetes health care teams, in strategies to improve diabetes care. Our results justify the need for community-based screening for diabetes control and complications in First Nation communities.

Objectives: Increasing type 2 diabetes in Aboriginal communities across North America raises concerns about metabolic syndrome in these populations. Some prevalence information for American Indians exists, but little has been available for Canada's First Nations., Study Design: We screened 60% of the eligible population of a single First Nation in Alberta for diabetes, pre-diabetes, cardiovascular risk, and metabolic syndrome., Methods: NCEP/ATP III and IDF criteria were used to identify metabolic syndrome in participants aged > or = 18; modified NCEP/ATP III criteria were used for participants aged < 18. Logistic regression identified factors associated with the metabolic syndrome., Results: 297 individuals were screened (176 adults, 84 children/adolescents, with complete data). 52.3% of adults had metabolic syndrome using NCEP/ATP III criteria, and 50% using IDF criteria. 40.5% of individuals aged < 18 had the condition. Waist circumference was the most prevalent correlate. Bivariate analysis suggested that age, BMI, weight, Alc, LDL-C, ADA risk score and activity pattern were associated with metabolic syndrome., Conclusions: Our data represent the first available for Western Cree and are consistent with prevalence reported for Aboriginal populations in Ontario and Manitoba. High rates of obesity, pre-diabetes and metabolic syndrome for participants aged < 18 raise concerns about future prevalence of diabetes and cardiovascular disease.

Objective/background: Aboriginals constitute a substantial portion of the population of Northern Alberta. Determinants such as poverty and education can compound health-care accessibility barriers experienced by Aboriginals compared to non-Aboriginals. A diabetes care enhancement study involved the collection of baseline and follow-up data on Aboriginal and non-Aboriginal patients with known type 2 diabetes in two rural communities in Northern Alberta. Analyses were conducted to determine any demographic or clinical differences existing between Aboriginals and non-Aboriginals., Methods: 394 diabetes patients were recruited from the Peace and Keeweetinok Lakes health regions. 354 self-reported whether or not they were Aboriginal; a total of 94 self-reported being Aboriginal. Baseline and follow-up data were collected through interviews, standardized physical assessments, laboratory testing and self-reporting questionnaires (RAND-12 and HUI3)., Results: Aboriginals were younger, with longer duration of diabetes, more likely to be female, and less likely to have completed high school. At baseline, self-reported health status was uniformly worse, but the differences disappeared with adjustments for sociodemographic confounders, except for perceived mental health status. Aboriginals considered their mental health status to be worse than non-Aboriginals at baseline. Some aspects of health utilization were also different., Discussion: While demographics were different and some utilization differences existed, overall this analysis demonstrates that "Aboriginality" does not contribute to diabetes outcomes when adjusted for appropriate variables.

Objective: Most quality improvement efforts for type 2 diabetes have neglected cardiovascular risk factors and are limited by a lack of information about generalizability across settings or persistence of effect over time., Research Design and Methods: We previously reported 6-month results of a controlled study of an intervention that improved cardiovascular risk factors for rural patients with type 2 diabetes. We subsequently provided the identical intervention to the control region after the main study was completed. The primary outcome was 10% improvement in systolic blood pressure, total cholesterol, or HbA(1c). We compared the previously reported 6-month effect of the original intervention with the effect of the crossed-over intervention to the former control region and remeasured outcomes in the original intervention region 12 months later., Results: Our analysis included 200 original intervention and 181 crossed-over intervention subjects. The age of the population was 62.4 +/- 12.4 years (mean +/- SD), and 54.3% were women. A similar proportion of patients in the crossed-over intervention group achieved improvement in the primary composite outcome compared with the original intervention group (38 vs. 44%, respectively; P = 0.29). In adjusted analyses, we observed less improvement in blood pressure (adjusted odds ratio 0.40 [95% CI 0.17-0.75]) but greater improvements in total cholesterol (1.86 [0.93-3.7]) with the crossed-over intervention compared with the original intervention. We observed sustained improvements in total cholesterol and HbA(1c) levels in the original intervention group, whereas previous large gains in control of blood pressure diminished over time., Conclusions: We found that our intervention was generalizable across settings, and its effect persisted over time. Nevertheless, without ongoing intervention or reinforcement, we noted some loss of the original benefits that had accrued. Future translational work should incorporate interventions such as ours into ongoing systems of rural care.

Background: Public insurance for testing supplies for self-monitoring of blood glucose is highly variable across Canada. We sought to determine if insured patients were more likely than uninsured patients to use self-monitoring and whether they had better glycemic control., Methods: We used baseline survey and laboratory data from patients enrolled in a randomized controlled trial examining the effect of paying for testing supplies on glycemic control. We recruited patients through community pharmacies in Alberta and Saskatchewan from Nov. 2001 to June 2003. To avoid concerns regarding differences in provincial coverage of self-monitoring and medications, we report the analysis of Alberta patients only., Results: Among our sample of 405 patients, 41% had private or public insurance coverage for self-monitoring testing supplies. Patients with insurance had significantly lower hemoglobin A(1c) concentrations than those without insurance coverage (7.1% v. 7.4%, p = 0.03). Patients with insurance were younger, had a higher income, were less likely to have a high school education and were less likely to be married or living with a partner. In multivariate analyses that controlled for these and other potential confounders, lack of insurance coverage for self-monitoring testing supplies was still significantly associated with higher hemoglobin A(1c) concentrations (adjusted difference 0.5%, p = 0.006)., Interpretation: Patients without insurance for self-monitoring test strips had poorer glycemic control.

Objective: The aim of this study was to examine patient-reported outcomes in a controlled trial of a multifaceted provider-level intervention to improve quality of care for rural patients with type 2 diabetes., Research Design and Methods: We conducted a before/after intervention study with concurrent controls in two rural regions in Alberta, Canada. The intervention consisted of six monthly visits by a multidisciplinary health care team and was primarily directed at primary care providers. Clinical and patient-reported outcomes were assessed after 6 months. Patient-reported outcomes included changes in health-related quality of life (Health Utilities Index Mark 3 [HUI3]), satisfaction with care, lifestyle (Diabetes Lifestyle Form), and adherence to self-care activities. Analysis of covariance was used to assess differences over time between the control and intervention regions., Results: A total of 200 intervention and 172 control subjects were included in this analysis. After adjusting for important clinical and demographic differences, a statistically significant and clinically important improvement in the overall HUI3 score was seen at the 6-month follow-up in the intervention region (0.06 [95% CI 0.02-0.10]) compared with the control region (0.01 [-0.04 to 0.04]) (P = 0.03 for the difference between groups). Satisfaction with general medical care (P < 0.001 between groups) and diabetes care (P < 0.001 between groups) increased among patients in the intervention region compared with the control region. Self-efficacy, attitudes, and beliefs about diabetes control all increased in the intervention region when compared with the control region, but adherence to self-care activities did not., Conclusions: A provider-level intervention directed at improving quality of clinical care for patients with type 2 diabetes also had a favorable impact on overall health-related quality of life, satisfaction with care, and other humanistic outcomes.

Objective: With increasing emphasis on the recognition of the metabolic syndrome and early type 2 diabetes, a clinically useful measure of insulin resistance is desirable. The purpose of this study was to evaluate whether an index of glucose metabolism, as measured by (13)CO(2) generation from ingested [(13)C]glucose, would correlate with indexes from the hyperinsulinemic-euglycemic clamp., Research Design and Methods: A total of 26 subjects with varying degrees of insulin sensitivity underwent both the [(13)C]glucose breath test and the hyperinsulinemic-euglycemic clamp. Results from the [(13)C]glucose breath test were compared with measures of insulin sensitivity from the glucose clamp as well as with other commonly used indexes of insulin sensitivity., Results: There was a strong correlation between the [(13)C]glucose breath test result and the glucose disposal rate (r = 0.69, P < 0.0001) and insulin sensitivity index (r = 0.69, P < 0.0001) from the insulin clamp. The magnitude of these correlations compared favorably with QUICKI and were superior to the homeostasis model assessment., Conclusions: The [(13)C]glucose breath test may provide a useful noninvasive assessment of insulin sensitivity.

Background: Diabetes is a chronic medical condition accompanied by a considerable health-related quality of life (HRQL) burden. The purpose of this analysis was to use generic measures of HRQL to describe HRQL deficits associated with varying degrees of severity of type 2 diabetes., Methods: The RAND-12 physical and mental health composites (PHC and MHC, respectively) and Health Utilities Index Mark 3 (HUI3) were self-completed by 372 subjects enrolled in a prospective, controlled study of an intervention to improve care for individuals with type 2 diabetes in rural communities. Analysis of covariance was used to assess differences in HRQL according to disease severity and control of blood glucose. Disease severity was defined in terms of treatment intensity, emergency room visits and absenteeism from work specifically attributable to diabetes. To control for potential confounding, the analysis was adjusted for important sociodemographic and clinical characteristics., Results: The PHC and MHC were significantly lower for individuals treated with insulin as compared to diet alone (PHC: 41.01 vs 45.11, MHC: 43.23 vs 47.00, p < 0.05). Individuals treated with insulin had lower scores on the vision, emotion and pain attributes of the HUI3 than individuals managed with oral medication or diet. The PHC, MHC, pain attribute and overall score on the HUI3 captured substantial decrements in HRQL associated with absenteeism from work due to diabetes, while the burden associated with emergency room utilization for diabetes was seen in the PHC and HUI3 pain attribute., Conclusions: We concluded that generic measures of HRQL captured deficits associated with more severe disease in type 2 diabetes.

Objective: Despite good evidence and clinical practice guidelines, studies document that treatment of type 2 diabetes is less than optimal. Lack of resources or limited access may put patients in rural communities at particular risk for suboptimal care., Research Design and Methods: We conducted a prospective, before/after study with concurrent controls to assess the effectiveness of a multidisciplinary diabetes outreach service (intervention) for improving the quality of care for rural patients with type 2 diabetes. Our intervention consisted of six monthly visits by a traveling team of specialist physicians, nurses, dieticians, and a pharmacist. The core of this service was specialist-to-rural primary care physician academic group detailing. Two comparable regions in Northern Alberta were randomly allocated to control or intervention. Data were collected before and 6 months after intervention in a representative volunteer sample. The primary outcome was a 10% improvement in any one of the following: blood pressure, total cholesterol, or HbA(1c)., Results: Our analysis included 200 intervention and 179 control subjects; 14 subjects were at all three primary outcome targets at baseline. The intervention was associated with a trend toward improvement in primary outcome at 6 months (44% intervention vs. 37% control; odds ratio 1.32, 95% CI 0.87-1.99). The intervention was associated with a significant improvement in blood pressure (42% intervention vs. 25% control, P = 0.004); however, there were only small, nonsignificant changes in cholesterol or HbA(1c). The intervention was associated with a significant increase in satisfaction with diabetes care. Multivariate adjustment for baseline differences between intervention and control subjects did not affect any of the main results., Conclusions: A diabetes outreach service has the potential to improve the quality of diabetes care for rural patients. Future studies need to involve longer timelines and larger sample sizes.

Objective: To emphasize preconception care of women with type 1 diabetes and the role of primary care physicians in evaluating and counseling them., Quality of Evidence: Substantial level II evidence indicates that tight glycemic control before conception and early in pregnancy reduces the rate of congenital malformations. Most evidence concerning maternal and fetal risks during pregnancy in patients with type 1 diabetes is level III or IV. Little is published on the role of family physicians in providing preconception counseling or care., Main Message: Preconception care is effective in improving glycemic control early in pregnancy and in reducing the rate of congenital malformations. Preconception evaluation of type 1 diabetic patients involves assessment of prepregnancy glycemic control and diabetic complications. Preconception counseling includes discussing the rate of transmission of diabetes, the effects of pregnancy on maternal and fetal complications, and the use of contraception until optimal glycemic control can be attained., Conclusion: Primary care physicians often have frequent and early contact with women of reproductive age; they are ideal candidates for providing type 1 diabetic women with preconception evaluation and counseling.

Objective: The aim of this study was to examine the relationship between use of metformin and sulfonylurea and mortality in new users of these agents., Research Design and Methods: Saskatchewan Health databases were used to examine population-based mortality rates for new users of oral antidiabetic agents. Individuals with prescriptions for sulfonylurea or metformin in 1991-1996 and no use in the year prior were identified as new users. Prescription records were prospectively followed for 1-9 years; subjects with any insulin use were excluded. Causes of death were identified based on ICD-9 codes in an electronic vital statistics database. Multivariate logistic regression and survival analyses were used to assess the differences in mortality between drug cohorts, after adjusting for potential confounding variables., Results: The total study sample comprised 12,272 new users of oral antidiabetic agents; the average length of follow-up was 5.1 (SD 2.2) years. In subjects with at least 1 year of drug exposure and no insulin use, mortality rates were 750/3,033 (24.7%) for those receiving sulfonylurea monotherapy, 159/1,150 (13.8%) for those receiving metformin monotherapy, and 635/4,683 (13.6%) for those receiving combination therapy over an average 5.1 (SD 2.2) years of follow-up. The adjusted odds ratio (OR) for all-cause mortality for metformin monotherapy was 0.60 (95% CI 0.49-0.74) compared with sulfonylurea monotherapy. Sulfonylurea plus metformin combination therapy was also associated with reduced all-cause mortality (OR 0.66, 95% CI 0.58-0.75). Reduced cardiovascular-related mortality rates were also observed in metformin users compared with sulfonylurea monotherapy users., Conclusions: Metformin therapy, alone or in combination with sulfonylurea, was associated with reduced all-cause and cardiovascular mortality compared with sulfonylurea monotherapy among new users of these agents.

Objective: To review the best evidence-based literature on the insulin analogue, lispro insulin, and to provide guidelines for its use., Quality of Evidence: Using the MeSH terms, lispro and insulin analogues, we searched PubMed, Current Contents, MEDLINE, and EMBASE from January 1986 to July 1998 and selected 42 articles out of 97 for high quality and relevance to family medicine. Twenty-eight were randomized controlled trials, but only two studies were blinded because lispro and regular insulin have different optimal times of administration., Main Message: The new insulin analogue, lispro, produces a much more rapid, higher, and shorter-lasting peak level of insulin than regular human insulin, thus mimicking physiologic secretion of insulin more closely. This allows insulin administration just before or just after meals and means patients can manage with fewer snacks. Lispro controls postprandial blood glucose levels better and does not cause hypoglycemia. Although most older studies showed no change in glycosylated hemoglobin (HbA1c) levels, a few recent studies involving refinements, such as continuous subcutaneous insulin infusion or basal insulin to reduce preprandial glucose levels, have found small but significant improvements. Insulin lispro has also been used successfully in cases of insulin resistance and insulin allergy., Conclusions: Lispro is a useful addition for motivated diabetic patients who like to achieve better control of HbA1c without increased hypoglycemia and to match mealtime insulin injections with diet, exercise, and various lifestyles.

A large Canadian kindred of Irish extraction extending from Quebec to British Columbia with autosomal dominant diabetes insipidus responsive to exogenous antidiuretic hormone (ADH) is described. Out of 121 individuals 34 have been identified as affected in seven generations. The disorder is characterized by variability in age at onset and in severity, and by apparently spontaneous abatement in old age. The affected subjects do not appear to manifest hypertension or its sequelae. In three individuals tested the plasma ADH level was very low in spite of adequate osmotic stimulation. However, the level rose in two of them when they were given furosemide, which suggests an osmoreceptor defect and a normal ADH response to volume change.