Diabetes, primarily type 2 diabetes, has increased in prevalence throughout the world and current projections suggest a continued rise worldwide for at least the next quarter century. Insulin resistance, which frequently accompanies obesity, is known to be a key factor in the pathogenic development of type 2 diabetes (1–6). Type 2 diabetes occurs when insulin secretion is no longer sufficient to compensate for the resistance to the actions of insulin. Measurements of insulin sensitivity and secretion are currently done only for research purposes and are only comparable in individual studies. There are no clinical applications for these measures. In fact, there are no criteria by which an individual could be classified as being insulin sensitive or resistant or as having mild, moderate, or severe impairment of insulin secretion. In theory, one could envision that knowledge of an individual's response to insulin or the ability to secrete insulin might be useful for selecting patients for intensified prevention efforts, in the choice of initial therapy upon onset of overt hyperglycemia, or in evaluating the response to therapy beyond glycemia. For example, if a person newly diagnosed with diabetes could be determined to be very insulin resistant, the choice of initial therapy could be a drug that primarily improves insulin sensitivity. On the other hand, if the person was only moderately insulin resistant but had more of a defect in insulin secretion, a drug that improves insulin secretion might …

In their recent commentary, Staten et al. (1) describe their very valuable attempt to standardize insulin assays. Their aim is to allow quantitative comparison of the results obtained in one lab with those measured by a different assay in another lab. I'd like to highlight an issue when it comes to reporting the results. The insulin concentration must be stated in SI units nowadays, i.e., in pmol/l instead of μU/ml. The latter unit refers to the biologic action of this hormone (i.e., its blood glucose–lowering activity) and the former to the number of insulin molecules in a given volume. A fixed conversion factor is used to convert the microunits …

BACKGROUND Circulating insulin concentration in serum or plasma provides important information for the estimation of insulin secretion and insulin resistance. Currently, lack of standardization of insulin assays hinders efforts to achieve consistent measures for treatment guidelines. METHODS A Workgroup convened by the American Diabetes Association evaluated 12 different commercial insulin methods from 9 manufacturers. RESULTS The within-assay CVs ranged from 3.7% to 39.0%, with 7 of 10 assays having a CV < or =10.6%. The among-assay CVs ranged from 12% to 66%, with a median value of 24%. A common insulin reference preparation did not change the among-assay CV and failed to improve harmonization of results among assays. Results from 6 of 10 assays agreed within the total error of 32% that is allowable based on biological variability criteria. Seven of 10 assays recovered insulin added to a serum pool within 15.5% of the expected concentration. In 9 of 10 methods, there was <2% cross-reactivity with intact human proinsulin, and 8 of 10 methods had <3% cross-reactivity with split (32, 33) proinsulin. For 9 of 10 assays, the cross-reactivity of des (64, 65) proinsulin exceeded 40%. Overall, most assays had acceptable imprecision and specificity for insulin. CONCLUSION The discordance in test results for commercial insulin reagent sets is likely multifactorial and will require a continuing effort to understand the differences and achieve the desired consistency and harmonization among commercial immunoassays.

Changesinhemodynamic loadcause alterations incardiac myocyte size, withregional variations inmyocyte size distribution possible within theventricular wall. Westudied regional changes incellular dimensions andtheir distribution intwomodelsofcardiac hypertrophy and incardiac atrophy intherat.Combinedvolume-pressure overload was produced by3,3',5- triiodo-L-thyron ine (T3) treatment; atrophy was produced byheterotopic isotransplantation. Ourprevious datafromlong-term pressureoverload after aortic constriction were usedfor comparison. Isolated ventricular myocytes wereobtained after invitro coronaryperfusion with collagenase. Cellvolumeanditsdistribution were determined; celllength was directly measured byimageanalysis, andcross-sectional areawas estimated fromthecell volume/cell length ratio, assuming a cylindrical model.Myocyte hypertrophy resulting fromhyperthy- roidism andaortic constriction was primarily duetoincreased cross-sectional area.Inboth cases,therelative responsewas greater intheright ventricle thanintheleft ventricle. Within theleftventricle, epimyocardial myocytes enlarged themost.Aorticconstriction and T3 treatment predominantly increased thesize ofsmaller myocytes. Heterogeneity inmyocyte size increased after constriction butremained relatively unaffected after T3treatment. Atrophy of left ventricular myocytes was duetoa proportional decrease incell length andcross-sectional area,withthegreatest decrease intheleft ventricular endomyocardium. Atrophy predomi- nantly affected larger myocytes, resulting ina more homogeneous overall population ofsmaller myocytes. We conclude thatvarious alterations inloadleadtodiverse remodeling inthe myocytepopulation throughout theventricular wall. Ingeneral, smaller myocytes showthe highest growth potential, whereas larger myocytes exhibit thehighest potential toatrophy. (Circulation Research 1991;68:984-996)