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Type 2 Diabetes and Obesity Research

r-DIABETES-PREVENTION-large570Over the past 3 decades, sedentary lifestyles coupled with excessive caloric intake have been major determinants to the increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM). According to the American Diabetes Association (ADA), there are approximately 26 million Americans now living with diabetes1. In adults, type 2 diabetes accounts for 85 to 95 percent of all diagnosed cases2.

The UF Health Diabetes Institute’s Type 2 Diabetes Research Program involves an interdisciplinary network of providers from UF Adult and Pediatric Endocrinology Divisions who are committed to unlocking the causes of T2DM, identifying risk factors, and exploring novel ways to treat, educate, and ultimately prevent the disease. 

Accurate Diagnosis

Particularly among adults, diagnosis of type 1 vs. type 2 diabetes can be challenging. Around 5–15% of adults diagnosed with type 2 diabetes might actually have type 1 disease with islet autoantibodies present; if this is the case, perhaps as many as 50% of actual type 1 diabetes cases are misdiagnosed as type 2.3 In addition, rare genetic forms of diabetes, alternative to type 1 and 2, have also been identified4,5. UF researchers are paving the way to enhanced routine patient screening methods to ensure an accurate diagnoses and offer an array of available treatment options.

Education

The University of Florida is proud to be recognized as one of 4 demonstration sites for the American Association for Diabetes Educators‘ pilot study of the effectiveness and sustainability of a flexible, 5- tier type 2 diabetes education and support team that serves minority populations and utilizes professional and lay health workers.  This project addresses the challenge of creating the necessary workforce to meet HHS/CDC goals for diabetes self- management education and support. Learn more.

Risk Factors

Image courtesy of the laboratory of Kenneth Cusi, MD, Gainesville, FL USA.

Image courtesy of the laboratory of Kenneth Cusi, MD, Gainesville, FL USA.

Currently two out of three adult Americans are overweight or obese. More worrisome, one out of three children ages 9-17 are overweight or obese, raising concerns about the health of future generations.

Extending outward from the traditional role of diabetic complications, UF faculty from the Division of Adult Endocrinology are increasing their attention to early diagnosis and treatment of a novel genre of lipotoxicity-related complications, mainly nonalcoholic fatty liver disease (NAFLD). A fatty liver is now the most common chronic liver condition in adult Americans and will soon be the leading cause of end-stage liver disease in patients that are obese or have T2DM.

Although uncertain, the presence of NAFLD may play a pathogenic role, or at least be a hallmark of future T2DM6, and it is likely that this condition carries an inherent health risk to many patients with this disease:

  • UF researchers have discovered that the prevalence of prediabetes and newly diagnosed T2DM is 3x higher in obese patients with NAFLD compared to patients without fatty liver.
  • T2DM is associated with worse liver disease, including a two to four-fold increase in advanced liver disease, cirrhosis and hepatocellular carcinoma.
  • UF researchers found that sugars fructose and sucrose play a key role in the development of fatty liver and nonalcoholic steatohepatitis (NASH)7.

The nature of this relationship remains to be established and continues to be understood through interdisciplinary research efforts at UF Health.

  • Routine screening of NAFLD- Magenetic Resonance Imaging & Spectroscopy (MRS) techniques are employed to screen patients with NAFLD for T2DM and NASH, in addition to liver biopsies for individuals who are at highest risk of disease progression
  • Exploring Patient Metabolic Profile- UF research continues to unlock the complex role of ethnic makeup in patients diagnosed with NAFLD, such as high rates of sedentarism, obesity, and Hispanic ancestry
  • Identifying plasma biomarkers for diagnosis- Basic research labs focus on understanding the role of mitochondrial metabolism in the pathophysiology of obesity, insulin resistance, and fatty liver and defining how ‘nutrient overload’ causes alterations in glucose and mitochondrial metabolism in the liver8
  • Employing novel imaging techniques (ie transient elastography)- Evalute dysfuntcional metabolic pathways in the liver which could be a target for future therapeutic interventions
  • Asses the benefits and risks of pharmacological agents in the management of T2DM9
  • Combining surgery, diet, and exercise techniques

Pediatric Diabetes

Researchers at UF Health are focused on addressing the rapid emergence of childhood obesity; a precursor to T2DM. Investigators like Dr. Janet Silverstein have provided decades’ worth of evidence-based recommendations regarding the disease in youth. Current interests among UF Health Pediatric researchers include comprehensive understanding of:

  • Current and existing medication management options for reducing calorie intake (ie incretins)10
  • Benefits and risks of adult diabetes medications used in pediatric populations (ie metformin)11
  • Further understanding of novel therapies which target physiologic modalities other than enhancing or replacing insulin secretion or improving insulin sensitivity
  • Understanding pediatric-to-adult healthcare provider transitioning issues12
  • Novel gene therapy for obesity based on viral expression of adiponectin. AAV vector design. Link.

The Healthy Kids Program, sponsored by the University of Florida and the Cooperative Extension Offices, is designed to help parents and children ages 3 to 7 who are at the higher end of the growth chart improve diet, increase physical activity and modify the home environment in order to promote healthy lifestyles. The no-cost program helps families throughout the state work together to learn how to manage real-life problems and make gradual changes.

Sources:

1. American Diabetes Association. Diabetes Statistics.

2. National Diabetes Education Program. The Facts About Diabetes.

3. Tuomi T. Type 1 and type 2 diabetes: what do they have in common? Diabetes 2005; 54 (s uppl 2): 40–45.

4. Steck AK, Winter WE. Review on monogenic diabetes. Curr Opin Endocrinol Diabetes Obes. 2011 Aug;18(4):252-8.

5. Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med 2009; 360: 1646–54.

6. Lomonaco R, Cusi K. Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster? Evidence-Based Management of Diabetes; 2012 (Chapter 21).

7. Sautin, Y, Ishimoto, T, et. al. High-Fat and High-Sucrose (Western) Diet Induces Steatohepatitis That Is Dependent on Frucotkinase. Hepatology 2013: 1632-1643.

8. Cusi, K, Chang, Z, et. al. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol. 2014 Jan;60(1):167-74.

9. Lomonaco R, Cusi K., et. al. The Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus. Current Diabetes Reports 2013; Volume 13, Issue 3, pp 329-341

10. Wood JR, Silverstein J. Incretins and amylin in pediatric diabetes: new tools for management of diabetes in youth. Curr Opin Pediatr. 2013 Aug;25(4):502-8.

11. Copeland K, Silverstein J, Moore K. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics 2013; 131:364–382.

12. Cusi, K., Schatz, D., Turner, J., Strumph, P. Healthcare Transition from Pediatric to Adult Medical Homes in Diabetes Mellitus. Endocrine Practice. Feb 2014 24(2);1-25.