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.Indigenous peoples experience an excess burden of diabetes-related end-stage renal disease,^1–4 but the reasons for this disparity are incompletely understood. Although the increase in end-stage renal disease among indigenous peoples has paralleled the global emergence of type 2 diabetes mellitus,⁵ disparities in end-stage renal disease among Canada’s First Nations adults persist² after adjustment for elevated prevalence of diabetes.⁶ In an earlier study, we suggested that First Nations adults might be more prone to diabetic nephropathy and might experience more rapid progression to end-stage renal disease.⁷ However, although albuminuria is more prevalent in this population,⁸ affected individuals unexpectedly have a longer average time from diagnosis of diabetes to end-stage renal disease than people from non–First Nations populations.² These findings could be explained by a younger age at the time of diabetes diagnosis⁶ and lower mortality among those with chronic kidney disease.⁸ An age-related survival benefit among First Nations adults with diabetes could lead to longer exposure to the metabolic consequences of diabetes and greater likelihood of end-stage renal disease.Our objective was to examine the contribution of differential mortality to disparities in diabetes-related end-stage renal disease within large populations of indigenous and non-indigenous North Americans. Accordingly, we used competing-risks survival analysis to compare the simultaneous risks of diabetes-related end-stage renal disease and death without end-stage renal disease among First Nations and non–First Nations adults.⁹     

Recent epidemiologic trends of diabetes mellitus among status Aboriginal adults

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.The health of Aboriginal people in Canada is generally poorer than their non-Aboriginal counterparts, and diabetes mellitus is a significant contributor.^1,2 Studies have shown that type 2 diabetes and its complications occur at rates two to five times higher in Canada’s Aboriginal population than in the general population.^3–7 In response, diverse diabetes programs have materialized, including various community-based prevention and screening projects.^8–10 The federally funded Aboriginal Diabetes Initiative was created to emphasize health promotion and diabetes prevention.¹¹ In addition, numerous Aboriginal communities have established their own diabetes and health programs.¹²Accurate diabetes surveillance data are essential for governments and health care organizations to plan health care delivery and translate knowledge into policy and funding decisions. However, research into the longitudinal trends of diabetes in Aboriginal populations is scarce. For the most part, data have come from small, community-based studies and self-reported surveys. Population-based studies of primary data are few and have been conducted only for limited periods. Even less is known about outcomes, mortality in particular, among Aboriginal individuals with diabetes.The use of administrative data is becoming more common for tracking diabetes in Canada.¹³ The National Diabetes Surveillance System uses administrative health data to document the burden of the disease, but it has little information on Aboriginal people. Dyck and colleagues recently used the methodology of the National Diabetes Surveillance System to examine the incidence and prevalence of diabetes among Aboriginal people in the province of Saskatchewan,¹⁴ and similar analyses were conducted in Manitoba and Ontario.^15,16As part of the Alberta Diabetes Surveillance System, we conducted this study to compare the incidence and prevalence of diabetes among people 20 years and older in the status Aboriginal population (First Nations and Inuit people with treaty status) and the general population in the province of Alberta between 1995 and 2007. We also compared trends in mortality in the two populations among people with and without diabetes.     

Serum C-peptide levels and risk of death among adults without diabetes mellitus

Background:

Connecting peptide (C-peptide) plays a role in early atherogenesis in patients with diabetes mellitus and may be a marker for cardiovascular morbidity and mortality in patients without diabetes. We investigated whether serum C-peptide levels are associated with all-cause, cardiovascular-related and coronary artery disease–related mortality in adults without diabetes.

Methods:

We used data from the Third Nutrition and Health Examination Survey (NHANES III) and the NHANES III Linked Mortality File in the United States. We analyzed mortality data for 5902 participants aged 40 years and older with no history of diabetes and who had available serum C-peptide levels from the baseline examination. We grouped the participants by C-peptide quartile, and we performed Cox proportional hazards regression analysis. The primary outcome was all-cause, cardiovascular-related and coronary artery disease–related mortality.

Results:

The mean serum C-peptide level in the study sample was 0.78 (± standard deviation 0.47) nmol/L. The adjusted hazards ratio comparing the highest quartile with the lowest quartile was 1.80 (95% confidence interval [CI] 1.33–2.43) for all-cause mortality, 3.20 (95% CI 2.07–4.93) for cardiovascular-related mortality, and 2.73 (95% CI 1.55–4.82) for coronary artery disease–related mortality. Higher C-peptide levels were associated with increased mortality among strata of glycated hemoglobin and fasting serum glucose.

Interpretation:

We found an association between serum C-peptide levels and all-cause and cause-specific mortality among adults without diabetes at baseline. Our finding suggests that elevated C-peptide levels may be a predictor of death.Connecting peptide (C-peptide), a cleavage product of proinsulin, is secreted by pancreatic β cells in equimolar amounts along with insulin.¹ Although a considerable amount of insulin is extracted by the liver, C-peptide is subjected to negligible first-pass metabolism by the liver, thereby serving as a surrogate marker for endogenous insulin secretion.² C-peptide has been considered an inert by-product of insulin synthesis and has also been of great value in the understanding of the pathophysiology of type 1 and type 2 diabetes mellitus.^2,3 However, C-peptide has recently been re-evaluated as a bioactive peptide in its own right. The administration of C-peptide to patients and animals with type 1 diabetes has been reported to have a beneficial effect on diabetes-induced abnormalities of the peripheral nerves and renal and microvascular function.^4,5 C-peptide deposition occurs in the atherosclerotic lesions of patients with diabetes.⁶ Recent studies have suggested that C-peptide may be a valuable predictor of cardiovascular events and mortality (all-cause and cardiovascular-related mortality).^6–12In this study, we investigated the association between serum C-peptide level and all-cause, cardiovascular-related and coronary artery disease–related mortality among patients without diabetes. We also estimated mortality as C-peptide increased across glycated hemoglobin and fasting blood glucose quartiles.     

Likelihood of coronary angiography among First Nations patients with acute myocardial infarction

Background:

Morbidity due to cardiovascular disease is high among First Nations people. The extent to which this may be related to the likelihood of coronary angiography is unclear. We examined the likelihood of coronary angiography after acute myocardial infarction (MI) among First Nations and non–First Nations patients.

Methods:

Our study included adults with incident acute MI between 1997 and 2008 in Alberta. We determined the likelihood of angiography among First Nations and non–First Nations patients, adjusted for important confounders, using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database.

Results:

Of the 46 764 people with acute MI, 1043 (2.2%) were First Nations. First Nations patients were less likely to receive angiography within 1 day after acute MI (adjusted odds ratio [OR] 0.73, 95% confidence interval [CI] 0.62–0.87). Among First Nations and non–First Nations patients who underwent angiography (64.9%), there was no difference in the likelihood of percutaneous coronary intervention (PCI) (adjusted hazard ratio [HR] 0.92, 95% CI 0.83–1.02) or coronary artery bypass grafting (CABG) (adjusted HR 1.03, 95% CI 0.85–1.25). First Nations people had worse survival if they received medical management alone (adjusted HR 1.38, 95% CI 1.07–1.77) or if they underwent PCI (adjusted HR 1.38, 95% CI 1.06–1.80), whereas survival was similar among First Nations and non–First Nations patients who received CABG.

Interpretation:

First Nations people were less likely to undergo angiography after acute MI and experienced worse long-term survival compared with non–First Nations people. Efforts to improve access to angiography for First Nations people may improve outcomes.Although cardiovascular disease has been decreasing in Canada,¹ First Nations people have a disproportionate burden of the disease. First Nations people in Canada have a 2.5-fold higher prevalence of cardiovascular disease than non–First Nations people,² with hospital admissions for cardiovascular-related events also increasing.³The prevalence of cardiovascular disease in First Nations populations is presumed to be reflective of the prevalence of cardiovascular risk factors.^4–7 However, the disproportionate increase in rates of hospital admission suggests that suboptimal management of cardiovascular disease or its risk factors may also influence patient outcomes.^2,3 Racial disparities in the quality of cardiovascular care resulting in adverse outcomes have been documented, although most studies have focused on African-American, Hispanic and Asian populations.^8,9 As a result, it is unclear whether suboptimal delivery of guideline-recommended treatment contributes to increased cardiovascular morbidity and mortality among First Nations people.^10–12We undertook a population-based study involving adults with incident acute myocardial infarction (MI) to examine the receipt of guideline-recommended coronary angiography among First Nations and non–First Nations patients.^10–12 Among patients who underwent angiography, we sought to determine whether there were differences between First Nations and non–First Nations patients in the likelihood of revascularization and long-term survival.     

Hepatitis C virus infection among First Nation and non-First Nation people in Manitoba, Canada: a public health laboratory study

Demographic information and laboratory test results on 136 169 clinical serum specimens submitted to the public health laboratory in Manitoba, Canada, for hepatitis C virus (HCV) testing between January 1995 and December 2003 were analyzed. The difference in the clearance rates of HCV infection, without therapeutic intervention, and the HCV genotypes infecting First Nation and non-First Nation people were studied. The rates of co-infection of HCV-positive individuals with other hepatitis viruses were also compared between the two study groups. The results of the analyses of the data indicated that there was a 4.4-fold increase in the number of specimens tested and a 4.9-fold decrease in HCV antibody (anti-HCV) positive cases during the study period. The proportion of specimens submitted for testing from First Nation individuals was lower than their proportion in the Manitoba population. Our study also indicated that there was a significantly higher proportion of First Nation patients who had self-limiting infection (patients cleared the infection and became HCV RNA negative without anti-HCV treatment) in comparison to non-First Nation patients. The proportion of First Nation females who had self-limiting infection was significantly higher than non-First Nation females. HCV genotype 1 infection represented more than 60% of HCV infection in Manitoba. The rate of individuals positive for the hepatitis A virus antibody in the HCV-positive population was higher among First Nation than non-First Nation individuals. On the other hand, there were more HCV-infected First Nation patients than non-First Nation patients who were not immune to the hepatitis B virus. The data indicate that fewer First Nation patients seek anti-HCV therapy in comparison to non-First Nation. In conclusion, the differences in the rates of HCV self-limiting infection between First Nation and non-First Nation individuals in Manitoba may reflect the genetic differences between the two cohorts, which may consequently affect the immune response to the HCV infection.     

Association of macrosomia with perinatal and postneonatal mortality among First Nations people in Quebec

Background

High prevalence of infant macrosomia (up to 36%, the highest in the world) has been reported in some First Nations communities in the Canadian province of Quebec and the eastern area of the province of Ontario. We aimed to assess whether infant macrosomia was associated with elevated risks of perinatal and postneonatal mortality among First Nations people in Quebec.

Methods

We calculated risk ratios (RRs) of perinatal and postneonatal mortality by birthweight for gestational age, comparing births to First Nations women (n = 5193) versus women whose mother tongue is French (n = 653 424, the majority reference group) in Quebec 1991–2000.

Results

The prevalence of infant macrosomia (birthweight for gestational age > 90th percentile) was 27.5% among births to First Nations women, which was 3.3 times (confidence interval [CI] 3.2–3.5) higher than the prevalence (8.3%) among births to women whose mother tongue is French. Risk ratios for perinatal mortality among births to First Nations women were 1.8 (95% CI 1.3–2.5) for births with weight appropriate for gestational age, 4.1 (95% CI 2.4–7.0) for small-for-gestational-age (< 10th percentile) births and < 1 (not significant) for macrosomic births compared to births among women whose mother tongue is French. The RRs for postneonatal mortality were 4.3 (95% CI 2.7–6.7) for infants with appropriate-for-gestational-age birthweight and 8.3 (95% CI 4.0–17.0) for infants with macrosomia.

Interpretation

Macrosomia was associated with a generally protective effect against perinatal death, but substantially greater risks of postneonatal death among births to First Nations women in Quebec versus women whose mother tongue is French.A trend toward higher birthweights has emerged in recent decades.^1–3 Reflected in this trend is a rise in the prevalence of infant macrosomia, commonly defined as either a birthweight greater than 4000 g or a birthweight for gestational age greater than the 90th percentile relative to a fetal growth standard.^4–8 Maternal obesity, impaired glucose tolerance and gestational diabetes mellitus are important risk factors for infant macrosomia^9,10 and are known to afflict a much higher proportion of people in Aboriginal populations than in the general population.^11–14 This is true especially for Aboriginal populations in which a traditional lifestyle has changed to a less physically active, modern lifestyle in recent decades. A high prevalence of infant macrosomia (up to 36%, which, to the best of our knowledge, is the highest in the world) has been reported in some First Nations communities of Quebec and eastern Ontario in Canada.^15–17 However, little is known about the implications of this high prevalence for perinatal and infant health of First Nations people in these regions. We examined whether infant macrosomia was associated with increased risk for perinatal and postneonatal death among First Nations infants in Quebec.     

Fracture risk among First Nations people: a retrospective matched cohort study

Background

Canadian First Nations people have unique cultural, socioeconomic and health-related factors that may affect fracture rates. We sought to determine the overall and site-specific fracture rates of First Nations people compared with non-First Nations people.

Methods

We studied fracture rates among First Nations people aged 20 years and older (n = 32 692) using the Manitoba administrative health database (1987–1999). We used federal and provincial sources to identify ethnicity, and we randomly matched each First Nations person with 3 people of the same sex and year of birth who did not meet this definition of First Nations ethnicity (n = 98 076). We used a provincial database of hospital separations and physician billing claims to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for each fracture type based on a 5-year age strata.

Results

First Nations people had significantly higher rates of any fracture (age- and sex-adjusted SIR 2.23, 95% CI 2.18–2.29). Hip fractures (SIR 1.88, 95% CI 1.61–2.14), wrist fractures (SIR 3.01, 95% CI 2.63–3.42) and spine fractures (SIR 1.93, 95% CI 1.79–2.20) occurred predominantly in older people and women. In contrast, craniofacial fractures (SIR 5.07, 95% CI 4.74–5.42) were predominant in men and younger adults.

Interpretation

First Nations people are a previously unidentified group at high risk for fracture.Most of the epidemiologic data describing fractures have been derived from white populations,¹ although it is known that there is ethnic variation in the epidemiology of fractures.^2,3,4 Canadian First Nations people are known to suffer from a heavy burden of medical and social problems that may affect fracture rates.⁵ To date, however, there have been no satisfactory studies of fracture rates among North American Aboriginal groups. We sought to determine the overall and site-specific fracture rates of First Nations people compared with non-First Nations people in Manitoba.     

Monitoring,treatment and control of blood glucose and lipids in Ontario First Nations people with diabetes

BACKGROUND:Indigenous people worldwide are disproportionately affected by diabetes and its complications. We aimed to assess the monitoring, treatment and control of blood glucose and lipids in First Nations people in Ontario.METHODS:We conducted a longitudinal population-based study using administrative data for all people in Ontario with diabetes, stratified by First Nations status. We assessed age- and sex-specific rates of completion of recommended monitoring for low-density lipoprotein (LDL) and glycated hemoglobin (A_1c) from 2001/02 to 2014/15. We used data from 2014/15 to conduct a cross-sectional analysis of rates of achievement of A_1c and LDL targets and use of glucose-lowering medications.RESULTS:The study included 22 240 First Nations people and 1 319 503 other people in Ontario with diabetes. Rates of monitoring according to guidelines were 20%–50% for A_1c and 30%–70% for lipids and were lowest for younger First Nations men. The mean age- and sex-adjusted A_1c level was higher among First Nations people than other people (7.59 [95% confidence interval (CI) 7.57 to 7.61] v. 7.03 [95% CI 7.02 to 7.03]). An A_1c level of 8.5% or higher was observed in 24.7% (95% CI 23.6 to 25.0) of First Nations people, compared to 12.8% (95% CI 12.1 to 13.5) of other people in Ontario. An LDL level of 2.0 mmol/L or less was observed in 60.3% (95% CI 59.7 to 61.6) of First Nations people, compared to 52.0% (95% CI 51.1 to 52.9) of other people in Ontario. Among those aged 65 or older, a higher proportion of First Nations people than other Ontarians were using insulin (28.1% v. 15.1%), and fewer were taking no medications (28.3% v. 40.1%).INTERPRETATION:As of 2014/15, monitoring and achievement of glycemic control in both First Nations people and other people in Ontario with diabetes remained suboptimal. Interventions to support First Nations patients to reach their treatment goals and reduce the risk of complications need further development and study.

Diabetes and its related complications are major contributors to morbidity and mortality worldwide.^1–3 Indigenous populations in Canada and around the world are disproportionately affected by diabetes owing to the complex relations among colonization, social disadvantage, stress, trauma and metabolic health.^4–7 In addition to our own work showing persistently higher rates of peripheral vascular disease, stroke, cardiac disease, renal dysfunction and ophthalmologic complications in Ontario First Nations,^8–12 other Canadian and international studies also showed higher complication rates in diverse Indigenous populations.^6,7,13–15Glycemic control is fundamental to the management of diabetes and the prevention of complications.¹⁶ Glycated hemoglobin (A_1c) is a reliable way to estimate the average level of glucose in the blood.¹⁷ Since A_1c levels higher than 7.0% have been associated with an increased risk of microvascular complications,^18–20 treatment guidelines suggest A_1c should be measured every 3–6 months to ensure that glycemic goals are being met or maintained.²¹ Since people with diabetes also have an elevated risk for cardiovascular disease,^22–24 management and control of cardiovascular risk factors, particularly lipids such as low-density lipoprotein (LDL) cholesterol, are also important.^25–27 Guidelines further recommend that a full lipid profile be measured every 1–3 years, depending on cardiovascular risk, and suggest that LDL be consistently less than 2.0 mmol/L.²⁸ Control of A_1c and lipids has been shown to be associated with reduced morbidity and mortality in patients with diabetes.^18,29–32One possible reason for the high burden of complications among Indigenous people with diabetes may be failure to achieve control of these 2 key clinical parameters. We examined differences between Status First Nations people with diabetes in Ontario and all other Ontario residents with diabetes in rates of monitoring of A_1c and lipids, achievement of targets for A_1c and LDL outlined in clinical guidelines, and patterns of medication use to help attain these targets.     

Income-related differences in mortality among people with diabetes mellitus

Background

Mortality has declined substantially among people with diabetes mellitus over the last decade. Whether all income groups have benefited equally, however, is unclear. We examined the impact of income on mortality trends among people with diabetes.

Methods

In this population-based, retrospective cohort study, we compared changes in mortality from Apr. 1, 1994, to Mar. 31, 2005, by neighbourhood income strata among people with diabetes aged 30 years or more in the province of Ontario, Canada.

Results

Overall, the annual age- and sex-adjusted mortality declined, from 4.05% in 1994/95 (95% confidence interval [CI] 3.98%–4.11%) to 2.69% in 2005/06 (95% CI 2.66%–2.73%). The decrease was significantly greater in the highest income group (by 36%) than in the lowest income group (by 31%; p < 0.001). This trend was most pronounced in the younger group (age 30–64 years): the mortality rate ratio widened by more than 40% between the lowest and highest income groups, from 1.12 to 1.59 among women and from 1.14 to 1.60 among men. Income had a much smaller effect on mortality trends in the older group, whose drug costs are subsidized: the income-related difference rose by only 0.9% over the study period.

Interpretation

Mortality declined overall among people with diabetes from 1994 to 2005; however, the decrease was substantially greater in the highest income group than in the lowest, particularly among those aged 30–64 years. These findings illustrate the increasing impact of income on the health of people with diabetes even in a publicly funded health care setting. Further studies are needed to explore factors responsible for these income-related differences in mortality.The number of people with diabetes mellitus has increased dramatically over the last 20 years^1,2 and is estimated to double to about 366 million by 2030.³ Diabetes is associated with a 2-fold increase in mortality, with the majority of deaths attributed to cardiovascular causes.⁴ However, survival among people with diabetes has improved substantially over the last decade,^1,5,6 in part because of better diabetes care and a reduction in cardiovascular events.⁶Income is a well-known predictor of survival.^7,8 Even in Canada, where much of health care is universally funded, income-based inequities in health and access to care remain.^9–12 Although income-related differences in all-cause mortality have decreased since the advent of provincially subsidized health care in Canada,^8,9 the income gap may be increasing for certain causes of death, including those related to diabetes.⁸ The shift to more complex medical care involving a greater number of drug therapies has resulted in improved diabetes-related outcomes overall.¹³ However, patients in lower-income groups may not have benefited from advances in diabetes care as much as more affluent patients have because of the financial burden of out-of-pocket expenses for such medications and diabetes supplies.We conducted a population-based study to examine income-related differences in mortality from 1994 to 2005 among people with diabetes.     

Predictors of decrease in ankle-brachial index among patients with diabetes mellitus

Diabet. Med. 29, e304-e307 (2012) ABSTRACT: Aim Screening for peripheral arterial disease, a complication among patients with diabetes, is performed by periodic assessment of ankle-brachial index. We aimed to study the degree of ankle-brachial index change over time and factors associated with significant change. Method We assessed difference between two ankle-brachial index measurements over time in a consecutive series of 82 patients with Type?2 diabetes. All patients had ankle-brachial index >?0.9 but ≤?1.3 for the first measurement, and significant ankle-brachial index decrease was defined as a decrease of >?0.1 in the follow-up measurement compared with the baseline. Results The mean follow-up duration was 27.6 (median 30.0) months. Significant ankle-brachial index decrease was seen in 20.7% of patients, including 5% with follow-up ankle-brachial index of ≤?0.9, consistent with the diagnosis of peripheral arterial disease. After adjusting for age and gender, higher baseline HbA(1c) and serum creatinine levels, increase in follow-up serum LDL cholesterol levels compared with baseline and history of retinopathy were predictors of significant ankle-brachial index decrease. Conclusions Our study suggests that, within two?years, one in five patients with diabetes and a normal ankle-brachial index may have significant progression of peripheral arterial disease. Annual ankle-brachial index assessment and better control of hyperlipidaemia may thus be required for at-risk patients with poor glycaemic control, renal impairment and retinopathy.     

Prevalence and determinants of diabetes mellitus among Iranian patients with chronic liver disease

BACKGROUND: Alterations in carbohydrate metabolism are frequently observed in cirrhosis. We conducted this study to define the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in Iranian patients with chronic liver disease (CLD), and explore the factors associated with DM in these patients. METHODS: One hundred and eighty-five patients with CLD were enrolled into the study. Fasting plasma glucose and two-hour plasma glucose were measured in patients' sera. DM and IGT were diagnosed according to the latest American Diabetes Association criteria. RESULTS: The subjects included 42 inactive HBV carriers with a mean age of 42.2 +/- 12.0 years, 102 patients with HBV or HCV chronic hepatitis with a mean age of 41.2 +/- 10.9 years, and 41 cirrhotic patients with a mean age of 52.1 +/- 11.4 years. DM and IGT were diagnosed in 40 (21.6%) and 21 (11.4%) patients, respectively. Univariate analysis showed that age (P = 0.000), CLD status (P = 0.000), history of hypertension (P = 0.007), family history of DM (P = 0.000), and body mass index (BMI) (P = 0.009) were associated with DM. Using Multivariate analysis, age (OR = 4.7, 95%CI: 1.8-12.2), family history of DM (OR = 6.6, 95%CI: 2.6-17.6), chronic hepatitis (OR = 11.6, 95%CI: 2.9-45.4), and cirrhosis (OR = 6.5, 95%CI: 2.4-17.4) remained as the factors independently associated with DM. When patients with cirrhosis and chronic hepatitis were analyzed separately, higher Child-Pugh's score in cirrhotic patients (OR = 9.6, 95%CI: 1.0-88.4) and older age (OR = 7.2, 95%CI: 1.0-49.1), higher fibrosis score (OR = 59.5, 95%CI: 2.9-1211.3/ OR = 11.9, 95%CI: 1.0-132.2), and higher BMI (OR = 30.3, 95%CI: 3.0-306.7) in patients with chronic hepatitis were found to be associated with higher prevalence of DM. CONCLUSIONS: Our findings indicate that patients with cirrhosis and chronic hepatitis are at the increased risk of DM occurrence. Older age, severe liver disease, and obesity were associated with DM in these patients.     

Preventing insulin dependent diabetes mellitus: the environmental challenge. Diabetes Epidemiology Research International.

The epidemiology of insulin dependent diabetes mellitus was evaluated to determine the degree to which the disease results from environmental agents and therefore might be prevented. The results of research indicate that insulin dependent diabetes can be produced in animal models by environmental factors, there are major geographical variations in diabetes, certain populations have shown rapid changes in incidence over time, migrants appear to take on the risk of diabetes in their new country, and certain viruses and chemicals cause insulin dependent diabetes in humans. The results of genetic and epidemiological studies also show that at least 60% of insulin dependent diabetes world wide, and perhaps over 95%, is environmentally determined and thus potentially avoidable. It is concluded that the primary worldwide determinants of diabetes are environmental not immunogenetic and that identifying and altering the diabetogenic environmental factor(s) are likely to be more effective and less risky in preventing insulin dependent diabetes than current immunogenetic approaches.