-
Overweight
- -excess amount of body weight
- -may be from muscle, bone, fat, body water
BMI = 25-29.9
-
Obese
-presence of an abnormal amount or relative proportion of body fat
BMI > 30
-
BMI Calculation
BMI = weight(kg)/Height2(m)
BMI = (weight(lbs)/Height(in))703
-
Association of obesity with risk of DM2
- -overweight --> increased risk of 3-4x
- -obese --> increased risk of 18x
-
Android vs Gynoid Obesity
- Android: central abdominal (increase CV risk)
- Gynoid: hips, thighs buttocks (NO increase CV risk)
Waist to Hip ratio < 0.8 is good!
-
Waist Circumference
- male > 40 in
- female > 35 in
-
Metabolic Syndrome
- -cluster of CV risk factors associated with low cardiorespiratory fitness
- -increased lifetime risk for developing DM2 and CV disease
- Diagnosis:
- -abdominal obesity
- -hypertriglyceridemia
- -low HDL
- -HTN
- -Hyperglycemia
-
Carbs and Obesity
- -storage pool for carbs is small (glycogen in muscle)
- -excess carbs are converted to fat
-
Genes associated with obesity
- -FTO region: explains about 1% of BMI heritability
- -homozygous adults have 2-3kg higher weight
- -genetic factors are important in obesity but aren't the only factor
- -epigenetics may play a role
- -along with permissive environment
-
Obesity: Medications for Treatment
- 1. Orlistat (xenical)
- 2. Phentermine and topiramate (Qsymia)
- 3. Lorcaserin (Belviq)
-
Orlistat (xenical)
- -binds pancreatic lipase and inhibits its function
- -fats (TGs) leave intestines without being degraded
- -take with meals
- Adverse Effects
- -cramping
- -passing gas
- -leakage of oily stool
sx worse with fatty meals --> encourages healtier eating
avg weight loss = 5-7lbs
-
Qysmia
- -Phentermine: sympathomimetic amine anorectic
- -amphetamines stimulate breakdown of fat from adipocytes, increase metabolism and decrease appetite
- -Topiramate: anti-epileptic
- -appetite suppression, satiety enhancement
-avg weight loss = 12lbs
-
Lorcaserin
- -selective 5HT2CR agonist (in brain)
- -satiety enhancement
- -longer studies on CV outcomes in progress
avg weight loss = 7lbs
-
Obesity: Surgical Treatment
- 1. Restrictive (AGB, Sleeve gastrectomy)
- 2. Malabsorptive (biliopancreatic diversion, jujunoileal bypass)
- 3. Combined (gastric bypass)
-
Gastric Bypass
- PROs:
- -rapid initial weight loss (can resolve diabetes)
- CONs:
- -more operative complications
- -reduced absorption of intestinal nutrients
- -complications due to malabsorption
- -non-adjustable
- -higher mortality than AGB
-
Adjustable Gastric Band
- PROs:
- -least invasive approach
- -adjustable
- -reversible
- -lowest mortality rate
- -low malnutrition risk
- -fewer food intolerances
- CONs:
- -slower initial weight loss
- -regular F/U required
- -slips/erosions
-
Sleeve Gastrectomy
- PROs:
- -fewer food intolerances
- -faster weight loss than AGB
- -no slips/erosions
- -decreased risk vs bypass with equal weight loss
- -less intense F/U
- CONs:
- -less time tested
- -not adjustable/ non-reversible
- -slightly higher riks of complication
- -annecdotal weight gain over years
-
When to Start Medical Therapy
-BMI 27 - 29.9 with comorbidities
-BMI 30+ without comorbidities
-
When to do surgery
- AGB
- -BMI 30-34.9 with comorbidities
- Any
- -BMI 35-39.9 with comorbidities
- -BMI 40+ withoutcomorbidites
-
DM1: Epidemiology
- -relative risk in general pop = 0.3%
- -relative risk with affected sibling = 4%
- -affected mother = 3%
- -affected father = 7%
- -both affected parents = 50%
-
DM1: natural history
- 1. Genetic Predisposition
- -putative trigger (cocksackie virus, stress, environment)
- -can happen at any age
- 2. Damage to cells of pancreas
- -immune system dysfunction leads to circulating autoantibodies (ICA, GAD)
- 3. Prediabetes
- -overtime the number of viable beta cells declines
- 4. Diabetes
- -symptoms occur with onset of full diabetes
- -<20% functional beta cells
-
DM1: Autoimmune Attack
- -mainly due to autoreactive T cells (autoantibodies are markers)
- -trigger causes break in tolerance
-
ICA
- -islet cell antibodies
- -produced in early stages (2-3 years before diabetes)
- -titres go away after diagnosis
-
GAD
- -glutamic acid decarboxylase antibodies
- -titres stay elevated long term
-
DM1: Screening
- -screen immediate family members
- -screen extended family if diagnosed before 20
- -screen blood for autoantibodies
-
DM1: Prevention
-doesn't exist
- Primary: with genetic predisposition
- Secondary: after beta cell injury begins
- Tertiary: within three months of diagnosis to slow or reverse beta cell dysfunction
-
Physiologic Insulin and Amylin Delivery
- -both secreted by beta cells
- -secreted into portal vein (work within sec-min)
-
Amylin Functions
- -has CNS effects
- 1. reduces appetite
- 2. suppresses glucagon in glucose dependent manner
- 3. normalizes stomach motility
-
DM1: gastric motility
- -faster gastric and peristaltic motility
- -leads to faster absorption of nutrients
- -causes high post meal glucose
-
Basal Insulin
- (50%)
- -necessary to control hepatic glucose output independent of meals
- -nearly constant level
-
Bolus Insulin
- (50%)
- -limites hyperglycemia after meals
- -immediate rise and sharp peak at 1 hour
-
Bolus Options with pump therapy
- 1. standard (quickly absorbed foods)
- 2. square wave (gasroparesis, fatty meals)
- 3. dual wave
-
Insulin to Carb ratio calculation
start with 1:15 (DM1) or 1:10 (DM2)
-
Correction Factor
- -estimate how much blood sugar will drop with 1U of fast acting insulin
- -usually 1:50 (DM1) 1:25 (DM2)
-1800 rule (divide total daily insulin dose into 1800)
-
Latent Autoimmune Diabetes in Adults (LADA)
- -DM1 later in life
- -often misdiagnosed
- -oral meds not very effective
- -thin (don't look like DM2)
- -need insulin tx
-
______________________________________________
-
Impaired Fasting Glucose
- Normal < 100
- Prediabetes = 100-125
- Diabetes > 126
-
Impaired Glucose Tolerance
* test with OGTT
- Normal < 140
- Prediabetes = 140-199
- Diabets > 200
-
A1c value
- Normal < 5.7
- Prediabetes = 5.7-6.4
- Diabetes > 6.5
-
DM2: causes of hyperglycemia
- 1. insulin resistance (big genetic component)
- 2. defects in pancreas (decreased insulin production)
- 3. increased HGO
- 4. Adipose tissue may contribute to impaired insulin secretion
-
Insulin Sensitivity
- -ability of insulin to lower circulating glucose concentration
- -upregulate glut4 on muscle and fat
- -suppress HGO
-
DM2: Insulin Dysregulation
- -decreased production
- -impaired response (insulin resistance)
-
DM2: Glucagon Dysregulation
- -decreased postprandial suppression
- -increases postprandial HGO
- -tends to be elevated
- -increases after meal (vs normal, declines)
-
DM2: Incretin Dysregulation
- -decreased production
- -impaired response
- -not in all patients
-
DM2: Insulin profile overtime
- -early see hypersecretory response
- -disease progression to the point where insulin can no longer stay high
-
DM2: Insulin Secretion Phases
- 1. Quick Peak (release of Pre-formed)
- 2. Second peak (long)
DM2 lacks first phase and second phase is blunted
*** insulin levels never 0, vs DM1
-
DM2: Natural History
 - -post prandial glucose levels rise earlier than fasting glucose levels
- -in prediabetes insulin resistance progressively increases but diabetes doesn't develop right away b/c beta cells produce more insulin
- -at time of diagnosis beta cell function starts to decline
-
DM2: Incretin Effect
- -insulin secretion greater with oral glucose than IV glucose
- -due to L cell secretion of incretins
- -impaired in DM2
-
GLP1
- -stimulates glucose dependent insulin secretion
- -slows accelerated gastric emptying
- -associated with satiety and weight loss
- -inhibits excessive glucagon
more important in DM2 that GIP
-
GIP
- -stimulates glucose dependent insulin secretion
- -little effect on gastric motility, satiety and glucagon secretion
-
DM2: GLP1 analogs
- -improves glycemic control
- -can normalize PP glucose (w/o hypoglycemia)
- -delays gastric emptying
- -decreases food intake and reduces appetite
-
Metabolism of GLP1 and GIP
-rapidly cleaved by DPP4
-
DM2: adipose accumulation
- -weak association with subcutaneous adipose tissue
- -strong association with visceral adipose tissue
-
DM2: Adisopathy
- -insulin resistance
- -ectopic lipid accumulation in liver/muscle/beta cells
- -failure to expand adipose tissue during positive energy balance
-
DM2: Insulin Secretagogues
- 1. Sulfonylureas
- -Glyburide
- -Glimiperide
- -Glipizide
- 2. Meglitinides
- -repaglinide
- -nateglinide
- 3. Incretins
- -GLP1 agonists (Exenatide, Liraglutide)
- -DPP4 inhibitor (Sitagliptin, Saxagliptin, Linagliptin)
-
Sulfonylureas
- PROs:
- -increase insulin secretion
- -effective glucose lowering
- CONs:
- -hypoglycemia
- -weight gain
- -secondary failure
-
Meglitinides
- PROs:
- -increase insulin secretion
- -effective glucose lowering
- CONs:
- -hypoglycemia
- -weight gain
- -secondary failure
-
Incretins
- PROs:
- -glucose-mediated insulin release
- -effective glucose lowering
- -no hypoglycemia
- -decreased gastric emptying
- -decreased appetite (weight loss)
- -trophic effects on beta cell
- -possible beneficial CV effects
- CONs:
- -nausea/vomiting
- -pancreatitis
- -thyroid cancer
-
DM2: Insulin Sensitizers
- 2. Thiazolidinediones
- -Rosiglitazone
- -Pioglitazone
-
Biguanides
- PROs:
- -effective glucose lowering
- -no hypoglycemia
- -weight loss
- -possible beneficial CV effects
- CONs:
- -diarrhea, abdominal pain
- -caution in renal disease (lactic acidosis)
- -caution in CHF
- -secondary failure
-
Thiazolidinediones
- PROs:
- -effective glucose lowering
- -no hypoglycemia
- -May have trophic effects on beta cells
- CONs:
- -weight gain (expands subcu fat)
- -pedal edema
- -caution in CHF
- -CV effects
- -Bone loss
- -Bladder tumors
NOT FREQUENTLY USED
-
DM2: Other Agents
- 1. a-glucosidase inhibitors
- -acarbose
- -miglitol
- 2. bile acid sequestrants
- -colesevelam
- 4. Amylin analog
- -Parmlintide
-
a-glucosidase inhibitors
-carb blockers (prevent glucose absorption)
- PROs:
- -no hypoglycemia
- -weight neutral
- CONs:
- -less glucose lowering
- -gas
- -caution in LV disease
-
Bile Acid Sequestrants
-lower XOL
- PROs:
- -no hypoglycemia
- -weight neutral
- -XOL lowering
- CONs:
- -less glucose lowering
- -constipation
-
DA Agonists
-acts on circadian rhythm (small effects on A1c)
- PROs:
- -no hypoglycemia
- -weight neutral
- CONs:
- -less glucose lowering
- -nausea
- -hypotension
-
Amylin Analog
- PROs:
- -decreases postprandial glucose
- -weight loss
- CONs:
- -less glucose lowering
- -GI side effects
-
DM2: Starting basal insulin
- -continue oral agents
- -add single evening insulin dose
- -adjust dose by fasting SMBG
- -increase insulin dose weekly as needed
|
|