How To Know If You Have Hypoglycemia

Transcription

1 is a major issue in managing type1and type 2 diabetes mellitus Two conditions contribute to this problem: defective glucose counterregulation DANIEL PORTE JR M. D. UC SAN DIEGO VA SAN DIEGO HEALTH CARE SYSTEM hypoglycemia unawareness Clinical : Definition Clinical (low blood sugar) in a treated person with diabetes is a glucose value less than 70 mg/dl. DCCT DEFINITION OF SEVERE Requires: 1. Symptoms of hypoglycemia 2. Assistance of another 3. Blood glucose <50 mg/dl or prompt recovery after glucose or glucagon Symptoms of Autonomic system symptoms: Shakiness Palpitations Sweating Anxiety Nausea Symptoms of Neuroglycopenia symptoms: (effects on the brain) Confusion Unusual behavior Loss of consciousness Dizziness Headache Seizure 1

2 Question NEUROENDOCRINE SYTEM FOR THE COUNTERREGULATORY RESPONSE 1. what glucose was used in the DCCT to diagnose Severe hypoglycema? a) Blood glucose of <70 mg/dl b) Blood glucose of <50 mg/dl c) Blood glucose of <30 mg/dl MCCRIMMON, R DIABETIC MEDICINE 25:513-22, The Body s Response To Decrease insulin secretion Increase epinephrine (adrenaline) secretion Increase glucagon secretion Increase cortisol secretion Increase growth hormone secretion The Body s Response To Epinephrine and glucagon work within minutes to elevate glucose levels. Cortisol and growth hormone work several hours later to elevate glucose levels. EFFECT OF 3 DAY FAST PLUS IV ALCOHOL ON BASAL INSULIN BASAL INSULIN ( U/ml) PRE- FAST (88) POST- FAST (3 Days) ETHANOL NADIR P < 001 P <.001 LEAN TYPE 2 OBESE TYPE 2 LEAN NGT OBESE NGT Why Diabetics May Get If a person with diabetes is being treated with a sulfonylurea or insulin, insulin levels are increased, and insulin secretion cannot be completely shut off despite low glucose. BAGDADE, JD, BIERMAN, PORTE, D DIABETES 21:65-70,

3 Symptoms of The body s strategy Autonomic symptoms warn the body to prevent more serious hypoglycemic effects (neuroglycopenia). They are coupled to metabolic systems which are designed to inhibit endogenous insulin secretion, release glucose from the liver, and impair peripheral tissue glucose uptake Increased Hunger,Glucagon. Epinephrine, GH CLASSIC SITES OF INSULIN ACTION 1. MUSCLE-UPTAKE AND OXIDATION OF GLUCOSE 2. ADIPOSE TISSUE-UPTAKE OF GLUCOSE AND SYNTHESIS AND STORAGE OF FAT 3. LIVER-INHIBITION OF GLUCOSE PRODUCTION Question What hormones are changed within minutes to counter-regulate hypoglycemia? a) insulin b) epinephrine c) glucagon d) cortisol e) all of above f) a, b, c above g) just b,c above INSULIN ACTION IN THE BRAIN 1. REDUCE HEPATIC GLUCOSE PRODUCTION 2. SUPRESS APPETITE 3. REDUCE BODY FAT AND WEIGHT 4. INCREASE ENERGY EXPENDITURE MEAN CHANGE OF FOOD INTAKE (KCAL) FOOD INTAKE SUPPRESSION DURING CHRONIC INTRA-CEREBROVENTRICULAR INSULIN INFUSION IN BABOONS Mean Baseline Mock CSF Infusion Mock CSF Infusion DAYS MEAN CHANGE OF FOOD INTAKE (KCAL) Mean Baseline Insulin Infusion (100 U/kg/d) DAYS WOODS,SC;LOTTER,EC;MCKAY,LD &PORTE, D JR. Nature, 282:503,

4 REAL WORLD TREATMENT EFFECTS IN AUSTRALIA NEW ZEALAND AND FINLAND BEST, JD ET AL DIABETES CARE 35: , Why is there weight gain with Intensive Insulin Therapy? 98 one month old male rats treated weekly with insulin to lower glucose to mg/kg for three hours. 60 minute IV GTT was given 3-4 days before and after the test. Wt., Fat pad content, food intake, and motor activity were assessed at 4, 8, and 12 months RAT WEIGHT GAIN AFTER INSULIN INDUCED TO MG/DL FOR 3HR. WEEKLY FAT PAD WEIGHT 8MONTHS AFTER WEEKLY INSULIN INDUCED FOOD INTAKE AFTER INSULIN INDUCED WEEKLY ACTIVITY AT 12 MONTHS OF AGE AFTER INSULIN INDUCED WEEKLY 4

5 CONCLUSION IN THIS STUDY: IATROGENIC LEADS TO WEIGHT GAIN THAT IS ASSOCIATED WITH A INCREASED METABOLISM RATHER THAN AN INCREASE IN CALORIES WHAT IS THE CLINICAL EXPERIENCE WITH TYPE 1 DIABETES? PERCENT OF TYPE 1 DIABETIC PATIENTS WITH DEFECTIVE HORMONAL RESPONSESS Hypoglycemic Unawareness Patients do not get the autonomic warning symptoms. The first signs of hypoglycemia are the neuroglycopenic symptoms. This occurs in patients who have had frequent hypoglycemia or in some type 1 diabetic patients after having diabetes for many years. McCRIMMON, R DIABETIC MED 25: , 2008 FROM MOKAN M DIABETES CARE 17: , ASSOCIATED AUTONOMIC FAILURE -Associated Autonomic Failure in Type 1 Diabetes Mellitus Begets Absolute Insulin Deficiency INSULIN T1DM Imperfect Insulin Replacement No In glucagon No Glucagon Unawareness Defective Glucose Counterregulation Reduced Autonomic Symptoms Reduced Epinephrine Response HELLER SR AND CRYER PE DIABETES 40: 223-6,

6 Severe During the DCCT DCCT RISK OF SEVERE HbA 1c = 7.0% HbA 1c = 9.1% CONVENTIONAL INTENSIVE Diabetes Control and Complications Trial Research Group. Diabetes. 1997;46: THE DCCT TRIAL RESEARCH GROUP DIABETES 46: , 1997 RATE OF SEVERE IN 1683 WESTERN AUSTRALIAN YOUTH CHANGES IN DIABETES TREATMENT OF TYPE 1 DIABETES IN WESTERN AUSTRALIAN YOUTH Continuous Subcutaneous Insulin Infusion Twice Daily Injections Multiple Daily Injections < 6 years 6-12 years 12 years MEAN HbA1C=8.3% 0.07%/yr, p=0.03 O CONNELL SM DIABETES CARE 34: , COOPER, MN ET AL DIABETOLOGIA DOI /s ADULT TYPE 1 DIABETES REGISTRY- MEAN HbA1C/YEAR VS %SEVERE AND %KETOACIDOSIS/YEAR QUESTION >1 SEVERE HYPO >1 DKA WHICH ARE THE FACTORS THAT INCREASE RISK FOR PATIENTS WITH TYPE 1DIABETES? a) INSULIN TREATMENT b) RECENT c) EXERCISE d) SGLT-2 INHIBITOR TREATMENT e) ALL OF THE ABOVE f) a,b,c, Mean HbA1c. p adjusted for duration,income, Insurance,Education WEINSTOCK, RS ET AL J CLIN ENDO METAB JUNE

7 PERCENT OF PATIENTS WITH ONE OR MORE EPISODES IN THE UKPDS IN TYPE 2 DIABETES WRIGHT AD J DIABETES COMLICATIONS 20: , FREQUENCY OF SEVERE IN A YEAR SEVERE IN THE TYPE 2 DIABETES PATIENT FROM KAISER HEALTHCARE IN LIPSKA, KJ ET AL DIABETES CARE JULY 2013 PMID: UK STUDY GROUP DIABETOLOGIA 50: , 2007 SUMMARY OF IN THREE RECENT INSULIN TREATMENT TRIALS-ACCORD, ADVANCE AND VADT NO BENEFIT FOR INTENSIVE VS STANDARD TREATMENT FOR PREVENTION OF MACROVASCULAR OUTCOME HIGHER INCIDENCE OF SEVERE 41 Oral Diabetic Medications That Do Not Cause Metformin Thiazolidinedione (Actos, Pioglitizone) DPP4 Inhibitors (Sitagliptin, Januvia), (Saxagliptin, Onglyza), (Linagliptin, Tradjenta ) (Alogliptin, Nesina) GLP-1 Agonists (Exenatide, Byetta), (Liraglutide,Victoza), Alpha-glucosidase inhibitors (Acarbose,Precose),(Miglitotol,Glyset) SGLT-2 inhibitor ( Canagliflozin,Invokana) But cause hypoglycemia with SU or Insulin 7

8 What to do if you think you have hypoglycemia Check your blood sugar Symptoms may be caused by something else What to do if you have hypoglycemia If you have confirmed hypoglycemia (glucose < 70 mg/dl), ingest 15 grams of carbohydrate. Liquids work quickest: 4 oz of juice or soda; or 3 glucose tablets (5 gm each) What to do if you have hypoglycemia Recheck your glucose in minutes. (Re-treat if glucose is still < 70 mg/dl) What to do if you have severe hypoglycemia Glucagon injection Glucose gel (or cake frosting) inside the cheek Call 911 if patient is unconscious How to Minimize Test home glucose frequently Do not miss meals Know which medications are associated with hypoglycemia If you are having hypoglycemic reactions, be sure to discuss this with your doctor! QUESTION WHAT IS THE FIRST THING TO DO FOR AN UNCONSCIOUS PATIENT SUSPECTED OF HAVING SEVERE? a) check blood glucose b) give glucagon c) give oral glucose d) give IV glucose 8

9 SUMMARY 1. CLINICAL DEFINITION OF AND SEVERE 2. NEUROENDOCRINE SYSTEMS FOR GLUCOSE COUNTERREGULATION 3. SITES OF INSULIN ACTION 4. CLINICAL EXPERIENCE WITH IN TYPE 1 AND TYPE 2 DIABETES 5. PREVENTION AND TREATMENT OF 9