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Aim: The epidemiology of asymptomatic (silent) hypoglycaemia is not well‐described. We investigated incidence and risk factors for asymptomatic hypoglycaemia in Type 1 diabetes. Methods: A cohort of 153 people with Type 1 diabetes participated in 6 days of blinded continuous glucose monitoring (CGM) and recording of hypoglycaemia symptoms. At entry, hypoglycaemia awareness was classified (by three different methods) and HbA1c and C‐peptide were measured. Hypoglycaemic episodes were defined as interstitial glucose ≤ 3.9 mmol/l (IG3.9) or ≤ 3.0 mmol/l (IG3.0) for ≥ 15 min, and were considered asymptomatic if no hypoglycaemic symptoms were reported. Results: At thresholds IG3.9 and IG3.0, the incidence rates of hypoglycaemic episodes were 5.0 (7.9) [median (IQR)] and 1.3 (3.4) episodes/person‐week, respectively. Three‐quarters of episodes were asymptomatic. In total, 77% and 52% of participants experienced one or more episode of asymptomatic hypoglycaemia at IG3.9 and IG3.0 [3.0 (6.2) and 1.0 (2.3) asymptomatic episodes/person‐week]. At multivariate analysis, reduced awareness was positively associated with asymptomatic hypoglycaemia, particularly nocturnal events, and negatively with symptomatic hypoglycaemia. High insulin dose was associated with increased risk of both asymptomatic and symptomatic hypoglycaemia, whereas low HbA1c and long diabetes duration were risk factors only for symptomatic hypoglycaemia. Conclusions: Asymptomatic hypoglycaemia constitutes the majority of hypoglycaemic events in Type 1 diabetes. Reduced hypoglycaemia awareness and high insulin dose are risk factors for asymptomatic hypoglycaemia but other conventional risk factors for severe hypoglycaemia do not correlate with risk of asymptomatic episodes. What's new?: The existence of asymptomatic hypoglycaemia in Type 1 diabetes has been described previously but the epidemiology of these episodes has not been explored, thus rates of asymptomatic hypoglycaemia are unclear.This study reveals that asymptomatic hypoglycaemia constitutes the majority of hypoglycaemic episodes in Type 1 diabetes assessed by blinded CGM.Highlighting that self‐reported symptomatic hypoglycaemia comprises only a minor fraction of the total burden of hypoglycaemia in Type 1 diabetes; particularly, in individuals with impaired hypoglycaemia awareness.This study highlights the importance of the use of CGM in detecting asymptomatic episodes; particularly in individuals with impaired hypoglycaemia awareness. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 272-277 (2012) Abstract Aim To evaluate self-reported satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy among women with pregestational diabetes. Methods Fifty-four women with Type 1 diabetes and 14 women with Type 2 diabetes were offered continuous glucose monitoring for 6 days at median 9 (range 6-14) gestational weeks and were asked to answer a semi-structured questionnaire on patient satisfaction. Results Median HbA1c was 49 (range 34-86) mmol/mol) [6.6 (5.3-10.0) %] and duration of diabetes was 12 (0.5-37) years. Continuous glucose monitoring was used for 6 (0.5-7) days, with 43 (65%) women using continuous glucose monitoring for at least 5 days. The women experienced 2.7 (0-12) alarms per 24 h, of which approximately one third was technical alarms and one third disturbed their sleep. Sixteen women (24%) reported discomfort with continuous glucose monitoring during daytime and twelve (18%) during sleep. Many women reported improved diabetes understanding (52%) and would recommend continuous glucose monitoring to others (83%). Twenty-four patients (36%) had continuous glucose monitoring removed earlier than planned ( before the intended 6 days of initial monitoring). Ten women (15%) did not wish to use continuous glucose monitoring again in pregnancy. Main causes behind early removal of continuous glucose monitoring were self-reported skin irritation, technical problems and continuous glucose monitoring inaccuracy. No differences were found in continuous glucose monitoring use, inconvenience or compliance with respect to diabetes type. Conclusions The majority of pregnant women with diabetes found real-time continuous glucose monitoring useful and the intervention was equally tolerated regardless of diabetes type. Nevertheless, continuous glucose monitoring was frequently removed earlier than planned, primarily because of skin irritation, technical problems and inaccuracy. [ABSTRACT FROM AUTHOR]

Interleukin-1beta (IL-1beta) treatment of neonatal rat islets for 24 h induces changes in the expression of 105 of 2,200 proteins, as determined previously by two-dimensional (2D) gel electrophoresis. Nitric oxide (NO) has been implicated as one of the mediators of IL-1beta effects in insulin-containing cell lines and rat islets. The aims of this study were 1) to determine the involvement of NO in IL-1beta-induced alterations in protein expression and 2) to investigate the effects of chemically generated NO on protein expression by 2D gel electrophoresis of neonatal rat islet samples. IL-1beta-induced NO production was prevented by incubation of islets in arginine-free medium supplemented with the arginine analog NG-nitro-L-arginine. [35S]methionine-labeled islet proteins were separated using 2D gel electrophoresis and analyzed using the BioImage computer program. Analysis revealed that the expression levels of 23 protein spots of the 105 protein spots, altered by prior treatment with IL-1beta (60 U/ml) alone, were significantly affected (P < 0.01 [n = 4] and P < 0.05 [n = 19]) when NO production was prevented. The effects of chemically generated NO were investigated by exposing islets to the NO donor GSNO (100 micromol/l) for 24 h before labeling with [35S]methionine and 2D gel electrophoresis. Computer-based analysis identified alterations in the expression of 19 of a total of 1,600 detectable proteins in GSNO-treated islets (P < 0.01). We conclude 1) that the expression of up to 42 proteins is altered by cytokine-induced or chemically generated NO in the precise experimental conditions chosen and 2) that the majority of proteins altered by prior treatment with IL-1beta may be the result of NO-independent IL-1beta-mediated regulation of gene expression. This study demonstrates that the combination of 2D gel electrophoresis and mass spectrometry is a powerful tool in the identification of beta-cell proteins involved in the response to toxic mediators. [ABSTRACT FROM AUTHOR]

Proinflammatory cytokines are implicated as effector molecules in the pathogenesis of IDDM. Interleukin-6 (IL-6) alone or in combination with IL-1beta inhibits glucose-stimulated insulin release from isolated rat pancreatic islets by unknown mechanisms. Here we investigated 1) if the effects of IL-6 are mimicked by ciliary neurotrophic factor (CNTF), another member of the IL-6 family of cytokines signaling via gp130, 2) the possible cellular mechanisms for these effects, and 3) if islet endocrine cells are a source of CNTF. CNTF (20 ng/ml) potentiated IL-1beta-mediated (5-150 pg/ml) nitric oxide (NO) synthesis from neonatal Wistar rat islets by 31-116%, inhibition of accumulated insulin release by 34-49%, and inhibition insulin response to a 2-h glucose challenge by 31-36%. CNTF potentiated IL-1beta-mediated NO synthesis from RIN-5AH cells by 83%, and IL-1beta induced islet inducible NO-synthase (iNOS) mRNA expression fourfold. IL-6 (10 ng/ml) also potentiated IL-1beta-mediated NO synthesis and inhibition of insulin release, whereas beta-nerve growth factor (NGF) (5 or 50 ng/ml) had no effect. mRNA for CNTF was expressed in rat islets and in islet cell lines. In conclusion, CNTF is constitutively expressed in pancreatic beta-cells and potentiates the beta-cell inhibitory effect of IL-1beta in association with increased iNOS expression and NO synthesis, an effect shared by IL-6 but not by beta-NGF. These findings indicate that signaling via gp130 influences islet NO synthesis associated with iNOS expression. We hypothesize that CNTF released from destroyed beta-cells during the inflammatory islet lesion leading to IDDM may potentiate IL-1beta action on the beta-cells. [ABSTRACT FROM AUTHOR]