EXPLAINSHypoglycemia

EX PLAINS

•Exogenous InsulinBasal:

Lantus

Levemir

NPH

BolusNovolgHumologApidraRegular

Exubera(inhaled Insulin)

explains

• Pituitary tumor (adrenal Insuficency, GH deficency )

explains

• Liver disease (Cirrhosis,Tumor)

• Decresed gluconeogenesis and glycogenlysis)

explains

• Adrenal insuficency(lack of steroid for sustained glycemic control)

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)

explains

• Neoplasm: mainly pelvic tumor ,IGF-2 mediated)

explainss• Secretatogue(glyburide,glipizide,amaryl,

prandin, starlix)

• Sepsis

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

Incretin Effect*

*

*

*

**

*

GLP-1 secreted upon the ingestion of food

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)

Non insulin injection for DM2

GLP-1 analog(byetta)

Amylin(Symlin)

Insulin treatment for DM

• Basal:– Lantus– Levemir– NPH

• Bolus– Novolg– Humolog– Apidra– Regular

– Exubera(inhaled Insulin)