Post on 03-Jan-2016
transcript
EX PLAINS
•Exogenous InsulinBasal:
Lantus
Levemir
NPH
BolusNovolgHumologApidraRegular
Exubera(inhaled Insulin)
explains
• Insulin Resistance:• Most common reason for hypoglycemia• Overweight, family history of DM• Mainly postprandial:after meal ,peak in
insulin secretion led to hypoglymia• Labs: high insulin level,possible
hyperglycemia• TX: Metformin, TZD , precose, Glyset
Insulinomas
• Incidence: 0.4/100.000
• Median age: 47 years (8-82), 59% females
• Clinical Features:– Fasting hypoglycemia, but can also present
as post-prandial hypoglycemia– 20% of patients misdiagnosed with a
neurologic or psychiatric disorder
Insulinomas
– Weight gain has been described in 18% of patients
– Median duration of symptoms before diagnosis is less than 1.5 years
• Tumor distribution:– 87% single benign tumor– 7% multiple benign tumors– 6% malignant insulinoma (77% males, median
age 48 years)
Insulinomas
• MEN-I:– 8% of inulinomas have MEN-I – median age 25 years– 53% females– All have primary hyperparathyroidism, few
have prolactinomas, gastrinomas or Cushing’s– 59% have multiple islet cell tumors
Insulinomas (diagnosis)
• Blood glucose<45 mg/dl
• Insulin level > 6 mcu/ml (RIA) or 3 mcu/ml (ICMA)
• C-Peptide > 200 pmol/l (0.6 ng/ml)
• Proinsulin > 5pmol/l (ICMA)
• Betahydroxybutyrate < 2.7 mmol/l
• Increased BG at least 25 mg/dl after glucagon injection (10, 20, 30 min)
Functional Hypoglycemia• Presentation:young female with spells
• Etiology: rapid gastric emtying leading to peak in insulin secretion.especialy high carb meals
• Treatment: low carb meal, precose , glyset.
Workup for hypoglycemia
• When BG <45, draw the following labs:
• Insulin(>6 indicating insulinoma)
• C-peptide(>0.6 –insulinoma)
• Cortisol(>20)
• GH
• LFT,BMP,TSH
Mechanism of Action of Sitagliptin
Release ofactive incretinsGLP-1 and GIP Blood glucose
in fasting and postprandial
states
Ingestion of food
Glucagon(GLP-1)
Hepatic glucose
production
GI tract
DPP-4 enzyme
InactiveGLP-1
XJANUVIA(DPP-4
inhibitor)
• Incretin hormones GLP-1 and GIP are released by the intestine throughout the day, and their levels in response to a meal.
Insulin(GLP-1and
GIP)
Glucose-dependent
Glucose dependent
Pancreas
InactiveGIP
GLP-1=glucagon-like peptide-1; GIP=glucose-dependent insulinotropic polypeptide.
Section
12, 12.2
Beta cells
Alpha cells
Glucose uptake by peripheral
tissue
Oral Antidiabetic Agents: Sites of ActionSulfonylureasSulfonylureas
RepaglinideRepaglinide
LiverLiver
MetforminMetformin
RosiglitazoneRosiglitazone
PioglitazonePioglitazone
PancreasPancreasAcarboseAcarbose
MiglitolMiglitolGutGut
MuscleMuscle
RosiglitazoneRosiglitazone
PioglitazonePioglitazone
MetforminMetformin
HyperglycemiaHyperglycemia
Impairedinsulin secretion
GlucoseGlucose uptakeuptake
HGO*HGO*
AdiposeAdiposetissuetissue
Glucoseuptake
RosiglitazoneRosiglitazone
PioglitazonePioglitazone
*HGO, hepatic glucose output.
GlucoseGlucoseAbsorptionAbsorption
Natural History of Type 2 Diabetes Progression of Complications
Genetic susceptibility
Environmental factorse.g. nutrition physical inactivity
Onset of diabetes
Disability
Death
Hyperglycemia RetinopathyNephropathyNeuropathy
BlindnessRenal failureCHD† Amputation
Insulin resistanceHyperinsulinemiaObesity cell dysfunction ProinsulinHypertensionDyslipidemiaAtherosclerosis
IFG*
Pre-diabeticstate
*IFG = impaired fasting glucose *IFG = impaired fasting glucose ††Coronary heart diseaseCoronary heart disease
Complications
Abnormal glucose levels
Adapted from International Diabetes Center (IDC)Minneapolis, Minnesota
Seven-year incidence in a Finnish-based cohort.*P<.001Haffner SM, et al. N Engl J Med. 1998;339:229-234.
Type 2 Diabetes is a Type 2 Diabetes is a Cardiovascular Risk FactorCardiovascular Risk Factor
Fat
al o
r N
onfa
tal M
I
0
10
20
30
40
50
Nondiabetic Subjects (n=1373)
Type 2 Diabetic Subjects (n=1059)
3.5%
20.2%18.8%*
45.0%*No Prior MI
Prior MI
Diabetes and prior myocardial infarction (MI) carry the same mortality risk
Med
ian
Hb
A1c
(%
)
ConventionalInsulinChlorpropamideGlibenclamide (glyburide)Metformin
0 306
7
8
9
6 9 10
Time From Randomization (years)
Upper limit of normal range (6.2%)
ADA goal
ADA action
United Kingdom Prospective Diabetes Study (UKPDS)
UK Prospective Diabetes Study (UKPDS 34) Group. Lancet. 1998;352:854-65.
Intensive Treatments and Increase in Intensive Treatments and Increase in HbAHbA1c1c Over Time Over Time
4:004:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00
BreakfastBreakfast LunchLunch DinnerDinner
Pla
sma
insu
lin
Pla
sma
insu
lin
8:008:0012:0012:008:008:00
TimeTime
Normal Mealtime Insulin Response
Pills available for DM 2
• No hypoglycemia:• TZD(Actos, Avandia)• Metformin/glucophage)• Alpha glucosidase
inhibitor(Precose, Glyset)
• Combo(avandamet, actoplusmet)
• DPP IV inhibitor:– Januvia– Galvus
• Can Cause Hypoglycemia:
• SU(glyburide,Amaryl)• Prandin/Starlix• Combo(glucovance,
avandaryl, duetact)