1. The Effects of Hyperglycemia and Hypoglycemia on the Vasculature in Type 2 Diabetes
Stephen N. Davis, MBBS, FRCP, MACP
Professor and Chairman, Department of Medicine
University of Maryland School of Medicine

2. Overview
Prevalence of Diabetes, Obesity, and Cardiovascular Disease in the US
Effects of Hyperglycemia and Hypoglycemia
New Treatment Options for Type 2 Diabetes

3. 1994
Methodology
The percent of U.S. adults who are obese or who have diagnosed diabetes was determined by U.S.ing data from the Behavioral Risk Factor Surveillance System (BRFSS, available at An ongoing, yearly, state-based telephone survey of the non-institutionalized adult population in each state, the BRFSS provides state-specific information on behavioral risk factors for disease and on preventive health practices. Respondents who reported that a physician told them they had diabetes (other than during pregnancy) were considered to have diagnosed diabetes. Self reported weight and height were U.S.ed to calculate body mass index (BMI): weight in kilograms divided by the square of height in meters. A BMI greater than or equal to 30 was considered to be obese. Rates were age-Adjusted U.S.ing the 2000 U.S. Standard Population.

4. 1995

5. 1996

6. 1997

7. 1998

8. 1999

9. 2000

10. 2001

11. 2002

12. 2003

13. 2004

14. 2005

15. 2006

16. 2007

17. 2008

18. 2009

19. 2010

20. Prevalence of Obesity and Diabetes
among US adults
2013
Obesity
Diabetes
Centers for Disease control and Prevention, 2014

21. Centers for Disease control and Prevention, 2014

22. Centers for Disease control and Prevention, 2014

23. 1 out of 3 people will develop type 2 diabetes in their lifetime
Centers for Disease control and Prevention, 2014

24. Centers for Disease control and Prevention, 2014

25. Sedentary Lifestyle
&
Slide Index L:
DISCUSSION POINTS:
McCalories!

27. 27

28. Natural History of Type 2 Diabetes
Postprandial glucose
350
300
250
Glucose
(mg/dL)
Fasting glucose
200
150
100 50
Insulin resistance
Relative b-cell Function
Clinical Diagnosis
of Diabetes
Insulin level
Pre-diabetes (IFG, IGT)
Metabolic Syndrome
-10 -5
Onset
of DM 5 10 15 20 25 30
Years of Diabetes
© 2002 International Diabetes Center. All rights reserved.

29. Pathophysiology of Type 2 Diabetes
Pancreas
Gut =
Insulin
Deficiency
Impaired
Secretion
Carbohydrate Metabolism
Hyperglycemia
Muscle & Adipose Tissue =
Insulin
Resistance
 Glucose
Uptake
 Hepatic Glucose
Production
Liver

30. Diabetes and Chronic Inflammation
Obesity
Chronic inflammation
Diabetes
Vascular diseases

31. Complications of Diabetes Over time, poorly managed
Stroke
Over time, poorly managed
Diabetes can damage the cell’s ability to hold together, causing serious problems
Heart Disease
Neuropathy & Peripheral Vascular Disease
Sores & Amputations
As well as complications of pregnancy, dental disease, sexual dysfunction, depression, biochemical imbalances, inability to walk, susceptibility to disease

32. Tight glucose control can prevent or slow complications to diabetes
(Keeping your glucose as close to normal as possible)
Diabetic eye disease started in only one-quarter as many people.
75%
Kidney disease started in only half as many people.
50%
Nerve disease started in only one-third as many people.
Neuropathy
66%
Far fewer people who already had early forms of these three complications got worse.

33. Implications of tight diabetes control
Achieving as close to normal values of 70 and 130 mg/dl before meals, and less than 180 mg/dl two hours after starting a meal, with a glycated hemoglobin level less than 7 percent
Must pay more attention to diet and exercise and check blood sugar levels more often
May feel better and have more energy
Be able to increase and vary activities
Costs of diabetes care could increase
Possible weight gain
Risks of hypoglycemia may increase

36. ------------------------------
Ultrasound technology for measuring flow mediated dilation (FMD) of the
brachial artery
FMD is a non-invasive measurement of endothelial function.

37. First artificial pancreas

38. The Artificial Pancreas – Refined Insulin Replacement/ Adjustment
Image credit:
Image credit:

39. Management of Hypoglycemia
Prevention
Treatment: 15 gm oral carbohydrate, measure glucose 15 min later
If more severe, 25 gm glucose iv, or 1 mg glucagon, sc or im
Short-term increase of glycemic target may be useful to interrupt the vicious cycle
Slide 40
Efforts should be made to prevent hypoglycemia by rational treatment choice and awareness of factors which increase risk.
Mild-to-moderate hypoglycemia should be treated by ingesting 15 gm or carbohydrate and measuring blood glucose levels 15 minutes later.
In patients treated with alpha glucosidase inhibitors, this must be taken in the form of glucose.
Severe hypoglycemia, requiring assistance from an outside party should be treated with intravenous glucose or glucagon (sc or im) and followed by glucose ingestion to replenish liver glycogen.
If a patient experiences repeated hypoglycemic episodes a short-term increase of glycemic targets may be useful to interrupt the vicious cycle.

40. Novel Treatment Options Reduce Blood Sugar without Causing Hypoglycemia

41. Exenatide (Byetta®, Bydureon®),
GLP-1 Agonists
The Benefits:
Improvement in the HbA1c
Reduction in FBG
No significant hypoglycemia
Weight loss
Reduction in biomarkers of cardiovascular risk
Exenatide (Byetta®, Bydureon®),
albiglutide (Tanzeum®), dulaglutide (Trulicity®), liraglutide (Victoza®)

42. Dipeptidyl peptidase-4 inhibitors
The Benefits:
Oral agent
Improvement in the HbA1c
Reduction in FBG
No significant hypoglycemia
Reduction in biomarkers of cardiovascular risk
Sitagliptin (Januvia®), saxagliptin (Onglyza®),
linagliptin (Tradjenta®), alogliptin (Nesina®)
Medscape Diabetes. 2006;8(1) © 2006  Medscape

43. Sodium-glucose Cotransporter-2 Inhibitors
The Benefits:
Improvement in the HbA1c
Reduction in FBG
No hypoglycemia
Reduction in BP
Weight loss
Reductions in cardiovascular/all-cause mortality
Canagliflozin (Invokana®), empagliflozin (Jardiance®), dapagliflozin (Farxiga®)
U.S. Food and Drug Administration

44. Empagliflozin/linagliptin (Glyxambi®)
SGLT-2 & DPP-4 inhibitor
1. ↑ insulin production
2. ↓ sugar production
3. Removes some sugar

46. Newly approved long-acting insulin analogs for treatment of diabetes
Insulin Glargine U300 (Toujeo)
Insulin degludec U-200 (Tresiba) flex touch insulin pen
Both as effective as Lantus glargine but significantly less night-time low blood sugars

47. Concentrated long-acting basal insulins
Humulin-R U500
Insulin Degludec U200
Insulin glargine U300
Duration of Action hours hours >30 hours
Half-life hours hours hours
Steady state days days
Weight gain (T1DM) kg kg kg
(T2DM) kg kg
HbA1c from baseline % (T2DM) % (T1DM) % (T1DM)
-1.3% (T2DM) % (T2DM)

48. A long-acting human insulin analogue administered subcutaneously
Similar efficacy and safety as glargine

49. Insulin degludec (Tresiba®) vs. insulin glargine
Lower rate of hypoglycemia
Lower rate of nocturnal hypoglycemia
Similar efficacy

50. Toujeo® Compared to Glargine
Lower rate of severe hypoglycemia

51. Insulin Patch A thin silicon patch
100+ microneedles – each the size of an eyelash
Enzymes on the microneedles sense blood glucose levels.
When glucose levels increase, the enzymes trigger a rapid release of insulin into the tissue.
In the future – as with the artificial pancreas - glucagon will also be incorporated into this device.

52. Summary Type 2 diabetes and obesity are increasing yearly.
Hyperglycemia and hypoglycemia both damage blood vessels.
New treatments for type 2 diabetes reduce the risk of hyperglycemia and hypoglycemia