Because macrosomia was related to postprandial glucose but not fasting glucose, we conclude that postprandial glucose measurement should be a part of routine care for diabetes in pregnancy. A target 1-h postprandial glucose value of 7.3 mM (130 mg/dl) may be the level that optimally reduces the incidence of macrosomia without increasing the incidence of small-for-gestational-age infants.

The effect of a variety of cytokines on lipid metabolism in 3T3 Li mouse fibroblasts and adipocytes was studied. Uptake of [3H]acetate by adipocytes and heparinreleasable lipoprotein lipase activity was inhibited after treatments of the cells with picomolar concentrations of recombinant human tumor necrosis factor a (rHuTNF-a), human tumor necrosis factor 13 (rHuTNF-f, also called lymphotoxin), murine interferon-y (rMuIFN-y), and a human hybrid interferon-a [rHuIFN-a2/aj (Bgl I)]. Recombinant human interferon-y (rHuIFN-y), natural human colony-stimulating factor (HuCSF), and human interleukin 2 (HuIL-2) had no effect. Similar though less-marked suppression of [3H~acetate uptake by cytokines was seen in 3T3 Li fibroblasts. Cytokines inhibited the incorporation of [3H]acetate into both membrane and storage lipids in the adipocytes. In addition to blocking lipid uptake and synthesis, rHuTNF-a and -(3, and rMuIFN-y stimulated the release of free fatty acid into the medium from adipocytes. Binding studies suggest that rHuTNF-a and rHuTNF-P compete for the same cell-surface receptor on 3T3 Li adipocytes, while rMuIFN-y binds to a separate receptor.The binding of rTNF-a to both adipocytes and fibroblasts can be significantly enhanced by preexposure of the cells to rMuIFN-y. There appear to be both high-and low-affinity receptors for rHuTNF-a on adipocytes, whereas fibroblasts exhibit a single class of high-affinity receptors. These results suggest that a variety of structurally distinct cytokines possess lipid mobilization activity, which may be of critical importance to the host in defense against infection or malignancy.The invasion of the body by viruses, bacteria, or parasites usually elicits an integrated host response that kills and removes the infectious agents and provides immunity against future challenges. Much of the host response is modulated by a class of inducible proteins called cytokines (1-3). It is now clear that there are many distinct host cytokines that can be produced by a wide variety of cell types, including epithelial cells, fibroblasts, tumor cells, and particularly lymphocytes (lymphokines) and macrophages (monokines) (4-6). Tumor necrosis factors (TNFs), interleukins (ILs), and a-, ,B, and -interferons (IFN-a, -(3, and -y) are representative and well-characterized cytokines. Although there is considerable structural and functional heterogeneity among these families of cytokines, they all appear to have roles in the regulation of host immunity and inflammation (7-12). When administered parenterally at high doses they can be toxic, and many of the symptoms associated with the common cold and influenza such as fever, nausea, and muscle aches can be induced by the administration of pure cytokines (13,14). Unraveling the sequence of cytokine actions that occur during the host response to infection is very complex because (i) cytokines regulate the production of one another (15-17), (ii) an individual cell may produce many different cytokines (18, 19), and (iii) different cytokines may hav...

Tumor necrosis factor (TNF) administration produces an increase in plasma triglycerides that may be due to inhibition of adipose lipoprotein lipase activity and/or a stimulation of hepatic ipogenesis. We now report that TNF administration to insulinopenic diabetic rats increases serum triglycerides (2 h

Uncontrolled diabetes in man is associated with low serum T3 values and impaired production of T3 from T4. Because the thiol-dependent enzyme T4-5′-deiodinase catalyzes T4-deiodination to T3, the present study was conducted to determine whether these alterations in iodothyronine metabolism consequent to diabetes were due to a reduction in the tissue content of active enzyme or thiol cofactor availability. T4-5′- deiodinase activity and nonprotein sulfhydryl (NP-SH) groups were examined in liver homogenate preparations from groups of rats (T4-treated) diabetic (streptozotocin, 100 mg/kg i.p.) for 48-96 h and compared with controls. The mean hepatic T4-5′-deiodinase activity in the control group was 4.8 ± 0.4 pmol/min/100 mg protein (mean ± SEM). In each of the diabetic groups (48, 72, and 96 h), the mean enzyme activity was significantly less (P < 0.005) than the control mean. Homogenate enrichment with the thiol reagent dithiothreitol (DTT) (5 mM) failed to reverse this diabetic effect. Moreover, although the hepatic content of NP-SH groups was significantly less than the controls after 48 and 72 h of hyperglycemia, it had spontaneously reverted to normal by 96 h. Thus, the impaired enzyme activity could not be attributed to a deficiency of thiol cofactors. The dissociation between enzyme activity and tissue sulfhydryl groups was further illustrated by the response to insulin treatment. Insulin was given by continuous s.c. infusion to 48-h diabetic rats for 48-96 h. Although insulin therapy normalized both enzyme activity and the hepatic thiol content, the temporal profile of each response was different. Insulin therapy rapidly (48 h) corrected the hepatic content of NP-SH groups, whereas the normalization of T4-5′-deiodinase activity required 72-96 h of insulin treatment. There was a positive correlation (r = + 0.69, P < 0.025) between the serum T3 values and hepatic T4-5′-deiodinase activity. The mean serum T3 concentration was significantly reduced (P < 0.001) by the diabetes after 48 h and remained low at 72 and 96 h. Insulin treatment reversed this defect but, as in the case of enzyme activity, the normalization was delayed until 72-96 h of insulin therapy. These results indicate that (1) diabetes reduces serum T3 levels and hepatic T4-5′-deiodinase activity in T4-treated rats, (2) T4-5′-deiodinase is probably the major regulator of serum T3 levels under these conditions, and (3) the reduced T4 -5′-deiodinase activity is independent of changes in the hepatic content of NPSH groups and probably reflects a reduction in the hepatic content of active enzyme.