A comparison between different patient groups for diabetes management during phases of the COVID-19 pandemic: a retrospective cohort study in Ontario, Canada.

BACKGROUND: With the onset of the COVID-19 pandemic and the large uptake in virtual care in primary care in Canada, the care of patients with type 2 diabetes has been greatly affected. This includes decreased in-person visits, laboratory testing and in-person assessments such as blood pressure (BP). No studies have investigated if these changes persisted with pandemic progression, and it is unclear if shifts impacted patient groups uniformly. The purpose of this paper was to examine changes in diabetes care pre, early, and later pandemic across different patient groups. METHODS: A repeated cross-sectional design with an open cohort was used to investigate diabetes care in adults with type 2 diabetes for a 6-month interval from March 14 to September 13 over three consecutive years: 2019 (pre-pandemic period), 2020 (early pandemic period), and 2021 (later pandemic period). Data for this study were abstracted from the University of Toronto Practice-Based Research Network (UTOPIAN) Data Safe Haven, a primary care electronic medical records database in Ontario, Canada. Changes in diabetes care, which included primary care total visits, in-person visits, hemoglobin A1c (HbA1c) testing, and BP measurements were evaluated across the phases of the pandemic. Difference in diabetes care across patient groups, including age, sex, income quintile, prior HbA1c levels, and prior BP levels, were assessed. RESULTS: A total of 39,401 adults with type 2 diabetes were included in the study. Compared to the 6-month pre-pandemic period, having any in-person visits decreased significantly early pandemic (OR = 0.079 (0.076-0.082)), with a partial recovery later pandemic (OR = 0.162 (95% CI: 0.157-0.169). Compared to the pre-pandemic period, there was a significant decrease early pandemic for total visits (OR = 0.486 (95% CI: 0.470-0.503)), HbA1c testing (OR = 0.401 (95% CI: 0.389-0.413)), and BP measurement (OR = 0.121 (95% CI: 0.116-0.125)), with partial recovery later pandemic. CONCLUSIONS: All measures of diabetes care were substantially decreased early pandemic, with a partial recovery later pandemic across all patient groups. With the increase in virtual care due to the COVID-19 pandemic, diabetes care has been negatively impacted over 1-year after pandemic onset.

Metformin and breast cancer stage at diagnosis: a population-based study.

PURPOSE: The objective of the present study was to use a large, population-based cohort to examine the association between metformin and breast cancer stage at diagnosis while accounting for mammography differences. METHODS: We used data from Ontario administrative health databases to identify women 68 years of age or older with diabetes and invasive breast cancer diagnosed from 1 January 2007 to 31 December 2012. Adjusted logistic regression models were used to compare breast cancer stage at diagnosis (stages i and ii vs. iii and iv) between the women exposed and not exposed to metformin. We also examined the association between metformin use and estrogen receptor status, tumour size, and lymph node status in the subset of women for whom those data were available. RESULTS: We identified 3125 women with diabetes and breast cancer; 1519 (48.6%) had been exposed to metformin before their cancer diagnosis. Median age at breast cancer diagnosis was 76 years (interquartile range: 72-82 years), and mean duration of diabetes was 8.8 ± 5.9 years. In multivariable analyses, metformin exposure was not associated with an earlier stage of breast cancer (odds ratio: 0.98; 95% confidence interval: 0.81 to 1.19). In secondary analyses, metformin exposure was not associated with estrogen receptor-positive breast cancer, tumours larger than 2 cm, or positive lymph nodes. CONCLUSIONS: This population-based study did not show an association between metformin use and breast cancer stage or tumour characteristics at diagnosis. Our study considered older women with long-standing diabetes, and therefore further studies in younger patients could be warranted.

Osteoarthritis-related difficulty walking and risk for diabetes complications.

OBJECTIVES: To examine the effect of Osteoarthritis (OA)-related difficulty walking on risk for diabetes complications in persons with diabetes and OA. DESIGN: A population cohort aged 55+ years with symptomatic hip and knee OA was recruited 1996-98 and followed through provincial administrative data to 2015 (n = 2,225). In those with confirmed OA (examination and radiographs) and self-reported diabetes at baseline (n = 359), multivariate Cox regression modeling was used to examine the relationship between baseline difficulty walking (Health Assessment Questionnaire (HAQ) difficulty walking score; use of walking aid) and time to first diabetes-specific complication (hospitalization for hypo- or hyperglycemia, infection, amputation, retinopathy, or initiation of chronic renal dialysis) and cardiovascular (CV) events. RESULTS: Participants' mean baseline age was 71.4 years; 66.9% were female, 77.7% had hypertension, 54.0% had pre-existing CV disease, 42.9% were obese and 15.3% were smokers. Median HAQ difficulty walking score was 2/3 indicating moderate to severe walking disability; 54.9% used a walking aid. Over a median 6.1 years, 184 (51.3%) experienced one or more diabetes-specific complications; 191 (53.2%) experienced a CV event over a median 5.7 years. Greater baseline difficulty walking was associated with shorter time to the first diabetes-specific complication (adjusted HR per unit increase in HAQ walking 1.24, 95% CI 1.04-1.47, P = 0.02) and CV event (adjusted HR for those using a walking aid 1.35, 95% CI 1.00-1.83, P = 0.04). CONCLUSIONS: In a population cohort with OA and diabetes, OA-related difficulty walking was a significant - and potentially modifiable - risk factor for diabetes complications.

Short-term risk of cancer among women with previous gestational diabetes: a population-based study.

AIMS: To evaluate the relationship between gestational diabetes (GDM) and incidence of cancer in women within the first decade postpartum. METHODS: This population-based retrospective cohort study compared the risk of cancer in women with GDM with that of a matched control group comprising pregnant women without diabetes. We included women from Ontario, Canada aged 20-50 years with no history of cancer who had given birth between 1995 and 2008 (N = 149 049). Women with GDM (N = 49 684) were matched on age and year of giving birth, in a ratio of 1:2, to pregnant women without diabetes (N = 99 365). RESULTS: Over a median 8-year follow-up, there were a total of 2927 (1.5%) cancers. After adjustment for covariates, we found no significant difference in overall risk of cancer between women with GDM and matched control subjects; however, GDM was associated with a significantly greater risk of thyroid cancer (adjusted hazard ratio 1.24, 95% CI 1.05, 1.46) and a significantly lower risk of premenopausal breast cancer (hazard ratio 0.86, 95% CI 0.75, 0.98) compared with matched control subjects. CONCLUSIONS: This large population-based study did not find a greater risk of cancers among women with GDM during the first decade postpartum; however, GDM was associated with a higher risk of thyroid cancer and a lower risk of premenopausal breast cancer. Further studies are needed to confirm these findings.

Predictors of low diabetes risk perception in a multi-ethnic cohort of women with gestational diabetes mellitus.

AIM: To determine what proportion of women with gestational diabetes underestimate their diabetes risk and identify factors associated with low diabetes risk perception. METHODS: Participants included pregnant adult women with gestational diabetes between 2009 and 2012 across seven diabetes clinics in Ontario, Canada. Data were collected through chart review and a survey that included a diabetes risk perception question. RESULTS: Of the 614 of 902 women (68% response rate) with gestational diabetes, 89% correctly responded that gestational diabetes increases the risk for developing diabetes. However, 47.1% of women perceived themselves to be at low risk for developing diabetes within 10 years. On multivariable analysis, BMI < 25 kg/m(2) , absent previous gestational diabetes history, absent diabetes family history and absent insulin use were appropriately associated with low diabetes risk perception. However, compared with Caucasian ethnicity, high-risk ethnicity (Aboriginal, Latin American, West Indian, South Asian, Middle Eastern, Filipino, Black, Pacific Islander) [odds ratio (OR) 2.07; 95% CI 1.30-3.31] and East and South East Asian ethnicity (OR 2.01; 1.10-3.67) were associated with low diabetes risk perception. After further adjustment for immigration, only high-risk ethnicity remained a predictor of low diabetes risk perception (OR 1.86; 1.09-3.19), whereas East and South East Asian ethnicity did not (OR 1.67; 0.86-3.22). CONCLUSIONS: Although the majority of women recognized gestational diabetes as a risk factor for diabetes, almost half underestimated their personal high diabetes risk despite prenatal care. Furthermore, women from high-risk ethnic groups were more likely to underestimate their risk, even after adjusting for immigration. Interventions tailored to these groups are necessary to enhance perceived diabetes risk.

A population-based study of ethnicity and breast cancer stage at diagnosis in Ontario.

BACKGROUND: Breast cancer stage at diagnosis is an important predictor of survival. Our goal was to compare breast cancer stage at diagnosis (by American Joint Committee on Cancer criteria) in Chinese and South Asian women with stage at diagnosis in the remaining general population in Ontario. METHODS: We used the Ontario population-based cancer registry to identify all women diagnosed with breast cancer during 2005-2010, and we applied a validated surname algorithm to identify South Asian and Chinese women. We used logistic regression to compare, for Chinese or South Asian women and for the remaining general population, the frequency of diagnoses at stage ii compared with stage i and stages ii-iv compared with stage i. RESULTS: The registry search identified 1304 Chinese women, 705 South Asian women, and 39,287 women in the remaining general population. The Chinese and South Asian populations were younger than the remaining population (mean: 54, 57, and 61 years respectively). Adjusted for age, South Asian women were more often diagnosed with breast cancer at stage ii than at stage i [odds ratio (or): 1.28; 95% confidence interval (ci): 1.08 to 1.51] or at stages ii-iv than at stage i (or: 1.27; 95% ci: 1.08 to 1.48); Chinese women were less likely to be diagnosed at stage ii than at stage i (or: 0.82; 95% ci: 0.72 to 0.92) or at stages ii-iv than at stage i (or: 0.73; 95% ci: 0.65 to 0.82). CONCLUSIONS: Breast cancers were diagnosed at a later stage in South Asian women and at an earlier stage in Chinese women than in the remaining population. A more detailed analysis of ethnocultural factors influencing breast screening uptake, retention, and care-seeking behavior might be needed to help inform and evaluate tailored health promotion activities.

Gender differences in the impact of poverty on health: disparities in risk of diabetes-related amputation.

AIMS: To assess the combined impact of socio-economic status and gender on the risk of diabetes-related lower extremity amputation within a universal healthcare system. METHODS: We conducted a population-based cohort study using administrative health databases from Ontario, Canada. Adults with pre-existing or newly diagnosed diabetes (N = 606 494) were included and the incidence of lower extremity amputation was assessed for the period 1 April 2002 to 31 March 2009. Socio-economic status was based on neighbourhood-level income groups, assigned to individuals using the Canadian Census and their postal code of residence. RESULTS: Low socio-economic status was associated with a significantly higher incidence of lower extremity amputation (27.0 vs 19.3 per 10,000 person-years in the lowest (Q1) vs the highest (Q5) socio-economic status quintile. This relationship persisted after adjusting for primary care use, region of residence and comorbidity, and was greater among men (adjusted Q1:Q5 hazard ratio 1.41, 95% CI 1.30-1.54; P < 0.0001 for all male gender-socio-economic status interactions) than women (hazard ratio 1.20, 95% CI 1.06-1.36). Overall, the incidence of lower extremity amputation was higher among men than women (hazard ratio for men vs women: 1.87, 95% CI 1.79-1.96), with the greatest disparity between men in the lowest socio-economic status category and women in the highest (hazard ratio 2.39, 95% CI 2.06-2.77 and hazard ratio 2.30, 95% CI 1.97-2.68, for major and minor amputation, respectively). CONCLUSIONS: Despite universal access to hospital and physician care, we found marked socio-economic status and gender disparities in the risk of lower extremity amputation among patients with diabetes. Men living in low-income neighbourhoods were at greatest risk.

Impact of socio-economic status on breast cancer screening in women with diabetes: a population-based study.

AIMS: There is evidence to suggest that mammography rates are decreased in women with diabetes and in women of lower socio-economic status. Given the strong association between low socio-economic status and diabetes, we explored the extent to which differences in socio-economic status explain lower mammography rates in women with diabetes. METHODS: A population-based retrospective cohort study in Ontario, Canada, of women aged 50 to 69 years with diabetes between 1999 and 2010 age matched 1:2 to women without diabetes. Main outcome measure is the likelihood of at least one screening mammogram in women with diabetes within a 36-month period, starting as of either 1 January 1999, their 50th birthday, or 2 years after diabetes diagnosis--whichever came last. Outcomes were compared with those in women without diabetes during the same period as their matched counterparts, adjusting for socio-economic status based on neighbourhood income and other demographic and clinical variables. RESULTS: Of 504,288 women studied (188,759 with diabetes, 315,529 with no diabetes), 63.8% had a screening mammogram. Women with diabetes were significantly less likely to have a mammogram after adjustment for socio-economic status and other factors (odds ratio 0.79, 95% CI 0.78-0.80). Diabetes was associated with lower mammogram use even in women from the highest socio-economic status quintile (odds ratio 0.79, 95% CI 0.75-0.83). CONCLUSIONS: The presence of diabetes was an independent barrier to breast cancer screening, which was not explained by differences in socio-economic status. Interventions that target patient, provider, and health system factors are needed to improve cancer screening in this population.

Mortality trends in patients with and without diabetes in Ontario, Canada and the UK from 1996 to 2009: a population-based study.

AIMS/HYPOTHESIS: The aim of this study was to determine the contemporary rate ratio of mortality and changes over time in individuals with vs without diabetes. METHODS: Annual age- and sex-adjusted mortality rates were compared for adults (>20 years) with and without diabetes in Ontario, Canada, and the UK from January 1996 to December 2009 using The Health Improvement Network (THIN) and Ontario databases. The total number of individuals evaluated increased from 8,757,772 in 1996 to 12,696,305 in 2009. RESULTS: The excess risk of mortality for individuals with diabetes in both cohorts was significantly lower during later vs earlier years of the follow-up period (1996-2009). In Ontario the diabetes mortality rate ratio decreased from 1.90 (95% CI 1.86, 1.94) in 1996 to 1.51 (1.48, 1.54) in 2009, and in THIN from 2.14 (1.97, 2.32) to 1.65 (1.57, 1.72), respectively. In Ontario and THIN, the mortality rate ratios among diabetic patients in 2009 were 1.67 (1.61, 1.72) and 1.81 (1.68, 1.94) for those aged 65-74 years and 1.11 (1.10, 1.13) and 1.19 (1.14, 1.24) for those aged over 74 years, respectively. Corresponding rate ratios in Ontario and THIN were 2.45 (2.36, 2.54) and 2.64 (2.39, 2.89) for individuals aged 45-64 years, and 4.89 (4.35, 5.45) and 5.18 (3.73, 6.69) for those aged 20-44 years. CONCLUSIONS/INTERPRETATION: The excess risk of mortality in individuals with vs without diabetes has decreased over time in both Canada and the UK. This may be in part due to earlier detection and higher prevalence of early diabetes, as well as to improvements in diabetes care.

Incidence of diabetes among postmenopausal breast cancer survivors.

AIMS/HYPOTHESIS: Evidence is emerging of an association between breast cancer and diabetes; however, it is uncertain whether diabetes incidence is increased in postmenopausal breast cancer survivors compared with women without breast cancer. The objective of this study was to determine whether postmenopausal women who develop breast cancer have a higher incidence of diabetes than those who do not develop breast cancer. METHODS: We used population-based data from Ontario, Canada to compare the incidence of diabetes among women with breast cancer, aged 55 years or older, from 1996 to 2008, with that of age-matched women without breast cancer. We used Cox proportional hazard models to estimate the effect of breast cancer on the cause-specific hazard of developing diabetes overall and in the subgroup of women who received adjuvant chemotherapy. RESULTS: Of 24,976 breast cancer survivors and 124,880 controls, 9.7% developed diabetes over a mean follow-up of 5.8 years. The risk of diabetes among breast cancer survivors compared with women without breast cancer began to increase 2 years after diagnosis (HR 1.07 [95% CI, 1.02, 1.12]), and rose to an HR of 1.21 (95% CI, 1.09, 1.35) after 10 years. Among those who received adjuvant chemotherapy (n = 4,404), risk was highest in the first 2 years after diagnosis (HR 1.24 [95% CI 1.12, 1.38]) and then declined. CONCLUSIONS/INTERPRETATION: We found a modest increase in the incidence of diabetes among postmenopausal breast cancer survivors that varied over time. In most women the risk began to increase 2 years after cancer diagnosis but the highest risk was in the first 2 years in those who received adjuvant therapy. Our study suggests that greater diabetes screening and prevention strategies among breast cancer survivors may be warranted.

Diabetes and cancer (1): evaluating the temporal relationship between type 2 diabetes and cancer incidence.

Substantial evidence suggests that people with type 2 diabetes have an increased risk of developing several types of cancers. These associations may be due to a number of direct and indirect mechanisms. Observational studies of these associations, including the potential role for glucose-lowering therapy, are being increasingly reported, but face a number of methodological challenges. This paper is the first of two review papers addressing methodological aspects underpinning the interpretations of links between diabetes and cancer, and suggests potential approaches to study designs to be considered in observational studies. This paper reviews factors related to cancer incidence in the diabetic population; the second paper relates to studies of cancer mortality.

Association between serum 25-hydroxyvitamin D in early pregnancy and risk of gestational diabetes mellitus.

AIMS: There is emerging evidence of a relationship between vitamin D insufficiency and glucose intolerance. The aim of this study was to determine whether low serum 25-hydroxyvitamin D in early pregnancy is associated with an increased risk of gestational diabetes mellitus. METHODS: This nested case-control study examined the association between serum 25-hydroxyvitamin D and risk of gestational diabetes within a cohort of pregnant women from March 2008 to December 2009, who had undergone antenatal screening between 15 and 18 weeks gestation and subsequent glucose tolerance testing. Cases were women diagnosed with gestational diabetes and each case was matched to up to two controls without gestational diabetes on age, race and date of blood collection. Serum 25-hydroxyvitamin D was measured from stored antenatal screening samples and compared between cases and controls. RESULTS: Of the 116 women with gestational diabetes and 219 control subjects studied, the average age was 34.3 years and 41% were of non-Caucasian race. Women with gestational diabetes had significantly lower serum 25-hydroxyvitamin D compared with control subjects (56.3 vs. 62.0 nmol/l, P = 0.018). After adjusting for gestational age and maternal weight, serum 25-hydroxyvitamin D below the top quartile (< 73.5 nmol/l) was associated with a twofold greater likelihood of gestational diabetes (adjusted odds ratio 2.21, 95% confidence interval 1.19-4.13). CONCLUSIONS: Lower vitamin D status in early pregnancy was associated with a significantly increased risk of subsequent gestational diabetes that was independent of race, age, season and maternal weight. This study suggests that vitamin D may influence glucose tolerance during pregnancy and provides support for studies of vitamin D as a potential intervention to prevent gestational diabetes.

Missed opportunities for type 2 diabetes testing following gestational diabetes: a population-based cohort study.

OBJECTIVES: Few women with gestational diabetes (GDM) are tested for type 2 diabetes in the postpartum period. Whether women are having physician visits that could be an opportunity to improve testing rates is unknown. This study sought to evaluate population-level trends in postpartum diabetes testing after GDM, and to evaluate postpartum physician care for these women. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. POPULATION: Women who delivered between 1994 and 2008. METHODS: Using population-level healthcare databases, we identified 47,691 women with GDM. They were matched to women without GDM. MAIN OUTCOME MEASURES: An oral glucose tolerance test (OGTT) within 6 months postpartum, the specialty of the physician ordering the test, and ambulatory care visits with physicians from various specialties within 6 months postpartum were recorded. RESULTS: Most women with GDM did not receive an OGTT, although testing rates increased slowly over the 14 years of the study, compared with no change in testing for women who had not had GDM. Virtually all women with GDM had postpartum visits with a family physician or obstetrician, but few OGTTs were ordered by physicians from these specialties. CONCLUSIONS: Despite a slow increase in testing over time and high rates of postpartum visits to family physicians and obstetricians, few women with GDM received the recommended diabetes test. This represents a missed opportunity in a high-risk population. Interventions to change test ordering that target family physicians and obstetricians are most likely to increase the proportion of women with GDM who receive postpartum diabetes testing.

Glucose infusion partially attenuates glucose production and increases uptake during intense exercise.

Glucose infusion can prevent the increase in glucose production (Ra) and increase glucose uptake (Rd) during exercise of moderate intensity. We postulated that 1) because in postabsorptive intense exercise (>80% maximal O2 uptake) the eightfold increase in Ra may be mediated by catecholamines rather than by glucagon and insulin, exogenous glucose infusion would not prevent the Ra increment, and 2) such infusion would cause greater Rd. Fit young men were exercised at >85% maximal O2 uptake for 14 min in the postabsorptive state [controls (Con), n = 12] or at minute 210 of a 285-min glucose infusion. In seven subjects, the infusion was constant (CI; 4 mg . kg-1 . min-1), and in seven subjects it was varied (VI) to mimic the exercise Ra response in Con. Although glucose suppressed Ra to zero (with glycemia approximately 6 mM and insulin approximately 150 pM), an endogenous Ra response to exercise occurred, to peak increments two-thirds those in Con, in both CI and VI. Glucagon was unchanged, and very small increases in the glucagon-to-insulin ratio occurred in all three groups. Catecholamine responses were similar in all three groups, and correlation coefficients of Ra with plasma norepinephrine and epinephrine were significant in all. In all CI and VI, Rd at rest was 2x Con, increased earlier in exercise, and was higher for the 1 h of recovery with glucose infusion. Thus the Ra response was only partly attenuated, and the catecholamines are likely to be the regulators. This suggests that an acute endogenous Ra rise is possible even in the postprandial state. Furthermore, the fact that more circulating glucose is used by muscle during exercise and early recovery suggests that muscle glycogen is spared.