Type 2 Diabetes Research

Researcher in lab

From 1980 to 2011, the number of Americans with diagnosed diabetes more than tripled – from 5.6 million to 20.9 million – according to the Centers for Disease Control and Prevention. Sedentary lifestyles coupled with increased caloric intake have been major determinants to the increase in the prevalence of the disease. In adults, type 2 diabetes accounts for 95 percent of all diagnosed cases.

This is a manageable disease. It is also preventable. At the UF Diabetes Institute, we are working to unlock the mysteries of type 2 diabetes and its complications, and identifying risk factors and innovating new ways to treat, educate, and ultimately prevent the disease.

Accurate Diagnosis

Particularly among adults, diagnosis of type 1 versus type 2 diabetes can be challenging. Around 5–15 percent of adults diagnosed with type 2 diabetes might actually have type 1 diabetes with islet autoantibodies present; if this is the case, perhaps as many as 50 percent of actual type 1 diabetes cases are misdiagnosed as type 2. In addition, rare genetic forms of diabetes, alternative to type 1 and type 2, have been identified. UF researchers are improving screening standards for diabetes to ensure accurate diagnoses of disease manifestation and offer an array of available safe, available treatment options which may help to predict future risk.

Identify at Risk

Currently, two out of three adult Americans are overweight or obese — a precursor to type 2 diabetes. Lifestyle interventions can be effective in helping individuals lose weight, but participants commonly regain much of the weight after program completion. UF researchers are exploring ways to address the issue for all populations. In-person, extended care programs can help in maintaining weight loss, but individuals who live in rural areas—who are more likely to be obese—may find it difficult to travel to such programs.  A 2012 study led by University of Florida researchers found that almost 40 percent of rural adults were obese compared with just over 33 percent of urban adults. Several lifestyle differences may have an impact on higher obesity rates in rural areas, including a traditional farm diet of high-fat, high-calorie foods, and increased mechanization of rural occupations such as farming and logging. The UF Diabetes Institute, together with UF’s Institute of Food and Agricultural Sciences, is the coordinating agency for the development of an ongoing educational problem-solving model to address barriers to maintaining eating and exercise behaviors required to sustain weight loss. Researchers with UF IFAS are also using chemistry, genetics and taste to develop better-tasting fruits and vegetables that can inspire better diet choices. 

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

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

Finding Real Solutions

Left untreated, diabetes can damage the retina, causing blindness, and destroy the kidneys. Over time, high blood sugar levels can also reduce circulation in the limbs, ultimately requiring amputation. Extending outward from the traditional role of diabetic complications, UF Health clinicians are increasing their attention to early diagnosis and treatment of a novel genre of lipotoxicity-related complications, including nonalcoholic fatty liver disease. 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 type 2 diabetes. As many as 80% of obese subjects and patients with diabetes have non-alcoholic fatty liver disease (NAFLD). 

Although uncertain, this rather silent condition may lead to T2DM, and it is likely that this condition also carries an inherent health risk for patients diagnosed with cardiovascular disease, cirrhosis and/or liver cancer.

  • UF researchers have discovered that the prevalence of prediabetes and newly diagnosed T2DM is three times 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).

UF researchers are also working to improve screening for a number of disease-related complications, including peripheral arterial disease (PAD); a condition that carries an inherent risk for type 2 diabetes, stroke, morbidity and death. PAD occurs in nearly 30% of patients over the age of 70 or in patients between 50 to 69 years old who have diabetes or past history of smoking. 

Interdisciplinary efforts in type 2 diabetes research include:

  • Evaluating pharmacological agents and experimental therapies for treatment and management of type 2 diabetes, lipid disorders, and hypertension
  • Exploring Patient Profile- UF research continues to unlock the complex role of ethnic makeup in patients diagnosed with T2DM and NAFLD, such as high rates of sedentarism, obesity, and family history
  • 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 liver
  • Utilize non-invasive imaging techniques (ie transient elastography, MRI)- Evaluate dysfunctional metabolic pathways in the liver which could be a target for future therapeutic interventions
  • Blended-Patient Approach- Combining bariatric surgery, diet, and exercise techniques

Our Next Generation

One decade ago, type 2 diabetes was referred to “adult-onset diabetes.” Today, one out of three children ages 9-17 are classified as overweight or obese — raising concerns about the health of future generations. Emerging research shows that the progression of diabetes appears more rapidly in children than adults. It has also been shown to be more challenging to treat. UF investigators like Dr. Janet Silverstein  have influenced school training standards and standards of care for children with diabetes at the local, state, and national level for decades.

Current research efforts in youth include:

  • Medication management options for reducing caloric intake (ie incretins)
  • Assesing benefits and risks of using adult diabetes medications in pediatric populations (ie metformin)
  • Addressing unique pediatric-to-adult healthcare provider transition issues
  • Reducing the intake of sugar-sweetened beverages
  • Novel therapies targeting physiologic modalities alternative to enhancing or replacing insulin secretion

The TODAY Genetics study explores the the role genetics plays in type 2 diabetes, insulin resistance and cardiac risk in youth. The information made available through this study may help scientists to develop new diagnostic tests, new treatments and new ways to prevent diseases.

The Healthy Kids Program, sponsored by the University of Florida and UF/IFAS 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.

Selected Bibliography:

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. Befort, C. A., Nazir, N. and Perri, M. G. (2012), Prevalence of Obesity Among Adults From Rural and Urban Areas of the United States: Findings From NHANES (2005-2008). The Journal of Rural Health, 28: 392–397.

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

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

9. 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.

10. 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

11. 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.

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

13. 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.