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Diabetes A Major Health Problem for All. Stuart R. Chipkin, MD, FACE School of Public Health and Health Sciences University of Massachusetts, Amherst. Diabetes- Precursors and Complications. I. Diabetes- M ajor cause of morbidity and mortality in US and Russia II. Risk factor analysis
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DiabetesA Major Health Problem for All Stuart R. Chipkin, MD, FACE School of Public Health and Health Sciences University of Massachusetts, Amherst
Diabetes- Precursors and Complications I. Diabetes- Major cause of morbidity and mortality in US and Russia II. Risk factor analysis • Nutrition- Diet choices • Physical activity and inactivity • Other Risk factors- blood pressure, tobacco, cholesterol, III. Research/program description 1. Pre-diabetes: Research study to compare physical activity, medication or combination - Outcome: insulin sensitivity 2. Diabetes: Share diabetes personnel with four primary care sites - Outcome: laboratory data (a1c) and ER visits 3. Risk factors for complications: Electronic Medical Record data collection, state guidelines promotion, case manager utilization - Blood pressure, cholesterol, foot examinations, eye examinations
Classification of Diabetes Mellitus by Etiology Type 1-cell destruction—complete lack of insulin Type 2-cell dysfunction and insulin resistance Gestational-cell dysfunction and insulin resistance during pregnancy Other specific types • Genetic defects of -cell function • Exocrine pancreatic diseases •Endocrinopathies • Drug- or chemical-induced • Other rare forms 11
Defects in Diabetes • Type 1 diabetes • The main abnormality is absolute insulin deficiency • Type 2 diabetes • Both insulin resistance and relative insulin deficiency contribute • Glucotoxicity and lipotoxicity • Poor metabolic control worsens insulin deficiency and insulin resistance
Diabetes in the U.S. • Current estimates: • Over 24 million people in U.S. (7%) • Over age 60, rates exceed 20% • Recent increases of 20% may be reaching a plateau • type 1 = 10% (2 million) • type 2 = 90% (21 million) • Currently 6-7 million are still undiagnosed • Prevalence of “pre-diabetes” over 42 million • Total treatment cost: $174 billion/yr
Medical Complications of Hyperglycemia • Microvascular • Eye: retinopathy, cataracts, glaucoma • Renal: kidney failure • Nerve: peripheral neuropathy (sensory, painful), autonomic neuropathy (cardiac, gastrointestinal, urological) • Macrovascular • Cardiovascular disorders: Coronary artery disease, heart failure, cardiomyopathy • Cerebrovascular disorders: stroke • Peripheral vascular disease 3
Retinopathy in Diabetes Patients- Northwest Russia (Arkhangelsk ) Dedov I et al; Rev Diabet Stud. 2009 Summer; 6(2): 124–129.
Cataract Prevalence in Diabetes Patients- Northwest Russia Dedov I et al; Rev Diabet Stud. 2009 Summer; 6(2): 124–129.
Diabetes Patients- Northwest Russia Dedov I et al; Rev Diabet Stud. 2009 Summer; 6(2): 124–129.
Consequences of Diabetes • Premature morbidity and mortality • Cardiovascular disease risk increased 2-4 times • Exceeds cost of treating all other complications combined • Stroke risk increased 2.5 times • Leading cause of new blindness in people 20-74 years old • Leading cause of non-traumatic amputation • Reportedly higher rates in Russia • Leading cause of kidney failure
Key Facts- World Health Organization • Worldwide, more than 220 million people have diabetes. • In 2005, an estimated 1.1 million people died from diabetes. • Almost half of diabetes deaths occur in people under the age of 70 years; 55% of diabetes deaths are in women. • WHO projects that diabetes deaths will double between 2005 and 2030. • Healthy diet, regular physical activity, maintaining a normal body weight and avoiding tobacco use can prevent or delay the onset of diabetes.
Measures of Hyperglycemia • Random plasma glucose (RPG)— without regard to time of last meal • Fasting plasma glucose (FPG)— before breakfast • Oral glucose tolerance test (OGTT)— 2 hours after a 75-g oral glucose drink • Postprandial plasma glucose (PPG)— 2 hours after a meal • Hemoglobin A1c (A1C)— reflects mean glucose over 2–3 months • Fructosamine/glycated serum protein— reflects mean glucose over 1–2 weeks 5
Making the Diagnosis of Diabetes Symptoms of diabetes plus random plasma glucose 200 mg/dL (11.1 mM)* or Fasting Plasma Glucose 126 mg/dL (7mM)* or 2-h PG during a 75-g OGTT 200 mg/dL (11.1 mM)* or A1c > 6.5% *Requires confirmation by repeat testing American Diabetes Association. Diabetes Care.2010; (suppl1)
Glucose Tolerance Categories 2-hr Post Prandial Glucose (OGTT) Fasting Plasma Glucose Plasma glucose (mg/dL) 240 Diabetes Mellitus 220 200 Diabetes Mellitus 180 IGT 160 140 126 120 IFG Normal 100 Normal 80 60 American Diabetes Association. Diabetes Care.2010; (suppl1)
Impaired Glucose Tolerance (IGT) 2-h PG on OGTT 140 but 200 mg/dL Predicts increased risk of diabetes and cardiovascular disease Impaired Fasting Glucose (IFG) FPG 100 but 126 mg/dL Predicts increased risk of diabetes and micro- and macrovascular complications Impaired Fasting Glucose and Impaired Glucose ToleranceDifferent conditions intermediate Between Normal and Diabetes 9
Who Should Be Tested for Diabetes?Consider if One or More of the Following Apply • Symptoms suggesting diabetes: weight loss, hunger, urinary frequency, blurred vision • Age >45 (>30 if patient has other risk factors) • Prior IGT or IFG or family history of diabetes • Prior gestational diabetes or baby weighing >9 lb (4.1kg) • Women with polycystic ovarian syndrome (PCOS) • Obesity (BMI 25 kg/m2), especially adolescents • African, Latino, Asian, or Native American ancestry • History of vascular disease or hypertension American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S11-S14;AACE/ACE medical guidelines. EndocrPract. 2002;8(suppl 1):40-82
Prerequisites for a Prevention Program • Important health problem posing a significant health burden on society • Well-understood natural history with identifiable parameters that measure progression to disease • Test to identify the pre-disease state that is safe, acceptable and predictive • Safe, effective and reliable means of preventing or delaying disease • Ability to find high-risk individuals and the cost of the intervention should be cost-effective and not burdensome Sherwin R et al; Diabetes Care 27:S48-S54, 2004
Etiology of Type 2 DiabetesImpaired Insulin Secretion and Insulin Resistance Genes and environment Impaired insulin secretion Insulin resistance Impaired glucose tolerance Type 2 diabetes Progressive hyperglycemia and high free fatty acids
Natural History of Type 2 Diabetes Impaired glucose tolerance Undiagnosed diabetes Known diabetes Insulin resistance Insulin secretion Postprandial glucose Fasting glucose Microvascular complications Macrovascular complications Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789 17
Prevention of Type 2 Diabetes • Insulin resistance may be an important early stage of intervention • Evidence exists for interventions to increase insulin sensitivity
Clustering of Factors Reflecting Insulin Resistance in Russia Sidorenkov et al. BMC Public Health 2010, 10:23
Diabetes Prevention • Case study 45 year old woman comes to see you because her older brother was recently diagnosed with diabetes. She is overweight, tries to avoid sugar, and says that she exercises when she cleans her house. She has been told of high blood pressure and high cholesterol. She was told to exercise and decrease her salt. Her father had diabetes and had a leg amputation.
Diabetes prevention • Case study Physical examination notes a blood pressure of 150/88, pulse of 76 and BMI of 29 kg/m2. Fasting laboratory test shows: - Glucose of 122 mg/dl (6.8 mM) - Electrolytes and kidney function normal - Liver tests (ALT/AST are twice normal) - Triglyceride= 280 (3.2 mmol/L) - HDL= 29 (0.75 mmol/L) - LDL= 150 mg/dl (3.9 mmol/L)
Diabetes Prevention • Which of these would you do next? • Tell her to keep exercising and watching her diet. • Tell her to cut out all sugar in her diet. • Find out more about why she doesn’t exercise more. • Find out how she defines a healthy diet. • Discuss barriers to physical activity. • Start medication. • Are there other resources for her? • Family • Work • Community
Diabetes Prevention- Finnish Study • Incidence of diabetes • Control group: 59 (23%) • 6% per year • Intervention group: 27 (11%) • 3% per year • Overall risk reduction of 58% • Diabetes did not develop in any of the subjects who reached at least four of five goals
Diabetes Prevention Program • Crude incidence (cases per 100 person-years) • Placebo 11.0 • Metformin 7.8 • Lifestyle 4.8 • Estimated cumulative incidence of diabetes • Placebo 28.9% • Metformin 21.7% • Lifestyle 14.4% • Compared with placebo, diabetes risk was • 58% lower in lifestyle group • 31% lower in metformin group
Diabetes Prevention Program • Number needed to treat (three years) • Lifestyle 6.9 • Metformin 13.9 • Advantage of lifestyle was greater in • Older subjects • Lower BMI
What about metformin PLUS lifestyle? Progress to DM Cntrl= 55% Green= Control Relative Risk Reduction: - Turquoise= Lifestyle (p=0.018) - Red= Metformin (0.029) - Blue= Metformin + Lifestyle (0.022) LSM=39.3% MET=40.5% LSM+MET= 39.5% Ramachandran A et al; Diabetologia 49: 289-297, 2006
India Diabetes Prevention Program • While metformin and lifestyle both prevented or delayed onset of diabetes, there was no additive effect. • Compared with U.S. DPP, India DPP: • Used smaller dose of metformin • Had baseline diets close to recommended • Subjects did not lose weight
Impact of Energy Deficit on Insulin Sensitivity Black SE et al: J ApplPhysiol, 99:2285-2293, 2005
Research QuestionEnergy Metabolism Laboratory • Examine the impact of three strategies on insulin sensitivity in people with pre-diabetes (either IFG alone or IFG with IGT) • Metformin alone • Structured, supervised exercise program (3x per week for 12 weeks) • Metformin + exercise • Outcome measures • Insulin sensitivity (euglycemichyperinsulinemic clamp) • Weight, BMI, waist circumference, blood pressure • Fasting glucose, lipid profile, body composition
Impact of metformin, lifestyle or both “Pre-diabetes” subjects Malin S et al IPE, Miami, FLA 2010;
Diabetes • Case study 51 year old man presents with increasing fatigue and muscle weakness. He does manual work and has noticed a change in his endurance. While he thought he was just getting older, a fellow employee saw him going to urinate several times in one shift and checked his blood sugar using a meter; the glucose was 360 mg/dl (20 mM). He has not been to the doctor in many years. He smokes 1 pack of cigarettes per day and drinks 1 liter of vodka every 2 days. He plays soccer on weekends “but only in nice weather”. He lives alone. His mother had diabetes- so did her siblings.
Diabetes- case study Physical examination: Pulse= 96 BP=160/98 BMI=36 kg/m2 Fundi: small microaneurysms Neck: no goiter, no bruits Lungs: clear. Heart: normal heart sounds (tachycardia) Abdomen: soft, bowel sounds present. No liver/spleen enlargement Ext: no swelling. Pulses in feet present. Skin is dry and cracked. Neuro: No Achilles reflexes but patellar 2/2
Diabetes- case study • Laboratory tests: • Glucose= 480 mg/dl (23.3 mmol/L) • Potassium= 3.8 meq/L • Creatinine= 1.9 mg/dl (168 umol/L) • Triglycerides= 480 mg/dl (5.4 mmol/L) • HDL cholesterol= 18 mg/dl (0.47 mmol/L) • LDL cholesterol= 175 mg/dl (4.5 mmol/L) • Urine: no ketones, 3+ glucose
Diabetes- new onset • What are next steps • Education- who does this? • Diet • Physical activity • Self blood glucose monitoring • Medications • How can you implement your plan? • Family • Work • Community
Estimates for Diabetes in Russia2010 http://www.diabetesatlas.org/map
Survey of Diabetes Awareness • Russia Longitudinal Monitoring Survey (RLMS- www.cpc.unc.edu/rlms): • 38 sites across Russian Federation (St. Petersburg, Moscow and 36 districts based on SES, urban/rural status status • Major findings: • Over half the individuals who reported having diabetes did not receive any formal medical treatment or dietary advice. • Half those who were “diabetes aware” in this survey were receiving no medical treatment, not even advice about weight loss or diet. • Limiting factor for medication changed during the study from availability to affordability Perlman F and McKee Martin Diab Res and ClinPract 80:305-313, 2008.
Percent of Patients with Diabetes Reaching A1C Goal < 7% in 2010
Diabetes- Risk Factors for Complications • Case study 67 year old man comes to see you after being seen in hospital for infected foot ulcer. He has had diabetes for 18 years. Also has poorly controlled hypertension and high cholesterol. He is on a diuretic for HTN and a low dose statin for cholesterol. He was told he should take insulin for his diabetes. He went to a diabetes education program 10 years ago. He does not monitor his blood sugars at home. He “tries” to follow a diet. He does not exercise. He used to smoke more but has decreased. He did not smoke while in the hospital. His father died from kidney failure due to diabetes. His older brother had a stroke. He lives with his wife; he has two children who are married and live nearby.
Diabetes- Risk Factors for Complications Physical examination notes a blood pressure of 140/90, pulse of 72 and BMI of 31 kg/m2. He has background retinopathy, clear lungs, systolic heart murmur and benign abdomen. His feet are dry and pulses are poor. He does not feel a monofilament on his toes. There is a healing ulcer on the right foot- 3 cm in diameter over the lateral malleolus. Laboratory test: - a1c= 11% - Triglyceride= 160 mg/dl (1.81 mmol/L) - HDL= 30 mg/dl (0.77 mmol/L) - LDL= 118 mg/dl (3.1 mmol/L) - creatinine= 1.9 () - urine albumin:creat ratio= 80
Diabetes- Risk Factors for Complications • What other questions do you have for him? • How do you prioritize his problems? • How will you address his problems? • Immediate vs. Long-term • Other professionals to involve • Community resources
Percent of Patients with Diabetes Reaching LDL Goal < 100 mg/dl (<2.59 mmol/L) in 2010
UMass School of Public Health & Health SciencesAreas of Diabetes Research • Prevention • Focus has been on improving insulin sensitivity and contribution of combining medication with physical activity • Limitations: unclear applicability to clinical endpoint • Challenges: Controlling diet, measuring activity outside of protocol • Importance: Relatively poor understanding about details of • Type of exercise: aerobic vs. resistance • Duration or intensity of exercise • Frequency of exercise • If exercise is a drug, we know relatively little about the dose, frequency, or duration of this “medicine” in terms of preventing diabetes
UMass School of Public Health & Health SciencesAreas of Diabetes Research • Strategies to maximize diabetes care • Integrate specialized services within an outpatient primary care practice • Endocrinologist, physician assistant, nurse educator, dietitian • Involve other specialties (podiatry, behavioral health, physical therapy, ophthalmology, dental, renal) • Educational conferences on difficult cases and relevant topics • Limitations: • Data from electronic medical record combines all values from all patients (even repeats) • Applicable to patients participating in health services (but Massachusetts now requires all residents to have insurance) • Uncertain which components were most effective. • Challenges • How to evaluate program (Difficult to track visits/admissions to Emergency or Hospital, how quantify “prevented event”) • Implementing life style changes (diet and exercise • Importance • Increasing numbers of diabetes patients will utilize increasing health care dollars unless effective strategies identified to maximize care in outpatient setting.
UMass School of Public Health & Health SciencesAreas of Diabetes Research • Prevention of diabetes-related complications: Focus on risk factors • Utilize electronic medical record (EMR) to track • Lipid profile • Blood pressure • Urine albumin:creatinine ratio • Foot examinations • Limitations • Some aspects of EMR difficult to abstract (e.g., foot exams) • Unsure which interventions were most effective • Challenges • Multiple medicines with side effects • Implementing life style changes (diet and exercise) • Maintaining changes over time course needed to prevent poor outcomes • Importance • Large cost of diabetes relates to its complications