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Type 2 diabetes - A 2016 update by Zeena Nackerdien

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The International Diabetes Federation maintains that one in two adults are undiagnosed for diabetes and that estimates that one in eleven people had diabetes in 2015. If one takes into account that most of the cases involves the preventable condition of Type 2 diabetes, it comes as no surprise that many countries are being hit by staggering socioeconomic costs. Diabetes sites, chat rooms, aps, and ads for ever-evolving and increasingly complex disease management schemes are commonplace on Google. But what does all the information mean? The American Diabetes Association, American Association of Clinical Endocrinologists, The Canadian Diabetes Association, WebMD, and the International Diabetes Federation resources served as the major resources for this accompanying slide deck that tries to unpack some of the major subtopics related to prediabetes and Type 2 diabetes. The slide deck is organized according to disease definition, epidemiology, etiology/pathophysiology, diagnosis, treatment, and prevention. Particular topics such as the early use of insulin could be expanded into several separate slide decks narrating benefits and risks with supporting evidence. However, this deck is meant to provide interested readers with an overview of the Type 2 diabetes literature landscape, with the caveat that specific cases and Type 2 diabetes-related complications should always be discussed with a healthcare provider.
Image credits: slideteam.net; Wikimedia

Published in: Health & Medicine
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Type 2 diabetes - A 2016 update by Zeena Nackerdien

  1. 1. Type 2 Diabetes Definition Epidemiology Etiology Diagnosis Treatment Prevention Disease Characteristics and Goals Reduce risk of complications •BP, lipid, and glycemic management to reduce risk of macrovascular complications •BP control and glycemic management to reduce risk of microvascular complications Cardiovascular risk factor reduction a key goal •Treat cardiovascular risk factors to achieve individualized targets •Smoking cessations, antihypertensive agents, and lipid medications are among the recommended agents Individualize treatment •Lifestyle changes + metformin as initial antihyperglycemic therapy for most patients •Glycemic goals and treatment choices are individualized • Insulin resistance and relative insulin insufficiency https://online.epocrates.com/diseases/2411/Type-2-diabetes-mellitus-in-adults/Key-Highlights BP, blood pressure Key complications: Nerve, kidney, eye, and cardiovascular diseases
  2. 2. Type 2 Diabetes Definition Epidemiology Etiology Diagnosis Treatment Prevention Prediabetes • Prediabetes is a metabolic condition characterized by hyperglycemia – Diagnostic criteria below those used to define Type 2 diabetes eg, fasting plasma glucose concentrations are 5·6 mmol/L or higher but less than 7·0 mmol/L (termed impaired fasting glucose [IFG]) Est., estimated Garber AJ, Abrahamson MJ, Barzilay JI, Endocrine Practice. 2016;22(1):84-113. Stefan N, Fritsche A, Schick F, et al. TLancet Diabetes & Endocrinology. 2016;4(9):789-98. USA >38% est. to have prediabetes China >50% est. to have prediabetes In terms of pathophysiology, prediabetes reflects failing pancreatic islet β-cell compensation for an underlying state of insulin resistance, most commonly caused by excess body weight or obesity.
  3. 3. Type 2 Diabetes Definition Epidemiology Etiology Diagnosis Treatment Prevention Phenotyping of patients with prediabetes • Stefan et al. (2016) proposed stratifying patients into low- and high-risk groups – High-risk: low insulin secretion or low insulin sensitivity plus non-alcoholic fatty liver disease (NAFLD) – Low-risk: Other combinations related to insulin secretion, insulin sensitivity, and NAFLD eg, high body mass index or visceral obesity . CVD, cardiovascular diseases; NAFLD, non-alcohol fatty liver disease; NGR, normal glucose regulation Stefan N, Fritsche A, Schick F, et al. TLancet Diabetes & Endocrinology. 2016;4(9):789-98. Prediabetes and no stratification at baseline Maybe intensive lifestyle intervention will restore NGR Prediabetes and stratification at baseline Better predictive power as to the effectiveness of lifestyle intervention in restoring NGR; Improves classification of hyperglycemia and risk of CVD in prediabetics
  4. 4. Diabetes Epidemiology Definition Etiology Diagnosis Treatment Prevention Epidemiology 415 million people worldwide have diabetes; by 2040 this will rise to 642 million (2015 International Diabetes Federation estimates) The estimated annual global health expenditure attributable to diabetes ranged from USD 612 billion (to USD 1099 billion. Together, the North America and Caribbean Region and the Europe Region were responsible for over 69% of the costs, and less than 10% of the costs were from the Africa Region, South East Asia Region, and Middle East and North Africa Region combined. MENA, Middle East and North Africa da Rocha Fernandes J, Ogurtsova K, Linnenkamp U, et al. Diab. Res. Clinical Prac. 2016;117:48-54. http://www.diabetesatlas.org/ Every 6 seconds someone dies from diabetes 3.2% In Africa, more than two-thirds are undiagnosed; Prevalence in MENA: 9.1% Regional Prevalence (%) North America & Caribbean 12.9% South & Central America 9.4% South- East Asia 8.5% 9.1% 37% of the diabetics across the globe live in the Western Pacific (a region comprising 39 countries, including China)
  5. 5. Type 2 Diabetes: Etiology/Pathophysiology Definition Epidemiology Etiology Diagnosis Treatment Prevention • ≥40 years old • Hereditary predisposition • Pre-diabetic • Woman who had gestational diabetes • Woman who gave birth to a ≥9 lb baby • Overweight/excess abdominal weight • High BP or cholesterol issues • Psychosocial disorders/HIV infection/polycystic ovarian syndrome/acanthosis nigricans • Specific medications eg, antipsychotics/anti- inflammatory steroids What are the risk factors? BP, blood pressure; HIV, human immunodeficiency virus Cheng AY. and members of the Clinical Practice Guideline Committees. CJD. 2013;37 Suppl 1:227 pp.
  6. 6. Type 2 Diabetes: Etiology/Pathophysiology Definition Epidemiology Etiology Diagnosis Treatment Prevention • Blood glucose appearance is a function of meal-derived sources and hepatic glucose production – Regulation occurs by pancreatic and gut hormones – Liver and skeletal muscle responsiveness to insulin decline with progressive β-cell dysfunction – Insulin is a key anabolic hormone secreted in response to increased blood glucose and amino acids following a meal What role does insulin play? Brunton SA, Kruger DF, Funnell MM. Clinical Diabetes. 2016;34(1):34-43; www.slideteam.net Aronoff SL, Berkowitz K, Shreiner B et al.Diabetes Spectrum. 2004;17(3):183-90.
  7. 7. Type 2 Diabetes: Etiology/Pathophysiology Definition Epidemiology Etiology Diagnosis Treatment Prevention • Insulin resistance is aggravated by aging, physical inactivity, and overweight (BMI 25-29.9 kg/m2) or obesity (BMI >30 kg/m2) • Complexity of intracellular derangements suggest the disease may be stratified into many subtypes Etiology Pathophysiology The precise mechanism by which the diabetic metabolic state leads to microvascular and macrovascular complications is only partly understood. Uncontrolled BP and uncontrolled glucose, increasing the risk of microvascular complications such as retinopathy and nephropathy With respect to macrovascular complications, high BP and glucose raise risk, but so do lipid abnormalities and tobacco use. One unifying theory postulates a metabolic syndrome that includes diabetes mellitus, hypertension, dyslipidemias, and obesity, and predisposes to coronary heart disease, stroke, and peripheral artery disease. However, this theory is not universally accepted. https://online.epocrates.com/diseases/2424/Type-2-diabetes-mellitus-in-adults/Etiology
  8. 8. Type 2 Diabetes – Diagnostic Approach Definition Epidemiology Etiology Diagnosis Treatment Prevention • impaired glucose tolerance, impaired fasting glucose, or metabolic syndrome are risk factors – Any one of these factors is associated with a 5-fold increase in future T2D risk • Three tests indicate prediabetes – Fasting plasma glucose test (blood sugar is 100-125) – Oral glucose tolerance test (blood sugar is 140-199 after the second test) – A1C test: (blood sugar is 5.7 to 6.4%) Prediabetes http://www.webmd.com/diabetes/type-2-diabetes-guide/what-is-prediabetes-or-borderline-diabetes Garber AJ, Abrahamson MJ, Barzilay JI, et al,. Endocrine Practice 2016;22(1):84-113.
  9. 9. Type 2 Diabetes – Diagnostic Approach Definition Epidemiology Etiology Diagnosis Treatment Prevention • Symptomatic patients may present with: fatigue; polyuria, polydipsia, polyphagia, or weight loss (usually when hyperglycemia is more severe, e.g., >300 mg/dL); blurred vision; paresthesias; unintentional weight loss; nocturia; skin infections (bacterial or candidal); urinary infections; or acanthosis nigricans Diagnosis should be verified by repeat testing. 1 3 24 One of 4 tests can confirm a diagnosis of diabetes 1. Fasting plasma glucose (FPG) >125 mg/dL (most commonly used) 2. Random plasma glucose ≥200 mg/dL with diabetes symptoms such as polyuria, polydipsia, fatigue, or weight loss 3. 2-hour post-load glucose ≥200 mg/dL on a 75 g oral glucose tolerance tests 4. HbA1c ≥6.5% https://online.epocrates.com/diseases/2431/Type-2-diabetes-mellitus-in-adults/Diagnostic-Approach
  10. 10. Type 2 Diabetes – Goals for Glycemic Control Definition Epidemiology Etiology Diagnosis Treatment Prevention • Strong risk factors, which also indicate the need for screening, include: older age; overweight/obesity; black, Hispanic, or Native American ancestry; family history of Type 2 Diabetes; history of gestational diabetes; presence of prediabetes; physical inactivity; polycystic ovary syndrome; hypertension; dyslipidemia; or known cardiovascular disease For patients with concurrent serious illness and at high risk for hypoglycemia Diagnosis should be verified by repeat testing. A1C ≤6.5% A1C >6.5% For patients without concurrent serious illness and at low hypoglycemic risk A1C, glycated hemoglobin http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/a1c http://answers.webmd.com/answers/1180327/what-blood-sugar-levels-are-considered-normal-and-what-levels-are-diabetic http://www.webmd.com/diabetes/tc/criteria-for-diagnosing-diabetes-topic-overview/ Garber AJ, Abrahamson MJ, Barzilay JI, et al.Endocrine Practice 2016;22(1):84-113. 2. Glucose enters red blood cells and glycates with molecules of hemoglobin (A1C).. By measuring the percentage of A1C in the blood, one gets an overview of your average blood glucose control for the past few months. 1. Hemoglobin, a protein that links up with sugars such as glucose, is found inside red blood cells. Its job is to carry oxygen from the lungs to all the cells of the body.
  11. 11. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • Since patients are 2x likely to die from CVDs vs. the general population, a 1◦ goal is treatment of CVD risk factors to individualize targets Approach Cornerstonetreatmentforall patients Initialglucose-lowering pharmacotherapies CVDriskfactors Smoking cessation Blood pressure control Statin use Aspirin use for patients with known coronary heart disease ACE inhibitors for patients with chronic kidney disease/protei nuria Metformin Dual-drug combinations Self- management program Nutrition education This is a progressive disease and prompt initiation and intensification of pharmacotherapy to achieve and maintain clinical goals is central to diabetes care. https://online.epocrates.com/diseases/2441/Type-2-diabetes-mellitus-in-adults/Treatment-Approach CVD, cardiovascular disease
  12. 12. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • The priority in management is to minimize the risks of hypoglycemia and weight gain. The AACE preferentially recommends agents that do not increase these risks Pharmacologic Agentsa Smoking cessation Blood pressure control Statin use Aspirin use for patients with known coronary heart disease ACE inhibitors for patients with chronic kidney disease/protei nuria Metformin Dual-drug combinations Self- management program Nutrition education Abbreviations: AACE = American Association for Clinical Endocrinology; AGI = α-glucosidase inhibitors; BCR-QR = bromocriptine quick release; DPP4I = dipeptidyl peptidase 4 inhibitors; GLP1RA = glucagon-like peptide 1 receptor agonists; SGLT2I = sodium-glucose cotransporter 2 inhibitors; SU = sulfonylureas; TZD = thiazolidinediones; a Intensify therapy whenever A1C exceeds individualized target. Boldface denotes little or no risk of hypoglycemia or weight gain, few adverse events, and/or the possibility of benefits beyond glucose lowering. b Use with caution. Handelsman Y, Bloomgarden ZT, Grunberger G,et al. Endocrine Practice. 2015;21 Suppl 1:1-87. Metformin; GLP1RA; SGLT2I; DPP4I; AGI; TZDb; SU/glinideb GLP1RA; SGLT2I; TZDb; Basal insulinb; DPP4I; Colesevelam; BCR-QR; AGI; SU/glinideb GLP1RA; SGLT2I; DPP4I; TZDb; Basal insulinb; Colesevelam; BCR-QR; AGI; SU/glinideb 1First-line treatment 2Metformin (or other first-line agent) plus 3First- and second-line agent plus
  13. 13. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • Research on two incretins ie, glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), led to the development of GLP-1 receptor (GLP-1R) agonists and DPP-IV inhibitors Incretins: Key non-insulin therapies Smoking cessation Blood pressure control Statin use Aspirin use for patients with known coronary heart disease ACE inhibitors for patients with chronic kidney disease/protei nuria Metformin Dual-drug combinations Self- management program Nutrition education DPP IV, Dipeptidyl Peptidase IV; GLP-1,R Glucagon-like peptide- receptors; MOA, mechanism of action; Chatterjee S, Davies MJ. Postgrad Med J. 2015;91(1081):612-21. Can be used in conjunction with insulin to optimize control, reduce its weight gain effects and lower daily insulin dose requirements GLP-1R agonist use Improved HbA1c (up to 1.6%); minimal risk of hypoglycemia and often significant weight loss/neutrality depending on the incretin and patient factors Result Can be used safely in worsening renal impairment, with some agents such as linagliptin, which is mainly excreted enterohepatically requiring no dose adjustment even in end- stage renal failure DPP IV inhibitor use MOA Increase insulin secretion (via β cells) and reduce glucagon secretion, hepatic glucose production and glucose uptake from the stomach and promote satiety
  14. 14. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • Synthetic insulin (6,000 Da) consists of an A chain of 21 amino acids and a B chain of 30 amino acids • In the body, insulin is generated by cleavage of the C- peptide from proinsulin Insulin Synthesis Smoking cessation Blood pressure control Statin use Aspirin use for patients with known coronary heart disease ACE inhibitors for patients with chronic kidney disease/protei nuria Metformin Dual-drug combinations Self- management program Nutrition education Brunton SA, Kruger DF, Funnell MM. Role of Emerging Insulin Clinical Diabetes. 2016;34(1):34-43 Fu Z, Gilbert ER, Liu D. Current Diabetes Reviews. 2013;9(1):25-53; http://www.slideteam.net/.
  15. 15. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • Typically-used insulin classes are shown here – Administration modes are via pen/pump/syringe/subcutaneous infusion – Many novel insulin products and delivery systems may provide T2D patients to initiate insulin more comfortably and earlier in the disease process Types of Insulin Smoking cessation Blood pressure control Statin use Aspirin use for patients with known coronary heart disease ACE inhibitors for patients with chronic kidney disease/protei nuria Metformin Dual-drug combinations Self- management program Nutrition education http://guidelines.diabetes.ca/cdacpg_resources/Ch12_Table1_Types_of_Insulin_updated_Aug_5.pdf Bolus (prandial) insulins Basal insulins Premixed insulins
  16. 16. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • Insulin should be intensified within 3-6 months of failure to meet glycemic targets (Brunton et al, 2016) – Benefits of early use/intensification eg, improvements in glycemic control/QoL/treatment satisfaction – Insulin is often initiated late in the natural history of the disease The Insulin Conundrum Smoking cessation Blood pressure control Statin use Aspirin use for patients with known coronary heart disease ACE inhibitors for patients with chronic kidney disease/protei nuria Metformin Dual-drug combinations Self- management program Nutrition education QoL, quality of life Brunton SA, Kruger DF, Funnell MM. Clinical Diabetes. 2016;34(1):34-43. Patient Barriers Concerns over safety and efficacy of insulin Hypoglycemia or weight gain concerns Psychological eg, a perceived failure to take the hormone Concern that insulin is associated with complications or even death Fear of a loss of independence Clinician Barriers Need for education about the benefits of appropriately-initiated insulin therapy Patients reluctance to use injected insulin may preclude initiation of a chat about the hormone Time-consuming for staff to provide patient training regarding insulin use/Remote practices may not have access to needed training materials Overall goal of insulin and non-insulin therapies is to lower basal hepatic glucose production and increase muscle glucose uptake
  17. 17. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • Guidelines promote personalized management with a special focus on safety beyond efficacy based on prespecified approaches AACE/ACE Management Algorithm (Part 1) Metformin Dual-drug combinations education Garber AJ, Abrahamson MJ, Barzilay JI, et al. Endocrine Practice 2016;22(1):84-113. Lifestyle therapy, including medically Supervised weight loss. The A1C target must be individualized.; Glycemic control Targets include fasting & postprandial glucoses Patient characteristics, net costs to patients, formulary restrictions, & personal preferences are among the factors to be taken into account in the choice of therapies. Minimizing risk of hypoglycemia is a priority. Minimizing risk of weight gain is a priority. Total cost of care adds up eg, monitoring requirements, initial acquisition cost of medications, weight gain, safety etc..
  18. 18. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • Guidelines promote personalized management with a special focus on safety beyond efficacy based on prespecified approaches AACE/ACE Management Algorithm (Part 2) Metformin Dual-drug combinations education Garber AJ, Abrahamson MJ, Barzilay JI, et al. Endocrine Practice 2016;22(1):84-113. Algorithm stratifies choice of therapies based on initial A1C. Combination therapy Is usually required & should involve agents with complementary actions. Lipid/blood pressure profiles and related comorbidity assessments should form part of comprehensive management. Initially therapy should be evaluated frequently until stable & then less often.. Keep therapy as simple as possible to optimize adherence The algorithm includes every FDA-approved class of diabetes medications
  19. 19. Type 2 Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • 180 medicines are currently being developed to treat diabetes. Other therapies are listed here. Emerging therapies Smoking cessation Blood pressure control Statin use Aspirin use for patients with known coronary heart disease ACE inhibitors for patients with chronic kidney disease/protei nuria Metformin Dual-drug combinations Self- management program Nutrition education http://www.phrma.org/sites/default/files/pdf/diabetes2014.pdf https://online.epocrates.com/diseases/2443/Type-2-diabetes-mellitus-in-adults/Emerging-Therapies Bariatric surgery Cinnamon Other agents eg, salsalate, human insulin inhalation powder Therapeutic benefits vary; younger patients (40-50) with more recent-onset disease had higher benefits than older patients with longer-duration illness. More study is needed to confirm findings that cinnamon reduces blood sugars with minimal effect on HbA1c.. Further study is needed to confirm HbA1c-lowering capacity of salsalate; Although rapid-acting inhaled insulin Is FDA-approved, this drug is not preferred over injectable Insulins. The latter drugs have a longer safety track record.
  20. 20. Diabetes Treatment Definition Epidemiology Etiology Diagnosis Treatment Prevention • Novel therapies, including immunomodulation, are being investigated to treat/prevent all forms of diabetes Future Directions Smoking cessation Blood pressure control Statin use Aspirin use for patients with known coronary heart disease ACE inhibitors for patients with chronic kidney disease/protei nuria Metformin Dual-drug combinations Self- management program Nutrition education Chatterjee S, Davies MJ.. Postgrad Med J. 2015;91(1081):612-21. Preserving/increasing β-cell function • ‘Bionic’ pancreas • Islet transplants Immunomodulation • Antigen-specific and non- antigen-specific agents • Stem cell transplantation Intensify prevention strategies • Optimizing lifestyle changes/ using metformin in prediabetes may prevent T2DM, but difficult to translate clinical data into real-world practice Pharmacological therapies • Oral insulin • Fecal transplants
  21. 21. Type 2 Diabetes Definition Epidemiology Etiology Diagnosis Treatment Prevention • Goals Patient Education Cheng AY. and members of the Clinical Practice Guideline Committees. Canadian Diabetes Association 2013 clinical practice guidelines for the prevention and management of diabetes in Canada. CJD. 2013;37 Suppl 1:227 pp. Smoking cessation S M A R T Specific, Measurable, Attainable, Relevant, Time-bound Diabetes Education and Nutrition Enable timely, culturally and literacy appropriate diabetes education and resources Physical activity/ weight loss/medication Hypoglycemia/ Self-monitoring of blood glucose (SMBG) Foot care/Mental Health and Mood Disorders
  22. 22. Type 2 Diabetes: Prevention Definition Epidemiology Etiology Diagnosis Treatment Prevention • 86 million are living with prediabetes, a serious health condition that increases a person’s risk of type 2 diabetes and other chronic diseases. Control of the main disease drivers http://www.cdc.gov/chronicdisease/resources/publications/aag/diabetes.htm https://online.epocrates.com/diseases/2444/Type-2-diabetes-mellitus-in-adults/Prevention Modest weight loss; diet; exercise; certain phamracotherapies subject to consideration of side effects Annual influenza and pneumococcal polysaccharide vaccines as appropriate; Regular dental care; Diabetes education as needed Prediabetes Type 2 diabetes

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