Type 2 Diabetes Mellitus PDF

Type 2 Diabetes Mellitus Emily Bodfish, MPAS, PA-C PA 511- Clinical Medicine I Emory & Henry University Outline  Overview of Diabetes Mellitus  Type 2 Diabetes  Pathophysiology, Etiology, and Epidemiology  Presentation, Signs, and Symptoms  Diagnosis and Treatment  Medication...

Type 2 Diabetes Mellitus Emily Bodfish, MPAS, PA-C PA 511- Clinical Medicine I Emory & Henry University Outline  Overview of Diabetes Mellitus  Type 2 Diabetes  Pathophysiology, Etiology, and Epidemiology  Presentation, Signs, and Symptoms  Diagnosis and Treatment  Medication Overview  Complications  Management of Nonketotic Hyperosmolar State  Diabetes Mellitus: a group of metabolic diseases characterized by hyperglycemia Type 1A (95%) - Due to autoimmune B cell destruction Type 1: usually leading to absolute insulin deficiency Type 1B (5%) - idiopathic Type 2: Due to progressive loss of B cell insulin secretion with variable degree of tissue insensitivity to insulin  Diabetes Mellitus: a group of metabolic diseases characterized by hyperglycemia Gestational diabetes Diabetes diagnosed in the 2nd or 3rd trimester of pregnancy mellitus (GDM): without evidence of diabetes prior to pregnancy Maturity-onset diabetes of the young Genetic defects of pancreatic B cell function – several types (MODY): Latent autoimmune Slowly developing Type 1 DM in older adults diabetes in adults Initially have no insulin-dependence & ketoacidosis (LADA): Over time B cells diminish & insulin-dependence develops Type 2 DM: Overview  Pathophysiology: insulin resistance  Etiology: genetics + pancreatic exhaustion  Prevalence: 37 million Americans w/ T2DM, ~ 10.5% of the entire US population  Over 90-95% of all diabetes  Incidence: 1.5 million new cases per year  Lab Diagnostics: Clinical, FPG, RPG, A1C, C-Peptide, Insulin Levels  Treatment Gold Standard: Diet/Exercise, Metformin, Stepwise Tx Approach  PANCE Blueprint: Endocrinology 6 %  ** Cost of diabetes in the US: $327 billion per year in 2017 Pathophysiology, Etiology, & Epidemiology  Insulin: regulates blood glucose by facilitating the movement of glucose from the blood into cells for energy use Helps transport glucose to the liver and muscles for energy utilization Will also store glucose in fat tissue T2DM- produce insulin but often not enough for the body’s needs and may also struggle to use the produced insulin effectively. Insulin levels are sufficient to prevent ketoacidosis but not hyperglycemia : Diabetes. 2016;66(2):241-255. doi:10.2337/db16-0806 Date of Download: 9/18/2024 Copyright © 2024 American Diabetes Association. All rights reserved.  T2DM Etiology  The disease is multifactorial and has both genetic as well as environmental factors which play a role in the development of T2DM  Genetics  Heritability of T2DM is high (30-70%) with > 60 genetic variants  Genetic diagnostics are not routinely drawn  Environmental  Obesity highest absolute RF regardless of family hx  Visceral or central obesity  Reduced activity  Age  Poor diet  Prior gestational diabetes  T2DM Epidemiology Prevalence of DM over 20 in the  Peak incidence in minority groups: age > 45 United States yo  Slightly younger than non-Hispanic white onset American-Indian and Alaskan 14% Hispanic 12.5%  Slightly more common in male > females Non-Hispanic Black 11.7%  ~14 million more worldwide Asian Americans 9.2% Non-Hispanic White 7.5%  Highest prevalence in China overall  However, note the American-Indians in the US have highest prevalence by ethnic group  Projections show the prevalence to increase from 463 million in 2019 to 642 million by 2040 Citation: Chapter 403 Diabetes Mellitus: Diagnosis, Classification, and Pathophysiology, Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. Harrison's Principles of Internal Medicine, 21e; 2022. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=3095&sectionid=265445787 Accessed: September 18, 2024 Copyright © 2024 McGraw-Hill Education. All rights reserved Relationship of Obesity and DM: 2004 and 2019 Type 1 vs Type 2 Autoimmune destruction of β Insulin resistance often with cells, insulin → absolute absence hyperinsulinemia but relative insulin of insulin deficiency T2DM Presentation Signs and symptoms  Clinical Manifestations  Symptoms:  Often asymptomatic = insidious onset of disease  Often overweight or obese  ↑urination & thirst occasionally  Neurological or cardiovascular abnormalities possible if prolonged undetected/untreated disease  Signs:  Chronic skin infections = immune system dysfunction  Chronic yeast infections  Vulvovaginitis in women  Inflammation of foreskin & glans penis in men  ↑Centripetal fat distribution:  Men = waist circ. > 40 in.  Women = waist circ. > 35 in.  Clinical Manifestations  Acanthosis nigricans = associated with significant insulin resistance  Eruptive xanthomas = hyperchylomicronemia (↑TGs) Screening and Diagnostics Why do we screen?  Large percentage are asymptomatic and unaware they have the disorder  To prevent complications  Some patients with type 2 DM have one or more diabetes-specific complications at the time of their diagnosis  Prevent worsening or progression of disease  treatment of Type 2 DM may favorably alter the natural history of DM  Early intervention yields superior outcomes  Diagnosis of prediabetes should spur efforts for diabetes prevention  Cost-effectiveness Who needs screened for T2DM? Diagnostic Evaluation  3 broad categories for glucose tolerance:  Normal glucose homeostasis  Impaired glucose homeostasis  Diabetes mellitus  The diagnosis of diabetes in a nonpregnant patient may be based on any 1 of 4 abnormalities:  Elevated fasting plasma glucose (FPG or FBG)  Random elevated glucose with symptoms  Elevated hemoglobin A1C  Abnormal oral glucose tolerance test (OGTT)  Diagnostic Evaluation  Plasma or serum glucose:  advantage over blood glucose because it avoids RBC conc. (Hct) glucose interference:  Measures glucose concentrations to which body tissues are actually exposed  Glucose concentration is 10-15% higher than whole blood  Glycosylated hemoglobin (HgbA1c): Glucose attaches irreversibly to the beta chain of hemoglobin A  Hemoglobin A1c levels correspond to the average blood glucose over the prior 6 -12 wks  6-12 wks is avg. lifespan of RBCs  weighted to more recent glucose levels (prior 4 wks) – some RBCs don’t survive past 4 wks  ↑HgbA1c predicts risk of microvascular complications  This test is not appropriate to use in populations with high prevalence of hemoglobinopathies or in conditions with increased red cell turnover  Diagnostic Evaluation Oral glucose tolerance test  Consume 150-200 g of carbohydrates per day for 3 days preceding test  NPO past midnight prior to test day  Perform test in AM to avoid diurnal variation in glucose tolerance  Give 75 g of glucose/300 mL of water PO & consumed within 5 minutes  Obtain plasma glucose levels at 0 hrs (fasting) & 2 hrs Diagnostic Evaluation  Correlation of A1C with Estimated Average Glucose Values A1C% Mean plasma glucose mg/dL 5 97 6 126 7 154 8 183 9 212 10 240 11 269 12 298 Diagnostic Evaluation  Confirmation of diagnosis:  Without unequivocal symptomatic hyperglycemia, you must confirm the diagnosis by repeating the same test on a subsequent day OR...  Have two confirmatory tests performed on the same day  Preferred diagnostics (truly due to convenience)  FPG  A1C  Diagnostic Evaluation  Urine glucose:  urine dipstick for glucose→ can dip or urinate directly on dipstick  sensitive to 100 mg/dL of glucose  Urine & blood ketones:  Urine dipstick for ketones does not detect beta-hydroxybutyric acid, which lacks a ketone group  usually adequate for clinical purposes to estimate ketonuria  Blood evaluation can assess for all important ketones Treatment: A Stepwise Approach Goals of Therapy  Eliminate symptoms related to hyperglycemia  Reduce or eliminate the long-term microvascular and macrovascular complications of DM  Allow the patient to achieve as normal a lifestyle as possible  Diet & Exercise  1st step= Always start with diet and exercise (plus Metformin)  Weight loss of 5-10% associated with significant improvements in cardiac risk factors  Diet→ ↓carbohydrate intake to < 45% & substitute with monounsaturated fats such as olive oil, oils of nuts & avocados  Promotes ↓TGs & ↑HDL  ADA recommends food such as oatmeal, cereals, and beans with relatively high soluble fiber  Exercise→ aerobic training, resistance training DAILY  150 min/week (distributed over at least 3 days) of moderate aerobic physical activity with no gaps longer than 2 days  SOMETHING is better than NOTHING  Metformin (Glucophage)  Current recommendation is to start pharmacologic therapy at diagnosis and not wait to see whether the patient can achieve target glycemic control with weight management and exercise  First line initial treatment for type 2 diabetes  MOA: A biguanide that acts as an antihyperglycemic  hepatic glucose production, intestinal absorption of glucose, and insulin sensitivity by increasing peripheral glucose uptake and utilization  HgbA1C Reduction= 1-2%  ↓TGs in obese patients and promotes weight loss  Low risk of hypoglycemia  Long-term use associated with reduced micro- and macrovascular complications  Dosage 2000 mg PO daily  SE=GI upset  Contraindications  Alcohol, Liver disease, unstable CHF = Lactic Acidosis (D/C drug if suspected)  CKD = Severe renal impairment (eGFR < 30, Elevated Cr), DKA  Insulin Secretagogues: Sulfonylureas  2nd generation: Glyburide (Micronase ©, DiaBeta ©), Glipizide (Glucotrol ©), Glimepiride (Amaryl©)  MOA: Insulin secretagogues (stimulates release of insulin from pancreatic β cells)  HgbA1C Reduction= 1-2%  Adjunctive therapy to Metformin for A1C and FPG/RPG reduction  Cost effective  Oral- once daily dosing for many patients  Side effects: HYPOGLYCEMIA- especially in elderly  Weight gain  May have interactions with alcohol  Avoid in renal and liver insufficiency  Thiazolidinediones  Pioglitazone (Actos©), Rosiglitazone* (Avandia© )  MOA: Reduce insulin resistance in the periphery (sensitizes muscle and fat)  HgbA1C Reduction= 0.5-1.4%  Improves target-cell response to insulin without increasing insulin secretion from the pancreas  Increases insulin-dependent glucose use in skeletal muscle and adipose tissue  Lowers TGs  Adjunctive therapy to Metformin for A1C and FPG/RPG reduction  Pill form  Side effects: weight gain, fluid retention and HF, increased fracture risk in women, and possible increased risk of bladder cancer  Avoid in cardiac patients  CHF, renal/liver insufficiency  DPP4-Inhibitors  Sitagliptin (Januvia©), Saxagliptin (Onglyza ©), Linagliptin (Tradjenta©)  MOA: Prolongs endogenous GLP-1 action  ↑ insulin release and ↓ glucagon, and ↓ hyperglycemia  HgbA1C Reduction= 0.5-0.8%  Adjunctive therapy to Metformin for A1C and FPG/RPG reduction  1 pill PO daily  Side effects  Angioedema/urticarial and immune-mediated dermatologic effects  Reduce dose in renal insufficiency  Avoid in pancreatic disease  GLP-1 Receptor Agonists  Semaglutide (Ozempic©), Liraglutide (Victoza©), Exenatide (Byetta© )  MOA: Mimics endogenous incretin GLP-1→ stimulates glucose-dependent insulin release  Reduce glucagon and slow gastric emptying→ early satiety  Low risk of hypoglycemia  Lowers CV risk  HgbA1C Reduction= 0.5-1.0%  Adjunctive therapy to metformin, sulfonylureas, and thiazolidinediones for A1C and FPG/RPG reduction  SubQ injection: Qweekly or QD  Great medication→ Barriers to therapy may be COST  Side effects:  GI S/E, WEIGHT LOSS  Pancreatitis  Avoid in:  CKD, Pancreatitis, MEN 2, Medullar thyroid Cancer  SGLT 2 Inhibitors  Dapagliflozin (Farxiga©), Empagliflozin (Jardiance©), Sotagliflozin (Zynquista©)  MOA: inhibits the reabsorption of glucose in the kidneys→ increased renal glucose excretion  HgbA1C Reduction= 0.5-1.0%  Low risk of hypoglycemia  Weight reduction and mild reduction in blood pressure  Renal protective  Reduces CV events  Adjunctive therapy to metformin, sulfonylureas, and thiazolidinediones for A1C and FPG/RPG reduction  1 pill PO daily  Side effects  Hypotension, Acute Kidney Injury, DKA in Type 1 Diabetics**--DO not use  Yeast Infections, acute pharyngitis, changes in urinary habits Insulin  In someone newly diagnosed with type 2 DM: if very symptomatic and/or ↑glucose or A1C > 9, consider insulin, + other meds, from outset  Start with BASAL insulin first then add BOLUS if needed  Can start at 10 units or 0.1–0.2 units/kg and titrate q3 days by 3 units  Very hard to get patients off insulin once started  Try your best with other anti-hyperglycemics and max them out first Amylin  Pramlintide (Symlin©)  MOA: Synthetic Amylin, a hormone produced by and secreted by pancreatic beta cells  Injectable pen device, Starting Dose of 15 mcg (up to 120 mcg) with each meal of at least 30g carbs or 250 calories  Not used in the US a lot, more so in Europe  ONLY MED FDA APPROVED FOR TYPE 1 DIABETES BESIDES INSULIN  Side effects  Severe hypoglycemia (Consider mealtime insulin dosing adjustment)  Nausea, vomiting, stomach upset  Alpha-glucosidase inhibitors  Acarbose (Precose©), Miglitol (Glyset©)  MOA: Prolongs absorption of carbs and helps prevent PPG surge  HgbA1C Reduction= 0.5-0.8%  Only modest effect on glucose control  1-3 pills PO  Limited use in the US→ not routinely used  Side effects  Flatulence  Watch for LFT’s  Meglitinides  Repaglinide (Prandin ©), Nateglinide (Starlix ©)  MOA: Stimulates non-glucose-dependent insulin secretion in a similar mechanism to sulfonylureas but weaker  HgbA1C Reduction= 0.5-1.0%  Not routinely used in the US  Side effect: Hypoglycemia Barriers to Treatment  Compliance  Disbelief  “I don’t feel that bad”  And your BG’s are in the 400’s…  Cost  Delivery system  Make sure to differentiate non-insulin injectables vs. insulin  Some patients will think any shot is insulin  “My family member died when they took insulin and I’m not taking it”  Monitoring Check your blood glucose, kidneys, BP, and CHOLESTEROL  Glucose Monitoring  Self Monitoring of Blood Glucose (SMBG)  Using a small blood sample via finger prick to test serum glucose levels  Helps determine if patient is having an adequate response to treatment  The target= 80-120 mg/dL  When to check?  1 to 2 times daily, at least  Less monitoring in comparison to T1DM  With 50 strips per bottle, this means about ____ per month  Brands: One Touch, Freestyle, Contour, Accu-Check  Glucose Monitoring  Continuous Glucose Monitoring  Utilizes a sensor or electrode to detect interstitial glucose  Sensors are placed subcutaneously and are replaced every 3–14 days  Provides unlimited glucose datapoints that can be used to define a time in a glycemic range  Allows the patient to monitor the rate of glucose change and glucose trends that can be used to avoid predicted hyper- or hypoglycemia  Brands: Freestyle Libre! Dexcom G6 or G7, the Guardian, Eversense Glycemic monitoring and insulin administration options for treatment of diabetes. A. CGM profile and delivery of rapid-acting insulin analog by continuous subcutaneous insulin infusion pump involves a basal rate (light purple line) and prandial and correction boluses (purple circles) based on estimated carbohydrate intake (orange squares) and an insulin sensitivity factor. B. CGM profile with sensor-communicating insulin pump that automates insulin delivery by suspending delivery for predicted hypoglycemia and increasing basal delivery for predicted hyperglycemia (light purple curves) while still requiring user input for estimated carbohydrate intake (orange squares) to provide prandial insulin boluses (purple circles). C. CGM profile is used to generate an estimate of time-in-range with glycemic goal shown on the left side of the bar and target % time in that glycemic range shown on the right side of the bar. D. Pharmacokinetic profile of individual insulin products. (C. Reproduced with permission from T Battelino et al: Clinical targets for continuous glucose monitoring data interpretation: Recommendations from the International Consensus on Time in Range. Diabetes Care 42:1593, 2019; D. Adapted with permission from JJ Neumiller: Insulin update: New and emerging insulins. American Diabetes Association, 2018.) Citation: Chapter 404 Diabetes Mellitus: Management and Therapies, Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. Harrison's Principles of Internal Medicine, 21e; 2022. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=3095&sectionid=265445871 Accessed: September 22, 2024 Copyright © 2024 McGraw-Hill Education. All rights reserved Hypertension  Pts with BP >140/90 should, in addition to lifestyle therapy, start pharmacotherapy  Lifestyle therapy  Weight loss, if needed  DASH diet (↓Na, ↑K)  Moderation of EtOH;  ↑ physical activity  Pharmacotherapy should include ACEI or ARB  Multiple-drug therapy is generally required Cholesterol  Statin therapy is recommended in ALL pts with DM >40 yo regardless of presence or absence of CVD risk factors  One of Four “Statin Benefit Groups”  Persons with DM who are 40 to 75 y.o. with LDL-C levels of 70 to 189 but without known CVD benefit from statin therapy Guidelines for Ongoing, Comprehensive Care for Individuals with DM Complications Retinopathy, nephropathy, neuropathy and more Retinopathy  Vascular damage to the retina  #1 cause of blindness in people 20-74 yrs in the US  ~700K pts in US have proliferative diabetic retinopathy  Annual incidence of 65,000  Early stages can be asymptomatic but earliest clinical signs = microaneurysms viewed on fundoscopic  Later symptoms: floaters, distortion, blurred vision  Macular edema = MCC of vision loss in pts with nonproliferative diabetic retinopathy*  All T1D’s must get yearly fundoscopic exams  Prevention? Glucose/A1c control. Buzz word: Cotton wool spots!   #1 cause of CKD and ESRD in US Nephropathy  1st sign is microalbuminuria  Characterized by:  Damage to glomeruli (remember they are capillaries)  Persistent albuminuria (>300 mg/d or >200 μg/min) confirmed on at least 2 occasions 3-6 months apart  Progressive decline in GFR  ↑arterial BP  Treatment/Monitoring:  Optimal therapy is prevention  Yearly measurement of creatinine, urinary albumin excretion, K  Improve glycemic control  Strict BP management  Consider ACEI/ARB  Insulin dose adjustments based on GFR and refer to nephrology if GFR < 30   Distal symmetric polyneuropathy = MC form of diabetic Neuropathy neuropathy  Stocking-and-glove distribution in distal extremities  loss of balance, especially with the eyes closed, and painless injuries due to loss of sensation  Test with pinprick, vibration tuning fork, 10-g monofilament, and ankle reflexes  Treatment= Prevention with regular foot exams is best  Annual screening for DSPN should begin 5 years after diagnosis of type 1 DM and at the time of diagnosis of type 2 DM  Yearly thereafter  Medications may help sensation:  Pregabalin (Lyrica)  Gabapentin (Neurontin)  TCAs (amitriptyline, nortriptyline, imipramine)  Topical lidocaine or capsaicin can help  Neuropathy + poor perfusion (due to atherosclerosis/PAD) → non-healing foot ulcers, amputations CHECK YOUR PT’S FEET!  Refer to wound care or podiatry!  Autonomic Neuropathy  Generalized  Cardiovascular  ataxia, gait instability  Persistent sinus tach  Gastrointestinal  Orthostasis  Constipation– MC GI manifestation  Exercise intolerance  Dysphagia  GU  Abdominal pain, nausea/vomiting  Bladder neuropathy  Diarrhea, fecal incontinence  Poor urinary stream/ Straining  Gastroparesis  Feeling of incomplete emptying  May → to poor glucose control  Recurrent UTI, pyelo  may improve with diet changes and  Incontinence prokinetic agents e.g. erythromycin, cisapride, domperidone  ED, retrograde ejaculation  Anti-emetics  Sudomotor neuropathy  Metoclopramide for only severe cases  Heavy sweating of upper body/anhidrosis of lower  Gustatory sweating  Hyperglycemia Hyperosmolar Sate  Second MC form of hyperglycemic coma and a serious acute complication  Characterized by severe hyperglycemia, in the absence of significant ketosis, with hyperosmolality and dehydration leading to AMS  Etiology: T2DM + illness – fluid intake  No ketosis! There is insulin onboard with T2DM, unlike T1DM, but not enough to prevent hyperglycemia  Pathophysiology  Hyperglycemia Hyperosmolar Sate  Signs/Symptoms:  Develops over days to weeks  Polyuria +/- polydipsia  Weight loss, weakness  Tachycardia, hypotension  Dry skin, mucous membranes, poor skin turgor  Altered mental status without Kussmaul respirations.  Nonketotic hyperosmolar state  Diagnosis:  Plasma glucose level usually >600 mg/dL  Serum osmolality >320 mOsm/kg (nl = 280-290)  Profound dehydration, up to an average of 9 L  BUN/creat ↑↑/ ↑ (dehydration → poor perfusion)  No significant acidosis  Serum pH >7.30  Bicarbonate concentration >15 mEq/L  Small ketonuria and absent-to-low ketonemia  May have some ketosis from not eating  Treatment:  Rehydrate, correct hyperglycemia, treat underlying illness  May require insulin  Wrap-Up  Every T2DM needs:  Multidisciplinary team working w/ both pt and pt’s family  A WRITTEN PLAN that encompasses meds, diet/exercise, and goal setting  Medications (w/ adequate refills)  Most pt’s with T2DM are on multiple medications  Make sure they know how to use devices (i.e. pens) and have them DEMONSTRATE  Blood glucose monitoring through some sort of device  +/- testing strips (which are expensive), lacets for the meter, skin adhesives for CGM’s  Psychosocial Counseling  screen for psychosocial probs such as depression, diabetes-related distress, anxiety, eating disorders, and cognitive impairment (esp if > 65yo)  Quarterly to yearly visits including appropriate monitoring of complications