Current considerations for clinical management and care of non-alcoholic fatty liver disease: Insights from the 1st International Workshop of the Canadian NASH Network (CanNASH).

Non-alcoholic fatty liver disease (NAFLD) affects approximately 8 million Canadians. NAFLD refers to a disease spectrum ranging from bland steatosis to non-alcoholic steatohepatitis (NASH). Nearly 25% of patients with NAFLD develop NASH, which can progress to liver cirrhosis and related end-stage complications. Type 2 diabetes and obesity represent the main risk factors for the disease. The Canadian NASH Network is a national collaborative organization of health care professionals and researchers with a primary interest in enhancing understanding, care, education, and research around NAFLD, with a vision of best practices for this disease state. At the 1st International Workshop of the CanNASH network in April 2021, a joint event with the single topic conference of the Canadian Association for the Study of the Liver (CASL), clinicians, epidemiologists, basic scientists, and community members came together to share their work under the theme of NASH. This symposium also marked the initiation of collaborations between Canadian and other key opinion leaders in the field representative of international liver associations. The main objective is to develop a policy framework that outlines specific targets, suggested activities, and evidence-based best practices to guide provincial, territorial, and federal organizations in developing multidisciplinary models of care and strategies to address this epidemic.

Cardiovascular risk factor management in patients with diabetes: Does management differ with disease duration?

AIMS: Our objective was to examine risk factor modification targets and treatment in relation to duration of diabetes. METHODS: The Diabetes Mellitus Status in Canada (DM-SCAN) study collected data on 5109 patients with type 2 diabetes mellitus (T2DM) in 2012 in primary care. We compared the prevalence of vascular complications, treatment targets, and interventions between patients with diagnosed diabetes duration ≤10 and > 10 years. RESULTS: Physicians more frequently assigned HbA1c (glycated hemoglobin) targets of 7.1-8.5% (54-69 mmol/mol) to patients with longer duration of diabetes (n = 1647) (19.8% vs 9.5%, p < 0.001). Patients with longer duration of diabetes were less likely to achieve HbA1c targets of ≤7.0% (53 mmol/mol) (39% vs. 55%, p < 0.001), had similar likelihood of achieving blood pressure targets of ≤130/80 mmHg (38% vs. 36%, p = 0.26) and were more likely to achieve LDL-C targets of ≤2.0 mmol/L (≤77.3 mg/dL) (63% vs. 53%, p < 0.001) compared to patients with shorter duration of diabetes (n = 3462). Achievement of all three targets between both groups were similar (13% vs. 13%, p = 0.82). Overall, patients with longer duration of diabetes were more likely to be prescribed anti-hyperglycemic, anti-hypertensive, lipid-lowering medications and referred for diabetes education. CONCLUSIONS: Only 13% of patients achieved glycemic, blood pressure, and LDL-C targets irrespective of duration of diabetes. Despite being managed with more medications, patients with longer duration of diabetes were less likely to achieve glycemic targets. More focus is needed on developing methods to bridge best care and real-world practice.

Incretin agents in type 2 diabetes.

OBJECTIVE: To evaluate the emerging classes of antihyperglycemic agents that target the incretin pathway, including their therapeutic efficacy and side effect profiles, in order to help identify their place among the treatment options for patients with type 2 diabetes. QUALITY OF EVIDENCE: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched. Most evidence is level I and II. MAIN MESSAGE: Two classes of incretin agents are currently available: glucagonlike peptide 1 (GLP1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, both of which lower hyperglycemia considerably without increasing the risk of hypoglycemia. The GLP1 receptor agonists have a greater effect on patients' glycated hemoglobin A(1c) levels and cause sustained weight loss, whereas the DPP4 inhibitors are weight-neutral. CONCLUSION: The GLP1 and DPP4 incretin agents, promising and versatile antihyperglycemic agents, are finding their way into the therapeutic algorithm for treating type 2 diabetes. They can be used in patients not adequately controlled by metformin monotherapy or as initial therapy in those for whom metformin is contraindicated.

Glycated Hemoglobin Level Goal Achievement in Adults With Type 2 Diabetes in Canada: Still Room for Improvement.

OBJECTIVES: To describe the clinical histories and management of adults with type 2 diabetes who were not reaching their target glycated hemoglobin (A1C) levels and to identify barriers to achieving therapeutic goals. METHODS: Practice assessment surveys and practice audits were completed by 88 primary care physicians (PCPs) in the Diabetes Mellitus Assessment of Clinical managemenT In ONtario (DM-ACTION) program and by 56 diabetes specialists in the Diabetes Mellitus IMproving PAtient Care in our communiTies (DM-IMPACT) program. The DM-ACTION audit analyzed data from 1,173 adults with A1C levels ≥7.3% who were not prescribed insulin; the DM-IMPACT audit included 135 individuals with similar characteristics. RESULTS: Most PCPs (92%) and specialists (88%) stated that they typically recommend A1C levels of ≤7.0%; more than 90% indicated that they adjusted antihyperglycemic therapy within 3 months if suboptimal A1C targets endured. Among the DM-ACTION patients, the median A1C level was 7.8%; the median time between the last 2 A1C tests was 5 months; 58% were taking ≤2 noninsulin antihyperglycemic agents; and adjustment of glucose-lowering therapy was noted for only 56%. The corresponding values for the DM-IMPACT patients were 8.0%, 4 months, 43% and 68%, respectively. PCPs and specialists attributed patients' factors and patients' adherence as primary causes of poor achievement of guideline-recommended targets. PCPs perceived patients' factors as the predominant barrier to optimizing care, but the specialists believed that therapeutic inertia stems from a wide range and a varied combination of patient-centric factors. CONCLUSIONS: Type 2 diabetes remains a health-care challenge in Canada and globally. Primary care physicians and specialists attributed patients' factors as principal obstacles to optimal diabetes management. However, physician-associated therapeutic inertia may also be an important barrier to unmet therapeutic goals.

Considerations for Initiating a Sodium-Glucose Co-Transporter 2 Inhibitor in Adults With Type 2 Diabetes Using Insulin.

In order to meet and maintain glycemic control, pharmacological management of individuals with type 2 diabetes typically begins with metformin followed by the introduction of other oral antihyperglycemic agents as needed. In some patients, the aggressive and progressive degeneration of pancreatic ß cell activity means insulin therapy will become a given. The need to routinely monitor blood glucose levels coupled with the undesirable effects associated with insulin-primarily hypoglycemia and weight gain-commonly contribute to physician and patient inertia. The new ß-cell-independent sodium-glucose co-transporter 2 (SGLT2) inhibitors are approved for combination use with all of the currently approved oral and injectable antihyperglycemic classes. The addition of SGLT2 inhibitors to background insulin therapy has the potential to afford many benefits and, in some cases, may reduce the incidence of insulin-associated side effects. This article reviews the available literature on SGLT2 inhibitor-insulin combination therapy and underscores the issues that should be considered prior to introducing SGLT2 inhibitors to individuals with type 2 diabetes who are already on insulin (with or without other antihyperglycemic agents) to ensure individualization of therapy.

Glycemic control and morbidity in the Canadian primary care setting (results of the diabetes in Canada evaluation study).

The objective of this national, cross-sectional study was to provide insight into the care and treatment of type 2 diabetes (T2DM) in the Canadian primary care setting. Specifically, the study examines glycemic control, management and morbidity load among T2DM patients, and investigates the relationship of glycemic control and morbidity load with duration of diabetes. Participating primary care physicians (PCPs) (N=243) completed a chart audit for the first 10 patients with T2DM attending their clinics (2473 eligible patient records). The mean A1C was 7.3% with 49% of patients not at target (A1C>or=7.0%). Glycemic control eroded significantly with increasing duration of diabetes in spite of increasing therapeutic intervention. T2DM patients experienced a high morbidity load (hypertension 63%; dyslipidemia 59%; macrovascular complications 28%; microvascular complications 38%) each of which increased significantly with duration of diabetes. For 79% of patients not at target, PCPs identified lifestyle intervention as the strategy for achieving glycemic targets while more aggressive treatment plans were identified for only 56%. These results underscore the complexity of primary care management of T2DM and suggest that current treatment approaches are not intensive enough for a large proportion of patients especially those with longer duration of disease.

Safety and efficacy of dulaglutide, a once weekly GLP-1 receptor agonist, for the management of type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2D) is an increasingly common endocrine disorder that is characterized by chronic hyperglycemia and tissue compartment abnormalities, including macrovascular and microvascular complications. More than 90% of patients with T2D will be diagnosed and treated in the primary care setting. One of the relatively recent additions to the increasing array of approved antidiabetic medications is the glucagon-like peptide-1 receptor agonist class. Mechanisms of action for glucagon-like peptide-1 receptor agonists include: 1) stimulation of insulin secretion through ß-cells, though only when glucose levels are elevated (hence, minimizing risk for hypoglycemia); 2) blunting of glucagon secretion; 3) increased satiety; and 4) decreased rate of release of gastric contents into the small intestine, thereby reducing glycemic load. Recent T2D treatment guidelines encourage individualization of therapy. Many patients still do not achieve optimal glycemic control. Therefore, other treatment options are important. METHODS: A literature search was performed using PubMed and MEDSCAPE to retrieve abstracts and articles pertinent to topics discussed in this review. Original research articles, reviews, and clinical trial manuscripts were identified based on relevance. Only English language articles were considered. Results In 3 phase 3 registration trials in patients with T2D, once-weekly dulaglutide demonstrated superior efficacy at the primary endpoint to metformin as monotherapy, to sitagliptin as add-on to metformin, and to exenatide twice daily as add-on to metformin and pioglitazone. The safety profile of dulaglutide in these trials is similar to currently available glucagon-like peptide-1 receptor agonists, characterized predominantly by gastrointestinal symptoms (ie, nausea, vomiting, and diarrhea). Based on these results, once-weekly dulaglutide should be a relevant additional treatment option for the management of T2D.

A pilot program for physical exercise promotion in adults with type 1 diabetes: the PEP-1 program.

Physical inactivity is highly common in adults with type 1 diabetes (T1D) as specific barriers (i.e., hypoglycemia) may prevent them from being active. The objective of this study was to examine the efficacy of the Physical Exercise Promotion program in type 1 diabetes (PEP-1) program, a group program of physical activity (PA) promotion (intervention) compared with an information leaflet (control), to improve total energy expenditure (TEE) in adults with T1D after 12 weeks. TEE was measured with a motion sensor over a 7-day period at inclusion, after the program (12 weeks) and 1-year after inclusion. The 12 weekly sessions of the program included a 30-min information session (glycemic control and PA) and 60 min of PA. A total of 48 adults, aged 18 to 65 years with a reported PA practice <150 min per week, were recruited (45.8% men; aged 44.6 ± 13.3 years; 8.0% ± 1.1% glycated hemoglobin (A1c)) and randomized in this pilot trial. Ninety percent of participants completed the program and 88% completed the 1-year follow-up. No change was observed for TEE and A1c in both groups. After the 12-week program, the mean peak oxygen uptake increased (14%; p = 0.003) in the intervention group; however, at the 1-year follow-up, it was no longer different from baseline. In the control group, no difference was observed for the peak oxygen uptake. These results suggest that the PEP-1 pilot program could increase cardiorespiratory fitness. However, this benefit is not sustained over a long-term period. The PEP-1 program did not increase TEE in patients with T1D and other strategies remain necessary to counteract physical inactivity in this population.

Type 2 diabetes mellitus management in Canada: is it improving?

OBJECTIVE: To gain insight into the current management of patients with type 2 diabetes mellitus by Canadian primary care physicians. METHOD: A total of 479 primary care physicians from across Canada submitted data on 5123 type 2 diabetes patients whom they had seen on a single day on or around World Diabetes Day, November 14, 2012. RESULTS: Mean glycated hemoglobin (A1C) was 7.4%, low-density lipoprotein (LDL-C) was 2.1 mmol/L and blood pressure (BP) was 128/75 mm Hg. A1C ≤7.0% was met by 50%, LDL-C ≤2.0 mmol/L by 57%, BP <130/80 mm Hg by 36% and the composite triple target by 13% of patients. Diet counselling had been offered to 38% of patients. Of the 87% prescribed antihyperglycemic agents, 18% were on 1 non-insulin antihyperglycemic agent (NIAHA) (85% of which was metformin), 15% were on 2 NIAHAs, 6% were on ≥3 NIAHAs, 19% were on insulin only and 42% were on insulin + ≥1 NIAHA(s). Amongst the 81% prescribed lipid-lowering therapy, 88% were on monotherapy (97% of which was a statin). Among the 83% prescribed antihypertensive agents, 39%, 34%, 21% and 6% received 1, 2, 3 and >3 drugs, respectively, with 59% prescribed angiotensin-converting enzyme inhibitors and 35% angiotensin II receptor blockers. CONCLUSIONS: The Diabetes Mellitus Status in Canada survey highlights the persistent treatment gap associated with the treatment of type 2 diabetes and the challenges faced by primary care physicians to gain glycemic control and global vascular protection in these patients. It also reveals a higher use of insulin therapy in primary care practices relative to previous surveys. Practical strategies aimed at more effectively managing type 2 diabetes patients are urgently needed.

Cardiovascular burden and related risk factors among Nunavik (Quebec) Inuit: insights from baseline findings in the circumpolar Inuit health in transition cohort study.

BACKGROUND: The Inuit are commonly portrayed to be somehow protected from cardiovascular diseases (CVDs) through their traditional lifestyle and diet. However, actual sociocultural transition and related major, modifiable risk factors have scarcely been quantified in the Inuit population. Such knowledge is extremely valuable in terms of public health intervention. METHODS: A total of 887 Inuit residents from Nunavik, Quebec, participated in a cohort study. The estimates presented were derived from anthropometric and biological measurements gathered at the time of recruitment and enhanced by information collected in the medical file of each participant. All estimates were corrected for a complex sampling strategy and bootstrapped to ensure the representativeness of the general Nunavik population. RESULTS: Overall, 19% of Inuit had a disease of the circulatory system according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision. Among all disorders, peripheral circulatory system disease was the most prevalent (9%). Prevalences of ischemic heart disease and cerebrovascular disease were of similar magnitude (2.5%). No significant difference in disease prevalence was noted between sexes. The major modifiable CVD risk factors were smoking (84%), obesity (49%) [corrected] (body mass index of greater than 30 kgm2) and elevated blood pressure (13085 mmHg or greater) (18%). Prevalences were globally higher among women. CONCLUSION: The current belief that the Inuit are protected from CVD is seriously questioned by the results of the present study. Considering the extremely high prevalence of CVD risk factors, a population-based intervention reinforced for women is urgently needed to reduce their risk.

Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state.

Diabetic ketoacidosis and the hyperglycemic hyperosmolar state are the most serious complications of diabetic decompensation and remain associated with excess mortality. Insulin deficiency is the main underlying abnormality. Associated with elevated levels of counterregulatory hormones, insulin deficiency can trigger hepatic glucose production and reduced glucose uptake, resulting in hyperglycemia, and can also stimulate lipolysis and ketogenesis, resulting in ketoacidosis. Both hyperglycemia and hyperketonemia will induce osmotic diuresis, which leads to dehydration. Clinical diagnosis is based on the finding of dehydration along with high capillary glucose levels with or without ketones in the urine or plasma. The diagnosis is confirmed by the blood pH, serum bicarbonate level and serum osmolality. Treatment consists of adequate correction of the dehydration, hyperglycemia, ketoacidosis and electrolyte deficits.