ContextMicroalbuminuria is a risk factor for cardiovascular (CV) events. The
relationship between the degree of albuminuria and CV risk is unclear.ObjectivesTo estimate the risk of CV events in high-risk individuals with diabetes
mellitus (DM) and without DM who have microalbuminuria and to determine whether
levels of albuminuria below the microalbuminuria threshold increase CV risk.DesignThe Heart Outcomes Prevention Evaluation study, a cohort study conducted
between 1994 and 1999 with a median 4.5 years of follow-up.SettingCommunity and academic practices in North and South America and Europe.ParticipantsIndividuals aged 55 years or more with a history of CV disease (n =
5545) or DM and at least 1 CV risk factor (n = 3498) and a baseline urine
albumin/creatinine ratio (ACR) measurement.Main Outcome MeasuresCardiovascular events (myocardial infarction, stroke, or CV death);
all-cause death; and hospitalization for congestive heart failure.ResultsMicroalbuminuria was detected in 1140 (32.6%) of those with DM and 823
(14.8%) of those without DM at baseline. Microalbuminuria increased the adjusted
relative risk (RR) of major CV events (RR, 1.83; 95% confidence interval [CI],
1.64-2.05), all-cause death (RR, 2.09; 95% CI, 1.84-2.38), and hospitalization
for congestive heart failure (RR, 3.23; 95% CI, 2.54-4.10). Similar RRs were
seen for participants with or without DM, even after adjusting for other CV
risk factors (eg, the adjusted RR of the primary aggregate end point was 1.97
[95% CI, 1.68-2.31] in those with DM and 1.61 [95% CI, 1.36-1.90] in those
without DM).Compared with the lowest quartile of ACR (<0.22 mg/mmol), the
RRs of the primary aggregate end point in the second quartile (ie, ACR range,
0.22-0.57 mg/mmol) was 1.11 (95% CI, 0.95-1.30); third quartile, 1.38 (95%
CI, 1.19-1.60; ACR range, 0.58-1.62 mg/mmol); and fourth quartile, 1.97 (95%
CI, 1.73-2.25; ACR range, >1.62 mg/mmol) (P for trend
<.001, even after excluding those with microalbuminuria). For every 0.4-mg/mmol
increase in ACR level, the adjusted hazard of major CV events increased by
5.9% (95% CI, 4.9%-7.0%).ConclusionsOur results indicate that any degree of albuminuria is a risk factor
for CV events in individuals with or without DM; the risk increases with the
ACR, starting well below the microalbuminuria cutoff. Screening for albuminuria
identifies people at high risk for CV events.

https://jamanetwork.com/journals/jama/articlepdf/194038/JOC02030.pdf

Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals

OBJECTIVE: To determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. DESIGN: Prospective observational study. SETTING: 23 hospital based clinics in England, Scotland, and Northern Ireland. PARTICIPANTS: 4801 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. OUTCOME MEASURES: Primary predefined aggregate clinical outcomes: any complications or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, lower extremity amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photocoagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 10 mm Hg decrease in updated mean systolic blood pressure adjusted for specific confounders. RESULTS: The incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 15% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point. CONCLUSIONS: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure less than 120 mm Hg.

https://www.bmj.com/content/bmj/321/7258/412.full.pdf

Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study

See related commentary by Kanis, page [1829][1]

Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

/pdf/2010-clinical-practice-guidelines-for-the-diagnosis-and-4ttqfkm9wl.pdf

2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary

A number of hierarchies of evidence have been developed to enable different research methods to be ranked according to the validity of their findings. However, most have focused on evaluation of the effectiveness of interventions. When the evaluation of healthcare addresses its appropriateness or feasibility, then existing hierarchies are inadequate. This paper reports the development of a hierarchy for ranking of evidence evaluating healthcare interventions. The aims of this hierarchy are twofold. Firstly, it is to provide a means by which the evidence from a range of methodologically different types of research can be graded. Secondly, it is to provide a logical framework that can be used during the development of systematic review protocols to help determine the study designs which can contribute valid evidence when the evaluation extends beyond effectiveness. The proposed hierarchy was developed based on a review of literature, investigation of existing hierarchies and examination of the strengths and limitations of different research methods. The proposed hierarchy of evidence focuses on three dimensions of the evaluation: effectiveness, appropriateness and feasibility. Research that can contribute valid evidence to each is suggested. To address the varying strengths of different research designs, four levels of evidence are proposed: excellent, good, fair and poor. The strength of the proposed hierarchy is that it acknowledges the valid contribution of evidence generated by a range of different types of research. However, hierarchies only provide a guide to the strength of the available evidence and other issues such as the quality of research also have an important influence.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2702.2003.00662.x

Hierarchy of evidence: a framework for ranking evidence evaluating healthcare interventions

Background
Exercise is generally recommended for people with type 2 diabetes mellitus. However, some studies evaluate an exercise intervention including diet or behaviour modification or both, and the effects of diet and exercise are not differentiated. Some exercise studies involve low participant numbers, lacking power to show significant differences which may appear in larger trials.

Objectives
To assess the effects of exercise in type 2 diabetes mellitus.

Search methods
Trials were identified through the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and manual searches of bibliographies.

Selection criteria
All randomised controlled trials comparing any type of well-documented aerobic, fitness or progressive resistance training exercise with no exercise in people with type 2 diabetes mellitus.

Data collection and analysis
Two authors independently selected trials, assessed trial quality and extracted data. Study authors were contacted for additional information. Any information on adverse effects was collected from the trials.

Main results
Fourteen randomised controlled trials comparing exercise against no exercise in type 2 diabetes were identified involving 377 participants. Trials ranged from eight weeks to twelve months duration. Compared with the control, the exercise intervention significantly improved glycaemic control as indicated by a decrease in glycated haemoglobin levels of 0.6% (-0.6 % HbA1c, 95% confidence interval (CI) -0.9 to -0.3; P < 0.05). This result is both statistically and clinically significant. There was no significant difference between groups in whole body mass, probably due to an increase in fat free mass (muscle) with exercise, as reported in one trial (6.3 kg, 95% CI 0.0 to 12.6). There was a reduction in visceral adipose tissue with exercise (-45.5 cm2, 95% CI -63.8 to -27.3), and subcutaneous adipose tissue also decreased. No study reported adverse effects in the exercise group or diabetic complications. The exercise intervention significantly increased insulin response (131 AUC, 95% CI 20 to 242) (one trial), and decreased plasma triglycerides (-0.25 mmol/L, 95% CI -0.48 to -0.02). No significant difference was found between groups in quality of life (one trial), plasma cholesterol or blood pressure.

Authors' conclusions
The meta-analysis shows that exercise significantly improves glycaemic control and reduces visceral adipose tissue and plasma triglycerides, but not plasma cholesterol, in people with type 2 diabetes, even without weight loss.

Exercise for type 2 diabetes mellitus

Objective To revise and expand the 1992 edition of the clinical practice guidelines for the management of diabetes in Canada incorporating recent advances in diagnosis and outpatient management of diabetes mellitus and to identify and assess the evidence supporting these recommendations Options All aspects of ambulatory diabetes care, including organization, responsibilities, classification, diagnosis, management of metabolic disorders, and methods for screening, prevention and treatment of complications in all forms of diabetes were reviewed, revised as required and expressed as a set of recommendations Outcomes Reclassification of types of diabetes based on pathogenesis; increased sensitivity of diagnostic criteria; recommendations for screening for diabetes; improved delivery of care; recommendations for tighter metabolic control; and optimal methods for screening, prevention and treatment of complications of diabetes Evidence All recommendations were developed using a justifiable and reproducible process involving an explicit method for the citation and evaluation of the supporting evidence Values All recommendations were reviewed by an expert committee that included people with diabetes, family physicians, dietitians, nurses, diabetologists, as well as other subspecialists and methodologists from across Canada Benefits, harm and costs More aggressive screening strategies and more sensitive testing and diagnostic procedures will allow earlier detection and management of diabetes Cost-effectiveness analyses suggest that this will lead to savings in health care costs relating to diabetes care by reducing the incidence of complications of diabetes Similarly, tighter metabolic control in most people with diabetes, through intensive diabetes management, seeks to reduce the incidence of complications and, hence, their associated social and economic burdens Recommendations This document contains numerous detailed recommendations pertaining to all aspects of ambulatory diabetes care, ranging from service delivery to prevention and treatment of diabetes-related complications The terms "insulin-dependent diabetes mellitus" and "non-insulin-dependent diabetes mellitus" should be replaced by the terms "type 1" and "type 2" diabetes Testing for diabetes using fasting plasma glucose (FPG) level should be performed every 3 years in those over 45 years of age More frequent or earlier testing should be considered for people with additional specific risk factors for diabetes The FPG level at which diabetes is diagnosed should be reduced from 78 to 70 mmol/L to improve the sensitivity of the main diagnostic criterion and reduce the number of missed diagnoses Depending on the type of diabetes and the therapy required to achieve euglycemia, people with diabetes should generally strive for close metabolic control to achieve optimal glucose levels This entails receiving appropriate diabetes education through a diabetes health care team, diligent self-monitoring of blood glucose, attention to lifestyle and adjustments in diet and physical activity, and the appropriate and stepwise use of oral agents and insulin therapies needed to maintain glycemic control Also highlighted is the need for appropriate surveillance programs for complications and management options Validation All recommendations were graded according to the strength of the evidence and consensus of all relevant stakeholders Collateral efforts of the American Diabetes Association and the World Health Organization and the input of international experts were also considered throughout the revision process

1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association.

Objective: To revise and expand the 1992 edition of the clinical practice guidelines for the management of diabetes in Canada incorporating recent advances in diagnosis and outpatient management of diabetes mellitus and to identify and assess the evidence supporting these recommendations. Options: All aspects of ambulatory diabetes care, including organization, responsibilities, classification, diagnosis, management of metabolic disorders, and methods for screening, prevention and treatment of complications in all forms of diabetes were reviewed, revised as required and expressed as a set of recommendations. Outcomes: Reclassification of types of diabetes based on pathogenesis; increased sensitivity of diagnostic criteria; recommendations for screening for diabetes; improved delivery of care; recommendations for tighter metabolic control; and optimal methods for screening, prevention and treatment of complications of diabetes. Evidence: All recommendations were developed using a justifiable and reproducible process involving an explicit method for the citation and evaluation of the supporting evidence. Values: All recommendations were reviewed by an expert committee that included people with diabetes, family physicians, dietitians, nurses, diabetologists, as well as other subspecialists and methodologists from across Canada. Benefits, harm and costs: More aggressive screening strategies and more sensitive testing and diagnostic procedures will allow earlier detection and management of diabetes. Cost-effectiveness analyses suggest that this will lead to savings in health care costs relating to diabetes care by reducing the incidence of complications of diabetes. Similarly, tighter metabolic control in most people with diabetes, through intensive diabetes management, seeks to reduce the incidence of complications and, hence, their associated social and economic burdens. Recommendations: This document contains numerous detailed recommendations pertaining to all aspects of ambulatory diabetes care, ranging from service delivery to prevention and treatment of diabetes-related complications. The terms “insulin-dependent diabetes mellitus” and “non-insulin-dependent diabetes mellitus” should be replaced by the terms “type 1” and “type 2” diabetes. Testing for diabetes using fasting plasma glucose (FPG) level should be performed every 3 years in those over 45 years of age. More frequent or earlier testing should be considered for people with additional specific risk factors for diabetes. The FPG level at which diabetes is diagnosed should be reduced from 7.8 to 7.0 mmol/L to improve the sensitivity of the main diagnostic criterion and reduce the number of missed diagnoses. Depending on the type of diabetes and the therapy required to achieve euglycemia, people with diabetes should generally strive for close metabolic control to achieve optimal glucose levels. This entails receiving appropriate diabetes education through a diabetes health care team, diligent self-monitoring of blood glucose, attention to lifestyle and adjustments in diet and physical activity, and the appropriate and stepwise use of oral agents and insulin therapies needed to maintain glycemic control. Also highlighted is the need for appropriate surveillance programs for complications and management options. Validation: All recommendations were graded according to the strength of the evidence and consensus of all relevant stakeholders. Collateral efforts of the American Diabetes Association and the World Health Organization and the input of international experts were also considered throughout the revision process. Sponsors: These guidelines were developed under the auspices of the Clinical and

D. Lillie

Papers

1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association.

1998 clinical practice guidelines for the management of diabetes in Canada