Diabetes A Major Health Problem for All Stuart R. Chipkin, MD, FACE School of Public Health and...

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- Major cause of morbidity and mortality in US and Russia II. Risk factor analysis 1.Nutrition- Diet choices 2.Physical activity and inactivity 3.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 destructioncomplete lack of insulin Type 2 -cell dysfunction and insulin resistance Gestational -cell dysfunction and insulin resistance during pregnancy Other specific typesGenetic defects of -cell function Exocrine pancreatic diseases Endocrinopathies Drug- or chemical-induced Other rare forms 11

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 Defects in Diabetes

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 Diabetes in the U.S.

Diabetes Prevalence Russian Federation YearDefinitionSex Age Group Sample Size Prevalence(%) 2001 Questionnaire, self reported diabetic Males25-645332.3 2001 Questionnaire, self reported diabetic Females25-6411354.3

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): 124129.

Cataract Prevalence in Diabetes Patients- Northwest Russia Dedov I et al; Rev Diabet Stud. 2009 Summer; 6(2): 124129.

Diabetes Patients- Northwest Russia Dedov I et al; Rev Diabet Stud. 2009 Summer; 6(2): 124129.

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 A 1c (A1C) reflects mean glucose over 23 months Fructosamine/glycated serum protein reflects mean glucose over 12 weeks 5

American Diabetes Association. Diabetes Care. 2010; (suppl 1) *Requires confirmation by repeat testing 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% Making the Diagnosis of Diabetes

Glucose Tolerance Categories American Diabetes Association. Diabetes Care. 2010; (suppl 1) Fasting Plasma Glucose 2-hr Post Prandial Glucose (OGTT) 126 60 80 100 120 140 160 180 200 Plasma glucose (mg/dL) Normal Diabetes Mellitus 240 220 Diabetes Mellitus Normal IGT IFG

Impaired Fasting Glucose and Impaired Glucose Tolerance Different conditions intermediate Between Normal and Diabetes 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 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/m 2 ), 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. Endocr Pract. 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 Diabetes Impaired Insulin Secretion and Insulin Resistance Type 2 diabetes Genes and environment Impaired insulin secretion Insulin resistance Impaired glucose tolerance Progressive hyperglycemia and high free fatty acids

Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789 Natural History of Type 2 Diabetes Macrovascular complications Microvascular complications Insulin resistance Impaired glucose tolerance Undiagnoseddiabetes Known diabetes Insulin secretion Postprandial glucose Fasting glucose 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/m 2. 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 doesnt 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

Tuomilehto et al; NEJM 344: 1343-50, 2001

Diabetes Prevention Program Crude incidence (cases per 100 person-years) -Placebo11.0 -Metformin 7.8 -Lifestyle 4.8 -Estimated cumulative incidence of diabetes -Placebo28.9% -Metformin21.7% -Lifestyle14.4% Compared with placebo, diabetes risk was 58% lower in lifestyle group 31% lower in metformin group

N Engl J Med; 346: 393-403, 2002

Diabetes Prevention Program Number needed to treat (three years) Lifestyle 6.9 Metformin13.9 Advantage of lifestyle was greater in Older subjects Lower BMI

What about metformin PLUS lifestyle? Ramachandran A et al; Diabetologia 49: 289-297, 2006 Green= Control Relative Risk Reduction: - Turquoise= Lifestyle (p=0.018) - Red= Metformin (0.029) - Blue= Metformin + Lifestyle (0.022) Progress to DM Cntrl= 55% LSM=39.3% MET=40.5% LSM+MET= 39.5%

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 Appl Physiol, 99:2285-2293, 2005

Research Question Energy 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 ( euglycemic hyperinsulinemic 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/m 2 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

Number of people with diabetes9,624,900 Percent with impaired glucose tolerance (20-79 years) 16.7 New cases of type 1 diabetes (children

Survey of Diabetes Awareness Russia Longitudinal Monitoring Survey (RLMS- www.cpc.unc.edu/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 Clin Pract 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/m 2. 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 (

Diabetes A Major Health Problem for All Stuart R. Chipkin, MD, FACE School of Public Health and...

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