Despite a dramatically increasing burden of type 2 diabetes in Aboriginal Canadian communities (1–5), relatively little information is available regarding the prevalence of, and risk factors for, the complications of type 2 diabetes in this population (6). Although previous studies have documented micro- and macrovascular disease in Aboriginal Canadians with diabetes, the majority of these reports have relied heavily on hospital records, chart reviews, and disease registries (6). These approaches may underestimate the magnitude of the complications burden because only those with the severest disease are included, and standardized methods are infrequently used to document complications. The objective of the present research project was to systematically determine, using validated methods, the prevalence of micro- and macrovascular complications among Aboriginal Canadians who have type 2 diabetes and to identify risk factors that are associated with these conditions.
RESEARCH DESIGN AND METHODS
The Sandy Lake Diabetes Complications Study has been presented in detail previously (6). Briefly, all community members known to have type 2 diabetes were invited to participate; 189 of 250 (76%) eligible subjects were enrolled, although the sample size varies given time-limited access to certain equipment. Participants were older than nonparticipants and more likely to be male but did not differ in diabetes treatment. Signed informed consent was obtained from all participants, and the study was approved by the Sandy Lake First Nation Band Council and the Mount Sinai Hospital Ethics Review Committee.
We used validated measures to assess retinopathy, neuropathy, nephropathy, and cardiovascular disease risk factors, as described previously (6). Digital fundus photography was performed using a nonmydriatic retinal camera, with no pharmacological pupillary dilation. Three 45° images were taken in each eye, as described (7). After initial clinical assessment and referral by an ophthalmologist (B.S.), photographs were transferred to the Ocular Epidemiology Grading Center at the University of Wisconsin (Madison, WI), where they were graded for retinopathy (mild nonproliferative diabetic retinopathy [NPDR]), moderate/severe NPDR, or proliferative diabetic retinopathy [PDR]) and macular edema (8,9). Diabetic sensory neuropathy was determined using a modification of the Michigan Neuropathy Screening Instrument (10). (In the current study monofilament testing was added and the questionnaire portion was not used.) Scores range from 0 to 9, and individuals with scores >2 were considered to have neuropathy. Diabetic nephropathy was determined by measuring the albumin-to-creatinine ratio in a single, random, daytime urine sample (11) using the Bayer DCA 2000 Point-of-Care Analyzer, which has been validated (r = 0.95) against laboratory techniques (12). Intimal-media thickness (IMT) was determined using a high-resolution duplex ultrasound scanner (ATL 5000 HDI; Advanced Technology Laboratories, Seattle, WA), as described (13–15). The ankle-brachial blood pressure index was determined using a blood pressure cuff and Doppler stethoscope. Angina and intermittent claudication were assessed using the Rose questionnaire (16,17).
Risk factors were assessed using laboratory and physical measurements and standardized, interviewer-administered questionnaires (6). Measures included HbA1c (A1C) using the DCA 2000 Analyzer (validity 0.90–0.98 vs. laboratory measures) (18), high-sensitivity C-reactive protein and lipid concentrations (19), height, weight, waist circumference, duration of diabetes, method of diabetes and hypertension treatment, and cigarette smoking (2,6). Multivariate linear regression analysis was used to identify variables that were associated with the natural logs of albumin-to-creatinine ratio, neuropathy score, and IMT, and logistic regression was used to assess risk factors for retinopathy.
RESULTS
Kidney disease was common, with prevalence rates of 44% for microalbuminuria and 16.9% for macroalbuminuria (Table 1). In addition, early neuropathy was prevalent (46.3%), and although 23.3% of the population had some level of retinopathy, PDR was uncommon. The prevalence rates of poor glycemic control, hypertension, current smoking, and elevated LDL cholesterol, triglyceride, and C-reactive protein each exceeded 50% (Table 1).
Linear regression revealed that longer duration of diabetes and elevated A1C were independently associated with higher albumin-to-creatinine ratio (both P < 0.05). Age and longer diabetes duration were determinants of the log of the neuropathy score (both P < 0.05), while systolic blood pressure, age, and pack-years of smoking were significant determinants of the log of IMT (all P < 0.05). Duration of diabetes (odds ratio 2.3 [95% CI 1.2–4.6] per 5-year increase), systolic blood pressure (1.6 [1.1–2.3] per 10-mmHg increase), and A1C (1.8 [1.0–3.4] per 2% increase) were significantly associated with risk of retinopathy using logistic regression.
CONCLUSIONS
The high prevalence rates of both micro- and macroalbuminurua in this study are notable and consistent with previous data suggesting that Aboriginal Canadians may be especially susceptible to the renal complications of diabetes (6,20–26). The mechanism underlying this elevated renal risk is unknown, although suboptimal glucose and blood pressure control likely play a role. In addition, a variant of the gene encoding angiotensinogen, AGT 235, has been associated with a qualitative measure of microalbuminuria in this population (26).
Previous chart review studies in Aboriginal Canadians have documented neuropathy prevalence ranging from 0 to 12% (20–22,27); these rates are notably lower than the estimate from the present study (46.3%). This divergence is likely due to differences in procedures used to measure neuropathy. Cases of diabetic neuropathy recorded in medical charts likely represent only the severest portion of the disease spectrum, whereas the Michigan Neuropathy Screening Instrument will have also detected subjects in the earlier stages of sensory neuropathy (10).
Limited data are available on the prevalence of diabetic retinopathy among Aboriginal Canadians. Maberley et al. (28) reported prevalence rates of macular edema, NPDR, and PDR that were remarkably similar to those from the present study (24% NPDR, 5% macular edema, and 2% PDR). The relatively low prevalence rates of PDR and macular edema in this population, especially in light of the high rate of nephropathy, possibly reflect the low median duration of diabetes or the presence of protective genetic factors.
The strengths of this study include the high participation rate, the community-based setting, and the use of a wide range of validated, systematically applied exposure and outcome measures. Limitations include the small sample size and the cross-sectional design. Notwithstanding, this study represents the first comprehensive, systematic, and standardized documentation of diabetes complications and associated risk factors among Aboriginal Canadians.
In conclusion, in a community-based study of Aboriginal Canadians, we found high prevalence rates of both diabetes complications and associated risk factors and, furthermore, that well-established associations between risk factors and complications were apparent. These results highlight the urgent need to implement culturally appropriate strategies for the prevention of diabetes complications in this population.
Subject characteristics and prevalence of diabetes complications and associated risk factors, Sandy Lake Diabetes Complications Study, 2001
| . | Definition . | n . | . |
|---|---|---|---|
| Age (average years ± SD) | 46.5 ± 13.3 | ||
| Sex (% female) | 65.0 | ||
| Duration of diabetes [median years (interquartile range)] | 9.0 (3–11) | ||
| Complications | |||
| Microalbuminuria* | Albumin-to-creatinine ratio 2.0–20 mg/mmol (men), 2.8–28 mg/mmol (women) | 166 | 44.0% (36.4–51.9) |
| Macroalbuminuria* | Albumin-to-creatinine ratio >20 mg/mmol (men), >28 mg/mmol (women) | 166 | 16.9% (11.7–23.6) |
| Neuropathy† | >2 points on MNSI | 147 | 46.3% (38.1–55.6) |
| Retinopathy‡ | Mild NPDR | 8.3% (4.6–15.2) | |
| Moderate/severe NPDR | 13.5% (8.8–21.6) | ||
| PDR | 133 | 1.5% (0.3–6.1) | |
| Macular edema§ | Non-CSME or CSME | 132 | 3.1% (1.0–8.2) |
| Increased carotid IMT | IMT >1 mm | 140 | 9.3% (5.2–15.7) |
| Peripheral arterial disease‖ | Ankle-brachial index <0.95 | 141 | 14.9% (9.7–22.1) |
| Angina | Positive on Rose questionnaire | 183 | 10.9% (6.9–16.5) |
| Claudication | Positive on Rose questionnaire | 183 | 6.0% (3.2–10.8) |
| Risk factors | |||
| Poor glycemic control¶ | A1C >7% | 171 | 63.2% (55.4–70.3) |
| Hypertension (%)¶# | SBP/DBP >130/80 mmHg | 180 | 61.7% (54.1–68.7) |
| Elevated LDL¶ | LDL ≥2.5 mmol/l | 144 | 61.1% (52.6–69.0) |
| Elevated total-to-HDL cholesterol ratio¶ | Total-to-HDL cholesterol ratio ≥4 | 147 | 45.6% (37.4–54.0) |
| Elevated triglyceride¶ | Triglyceride ≥1.5 mmol/l | 147 | 61.2% (52.8–69.0) |
| Elevated C-reactive protein** | C-reactive protein ≥3 mg/l | 147 | 51.7% (43.3–60.0) |
| Duration of diabetes | >10 years | 189 | 47.1% (39.9–54.5) |
| Smoking | Currently smoking cigarettes | 183 | 51.4% (43.9–58.8) |
| . | Definition . | n . | . |
|---|---|---|---|
| Age (average years ± SD) | 46.5 ± 13.3 | ||
| Sex (% female) | 65.0 | ||
| Duration of diabetes [median years (interquartile range)] | 9.0 (3–11) | ||
| Complications | |||
| Microalbuminuria* | Albumin-to-creatinine ratio 2.0–20 mg/mmol (men), 2.8–28 mg/mmol (women) | 166 | 44.0% (36.4–51.9) |
| Macroalbuminuria* | Albumin-to-creatinine ratio >20 mg/mmol (men), >28 mg/mmol (women) | 166 | 16.9% (11.7–23.6) |
| Neuropathy† | >2 points on MNSI | 147 | 46.3% (38.1–55.6) |
| Retinopathy‡ | Mild NPDR | 8.3% (4.6–15.2) | |
| Moderate/severe NPDR | 13.5% (8.8–21.6) | ||
| PDR | 133 | 1.5% (0.3–6.1) | |
| Macular edema§ | Non-CSME or CSME | 132 | 3.1% (1.0–8.2) |
| Increased carotid IMT | IMT >1 mm | 140 | 9.3% (5.2–15.7) |
| Peripheral arterial disease‖ | Ankle-brachial index <0.95 | 141 | 14.9% (9.7–22.1) |
| Angina | Positive on Rose questionnaire | 183 | 10.9% (6.9–16.5) |
| Claudication | Positive on Rose questionnaire | 183 | 6.0% (3.2–10.8) |
| Risk factors | |||
| Poor glycemic control¶ | A1C >7% | 171 | 63.2% (55.4–70.3) |
| Hypertension (%)¶# | SBP/DBP >130/80 mmHg | 180 | 61.7% (54.1–68.7) |
| Elevated LDL¶ | LDL ≥2.5 mmol/l | 144 | 61.1% (52.6–69.0) |
| Elevated total-to-HDL cholesterol ratio¶ | Total-to-HDL cholesterol ratio ≥4 | 147 | 45.6% (37.4–54.0) |
| Elevated triglyceride¶ | Triglyceride ≥1.5 mmol/l | 147 | 61.2% (52.8–69.0) |
| Elevated C-reactive protein** | C-reactive protein ≥3 mg/l | 147 | 51.7% (43.3–60.0) |
| Duration of diabetes | >10 years | 189 | 47.1% (39.9–54.5) |
| Smoking | Currently smoking cigarettes | 183 | 51.4% (43.9–58.8) |
Data are prevalence (95% CI) unless otherwise indicated.
Micro- and macroalbuminuria cut points taken from Canadian Diabetes Association clinical practice guidelines (11); to convert cut points presented in mg/mmol to mg/g, multiply by 8.83.
Diabetic sensory neuropathy assessed using MNSI (range 0–9; subjects with scores >2 considered to have neuropathy) (10).
Retinopathy definitions based on the Early Treatment Diabetic Retinopathy Study adaptation of the modified Airlie House classification (8).
Macular edema graded as described in detail previously (9).
Peripheral artery disease was defined as an ankle-brachial index of <0.95; subjects with ankle-brachial index >1.40 were considered to have noncompressible vessels.
Risk factor cut points taken from Canadian Diabetes Association clinical practice guidelines (11).
Hypertension: systolic blood pressure (SBP) ≥130 mmHg and/or diastolic blood pressure (DBP) ≥80 mmHg or on hypertension treatment.
C-reactive protein risk cutoff proposed by Centers for Disease Control and Prevention/American Heart Association (29). CSME, clinically significant macular edema.
Article Information
This research has been supported through an operating grant from the Canadian Institutes of Health Research (CIHR) (MOP 4407). A.J.G.H. is supported through a Canadian Diabetes Association Research Scholarship and by a University of Toronto Banting and Best Diabetes Centre New Investigator Award. S.B.H. is a Career Scientist of the Ontario Ministry of Health. J.D.S. was supported by a grant from the Canadian Stroke Network. J.R.M. is an investigator of the CIHR. B.Z. holds the Sam and Judy Pencer Family Chair in Diabetes Research at Mount Sinai Hospital and the University of Toronto.
We are indebted to the leadership and community members of Sandy Lake First Nation for their enthusiastic partnership and participation in this project. We thank Maria DiCicco, RVT, and Janine Boere, RVT, for performing the carotid artery scans. Finally, we would like to thank the NORTH Network team for their essential contributions to the retinal screening aspects of this project.
REFERENCES
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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