Meng H Tan MD Clinical Professor of Medicine Metabolism, Endocrinology and Diabetes University of Michigan, Ann Arbor, Michigan 20th Anniversary Celebrations Diabetes Care Program of Nova Scotia April 28, 2011, Halifax, Nova Scotia

DCPNS MISSION 1991 To improve the quality of life of Nova Scotians affected by diabetes by bringing them the best quality of care possible. From a little acorn to a big oak tree

1991 CONGRATULATIONS 2011 Tan

•  Learning objective •  Translate Diabetes Research from 1991-2011 into Clinical Practice in 40 mins •  View from 30,000 feet…… •  Fasten your seat belt…..

•  Common…2009 246 million •  Growing…2025 380 million •  Costly…2007 in USA Total $178 billion (Direct 116 + Indirect 58 billion)

Tan

•  Serious....2005 in USA every 24 hours •  New Cases – 4,100 •  Deaths – 810 •  Amputations – 230 •  Kidney Failure – 120 •  Blindness – 55 Derived from NIDDK Fact Sheet on Diabetes 2005

•  42 experts responded with their rankings of advances in diabetes care 1991-2011 •  27 physicians •  11 diabetes educators •  3 patients •  1 diabetes business person Tan

•  To be included, there must be at least 4 votes for an advance in diabetes care.

Tan

1.  DCCT(33) [1993] 2.  UKPDS(30) [1998] 3.  GLP-1 mimetics(28) [2005] 4.  Rapid-acting insulin analogs(27) [1995] 5.  Basal insulin analogs(27) [2000] 6.  CGM(23) [2002, 2006]

7. Evidence base guidelines(20) [1998, …] 8. Prevention of T2D(15) [1991, 1997] 9.  UN Resolution 61/225 (13) [2006] 10. GLP-1 enhancers(13) [2010]

Access to Care ACE-I & Renal (9)

(5)

New drugs

(105)

Top Ten Categories

Patient Education (10)

Glycemic Control

(77)

Devices & Monitoring (43)

Prevention of T2DM

CVD Reduction (31)

(15)

Awareness (17)

Evidence base (20) Guidelines

Basal analogs 27

Metformin 4

Rapid acting Analogs 27

New Drugs

GLP-1 Enhancers 13

TZDs 6

GLP-1 mimetics 28

Exenatide (Exendin-4) •  Synthetic version of salivary protein found in the Gila monster •  Approximately 50% identity with human GLP-1 – Binds to known human GLP-1 receptors on  cells in vitro – Resistant to DPP-IV inactivation Exenatide

H G E G T F T S D L S K Q M E E E A V R L F I E W L K N G G P S S G A P P P S – NH2

GLP-1 Human

H A E G T F T S D V S S Y L E G Q A A K E F I A W L V K G R – NH2

Site of DPP-IV Inactivation Adapted from Nielsen LL, et al. Regulatory Peptides. 2004;117:77-88.; Fineman MS, et al. Diabetes Care. 2003;26:2370-2377. Reprinted from Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes, 77-88, Copyright 2004, with permission from Elsevier.

lispro/aspart 4–5 hours

  BOLUS INSULINS   BASAL INSULINS

Plasma Insulin levels

regular 5–8 hours NPH 12–18 hours

detemir ~ 12-20 hours glargine ~ 24 hours

Hours

Note: action curves are approximations for illustrative purposes. Actual patient response will vary. CDA Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Canadian Journal of Diabetes Dec, 2003;27(Suppl 2) Plank, J. et.al. Diabetes Care, Volume 28, Number 5, May 2005

UKPD (30)S

DCCT (33)

Glycemic control

Pregnancy (4)

Metabolic memory (9)

Type 1

Type 2

Type 2

DCCT1

Kumamoto2

UKPDS3

9  7%

9  7%

8  7%

Retinopathy

63%

69%

17-21%

Nephropathy

54%

70%

24-33%

Neuropathy Cardiovascular disease

60%

-

-

41%*

52*

16%*

A1c

*Not statistically significant due to small number of events.  Showed statistical significance in subsequent epidemiologic analysis4

DCCT Research Group. N Engl J Med. 1993;329:977-986. Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28:103-117. UKPDS 33: Lancet 1998; 352, 837-853. Stratton IM et al. BMJ. 2000;321:405-412.

Intensive 12%

Conventional

Retinopathy 0.5 progression (incidence) 0.4

10%

0.3

A1C

0.2

8%

0.1 6%

P