The following overview presents the prevalence and incidence of diabetes among the People with diabetes were defined as those who had a fasting plasma …
Diabetes: How It Happens, Why Its So Prevalent and How to Prevent It
Jack Leahy, MD Endocrinology, Diabetes and Metabolism Unit
Diabetes is a group of diseases characterized by an elevated level of blood glucose AND risk of end-organ complications - microvascular kidney, eye and nerves and macrovascular heart attacks, stroke and peripheral vascular disease
Diabetes in the US
18 million affected at a direct cost of 132 billion in 2002 41 million with prediabetes 6th disease specific cause of death Leading cause of: Kidney failure Adult blindness Nontraumatic limb amputation
US Diabetes Prevalence by Ethnic Group
Men and Women, Age 45-74 Years
50 with diabetes 40
Global Projections for the Diabetes Epidemic: 2003-2025 2003NA EUR
230 M 362 M 570
484 M 586 M 21
EMME
WP SEA
192 M 394 M 105
AFR
393 M 816 M 108
430 M 758 M 79
SACA
30 20 10 0
European Cuban Japanese African Mexican American American American American Puerto Rican Pima
World 2003 194 M 2025 333 M 72
142 M 262 M 85
71M 150 M 111
2003 2025
M million, AFR Africa, NA North America, EUR Europe, SACA South and Central America, EMME Eastern Mediterranean and Middle East, SEA South-East Asia, WP
Western Pacific Diabetes Atlas Committee Diabetes Atlas 2nd Edition: IDF 2003
Diabetes Mellitus
What is diabetes? Why is it increasing and occurring at an earlier age? Good news What should patients and the public know regarding prevention and optimal treatment? Whats new? Whats happening at FAHC/UVM?
Type 1 Diabetes
Disease in which the immune system destroys the cells within the pancreas that make insulin Disease of insulin deficiency Occurs over several years Current research is focused on: Early detection - prevention More effective therapies
Apoptosis HLA-DR3 or -DR4
x
??Trigger
Disease-specific antibodies
Technology in 2005
Henry Dolger at the 25th Anniversary of Insulins Discovery
JAMA 134:1289, 1947 The discovery of insulin twenty-five years ago served to avert the catastrophic threat to life represented by diabetes mellitus but unfortunately initiated an attitude of complacency in the members of the medical profession The optimism of that early period is now being dissipated by a number of anxious reports on the mounting evidence of seemingly inevitable degenerative sequelae Before After
Type 2 Diabetes
Islet ß-cell dysfunction Tissue insulin
resistance
Gary Hall
Metabolic Syndrome
Diagnosis of metabolic syndrome is established when 3 of the following risk factors are present:
Risk Factor Abdominal obesity Men Women Triglycerides HDL cholesterol Men Women Blood pressure Fasting glucose Defining Level Waist circumference 40 in 35 in 150 mg/dL 40 mg/dL 50 mg/dL 130/85 mm Hg 100 mg/dL 35 in 31 in WHO Asian Criteria
Evolution of Type 2 Diabetes
Genetic predisposition Environmental Factors
Normal glucose tolerance
Prediabetes
Type 2 DM
Prevalence of Diabetes and Obesity
Diabetes Mean Body Weight Prevalence
75 70 65 60 55 50 45 40 1990 1992 1994 1996 1998
75 74 73 72 78 77 76
Obesity Trends Among US Adults 1991-2002
BMI 30, or 30 lbs overweight for 5 4 woman
1991 1995
kg
Prevalence of obesity has increased by 61 since 1991 More than 60 of US adults are overweight Only 43 of obese persons advised to lose weight during checkups High BMI and weight gain are major risk factors for diabetes
No Data 10 1014 1519 2024 25
2002
2000
Year
Prevalence of Overweight in Vermont Children Grades 8-12
Grand Isle 8 Franklin 1 1 Lamoille Chittenden 8 Washington 8 Addison 1 0 Orange 1 1 9 Caledonia 1 2 Orleans 1 1 Essex 1
1
Grand Isle 8
Franklin 1 4 Lamoille Chittenden 1 0 Washington 9 Addison 1 2 1 3
Orleans 1 1
Essex 1 4
Caledonia 12
1999
2003
8-9 10-11 12-13 14
Orange 1 2
Rutland 1 0
Windsor 1 0
Rutland 13
Windsor 1 1
Bennington 9 Windham 1 0
Bennington 1 0 Windham 1 3
Evolution of Type 2 Diabetes
Acquired organ dysfunction Glucotoxicity? Lipotoxicity?
Normal glucose tolerance Prediabetes Type 2 DM
Therapy for Type 2 Diabetes: Sites of Action
Pancreas
Impaired insulin secretion Glucotrol, Amaryl Prandin Starlix Byetta
Gut
Excess dietary carbohydrate Acarbose Miglitol
Diabetes Mellitus
What is diabetes? Why is it increasing and occurring at an earlier age? Good news What should patients and the public know regarding prevention and optimal treatment? Whats new? Whats happening at FAHC/UVM?
Liver
Excess glucose production
Muscle
Insulin resistance Avandia Actos
Metformin
Diagnosis of Diabetes Mellitus
Fasting plasma glucose 126 mg/dL OR OR Random PG 200 mg/dL PLUS symptoms of diabetes polyuria, polydipsia, unexplained weight loss
How to screen for and diagnose diabetes
Prediabetes 100-125
2 hr PG during 75 g OGTT 200 mg/dL
Who To Screen For Diabetes?
NO major risk
factors, FPG every 3 years begin 45 yo Risk factors:
Overweight - BMI 25 1st degree relative with DM High risk ethnic group Hypertension 140/90 mm Hg HDL 35 mg/dl and/or triglycerides 250 mg/dl History of gestational diabetes or delivered baby 9 lb Polycystic ovary syndrome History of vascular disease Habitual physical inactivity
Medical care matters
Impact of Glycemic Control on Complications - UKPDS
0
ADA Standards of Care
Glycemia: HbA1c 70, FPG 90-130 mg/dl, 2-hr PP 180 mg/dl Blood Pressure: 130/80 Lipids: LDL 100 mg/dl; TG 150 mg/dl
Risk Reductio 
n
-5 -10 -15 -20 -25
Any Diabetes Related Endpoint
Microvascular Endpoints
Laser Rx
Cataract
Myocardial Infarction
-12
p029
-16
Yearly: Dilated eye exam; urinary protein; foot exam; flu shot Other: Aspirin usage; pneumococcal vaccine
pNS
-25 -24
-30 -35
p0099
p046
-29
p0031
Lancet 352: 837-853, 1998
Risk Factor Control in the US
Saydah SH et al JAMA 291:335-342, 2004
Questions to Ask Your Doctor
Whats my A1C? BP? Cholesterol? Triglycerides? Do I have albumin in my urine? Do I need a statin or ACE inhibitor? How can I minimize my chance of heart disease or a stroke? How do I get diabetes
education? Should I see a diabetes educator or dietitian? Should I see an endocrinologist?
NHANES 1988-1994 A1C 7 BP 130/80 Cholesterol 200 All 3 44 29 34 52
NHANES 1999-2000 37 36 50 73
Longterm Efficacy of Monotherapy
9
Type 2 diabetes is a progressive illness - despite best efforts, many patients will eventually require insulin to control their blood glucose
A1C
Diet
Patients at HbA1C 70
Median HbA1c
8
Su Metformin
7
Insulin
3 years 6 years 9 years
45 30 15
6 0 2 4 6 8 10
Time from randomization years
UKPDS 34, Lancet 1998; 352: 854-865 UKPDS 49 JAMA 1999; 281: 2005-12
Natural History of Type 2 Diabetes
Post-meal glucose Glucose mg/dL
Diabetes Mellitus
What is diabetes? Why is it increasing and occurring at an earlier age? Good news What should patients and the public know regarding prevention and optimal treatment? Whats new? Whats happening at FAHC/UVM?
350 300 250 200 150 100 50 -15 -10 125 100 75 50 25 0 -15 -10
IGT
Diabetes Fasting glucose
-5
0
5
10
15
20
25
Relative Function
Insulin resistance
ß-cell function
-5
0
5
10
15
20
25
Years of Diabetes Adapted from: International Diabetes Center Minneapolis, Minnesota
Incretin
Effect - Difference in the Insulin Response to Oral vs IV Glucose
Plasma Glucose mg/dL C-Peptide nmol/L
200
Oral glucose 50 g or isoglycemic infusion
Pleotrophic Effects of GLP-1
Insulin secretagogue and enhance insulin synthesis Lower glucagon secretion Flatten post-meal glycemia Slow gastric motility and emptying Weight loss Suppress appetite Promote islet ß-cell production and replacement Increased ß-cell mass in animals with type 2 diabetes
20
IV glucose Oral glucose
15 10 05 00
100
0 0 60 120 180
0
60
120
180
Time min
Time min
Adapted from Nauck MA, et al J Clin Endocrinol Metab 1986;63:492-498
Exenatide - Naturally Occurring Peptide in the Gila Monster That Acts Like GLP-1
Exendin-4 was originally isolated from the salivary secretions of the Gila monster Exendin-4 was subsequently found to circulate as a mealrelated peptide in this animal Exendin-4 has possible endocrine function in the lizard Heloderma suspectum Gila monster
Insulin Dry Aerosol Inhaler
Type 2 DM: Health-Related Quality of Life Inhaled Insulin vs SC Insulin
05
Inhaled Insulin
High preference over subcutaneous insulin ? Over OHA Better compliance to take doses as prescribed
than subcutaneous insulin Short term treatment satisfaction, quality of life, and symptom distress improve substantially in both type 1 and type 2 diabetes Increased willingness to start insulin
Mean Scale Score Change SD units
Improves
04 03 02
Overall QOL Mental Health Cognitive Functioning Symptom Distress Health Perceptions
P 01 different from SC insulin
01 0 -01 -02
Inhaled Insulin
SC
Worsens
Testa 2001
Diabetes Prevention Program
DPP Research Group NEJM 346: 393-403, 2002
12 Placebo Metformin 31 Lifestyle 58
Diabetes Mellitus
What is diabetes? Why is it increasing and occurring at an earlier age? Good news What should patients and the public know regarding prevention and optimal treatment? Whats new? Whats happening at FAHC/UVM?
3234 subjects with prediabetes, BMI 34, 45 minorities followed 28 years placebo metformin 850 mg bid lifestyle modification
Diabetes Incidence per 100 person years
10 8 6 4 2 0
Vermont Regional Diabetes Center Diabetes Clinical Research Center Pediatrics, Surgery, Cardiology, Opthamology, Transplantation
Diabetes Research Center
Di b
R
h
d
Do you take insulin at least twice a day for your type 2 diabetes?
You may be
eligible to participate in a new study conducted at the Diabetes Research Center for a new type of insulin In addition to taking insulin, qualified participants: Will have an HbA1c between 75 S 10 Will be 18-70 years of age May also be taking metformin If you qualify for this year-long study, you will receive: All study-related care All study medication and insulin at no cost
FAHC UVM
Cardiovascular Center of Excellence Diabetes Outcomes Research
For more information contact: DiabetesResearch@uvmedu
The Diabetes Research Center 802 847-8937
Islet Biology
Summary
Incidence of diabetes and associated medical burden/cost is exploding around the world Reflects modern society: Aging, lack of exercise, obesity, poor diet We know what to do for most patients: Patients should be advocates for their care Future holds enormous excitement to better understand the pathogenesis followed by novel therapies
Phone Numbers
Vermont Regional Diabetes Center 847-4576 Diabetes Research Center 847-8903 Obesity Prevention Program - Vermont Dept of Health 951-5151
Source:med.uvm.edu
