Chronic Disease Institute Diabetes: The Link to Obesity, CVD, Stroke and Cancer Presented by: Roberta M. Troy, PhD Health Disparities Institute for Research & Education June 26, 2014

Heart Disease Cancer Stroke Lung Disease Accidents Diabetes Alzheimers Influenza Kidney Disease Blood Poisoning Suicide Liver Disease Hypertension Top Leading Causes of Death in Alabama

African American Health Ten Leading Causes of Death for African Americans Heart Disease Cancer Stroke Diabetes Unintentional Injuries Nephritis, Nephrotic Syndrome, & Nephrosis Chronic Lower Respiratory Diseases Homicide Septicemia Alzheimer’s Disease Source: CDC, NCHS, National Vital Statistics System (NVSS), Mortality Data Deaths, Final Data for 2010

Link between Obesity, Diabetes, Heart Disease and Stroke High blood pressure leading cause of stroke Diabetes is an individual risk factor for stroke Obesity increases risk for stroke by having excess body fat leading to difficulty in blood flow and risk of blockage Source: American Heart Association

Global Burden of Diabetes In 2011, 366 million had diabetes 183 million with diabetes are undiagnosed Greatest number of those affected in the yr. age group Caused 4.6 million deaths in 2011 Diabetes cost $465 billion in healthcare expenditures in % of people live in low- and middle-income countries

Burden of Disease in Alabama In United States, 8.3% of population diabetes 7 th leading cause of death in U.S. In Alabama, 11.8% of population had diabetes 6 th leading cause of death in Alabama In Macon and Bullock Counties, 16% of residents with diabetes Source:

Prevalence of Diabetes in Alabama-2009

What is Diabetes, Really? Diabetes is a global disease Causes can be: Genetic Environmental Diabetes is a metabolic disorder that occurs because of poor utilization of insulin and thus an inability to utilize sugar (glucose) to produce energy. Insulin production good but insulin receptors defective Insulin production poor Beta cell defect in pancreas Glucose transport defects Insulin utilization poor, i.e. insulin resistance Fat increases Low Vitamin D Changes in human microflora (over- or under-abundance) in the gut

Glucose Production and Uptake

Diabetes Health Effects Leading cause of kidney failure Lower limb amputations Blindness Hypertension Nerve Damage Periodontal disease Major cause of heart disease and stroke

Obesity and Diabetes AMA recently designated obesity as a disease Defined in individuals with BMIs ≥30 Obesity is a major risk factor for diabetes, heart disease, and certain cancers In 2012, Alabama ranked 47 with respect to obesity and 46 with respect to diabetes In Macon County, 41% of adult population obese compared to 33% of population for Alabama In Bullock County, 39% of adult population obese Source: http://

Obesity and Diabetes

Insulin Resistance Promotes Several Disease States

Diabetes and Intestinal Bacteria (Methanobrevibacter smithii) In a study conducted by Mathur and colleagues (2013), people who tested positive for methane and hydrogen gases by breath analysis were observed to have higher body mass indexes and higher percentages of body fat. High levels of methane and hydrogen attributed to increased levels of the bacterium, M. smithii. This bacterium aids in conversion of food to energy in conjunction with other bacteria. Suggested that increases in the bacterium slows absorption of food and causes weight gain. Researchers also observed that individuals with higher levels of methane have higher levels of glucose in the blood.

DIABETES AND HEART DISEASE

Diabetic Heart Disease Diabetic heart disease --develops in people with diabetes Coronary artery disease Hypertension Congestive heart failure Arrythmia Heart attack

Diabetes, Heart Disease and Intestinal Microflora Recent investigations by Hazan and others (2013) show a microbial by-product contributes to heart disease and can serve as a predictor for heart attacks The compound is trimethylamine N-oxide (TMAO) It is produced after consuming foods containing lecithin such as eggs Antibiotic therapy reduced levels of TMAO with no further TMAO formed even after injesting lecithin-containing foods Increased levels of TMAO proposed to contribute to heart disease and even death Cleveland Clinic (2013, April 24). Gut bacteria byproduct predicts heart attack and stroke. ScienceDaily. Retrieved July 26, 2013, from /releases/2013/04/ htm

Diabetes and Cancer Certain cancers occur more frequently in individuals with type II diabetes: Pancreatic colorectal breast hepatobiliary bladder endometrial cancers Common risk factors Hyperinsulinemia Insulin resistance obesity

Mechanisms Linking Diabetes and Cancer Reference:

High Sugar Levels Induce Expression of Cancer- Causing Genes Under normal conditions, sugars in the intestine induce the release of the GIP hormone which induces the release of insulin from the pancreas The release of GIP is controlled by a protein called β- catenin β-catenin activity dependent upon sugar levels High levels of sugar promote accumulation of β-catenin in the cell nuclei Nuclear β-catenin causes increased cell growth or proliferation Increased cell proliferation causes cancer madrimasd (2013, February 1). Excess sugar linked to cancer. ScienceDaily. Retrieved July 25, 2013, from /releases/2013/02/ htm

Cancer and Intestinal Microflora Studies in obese and lean mice revealed changes in intestinal bacteria composition Increase in bacteria that produce deoxycholic acid (DCA) DCA damages DNA Investigators observed liver cancer development in the mice When mice were treated with an antibiotic, DCA levels were reduced, thereby reducing cancer risk This investigation shows a clear link between obesity and cancer development

Stroke Blood vessel blocked or ruptured preventing blood flow and oxygen to the brain Brain cells can die resulting in disability or death Occurs more in older women and African Americans Family history of stroke is a risk factor Act FAST to respond to stroke Face Arms Speech Time Contributing risk factors could be diet

Summary Intestinal microflora changes can result in increases of harmful bacteria These bacteria can produce by-products that alter the metabolism of individuals These alterations may give rise to obesity, diabetes, heart disease, stroke and cancer Since there is a high prevalence of obesity, diabetes, heart disease and certain cancers in racial/ethnic minorities, perhaps the high risk could be due to changes in the intestinal microflora Contributing factors could be diet

Management and Prevention Nutritional Management Physical Activity Smoking Cessation