Diabetes: We ve Come a Long Way, Baby! Amy Wachter, MD Christiana Care Endocrinology March 22, 2018

Transcription

1 Diabetes: We ve Come a Long Way, Baby! Amy Wachter, MD Christiana Care Endocrinology March 22, 2018

2 Title of My Talk

3 Ancient Times Diabetes has been affecting lives for thousands of years. Egyptians in manuscripts dating back to 1550 BC recognized the condition. Apollonius of Memphis around 250 BC. Diabetes mellitus Siphon= to pass through Mellitus= honeyed or sweet

4 Matthew Dobson makes a SWEET discovery Discovered that the blood of diabetics was sweet tasting Study What could you see when you allowed Urine to Evaporate?

5 1869 A German Medical Student (Paul Langerhans) discovers tissue clumps scattered throughout the pancreas when looking under the microscope The Islets of Langerhans

6 1889 Diabetes: Not a kidney disorder but a Pancreas Problem Joseph von Mering and Oskar Minkowski discovered that if you remove a pancreas from a dog, you would cause the symptoms of diabetes.

7 Lucy

8 Jan 11, the first insulin injection Jan 22, the second insulin injection March 1922 Banting and Best publish findings July 1922 Toronto Doctors have robbed diabetes of its TERRORS.

9 1936 Harold Himsworth distinguished between the two types of diabetes. Some people needed a little insulin Some people needed a lot of insulin He defined them as insulin-sensitive and insulin-insensitive.

10 What is Diabetes? Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in Insulin secretion, Insulin action, or BOTH. American Diabetes Association Standards of Care

11 Defect

12 Type 1 vs. Type 2 Type 1 Your body does not make enough insulin Diagnosis: usually in childhood or young adulthood Usually LEAN person Treatment is INSULIN 4 shots a day Insulin pump Labor intensive

13 Dosing insulin Type 1 Diabetes Long acting Short acting/mealtime

14 Type 1 vs. Type 2 Type 2 Your body is resistant to insulin Diagnosis: usually in adulthood but with rise in obesity cases being seen in toddlers Usually OVERWEIGHT OR OBESE person Treatment is pills (but can include insulin) Lifestyle changes are cornerstone

15 Back to our Story Banting, Best, McLeod, Carlip, and Eli Lilly and Company circa 1923

16 Jan 11, the first insulin injection Jan 22, the second insulin injection March 1922 Banting and Best publish findings July 1922 May 22, 1922, Macleod publishes paper and uses the term insulin By 1923, insulin was produced in seemingly unlimited quantities by the Eli Lilly Company of Indianapolis

17 Early Insulin Preparations All Insulin preparations before 1983 derived from

18 What about Oral Diabetes Drugs

19 1946 Sulfonylureas were discovered by the chemist Marcel Janbon and co-workers Studying sulfonamide antibiotics and discovered that the compound sulfonylurea induced hypoglycemia in animals.

20 1940 s The biguanide class of anti-diabetic drugs, originates from the French lilac, a plant used in folk medicine for several centuries. Glucophage = Sugar Eater 1970 s class taken off the market due to side effects lactic acidosis Galega officinalis

21 1977 Boston researchers develop a test to measure glycosylated hemoglobin (A1C).

22

23 1982 The FDA approves human insulin to be produced in microorganisms

24 1982 Human insulin is produced from bacteria and yeast E. Coli Eli Lilly Baker s Yeast Novo Nordisk

25 Insulin pens available 1985

26 1993 DCCT: Diabetes Control and Complications Trial

27 1995 Metformin back on the market Benefits: Less weight gain Less hypoglycemia Less risk of cardiovascular events

28 1996 First analog insulin - Lispro

29 2005 Incretin mimetic (GLP-1) available

30 GLP-1 Agonists

31 GLP-1 Agonists

32 2006

33 2006

34 2013 FDA approves SGLT-2 inhibitors

35 Formulations SGLT-2 inhibitors

36 Back to Insulin

37 Long Acting Insulin 1936: NPH insulin 2000: Glargine (Lantus) 2004: Detemir (Levemir) 2015: Concentrated Glargine (Toujeo) 2016: Degludec (Tresiba) How does it work?

38 Diabetes Management Technology

39 Insulin Pumps Delivering 2 types of insulin 24/7 Basal or background insulin Bolus or mealtime insulin Bolus/Mealtime insulin = Insulin for carbs in food Insulin to CORRECT if your blood sugar is high

40 Continuous Subcutaneous Insulin 1960 s: Arnold Kadish devises first insulin pump As large as Marine backpack and worn on back 1978: Auto Syringe model of Big Blue Brick commercially available Infusion

41 1983 Medtronic releases first portable, programmable insulin pump into the market

42 Insulin Pumps

43 Continuous Glucose Monitors

44 Continuous Glucose Monitors Dexcom Sensor lasts: 7 days Worn: abdomen Start up time: 2 hours Alarms: YES Libre Sensor lasts: 10 days Worn: back of arm Start up time: 12 hours Alarms: NO

45 Artificial Pancreas Technology

46 Medtronic 670G Data

47 The Future

48

49 Thanks Questions?

50 Classifications 1921 Insulin 1940 s Biguanides 1946 Sulfonyureas 1995 Biguanides 1996 Alphaglucosidase inhibitors 1997 Thiazolidiones 1998 Meglitinides 2005 Incretin mimetics (GLP-1 ) 2006 DPP-4 inhibitor 2013 SGLT-inhibitors

51 Glucometers Pre-1950s : Qualitative Urinalysis : solutions/tablets 1950s : Dry chemistry test-strips urine glucose, protein, ph 1960s : Blood glucose strips visual reading semi-quantitative 1970s : First Generation - Reflectance Meters (Qualitative) Second Generation no timing or blood removal refinements capillary filling, smaller blood volume (less pain, alternate site testing), shorter test time, better accuracy/precision, less interference, integration miniaturisation (portability), connectivity, no coding etc 2000 : Third Generation Biosensors for Continuous Glucose Monitoring (CGM)? Fourth Generation Non-invasive monitoring

52 The World of Insulin Analogs