1. EXPLAINS Hypoglycemia

2. EX PLAINS Exogenous Insulin Basal: Lantus Levemir NPH Bolus Novolg Humolog Apidra Regular Exubera(inhaled Insulin )

3. explains Pituitary tumor (adrenal Insuficency, GH deficency )

4. exp l ains Liver disease (Cirrhosis,Tumor) Decresed gluconeogenesis and glycogenlysis)

5. expl a ins Adrenal insuficency(lack of steroid for sustained glycemic control)

6. expla i ns 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

7. 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

8. 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)

9. 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

10. 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)

11. explai n s Neoplasm: mainly pelvic tumor,IGF-2 mediated)

12. s explain s Secretatogue(glyburide,glipizide,amaryl, prandin, starlix) Sepsis

13. 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.

14. 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

18. Incretin Effect * * * * * * *

20. Mechanism of Action of Sitagliptin Release of active incretins GLP-1 and GIP  Blood glucose in fasting and postprandial states Ingestion of food  Glucagon (GLP-1)  Hepatic glucose production GI tract DPP-4 enzyme Inactive GLP-1 X JANUVIA (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 Inactive GIP GLP-1=glucagon-like peptide-1; GIP=glucose-dependent insulinotropic polypeptide. S e c t i o n 12, 12.2 Beta cells Alpha cells  Glucose uptake by peripheral tissue

21. Oral Antidiabetic Agents: Sites of Action Sulfonylureas Repaglinide Liver MetforminRosiglitazonePioglitazone Pancreas AcarboseMiglitol Gut Muscle RosiglitazonePioglitazoneMetformin Hyperglycemia Impaired insulin secretion  Glucose uptake  HGO* Adiposetissue   Glucose uptake RosiglitazonePioglitazone *HGO, hepatic glucose output.  Glucose Absorption

22. Natural History of Type 2 Diabetes Progression of Complications Genetic susceptibility Environmental factors e.g. nutrition physical inactivity Onset of diabetes Disability Death HyperglycemiaRetinopathy Nephropathy Neuropathy Blindness Renal failure CHD † Amputation Insulin resistance Hyperinsulinemia Obesity  cell dysfunction  Proinsulin Hypertension Dyslipidemia Atherosclerosis IFG * Pre-diabetic state *IFG = impaired fasting glucose † Coronary heart disease Complications Abnormal glucose levels Adapted from International Diabetes Center (IDC) Minneapolis, Minnesota

23. Seven-year incidence in a Finnish-based cohort. *P<.001 Haffner SM, et al. N Engl J Med. 1998;339:229-234. Type 2 Diabetes is a Cardiovascular Risk Factor Fatal or Nonfatal MI 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

24. Median HbA 1c (%) Conventional Insulin Chlorpropamide Glibenclamide (glyburide) Metformin 0 3 0 6 7 8 9 69 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 HbA 1c Over Time

25. 4:0016:0020:0024:004:00 BreakfastLunchDinner Plasma insulin 8:00 12:008:00 Time Normal Mealtime Insulin Response

26. 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)

27. Non insulin injection for DM2 GLP-1 analog(byetta) Amylin(Symlin)

28. Insulin treatment for DM Basal: –Lantus –Levemir –NPH Bolus –Novolg –Humolog –Apidra –Regular –Exubera(inhaled Insulin)