Disease States

Adiponectin levels do not influence patients’ response to pioglitazone

Adiponectin levels do not influence patients’ response to pioglitazoneImpaired glucose tolerance (IGT) is classified as a raised level of glucose in the blood which is not high enough for the person to be classed as diabetic.  In 2012 in the UK alone it is estimated that there are around 850,000 people with undiagnosed diabetes (1). These statistics have resulted in guidelines on lifestyle modifications that can be implemented to ‘at risk’ individuals as well as numerous medications being developed to help treat patients before their symptoms turn into diabetes.

A new study published in Diabetes Care (4) assessed the drug pioglitazone to see whether its use helped to prevent type II diabetes. Researcher’s evaluated 602 participants with IGT for a mean time of 2.4 years. Participants fasted overnight and were subject to a baseline 2-hour oral glucose tolerance test which involved plasma samples taken every 15 minutes for 2 hours. Samples were tested for glucose, insulin and free fatty acids. Participants were then randomly assigned to either a placebo group, or pioglitazone.

Participants in the pioglitazone group were given a 30 mg daily dose for one month, upped to 45 mg dose for the remainder of the study (2 years after completion of enrolment). Glucose levels were taken from participants at the end of the study, at time of drop out or loss to follow-up, or time of conversion to type II diabetes.

It was found that pioglitazone decreased the conversion from IGT to diabetes by 72% in connection with improved beta-cell function by 64% and yielded an 88% increase in tissue sensitivity.

In the pioglitazone group, concentrations of plasma adiponectin increased threefold, from 13 mcg/mL to 38 mcg/mL (P<.001), and was strongly correlated with the improvement in insulin sensitivity (P<.001) and moderately correlated with glucose area under the curve during OGT (P<.005) and insulin secretion/insulin resistance index (P<.005).

The increase in adiponectin was highly predictive of a return to normal glucose tolerance and avoidance of type 2 diabetes. The baseline level of plasma adiponectin was inversely related to diabetes progression in the placebo group, but not in the pioglitazone group.

Researcher’s noted “The completely novel observation of the current study is that the increase in plasma adiponectin concentration after pioglitazone treatment correlates strongly with the prevention of type 2 diabetes and reversion to normal glucose tolerance in high-risk individuals with IGT. The potential success or failure of a specific medication or lifestyle intervention may be related to how effectively the therapy corrects the underlying pathophysiologic defect responsible for the low plasma adiponectin level.”

References:
1.)    Figure based on data from AHPO diabetes prevalence model figures http://bit.ly/aphodiabetes and the QOF 2010 figures http://bit.ly/prevalence2010
2.)    Roglic G, Unwin N, Bennett PH et al (2005). The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care 28; 2130–2135
3.)    Information Centre (2011) National diabetes Audit (NDA) Mortality Analysis 2007-2008 http://bit.ly/NDAmort
4.)    Diabetes Care- http://care.diabetesjournals.org/content/early/2014/04/02/dc13-1745.abstract

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The Randox Research division has a multitude of tests designed to aid in metabolic and nutrition research. Our Metabolic Syndrome Array II tests for adiponectic as well as Cystatin C and C-Reactive Protein allowing for multiplex analysis. For more information see Metabolic and Nutrition Research Brochure or e-mail research@randox.com.

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