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Diabet. Med. 29, 558-566 (2012) Abstract Aims To explore incidence, risk factors, possible pathophysiological factors and clinical management of hypoglycaemia during pregnancy in women with Type 1 diabetes. Methods Literature review. Results In women with Type 1 diabetes, severe hypoglycaemia occurs three to five times more frequently in early pregnancy than in the period prior to pregnancy, whereas in the third trimester the incidence of severe hypoglycaemia is lower than in the year preceding pregnancy. The frequency distribution of severe hypoglycaemia is much skewed, as 10% of the pregnant women account for 60% of all recorded events. Risk factors for severe hypoglycaemia during pregnancy include a history with severe hypoglycaemia in the year preceding pregnancy, impaired hypoglycaemia awareness, long duration of diabetes, low HbA1c in early pregnancy, fluctuating plasma glucose values (≤ 3.9 mmol/l or ≥ 10.0 mmol/l) and excessive use of supplementary insulin injections between meals. Pregnancy-induced nausea and vomiting seem not to be contributing factors. Conclusions Striving for near-normoglycaemia with focus on reduction of plasma glucose fluctuations during pregnancy should have high priority among clinicians with the persistent aim of improving pregnancy outcome among women with Type 1 diabetes. Pre-conception counselling, carbohydrate counting, use of insulin analogues, continuous subcutaneous insulin infusion (insulin pump) therapy and real-time continuous glucose monitoring with alarms for low glucose values might be relevant tools to obtain near-normoglycaemia without episodes of severe hypoglycaemia. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 303-312 (2012) Abstract Aims To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Methods A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of mild hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was calculated in terms of quality-adjusted life expectancy. Pharmacy costs were accounted using published prices and defined daily doses for both insulins. Costs were expressed in 2010 euros (€). Results Treatment with insulin detemir was associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of 26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality-adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life years (standard deviation). Annual costs were € 573.55 (110.42) vs. € 332.76 (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These values were € 545.79 (106.54) vs. € 306.12 (57.78) in Sweden, € 720.10 (140.74) vs. € 408.73 (78.61) in Finland and € 584.01 (109.47) vs. € 359.60 (64.84) in the Netherlands. Incremental cost-effectiveness ratios were approximately € 12 644 (Denmark), € 12 612 (Sweden), € 16 568 (Finland) and € 12 216 (the Netherlands) per quality-adjusted life year gained for insulin detemir vs. NPH insulin. Conclusions Insulin detemir is likely to be cost-effective vs. NPH insulin in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Increased pharmacy costs with insulin detemir should not be a barrier to therapy based on these findings. [ABSTRACT FROM AUTHOR]

Aims Severe hypoglycaemia is a significant problem in pregnant women with Type 1 diabetes. We explored whether frequent severe hypoglycaemia during pregnancy in women with Type 1 diabetes is related to placental growth hormone (GH) and insulin-like growth factor I (IGF-I) levels. Methods A prospective, observational study of 107 consecutive pregnant women with Type 1 diabetes. Blood samples were drawn for IGF-I and placental GH analyses at 8, 14, 21, 27 and 33 weeks. Severe hypoglycaemic events were reported within 24 h. Results Eleven women (10%) experienced frequent severe hypoglycaemia (≥ 5 events), accounting for 60% of all events. Throughout pregnancy, IGF-I levels were 25% lower in these women ( P < 0.005) compared with the remaining women, despite similar placental GH levels. Eighty per cent of the severe hypoglycaemic events occurred before 20 weeks when IGF-I levels were at their lowest. This finding was not explained by differences in insulin dose, median plasma glucose levels or glycated haemoglobin. History of severe hypoglycaemia the year preceding pregnancy and impaired hypoglycaemia awareness—being the only predictors of frequent severe hypoglycaemia in a logistic regression analysis—were not associated with IGF-I or placental GH levels at 8 weeks. Conclusions In women with Type 1 diabetes experiencing frequent severe hypoglycaemia during pregnancy, IGF-I levels are significantly lower compared with the remaining women despite similar placental GH levels. IGF-I levels are lowest in early pregnancy where the incidence of severe hypoglycaemia is highest. IGF-I may be a novel factor of interest in the investigation of severe hypoglycaemia in patients with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aim: To compare self-treatment of mild symptomatic hypoglycaemia in people with type 1 diabetes with national Danish guidelines recommending 10–20 g of refined carbohydrate initially followed by unrefined carbohydrates. Methods: A cohort of 201 patients with type 1 diabetes filled in a questionnaire including self-treatment of mild symptomatic hypoglycaemia and occurrence of mild and severe hypoglycaemia. Initial intake of less than 10 g of refined carbohydrate was defined as under treatment and intake of 20 g or more as over treatment. Results: A total of 147 patients (73%) answered both questions about initial and follow-up self-treatment of hypoglycaemia. Fifty per cent of patients treated themselves with 10–20 g refined carbohydrates (female:male = 59%:43%; p<0.05), whereas 37% over treated (female:male = 34%:39%; not significant) and 13% under treated (female:male = 6%:18%; p<0.05). Initial treatment was followed by consumption of unrefined carbohydrates in 70% of the patients. Overall, 37% (female:male = 49%:28%; p<0.05) of the patients adhered to guidelines. The number of severe hypoglycaemic episodes (lifetime) and amount of carbohydrate intake were positively correlated (r = 0.2; p<0.05). Adherence to guidelines was not related to occurrence of mild and severe (in the last year) hypoglycaemia, glycated haemoglobin, or fear of hypoglycaemia. Conclusions: Only about one-third of patients with type 1 diabetes treat mild hypoglycaemia according to guidelines. Female patients show better compliance. Patients with frequent episodes of severe hypoglycaemia over treat more often. Copyright © 2007 FEND. [ABSTRACT FROM AUTHOR]

Background: Appropriate self-treatment of mild symptomatic hypoglycaemia is essential to prevent severe hypoglycaemia. Danish national guidelines recommend 10–20 g of refined carbohydrate (CH) initially, followed by a non-specified amount of unrefined CH. Aim: Our aim was to explore the effect of the amount of CH taken on glucose concentrations recorded by the MiniMed Continuous Glucose Monitoring System (CGMS) at mild symptomatic hypoglycaemic episodes. Method: A total of 125 adult patients with type 1 diabetes underwent 6 days of CGMS. HemoCue blood glucose determinations were used for calibration. All mild symptomatic episodes with a concomitant CGMS value ≤ 3.5 mmol/l were included in the analysis. Participants completed a detailed diary documenting all meals and snacks, insulin doses, and episodes and self-treatment of hypoglycaemia. CGMS values recorded 30 and 60 minutes after the episode were compared to CH intake. An initial intake of <10 g CH was defined as under treatment, and an intake of >20 g CH as over treatment. Treatment target was CGMS values of 3.6–10.0 mmol/l; values ≤ 3.5 mmol/l were defined as insufficient treatment, and values >10.0 mmol/l as overshooting the target. Results: A total of 126 mild symptomatic episodes was experienced in 52 (42%) of the patients. Initial carbohydrate intake could be calculated for 93 episodes. At 30 minutes, under treatment was associated with increased risk of insufficient response (57% versus 30%; p<0.01). At 60 minutes, over treatment was associated with increased risk of overshooting the target (23% versus 7%; p<0.05). An independent effect of follow-up intake of unrefined CH is not detectable within the first 60 minutes after treatment. Conclusion: Current guidelines for treatment of mild symptomatic hypoglycaemia are appropriate to ensure achievement of the glycaemic target. Copyright © 2006 FEND. [ABSTRACT FROM AUTHOR]

Aims/hypo thesis: Plasma semicarbazide- sensitive amine oxidase (SSAO) is elevated in patients with type 1 and type 2 diabetes and has been implicated in the pathophysiology of diabetic late complications. The regulation of SSAO production remains unknown. We studied correlations between plasma SSAO activity and parameters associated with diabetic late complications. Methods: Plasma SSAO was measured in a well-characterised group of 287 patients with type 1 diabetes. Standard statistical methods were used to investigate correlations with clinical parameters and components of the renin-angiotensin system. Results: Overall, plasma SSAO was elevated, at 693±196 mU/1 (mean±SD; normal controls 352±102 mU/l). Plasma SSAO was higher in the group with late complications or hypertension, and in patients treated with ACE-inhibitors. In univariate analysis a significant positive correlation (p<0.001, r=0.27) was found between plasma SSAO and serum ACE activity in patients untreated with ACE inhibitors or angiotensin II receptor antagonists (n=22 1), but plasma SSAO did not differ by ACE l/D genotype. Plasma SSAO correlated positively with duration of diabetes, HbA1c and plasma renin, and negatively with plasma angiotensinogen and body mass index. A multiple regression analysis including these variables resulted in serum ACE activity (p<0.001), ACE genotype (negatively, p<0.001) and HbA1c (p=0.023) as explaining variables. Conclusions/ interpretation: Results suggest that a common factor is involved in the regulation of both plasma SSAO and serum ACE, which is different from the genetic determination of ACE activity. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. We have previously shown a strong relationship between high angiotensin-converting enzyme (ACE) activity, presence of the deletion (D) allele of the ACE gene and recall of severe hypoglycaemic events in patients with Type 1 diabetes. This study was carried out to assess this relationship prospectively. Methods. We followed 171 adult outpatients with Type 1 diabetes in a one-year observational study with the recording of severe hypoglycaemia. Participants were characterised by serum ACE activity and ACE genotype and not treated with ACE inhibitors or angiotensin II receptor antagonists. Results. There was a positive relationship between serum ACE activity and rate of severe hypoglycaemia with a 2.7 times higher rate in the fourth quartile of ACE activity compared to the first quartile (p=0.0007). A similar relationship was observed for the subset of episodes with coma (2.9 times higher rate in fourth quartile compared to first quartile; p=0.048). The impact of serum ACE activity was most pronounced in C-peptide negative subjects (4.2 times higher rate in fourth quartile compared to first quartile; p=0.003), and in this subgroup carriers of the D allele of the ACE gene had higher rates of severe hypoglycaemia compared to the group homozygous for the insertion (I) allele. In a multiple regression analysis high serum ACE activity and impaired awareness of hypoglycaemia were identified as the only significant predictors of severe hypoglycemia. Conclusion. High ACE activity and the presence of the D allele of the ACE gene predict a high rate of severe hypoglycaemia in Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Examines the cognitive function during hypoglycemia in type I diabetes mellitus. Measurement of mean blood glucose concentration; Evaluation of neuropsychological testing; Administration of insulin for the management of the disease.

The impact of pre-diabetes on clinical status was retrospectively studied in 38 cystic fibrosis (CF) patients with diabetes mellitus (DM) and 38 non-diabetic CF patients (control patients), matched in pairs for age, sex, and chronic Pseudomonas aeruginosa lung infection. Quarterly parameters of CF clinical status were collected for 6 years prior to the diagnosis of DM in the index case. Compared to the control patients, decreases in body weight, body mass index (BMI), forced expiratory volume in 1s (FEV1), and forced vital capacity (FVC) and an increase in the daily intake of pancreatic enzyme capsules were found in the pre-diabetic patients. Statistically significant differences in body weight, BMI, FEV1, FVC, and intake of pancreatic enzyme capsules between pre-diabetic and control patients emerged 4, 4, 1.25, 3 and 4.5 years prior to the diagnosis of DM, respectively. The number of lung infections did not differ between the two groups of patients. Thus, when DM develops in CF patients, an insidious decline in overall clinical status is observed for years prior to its diagnosis. Whether clinical deterioration in CF leads to DM, or pre-diabetes results in declining CF clinical status is presently unknown. Accumulating evidence suggests that the latter may be the case since insulin therapy seems to improve lung function in CF. [ABSTRACT FROM AUTHOR]

The article presents information on prospective and retrospective studies of severe hypoglycaemia (SH) along with evaluation on hypoglycaemia awareness in insulin-related Type 2 diabetes. The study defined SH as a need for assistance from others to treat the condition. The study assessed the feasibility and reproducibility of a classification of hypoglycaemia awareness that results in a total prevalence of impaired awareness of 31%.

Background Varenicline is a new drug indicated for smoking cessation. It has primarily been investigated in healthy adults. The commonest side-effects are nausea, headache, sleep disturbance, constipation, flatulence and vomiting. Hypoglycaemia has not been reported. As smoking cessation is important to reduce risk of cardiovascular morbidity, especially in diabetes, use of effective drugs indicated for smoking cessation is rational. Case report We report multiple episodes of severe hypoglycaemia after starting varenicline in a 53-year-old woman with Type 1 diabetes. Since onset of diabetes at age 25 years and until start of varenicline therapy, she had only experienced one episode of severe hypoglycaemia and hypoglycaemia awareness was not impaired. The severe hypoglycaemic episodes disappeared after withdrawal of varenicline. Conclusions We recommend cautious prescription of varenicline, intensified blood glucose monitoring and careful education of patients with diabetes treated with varenicline. Further investigation of the use of varenicline in patients with diabetes is warranted. [ABSTRACT FROM AUTHOR]