Diabetes Education: A Comprehensive Review

Transcription

1 Diabetes Education: A Comprehensive Review Module 1: Pathophysiology and Prevention of Diabetes Planning Committee: Michael Boivin, B. Pharm. Johanne Fortier, BSc.Sc, BPh.LPh, CDE Carlene Oleksyn, B.S.P. (Pharm) Accreditation Information: This version of the program is unaccredited and intended for informational purposes only. An accredited version is available online at until May 2, Sponsor: This certificate-level program is non-sponsored.

2 Contents Learning Objectives... 2 Introduction... 2 Normal Metabolism... 2 Hormones Involved in Metabolism... 3 Insulin... 3 Glucagon... 3 Incretin Hormones... 3 Catecholamines... 3 Growth hormone... 3 Glucocorticoids... 4 Glucose Homeostasis... 4 Knowledge Check... 4 Pathophysiology of Diabetes... 4 Type 1 Diabetes... 5 Latent autoimmune diabetes in adults... 5 Type 2 Diabetes... 6 Prediabetes... 6 Pathogenesis of type 2 diabetes... 7 Insulin Resistance... 7 Gestational Diabetes... 8 Other Types of Diabetes... 9 Knowledge Check Prevention of Diabetes Type 1 Diabetes Type 2 Diabetes Lifestyle Interventions Metformin Acarbose Orlistat Rosiglitazone Pioglitazone Combination Therapy Liraglutide Insulin Glargine Signs and Symptoms of Diabetes Post-Test References version is available online at until May 2, Page 1

3 Learning Objectives Upon successful completion of this continuing education lesson, you will be better able to: 1. Discuss the pathophysiology of diabetes mellitus 2. Discuss the role that different hormones play on glycemic control 3. Counsel a patient on the classification of diabetes mellitus 4. Educate patients on different prevention strategies for diabetes mellitus 5. Discuss common signs and symptoms of diabetes mellitus Introduction A solid foundation in the pathophysiology of diabetes is crucial for diabetes professionals to understand the role of new treatments and the impact of different conditions on overall glycemic control. This module focusses on the normal metabolic process, the pathophysiology of diabetes mellitus, as well as the prevention and symptoms of diabetes. Normal Metabolism Humans have a constant requirement for energy but only eat intermittently. 1 To manage this issue we ingest food in excess of our current needs and have the ability to store extra energy in a form that can be used at a later time. 1 Our bodies can store these extra calories as: 1 Hepatic and muscle glycogen Adipose tissue triglyceride Protein During periods of fasting, and in response to different stresses, our body can break down these stores and release the energy required to maintain organ function. 1 The two main circulating fuels in humans are glucose and free fatty acids (FFAs). 1 These products are stored intracellularly as glycogen and triglycerides, respectively. 1 Skeletal muscles can store between g of glycogen and the liver can store 75 g of glycogen. 1 The major site of triglyceride storage is adipose tissue. Adipose tissue triglyceride is the most efficient form of energy storage in humans. 1 A few hours after a meal, as the level of blood glucose decreases, the body switches from energy storage to energy production/release, mediated primarily by glucagon. 2 Glycogen in the liver breaks down, gluconeogenesis (making glucose from lactate, amino acids and glycerol) occurs in the liver and kidneys, and FFAs become a major source of fuel. 2 version is available online at until May 2, Page 2

4 Hormones Involved in Metabolism Insulin Energy in humans is built up and broken down in response to different hormones in the body. 1 The primary hormone messenger is insulin. 1 Insulin is a body-building, storing (anabolic) hormone produced in response to higher glucose levels and suppressed with lower glucose levels. 2 When a human consumes food, insulin levels increase and this promotes glycogen synthesis in the liver and muscles, lipid formation in the adipocytes and amino acid uptake and protein synthesis in most cells. 1 When blood glucose levels decrease, insulin levels decrease and promote glycogen breakdown, lipolysis, hepatic ketogenesis and a decreased synthesis and increased degradation of protein. 1 Glucagon Glucagon counters the effects of insulin. 1 Glucagon stimulates: 1 Glycogenolysis - conversion of glycogen to glucose o This occurs within the first 8-12 hours of fasting as glucagon promotes the breakdown and release of glycogen from the muscles and liver. 2 Gluconeogenesis - a metabolic pathway that results in the generation of glucose from noncarbohydrate substrates such as lactate, glycerol, and amino acids. o After 8-12 hours of fasting, glucagon promotes the formation of glucose from these non-carbohydrate substrates. 2 Ketogenesis - the process by which ketone bodies are produced as a result of fatty acid breakdown. o During prolonged periods of starvation, glucagon promotes the transformation of FFAs into ketone bodies (beta-hydroxybytrate and acetoacetate). 2 Incretin Hormones During food ingestion the small intestine releases two different types of hormones: Glucagon-like peptide-1 (GLP-1) Gastric inhibitory peptide (GIP). 2 Both GIP and GLP-1 stimulate the release of insulin in a glucose dependent fashion. 3 GLP-1 also suppresses glucagon production and promotes satiety through a delay in gastric emptying. 3 These two hormones have been shown to stimulate insulin biosynthesis and beta cell growth while suppressing apoptosis of these cells. 3 They both have a very short half-life in the body as they are rapidly broken down by the enzyme dipeptidyl peptidase-4 (DPP-4). Catecholamines Catecholamines have effects similar to those of glucagon on the liver and are key regulators of lipolysis in adipose tissue and glycogenolysis in muscle and other tissues. 1 Growth hormone Growth hormone stimulates lipolysis in adipose tissue, also has significant anabolic effects and enhances cell growth. 1 Growth hormone antagonizes the insulin effect and decreases insulin uptake. 2 version is available online at until May 2, Page 3

5 Glucocorticoids Glucocorticoids stimulate gluconeogenesis and decrease glucose use. 2 Glucose Homeostasis A principal objective of the interplay between insulin and the counter-regulatory or counter-insulin hormones (glucagon, catecholamines, growth hormones, glucocorticoids) in humans is the maintenance of normoglycemia. 1 The concentration of glucose in the circulation is more closely controlled than that of any other fuel. 1 Plasma glucose levels are maintained in a very tight range despite wide variations in glucose consumption and utilization. 1 The body is able to keep blood glucose (BG) levels continuously between 3.9 and 5.6 mmol/l preprandially and less than 7.8 mmol/l postprandially. 2 Prevention of hypoglycemia is essential as glucose is the only source of energy that can be utilized by the brain, therefore central nervous system (CNS) function is impaired at low plasma glucose concentrations. 1 The different counter-insulin hormones balance the effects of insulin in order to maintain normoglycemia. 1 Thus, glucagon, epinephrine, and norepinephrine are released into the circulation in response to hypoglycemia and during stresses such as exercise. 1 In addition to stimulating hepatic glycogenolysis and gluconeogenesis, the catecholamines inhibit insulin-stimulated glucose utilization in muscle and promote lipolysis in adipose tissue, thereby providing tissues with an alternative fuel to glucose. 1 Knowledge Check 1. Which of the following is a role of insulin in the body? a. Promotes glucose production from glycogen b. Promotes the formation of free fatty acid from lipids in adipose tissue c. Impairs ketogenesis d. All of the above 2. Which of the following is an incretin hormone? a. GIP b. Growth hormone c. Glucagon d. None of the above 3. Which of the following is NOT a counter-regulatory hormone? a. Glucagon b. Catecholamines c. Glucocorticoids d. GLP-1 Pathophysiology of Diabetes Diabetes mellitus is a metabolic disorder characterized by the presence of hyperglycemia due to defective insulin secretion, defective insulin action or both. 4 The chronic hyperglycemia of diabetes is version is available online at until May 2, Page 4

6 associated with significant long-term sequelae, particularly damage, dysfunction and failure of various organs especially: 4 The kidneys The eyes The nerves The heart The blood vessels In all types of diabetes, insulin levels are not sufficient for the effective transport of glucose into cells for storing fat, building protein and storing glycogen for future use. 2 Type 1 Diabetes Type 1 diabetes is the form of the disease primarily due to β-cell destruction. 5 This leads to the development of diabetes where exogenous insulin administration is required for the survival of the patient. 5 Individuals with type 1 diabetes are metabolically normal before the disease. 5 The process of β-cell destruction can be detected by the presence of certain autoantibodies such as: 5 Anti-glutamic acid decarboxylase (anti-gad) Anti-islet cell Anti-insulin The presence of these antibodies reflects an autoimmune process that leads to β-cell destruction. 5 However, many patients with type 1 diabetes are idiopathic in the cause of their diabetes with no evidence of autoimmunity being present. 2 The rate of beta-cell destruction is quite variable in type 1 diabetes, being rapid in some (mainly young people) and slow in others (mainly adults) and related to both genetic and environmental factors. 2 Latent autoimmune diabetes in adults Diabetes in a lean adult may be initially diagnosed as type 2 diabetes but may actually be latent autoimmune diabetes in adults (LADA). 2 This is similar to type 1 diabetes as the patient expresses islet autoantibodies and anti-gad antibodies. 5 If LADA develops, it usually (but not always) follows a disease course that is very slow, thus the reason it is diagnosed later in adulthood. 5 Given the presence of islet autoantibodies, however, once diagnosed, such individuals as a group rapidly (usually within 3 years) progress and require insulin therapy. 5 Since the diagnosis has implications for treatment, it is important to use clinical features to help discriminate these patients from those with type 2 diabetes. 2 Patients with LADA will normally have at least 2 of the 5 following clinical features: 2 1. < 50 years of age 2. Acute symptoms 3. Body mass index (BMI) <25 kg/m 2 4. Personal history of autoimmune disease version is available online at until May 2, Page 5

7 5. Family history of autoimmune disease At present it has not been proven that patients with LADA should be treated with insulin at the onset of diabetes. 5 Although oral hypoglycemic therapy will rapidly be ineffective in these patients and they are at increased risk for ketoacidosis, they are often treated with oral agents and observed for failure to maintain adequate glucose control. 5 Type 2 Diabetes Type 2 diabetes is the most common form of diabetes. 5 It is characterized by a problem with: 5 Insulin action - Insulin resistance Insulin secretion - β-cell dysfunction Or both In type 2 diabetes, the presence of insulin resistance (due to obesity, high-fat diets, inactivity, aging or a genetic basis) is well established. Beta-cell dysfunction is also always present, occurring early and likely predating hyperglycemia. 2 Patients with type 2 diabetes usually have insulin resistance and relative, rather than absolute, insulin deficiency. 5 At the time of diagnosis, and often throughout their lifetime, these patients do not need insulin treatment to survive (although ultimately many require it for glycemic control.) 5 This form of diabetes is associated with progressive β-cell failure with increasing duration of the disease. 5 Prediabetes Prediabetes includes impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and is a state where the blood glucose levels are elevated but not sufficient to meet the diagnosis of diabetes. 5 Persons with IGT do have a high risk of developing diabetes, although not all do so. 5 Persons with IGT have a greater risk than persons of similar age with normal glucose tolerance of developing cardiovascular disease, but they rarely develop the more specific microvascular complications of diabetes such as retinopathy or nephropathy, unless they develop diabetes. 4 IGT is more strongly associated with CVD outcomes than is IFG. 4 In most subjects, IGT represents a transient stage between normal glucose tolerance and the development of type 2 diabetes. 5 Clinical Practice Tip The development of diabetes can be reduced or delayed in patients with IGT and IFG by the use of lifestyle interventions such as dietary measures to reduce weight and increased physical activity. 6 Several drugs, such as metformin, acarbose, liraglutide, orlistat, pioglitazone and rosiglitazone also reduce the incidence of type 2 diabetes in persons with IGT. 6 IFG is also a state of impaired glucose homeostasis and includes individuals whose fasting glucose levels are above normal but below those diagnostic for diabetes. 5 IFG and IGT identify substantially different subsets of the population. 5 Both categories of prediabetes contain individuals with a high risk of progressing to type 2 diabetes, but the proportion of patients with IFG is smaller than that with IGT. 5 There is also a small proportion of patients who have both disorders. version is available online at until May 2, Page 6

8 Type 2 diabetes is now recognized as a disease that may progress from prediabetes to diabetes at a variable rate. 2 Pathogenesis of type 2 diabetes The pathogenesis of type 2 diabetes has become clearer over the last several years. The initial event is a genetic predisposition for glucose intolerance. 7 Lifestyle and environmental factors also determine whether glucose intolerance develops. 7 β-cell dysfunction is always found in type 2 diabetes and it occurs early and likely before the development of hyperglycemia. 7 Following the onset of diabetes, the β-cell dysfunction is reversible to a large degree by intensive glycemic control. 7 Over time, type 2 diabetes becomes less responsive to oral hypoglycemic therapy in tandem with worsening β-cell function. 7 Figure 1 reviews the proposed pathogenesis of type 2 diabetes. Clinical Practice Tip The distinctive β-cell defect in type 2 diabetes is the loss of the first phase of glucose-induced insulin secretion. 7 This results in hyperglycemia after ingestion of food and hyperinsulinemia at a later time. 2 Figure 1 - Proposed Pathogenesis of Type 2 Diabetes 7 Insulin Resistance The term insulin resistance generally refers to resistance to the metabolic effects of insulin, including: 8 The suppressive effects of insulin on endogenous glucose production The stimulatory effects of insulin on peripheral (predominantly skeletal muscle) glucose uptake and glycogen synthesis The inhibitory effects of insulin on adipose tissue lipolysis The importance of insulin resistance cannot be underestimated as there is considerable epidemiologic evidence linking insulin resistance with glucose intolerance and type 2 diabetes, hypertension, dyslipidemia, atherosclerosis, and many cancers. 8 Like β-cell dysfunction, insulin resistance is a version is available online at until May 2, Page 7

9 consistent finding in patients with type 2 diabetes. 8 The development of diabetes in these individuals, however, appears to require an additional defect in insulin secretion. 8 In the absence of a defect in β- cell function, individuals can compensate indefinitely for insulin resistance with appropriate hyperinsulinemia. 8 Hence, many individuals with marked insulin resistance may never progress to type 2 diabetes. 8 Skeletal muscle, adipose tissue and the liver are the principal sites of insulin resistance. 2 For this reason, when insulin resistance is present there is increased hepatic glucose production and decreased glucose transport at the muscle. 2 Most patients with type 2 diabetes are obese and their insulin resistance may improve with weight loss. 2 That being said, insulin resistance has also been described in lean patients with type 2 diabetes. 2 Clinical Practice Tip The risk of atherosclerosis is apparently comparable in the insulin resistant individual without diabetes and in those with type 2 diabetes. 8 Gestational Diabetes Pregnancy may be complicated by diabetes in two distinct forms: gestational and pregestational diabetes. 9 The rate of gestational diabetes varies widely, from 3.7% in non-aboriginal populations to between 8 and 18% in Aboriginal groups. 2 Gestational diabetes typically is diagnosed during the second half of pregnancy and occurs when the β-cell reserve is unable to counterbalance the insulin resistance caused by placental hormones. 9 Although gestational diabetes is usually asymptomatic, the consequences are significant. 9 Fetal complications include: 9 Stillbirth Macrosomia - (newborn of excessive birth weight) Increased risk of birth trauma Neonatal hyperbilirubinemia Hypoglycemia Pregnancies complicated by pregestational diabetes, either type 1 or type 2, carry additional risks to both the mother and the fetus (beyond the effects on fetal growth and development in mid-late pregnancy that occur with gestational diabetes.) 9 Metabolic derangements present at the time of conception and during blastogenesis and organogenesis increase the risk of spontaneous abortions and congenital malformations. 9 Clinical Practice Tip A woman diagnosed with gestational diabetes has a much higher risk of developing type 2 diabetes later in life. 2 The cumulative risk for type 2 diabetes after gestational diabetes is 30 to 60% over 10 years. 2 version is available online at until May 2, Page 8

10 Other Types of Diabetes There are other specific types of diabetes including relatively uncommon conditions. These are primarily genetically defined forms of diabetes or diabetes associated with other diseases or drug use. 4 These types are discussed in appendix 1 of the guidelines and are displayed in figure 2. Figure 2 - CDA Etiologic Classification of Diabetes Mellitus 10 version is available online at until May 2, Page 9

11 Knowledge Check Please answer if the following statements are true or false 1. All people with type 1 diabetes develop the disease through an autoimmune process. a. True b. False 2. Latent autoimmune diabetes in adults is more like type 1 diabetes than type 2. a. True b. False 3. If a patient has insulin resistance they will also have diabetes a. True b. False 4. Impaired fasting glucose is more common than impaired glucose tolerance a. True b. False Prevention of Diabetes Type 1 Diabetes Two major trials of interventions to prevent or delay the onset of type 1 diabetes have been completed. 6 The European Nicotinamide Diabetes Intervention Trial (ENDIT), a randomized, double-blind, placebocontrolled trial of high-dose nicotinamide therapy, recruited first-degree relatives of people who were >20 years old when diagnosed with type 1 diabetes, islet cell antibody-positive, > 40 years of age and had a normal oral glucose tolerance test (OGTT) result. 6 Although nicotinamide had proved protective in animal studies, no effect was observed in the ENDIT study during the 5-year trial period. 6 The Diabetes Prevention Trial Type 1 (DPT-1) studied the efficacy of low-dose insulin injections in highrisk (>50%) first-degree relatives of subjects with type 1 diabetes. 6 Overall, the insulin treatments had no effect, but in a subset of participants with high levels of insulin autoantibodies, a delay, and perhaps a reduction, in the incidence of type 1 diabetes was observed. 6 At this point in time there are no safe and effective strategies to prevent type 1 diabetes. 6 Type 2 Diabetes Preventing type 2 diabetes would result in significant public health benefits, including lower rates of cardiovascular disease (CVD), renal failure, blindness and premature mortality. 6 Primary approaches to preventing diabetes in a population include the following: 6 1. Programs targeting high-risk individuals in the community (such as those with impaired glucose tolerance [IGT] or obesity) 2. Programs targeting high-risk subgroups of the population, such as high-risk ethnic groups 3. Programs for the general population, such as those designed to promote physical activity and healthy eating in adults or children version is available online at until May 2, Page 10

12 Lifestyle Interventions Results of large, well-designed studies assessing lifestyle and pharmacologic interventions in adults to prevent the progression from IGT to diabetes have been published. 6 The Finnish Diabetes Prevention Study (DPS) and the Diabetes Prevention Program (DPP) are two with major findings. 6 Dietary modification that targeted a low-calorie, low-fat, low-saturated fat, high-fibre diet and moderateintensity physical activity of at least 150 minutes per week resulted in loss of approximately 5% of initial body weight. In both studies, the risk reduction for diabetes was 58% at 4 years. 6 On the basis of the observed benefits of lifestyle in the DPP, all participants were offered further lifestyle interventions for a median of 5.7 more years and benefits were sustained for up to 10 years. 6 In a trial of 458 Japanese males with IGT that were randomly assigned to standard invervention or intensive intervention for 4 years, the intensive treatment lead to a 67.4% reduction in the risk of diabetes. 6 Another trial of 641 overweight Japanese men (30-60 years) with IFG were to receive frequent intervention or control for 36 months. 6 The frequent intervention group received individual instructions and follow-up support for lifestyle modification from medical staff 9 times. The control group received similar individual instructions 4 times at 12-month intervals during the same period. Results showed an incidence of type 2 diabetes of 12.2% in the frequent intervention group and 16.6% in the control group. 6 A 20-year follow-up of the Chinese Da Qing Diabetes Prevention Trial showed that after 6 years of active lifestyle interventions versus no treatment and an additional 14 years of passive follow-up, led to a 43% (95% CI 19 59) relative risk reduction for incident diabetes persisted, and vision-threatening retinopathy was reduced by 47% (95% CI 1 71). There were, however, no identified reductions in nephropathy, neuropathy, cardiovascular events or mortality. 6 Metformin Metformin was used in a second arm of the DPP. 6 A dosage of 850 mg BID for an average of 2.8 years significantly decreased progression of IGT to diabetes by 31%. 6 In the DPP population, metformin did not have any significant effect in the older age group ( 60 years) and in less obese (BMI <35 kg/m 2 ) subjects. 6 A study was used to evaluate whether this reduction was transient or there was a sustained benefit. The study found that 26% of the diabetes prevention effect could be accounted for by the pharmacological action of metformin (which did not persist when the drug was stopped). 6 After the washout, the incidence of diabetes was still reduced by 25%. The benefits persisted for up to 10 years. 6 Acarbose The Study to Prevent Non-Insulin Dependent Diabetes (STOP-NIDDM) used acarbose at a dosage of 100 mg TID in a 5-year study with a mean follow-up of 3.3 years. 6 There was: 6 A 25% reduction in the risk of progression to diabetes when the diagnosis was based on 1 OGGT A 36% reduction in the risk of progression to diabetes when the diagnosis was based on 2 consecutive OGTTs. A beneficial effect was not affected by age or BMI of the patient. When acarbose was discontinued the beneficial effects of acarbose did not continue. 6 version is available online at until May 2, Page 11

13 Orlistat The Xenical in the Prevention of Diabetes in Obese Subjects (XENDOS) study examined the effect of orlistat in combination with an intensive lifestyle modification program (diet and exercise) on the prevention of diabetes in 3305 obese individuals. 6 Subjects were randomized to orlistat 120 mg or placebo TID with meals for 4 years. 6 Weight loss was observed in both groups, but the orlistat group lost significantly more. 6 Compared to placebo, orlistat treatment was associated with a further 37% reduction in the incidence of diabetes. 6 There were significant issues with this XENDOS trial: 6 1. There was a very high dropout rate 48% in the orlistat group and 66% in the placebo group. 2. The last observation carried forward was used for analysis, which is generally not favoured for prevention or survival studies Rosiglitazone The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial randomized 5269 subjects with IGT and/or IFG to take ramipril (15 mg/day) and/or rosiglitazone (8mg/day) vs. placebo. 6 Eligible subjects were 30 years old and not known to have cardiovascular disease. 6 Treatment with rosiglitazone resulted in a 60% reduction in the primary composite outcome of diabetes or death, this was primarily due to a 62% relative reduction in the risk of progression to diabetes. 6 There was a trend toward an increase in risk of the cardiovascular outcomes with rosiglitazone driven primarily by a significant increase in nonfatal congestive heart failure. 6 Pioglitazone The Actos Now for the Prevention of Diabetes (ACT NOW) study, involved 602 patients with IGT that were randomized to receive pioglitazone or placebo over 2.4 years. 6 Pioglitazone decreased the conversion of IGT to type 2 diabetes by 72%. 6 Combination Therapy The combination of metformin 500 mg twice daily with rosiglitazone 2 mg twice daily for a median of 3.9 years was found to reduce the risk of progression to diabetes by 66% in over 100 patients with IGT compared to placebo. 6 Liraglutide In a 20-week study, liraglutide was administered to 564 obese individuals who did not have diabetes, 31% of whom had IGT. Subjects were randomized to 1 of 4 liraglutide doses (1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg) or to placebo, or to orlistat 120 mg three times daily. A1C was reduced by 0.14% to 0.24% with liraglutide. 11 The prevalence of prediabetes decreased by 84% to 96% with liraglutide 1.8 mg, 2.4 mg and 3.0 mg doses. 6 Insulin Glargine The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) study randomized 12,537 patients with cardiovascular risk factors plus impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose of 5.3 mmol/l) for a version is available online at until May 2, Page 12

14 median follow-up of 6.2 years. 12 This study included 1456 patients with IGT or IFG with 737 assigned to insulin glargine therapy and 719 assigned to standard care. The patients assigned to insulin glargine were 28% less likely to develop diabetes from the time of randomization until the first oral glucosetolerance test than were participants assigned to standard care (Odds ratio 0.72, CI, 0.58 to 0.91; P=0.006). 12 This decrease in the risk of developing type 2 diabetes has to be balanced against an increased risk of hypoglycemia and weight gain in patients on glargine therapy. 12 Insulin glargine was also associated with a neutral effect on cardiovascular outcomes and cancer development. 12 CDA Key Recommendations on Prevention of Diabetes 6 1. As safe and effective preventive therapies for type 1 diabetes have not yet been identified, any attempts to prevent type 1 diabetes should be undertaken only within the confines of formal research protocols. 2. Intensive and structured lifestyle modification that results in loss of approximately 5% of initial body weight can reduce the risk of progression from impaired glucose tolerance to type 2 diabetes by almost 60% 3. Progression from prediabetes to type 2 diabetes can also be reduced by pharmacologic therapy with metformin (~30% reduction), acarbose (~30% reduction) and thiazolidinediones (~60% reduction). Signs and Symptoms of Diabetes Diabetes is generally a silent disease for many patients. This is the main reason that many patients are unaware they have this condition. The most common symptoms from this disease are associated with hyperglycemia. Hyperglycemia is a very common occurrence and if left untreated can result in chronic complications (damage to eyes, kidney, nerves, heart and blood vessels) and death. 13 Before diagnosis, many individuals with type 2 diabetes and all individuals with type 1 diabetes experience hyperglycemia of varying degrees and they may or may not be able to perceive significant signs or symptoms. 13 Symptoms can vary over time for the same individual as well. 13 The most common signs and symptoms of diabetes and hyperglycemia are listed in table 1. Table 1 - Signs and symptoms of Diabetes and Hyperglycemia 13 Thirst (polydipsia) Excessive urination (polyuria) Unexplained weight loss Fatigue Abdominal pain, nausea, vomiting Acetone breath Blurred vision Change in appetite Dry/itchy skin Slow-healing cuts version is available online at until May 2, Page 13

15 Post-Test Paula S. is in to see you for a diabetes education appointment. She was recently diagnosed with type 2 diabetes and wants to learn more about what is actually happening in her body. You decide to give her a brief review of the pathophysiology of type 2 diabetes. 1. You start by discussing the different hormones involved in glucose metabolism. Which of the following hormone is involved in maintaining glucose homeostasis? a. Insulin b. Glucagon c. Glucocorticoids d. All of the above 2. Paula asks what happens inside her body when she eats food. Which of the following is the MOST appropriate answer? a. Your body releases a hormone glucagon to lower your blood sugar and promote storage b. Your body converts the extra energy to glycogen stored in the muscles c. Your body breaks down glucose into free fatty acids to give it extra energy d. The incretin hormones are released and suppress the release of insulin 3. Paula says one of her friends carries a glucagon kit and wants to know what this hormone does in the body. Which of the following is a role of glucagon? a. Promotes glycogenolysis b. Suppresses gluconeogenesis c. Suppresses ketogenesis d. All of the above 4. Paula asks what range the blood sugar should be in a person without diabetes. What is the preprandial range for blood glucose for patients without diabetes? a mmol/l b mmol/l c mmol/l d mmol/l 5. Paula asks you a question about her husband. He was recently diagnosed with prediabetes and she was wondering if you have some information on prediabetes. Which of the following statements regarding prediabetes is TRUE? a. All patients with prediabetes will eventually develop type 2 diabetes b. Patients with prediabetes are at greater risk of arterial disease c. A diet low in saturated fat, high in fibre and regular exercise can lower his risk of diabetes by 16% d. Metformin is more effective than diet and exercise at preventing the development of type 2 diabetes in patients with IGT version is available online at until May 2, Page 14

16 References 1. Ruder, Myers MG, Chipkin SR, Tornheim K. Hormone-Fuel Interrelationships: Fed State, Starvation, and Diabetes Mellitus. In: Joslin s Diabetes Mellitus. 14th Revised edition. Lippincott Williams and Wilkins; 2004: Pathophysiology. In: Building Competency in Diabetes Education: The Essentials. Toronto: Canadian Diabetes Association; 2009:3/1-3/ McIntosh C. Incretin-based Therapies for Type 2 Diabetes. Can J DIABETES. 2008;32(2): Goldenberg R, Punthakee Z. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Can J Diabetes. 2013;37, Supplement 1:S8-S11. doi: /j.jcjd Bennett PH, Knowler WC. Definition, Diagnosis, and Classification of Diabetes Mellitus and Glucose Homeostasis. In: Joslin s Diabetes Mellitus. 14th Revised edition. Lippincott Williams and Wilkins; 2004: Ransom T, Goldenberg R, Mikalachki A, Prebtani APH, Punthakee Z. Reducing the Risk of Developing Diabetes. Can J Diabetes. 2013;37, Supplement 1:S16-S19. doi: /j.jcjd Leahy J. β-cell Dysfunction in Type 2 Diabetes Mellitus. In: Joslin s Diabetes Mellitus. 14th Revised edition. Lippincott Williams and Wilkins; 2004: Hawkins M, Rossetti L. Insulin Resistance and Its Role in the Pathogenesis of Type 2 Diabetes. In: Joslin s Diabetes Mellitus. 14th Revised edition. Lippincott Williams and Wilkins; 2004: Brown F, Goldfine AB. Diabetes and Pregnancy. In: Joslin s Diabetes Mellitus. 14th Revised edition. Lippincott Williams and Wilkins; 2004: Appendix 1: Etiologic Classification of Diabetes Mellitus. Can J Diabetes. 2013;37, Supplement 1:S197. doi: /j.jcjd Astrup A, Rössner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. The Lancet. 2009;374(9701): doi: /s (09) Origin Trial Investigators. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia. N Engl J Med doi: /nejmoa Canadian Diabetes Association. Acute complications of diabetes. In: Building Competency in Diabetes Education: The Essentials. Toronto: Canadian Diabetes Association; 2009:8/1-8/32. version is available online at until May 2, Page 15