Term
| Pathophysiology: DM Type 1 |
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Definition
• Autoimmune destruction of B cells
• Viral infection thought to stimulate antibody production against viral proteins trigger autoimmune response against beta cells |
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Term
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Definition
• Absolute insulin deficiency
• Most common antibody: anti-GAD |
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Term
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Definition
- Increased rates in presence of other autoimmune diseases
- Genetic predisposition: • HLA polymorphisms
- Environmental risk factors (conflicting evidence)
• Viral triggers (enterovirus) • Obesity
• Vitamin D deficiency
• Advanced maternal age |
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Term
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Definition
• Relative insulin deficiency
• Initial beta cell function is maintained, insulin resistance is present |
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Term
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Definition
| >45, physically active<3x/week, family hx of type 2 diabetes, high BP, hgx of gestational diabetes, overweight |
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Term
| Metabolic Syndrome: 3 or more of 5 |
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Definition
• Waist circumference >40 inches men, >35 in women • BP >130/85 mmHg
• Fasting triglyceride >150 mg/dL
• FastingHDL<40mg/dLmen,<50mg/dLwomen
• Fasting blood sugar >100 mg/dL |
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Term
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Definition
absolute insulin deficiency
• Autoimmune destruction of pancreatic beta cells
• 5–10% of all adult DM
• 66% of all youth DM
• 25% present with DKA |
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Term
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Definition
relative insulin deficiency
• Insulin resistance and eventual deficiency • More insidious onset |
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Term
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Definition
• DM1:
• No gender differences
• Despite autoimmune conditions >in females
• Incidence is rising in all groups
• Highest rates in non-Hispanic whites
• DM2:
• Prevalence in U.S. >12% (and growing) • Highest in AI/AN (15.9%) |
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Term
| Symptoms of hyperglycemia |
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Definition
• Polyuria
• Polydipsia
- Increased serum osmolality
• Weight loss
- Hypovolemia and increased catabolism
• Blurry vision
• Fatigue
• Nocturia |
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Term
| Clinical Presentation: Type 1 |
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Definition
• 25% of adults present with DKA
• Rapid onset of symptoms
- Adults slightly slower than youth
• Frequently present to clinic with very vague complaints |
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Term
| Maturity onset diabetes of the young (MODY) |
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Definition
| Dominant inherited form of diabetes |
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Term
| Latent autoimmune diabetes in adults (LADA) |
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Definition
| DM2->autoantibodies present->insulin therapy |
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Term
| Diagnose diabetes if any one of the following: |
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Definition
• A1C ≥6.5%
• FPG ≥126 mg/dL
• OGTT 2 hour plasma glucose ≥200 mg/dL • 75g glucose load, test two hours later
• Random plasma glucose ≥200 mg/dL in patient with symptoms |
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Term
| Diagnose prediabetes if any one of the following: |
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Definition
• A1C 5.7–6.4%
• FPG 100–125 mg/dL
• OGTT 2 hour plasma glucose 140–199 mg/dL • 75 g glucose load, test two hours later |
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Term
Who Do We Test?
• Anyone with symptoms of hyperglycemia • And: |
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Definition
| as part of CV risk assessment in age 40-70 in overweight and obese adults |
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Term
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Definition
- Usually clear by presentation
- If think type 2, consider screening for anti- GAD antibodies if:
• <50 years of age at onset
• BMI <25
• Personal or family history of autoimmune disease
- Type 1: anit-GAD antibodies, islet cell, insulin, tyrosine phosphatases, zinc transporter present |
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Term
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Definition
| pos for autoantibodies, clear genetic linkages to HLA, very low levels of C-peptides |
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Term
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Definition
| usually neg for autoantibodies, no linkage to HLA, normal levels of C-peptides |
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Term
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Definition
| pos for autoantibodies, some linkage to HLA, low levels of c-peptides |
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Term
| preproinsulin->proinsulin-> |
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Definition
| mature insulin and C peptide |
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Term
| Target A1C is tailored to the individual: |
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Definition
• A1C<6
• Someduringpregnancy
• A1C<7
• Typicaladults
• A1C<8
• Olderadults,comorbidities,limitedlifeexpectancy,recurrent hypoglycemic events |
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Term
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Definition
• Lispro (rapid)
• Aspart (rapid)
• Glulisine (rapid)
• Regular (short) |
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Term
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Definition
• NPH (intermediate)
• Detemir (long)
• Glargine (long) |
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Term
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Definition
| Lispro, Aspart, Glulisine |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
| Type 1: Management Basics |
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Definition
• Insulin is required
• Combination of basal and bolus doses
- Multiple daily injections (MDI)
- Continuous subcutaneous insulin infusion (CSII)
• Bolus amount?
- Premeal blood glucose
- Meal size and composition
- Anticipated activity level
• Previous approach: twice-daily injections of mixed short and intermediate (NPH) insulins
• Current approach: physiologic insulin replacement |
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Term
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Definition
• Glargine (long acting) given once daily with lispro (rapid acting) premeal
- Glargine administration before breakfast
- Glargine administration bid
• Detemir and NPH require injections bid
- NPH: 2/3 am and 1/3 pm
• Rapid-acting insulin analogs are typically preferred over regular insulin |
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Term
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Definition
- Ideal: 4–7 times daily
• Before breakfast
• Midmorning
• Before lunch
• Midafternoon
• Before evening meal
• Before bedtime
• Middle of night
• Before or after exercise
- ADA goals:
• Preprandial: 80–130 mg/dL
• 2 hrs postprandial: <180 mg/dL |
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Term
| How Much Insulin Do We Give? |
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Definition
Start:
• Total daily dose (TDD) 0.2–0.4 units/kg/day • Usually need 0.6–0.7 units/kg/day
Breakdown:
• 40–50% given as basal
• 50–60% given divided premeals
• 220lbs->100kg
• Total:
• 100kg * 0.4 units/kg/day->40 units/day
• Basal:
• 40 units/day * 0.4->16 units
• Prandial:
• 40 units/day * 0.6->24 units
• Divided between three meals (8 units/meal) |
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Term
| Example premeal insulin correction dose (sliding scale) |
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Definition
1. 1800/total daily dose
1. 1800/40units=45pointdropperunitinsulin
2. Bolus (8 units) + correction amount
1. 45 to 90: subtract 1 unit from bolus
2. 91to135:add0unitstobolus
3. 136to180:add1unittobolus
4. 181to225:add2unitstobolus
5. 126to270:add3unitstobolus
6. Etc. |
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Term
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Definition
- Manage the ABC’s
• A1C
• Blood pressure
• Cholesterol (LDLs)
- Exercise
- Nutrition counseling |
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Term
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Definition
Target A1C is tailored to the individual
• A1C<6
• Someduringpregnancy
• A1C<7
• Typicaladults
• A1C<8
• Olderadults,comorbidities,limitedlifeexpectancy,recurrent hypoglycemic events
• A1C reduction linked to improved microvascular complications
• Less evidence to support macrovascular risk |
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Term
Type 2: Management Approach
• Initiate medication if: |
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Definition
• A1C <7.5 can start with lifestyle modification
- Highly motivated
- Must reassess 3–6 months
• A1C >7.5 begin oral medications • A1C >9 consider insulin |
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Term
| Set A1C Target for the Newly Diagnosed Type 2 Diabetic Patient |
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Definition
Stage 1- lifestyle intervention +/- metformin- A1c>/=7.5% consider combination therapy. A1c>/= 9 consider insulin. Stage 2: HbA1c not at target (3-6 mo): BMI<30- DPP-4 inhibitor (Consider GBP-1). 35>BMI>30- GLP-1 and DPP-4 inhibitors. BMI>35- GLP-1, consider bariatric surgery in nonresponders
Stage 3: HbA1c not at target (3-6 mo)- high post prandial- SU/Glinides-pioglitazone- rapid/mix insulin. High fasting glucose- basal insulin (consider ploglitazone) |
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Term
| Common Diabetes Medications |
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Definition
Class and common meds:
Biguanides- Metformin
Sulfonylureas- Glyburide, Glipizide
Thiazolidinediones (TZDs)- Pioglitazone, Rosiglitazone
Meglitinides- Repaglinide, Nateglinide
alpha-glucosidase inhibitors- Acarbose, Miglitol
DPP-4 inhibitors- Sitagliptin, Saxagliptin
Incretin mimetics- Exenatide
-don't forget ACT/ARB for renal protection |
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Term
| Hyperglycemia insulin secretion acting drugs |
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Definition
| inc'd by Sulfonylureas Meglitinides Incretins |
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Term
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Definition
| Incretins α glucosidase inhibitors Amylin Bile acid sequestrant |
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Term
| hyperglycemia hepatic glucose output drugs |
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Definition
| dec'd by Metformin, Thiazolidinediones |
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Term
| Hyperglycemia Lipotoxicity drugs |
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Definition
| Thiazolidinediones, Salicylates |
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Term
| Hyperglycemia glucagon secretion drugs |
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Definition
| dec'd by incretins, amylin |
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Term
| Hyperglycemia appetite control drugs |
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Definition
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Term
| Hyperglycemia glucose reabsorption drugs |
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Definition
| dec'd by SGLT2 inhibitors |
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Term
| hyperglycemia and glucose uptake and utilization drugs |
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Definition
| inc'd by Thiazolidinediones and Metformin |
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Term
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Definition
500mg PO with dinner
• If tolerated: 500mg PO bid->1000mg PO bid |
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Term
| Type 2: Lifestyle Modifications |
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Definition
• Exercise
• Nutrition counseling
• Weight reduction |
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Term
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Definition
| • Blood glucose <70 mg/dL |
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Term
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Definition
| sleepiness, sweating, pallor, lack of coordination, irritability, hunger |
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Term
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Definition
| dry mouth, increased thirst, blurred vision, weakness, headache, frequent urination |
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Term
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Definition
• Blood glucose testing at time of symptoms
• If no prior DM confirmed: glucose, insulin, c-peptide
If suspected->treat |
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Term
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Definition
- If able to swallow safely:
• 51–70: 10–15 g fast-acting carbohydrate
• ≤50 mg/dL: 20–30 g fast-acting carbohydrate
• Recheck 15 minutes
- If AMS, unable to swallow:
• IV bolus 12.5–25 g glucose • Glucagon 1 mg IM
Varied by cause and response |
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Term
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Definition
- Common if twice daily mixed short-acting and NPH insulin
- Reduction of incidence with:
• Morning: mixed
• Dinner: short acting
• Bed: NPH |
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Term
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Definition
• Serious complication
• Fear often not expressed by patients
• Possible barrier to tight glycemic control |
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Term
| Type 1: Diabetic Ketoacidosis (DKA) |
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Definition
• Metabolic acidosis present
• Serum glucose concentration typically 350– 500mg/dL
• Evolves rapidly, over 24 hours
• Present with hyperventilation, nausea, abdominal pain, vomiting, volume depletion, tachycardia, hypotension, fruity breath |
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Term
| Type 2: Hyperosmolar Hypoglycemic State (HHS) |
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Definition
• No keto acid accumulation
• Glucose frequently exceeds 1000mg/dL
• Coma present in 25–50% of cases
• Evolves slowly
- Polyuria, polydipsia, and weight loss for days
- Neurological symptoms more common • AMS, coma
- Volume depletion |
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Term
| Hyperosmolar Hypoglycemic State (HHS) Management |
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Definition
• IV isotonic saline (rapidly)
• Once volume restored and Na+ normal one-half isotonic saline
• Glucose reaches approximately 200mg/dL -> add dextrose to saline
• K+, insulin, and sodium bicarbonate
- Amount and frequency will vary based on labs
- UpToDate is a great resource for specifics |
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Term
| Diabetes: Chronic Complications |
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Definition
| Retinopathy, Microvascular Disease, Nephropathy, Neuropathy |
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Term
| Type 1: Chronic Complications |
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Definition
Retinopathy
• Most common
microvascular
complication
• Refer for annual eye exams!
Nephropathy:
• Most common cause of renal failure in the U.S.
• ACE inhibitors and ARBs are renal protective
Neuropathy:
• Stocking-glove distribution
• Improvement with risk reduction (hypertriglyceridemia, obesity, smoking, hypertension)
• Contributes to diabetic foot disease
Macrovascular disease:
• Increased risk of atherosclerosis
• CHD equivalent for hypercholesterolemia • Rates have decreased over past 50 years • Increased risk of MI, CVA, PVD |
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Term
| Diabetic Retinopathy fundoscopic exam |
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Definition
-hemorrhages
-abnormal growth of blood vessels
-aneurysm
-"cotton wool" spots
-hard exudates |
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Term
| microvascular v macrovascular complications of diabetes |
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Definition
microvascular- eye, kidney, neuropathy
macrovascular- brain, heart extremities |
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