title: Pressure-induced pain: early sign of diabetes-associated impairment of insulin production in rats.
abstract: The lack of simple, non-invasive tests for a sub-clinical decline in insulin production hampers detection of early-stage type 1 pre-diabetes. Pressure pain withdrawal threshold (PPT) is a sensitive index of insulinopenia in diabetic and 'pre-diabetic' rats, but its ability to detect human insulin insufficiency is not known; if predictive, PPT testing of those at risk for diabetes would be warranted. To address this question, we used meta-analyses to demonstrate (i) a similar relationship between blood glucose and insulin levels in humans and diabetic rats and (ii) the predictive value of PPT for insulinopenia in a composite group (n=53) of control, streptozotocin (STZ)-diabetic (STZ-HG), and normoglycemic (STZ-NG) rats. The frequency distributions of pooled insulin levels (ng/ml) consisted of three sub-populations, with peak values of <0.5, 1.5+/-0.05, and 3.2+/-0.04. Using the 2.3rd percentile of the sub-population with the highest insulin level (2.81 ng/ml) as a cut-off to define insulinopenia, 40 animals (98% of STZ and 25% of controls) were identified with compromised insulin production. The frequency distribution of pooled PPT values also consisted of three sub-populations (peaks at 75.9+/-0.6 g, 97+/-0.3 g and 122+/-0.8 g), and when 106 g (the 2.3rd percentile of the most pressure-tolerant sub-population) was used as a cut-off, PPT measurements identified 92% of STZ-injected rats and 83% of rats with insulinopenia, as defined by 2.81 ng/ml insulin cut-off. Assuming similar between-species pain mechanisms, these findings support the potential usefulness of PPT measurements for detection of early-stage human type 1 diabetes.
authors.affiliation: Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Romanovsky
authors.forename: Maxim
authors.initials: M
authors.lastname: Dobretsov
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D004195:Disease Models, Animal; D042241:Early Diagnosis; D006801:Humans; D007328:Insulin / Q000096:biosynthesis* / Q000097:blood / Q000172:deficiency*; D008297:Male; D010147:Pain Measurement / Q000379:methods*; D017288:Pain Threshold / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects / Q000379:methods; D011312:Pressure / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007328:Insulin