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Equip yourself with state-of-the-art care guidelines for diabetic patients, covering glycemic control, hypertension management, cardiovascular protection, and oral/injectable medications. Stay updated on evidence-based practices and tools to enhance patient outcomes. Learn about foot and eye care, obesity's role, and pre-diabetes identification. Takeaways include methods for glycemic control, CV risk factor control, and recognizing diabetic retinopathy. Enhance your clinical practice by focusing on patient education, lifestyle modifications, and regular monitoring.
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Goals For Today • Review evidence based guidelines and equip you to deliver state of the art care to your diabetic patients • Understand tools that support practice performance and improvement • Review oral and injectable medicines hypoglycemics • Review multifaceted approach to cardiovascular disease protection
Effect of Tighter Glycemic Control on Progression of Retinopathy DCCT
United Kingdom Prospective Diabetes Study • Study summary – 10 years • Type 2 diabetics – convention vs. intense control • Glycemic control – 7.0 vs. 7.9 • Hypertension control – 144/82 vs. 154/87 • Glycemic control • metformin, sulfonylureas, and insulin • Hypertension • captopril, atenolol
UKPDS Blood Pressure Study:Tight vs. Less Tight Control • 1148 type 2 patients • BP lowered to avg. 144/82 (controls-154/87); 9 yr follow-up Endpoint Risk Reduction(%) P Value______ Any diabetes related endpoint 24 0.0046 Diabetes related deaths 32 0.019 Heart failure 56 0.0043 Stroke 44 0.013 Myocardial infarction 21 NS Microvascular disease 37 0.0092 UKPDS. BMJ. 317: 703-713. 1998.
Glycemic Control Reduces Complications Diabetes Control and Complications Trial (DCCT) Research Group. N Engl J Med 1893:329:977-988 UK Prospective Diabetes Study (UKPDS) Group. Lancet 1993; 352:837-853.
ABCs Of Diabetes Management Diabetes Care 2009;32:S6-12
Control of CV Risk Factors in Diabetic Hypertensive Patients in Academic Medical Centers • A1C <7% • 27% • LDL <100 • 36% • BP <130/85 mmHg • 27% • Daily Aspirin (ASA) Use • 46% • BP, Lipids and A1C • 3% • BP, Lipids, A1C + ASA • 2% McFarlane SI. DiabetesCare 2002;25:718
Metabolic Syndrome • Requires 3 or more: • Triglycerides > 150 • HDL < 40 • Waist size >40” men, >35” women • BP > 130/85 • Fasting glucose > 100 • Caveat: Treatment counts for requirements… (Grundy, Circulation, 2005)
Pre-Diabetes Definition If FBG >100 there is a 10-15% risk of DM within 7 years… or Fasting GTT
Who and When to Screen? • Family history • Overweight (BMI 25) • Dyslipidemia • HTN • High risk ethnicity • Vascular disease • Prior glucose elevation • Hx or exam findings • Starting at age 45, a fasting blood glucose every three years • More frequent screening if:
Role of Obesity in Diabetes • Obesity (specifically abdominal) has one of the highest associations with insulin resistance and glucose intolerance • Numerous studies have tied weight loss to diabetes prevention • A 5-10% weight loss yields a 58% reduction in the incidence of diabetes! • At the end of four years • Diet and exercise regimens average a 4kg loss after two years • Advice alone results in a 1kg gain (Franz, Journal Amer. Diabetes Assoc, 2007)
Quantifying Obesity • Easiest is by waist circumferences. • 40” males, 35” females • Some variation by ethnicity (35” and 31” for Asians) • Measured across iliac crest in the back and the umbilicus in the front
Healthcare Maintenance • Latest ADA guidelines (2009) • Lab surveillance • Diabetic education • Vaccinations/routine healthcare • Smoking cessation • Foot exams • Eye exams
Reasons to Look at Feet • Up to 70% of diabetics eventually develop a neuropathy • Up to 25% develop foot ulcers • Diabetes doubles your risk of LE disease (vascular, neuro, skin) • More than half of the foot ulcers become infected at some point
Foot Surveillance • Examine the feet at every visit • Annual comprehensive evaluation • Sensation • Pulses • Skin condition (ulcers, hair, nails) • Anatomic deformities • Shoe evaluation
Sensory Exam • 10-gram monofilament • Patient should not watch • Five sites per foot • Apply filament perpendicular to skin • Allow slight buckle of filament in one motion • Each site should take 1-2 sec • Do not apply to ulcers or calluses
Eye Care • Diabetic retinopathy is the leading preventable cause of blindness • Prevalence of DR increases with duration of diabetes (100% Type 1, 60% Type 2 after 20 years) • Of all recommendations, eye screening is the least likely to get done
Pathogenesis • Increased circulating glucose leads to weakness of capillary walls • Microaneurysms and leakage occurs causing eventual infarction of the nerve fiber layers (cotton wool spots) • The localized hypoxia then leads to vasoproliferation • Extension into the vitrea (+/- hemorrhage) leads to fibrosis and vision loss
Diabetic Retinopathy Normal Retina (left) contrasted with Proliferative Diabetic Retinopathy (right) Refer patients for ophthalmologist evaluation
General RulesHypoglycemic Therapy • Normalize fasting glucose levels first (90-130 mg/dl) • Many patients will achieve A1C < 7% • When to target postprandial glucose levels? • Fasting and preprandial values are at goal • A1C levels are not met • Measure 1-2 hours after beginning of the meal • Glucose are generally at their peak
Glycemic Goals of Therapy Verbal Target ~100 <<200 As low as possible w/o unacceptable adverse effects Goal Premeal plasma glucose (mg/dL) 2-h postprandial plasma glucose A1C ADA 90-130 <180* <7%** * Evaluation and treatment of postprandial glucose may be useful in the setting of suspected postprandial hyperglycemia, with the use of agents targeting postprandial hyperglycemia and for suspected hypoglycemia ** More stringent glycemic goals (i.e. a normal A1C, <6%) may further reduce complications at the cost of increased risk of hypoglycemia Diabetes Care 2009;32:S6-12
Biguanides: Metformin Mechanism of action • Reduces hepatic glucose production • Depends upon presence of insulin Safety and efficacy • Decreases A1C 1-2% • Adverse effects: diarrhea and nausea; main risk: lactic acidosis • Discontinuation rate 5% • Contraindications: renal, cardiac, hepatic insufficiency; IV contrast • No direct effect on kidney Dosing • Initial dose: 500 mg once a day; dosing: usually BID • Maximum effective dose: 2,000 mg per day • Titration frequency: week(s) to months • Alternate formulations: “XR” and combinations
Metformin Outperformed Other Meds in Obese Patients (UKPDS) Lancet 1998 Sep 12;352(9131):854-65.
Insulin Secretagogues: Sulfonylureas (SFU) and “Glinides” Mechanism of action • Stimulate basal and postprandial insulin secretion • Require functioning beta cells (no effect on beta cell dysfunction) • Work quickly Safety and efficacy • Decrease A1Capproximately1-2% • Lower fasting glucose 20% • Adverse events: weight gain, allergy (rare); main risk, hypoglycemia Dosing • Initial dose: 1/8 to 1/4 maximum dose; dosing: 1-2 times/day (SFU), 3 times/day (glinides) • Maximum effective dose: 1/2 maximum(full dose with nateglinide) • Titration frequency: day(s) to weeks
Preferred Sulfonylureas • All available as generic agents Glipizide ER 5-20 mg once per day • Once daily, flat profile, low plasma levels resulting in a low risk of weight gain and hypoglycemia Glipizide 2.5 to 20 mg twice a day • Twice daily. Half-life 2-4 hours, peaks in 2-3 hours. By taking it once a day at low dose it stimulates insulin secretion for 6-12 hours Glimepiride 1-8 mg per day • Once daily. Half-life 9 hours, peak action for 4 hours. Special utility like with glipizide but with longer half-life Buse J. Personal Opinion Melander A. Diabetes 2004;53 Suppl 3:S151
Thiazolidinediones (TZD’s or Glitazones): Pioglitazone and Rosiglitazone Mechanism of action • Enhance insulin sensitivity in muscle, adipose tissue • Inhibit hepatic gluconeogenesis • Reduced rate of beta cell dysfunction Safety and efficacy • Decrease A1C1-2% • Adverse events: edema, weight gain, anemia; rare serious risk: liver failure Dosing • Initial dose (monotherapy): 1/2 to 2/3 maximum; dosing,1-2 x/day • Maximum effective dose: maximum dose • Titration frequency: weeks to month(s)
Oral Hypoglycemics TZD Lipid Effects • Rosiglitazone(Avandia) • +LDL • +HDL • +Triglycerides • Pioglitazone (Actos) • +LDL • +HDL • -Triglycerides • Rosiglitazone – Black box warning for CHF and ischemic heart disease; warnings about increased fracture risk in women • Pioglitzaone – Black box warning for CHF and warning about increase fracture risk. No evidence to suggest increased ischemic heart disease.
AHA/ADA Consensus Statement for TZDs • Not recommended for patients with NY Heart Association class III or IV heart failure • TZDs alone, or particularly in combination with insulin, may cause fluid retention which can lead to heart failure • Incidence of CHF <1% with TZD monotherapy • Increased to 2%-3% in combination with insulin • Patients should be observed for signs and symptoms of heart failure • TZDs should be discontinued if any deterioration in cardiac status occurs Nesto RW et al. Diabetes Care 2004;27:256
Alpha-Glucosidase Inhibitors: Acarbose And Miglitol Mechanism of action • Delay absorption of carbohydrates • Depend upon postprandial hyperglycemia Safety and efficacy • Decrease A1C0.5-1% • Adverse events: flatulence; main risk: rare liver enzyme elevation Dosing • Initial dose: 1/4 maximum once daily; dosing: 3 times daily • Maximum effective dose: 1/2 maximum dose • Titration frequency: week(s) to months • Used infrequently by most clinicians
INCRETINSRole of Glucagon Like Peptide (GLP-1) in Glucose Homeostasis
Incretin Drugs Exenatide (Byetta) – GLP-1 analog • Injection twice daily • 5mcg bid AC x 1 month, then 10mcg bid AC • Beneficial effects described previously • Expensive • Weight loss • Reduction in HgBA1C Sitagliptin (Januvia)– DPP4 inhibitor • Technically not an incretin but similar effects • Oral administration • 100mg daily • Weight neutral
Key Points to Consider for Therapy Maximal benefits of metformin are observed at the recommended daily dose of 2000 mg (1 g BID)1 Thiazolidinediones should be started at low doses and slowly increased to minimize side effects2 Glucose-lowering effects of a sulfonylurea plateau at half the maximum recommended dose3 Garber AJ et al. Am J Med 1997;103:491 Nesto RW et al. Diabetes Care 2004;27:256 Stenman S et al. Ann Intern Med 1993;118:169
12.4% 37.2% >8% 7.8% 63% 7% 17.0% 25.8% 37.0% 63% Of Patients with DiabetesAre Not at ADA A1CGoal <7% Adults aged 20-74 years with previously diagnosed diabetes who participated in the interview and examination components of the National Health And Nutrition Examination Survey (NHANES), 1999-2000 A1C % of Subjects n=404 Saydah SH et al. JAMA 2004;291:335
Difficulties In AchievingTarget A1C Values • Challenges • Late diagnosis and initiation of therapy • Therapeutic inertia • Lack of effective lifestyle intervention • Secondary failure • Adverse events associated with antihyperglycemic therapies • Complexity of care • Role of postprandial glucose in failure
Common Concerns When Transitioning To Insulin • Fear of needles or pain from injections • Fear of hypoglycemia • Weight gain Funnel M. Self-management Support for Insulin Therapy in Type 2 Diabetes. The Diabetes Educator 2004;30:274
Common Concerns When Transitioning To Insulin • Adverse impact on lifestyle; inconvenient; loss of personal freedom and independence • Belief that insulin means diabetes is worse or more serious disease • Insulin as a personal failure • Insulin causes complications • Treated differently by family members Funnel M. Self-management support for insulin therapy in type 2 diabetes. The Diabetes Educator 2004;30:274
Potential Insulin Regimens • Insulin pump Physiologic/COMPLEX/Flexible • Multiple daily injections • Free mixing - twice daily • Pre-mixed - twice daily • Basal only SIMPLE/Inflexible How do we balance simplicity and flexibility to achieve glycemic control?
Indications for Insulin • Not contraindicated at anytime • Consider as initial therapy • HgbA1C > 10% • Fasting glucose > 250mg/dl • Random glucose > 300 • Recommended as initial therapy • Polyuria, polydipsia, weight loss, ketones
Insulin InitiationAnswers to Provider Concerns • Normalize the fasting glucose • Fasting FSBS 70-130 • Once Daily Options • Start 10 units or 0.2 u/kg • Basal Insulin (glargine or detemir) • NPH (bedtime) • Premixed before dinner • Increase 2-3 units every 3 days prn to reach target of 70-130 fasting • Decrease 3 units for fasting < 70
Rapid (Glulisine,Lispro, Aspart,) Long (Glargine) Insulin ActionEffect Of Various Formulations 140 120 100 Short (Regular) Insulin Level (U/ml) 80 Intermediate (NPH) 60 40 Detimir 20 0 0 2 4 8 10 12 14 16 6 Hours
Fasting Glucose at TargetHgbA1C Not at Goal • Must Normalize Post Prandial Glucose • Options • Change HS NPH to BID NPH • Change Pre-mixed Insulin from QD to BID • Add Mealtime Insulin to Basal Insulins
Monomeric Insulin Analogs • How to switch or start • Insulin immediately before the meal (or after) • Review signs, symptoms and management of hypoglycemia • Safety • Arguably, glulisine, aspart, lispro and are safer than regular human insulin • Patient preference • Significant patient preference for monomeric analog versus regular human insulin • Duration of action • Covers postprandial glucose surge well • In type 1 diabetes, will need an additional injection of basal or NPH
Carbohydrate Counting • Technique based on the concept that most meal-related glucose increase is due to the carbohydrate content • Patients count either • Carbohydrate choices (milk, fruit, breads, sweets, starchy vegetables) • Grams of “total carbohydrates” on food label • Providers prescribe insulin-to-carbohydrate ratio • Start with 1 unit per choice or 1 unit per 15 grams • Typical dose is 2-4 units per choice in type 2 diabetes • Titrate based on postprandial glucose monitoring • Generally, start with glulisine/lispro/aspart administered just after meals