Treatment Of T1DM Research Articles

Safety and efficacy of hematopoietic and mesanchymal stem cell therapy for treatment of T1DM: a systematic review and meta-analysis protocol

IntroductionInsulin standard treatment of T1DM cannot cure the patients as different chronic complications occurred subsequently. Investigations on a curative treatment in T1DM propose cell replacement or maintenance instead of exogenous insulin therapy, but different dimensions of this novel treatment are not clarified.Methods and analysisWe will include all clinical trials which have evaluated the efficacy MSC or HSC transplantation in T1DM treatment; electronically search bibliographic databases, country registration data banks, and gray literatures; and hand-search two key journals, two experts’ article, and references of the included articles with no language restriction. Primary outcome is the extent of reduction in insulin requirement and secondary outcomes are safety of MSC and HSC therapy, effect of this therapy on diabetic parameters, effect of the rout of transplantation and origin of the MSC or HSC on efficacy of treatment, studies heterogeneity and potential reasons of it. Heterogeneity and its severity will be calculated with Q Cochrane test, P value, and I2 index. STATA software version 12 will be used for meta-analysis. PROSPERO Registration number: CRD42016047176.Ethics and disseminationWe will publish the systematic review in a peer review journal; as it presents an analysis of published literature, the study does not require ethical approval.Strengths and limitations of this studyThis systematic review and meta-analysis will investigate the efficacy of MSC and HSC transplantation in T1DM treatment with no language restriction. Also we will evaluate gray literatures after hand searching.This protocol is prepared according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P).Two reviewers will evaluate screened full texts, extract data, and asses risk of bias of eligible primary studies independently.As there is the possibility that we miss some unpublished primary studies due to negative results, we will use funnel plot to detect this and correct it with fill and trim method.

Mesenchymal stem cells for diabetes mellitus treatment: new advances

Mesenchymal stem cells (MSCs) are the most widely used stem cells of the human body due to ease of successful isolation and expansion for many years. In particular, from 2012 until now, MSCs have been widely clinically used to treat various diseases, including graft versus host disease (GVHD), Crohn’s disease, and knee osteoarthritis. In this review, the applications of MSCs in diabetes will be reviewed and discussed. Diabetes mellitus type 1, also known as Type 1 diabetes (T1DM), is an autoimmune disease in which immune cells attack the beta cells in islets of Langerhans (pancreatic islets). Although type 2 diabetes (T2DM) is considered to be a disease related to insulin resistance, several recent studies have shown some relation of immune dysfunction in this disease. Therefore, MSC transplantation may be a beneficial treatment for both T1DM and T2DM. MSC transplantation in preclinical trials and clinical trials for T1DM and T2DM have shown a moderate to significant improvement in diabetes without adverse side effects. In this review, we will discuss some of the updates from preclinical and clinical trials of MSC transplantation for diabetes.

PDB42 - COST EFFECTIVENESS OF ALLOGENIC PANCREATIC ISLET TRANSPLANTATION VERSUS WHOLE PANCREAS TRANSPLANTATION IN THE UNITED KINGDOM

The study objective was to evaluate the cost-effectiveness of allogenic pancreatic islet transplantation (PIT) compared to whole pancreas transplantation (WPT) in adult patients with brittle type 1 diabetes (T1DM) and eligible for β-cell replacement in UK. A life-time horizon Markov model was developed to reflect the progression of patients who undergo β-cell replacement. The cohort moves across 8 health states: transplant, insulin independent, insulin dependent without and with complete graft function loss, macrovascular complications, microvascular complications, macro- and microvascular complications, death. Acute adverse events were also considered. Parametric extrapolations of insulin independence and graft survival were performed based on data from the Collaborative Islet Transplantation Registry (CITR) and the International Pancreas Transplant Registry (IPTR). All other clinical and quality of life data were derived from literature. Costs from the 3rd party payer perspective were obtained from official sources and from the literature. Both costs and health outcomes, life years (LYs) and quality adjusted LYs (QALYs), were annually discounted at 3.5%. As expected, better overall survival and lower complication rates increased both LYs and QALYs gained in PIT vs WPT, resulting in incremental values of 1.15 and 0.62 respectively. PIT was also associated with an incremental cost of £18,132 vs WPT. The resulting cost per LY and QALY gained with PIT vs WPT were £15,784 and £29,281 respectively. Deterministic and probabilistic sensitivity analysis showed overall robustness of the basecase results, with 74% of simulations located below the threshold of £100,000/QALY, usually considered for the assessment of orphan drugs in UK. To our knowledge, this is the first model to assess PIT against WPT for the treatment of brittle T1DM. Recognizing limitations, mainly due to the lack of direct comparative evidence, PIT seems to represent a cost-effective option to WPT in UK.

Insulin Glargine Dosing Every 16 Hours for a Complicated Type I Diabetes Case

ABSTRACT Objective: Type I diabetes mellitus (T1DM) is the most common type of diabetes during childhood. Insulin therapy is the mainstay of T1DM treatment, and glargine is long-acting insulin that is most commonly prescribed as a basal insulin therapy. Although glargine is typically administered once daily in the evening, alternative dosing frequencies and timings have been associated with promising results. Methods: A 23-year-old woman with a 16-year history of T1DM who was initially started on regular and neutral protamine Hagedorn insulin continued to have a poorly controlled glycated hemoglobin (HbA1c) level of 9.8% (84 mmol/mol). She was switched to glargine and glulisine, and her HbA1c improved to 8.5% (69 mmol/mol) with frequent high blood glucose readings at 12 PM. Her case was later complicated with gastroparesis and she was switched to an insulin pump. However, she suffered from two unexplained diabetic ketoacidosis episodes and opted to discontinue the pump therapy. Next, she was switched back...

GLP-1 Receptor Agonists and Type 1 Diabetes - Where Do We Stand?

Type 1 diabetes (T1DM) is a disease characterized by autoimmune mediated destruction of the insulin producing beta cells of endocrine pancreas. Beside insulin deficiency, T1DM is also characterized by abnormal suppression of glucagon secretion in response to hyperglycemia. All these abnormalities are likely to leave patients dependent upon exogenous insulin administration for survival. GLP-1 is a hormone secreted by L-cells of distal small intestine and colon. GLP-1 exerts its effects through the interaction with GLP-1 receptor expressed in the pancreatic islets, lung, hypothalamus, stomach, heart and kidney. It belongs to the group of incretin peptides and it stimulates insulin and inhibits glucagon secretion. Actions of GLP-1 also include delaying of gastric emptying, reduction of appetite and induction of satiety. On the other hand, evidences mainly collected from animal models, have indicated the role of GLP-1 in increasing beta cell proliferation and differentiation and in decreasing the rate of beta cell apoptosis. GLP-1 receptor agonists are approved for the treatment of type 2 diabetes where they have established very important position. However, they are still not approved for use in T1DM, although they could have beneficial effects in both new onset and longstanding T1DM patients, mainly as an adjunctive therapy to insulin in order to improve glycemic control and body weight management in longstanding disease or to reduce insulin requirements or even to delay the absolute dependence upon insulin administration in new onset T1DM. Randomized, long-term, placebo controlled clinical trials are warranted before the official implementation of GLP-1 receptor agonists in the treatment of T1DM.

Outpatient Management of Pediatric Type 1 Diabetes.

The incidence of both type 1 and type 2 diabetes (T1DM and T2DM) continues to rise within the pediatric population. However, T1DM remains the most prevalent form diagnosed in children. It is critical that health-care professionals understand the types of diabetes diagnosed in pediatrics, especially the distinguishing features between T1DM and T2DM, to ensure proper treatment. Similar to all individuals with T1DM, lifelong administration of exogenous insulin is necessary for survival. However, children have very distinct needs and challenges compared to those in the adult diabetes population. Accordingly, treatment, goals, and age-appropriate requirements must be individually addressed. The main objectives for the treatment of pediatric T1DM include maintaining glucose levels as close to normal as possible, avoiding acute complications, and preventing long-term complications. In addition, unique to pediatrics, facilitating normal growth and development is important to comprehensive care. To achieve these goals, a careful balance of insulin therapy, medical nutrition therapy, and exercise or activity is necessary. Pharmacological treatment options consist of various insulin products aimed at mimicking prior endogenous insulin secretion while minimizing adverse effects. This review focuses on the management of pediatric T1DM in the outpatient environment, highlighting pharmacotherapy management strategies.

Comparison of several data‐driven non‐linear system identification methods on a simplified glucoregulatory system example

In this paper, several advanced data-driven nonlinear identification techniques are compared on a specific problem: a simplified glucoregulatory system modeling example. This problem represents a challenge in the development of an artificial pancreas for T1DM treatment, since for this application good nonlinear models are needed to design accurate closed-loop controllers to regulate the glucose level in the blood. Block-oriented as well as state-space models are used to describe both the dynamics and the nonlinear behavior of the insulin-glucose system, and the advantages and drawbacks of each method are pointed out. The obtained nonlinear models are accurate in simulating the patient's behavior, and some of them are also sufficiently simple to be considered in the implementation of a model-based controller to develop the artificial pancreas.

Laminin 411 acts as a potent inducer of umbilical cord mesenchymal stem cell differentiation into insulin-producing cells.

BackgroundDiabetes mellitus (DM) is an incurable metabolic disease constituting a major threat to human health. Insulin-producing cells (IPCs) differentiated from mesenchymal stem cells (MSCs) hold great promise in the treatment of DM. The development of an efficient IPC induction system is a crucial step for the clinical application of IPCs for DM. Laminin 411 is a key component of the basement membrane and is involved in the regulation of cell differentiation; however, little is known about a role of laminin 411 in the regulation of IPC differentiation from human MSCs.MethodsMSCs were isolated from human umbilical cord (UC-MSCs) and expanded in an in vitro culture system. UC-MSCs were then cultured in the IPC induction and differentiation medium in the presence of laminin 411. Flow cytometry, Quantitative realtime PCR, immunofluorescence staining, ELISA, Western blotting and other techniques were applied to determine IPC generation, insulin expression and related mechanisms. To evaluate potential therapeutic efficacy of IPCs induced from UC-MSCs, a type-1 diabetes (T1DM) rat model was generated using streptozotocin. Blood glucose, insulin levels, and survival of rats were monitored periodically following intravenous injection of the tested cells.ResultsLaminin 411 markedly induced the expression of the genes Foxa2 and Sox17, markers for pancreatic precursor cells, efficiently induced IPC differentiation from MSCs, and up-regulated insulin expression at both mRNA and protein levels. Furthermore, the expression of the genes known to govern insulin expression including Pdx1 and Ngn3 was markedly induced by laminin 411, which suggests that Pdx1 and Ngn3 signaling pathways are involved in laminin 411 induced-insulin expression machinery. More importantly, administration of laminin 411-induced IPCs rapidly and significantly down-regulated fasting blood glucose levels, significantly reduced the HbA1c concentration and markedly improved the symptoms and survival of T1DM rats.ConclusionsOur results demonstrate that laminin 411 acts as a potent differentiation inducer of IPCs from UC-MSCs via the Pdx1 and Ngn3 signaling pathways. Moreover, transfusion of laminin 411 induced-IPCs more efficiently improves symptoms and survival of T1DM rats. These novel finding highlights a potential clinical application of laminin 411 induced-IPCs in the treatment of T1DM, which calls for further studies.

PDB66 - The Cost-Utility of Insulin Degludec Compared with Current Standard of Care in the Management of Type One and Type Two Diabetes Mellitus in Belgium

Insulin degludec (IDeg) is a basal insulin with an ultra-long duration of action for management of patients with type 1 (T1DM) and patients with type 2 (T2DM) diabetes. IDeg has demonstrated efficacious blood glucose control, with less hypoglycaemic events, and with an option for flexibility in dose time, compared with insulin glargine (IGlar). The objective was to assess the cost-effectiveness of IDeg in Belgium, compared with IGlar. The analysis focused on patients in three treatment regimens: T1DM, T2DM treated with basal insulin in combination with oral anti-diabetics (BOT) and T2DM treated with basal-bolus (BB). A one-year cost-utility model driven by differences in hypoglycaemia was used. Published dis-utilities for hypoglycaemic events were multiplied by the rate of hypoglycaemia to calculate quality-adjusted life years (QALYs). Costs and utilities were also calculated for potential use of less blood glucose test strips. A utility gain was attributed to the additional benefit of dosing flexibility. Unit costs pertained to public tariffs and reflected the payer perspective in Belgium. Baseline incidence rates of hypoglycaemic events and related resource utilization pertained to a Belgian patient-reported outcomes study. Hospitalization costs following severe hypoglycaemia were estimated using the IMS Hospital Disease Database. IDeg was associated with an incremental cost-effectiveness ratio of 14,677€/QALY in T1DM, 4,976€/QALY in T2DM BOT, and 12,930€/QALY in T2DM BB. Univariate and probabilistic sensitivity analyses confirmed robust results. Results were most sensitive to variations in number of IGlar doses per day, and number of glucose-monitoring tests. At a willingness to pay threshold of 30,000€/QALY, IDeg would be cost-effective in 54%, 100% and 93% of the cases in the T1DM, T2DM BOT or T2DM BB treatment regimens respectively. These analyses demonstrate that IDeg is cost-effective in Belgium, when used in patients with T1DM and T2DM currently treated with long-acting insulin analogues.

Safety, effectiveness, and cost of long-acting versus intermediate-acting insulin for type 1 diabetes: Protocol for a systematic review and network meta-analysis

BackgroundType 1 diabetes mellitus (T1DM) causes progressive destruction of pancreatic beta cells leading to absolute insulin deficiency. Treatment of T1DM requires insulin, and some evidence suggests that longer acting insulin analogues might have a higher effectiveness and greater safety profile compared to intermediate-acting insulin. Our objective is to evaluate the comparative effectiveness, safety, and cost of long-acting insulin versus intermediate-acting insulin through a systematic review and network meta-analysis.Design/methodsStudies examining long-acting versus intermediate-acting insulin or placebo preparations for adult T1DM patients will be included. The primary outcome is glycosylated hemoglobin (A1C), and secondary outcomes include emergency department and physician visits, hospital admissions, weight gain, quality of life, microvascular complications (e.g., retinopathy), macrovascular complications (e.g., cardiovascular disease), all-cause mortality, incident cancers, and cost. We will include experimental [randomized clinical trials (RCTs), quasi-RCTs, non-RCTs], quasi-experimental (controlled before-after, interrupted time series), observational (cohort), and cost studies, of any duration of follow-up, conducted during all time periods, and disseminated in any language.We will conduct comprehensive searches of electronic databases from inception onwards, including MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. We will also search for difficult to locate and unpublished literature by searching dissertation databases, public health organization websites, and trial registries. After a calibration exercise using our eligibility criteria and data abstraction forms, two reviewers will screen all citations, full-text articles, and abstract data in duplicate. Conflicts will be resolved by team discussion. Using a similar process, the Cochrane Effective Practice and Organization of Care Risk of Bias tool will be used to appraise the risk of bias of experimental and quasi-experimental studies, while the Newcastle Ottawa Scale will be used to assess the methodological quality of cohort studies. If feasible and appropriate, we will conduct a random effects meta-analysis, as well as a network meta-analysis.DiscussionOur systematic review will be of utility to healthcare providers, policy-makers, T1DM patients and family members regarding treatment options of long-acting versus intermediate-acting insulin preparations.Trial registrationPROSPERO registry number: CRD42013003610

Multifunctional Capsule‐in‐Capsules for Immunoprotection and Trimodal Imaging

Type I diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease that results in destruction of insulin-producing β cells and subsequent hyperglycemia.[1,2] The current way of treating T1DM is insulin replacement therapy through repetitive injections of recombinant insulin. In more serious cases, a cadaveric pancreas[3] or purified pancreatic islets[4,5] can be transplanted to restore proper glucose regulation. However, the risks of surgery and the accompanying life-long immunosuppression outweigh the disadvantages of continued administration of insulin. The immunoisolation of islets by alginate microencapsulation is an emerging and promising solution to circumvent immune rejection and so overcome this limitation.[6] While the semipermeable alginate membrane blocks penetration of immune cells and antibodies, it allows the unhindered passage of nutrients, metabolites, and insulin that are produced by encapsulated islet cells.[7] Intraperitoneal administration of microencapsulated islets in monkeys and humans has showed considerable promise for the treatment of T1DM.[8,9]

Modeling the lifetime costs of insulin glargine and insulin detemir in type 1 and type 2 diabetes patients in Canada: a meta-analysis and a cost-minimization analysis

Background:Two basal insulin analogues, insulin glargine once daily and insulin detemir once or twice daily, are marketed in Canada.Objective:To estimate the long-term costs of insulin glargine once daily (QD) versus insulin detemir once or twice daily (QD or BID) for type 1 (T1DM) and type 2 (T2DM) diabetes mellitus from a Canadian provincial government’s perspective.Methods:A cost-minimization analysis comparing insulin glargine (IGlarg) to insulin detemir (IDet) was conducted using a validated computer simulation model, the CORE Diabetes Model. Lifetime direct medical costs including costs of insulin treatment and diabetes complications were projected. T1DM and T2DM patients’ daily insulin dose (T1DM: IGlarg QD 26.2 IU; IDet BID 33.6 IU; T2DM: IGlarg QD 47.2 IU; IDet QD 65.7 IU or IDet BID 80.4 IU) was derived from a meta-analysis of randomized trials. All patients were assumed to stay on the same treatment for life. Costs were discounted at 5% per annum and reported in 2010 Canadian Dollars.Results:The meta-analysis showed T1DM and T2DM patients had similar HbA1c change from baseline when receiving IGlarg compared to IDet (T1DM: 0.002%-points; p = 0.97; T2DM: −0.05%-points; p = 0.28). Treatment of T1DM patients with IGlarg versus IDet BID resulted in lifetime cost savings of $4231 per patient. Treatment of T2DM patients with IGlarg resulted in lifetime cost savings of $4659 per patient versus IDet QD and cost savings of $8709 per patient versus IDet BID.Conclusions:Similar HbA1c change from baseline can be achieved with a lower IGlarg than IDet dose. From the perspective of a Canadian provincial government, treatment of T1DM and T2DM patients with IGlarg instead of IDet can generate long-term cost savings. Main limitations include trial data were derived from multi-country studies rather than the Canadian population and self-monitoring blood glucose costs were not included.

Study progression of GLP-1 analogues in type 1 diabetes and islet transplant

Type 1 diabetes mellitus (TlDM) is an autoimmune disease characterized by the destruction of pancreatic β cells, which sequentially leading to the reduction of insulin secretion. Numerous susceptibilities, including genetic and environmental factors, may be involved in triggering the T1DM. The ideal therapy for T1DM should focus on both preventing the immune system from attacking β cells, and also the stimulation of β cell neogenesis. In vitro and in vivo studies both demonstrated that GLP-1 analogues were able to promote the synthesis and secretion of insulin, stimulate neogenesis of β cells, increase β cells replication, and reduce β cell apoptosis. Hence, GLP-1 analogues have been shown to be potential treatment for T1DM. This work reviewed recent publications regarding to GLP-1 application in TlDM and pancreatic islet transplantations and prospected the future research directions. Key words: Glucagon-like peptide-1 analogue; Diabetes mellitus,type 1; Islet transplant; Liraglutide

Bioactive Long-Term Release from Biodegradable Microspheres Preserves Implanted ALG-PLO-ALG Microcapsules from In Vivo Response to Purified Alginate

To assess whether prevention of unexpected in vivo adverse inflammatory and immune responses to biohybrid organ grafts for the treatment of Type I Diabetes Mellitus (T1DM) is possible by superoxide dismutase and ketoprofen controlled release. Superoxide dismutase and ketoprofen-loaded polyester microspheres were prepared by W/O/W and O/W methods, embodied into purified alginate-poly-L-ornithine-alginate microcapsules and intraperitoneally implanted into CD1 mice. The microspheres were characterized for morphology, size, encapsulation efficiency, enzyme activity and in vitro release. Purified alginate contaminants were assayed, and the obtained microcapsules were investigated for size and morphology before and after implantation over 30 days. Cell pericapsular overgrowth and expression were evaluated by optical microscopy and flow cytometry. Superoxide dismutase and ketoprofen sustained release reduced cell pericapsular overgrowth in comparison to the control. Superoxide dismutase release allowed preserving the microcapsules over 30 days. Ketoprofen-loaded microspheres showed some effect in the immediate post-grafting period. A higher macrophage and T-cell expression was observed for the control group. Microspheres containing superoxide dismutase and ketoprofen may represent novel tools to limit or prevent unpredictable adverse in vivo response to alginate, thus contributing to improve cell transplantation success rates in T1DM treatment.

Physical Activity Does Not Improve Control of Type 1 Diabetes in Adolescents

Source: Aman J, Skinner TC, de Beaufort CE, et al. Associations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: the Hvidoere Study Group on Childhood Diabetes. Pediatr Diab. 2009; in press; doi:10.1111lj.1399-5448.2008.00495.xThe Hvidoere Study Group (HSG) on Childhood Diabetes, a worldwide consortium of pediatric diabetes caregivers, sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes in adolescents with type 1 diabetes (T1DM).Youth aged 11–18 years with T1DM for at least one year were invited to participate in the study which was conducted at 21 centers located on multiple continents. In addition to standard clinical data, diabetes-specific quality of life was assessed in study patients using an edited version of the Diabetes Quality of Life-Short Form (DQOL-SF) questionnaire.Psychological status and health perception were assessed using the World Health Organization’s Health Behavior School-aged Children Questionnaire (HBSC survey 2001). Questions on the survey included number of days during the last week being moderately physically active for more than one hour, the usual number of hours watching television during one day, the usual daily number of hours doing school homework, and the usual daily hours of computer activity. Hemoglobin A1c (HbA1c) level, assayed in one central laboratory, was the primary study outcome.Of the 2,269 patients with insulin-treated T1DM, 2,093 (92%) completed the questionnaires, and 89% had an HbA1c performed. Mean age was 14.5±2.1 years for males and 14.5±2.1 for females; insulin pump therapy was used by 15.9% of patients.Mean body mass index (BMI) was 22.8±4.2 in females and 21.7±3.7 in males and did not correlate with HbA1c or insulin regimen. The mean HbA1c in study patients was 8.2±1.4% (males 8.1±1.3%; females 8.3±1.5%) and was positively but modestly correlated to age and duration of diabetes. Adolescents whose families had language problems had significantly higher HbA1c than those from families with no language problems.Older participants and females reported less physical activity. Physical activity was not associated with metabolic outcome (HbA1c), frequency of hypoglycemia, ketoacidosis, or BMI.However, it was positively associated with all markers of psychological health including general quality of life.There were significant differences among centers for physical activity, watching television, playing on the computer, and time spent doing school homework. However, these center differences did not account for the center differences in metabolic outcomes. The authors conclude that physical activity is strongly associated with general well-being and psychological well-being but not with metabolic control.Dr. Varma has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Multicenter studies, particularly those with centers on multiple continents with a broad range of cultural norms, present challenges in reaching a straightforward conclusion using the same questionnaire form.Although a large group of adolescents were enrolled in the current study, the complexities of the study issues across cultures may interfere with defining a clear explanation of differences in clinical outcomes. Also, as the authors note, self-reporting on questionnaires may not be accurate. Furthermore, a single value of HbA1c may not reflect long-term control.The authors’ finding that regular physical activity was associated with better psychological health of adolescents is not surprising. Physical activity is one of the major tools for treatment of T1DM, and it has been shown to improve insulin sensitivity and increase lean body mass. The improved physical and psychological well-being also will positively affect lipid metabolism.1The authors’ conclusion, that there is no correlation between physical activity and glycemic control in adolescents, is a discouraging finding that echoes prior studies.2,3 However, recommending physical activity on a daily basis in patients with T1DM should at least benefit psychosocial health status, an important outcome for patients with chronic disease.

Nocturnal hypoglycaemias in type 1 diabetic patients: what can we learn with continuous glucose monitoring?

Aim In type 1 diabetic patients (T1DM), nocturnal hypoglycaemias (NH) are a serious complication of T1DM treatment; self-monitoring of blood glucose (SMBG) is recommended to detect them. However, the majority of NH remains undetected on an occasional SMBG done during the night. An alternative strategy is the Continuous glucose monitoring (CGMS), which retrospectively shows the glycaemic profile. The aims of this retrospective study were to evaluate the true incidence of NH in T1DM, the best SMBG time to predict NH, the relationship between morning hyperglycaemia and NH (Somogyi phenomenon) and the utility of CGMS to reduce NH. Methods Eighty-eight T1DM who underwent a CGMS exam were included. Indications for CGMS evaluation, hypoglycaemias and correlation with morning hyperglycaemias were recorded. The efficiency of CGMS to reduce the suspected NH was evaluated after 6–9 months. Results The prevalence of NH was 67% (32% of them unsuspected). A measured hypoglycaemia at bedtime (22–24 h) had a sensitivity of 37% to detect NH (OR = 2.37, P = 0.001), while a single measure ≤ 4 mmol/l at 3-hour had a sensitivity of 43% (OR = 4.60, P < 0.001). NH were not associated with morning hyperglycaemias but with morning hypoglycaemias (OR = 3.95, P < 0.001). After 6–9 months, suspicions of NH decreased from 60 to 14% ( P < 0.001). Conclusion NH were highly prevalent and often undetected. SMBG at bedtime, which detected hypoglycaemia had sensitivity almost equal to that of 3-hour and should be preferred because it is easier to perform. Somogyi phenomenon was not observed. CGMS is useful to reduce the risk of NH in 75% of patients.

Child Routines and Youths' Adherence to Treatment for Type 1 Diabetes

Type 1 diabetes (T1DM) is a chronic life-threatening disease that requires strict adherence to daily treatment tasks. Although necessary for survival, children who present with behavior problems tend to show problems complying with the treatment regimen, thereby increasing their risk for morbidity and premature mortality. The risk of poor treatment adherence is hypothesized to be lower for these children, however, if they engage in more routine behaviors. Given the potential clinical implications, this hypothesis and two theoretical models proposed to elucidate the underlying psychological process for the role of child routines in treatment adherence were evaluated empirically. The first model hypothesized that child routines protect (moderator variable) behaviorally problematic children from poor treatment adherence, whereas the alternative model hypothesized that child routines mediate the relation between childhood behavior problems and poor treatment adherence. Parents of T1DM patients (N = 111) ranging from 6 to 16 years of age (M = 12 years) reported on their child's behavior problems, routine behaviors, and adherence to treatment for T1DM using standardized measures. Baron and Kenny's statistical procedures for testing moderation and mediation hypotheses were used to evaluate the proposed models. Regression analyses did not support the moderation hypothesis but did support the hypothesis that engaging in child routines mediates the relation between childhood behavior problems and poor treatment adherence. Parents of behaviorally problematic children diagnosed with T1DM might be advised to instill routines in their child's daily activities to increase the likelihood of treatment adherence, and thereby reduce the risk of morbidity and early mortality. Implications for clinical interventions are discussed.

Better long‐term glycaemic control with the basal insulin glargine as compared with NPH in patients with Type 1 diabetes mellitus given meal‐time lispro insulin

Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but no study has proven superiority. The aim of this study was to test superiority of glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia vs. NPH. One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal, were randomized to either continuation of NPH four times/day (n = 60), or once daily glargine at dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in both groups. In 11 patients from each group, responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's treatment. Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05). HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from 7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/- 0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes, blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2 +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH treatment resulted in no change of responses to hypoglycaemia, whereas with glargine plasma glucose, thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved (P < 0.05). The simpler glargine regimen decreases the percentage of HbA(1c) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus, glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM.