How many diabetes cases are type 2?
> 90%
Characteristics of DM type 2?
Characterized by hyperglycemia and varying degrees of insulin deficiency and resistance
Micro- and macrovascular complications
What is impaired glucose tolerance?
during an OGTT, blood glucose values are between normal and overt diabetes (140-199 mg/dL)
What glucose level is considered impaired fasting glucose?
fasting BS 100-125
What is pre diabetes?
increased risk for DM
IGT or IFG or A1c of 5.7-6-4%
% of ppl who have DM but are not diagnosed?
25-40%
Risk factors for DM?
Genetic
Anthropometric factors (BMI, waist circumference)
Environmental/lifestyle factors
- physical inactivity
- smoking
- diet
- meds
What drugs can impair glucose tolerance?
LOTS
Fluroquinolones
Thiazide diuretics *
glucocorticoids
oral contraceptives
What comorbidities put pts at increased risk for development of DM?
Prediabetes
Gestational diabetes
CV disease (HF, MI, HTN)
Dyslipidemia
Hyperuricemia
PCOS
Metabolic syndrome
Metabolic syndrome is also known as…
Insulin resistance syndrome or syndrome X
Definition of metabolic syndrome?
Abdominal obesity
Measured by waist circumference
(≥ 102 cm (40 inches) in men
≥ 88 cm (35 inches) in women)
Triglycerides ≥ 150
Low HDL
(< 40 mg/dL in men
< 50 mg/dL in women)
Blood pressure ≥ 130/85 mmHg
FPG ≥ 100 mg/dL
Metabolic syndrome increases with…
age
also higher prevalence with overweight/obese
How common is metabolic syndrome?
22% in US
Management goals for metabolic syndrome?
Treat underlying causes
Treat CVD risk factors
What should be included in tx of metabolic syndrome?
aggressive lifestyle modification
weight reduction
increases physical activity
reduction of other risk factors
pharm options
Weight loss goal for pts with metabolic syndrome?
Goal of 7-10% reduction in body weight within 1 year
How much physical activity should you recommend for a patient with metabolic syndrome?
150 min/wk
Where do we get blood glucose from?
diet
gluconeogenesis
glucogeneolysis of liver glycogen
How is glucose regulated?
Glucose homeostasis requires hepatic glucose production to be balanced with peripheral glucose uptake and utilization
Insulin produced by beta cells –> causes glucose transport into adipose tissue and muscle
Glucagon produced by alpha cells –> stimulates glycogenolysis and gluconeogenesis
What regulates insulin secretion?
glucose
also influenced by amino acids, ketones, various nutrients, GI peptides, & neurotransmitters
Insulin/glucagon levels during fasting state?
during postprandial state?
low insulin, high glucagon
high insulin, low glucagon
How does the body compensate when there is insulin resistance? What does this eventually lead to?
beta cells compensate by increasing insulin
–> impaired glucose tolerance (beta cells can’t keep up)
–> overt diabetes (fasting hyperglycemia, beta cell failure)
Describe insulin resistance
decreased ability of insulin to act effectively on target tissues
impairs glucose utilization by insulin sensitive tissues
Describe impaired insulin secretion
in response to insulin resistance insulin secretion is initially increased >
beta cell failure >
chronic hyperglycemia impairs islet func., >
reduced insulin secretion
Why is there excessive hepatic glucose production in DM?
insulin resistance in the liver results in failure of hyperinsulinemia to suppress gluconeogenesis
Why is there abn. fat metabolism in DM?
Insulin resistance in adipose tissue > increased liplysis and free fatty acid flux from adipocytes causing increased VLDL & TG synthesis in liver
lipid storage in liver > NAFLD and dyslipidemia
Clinical presentation of DM?
Usually asymptomatic
Hyperglycemia on routine labs
Symptoms of hyperglycemia:
- Polyuria
- Polydipsia
- Nocturia
- Blurred vision
- Weight loss
ADA screening recommendation for DM?
All adults with BMI ≥ 25 + additional risk factor(s) q 3 years
Start at age 45 if no risk factors
Screen patients with prediabetes annually
Women with GDM should be screened q 3 years
USPSTF screening recommendations for DM?
Adults aged 40-70 y/o who are overweight or obese should be screened as a part of CV risk assessment q 3 years
Diagnostic criteria for DM?
sxs + random blood glucose > 200
If asxs
- FPG >126
- 2 hour glucose >200 during OGTT
- A1C >6.5
repeat on different day
Normal 2 hour glucose during OGTT? normal FPG?
<140mg/dL
<100
IFG?
IGT?
100-125 mg/dl
2 hr glucose during OGTT between 140-199
Glucated hemoglobin (A1c) correlates with?
what can effect this?
mean glucose concentration and DM complication
RBC turnover
-low cell turnover: false high
-high cell turnover: false low
Hemoglobinopathy, CKD
What should you eval for in a DM pt?
Assess nutrition, weight, physical activity
Assess CV risk
Evaluate for diabetes related comps
Inquire about hypoglycemic episodes
What labs should you check regularly in a DM pt?
A1c
Fasting lipids
Liver enyzmes
Urine albumin excretion
Serum creatinine
What should be included in annual DM visit?
vitals
orthostatic BP
fundoscopic exam
thyroid palpation
skin exam
comprehensive foot exam
What labs should you check annually in pt with DM?
A1c
lipid panel
LFTs
urine albumin-Cr ratio
TSH (type 1 DM)
+/- Vit B12
Serum K in pt on ACE/ARB or diuretics
What is included in management of DM?
glycemic control: pharm/nonpharm
monitoring/prevent comps
Pt education
health maintenance
What kind of pt education should you give to DM pt?
nutrition
hypoglucemia
CV risk
vision
kidneys
Target A1c for DM?
individualized based on pt
most: <7.0%
more stringent
less stringent: hx severe hypoglycemia, limit life expectancy, older pts, comorbid conditions
How freq. should you monitor A1c?
at least 2x/yr in controlled, quarterly in pts with changes in therapy or not meeting goals
What else should be included in management for DM type 2?
self monitor blood glucose, more often when titrating medications assoc. with hypoglycemia
several times per wk
more freq. with illness/change in diet/exercise
Nonpharm therapy for DM type 2?
diet
exercise
weight reduction
psychological interventions
diabetes education
goals of pharm therapy for DM type 2?
Increase insulin availability
Improve sensitivity to insulin
Delay delivery and absorption of carbohydrates from the GI tract
Increase urinary glucose excretion
A1c of …..at rx you should start Rx.
A1c of ….at dx, you can start with 3-6 months of lifestyle modifications
> 7.5-8%
<7.5
Initial pharm therapy for DM type 2?
Metformin for most pts
Insulin is an alternative
What are the classes of drugs that can be used for tx of DM type 2?
Metformin
Sulfonylureas
GLP-1 receptor agonist
Dipeptidyl peptidase-4 inhibitors (DPP-4)
Sodium-glucose co-transporter 2 (SGLT2) inhibitor
Thiazolidinediones (TZD)
Meglitinides
Alpha-glucosidase inhibitor
Insulin
Drug class for Metformin? MOA?
Biguanide
Decrease hepatic glucose output by inhibiting gluconeogenesis
Increases insulin-mediated glucose utilization in peripheral tissues (muscle, liver)
1st line drug tx for DM?
METFORMIN
1-2% drop in A1c
weight neutral
ADE of Metformin?
GI sxs
can reduce intestinal absorption of vit B12
Contraindications for Metformin?
renal insufficiency
IV contrast concerns
MOA of sulfonylureas? effect?
Stimulate insulin secretion from pancreatic beta cells
1-2% decrease in A1c
ADEs of sulfonylureas?
risk of hypoglycemia
weight gain
Examples of Sulfonylureas?
Glipizide (Glucotrol)
Glyburide (Diabeta, Glynase)
Glimepiride (Amaryl)
MOA of GLP- 1 agonists?
GLP-1 stimulates glucose dependent insulin release from pancreatic islet cells
GLP-1 slows gastric emptying
GLP-1 inhibits post-meal glucagon release
Incretin effect of GLP-1 agonists?
oral glucose better stimulates insulin secretion than IV glucose secondary To GI peptides (GLP-1) released in response to a meal stimulating insulin synthesis and secretion
How is GLP-1 agonist typically prescribed?
as an add on therapy (to Metformin)
0.5-1% drop in A1c
weight loss
ADEs of GlP-1 agonists?
Possible improved cardiovascular outcomes with liraglutide and semaglutide
GI side effects: N/V/D (10-50%)
Examples of GLP-1 agonists?
Exenatide (Bydureon, Byetta)
Liraglutide (Victoza)
Dulaglutide (Trulicity) etc.
MOA of DPP-4 inhibitors ?
GLP-1 secreted in response to nutrients >
GLP-1 stimulates glucose dependent insulin release from pancreatic islet cells
GLP-1 slows gastric emptying
GLP-1 inhibits post-meal glucagon release
DPP-4 is an enzyme that deactivates GLP-1
How is DPP-4 inhibitors usually prescribed? effect on weight?
usually add on therapy
0.5-.8 drop in A1c
weight neutral
Examples of DPP-4 inhibitors?
Sitagliptan (Januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Alogliptin (Nesina)
MOA of SGLT2 inhibitor? effect on A1c?
SGLT2 inhibitors increase urinary glucose excretion leading to reduced blood glucose
0.5-0.7% decrease in A1c
usually add on therapy, Weight loss, reduced BP, possible reduced CV mortality
ADEs of SGLT2 inhibitors?
vulvovaginal candidiasis, UTIs
Examples of SGLT2 inhibitors?
Empagliflozin (Jardiance)
Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
MOA of TZDs?
Improve insulin action
Increase insulin
sensitivity by acting on adipose, muscle, and liver to increase glucose utilization and decrease glucose production
effect of TZDs?
usually used as add on therapy
0.5-1.4% drop in A1c
ADEs of TZDs?
Fluid retention, HF, weight gain, bone fractures, possible increase in MI (rosiglitazone), possible increase in bladder cancer (pioglitazone)
Contraindications for TZDs?
symptomatic or class III-IV HF, bladder cancer, high fracture risk, liver disease
Examples of TZDs?
Pioglitazone (Actos)*preferred
Rosiglitazone (Avandia)
MOA of Meglitinides? effect?
Stimulate insulin secretion from pancreatic beta cells
Add on therapy
0.5-1% decrease in A1c
Admin of Meglitinides?
take with meals to reduce postprandial hyperglycemia
ADEs of Meglitinides?
hypoglycemia
weight gain
Examples of Meglitinides?
Nateglinide (Starlix)
Repaglinide (Prandin)
MOA of alpha glucosidase Inhibitors?
decrease absorption of glucose
0.5-.8 % decrease
weight neutral
give with food
ADEs of Alpha glucosidase inhibitors?
flatulence and diarrhea
Examples of alpha glucosidase inhibitors?
Acarbose (Precose)
Miglitol (Glyset)
Options for insulin therapy?
Basal therapy: NPH, Glargine, Detemir, Degludec
Intensive insulin therapy
ADEs of insulin?
weight gain
hypoglycemia
Examples of Prandial insulin?
Short-acting: Regular (Humilin R, Novolin R)
Rapid-acting: lispro (Admelog, Humalog), aspart (Fiasp, Novolog), glulisine (Apidra)
When should you considered dual therapy for T2DM?
When should you considered combo injectable therapy?
if A1c grater than or equal to 9%?
A1c greater than or equal to 10%, blood glucose >300 or pt very sxs
What are some microvascular diseases that may be complications of T2DM?
what about macrovascular diseases?
Retinopathy
Nephropathy
Neuropathy
Atherosclerosis (MI, CVA)
-these may be present at dx
MCC of blindness in adults 20-74 yo?
diabetic retinopathy
Chronic hyperglycemia causes vascular changes leading to retinal injury and ischemia
Why is there vision loss in diabetic retinopathy?
Macular edema
Hemorrhage from new vessels
Retinal detachment
Neovascular glaucoma
Presentation of diabetic retinopathy?
asxs until late stages
Screening for diabetic retinopathy?
dilated and comprehensive eye exam by ophtho or optometrist
at time of dx in type 2, within 5 yrs of type 1
repeat annually
Treatment for diabetic retinopathy?
laser therapy- photocoagulation
Intravitreous injections of anti-vascular endothelial growth factor (ranibizumab)
Vitrectomy
How can we prevent diabetic retinopathy?
glycemic control
control BP
How can we screen for diabetic kidney disease?
assess urinary albumin
Assess eGFR
time of diagnosis in T2DM
Within 5 years of diagnosis in T1DM
In all patients with comorbid HTN
Repeat annually
Dx for diabetic kidney disease?
mod increased albuminuria (mircoalbuminuria)
- 30-300/day
- > 300 = severe
requires 2 of 3 specimens abn. over 3-6 months
Tx for diabetic kidney disease?
ACE/ARB
Protein Intake
- Non dialysis: 0.8
- dialysis: higher levels
refere for renal replacement tx
How can we prevent diabetic kidney disease?
optimize glucose control
optimize BP control
Presentation of diabetic neuropathy?
up to 50% asxs
foot ulcers and amputation common
dx of exclusion
other risk factors for ulcers/amputations?
smoking
foot deformities
pre-ulcerative callus/corn
PAD
visual impairment
DKD
Screening for diabetic neuropathy?
Assess with hx + temp/pinprick sensation/vibration sensation
annual monofilament testing
At time of dx of T2DM, within 5 yrs for T1DM
repeat annually
How can we prevent diabetic neuropathy?
optimize glucose control
Tx for diabetic neuropathy?
1st line: Pregabalin or Duloxetine
foot self care education
specialized footwear for high risk pts
Foot care for diabetic neuropathy?
comprehensive foot eval annually
Consider ABI and/or vascular referral for symptoms of claudication or decreased or absent pedal pulses
Consider podiatry for smokers or hx of prior LE complications, loss of protective sensation, structural abnormalities, or PAD
If a pt with DM and HTN has albuminuria, which kind of antihypertensive should they be placed on?
ACE or ARB
Anti platelet recommendations for T2DM pts?
ASA as secondary prevention
Clopidogrel if ASA allergy
Routine health maintenance in pts with T2DM?
flu vaccine annually
Pneumococcal vaccination
HBV to unvaccinated adults age 19-59
Update tetanus and diphtheria
Reproductive counseling
Indicated screenings