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Barnstable Brown Kentucky Diabetes and Obesity Center

BBDOC

BARNSTABLE BROWN OBESITY AND DIABETES RESEARCH DAY


Robert Lodder, Ph.D.

Picture of Dr. Lodder   
   


          Professor, Department of Pharmaceutical Sciences






Contact Information

Training and Publications

University of Kentucky CV Summary from the Community of Science Database
A123 ASTeCC Building Publication Listing on PubMed
145 Graham Avenue
Lexington, KY 40536-0286  
Telephone: (859) 257-9232  
Fax: (859) 257-2489  
 

Research Interests

Dr. Lodder's research is on the use of D-tagatose as an oral therapy for diabetes.
Tagatose is now in phase 3 clinical trial. An epimer of fructose, the natural hexose tagatose was originally developed by Spherix, Inc. as a low-calorie sugar substitute. Only 20% of orally ingested tagatose is fully metabolized, principally in the liver, following a metabolic pathway identical to that of fructose. Tagatose is generally recognized as safe for use in foods and beverages under US FDA regulations. The simple sugar is commercially produced by isomerization of galactose, which is prepared from lactose. Early human studies suggested tagatose as a potential antidiabetic drug through its beneficial effects on postprandial hyperglycemia and hyperinsulinemia. A subsequent 14-month trial confirmed its potential for treating type 2 diabetes, and tagatose showed promise for inducing weight loss and raising high-density lipoprotein cholesterol, both important to the control of diabetes and constituting benefits independent of the disease. Furthermore, tagatose has been shown to be an antioxidant and a prebiotic.

In an ongoing single-blind study designed to establish the minimum dose of tagatose capable of causing a beneficial effect, tagatose is administered orally with meals, three times daily (TID) at three different doses: 2.5, 5.0, and 7.5 g. The comparator is the 2.5 g dose.

The primary endpoint for the study is reduction in HbA1c after 6 months on the drug. After 6 months on drug, the patients in the 7.5 g group experienced an average reduction of 0.3% in HbA1c from the HbA1c of the 2.5 g group. At that same 6-month point, the 5.0 g group averaged a reduction in HbA1c of 0.05% from the 2.5 g group. Tagatose appears to begin showing an effect on HbA1c within the range of doses selected for this minimum-dose study. The ongoing Phase 3 double-blinded study of efficacy is being conducted at a 15 g dose (TID), and is powered to detect a 0.5% reduction in HbA1c.

Over the course of the Phase 2 trial, tagatose also decreased the average serum triglycerides of the patients by -59 mg/dl by the end of the first month on therapy, a decrease from baseline that remained at -41 mg/dl by the end of the 6 months of the trial. Tagatose also decreased serum LDL by an average -13 mg/dl by the end of the first month on therapy, while serum HDL was essentially unchanged (+0.9 mg/dl). The LDL:HDL ratio was improved for two of the three dose groups by an average of 0.3.

Other studies examine the effect of D-tagatose on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low-density lipoprotein receptor deficient (LDLr –/– ) mice. Food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis are measured.

Macrophage immunostaining and collagen content are examined in aortic root lesions. Control and tagatose-fed mice exhibit similar energy intake, body weights and blood glucose and insulin concentrations, but sucrose-fed mice exhibit increased energy intake and became obese and hyperglycemic. Adipocyte diameter increases in female sucrose-fed mice compared to tagatose and control. Male and female sucrose-fed mice show increased serum cholesterol and triglyceride concentrations compared to tagatose and controls. Atherosclerosis is increased in sucrose-fed mice of both genders compared to tagatose and control. Lesions from sucrose-fed mice exhibit pronounced macrophage immunostaining and reductions in collagen content compared to tagatose and control mice.

These results demonstrate that in comparison to sucrose, equivalent substitution of tagatose as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.

Recently, Dr. Lodder has conducted studies in mouse models of the metabolic syndrome to test the synergistic effects of D-tagatose with trans piceid. In experiments with apoE -/- mice, with treatment an almost 500% reduction in atherosclerosis was found in the aortic arch (p<0.01), the thoracic aorta (p<0.05), and the aortic sinus (p<0.05). A 50% reduction in serum cholesterol was also observed. New results in abdominal aortic aneurysm studies in both LDLr -/- and ApoE -/- mice revealed a statistically significant reduction in the rate of growth of established aneurysms with treatment as well.

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Page last updated Tuesday, March 12, 2013