OBJECTIVETo assess whether intermittent real-time continuous glucose monitoring (CGM) improves glycemic control and pregnancy outcome in unselected women with pregestational diabetes.RESEARCH DESIGN AND METHODSA total of 123 women with type 1 diabetes and 31 women with type 2 diabetes were randomized to use real-time CGM for 6 days at 8, 12, 21, 27, and 33 weeks in addition to routine care, including self-monitored plasma glucose seven times daily, or routine care only. To optimize glycemic control, real-time CGM readings were evaluated by a diabetes caregiver. HbA1c, self-monitored plasma glucose, severe hypoglycemia, and pregnancy outcomes were recorded, with large-for-gestational-age infants as the primary outcome.RESULTSWomen assigned to real-time CGM (n = 79) had baseline HbA1c similar to that of women in the control arm (n = 75) (median 6.6 [range 5.3–10.0] vs. 6.8% [5.3–10.7]; P = 0.67) (49 [34–86] vs. 51 mmol/mol [34–93]). Forty-nine (64%) women used real-time CGM per protocol. At 33 weeks, HbA1c (6.1 [5.1–7.8] vs. 6.1% [4.8–8.2]; P = 0.39) (43 [32–62] vs. 43 mmol/mol [29–66]) and self-monitored plasma glucose (6.2 [4.7–7.9] vs. 6.2 mmol/L [4.9–7.9]; P = 0.64) were comparable regardless of real-time CGM use, and a similar fraction of women had experienced severe hypoglycemia (16 vs. 16%; P = 0.91). The prevalence of large-for-gestational-age infants (45 vs. 34%; P = 0.19) and other perinatal outcomes were comparable between the arms.CONCLUSIONSIn this randomized trial, intermittent use of real-time CGM in pregnancy, in addition to self-monitored plasma glucose seven times daily, did not improve glycemic control or pregnancy outcome in women with pregestational diabetes.

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Interleukin-1␤ (IL-1␤) is cytotoxic to rat pancreatic ␤-cells by inhibiting glucose oxidation, causing DNA damage and inducing apoptosis. Nitric oxide (NO) is a necessary but not sufficient mediator of these effects. IL-1␤ induced kinase activity toward Elk-1, activation transcription factor 2, c-Jun, and heat shock protein 25 in rat islets. By Western blotting with phosphospecific antibodies and by immunocomplex kinase assay, IL-1␤ was shown to activate extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (p38) in islets and rat insulinoma cells. Specific ERK1/2 and p38 inhibitors individually reduced but in combination blocked IL-1␤-mediated islet NO synthesis, and reverse transcription-polymerase chain reaction of inducible NO synthase mRNA showed that ERK1/2 and p38 controlled IL-1␤-induced islet inducible NO synthase expression at the transcriptional level. Hyperosmolarity caused phosphorylation of Elk-1, activation transcription factor 2, and heat shock protein 25 and activation of ERK1/2 and p38 in islets comparable to that induced by IL-1␤ but did not lead to NO synthesis. Inhibition of p38 but not of ERK1/2 attenuated IL-1␤-mediated inhibition of glucose-stimulated insulin release. We conclude that ERK1/2 and p38 activation is necessary but not sufficient for IL-1␤-mediated ␤-cell NO synthesis and that p38 is involved in signaling of NO-independent effects of IL-1␤ in ␤-cells.

A model of the pathogenesis of insulin-dependent diabetes mellitus, i.e. the initial phase of beta-cell destruction, is proposed: in a cascade-like fashion efficient antigen presentation, unbalanced cytokine, secretion and poor beta-cell defence result in beta-cell destruction by toxic free radicals (O2- and nitric oxide) produced by the beta cells themselves. This entire process is under polygenetic control.

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