Insulin-like growth factor-I in diabetes mellitus: its physiology, metabolic effects, and potential clinical utility

Type 1 diabetes mellitus (DM) is a disease of insulin deficiency, resulting from the autoimmune-mediated destruction of pancreatic beta cells. However, as a likely consequence of intraportal insulin deficiency, patients with type 1 DM also exhibit abnormalities of the growth hormone (GH)/IGF/IGF-binding protein (IGFBP) axis, including GH hypersecretion, reduced circulating levels of insulin-like growth factor-I (IGF-I) and IGFBP-3, and elevated levels of IGFBP-1. These abnormalities not only exacerbate hyperglycemia in patients with type 1 DM, but may contribute to the pathogenesis of diabetes-specific complications, including diabetic neuropathy, nephropathy, and retinopathy. Therefore, therapeutic modalities aimed at restoring the GH-IGF-IGFBP axis are being considered. Herein, we review the efficacy of one such therapy, specifically IGF-I replacement therapy. To date, short-term beneficial metabolic effects of recombinant human IGF (rhIGF)-I therapy have been demonstrated in numerous diabetic conditions, including type 1 DM, type 2 DM, and type A insulin resistance. However, the long- term safety and metabolic efficacy of rhIGF-I therapy remains to be established. Moreover, the potential impact of rhIGF-I on the natural history of diabetic complications has yet to be explored.     

Continuous subcutaneous insulin infusion (CSII) in children with type 1 diabetes

Recent studies have shown that continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, provides a treatment option that can assist in the attainment of current goals of treatment in children and adolescents with type 1 diabetes (T1DM). In pediatric patients, CSII has been demonstrated to reduce both glycosylated hemoglobin levels and frequency of severe hypoglycemia, without sacrifices in safety, quality of life, or excessive weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology. Clinical studies of safety and efficacy of CSII in children are reviewed.     

Effects of Carbohydrate Counting Method on Metabolic Control in Children with Type 1 Diabetes Mellitus

Ob­jec­ti­ve: Medical nutritional therapy is important for glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM). Carbohydrate (carb) counting, which is a more flexible nutritional method, has become popular in recent years. This study aimed to investigate the effects of carb counting on metabolic control, body measurements and serum lipid levels in children and adolescents with T1DM. Methods: T1DM patients aged 7-18 years and receiving flexible insulin therapy were divided into carb counting (n=52) and control (n=32) groups and were followed for 2 years in this randomized, controlled study. Demographic characteristics, body measurements, insulin requirements, hemoglobin A1c (HbA1c) and serum lipid levels at baseline and at follow-up were evaluated. Results: There were no statistically significant differences between the groups in mean HbA1c values in the year preceding the study or in age, gender, duration of diabetes, puberty stage, total daily insulin dose, body mass index (BMI) standard deviation score (SDS) and serum lipid values. While there were no differences in BMI SDS, daily insulin requirement, total cholesterol, low-density lipoprotein and triglyceride values between the two groups (p>0.05) during the follow-up, annual mean HbA1c levels of the 2nd year were significantly lower in the carb counting group (p=0.010). The mean values of high-density lipoprotein were also significantly higher in the first and 2nd years in the carb counting group (p=0.02 and p=0.043, respectively). Conclusion: Carb counting may provide good metabolic control in children and adolescents with T1DM without causing any increase in weight or in insulin requirements.     

Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels: potential impact for glucotoxicity in vivo

OBJECTIVE: To evaluate the interplay between hyperglycaemia, insulin resistance, hormones and adipokines in patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: Ten patients with T2DM with good glycaemic control (G), 10 with poor control (P) and 10 nondiabetic control subjects (C) were matched for sex (M/F 6/4), age and body mass index. A hyperinsulinaemic, euglycaemic clamp was performed and cytokines and endocrine functions, including cortisol axis activity were assessed. RESULTS: Patients with diabetes were more insulin resistant than group C, and group P exhibited the highest degree of insulin resistance (P = 0.01, P vs C). Tumour necrosis factor (TNF)-alpha levels were elevated in patients with diabetes (P = 0.05) and group P had the highest levels of fasting serum cortisol (P = 0.05), nonesterified fatty acids (NEFA; P = 0.06) and C-reactive protein (CRP; P = 0.01). Adiponectin levels were lower in the P group. In partial correlation analyses, significant associations were found: glycaemic level (HbA1c) with insulin resistance, TNF-alpha, CRP and basal and ACTH-stimulated cortisol levels, insulin resistance with plasma NEFA, TNF-alpha and stimulated cortisol levels. CONCLUSION: Poor glycaemic control in patients with T2DM was associated with insulin resistance and with elevated TNF-alpha, CRP and basal as well as stimulated cortisol levels. Inflammatory mediators, e.g. TNF-alpha, may contribute to insulin resistance in hyperglycaemic patients with T2DM and this might be a partial explanation for glucotoxicity.     

Growth, puberty, and final height in children with Type 1 diabetes

OBJECTIVE: The aims of this study were to assess the physical growth and pubertal development in a group of diabetic children and to evaluate the effect of height at diagnosis, duration of illness, and degree of glycemic control on final height and sexual maturation. RESEARCH DESIGN: A cohort of 72 Sudanese diabetic children, 7-13 years of age at diagnosis, was followed longitudinally from the onset of diabetes until the attainment of final height. RESULTS: The mean height standard deviation scores (SDS) at diagnosis were 0.04 in boys and -0.15 in girls, which was greater than their genetic target height (GTH). The growth velocity between diagnosis and final height was slow, with significant reduction in pubertal growth spurt. The mean final height attained by these children was lower than their GTH, a finding that contradicts most of the recently published reports. The average age at menarche in girls (15.1 years) and the mean age of full sexual maturation in boys (17.2 years) were significantly delayed in this group of diabetic patients. This retardation in physical growth and pubertal development was positively correlated with the duration of diabetes before the onset of puberty and glycated haemoglobin (HbA1c) concentration. The majority of these patients were thin at diagnosis of diabetes, with median body mass index (BMI) <22, but showed a remarkable, progressive weight gain during puberty, which was more evident in girls. The weight gain was independent of weight at diagnosis and duration of diabetes, but was positively correlated with the daily dose of insulin and HbA1c concentration. CONCLUSION: Conventional therapy of diabetic children is associated with impairment of physical growth and delayed sexual maturation.     

Efficacy of the Novel Degludec/Aspart Insulin Co-formulation in Children and Adolescents with Type 1 Diabetes: A Real-life Experience with One Year of IDegAsp Therapy in Poorly Controlled and Non-compliant Patients

Objective:To evaluate the efficacy of degludec/aspart (IDegAsp) insulin co-formulation in children and adolescents with poorly controlled type 1 diabetes (T1DM).Methods:Patients with poorly controlled T1DM on basal-bolus insulin regimes and having compliance problems related to insulin injections were switched to IDegAsp and were included. Data on hemoglobin A1c (HbA1c) levels, hypoglycemic episodes, frequency of diabetic ketoacidosis (DKA) and insulin doses were recorded at baseline and after one year of IDegAsp treatment.Results:Fifty patients (22 girls; 44%) were started on IDegAsp. The mean±standard deviation (range) age and duration of diabetes were 12.9±3.4 (4-18) and 5.2±3.1 (1.0-13.7) years, respectively. At the end of one year, 38 patients were still on IDegAsp, whereas 12 patients had opted to resume their original treatments. In those who continued on IDegAsp, HbA1c levels did not change, but the number of self-reported mild-moderate hypoglycemic episodes decreased significantly (p<0.05). In the year before switching to IDegAsp, 11 DKA attacks in 9 patients were observed, whereas this decreased to 4 DKA attacks in 4 patients after one year of IDegAsp therapy (p=0.06).Conclusion:IDegAsp regimen may improve clinical management in poorly controlled basal-bolus insulin regimen T1DM patients who have frequent hypoglycemia and DKA attacks, as well as in those with poor compliance with multiple injections. Although a simplified basal-bolus IDegAsp regimen is an attractive option for patients with T1DM, some may not adapt to this treatment due to the fixed IAsp dose of IDegAsp.     

Management of diabetes mellitus: is the pump mightier than the pen?

Continuous subcutaneous insulin infusion (CSII, or insulin pump therapy) reduces HbA1c levels and hypoglycaemia in patients with type 1 diabetes mellitus (T1DM) compared with multiple daily insulin injections (MDI). The greatest reduction in HbA(1c) levels with CSII occurs in patients with the worst glycaemic control; therefore, the most appropriate and cost-effective use of CSII in adults with T1DM is in those who have continued, elevated HbA(1c) levels or disabling hypoglycaemic episodes with MDI (including the use of long-acting insulin analogues and structured patient education). The disadvantages of CSII include higher costs than MDI and the risk of ketosis in the event of pump failure. In children with T1DM, CSII may be used when MDI is considered impractical or inappropriate. Pumps are not generally recommended for patients with type 2 diabetes mellitus but may improve control in some subgroups. A new generation of smaller insulin infusion pumps with an integrated cannula, called patch pumps, could improve uptake of CSII in general. The important clinical question is not whether CSII is more efficacious than MDI in general adult T1DM, but whether CSII further improves glycaemic control when this control continues to be poor with MDI, and evidence exists that in most cases it does.     

Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor

OBJECTIVE: Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim of our study was to investigate potential metabolic factors that may be associated with the induction of the sOB-R release from its membrane receptor. MATERIALS AND METHODS: Twenty-five children (aged between 1.5 and 17.0 years) were studied at the onset of T1DM. Blood samples were collected before (n = 25), during the first 18 h (mean +/- S.D. 11.1 +/- 4.3 h, n = 16) and 92 h (47.5 +/- 22.5 h; n = 14) after beginning insulin therapy. Serum sOB-R and leptin levels were determined by in-house immunoassays. RESULTS: The sOBR-level and the molar sOB-R/leptin ratio were significantly higher before than after starting insulin treatment (P < 0.05). In contrast, leptin levels were significantly lower (P < 0.05) before insulin therapy. The correlation between sOB-R and blood glucose (r = 0.49; P < 0.05), as well as sOB-R with parameters of ketoacidosis, such as pH (r = -0.72), base excess (r = -0.70), and bicarbonate (r = -0.69) (P < 0.0001) at diagnosis of T1DM remained significant during the first 18 h of insulin treatment. Multiple regression analysis revealed that base excess predicted 41.0% (P < 0.001), age 16.4% (P < 0.05), and height SDS 13.9% (P < 0.01) of the sOB-R variance. CONCLUSIONS: Metabolic decompensation in children with new onset T1DM is associated with dramatic changes of the leptin axis; serum levels of sOB-R are elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median 11.3) in this condition may contribute to leptin insensitivity. Upregulation of the soluble leptin receptor appears to be a basic mechanism to compensate for intracellular substrate deficiency and energy-deprivation state.     

初诊2型糖尿病患者短期胰岛素泵强化治疗对血浆FGF-21水平及胰岛素敏感性的影响

目的 探讨短期胰岛素泵强化治疗对初诊2型糖尿病(T2DM)患者胰岛素敏感性和血浆成纤维细胞生长因子-21(FGF-21)水平的影响.方法 采用自身前后对照,运用高胰岛素-正葡萄糖钳夹术评价30例新诊断T2DM患者接受2 w短期胰岛素泵 (CSII) 强化治疗前后胰岛素敏感性的变化,并采用酶免法测定治疗前后血浆FGF-21水平.结果 T2DM患者血浆FGF-21水平明显高于对照组[(1.6±0.1) vs (1.1±0.4) μg/L,P<0.01].T2DM患者经胰岛素泵强化治疗2 w后,血浆FGF-21水平较治疗前明显下降[(1.6± 0.1) vs (1.3 ± 0.1) μg/L,P<0.05].多元逐步回归分析表明,WHR、2 h PBG、SBP及FFA是影响血浆FGF-21水平的独立相关因素(YFGF-21=0.625XWHR+0.034XPBG+0.003XSBP-0.419XFFA+0.626).结论 短期胰岛素泵强化治疗可明显降低T2DM患者血浆FGF-21水平,血浆FGF-21水平与代谢紊乱有关,并可能参与了T2DM的发生和发展.     

Inverse relationship of serum adiponectin concentration with type 2 diabetes mellitus incidence in middle-aged Japanese workers: six-year follow-up

Background It was suggested that inflammation may mediate or modify biological effects of adiponectin. Few studies examined the association between circulating adiponectin levels and type 2 diabetes (T2DM) while controlling for variables related to inflammation. In addition, East Asians were reported to have lower adiponectin levels but higher diabetes prevalence at a given degree of obesity than Caucasians, raising some possibility that the adiponectin–diabetes association may differ by race. Therefore, we prospectively investigated the associations with a number of covariates including C‐reactive protein and smoking status in a cohort of Japanese workers aged 35–66 years. Methods Serum adiponectin concentration and other covariates were obtained in 2002 for 3008 civil servants free of T2DM at baseline in urban/suburban Japan. T2DM incidence was defined as the year when annually assessed fasting blood glucose level first exceeded 126 mg/dL or self‐reported initiation of medication through 2007. T2DM incidence was examined in relation to the adiponectin quintile. Results Age‐ and sex‐adjusted homeostasis model assessment insulin resistance was inversely associated with adiponectin quintiles at baseline. During six years of follow‐up, 164 individuals developed T2DM. In a fully adjusted model, hazard ratios (95% confidence intervals) of T2DM in Q2 to Q5 compared with that in Q1 were 0.62 (0.41–0.94), 0.44 (0.25–0.77), 0.40 (0.20–0.78) and 0.85 (0.48–1.49), respectively. Conclusions Low adiponectin was related to increased incidence of T2DM independent of baseline levels of blood glucose, insulin and C‐reactive protein as well as other confounding variables in middle‐aged Japanese. Whether high adiponectin is linearly associated with decreased T2DM risk needs further investigation. Copyright © 2012 John Wiley & Sons, Ltd.     

儿童1型糖尿病合并自身免疫性甲状腺疾病12例临床分析

目的 分析儿童1型糖尿病(T1DM)合并自身免疫甲状腺疾病(AITD)对T1DM治疗的影响。方法 1993～2002年在我院诊治的T1DM患儿合并甲状腺疾病者12例。对患儿的病史、家族史、体格检查及内分泌相关检查的结果进行分析。抗体检查：GAD-Ab、IAA、ICA、TG-Ab、TPO-Ab、TRAb和肾上腺皮质细胞浆抗体(ACC)。采用t检验将T1DM合并Graves病(GD)与合并桥本甲状腺炎(HT)者进行糖化血红蛋白(HbA1c)和胰岛素用量的分组比较；采用秩和检验对病程进行比较。结果 该组儿童患GD和HT者，分别为4例和8例。T1DM和AITD发病间隔为0～10年；GD的临床表现可不突出。有内分泌家族史者占25％。GD控制前患儿的HbA1c分别为10％、12％和14％，1例结束GD疗程者的HbA1c为7．8％。合并HT者的糖尿病代谢控制相对较好，HbA1c为7．2％～10％，1例新诊断T1DM合并HT且尚未治疗HT的患儿，HbA1c为6．3％。经t检验显示两组患儿的HbA1c差异有显著意义(P=0．011)，而病程和胰岛素用量差异无显著意义。结论该组患儿女性多于男性；HT患儿较GD患儿为多；有较强的内分泌疾病家族史。AITD影响糖尿病控制。T1DM患儿宜定期进行甲状腺自身抗体和甲状腺功能检查。     

Opportunities for using lipoprotein subclass profile by nuclear magnetic resonance spectroscopy in assessing insulin resistance and diabetes prediction

The incidence of type 2 diabetes mellitus (T2DM) has reached epidemic levels, and current trends indicate that its prevalence will continue to rise. The development of T2DM can be delayed by several years, and may even be prevented, by identifying individuals at risk for T2DM and treating them with lifestyle modification and/or pharmacological therapies. There are a number of methods available for assessing the insulin resistance (IR) that characterizes, and is the precursor to, T2DM. However, current clinical methods for assessing IR, based on measures of plasma glucose and/or insulin are either laborious and time-consuming or show a low specificity. IR manifests its earliest measurable abnormalities through changes in lipoproteins, and thus we propose that by examining lipoprotein subclass profile, it may be possible to alert physicians and patients to a heightened risk of developing diabetes. This will allow us to institute appropriate lifestyle changes and treatment potentially to delay the onset or possibly prevent the progression to diabetes.     

Plasma glucagon decreases during night-time sleep in Type 1 diabetic patients and healthy control subjects.

AIMS: In Type 1 diabetes mellitus (T1DM), the glucagon response to hypoglycaemia is known to disappear within a few months after the onset of the disease, whereas the response to other stimuli remains intact. The dynamics of spontaneous glucagon release have rarely been assessed. We monitored spontaneous glucagon release in T1DM patients and healthy subjects during a 7-h period of night-time sleep. METHODS: Measurements were made in 14 T1DM patients and 14 control subjects matched for age, gender and body mass index after one night's adaptation in our laboratory. Circulating glucose, insulin and glucagon concentrations were measured at 30-min intervals. In diabetic patients, hypoglycaemia (< 3.9 mmol/l) was avoided by infusion of glucose whenever necessary. RESULTS: During the entire night, plasma glucose and serum insulin levels were higher in T1DM patients than in healthy subjects (P < 0.03 and P < 0.001, respectively). Plasma glucagon concentrations decreased throughout the night in both groups (P < 0.001). Glucagon levels were similar in T1DM patients and healthy subjects (P > 0.87). The duration of diabetes (less and more than 5 years) did not affect glucagon secretion (P > 0.87). CONCLUSIONS: Plasma glucagon levels decrease significantly during night-time sleep in healthy control subjects. This nocturnal decrease is preserved in T1DM patients regardless of the duration of diabetes. These observations point to distinct nocturnal regulation of spontaneous glucagon release that does not depend on circulating glucose and insulin levels and is unaltered in T1DM patients.     

Diabetic retinopathy in children and adolescents

Diabetic retinopathy rarely occurs before puberty and is never proliferative in prepubescent children. On the opposite, puberty and adolescence are high-risk periods for diabetic retinopathy progression, and call for strict ophthalmologic monitoring. The period between 16 and 18 years of age is particularly critical. Progression towards florid diabetic retinopathy is to be especially feared and should be prevented in the course of adolescence, as this form can be severe and can lead to blindness. Risk factors are probably many, including diabetes duration, difficulties in achieving glycemic control due to increase in insulin requirements, low compliance to treatment, and hormonal changes related to puberty (abnormalities of the growth hormone (GH)/insulin-like growth factor-I (IGF-1) axis). Systematical diabetic retinopathy screening should be performed in adolescents, notably by non-mydriatic fundus photographs. Furthermore, the anticipation of the switch from pediatric to adult structures, together with the careful information and education of parents and children may improve visual prognosis of young diabetic patients, whose life expectancy is high.     

Therapeutic Potential of Insulin-Like Growth Factor-1 in Patients with Diabetes Mellitus

Insulin-like growth factor-1 (IGF-1) and its receptors share considerable homology with insulin and insulin receptors, and their respective signaling pathways interact at the post receptor level. While the growth hormone (GH)-IGF-1 axis principally regulates tissue growth and differentiation, insulin exerts it primary effects on fuel metabolism. However, these two endocrine systems interact at multiple levels and in diabetes mellitus the GH-IGF-1 axis is grossly disturbed, with increased secretion of GH, reduced plasma levels of IGF-1, and complex tissue-specific changes in IGF binding proteins (IGFBPs). These observations have given rise to the view that GH-IGF-1 axis dysfunction, particularly low plasma levels of circulating IGF-1, probably play a significant role in several aspects of the pathophysiology of diabetes mellitus, including insulin resistance and poor glycemic control, and may also influence the development of microvascular complications. The availability of recombinant human IGF-1 (rhIGF-1; mecasermin), used either alone or in combination with insulin, has led to experimental studies and clinical trials in humans testing these hypotheses. These studies have examined the impact of subcutaneous rhIGF-1 injections on sensitivity and metabolic parameters. In patients with type 1 and 2 diabetes mellitus, insulin sensitivity is significantly improved, insulin requirements are reduced, and glycemic control of dyslipidemia is generally improved in short-term studies. rhIGF-1 is a particularly attractive possibility in patients with type 2 diabetes mellitus, where insulin resistance is the fundamental problem. Some patients with genetic syndromes of severe insulin resistance also benefit from treatment with rhIGF-1, which can bypass blocks in the insulin signaling pathway. The common adverse effects reported for rhIGF-1 are dose-related and include edema, jaw pain, arthralgia, myalgia, hypotension, injection site pain, and less commonly, Bell's palsy and raised intracranial pressure. Although disturbance of the GH-IGF-1 axis participates in the development of diabetic complications, the functional consequences of the complex changes in IGFBP expression at the tissue level are uncertain, and it is not known whether systemic IGF-1 therapy or other manipulations of the GH-IGF-1 axis would be helpful or harmful. Experimentally, IGF-1 has a protective effect on neuropathy, and could find an application in the healing of neuropathic ulcers. The potential benefits of IGF-1 therapy in diabetes mellitus have yet to be realised.     

Metabolic control in children and adolescents with insulin-dependent diabetes mellitus at King Abdul-Aziz University Hospital

Objective: Preventing long-term diabetic complications requires good metabolic control, especially in type 1 diabetes mellitus (T1DM). We describe the metabolic control of T1DM and the factors affecting it among children and adolescents attending the Pediatric Clinic at King Abdul-Aziz University Hospital. Methods: A retrospective cross-sectional study was conducted on T1DM children and adolescents who had attended the Pediatric Clinic at King Abdul-Aziz University Hospital from 2006 to 2010. Both clinical and laboratory data were reviewed for the enrolled cases. The mean age of the patients was 12.5±4.1 years. Ages ranged from 1 to 18 years (n=484: male=213, female= 271). 38.6% of the patients were pre-pubertal and 61.4% - pubertal. The patients were categorized into 3 age groups as 1-6 years (10.3%), 7-12 years (33.5%) and 13-18 years (56.2%). Results: The overall mean HbA1c was 9.4±2.4% and the duration of patient follow-up was 26±17 months. 10.3% of the patients were on conventional insulin regimens and 89.7% - on intensive insulin therapy. 31.4% had satisfactory HbA1c according to the American Diabetes Association guidelines. The duration of T1DM was 2.9±1.4 years. The patients with diabetes duration ≤2 years (45%) had a mean HbA1c of 8.7±1.8% and those with diabetes duration >2 years (55%) had a mean HbA1c value of 9.8±2.3% (p< 0.001). Conclusions: The metabolic control of T1DM children in our cohort was less satisfactory than in other studies. We recommend the promotion of physical exercise and family educational programs to improve the metabolic control of T1DM pediatric patients in our population.Conflict of interest:None declared.     

空腹C-P、INS及胰岛细胞自身免疫抗体诊断儿童1型糖尿病的价值

为探讨儿童初发1型糖尿病（T1DM）的诊断指标，对33例T1DM患儿（观察组）分别测定其空腹血糖（FPG），糖化血红蛋白（HbA1c)，C－肽（C－P），胰岛素（INS），胰岛细胞抗体（ICA）及谷氨酸脱羧酶抗体（GAD），并与33例年龄，性别配对的健康儿童（对照组）作比较。结果显示，观察组除FPG，HbA1c显著升高外，C－P，INS，C－P／FPG，INS／FPG均显著低于对照组，以C－P／FPG最明显。提示空腹C－肽，INS，C－P／FPG，INS／FPG测定对诊断儿童初发T1DM有重要价值；胰岛细胞自免疫抗体测定对诊断T1DM有重要价值。     

Continuous subcutaneous insulin infusion in diabetes: patient populations,safety, efficacy,and pharmacoeconomics

The level of glycaemic control necessary to achieve optimal short‐term and long‐term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid‐acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health‐related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid‐acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost‐effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid‐acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients' health‐related quality of life; reviews relevant pharmacoeconomic data; and discusses recent advances in pump technology, including the development of closed‐loop ‘artificial pancreas’ systems. © 2015 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.     

Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil

Background

Hypoglycemia affects patient safety and glycemic control during insulin treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The Hypoglycemia Assessment Tool study in Brazil aimed to determine the proportion of patients experiencing hypoglycemic events and to characterize patient awareness and fear about hypoglycemia, among insulin-treated T1DM or T2DM patients.

Methods

This was a non-interventional, multicenter study, with a 6-month retrospective and a 4-week prospective evaluation of hypoglycemic events. Patients completed a questionnaire at baseline and at the end of the study, and also a patient diary. The answers ‘occasionally’ and ‘never’ to the question ‘Do you have symptoms when you have a low sugar level?’ denoted impaired hypoglycemia awareness. Fear was reported on a 10-point scale, from ‘not afraid at all’ to ‘absolutely terrified’.

Results

From 679 included patients, 321 with T1DM and 293 T2DM, median age of 33.0 and 62.0 years, 59% and 56% were female, and median diabetes duration was 15.0 and 15.0 years, respectively. Median time of insulin use was 14.0 and 6.0 years. During the prospective period, 91.7% T1DM and 61.8% T2DM patients had at least one hypoglycemic event. In the same period, 54.0% T1DM and 27.4% T2DM patients had nocturnal hypoglycemia, 20.6% T1DM and 10.6% T2DM patients had asymptomatic hypoglycemia, and severe events occurred in 20.0% and 10.3%, respectively. At baseline, 21.4% T1DM and 34.3% T2DM had hypoglycemia unawareness. The mean score of hypoglycemia fear was 5.9?±?3.1 in T1DM and 5.4?±?3.9 in T2DM. The most common attitude after hypoglycemic events were to increase calorie intake (60.3%) and blood glucose monitoring (58.0%) and to reduce or skip insulin doses (30.8%).

Conclusions

Referred episodes of hypoglycemia were high, in both T1DM and T2DM insulin users. Patient attitudes after hypoglycemia, such as reduction in insulin and increase in calorie intake, can affect diabetes management. These findings may support clinicians in tailoring diabetes education and insulin treatment for patients with diabetes, in order to improve their glycemic control while reducing the risk of hypoglycemic events.