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Background Obese subjects show major abnormalities in the growth hormone (GH)/insulin‐like growth factor (IGF) system. Furthermore, they are prone to develop Type 2 diabetes, but the impact of diabetes plus obesity on the GH/IGF system remains unknown. Methods We compared overnight fasting serum levels of free and total (extractable) IGF‐I and ‐II, IGF‐binding protein (IGFBP) ‐1, ‐2 and ‐3, and the high affinity GH‐binding protein (GHBP) in matched groups of lean subjects (n=26) and obese subjects without (n=24) and with (n=29) Type 2 diabetes. Two groups (n=7) of healthy and Type 1 diabetic subjects were also studied. Results Non‐diabetic obese subjects had increased free IGF‐I and ‐II, total IGF‐II, IGFBP‐3 and GHBP, reduced IGFBP‐1 and ‐2 (p<0.05), but normal total IGF‐I, when compared to lean subjects. In obese Type 2 diabetics free IGF‐I was insignificantly reduced by 9% (p=0.3), when compared to non‐diabetic obese subjects. However, the concentration was not significantly elevated when compared to that of lean controls (p=0.13). Also IGFBP‐1 and total IGF‐I were normal in obese Type 2 diabetics, whereas free and total IGF‐II and IGFBP‐3 remained elevated to a similar extent as in simple obesity (p<0.05). In contrast, GHBP was further increased and IGFBP‐2 further reduced in obese Type 2 diabetics (p<0.05). In Type 1 diabetics total IGF‐I and ‐II, and IGFBP‐3 were normal. In contrast, free IGF‐I and ‐II and GHBP were markedly reduced, whereas IGFBP‐1 and ‐2 were increased (p<0.05). Conclusions Simple obesity was associated with marked changes in the GH/IGF system. Many of these abnormalities were unaffected by the concomitant presence of Type 2 diabetes (total IGF‐I, free and total IGF‐II and IGFBP‐3). However, some changes became accentuated (GHBP and IGFBP‐2), while others (free IGF‐I and IGFBP‐1) were no longer present. Notably, the impact of Type 1 diabetes on the GH/IGF system was clearly different from that of Type 2 diabetes. Copyright © 1999 John Wiley & Sons, Ltd.

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We present a sensitive time-resolved fluorometric immunofunctional assay (TR-FIA) for direct quantitation of functional growth hormone-binding protein (GHBP), using an immunoassay kit for growth hormone (GH-DELFIA). In addition to the immobilized GH antibody, one monoclonal antibody against GHBP was used. This anti-GHBP was labelled with the chelate of europium. The assay was performed in one step. The detection limit for GHBP was 0.044 nmol L-1 (NBS + 3 SD). The calibration curve was linear in the interval 0.11-8.03 nmol L-1. Average intra-assay coefficient of variation (CV) was 3.44%. Average interassay CV at GHBP concentrations 0.563 nmol L-1 and 1.40 nmol L-1 were 12% and 6.3% respectively. Analytical recovery in serum ranged from 76% to 127% with a mean of 101 +/- 3.6%. Serum GHBP in 102 normal subjects ranged from 0.513 to 3.772 nmol L-1 and was positively related to body mass index (P < 0.001). In growth hormone-deficient sera GHBP was higher than in control subjects (1.751 +/- 0.179 nmol L-1 and 1.257 +/- 0.140 nmol L-1 respectively, P < 0.001). Acromegalic patients had lower levels of GHBP than controls (0.946 +/- 0.251 and 1.234 +/- 0.144 nmol L-1 respectively, P = 0.005). This assay also allowed detection of GH-complexed GHBP in serum. These results were in agreement with theoretical values calculated from the measured GH and the functional GHBP concentrations. Results were compared with data obtained by a recently reported, validated ligand immunofunctional assay (LIFA), which is fundamentally different. There was a significant linear relationship between the results from the two assays (r = 0.89, P = 0.001). The slope of the regression line was 0.65. In conclusion, this new convenient GHBP TR-FIA provides a sensitive and precise method for detecting total GHBP as well as complexed GHBP in human serum, and allows easy processing of large numbers of samples.

Low birth weight has been proposed as a risk factor for development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease in the adult. To ascertain the extent to which birth weight was associated with cardiovascular risk factors, we examined 620 subjects (median age 48 years) in a cross-sectional study. Of these 317 were offspring of diabetic patients and 303 were offspring of non-diabetic control subjects. Known risk factors for development of cardiovascular disease were correlated to birth weight and examined as dependent variables by multiple linear regression. Age, body mass index (BMI), subjects gender along with parental gender, diabetes status of the parents, and birth weight were independent variables. The variance of the risk factors as dependent variables explained by age, gender, and BMI as independent variables was examined and birth weight was added as an independent variable. We found birth weight was inconsistently correlated to the different risk factors in the different groups of subjects. When adjusted for age, BMI, subject's gender, parental gender, and the diabetes status of the parents, birth weight was negatively correlated to fasting blood glucose. In offspring of diabetic patients the explained variance of risk factors did not change as we added birth weight to the model. In offspring of non-diabetic subjects we found that the explained variance of diastolic blood pressure, fasting blood glucose, HbA1c, and cholesterol increased 1-3% as birth weight was added to the model. We conclude that birth weight may not be a major risk factor for development of hypertension and cardiovascular disease in our population.