Hum

rigin

A part of something great

Li-Te ChinDept. of Microbiology & Immunology, National Defense Medical Center, Taipei, Taiwan, R O C Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, R O C Dept. of Immunotechnology, University of Lund, Lund, SwedenAdjunct Associate Professor, Inst. of Life Science, Fu-Jen Catholic University Research Director, Chinese Blood Services Foundation Adjunct PI, Chinese Blood Services Foundation1. Assistant Professor, Dept. of Medical Technology, National Cheng-Kung University 2. Technical and Quality Supervisor, The Blood Bank of NCKU University Hospital

Dept. of Biology, Fu-Jen Catholic University, Taipei, Taiwan, R O C

Technical Director, General Biologicals Corp., Taiwan CCO, SCI Inc., USA CEO, Apex Biotechnology Corp., Taiwan CEO, HumOrigin, Taiwan Adjunct Associate Professor, Dept. of Medical Technology, China Medical University Broad Member, Hsinchu Biomedical Industrial Park, National Taiwan University

1982 ~ 1985

1985 1987 ~ ~ 1997 1990

1990 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 ~ 1994

57% 24% 23%17.5 14.2 15,000 10,000 5,000 0U$2,560

132.3 84.5

50 40 30 20 10 0U$ 13,243

32.9 26.5 42.3

50%20.8 9.4 14.1

Non-diabetic Diabetic 22.5 2002 15.6 medical expenses annual

44%

2000

2030

33%2004-11-091 1.3

World 2000=151 million 2010=221 million Increase: 46%

5000

American Diabetes Association Economic Costs of Diabetes in the U.S. in 2002 DiabetesWild, 26(3):917-932,P et al. Nature. 2001;414:782. SOURCE: Care S. Diabetes Care, May 2004; vol 27: pp 1047-1053. Source: Zimmet 2003.

Million people with diabetes300

150

2000

2025

Source: World Health Organisation September 1998

By Li-Te Chin, Ph.D. in Engineering copyright reserved

The worldwide market for diabetes therapeutics and diagnostics in 2000 was estimated at $12.4 billion. Fueled byA. increasing prevalence of the disease B. improved therapeutics, delivery systems, and diagnostics,

the market will grow at a compound annual growth rate (CAGR) of 12% to reach approximately $27 billion in 2010. For glucose monitoring, the world market was estimated at $3.7 billion in 2000, and Theta Reports projects this market to grow to nearly $10 billion by 2010. Market growth will also depend on manufacturers' abilities to meet market needs, including patients' demands forA. smaller blood test samples, B. less invasive and painful testing, C. easy-to-use features like: D. more cost-effective consumables, large display screens, larger E. patent integrity test memory, and more rapid results. June 15, 2004

8

Market Size ($billions)

64.9B

6.0B

43.7B

21.1B

0

Blood Glucose Monitoring

Insulin delivery

Insulin therapy

Oral medication therapySource: 2002

By Li-Te Chin, Ph.D. in Engineering copyright reserved

Rest of the world 14% 24% Europe USA 62%

2000 1500 1000 500478 564 660 782 880 1,000 1,214

Meter: 13% 1,378 1,478

1,635

Strips: 87%1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

($M) 0

1000 800 600880

Blood glucose selfmonitoring products 75.27% = $1.4 B The 2000 OTC market worldwide = $3 billionBy Li-Te Chin, Ph.D. in Engineering copyright reserved

400 200300 220

0 ($M) Fingerstick HbA1c F ructosablood glucose testing mine, urine testing and others

Source: The US Market for Over-the-Counter Diagnostics , 2001

12,000 10,000

11.2%8,106 7,316 6,553 5,826 5,140

9,732 8,915

($ millions)

8,000 6,000 4,000 2,000 0 2003 2004

2005

2006

2007

2008

2009

YearBy Li-Te Chin, Ph.D. in Engineering copyright reserved

Source: Diagnostics & Imaging WeekITIS(2004/07)

(Surgical) (Orthopedic and prosthetic)

(IVD)

(Medical Device)

(Dental)

(Electromedical)By Li-Te Chin, Ph.D. in Engineering

(Radiological)

30,000

28,861 25,554

Value of Shipments ($ millions)

25,000474

93820,624

20,000

1.4%

17,846

: 1979 : 1989 : 1999 : 200416,713 13,507

16,113

15,00010,660

22.9%

12,166 9567

10,000

9379

56.3%5,0002254 3443

5298

17.2%

(Ortho 2.1% and (Surgical) pedic prosthetic)By Li-Te Chin, Ph.D. in Engineering copyright reserved

/

3888 2932 1335 1080

3949 1926 681

4821 1667 2325 717

(Electro(Dental) (Radiological) (IVD) Source: Espicom Business Intelligence medical)

www.epsbio.com.tw

www.hmdbio.com

www.eumed.com.tw

www.oncoprobe.com.tw

www.tysonbio.com

www.bestgen.com.tw

www.hdiasc.com.tw www.biotestsystems.com (www.bionime.com) http://www.wegene.com.tw/By Li-Te Chin, Ph.D. in Engineering copyright reserved

www.gtm.com.tw/bi001_ch.html www.taidoc.com.tw myweb.hinet.net/home3/stcds-1/corp.htm

Updated: Feb, 2005

10 5

41.25 60 80

1988113360

>25.58E

83.19 366 72.89 150 289 717.68 110 113 100

0By Li-Te Chin, Ph.D. in Engineering copyright reserved

200

400

600

800Updated: Feb, 2005

() 500 1000 0

2004 (910) 2003 (896) 2004 (610) 2003 (694)

+1.6%

-13.6%

+23.0%

2004 (3283.0) 2003 (2528.6) +35.3%3000 3500

2004 (2777.0)2003 (1798.1)2500 2000

1500

1U$ = 33.4 NTDBy Li-Te Chin, Ph.D. in Engineering copyright reserved

U$ in millionSource: IT IS,2005

50 40

% of Death

30 20 10 0 Ischemic Heart Disease Other Heart Disease Diabetes Cancer Stroke Infection Infection Other

Common bile duct

Pancreatic duct Small intestine (duodenum)

Exocrine cells Endocrine cells Islet of Langerhans

: cell secrets glucagon : cell secrets insulin & amylin : D cell secrets somatostatin

cells cellsD cells By Li-Te Chin, Ph.D. in Engineering copyright reserved

Glycogen Triglycerides ProteinsGlucose oxidation Glycogen synthesisINSULIN Fat synthesis Protein synthesisBy Li-Te Chin, Ph.D. in Engineering copyright reserved

Glucose Fatty Acids Amino AcidsGlycogenolysis Gluconeogenesis

GLUCAGON Ketogenesis

Plasma (Pancreas)InsulinGlucose

Amino acids

{

Fatty acids Amino acids GlucoseInsulin receptor

Insulin Fatty acids

To receptors

(Brain) (RBC)Fatty acids

Promotes anabolic processes & Inhibits catabolic processes (Muscle)By Li-Te Chin, Ph.D. in Engineering copyright reserved

(Liver)

(Adipose tissue)

Insulin deficiencyInsulin secreted into bloodstream capillary

Pancreatic -cell destruction Insulin-dependent diabetes mellitus (IDDM) Children and adolescents

: Insulin-producing cells

: Insulin-producing cells destroyed

Ketoacidosis ~5%

By Li-Te Chin, Ph.D. in Engineering copyright reserved

Genetic Acquired Glucotoxicity People whose pancreas Lipotoxicity

makes insulin but not enough, or who

Insufficient glu have insulin -cose disposal

resistance, or bothInsulin deficiency Insulin resistance (decreased insulin receptor sensitivity)Hepatic A progressive Glucose-induced disease associated with a combination of risk cell beta factors, Glucoseglucose function insulin secretion including: production Impaired

1. abdominal obesity, Tissue responseto insulin

HyperglycemiaGlucose uptake Glucose transport Basal hyperhyperinsulinemia

Post receptor defect

2. high triglycerides, low high-density lipoprotein (HDL-C) cholesterol levels, and resistance Insulin 3. hypertensionGenetic ~95% Genetic Acquired Obesity AgeInsulin binding

By Li-Te Chin, Ph.D. in Engineering copyright reserved

2.5 million years

50 years

By Li-Te Chin, Ph.D. in Engineering copyright reserved

Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Gall bladder disease Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Osteoarthritis Skin GoutBy Li-Te Chin, Ph.D. in Engineering copyright reserved

Idiopathic intracranial hypertension Stroke Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension Severe pancreatitis Cancer breast, uterus, cervix colon, esophagus, pancreas kidney, prostate Phlebitis

Genetics

Insulin resistance Hyperinsulinemia

Acquired: Obesity, Aging & Sedentary lifestyle :

Compensated insulin resistance (Normal Glucose Tolerance)

Impaired glucose tolerance

-cell failure

Genetics

Type 2 diabetes By Li-Te Chin, Ph.D. in Engineering copyright reserved

Increased hepatic glucose output

Glucose

Macrovascular and Microvascular Complications The Heart attack (Cardiovascular out of the blood kidneys filter some glucose diseases) Kidneymay get needing dialysis or transplant into the urine, making the person urinate more. Vision failure, blurred. (Retinopathy) (Nephropathy) Cuts may not heal as fast. Vision loss Urinating more makes the person thirsty, to rePeopledamage more skin infections. Nerve may get place the fluid lost. (Neuropathy) Womenproblems more vaginallack of infections. Sexual may get [impotence, yeast arousal, dry vagina] People may get drier skin. Losing the problems in thedisease, loss of people Dental glucose burningurine makes their feet. [gum or tingling in teeth] lose People may feel weight, without trying to do so.

All these changes make people tired all the time.

By Li-Te Chin, Ph.D. in Engineering copyright reserved

Plasma glucose levels (mg glucose/dL): Plasma glucose levels (mmol glucose/L): FPG OGTT Diabetes 126 7.0 or 200 11.1 >140