Introduction Of Insulin Treatment Research Articles

Circulating C1q/TNF-Related Protein 3, Omentin-1 and NGAL in Obese Patients with Type 2 Diabetes During Insulin Therapy.

The aim of the study was to quantify the plasma concentration of omentin-1, neutrophil gelatinase-associated lipocalin (NGAL), and complement C1q tumor necrosis factor-related protein-3 (CTRP3) in obese patients with type 2 diabetes, before introducing insulin therapy, in relation to the plasma expression profiles of these regulatory molecules in the same patients after a 6-month insulin mixture therapy and in obese controls. Elevated plasma NGAL concentrations were found in type 2 diabetic patients as compared with subjects with metabolically healthy obesity. In turn, a 6-month insulin mixture therapy has shown a marked increase in the plasma concentration of omentine-1 and a significant decrease in plasma CTRP3 concentration in obese patients with type 2 diabetes, in relation to the values found in these patients before the implementation of insulin therapy. Insulin mixture therapy has also proved to be an important factor modifying the plasma profile of NGAL, increasing the concentration of this bioactive molecule in the plasma of patients with type 2 diabetes, after 6 months of its use, in relation to the concentration before treatment. The significant changes in the plasma profile of omentin-1, NGAL and CTRP3 during insulin therapy suggest their potential diagnostic utility in monitoring metabolic changes associated with the introduction of insulin treatment in type 2 diabetic patients.

Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT).

The best treatment strategy for a patient with type 2 diabetes who shows pronounced weight gain after the introduction of insulin treatment is unclear. We determined whether addition of a glucagon-like peptide-1 (GLP-1) analogue could reverse pronounced insulin-associated weight gain while maintaining glycaemic control, and compared this with the most practised strategy, continuation and intensification of standard insulin therapy. In a 26-week, randomised controlled trial (ELEGANT), conducted in the outpatient departments of one academic and one large non-academic teaching hospital in the Netherlands, adult patients with type 2 diabetes with ≥ 4% weight gain during short-term (≤ 16 months) insulin therapy received either open-label addition of liraglutide 1.8 mg/day (n = 26) or continued standard therapy (n = 24). A computer-generated random number list was used to allocate treatments. Participants were evaluated every 4-6 weeks for weight, glycaemic control and adverse events. The primary endpoint was between-group weight difference after 26 weeks of treatment (intention to treat). Of 50 randomised patients (mean age 58 years, BMI 33 kg/m(2), HbA1c 7.4% [57 mmol/mol]), 47 (94%) completed the study; all patients were analysed. Body weight decreased by 4.5 kg with liraglutide and increased by 0.9 kg with standard therapy (mean difference -5.2 kg [95% CI -6.7, -3.6 kg]; p < 0.001). The respective changes in HbA1c were -0.77% (-8.4 mmol/mol) and +0.01% (+0.1 mmol/mol) (difference -0.74% [-8.1 mmol/mol]) ([95% CI -1.08%, -0.41%] [-11.8, -4.5 mmol/mol]; p < 0.001); respective changes in insulin dose were -29 U/day and +5 U/day (difference -33 U/day [95% CI -41, -25 U/day]; p < 0.001). In five patients (19%), insulin could be completely discontinued. Liraglutide was well tolerated; no severe adverse events or severe hypoglycaemia occurred. In patients with pronounced insulin-associated weight gain, addition of liraglutide to their treatment regimen reverses weight, decreases insulin dose and improves glycaemic control, and hence seems a valuable therapeutic option compared with continuation of standard insulin treatment. Trial registration ClinicalTrials.gov NCT01392898. Funding The study was funded by Novo Nordisk.

Long-Term Benefits in Lung Function and Nutritional Status of Strict Metabolic Control of Cystic Fibrosis-Related Diabetes

Cystic fibrosis related diabetes (CFRD) is a strong determinant for lung function decline and increased mortality. Insulin treatment of CFRD is reportedly beneficial for this situation. We report on the long-term impact of insulin treatment of CFRD on pulmonary function and nutritional status in a CF male patient since diagnosis of diabetes. We report the case of a patient diagnosed with CF at the age of 16. Two years later, he experienced a rapidly evolving decrease in pulmonary function, some months later criteria were met warranting lung transplantation. Concomitantly, he was diagnosed with CFRD and insulin therapy was started. Lung function (spirometry), nutritional status (body mass index) and metabolic control (HbA 1c) were determined every 3 months. After the introduction of insulin treatment, pulmonary function and nutritional status progressively improved and good glycemic control was achieved. The significant and sustained improvement in pulmonary function allowed for the patient's withdrawal from the lung transplantation program within 4 months, a situation which has been maintained until now, 8 years later. The long follow-up of our patient documents the rapid and prolonged beneficial effect of proper metabolic control of CFRD on the respiratory deterioration in CF.

Efecto beneficioso y prolongado del buen control metabólico de la diabetes relacionada con fibrosis quística sobre la función pulmonar y el estado nutricional

Cystic fibrosis related diabetes (CFRD) is a strong determinant for lung function decline and increased mortality. Insulin treatment of CFRD is reportedly beneficial for this situation. We report on the long-term impact of insulin treatment of CFRD on pulmonary function and nutritional status in a CF male patient since diagnosis of diabetes. We report the case of a patient diagnosed with CF at the age of 16. Two years later, he experienced a rapidly evolving decrease in pulmonary function, some months later criteria were met warranting lung transplantation. Concomitantly, he was diagnosed with CFRD and insulin therapy was started. Lung function (spirometry), nutritional status (body mass index) and metabolic control (HbA 1c) were determined every 3 months. After the introduction of insulin treatment, pulmonary function and nutritional status progressively improved and good glycemic control was achieved. The significant and sustained improvement in pulmonary function allowed for the patient's withdrawal from the lung transplantation program within 4 months, a situation which has been maintained until now, 8 years later. The long follow-up of our patient documents the rapid and prolonged beneficial effect of proper metabolic control of CFRD on the respiratory deterioration in CF.

Holter glycémique et dépistage du diabète chez l’enfant atteint de mucoviscidose

In the past few years, survival has increased for people with cystic fibrosis (CF). Diabetes is an important complication of CF caused by pancreatic insufficiency, which reduces insulin secretion. Because of increased longevity of patients with CF, the prevalence of CF-related diabetes (CFRD) has increased. CFRD is associated with increased mortality and morbidity. Several studies have reported a decline in nutritional and pulmonary status 2-4 years before the diagnosis of CFRD. The introduction of insulin treatment can produce clinical improvement in weight and lung function. The oral glucose tolerance test is currently the reference method in screening for CFRD, but the current definition of diabetes based on the 2-h post-load plasma glucose level may not be the most accurate method for early detection of glucose tolerance abnormalities in CF. The continuous glucose monitoring system (CGMS) has been described as a useful tool for early detection of hyperglycemia in the CF patient. We tested the CGMS in CF patients with unexplained alteration of their general status. The aim of this study was to assess the value of the CGMS in this population. An annual OGTT (following World Health Organization recommendations) was conducted as a screening test to identify CFRD in patients aged over 10 years or patients aged under 10 years with a poorer clinical status. The CGMS was performed in patients with unexplained worsened clinical status and without diabetes in OGTT. Forty-two patients aged from 8.5 to 19 years were screened using OGTT for CFRD. According to ADA criteria, 23 patients (54.8%) displayed normal glucose tolerance, 14 (33.3%) impaired glucose tolerance, and 5 diabetes (11.9%). Out of 37 nondiabetic, the CGMS was used in 20 patients with unexplained altered general status. The CGMS revealed peaks of glucose values greater than 2 g/L in 16 patients, 9 patients with normal glucose tolerance, and 7 patients with impaired glucose tolerance. The mean CGMS glucose and time of glycemic monitoring above 1.4 g/L increased in patients with peaks greater than 2 g/L compared to patients without peaks (p=0.0016 and p=0.0069 respectively). After analysis of the CGMS, the prevalence of diabetes increased from 11.9 to 50%. Three patients aged less than 10 years with a normal OGTT profile presented glycemic peaks greater than 2 g/L during CGMS. CGMS revealed more glucose metabolism abnormalities than OGTT in patients with unexplained altered general status.

Exploring the idiotypes of insulin antibodies as markers for remission in Type 1 diabetes

Complete or partial remission can occur in newly diagnosed Type 1 diabetes patients. We created idiotype-specific reagents to explore the idiotypes of insulin antibodies (IA) in a patient in remission, and to compare with a patient who was not. Phage display was used to create a library of phagotopes specific to insulin binding in four sera. Sera from a Type 1 diabetes subject deemed to have undergone remission were taken at diagnosis and again during remission. Sera from a non-remitter were taken at diagnosis and after 3 months on insulin. Phagotopes from the four sera were randomly selected and tested for insulin specificity in a radiobinding assay by using sera from remitters and non-remitters. IA-binding phagotope selected from serum during remission displaced insulin binding in all nine IA(+) remitters and all 10 IA(+) non-remitters. IA-binding phagotope selected from the non-remission patient (3 months after insulin therapy) displaced insulin binding in 8/9 IA(+) remitters and 8/10 IA(+) non-remitters. The consensus peptide sequences adduced from the phages were identical for both these phagotopes. Phagotopes derived from insulin autoantibody-positive individuals at diagnosis were unable to displace insulin binding in the IA(+) sera 3 months later, whether in remission or not. We have established the principle of using phage display in the investigation of insulin antibodies during remission in Type 1 diabetes. The immunological characteristics of IA 3 months after the introduction of insulin treatment were different from those at diagnosis of Type 1 diabetes (IAA). Using phage display technology, it was not possible to distinguish insulin antibodies according to remission status.

Increasing incidence of Type 1 diabetes – role for genes?

BackgroundThe incidence of Type 1 diabetes (T1DM) is increasing fast in many populations. The reasons for this are not known, although an increase in the penetrance of the diabetes-associated alleles, through changes in the environment, might be the most plausible mechanism. After the introduction of insulin treatment in 1930s, an increase in the pool of genetically susceptible individuals has been suggested to contribute to the increase in the incidence of Type 1 diabetes.ResultsTo explore this hypothesis, the authors formulate a simple population genetic model for the incidence change driven by non-Mendelian transmission of a single susceptibility factor, either allele(s) or haplotype(s). A Poisson mixture model is used to model the observed number of cases. Model parameters were estimated by maximizing the log-likelihood function. Based on the Finnish incidence data 1965–1996 the point estimate of the transmission probability was 0.998. Given our current knowledge of the penetrance of the most diabetic gene variants in the HLA region and their transmission probabilities, this value is exceedingly unrealistic.ConclusionsAs a consequence, non-Mendelian transmission of diabetic allele(s)/haplotype(s) if present, could explain only a small part of the increase in incidence in Finland. Hence, the importance of other, probably environmental factors modifying the disease incidence is emphasized.

A4. A retrospective review of the effect of insulin therapy on metabolic control, weight, lipid levels and blood pressure in people with type II diabetes

Background The role of insulin in the treatment of type II diabetes has been the subject of many debates. Exogenous insulin has been suggested to have both beneficial and detrimental effects in the health and well-being of diabetic patients ( Genuth, 1996). The beneficial effect is the result of reducing hyperglycaemia ( Henry, 1996). On the other hand, insulin treatment is considered to accelerate the development of cardiovascular disease by increasing cardiovascular disease risk factors ( Turner, 1996). Aim The aim of this retrospective review was to monitor the effect of insulin therapy on metabolic control, and in addition to monitor the contact with a dietitian on starting insulin. Methods The study involved 202 patients with type II diabetes. Group A: 149 subjects (mean age 64 years) poorly controlled patients who had switched to insulin treatment and Group B: 53 subjects (mean age 68 years) who were maintained on oral hypoglycaemic agents. All variable were collected (a) on starting insulin (or reference date) and (b) one year later. Changes within each group in glycaemic control, weight serum lipid levels and blood pressure were evaluated using Two-sample t-test assuming equal variances. Changes in the two groups were compared using the Two-sample t-test assuming unequal variances. Results Type II diabetic patients who had switched to insulin treatment had experienced a significant increase in body weight (5.4 kg) in comparison to control subjects at the year after insulin commencement. Mean HbA1c and fasting blood glucose (FBG) decreased significantly in the insulin group (from 9.9 ± 2.1 to 8.5 ± 1.6% and from 14.6 ± 5.6 to 10.3 ± 3.9 mmol L−1, respectively). In contrast no statistically significant difference was noted in the control group for either HbA1c or FBG. Blood lipids did not change significantly in either group, and blood pressure also remained statistically unchanged. 36% of the insulin treated patients had dietetic input at the time of insulin commencement. Conclusions Weight gain and improvement in glycaemic control, has been demonstrated in previous studies. Even though the current study did not show changes in lipid levels, other studies have shown a reduction in both triglyceride and cholesterol levels. The introduction of insulin treatment in individuals with poorly controlled type II diabetes appears to positively affect metabolic control. Long-term improvement in metabolic control has been shown to have many effects on the health and longevity of diabetic individuals, as has a reduction in the individual’s weight. Prospective studies in this area could fully determine the effects of insulin introduction on these variables, enabling fuller conclusions to be made with respect to longevity and future disease risks.

A Force of Magical Activity: The Introduction of Insulin Treatment in Britain 1922–1926

The discovery of insulin by Banting and Best in 1992 is the subject of many papers and one authoritative book (Bliss M. The Discovery of Insulin. Chicago: University of Chicago Press, 1982. See also Bliss M. Rewriting medical history: Charles Best and the Banting and Best myth. J Med Hist 1993; 48: 253-274.). This paper charts the introduction of insulin in England and examines its effects on medical practice. Before 1922 there were few effective drugs and only one (thyroid extract) which had to be taken continuously. Insulin was radically different; it restored weight and vigour and allowed survival in diabetic coma and after surgery but was potentially dangerous because of the possibility of hypoglycaemia, had to be given by injection, and the dose varied with the amount of food and exercise. The immediate questions to be answered after the supply of insulin was assured were how could such a powerful drug be kept out of the hands of ignorant people (a phrase used by The Times), who would administer it, and who would supervise the treatment? Within a year further problems were identified. Should the aims of treatment be the same as those in the starvation era? Could the diet be liberalized? How much biochemical monitoring was necessary? I set the scene by describing how, from Minkowski's announcement (1889) that pancreatectomy caused severe diabetes, most clinicians and physiologists believed that the pancreas (and specifically the islets of Langerhans) produced an internal secretion which controlled carbohydrate metabolism. After Murray's (1891) demonstration that myxoedema could be cured by thyroid extract, it was assumed that diabetes would soon yield in the same way. Yet by the beginning of the First World War most experts were pessimistic about isolating the hypothetical internal secretion and had pinned their hopes on starvation treatment. In the decade before the introduction of insulin the management of diabetes was grim; patients were kept in hospital for weeks or months, while their calorie intake and glucose excretion was meticulously recorded. They were in the wards of physicians with a strong interest in biochemistry whose forte was analysing urine not looking after patients. When the Medical Research Council set up a multicentre trial of insulin in late 1922 they enrolled the physician biochemists who produced the early publications and became the experts. The narrow views and innate conservatism of these doctors with the inflexibility of the system in (London) teaching hospitals meant that insulin treatment became a straightjacket for many patients.(ABSTRACT TRUNCATED AT 400 WORDS)