Pathology of Diabetes:

- Type I: lack of insulin- beta cells in pancreas dont produce

o Sudden onset
o Ketoacidosis common
- Type II: have insulin but cells dont respond to it
o Gradual onset
- Risk factors:
o Family history
o Overweight/obesity
o Metabolic syndrome
o Sedentary lifestyle
o Ethnicity
o Poverty
o Aging
o Smoking
o Hx. of gestational diabetes
- Regulation of insulin secretion:
o Stimulated in pancreas when beta cells sense high glucose concentrationssent
out to uptake glucose for storage
- Glucose lowering effects of Insulin
o Liver: inhibits hepatic glucose production
Stimulates hepatic glucose uptake
o Muscle: stimulates glucose uptake
Inhibits flow of gluconogenic precursors to the liver
o Adipose tissue: stimulates glucose uptake
- HbA1c- Glycosyalated HemoglobinCritical biomarker for glucose control
o Reflects the overall efficacy of diet, exercise, rx. On glycemic control
o Doesnt reflect acute day to day changes
- Pre-Diabetes
o Fasting glucose >100 to <125 mg/dL
o At risk for CVD and T2DM
o To have a diagnosis have to have at least 3 of the following
Central adiposity
Elevated BP
Elevated triglycerides in blood
Elevated cholesterol in blood
Fasting glucose >100 mg/dL
- Role of kidney in glucose metabolism
o Production/gluconeogenesis
o Uptake/utilization
 o Reabsorption
- Acute complications:
o Diabetic ketoacidosisroot cause = no insulin
- Chronic complications:
o CV disease
Stroke, hypertension, heart attack, dyslipidemia
o Retinopathy
o Nephropathy
o Neuropathy
o Impaired wound healing

Management of Diabetes:

Exercise:

- Insulin dependent pathway

o Stimulates glucose uptake by skeletal muscle
o Can increase up to 50-fold during bouts of exercise
o Improves insulin sensitivity up to 48 hours after exercise
- remodels adipose tissue and improves whole-body metabolism
o Brown adipose tissue has more mitochondria = burns energy, improves whole-
body metabolism
- Type I diabetics
o Greater risk for hypoglycemia
o Increased risk for ketoacidosis
Glycogen regulation is not working properlly
o Need to monitor sugar before and after exercise
o Exercise alters blood flow and may alter insulin absorption (gets absorbed more
quickly and can lead to hypoglycemia)
o Injuries due to peripheral neuropathy
- Management of Insulin (type I)
o Insulin cannot be taken orally d/t degradation in the GI tract (polypeptide)
needs to be taken as an injection
o Rapid and short acting
Most flexibility
Most often at mealtime
o Intermediate and long acting
o Continuous insulin infusion pump- best mimics physiological insulin activity
Careful monitoring needed
o Most common adverse effect = hypoglycemia
- Management of type II diabetes
o Protect the pancreatic beta cell as long as you can
 o If you can maintain the pancreas they dont have to go on insulin
o Metformin = first line therapy for Type II and prediabetes
Liver concentrates it
Not metabolized (exerted when you go to the bathroom)
Hepatic glucose output (dysregulated/reduced in diabetes)metformin
regulates the output to more normal levels
Requires insulin for efficacy but doesnt impact insulin secretion--Doesnt
affect the pancreas so you dont have a risk of hypoglycemia
Slows glucose absoption from GI tract
Clinical advantages
Inexpensive, safe, specific reduction in hepatic glucose output,
improvement in peripheral insulin sensitivity
o Sulfonylureas
Make beta cell push out more insulin in pancreas
Not coupled to glucose
Can have hypoglycemia, can burn out the pancreas
Less expensive
o Thiazolidinediones
Most powerful insulin sensitizers
Dont cause insulin secretion but cause muscle/cell/liver to be
more sensitive to insulin
A lot of side effects: weight gain, edema, liver toxicity, CV complications
Only used for severely insulin-resistant pt.
o Incretin therapies
Counter the incretin effect-- Incretin hormones released by your gut are
reduced
Increase insulin secretion, decreases glucagon, decreased appetite/ fatty
liver
o Medications that regulate kidneys
Can be used before metformin
Safe/dont need insulin
Excreting glucose in the urine
- Medications for the treatment of Obesity
o Lipase Inhibitors
Orlistat/Xenical (only reasonably safe obesity drug in the market)
inhibitor of gastroc and pancreatic lipases
o Serotonin Agonists
Lorcaserin/Belviq
o Anorexiant/Stimulants
Phentermine/ADIPEX-Ptargeting the brain
o Combination Therapies
 Phentermine+Topiramate/QsmiaCV side effects/short term use
targeting the brain
Bupropion + Naltrexone/Contrave
- Diabetes Management in elderly patients
o Challenges
Cognitive impairment
Depression/suicide/social isolation
Amputation
Decreased pain threshold
Functional impairment
Falls
Dehydration (reduced thirst perception)
Incontinence, tuberculosis and hypogonadism
- Mental Health Implications of Diabetes
o Mood spectrum disorders (schizophrenia, bipolar, depression, PTSD, anxiety)4x
more likely to have diabetes
o Atypical antipsychotic medicationscan have adverse side effects
Significant off label usagecan result in metabolic disease, diabetes,
osteoporosis