Risk of kidney disease following a pregnancy complicated by diabetes: a longitudinal, population-based data-linkage study among Aboriginal women in the Northern Territory, Australia.

AIMS/HYPOTHESIS: The aim of this work was to investigate the risk of developing chronic kidney disease (CKD) or end-stage kidney disease (ESKD) following a pregnancy complicated by gestational diabetes mellitus (GDM) or pre-existing diabetes among Aboriginal women in the Northern Territory (NT), Australia. METHODS: We undertook a longitudinal study of linked healthcare datasets. All Aboriginal women who gave birth between 2000 and 2016 were eligible for inclusion. Diabetes status in the index pregnancy was as recorded in the NT Perinatal Data Collection. Outcomes included any stage of CKD and ESKD as defined by ICD-10 coding in the NT Hospital Inpatient Activity dataset between 2000 and 2018. Risk was compared using Cox proportional hazards regression. RESULTS: Among 10,508 Aboriginal women, the mean age was 23.1 (SD 6.1) years; 731 (7.0%) had GDM and 239 (2.3%) had pre-existing diabetes in pregnancy. Median follow-up was 12.1 years. Compared with women with no diabetes during pregnancy, women with GDM had increased risk of CKD (9.2% vs 2.2%, adjusted HR 5.2 [95% CI 3.9, 7.1]) and ESKD (2.4% vs 0.4%, adjusted HR 10.8 [95% CI 5.6, 20.8]). Among women with pre-existing diabetes in pregnancy, 29.1% developed CKD (adjusted HR 10.9 [95% CI 7.7, 15.4]) and 9.9% developed ESKD (adjusted HR 28.0 [95% CI 13.4, 58.6]). CONCLUSIONS/INTERPRETATION: Aboriginal women in the NT with GDM or pre-existing diabetes during pregnancy are at high risk of developing CKD and ESKD. Pregnancy presents an important opportunity to identify kidney disease risk. Strategies to prevent kidney disease and address the social determinants of health are needed.

Asthma diagnosis among children along an urban-rural gradient.

OBJECTIVE: Studies have reported lower asthma prevalence in rural compared to urban areas. While environmental factors have mostly been implicated for these differences, the lower asthma prevalence could also be linked to asthma under-diagnosis in rural children. We investigate if rural children experience under-diagnosis of asthma more compared to urban children. METHODS: In 2013, we conducted a cross-sectional survey of schoolchildren across an urban-rural gradient in Saskatchewan, Canada. The participants formed sampling frame for future studies. In 2015, we approached those who gave consent in 2013 for further testing, repeated the survey, and conducted clinical testing. Based on survey responses, children were classified into "no asthma," "at-risk-for-asthma," and "diagnosed asthma." We then classified asthma status as either "no asthma" or "probable asthma" based on a validated asthma algorithm. RESULTS: The study population of 335 schoolchildren (aged 7-17 years) comprised of 73.4% from large urban, 13.7% from small urban, and 12.8% from rural areas. Proportion with report of physician-diagnosed asthma was 28.5% (Large urban), 34.8% (Small urban), and 20.9% (Rural). Mean percent predicted FEV1 and FEF25%-75% were lower in rural compared to small urban and large urban children (p < 0.05). Among those not classified as with "diagnosed asthma" by the survey, the algorithm further identified presence of asthma in 5.5% large urban, 8.1% small urban, and 18.8% rural children (p = 0.03). CONCLUSION: The study revealed evidence of asthma underdiagnosis in rural areas and further supports the use of objective measures in addition to symptoms history when investigating asthma across urban-rural gradients.

The association between endotoxin in house dust with atopy and exercise-induced bronchospasm in children with asthma.

BACKGROUND: Studies have reported protective and adverse associations between microbial exposure and childhood asthma. However, among children with asthma the relationships between endotoxin and exercise-induced bronchospasm (EIB) is less clear. OBJECTIVE: We investigated the association between exposure to endotoxin in house dust with atopy and EIB in children with asthma. METHODS: A cross-sectional survey was conducted among schoolchildren (aged 7-17 years) in the province of Saskatchewan, Canada. A subpopulation with asthma (n = 116) were identified from 335 participants using a validated asthma algorithm. We determined atopy among the asthma subpopulation by skin prick testing (SPT) while EIB was evaluated using exercise challenge testing (ECT). Dust samples were collected from mattress and play area floors, and endotoxin was measured in dust extracts. Logistic regression analyses were used to explore associations between endotoxin with atopy and EIB. RESULTS: Among the 116 children with asthma, 99 completed SPT and all had completed ECT. Of these, 71/99 (71.7%) were atopic and 26/116 (22.4%) had EIB. Exposure to high play area endotoxin concentration [adjusted odds ratio (aOR) = 0.15, 95% CI: 0.03-0.85] and load (aOR = 0.11, 95% CI: 0.02-0.73) were negatively associated with atopy. In contrast, EIB was positively associated with high mattress endotoxin concentration (aOR = 6.01, 95% CI: 1.20-30.13). CONCLUSION: Indoor microbial endotoxin exposure has varied associations with atopy and exercise-induced bronchospasm among children with asthma.

Projecting prevalence, costs and evaluating simulated interventions for diabetic end stage renal disease in a Canadian population of aboriginal and non-aboriginal people: an agent based approach.

BACKGROUND: Diabetes-related end stage renal disease (DM-ESRD) is a devastating consequence of the type 2 diabetes epidemic, both of which disproportionately affect Indigenous peoples. Projecting case numbers and costs into future decades would help to predict resource requirements, and simulating hypothetical interventions could guide the choice of best practices to mitigate current trends. METHODS: An agent based model (ABM) was built to forecast First Nations and non-First Nations cases of DM-ESRD in Saskatchewan from 1980 to 2025 and to simulate two hypothetical interventions. The model was parameterized with data from the Canadian Institute for Health Information, Saskatchewan Health Administrative Databases, the Canadian Organ Replacement Register, published studies and expert judgement. Input parameters without data sources were estimated through model calibration. The model incorporated key patient characteristics, stages of diabetes and chronic kidney disease, renal replacement therapies, the kidney transplant assessment and waiting list processes, costs associated with treatment options, and death. We used this model to simulate two interventions: 1) No new cases of diabetes after 2005 and 2) Pre-emptive renal transplants carried out on all diabetic persons with new ESRD. RESULTS: There was a close match between empirical data and model output. Going forward, both incidence and prevalence cases of DM-ESRD approximately doubled from 2010 to 2025, with 250-300 new cases per year and almost 1300 people requiring RRT by 2025. Prevalent cases of First Nations people with DM-ESRD increased from 19% to 27% of total DM-ESRD numbers from 1990 to 2025. The trend in yearly costs paralleled the prevalent DM-ESRD case count. For Scenario 1, despite eliminating diabetes incident cases after 2005, prevalent cases of DM-ESRD continued to rise until 2019 before slowly declining. When all DM-ESRD incident cases received a pre-emptive renal transplant (scenario 2), a substantial increase in DM-ESRD prevalence occurred reflecting higher survival, but total costs decreased reflecting the economic advantage of renal transplantation. CONCLUSIONS: This ABM can forecast numbers and costs of DM-ESRD in Saskatchewan and be modified for application in other jurisdictions. This can aid in resource planning and be used by policy makers to evaluate different interventions in a safe and economical manner.

Childhood asthma, asthma severity indicators, and related conditions along an urban-rural gradient: a cross-sectional study.

BACKGROUND: Asthma prevalence is generally lower in rural locations with some indication of an urban-rural gradient. However, among children with asthma, certain rural exposures thought to protect against the development of asthma could aggravate the condition. We examined childhood asthma prevalence and related conditions along an urban-rural gradient and also examined the characteristics of those with asthma along the urban-rural gradient. METHODS: In 2013 we completed a cross-sectional survey of 3509 children aged 5-14 years living in various population densities of Saskatchewan, Canada. Location of dwelling was identified as belonging to one of the following population densities: large urban region (approximately 200,000), small urban (approximately 35,000), or rural (small town of <1,500 or farm dweller). Physician-diagnosed asthma and asthma-related symptoms were ascertained from responses in the parental-completed questionnaires. RESULTS: Of the study population, 69% lived in a large urban region, 11% lived in a small urban centre and 20% were rural dwellers. Overall, asthma prevalence was 19.6% with differences in asthma prevalence with differences between locations (large urban = 20.7%; small urban = 21.5%; rural = 15.1%; p = 0.003). After adjustment for potential confounders, the association between location of dwelling and asthma remained significant. Despite a lower prevalence of asthma in the rural area, the prevalence and risk of ever wheeze and having more than 3 wheezing episodes in the past 12 months among those who reported asthma, was higher in rural locations after adjustment for potential confounders. CONCLUSIONS: The results of this study support the evidence of a difference in childhood asthma prevalence between urban and rural locations and that once a child has asthma, certain rural exposures may aggravate the disease.

The FORGE AHEAD clinical readiness consultation tool: a validated tool to assess clinical readiness for chronic disease care mobilization in Canada's First Nations.

BACKGROUND: Given the astounding rates of diabetes and related complications, and the barriers to providing care present in Indigenous communities in Canada, intervention strategies that take into account contextual factors such as readiness to mobilize are needed to maximize improvements and increase the likelihood of success and sustainment. As part of the national FORGE AHEAD Program, we sought to develop, test and validate a clinical readiness consultation tool aimed at assessing the readiness of clinical teams working on-reserve in First Nations communities to participate in quality improvement (QI) to enhance diabetes care in Canada. METHODS: A literature review was conducted to identify existing readiness tools. The ABCD - SAT was adapted using a consensus approach that emphasized a community-based participatory approach and prioritized the knowledge and wisdom held by community members. The tool was piloted with a group of 16 people from 7 provinces and 11 partnering communities to assess language use, clarity, relevance, format, and ease of completion using examples. Internal reliability analysis and convergence validity were conducted with data from 53 clinical team members from 11 First Nations communities (3-5 per community) who have participated in the FORGE AHEAD program. RESULTS: The 27-page Clinical Readiness Consultation Tool (CRCT) consists of five main components, 21 sub-components, and 74 items that are aligned with the Expanded Chronic Care Model. Five-point Likert scale feedback from the pilot ranged from 3.25 to 4.5. Length of the tool was reported as a drawback but respondents noted that all the items were needed to provide a comprehensive picture of the healthcare system. Results for internal consistency showed that all sub-components except for two were within acceptable ranges (0.77-0.93). The Team Structure and Function sub-component scale had a moderately significant positive correlation with the validated Team Climate Inventory, r = 0.45, p < 0.05. CONCLUSIONS: The testing and validation of the FORGE AHEAD CRCT demonstrated that the tool is acceptable, valid and reliable. The CRCT has been successfully used to support the implementation of the FORGE AHEAD Program and the health services changes that partnering First Nations communities have designed and undertaken to improve diabetes care. TRIAL REGISTRATION NUMBER: Current ClinicalTrial.gov protocol ID NCT02234973 . Date of Registration: July 30, 2014.

Persistent Albuminuria in Children with Type 2 Diabetes: A Canadian Paediatric Surveillance Program Study.

OBJECTIVE: To determine the prevalence and the clinical features associated with persistent albuminuria in Canadian children aged <18 years with type 2 diabetes. STUDY DESIGN: This national prospective surveillance study involved a network of pediatricians and pediatric endocrinologists. Cases of persistent albuminuria in children with type 2 diabetes were reported during a 24-month period from 2010 to 2012. Persistent albuminuria was defined as an elevated albumin-to-creatinine ratio in a minimum of 2 out of 3 urine samples obtained at least 1 month apart over 3-6 months and confirmed with a first morning sample. Descriptive statistics were used to illustrate demographic and clinical features of the population. The prevalence of persistent albumuria was estimated using data from a previous national surveillence study of type 2 diabetes in children. RESULTS: Fifty cases were reported over the 24-month study period. The estimated prevalence of persistent albuminuria in children with type 2 diabetes in Canada was 5.1%. The median duration of diabetes at the time of diagnosis of albuminuria was 21 days (IQR, 0-241 days). Almost two-thirds (64%) were female, 80% were of Canadian First Nations heritage, and 76% were from Manitoba. Exposure to gestational or pregestational diabetes in utero occurred in 65%, and 48% had a family history of diabetes-related renal disease. Structural anomalies of the kidney were found in 37%. CONCLUSION: Persistent albuminuria occurs in youths with type 2 diabetes in the first year after diagnosis, demonstrates regional variation, and is associated with First Nations heritage and exposure to maternal diabetes during pregnancy.

Income adequacy and education associated with the prevalence of obesity in rural Saskatchewan, Canada.

BACKGROUND: Obesity is prevalent in rural communities in Canada, however little is known about the social determinants of health and obesity in rural populations. Socioeconomic status has been found to be inversely associated with the risk of obesity in developed countries. This study investigated the relationship between income adequacy, education and obesity in a rural setting. METHODS: The study used data from 5391 adults aged 18-69 who participated in the Saskatchewan Rural Health Study in 2010. Participants completed a survey that included questions about location of residence, body weight, height, and socio-demographic and behavioral factors. Obesity was defined as body mass index being ≥ 30 kg/m(2). Logistic regression using generalized estimating equation was conducted to assess the associations of income adequacy and education level with the prevalence of obesity taking covariates into consideration. RESULTS: Approximately a third of the participants were obese and the prevalence of obesity was similar for men and women. The prevalence of obesity was significantly higher for rural residents not living on farm compared with those living on farm (p < 0.05). After adjustment for potential confounders, the risk of obesity was increased for those with ≤ 12 years of education compared with those with > 12 years of education (aOR: 1.18; 95% CI: 1.05-1.34). Low income adequacy was significantly associated with an increased risk of obesity but only among those not living on farm (aOR: 1.80; 95% CI: 1.16-2.79). CONCLUSIONS: Home location was associated with obesity prevalence in rural Saskatchewan and modified the influence of income adequacy, but not the influence of education, on obesity. Adults not living on farm had an increased risk of obesity and showed a significant impact of income adequacy on obesity.

Do discrimination, residential school attendance and cultural disruption add to individual-level diabetes risk among Aboriginal people in Canada?

BACKGROUND: Aboriginal peoples in Canada (First Nations, Metis and Inuit) are experiencing an epidemic of diabetes and its complications but little is known about the influence of factors attributed to colonization. The purpose of this study was to investigate the possible role of discrimination, residential school attendance and cultural disruption on diabetes occurrence among First Nations adults. METHODS: This 2012/13 cross sectional survey was conducted in two Saskatchewan First Nations communities comprising 580 households and 1570 adults. In addition to self-reported diabetes, interviewer-administered questionnaires collected information on possible diabetes determinants including widely recognized (e.g. age, sex, lifestyle, social determinants) and colonization-related factors. Clustering effect within households was adjusted using Generalized Estimating Equations. RESULTS: Responses were obtained from 874 (55.7 %) men and women aged 18 and older living in 406 (70.0 %) households. Diabetes prevalence was 15.8 % among women and 9.7 % among men. In the final models, increasing age and adiposity were significant risk factors for diabetes (e.g. OR 8.72 [95 % CI 4.62; 16.46] for those 50+, and OR 8.97 [95 % CI 3.58; 22.52] for BMI 30+) as was spending most time on-reserve. Residential school attendance and cultural disruption were not predictive of diabetes at an individual level but those experiencing the most discrimination had a lower prevalence of diabetes compared to those who experienced little discrimination (2.4 % versus 13.6 %; OR 0.11 [95 % CI 0.02; 0.50]). Those experiencing the most discrimination were significantly more likely to be married and to have higher incomes. CONCLUSIONS: Known diabetes risk factors were important determinants of diabetes among First Nations people, but residential school attendance and cultural disruption were not predictive of diabetes on an individual level. In contrast, those experiencing the highest levels of discrimination had a low prevalence of diabetes. Although the reasons underlying this latter finding are unclear, it appears to relate to increased engagement with society off-reserve which may lead to an improvement in the social determinants of health. While this may have physical health benefits for First Nations people due to improved socio-economic status and other undefined influences, our findings suggest that this comes at a high emotional price.

A novel system dynamics model of female obesity and fertility.

OBJECTIVES: Our objective was to create a system dynamics model specific to weight gain and obesity in women of reproductive age that could inform future health policies and have the potential for use in preconception interventions targeting obese women. METHODS: We used our system dynamics model of obesity in women to test various strategies for family building, including ovulation induction versus weight loss to improve ovulation. Outcomes included relative fecundability, postpartum body mass index, and mortality. RESULTS: Our system dynamics model demonstrated that obese women who become pregnant exhibit increasing obesity levels over time with elevated morbidity and mortality. Alternatively, obese women who lose weight prior to pregnancy have improved reproductive outcomes but may risk an age-related decline in fertility, which can affect overall family size. CONCLUSIONS: Our model highlights important public health issues regarding obesity in women of reproductive age. The model may be useful in preconception counseling of obese women who are attempting to balance the competing risks associated with age-related declines in fertility and clinically meaningful weight loss.

Differential mortality and the excess burden of end-stage renal disease among First Nations people with diabetes mellitus: a competing-risks analysis.

BACKGROUND: Diabetes-related end-stage renal disease disproportionately affects indigenous peoples. We explored the role of differential mortality in this disparity. METHODS: In this retrospective cohort study, we examined the competing risks of end-stage renal disease and death without end-stage renal disease among Saskatchewan adults with diabetes mellitus, both First Nations and non-First Nations, from 1980 to 2005. Using administrative databases of the Saskatchewan Ministry of Health, we developed Fine and Gray subdistribution hazards models and cumulative incidence functions. RESULTS: Of the 90 429 incident cases of diabetes, 8254 (8.9%) occurred among First Nations adults and 82,175 (90.9%) among non-First Nations adults. Mean age at the time that diabetes was diagnosed was 47.2 and 61.6 years, respectively (p<0.001). After adjustment for sex and age at the time of diabetes diagnosis, the risk of end-stage renal disease was 2.66 times higher for First Nations than non-First Nations adults (95% confidence interval [CI] 2.24-3.16). Multivariable analysis with adjustment for sex showed a higher risk of death among First Nations adults, which declined with increasing age at the time of diabetes diagnosis. Cumulative incidence function curves stratified by age at the time of diabetes diagnosis showed greatest risk for end-stage renal disease among those with onset of diabetes at younger ages and greatest risk of death among those with onset of diabetes at older ages. INTERPRETATION: Because they are typically younger when diabetes is diagnosed, First Nations adults with this condition are more likely than their non-First Nations counterparts to survive long enough for end-stage renal disease to develop. Differential mortality contributes substantially to ethnicity-based disparities in diabetes-related end-stage renal disease and possibly to chronic diabetes complications. Understanding the mechanisms underlying these disparities is vital in developing more effective prevention and management initiatives.

Prevalence, risk factors and co-morbidities of diabetes among adults in rural Saskatchewan: the influence of farm residence and agriculture-related exposures.

BACKGROUND: Although rural Canadians are reported to have higher rates of diabetes than others, little is known about the relative influence of known versus agriculture-related risk factors. The purpose of this research was to carry out a comprehensive study of prevalence, risk factors and co-morbidities of diabetes among adults in rural Saskatchewan and to determine possible differences between those living on and off farms. METHODS: In 2010, we conducted a baseline mail-out survey (Saskatchewan Rural Health Study) of 11,982 households located in the province's four agricultural quadrants. In addition to self-reported physician-diagnosed diabetes, the questionnaire collected information from farm and small town cohorts on possible diabetes determinants including lifestyle, family history, early life factors and environmental/agricultural-related exposures. Clustering effect within households was adjusted using Generalized Estimating Equations approach. RESULTS: Responses were obtained from 4624 (42%) households comprising 8208 males and females aged 18 years or older and 7847 self-described Caucasian participants (7708 with complete information). The overall age-standardized diabetes prevalence for the latter was 6.35% but people whose primary residence was on farms had significantly lower diabetes prevalence than those living in non-farm locations (5.11% versus 7.33% respectively; p<0.0001). Diabetes risk increased with age and affected almost 17% of those older than 65 (OR 2.57; CI' 1.63, 4.04 compared to those aged 18-45). Other known independent risk factors included family history of diabetes (OR 2.50 [CI's 1.94, 3.23] if father; OR 3.11 [CI's 2.44, 3.98] if mother), obesity (OR 2.66; CI's 1.86, 3.78), as well as lower socioeconomic status, minimal/no alcohol intake and smoking. The most original finding was that exposure to insecticides conferred an increased risk for diabetes among males (OR 1.83; CI's 1.15, 2.91). Finally, the co-morbidities with the strongest independent association with diabetes were heart disease and hypertension. CONCLUSIONS: While known diabetes risk factors are important determinants of diabetes in the agricultural zones of Saskatchewan, on-farm residence is protective and appears related to increased outdoor activities. In contrast, we have now shown for the first time that exposure to insecticides is an independent risk factor for diabetes among men in rural Canada.

The Contribution of Gestational Diabetes to Diabetes Risk Among First Nations and Non-First Nations Women in Saskatchewan: Results From the DIP: ORRIIGENSS Project.

OBJECTIVES: Our aim in this study was to determine the risk for diabetes mellitus (DM) among Saskatchewan First Nations (FN) and non-FN women with prior gestational DM (GDM). METHODS: Using Ministry of Health administrative databases, we conducted a retrospective cohort study of DM risk by GDM occurrence among FN and non-FN women giving birth from 1980 to 2009 and followed to March 31, 2013. We determined frequencies and odds ratios (ORs) of DM in women with/without prior GDM after stratifying by FN status, while adjusting for other DM determinants. Survival curves of women until DM diagnosis were obtained by prior GDM occurrence and stratified by ethnicity and total parity. RESULTS: De-identified data were obtained for 202,588 women. Of those who developed DM, 2,074 of 10,114 (20.5%) had previously experienced GDM (811 of 3,128 [25.9%]) FN and 1,263 of 6,986 [18.1%] non-FN). Cumulative survival of women with prior GDM until DM was higher for FN than for non-FN women (82% vs 46%), but prior GDM was a stronger predictor of DM within the non-FN cohort (prior GDM vs no GDM: OR, 9.64 for non-FN; OR, 7.05 for FN). Finally, higher total parity interacted with prior GDM to increase DM risk in both groups. With prior GDM and parity ≥3, 93% of FN and 57% of non-FN women subsequently developed DM. CONCLUSIONS: GDM is a leading determinant of T2DM among FN and non-FN women, amplified by higher parity. This contributes to earlier onset diabetes, affecting subsequent pregnancies and increasing risk for chronic diabetic complications. It may also factor into higher type 2 DM rates observed in FN women compared with men.

Prevalence, determinants and co-morbidities of chronic kidney disease among First Nations adults with diabetes: results from the CIRCLE study.

BACKGROUND: Indigenous peoples worldwide are experiencing elevated rates of type 2 diabetes and its complications. To better understand the disproportionate burden of diabetic end stage renal disease (ESRD) among Canadian First Nations people (FN), we examined prevalence, determinants, and co-morbidities of chronic kidney disease (CKD) within this population. METHODS: The 2007 Canadian FN Diabetes Clinical Management and Epidemiologic (CIRCLE) study conducted a cross-sectional national medical chart audit of 885 FN adults with type 2 diabetes to assess quality of diabetes care. In this sub-study, participants were divided by estimated glomerular filtration rate (eGFR in ml/min/1.73 m2), as well as by albuminuria level in those with eGFRs = > 60. Those with eGFRs = > 60 and negative albuminuria were considered to have normal/near normal kidney function (non-CKD). Using univariate and logistic regression analysis, they were compared with participants having eGFRs = > 60 plus albuminuria (CKD-alb) and with participants having eGFRs <60 (CKD-eGFR <60). RESULTS: While 84.5% of total CIRCLE participants had eGFRs = > 60, almost 60% of the latter had CKD-alb. Of the 15.5% of total participants with CKD-eGFR <60, 80% had eGFRs 30-60 (Stage 3 CKD) but over 10% (1.6% of total participants) had ESRD. Independent determinants of CKD-alb were male gender and increasing diabetes duration, systolic BP, A1C and total cholesterol. These plus smoking rates also discriminated between FN with micro- and macro-albuminuria. Independent determinants of CKD-eGFR <60 were increasing age at diabetes diagnosis, diabetes duration, total cholesterol and systolic BP. However, participants with CKD-eGFR <60 also displayed a decreasing mean age of diabetes diagnosis as eGFR declined. Micro-vascular co-morbidities were significantly associated with CKD-alb but both micro- and macro-vascular co-morbidities were associated with CKD-eGFR <60. Only 35-40% of participants with CKD used insulin. CONCLUSIONS: High prevalences of CKD-alb and early CKD-eGFR <60 among diabetic FN were largely related to modifiable and treatable risk factors. However, an earlier age of diabetes diagnosis and longer duration of diabetes characterized those with ESRD. These findings suggest that a failure to meet current standards of diabetes care interacting with an age-related survival benefit contribute to the disproportionate burden of ESRD among FN and possibly other Indigenous peoples.

The inter- and intragenerational impact of gestational diabetes on the epidemic of type 2 diabetes.

OBJECTIVES: We investigated the contribution of gestational diabetes mellitus (GDM) to the historic epidemic of type 2 diabetes mellitus (T2DM) in Saskatchewan. METHODS: We constructed a population-level simulation model of the inter- and intragenerational interaction of GDM and T2DM for the period 1956 to 2006. The model was stratified by gender, ethnicity, and age; parameterized with primary and secondary data; and calibrated to match historic time series. Risk of diabetes was sigmoidally trended to capture exogenous factors. RESULTS: Best-fit calibrations suggested GDM may be responsible for 19% to 30% of the cases of T2DM among Saskatchewan First Nations people, but only for approximately 6% of cases among other persons living in Saskatchewan. The estimated contribution of GDM to the growth in T2DM was highly sensitive to assumptions concerning the post-GDM risk of developing T2DM. CONCLUSIONS: GDM may be an important driver for the T2DM epidemic in many subpopulations. Because GDM is a readily identifiable, preventable, and treatable condition, investments in prevention, rapid diagnosis, and evidence-based treatment of GDM in at-risk populations may offer substantial benefit in lowering the T2DM burden over many generations. Model-informed data collection can aid in assessing intervention tradeoffs.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): An Emerging Relationship With Pregestational Diabetes Mellitus Among First Nations and Non-First Nations People in Saskatchewan-Results From the DIP: ORRIIGENSS Project.

OBJECTIVES: Because congenital anomalies of the kidneys and urinary tract (CAKUT) represent a frequent cause of end stage renal disease (ESRD) in the young, we explored the epidemiology of CAKUT and the role of diabetes in pregnancy. METHODS: This was a retrospective cohort study of CAKUT, by maternal diabetes status, from among all 1980‒2009 births in Saskatchewan First Nations (FN) and non-First Nations (non-FN) people. We determined frequencies, predictors and complications of CAKUT, as well as cumulative survival (to 2014) of affected persons until ESRD and death. RESULTS: Of the 411,055 babies (204,167 mothers) in the Saskatchewan maternal-infant database, 2,540 had CAKUT (391 FN and 2,149 non-FN). Overall annual CAKUT incidence was 0.63% for non-FN and 0.57% for FN (p=0.082), but 5-year CAKUT incidence only increased among FN (0.40% in 1980‒1984 and 0.76% in 2005‒2009, p<0.0001) and was highest among offspring of FN mothers with pregestational diabetes (pre-G/DM) (0% before 1995, 2.51% in 2000‒2004 and 1.66% in 2005-2009). Pre-G/DM, but not gestational diabetes mellitus (GDM), was an independent predictor of CAKUT in non-FN (odds ratio, 1.79; 95% confidence interval, 1.20 to 2.69), and in FN interacting with maternal history of stillbirth (odds ratio, 7.90; 95% confidence interval, 1.14 to 54.6). ESRD was >100-fold more likely among offspring with CAKUT compared with all other offspring and was responsible for 40% of ESRD cases in young FN and non-FN people. CONCLUSIONS: In Saskatchewan, pre-G/DM is an emerging cause of CAKUT, accounting for 40% of ESRD cases in FN/non-FN children and young adults. Because pre-G/DM‒related CAKUT is potentially preventable with optimal glycemic management, increased recognition of this serious complication is required.

Epidemiology of diabetes mellitus among First Nations and non-First Nations adults.

BACKGROUND: First Nations people in Canada experience a disproportionate burden of type 2 diabetes mellitus. To increase our understanding of this evolving epidemic, we compared the epidemiology of diabetes between First Nations and non-First Nations adults in Saskatchewan from 1980 to 2005. METHODS: We used administrative databases to perform a population-based study of diabetes frequency, incidence and prevalence in adults by ethnic background, year, age and sex. RESULTS: We identified 8275 First Nations and 82,306 non-First Nations people with diabetes from 1980 to 2005. Overall, the incidence and prevalence of diabetes were more than 4 times higher among First Nations women than among non-First Nations women and more than 2.5 times higher among First Nations men than among non-First Nations men. The number of incident cases of diabetes was highest among First Nations people aged 40-49, while the number among non-First Nations people was greatest in those aged 70 or more years. The prevalence of diabetes increased over the study period from 9.5% to 20.3% among First Nations women and from 4.9% to 16.0% among First Nations men. Among non-First Nations people, the prevalence increased from 2.0% to 5.5% among women and from 2.0% to 6.2% among men. By 2005, almost 50% of First Nations women and more than 40% of First Nations men aged 60 or older had diabetes, compared with less than 25% of non-First Nations men and less than 20% of non-First Nations women aged 80 or older. INTERPRETATION: First Nations adults are experiencing a diabetes epidemic that disproportionately affects women during their reproductive years. This ethnicity-based pattern suggests diverse underlying mechanisms that may include differences in the diabetogenic impact of gestational diabetes.

Methods of competing risks analysis of end-stage renal disease and mortality among people with diabetes.

BACKGROUND: When a patient experiences an event other than the one of interest in the study, usually the probability of experiencing the event of interest is altered. By contrast, disease-free survival time analysis by standard methods, such as the Kaplan-Meier method and the standard Cox model, does not distinguish different causes in the presence of competing risks. Alternative approaches use the cumulative incidence estimator by the Cox models on cause-specific and on subdistribution hazards models. We applied cause-specific and subdistribution hazards models to a diabetes dataset with two competing risks (end-stage renal disease (ESRD) or death without ESRD) to measure the relative effects of covariates and cumulative incidence functions. RESULTS: In this study, the cumulative incidence curve of the risk of ESRD by the cause-specific hazards model was revealed to be higher than the curves generated by the subdistribution hazards model. However, the cumulative incidence curves of risk of death without ESRD based on those three models were very similar. CONCLUSIONS: In analysis of competing risk data, it is important to present both the results of the event of interest and the results of competing risks. We recommend using either the cause-specific hazards model or the subdistribution hazards model for a dominant risk. However, for a minor risk, we do not recommend the subdistribution hazards model and a cause-specific hazards model is more appropriate. Focusing the interpretation on one or a few causes and ignoring the other causes is always associated with a risk of overlooking important features which may influence our interpretation.

Differences in glycemic control and survival predict higher ESRD rates in diabetic First Nations adults.

PURPOSE: Diabetic First Nations people (FN) have higher ESRD rates than other Canadians but the reasons remain unclear. We sought to better understand this disparity by comparing demographic, laboratory and survival features of diabetic FN and other Saskatchewan residents (OSK) by renal function stage. METHODS: Prevalent diabetes cases in 2005/06 were identified in Saskatchewan's two largest health regions using administrative databases, and linked with centralized laboratory tests. They were sub-divided into five stages of renal function using estimated glomerular filtration rates (eGFR) that were determined in 992 of 2,321 FN (42.7%) and 14,054 of 21,886 OSK (64.2%). Age, sex, urine microalbumin (MA), glycosylated hemoglobin (A1C), low density lipoprotein cholesterol (LDL-C) and two year mortality risk was compared for all subjects. RESULTS: Diabetic FN were younger (mean age 52.7 vs. 64.2, p < 0.0001), more likely to be female (59.6% vs.45.4%, p < 0.001), had increased MA (56.6% vs. 48.4%, p < 0.0001) and displayed higher mean A1C levels (8.16% vs.7.36%, p < 0.0001) than OSK. Despite a larger proportion having eGFR's > 60 ml/min (87.0% vs.77.3%, p < 0.001), FN were also more likely to have ESRD (2.3% vs.0.8%, p < 0.001). Although FN with eGFR's > 30 ml/min experienced higher age/sex adjusted mortality risk than OSK, the trends for both adjusted and unadjusted mortality risks for those with advanced pre-ESRD renal failure were lower for FN than for OSK. CONCLUSIONS: Elevated rates of ESRD experienced by FN with diabetes are related to poorer glycemic control at all levels of renal function, and lower age-related mortality at advanced stages of chronic kidney disease.

Risk factors, incidence, and prevalence of diabetes among rural farm and non-farm residents of Saskatchewan, Canada; a population-based longitudinal cohort study.

PURPOSE: Saskatchewan has a high prevalence of diabetes. It is the largest, rurally populated, predominantly agricultural province in Canada. This research aims to determine the risk factors associated with the incidence and longitudinal changes in the prevalence of diabetes among Saskatchewan's adult rural farm and non-farm residents. METHODS: The Saskatchewan Rural Health Study (SRHS) is a prospective cohort study conducted in two phases: a baseline survey (2010, 8261 participants) and a follow-up survey (2014, 4867 participants). Generalized estimation equations and survival analysis techniques were used to determine diabetes prevalence and incidence risk factors, respectively. RESULTS: Incidence of diabetes among rural residents was 2.75%. Positive family history, high BMI, sleep apnea and an abnormal Epworth Sleepiness Score (ESS) were significant predictors for diabetes incidence. A substantial increase (1.98%) of diabetes prevalence was observed after four years of follow-up. Risk factors of diabetes prevalence were increasing age, male, low income, positive family history, high BMI, hypertension and heart attack. CONCLUSION: A mix of individual and contextual factors interacting in complex pathways were responsible for the high incidence and prevalence of diabetes among rural residents. The most original finding of that study was a positive association of sleep apnea, and ESS with incident diabetes warrants further research to identify a causal linkage. Increased diabetes risk among rural male insecticide users indicates an adverse consequence of unprotected chemical exposures in the agricultural field. Urgent population-based preventive measures should initiate to slow the increasing trend of diabetes prevalence among rural residents.