Presented By Christopher Theberge, B. S

The Potential Role of Vanadyl Sulfate As An Anti-diabetic Agent Used to Treat Non-Insulin-Dependent Diabetes Mellitus

• Presented By

• Christopher Theberge, B.S.

NIDDM Statistics

• 90%-95% of diabetes diagnoses

• 15.7 million Americans inflicted

• About 800,000 new diagnoses per year

• Increases risk of other life-threatening diseases

• Costs taxpayers $105 billion dollars per year

Vanadium

• Shellfish, mushrooms, and parsley rich in the element

• Upper limit 1.8 mg/day of elemental vanadium set for adults 19 years and older

• Most diets supply ~15 ug/day

• Needed for normal growth and development but exact role undefined

Why Vanadium?

Some Reasoning Behind the Following Studies

Metabolic Effects of Vanadyl Sulfate in Humans With Non-Insulin -Dependent Diabetes Mellitus: In Vivo and In Vitro Studies

Goldfine et al.

Goldfine et al.

• Weeks 4-10: VOSO4 ingested at 25, 50, or 100 mg doses 3x/day

• 75, 150, and 300 mg/day

• Weeks 10-12: Insulin sensitivity with 2-step euglycemic clamp

Goldfine et al.

Goldfine et al.

Goldfine et al.

• GI disturbances with 150 mg VOSO4/day in some subjects

• Cramping, abdominal discomfort, or diarrhea in all with 300 mg VOSO4/day

• Peak serum levels and time to achieve them varied greatly between subjects

• Linear correlation between peak serum level and VOSO4 dose

Goldfine et al.

Goldfine et al.

• Mean fasting glucose significantly only in 300 mg group

• Insulin sensitivity improved in several subjects at 150 mg and 300 mg doses only.

Goldfine et al.

• Basal HGP and suppression from insulin at all doses

• Oxidative and nonoxidative glucose metabolism

• TBARS @ 300 mg/day

• Glycogen synthase

• Phosphotyrosine phosphatase

• Subject weight

• Serum TG Apo A or Apo B

Effect of 150 mg/day VOSO4 on PI 3-K, insulin receptor, IRS-1 and Shc

Results/Conclusions

Limitations

• Small sample size (More Males)

• Significant distribution of age and BMI

• Meal content and inconsistent meal timings

• Absorption rates and GI side effects

Vanadyl Sulfate Improves Hepatic and Muscle Insulin Sensitivity in Type 2 Diabetes

Cusi et al.

Results

• Plasma fructosamine significantly decreased at 4 weeks and HbA1c at 6 weeks

• Diarrhea (n=4) & abdominal discomfort (n=2)

• Plasma glucose concentration reduced about 30 mg/dL during OGTT

• Plasma insulin lower during OGTT suggesting improved insulin sensitivity

Results (cont.)

Basal EGP Before and After VOSO4 Treatment

Whole Body Insulin-Mediated Glucose Disposal Before and After VOSO4 Treatment

Conclusions

• Close correlation between basal EGP reduction and improved FPG suggesting VOSO4 has an impact on liver

• Insulin sensitivity did not correlate with the decline in FPG after treatment with skeletal muscle

• VOSO4 did not stimulate insulin secretion

• Serum Vanadium levels returned to normal after 6 weeks discontinuation

Limitations

• Small sample size (Again, more males)

• Changing diet for study may have affected results

• Subjects had poorly controlled diabetes

• Sulfonylureas and diet or alone

Conclusions

• VOSO4 appears to be effective on lowering glucose levels through improved insulin sensitivity in muscle tissue without change in weight

• Appears to be relatively well-tolerated and safe short-term

• Vanadium reduced basal EGP suggesting has ability to ameliorate hepatic insulin resistance

Conclusions

• VOSO4 did not correlate with overall muscle tissue phosphatases

• Activity of specific phosphatases hard to isolate may be affected by VOSO4

• Phosphatases in specific tissues differentially affected

• Inhibition in vivo is lost in vitro

Conclusions

• Finally:

• VOSO4 is capable of becoming oxidized to vanadate in vivo, leading to less activating potential

• Effects may be different in non-Caucasian population

Future Implications

• Long term effects of Vanadium must be assessed

• More studies needed on humans (Races?)

• Effects are minimal to consider it a pharmacological option

• Newer and more effective Vanadium analogues are under development