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Chantal Mathieu

Publications and source records attributed to Chantal Mathieu.

At least 19 recordsLinked to original sources
PubMed2025

The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.

This article summarizes the current understanding of the heterogeneity of type 1 diabetes from a June 2024 international Expert Forum organized by the editors of Diabetes, Diabetes Care, and Diabetologia. The Forum reviewed key factors contributing to the development and progression of type 1 diabetes and outlined specific, high-priority research questions. Knowledge gaps were identified, and, notably, opportunities to harness disease heterogeneity to develop personalized therapies were outlined. Herein, we summarize our discussions and review the heterogeneity of genetic risk and immunologic and metabolic phenotypes that influence and characterize type 1 diabetes progression (presented as a palette of risk factors). We discuss how these age-related factors determine disease aggressiveness (along gradients) and describe how variable immunogenetic pathways aggregate (into networks) to affect β-cell and other pancreatic pathologies to cause clinical disease at different ages and with variable severity (described as disease-related thresholds). Heterogeneity of pathogenesis and clinical severity opens avenues to prevention and intervention, including the potential of disease-modifying immunotherapy and islet cell replacement. We conclude with a call for 1) continued research to identify more factors contributing to the disease, both overall and in specific subgroups; 2) investigations focusing on both individuals who surpass metabolic and immune thresholds and develop diabetes and those who remain disease free with the same level of immunogenetic risk; and 3) efforts to identify where the current type 1 diabetes staging system may fall short and determine how it can be improved to capture and leverage heterogeneity in prevention and intervention strategies.

Humans↗
PubMed2007

Therapy with the hsp60 peptide DiaPep277 in C-peptide positive type 1 diabetes patients.

BACKGROUND: Type 1 diabetes results from a T-cell mediated autoimmune destruction of insulin-producing pancreatic beta-cells. The 60-kDa heat-shock protein (hsp60) is one of the known target self-antigens. An immunogenic peptide from hsp60, p277, arrested beta-cell destruction and maintained insulin production in newly diabetic non-obese diabetic (NOD) mice. A randomized, double-blind, phase Ib/II study of peptide treatment was undertaken in recent onset type 1 diabetes patients with remaining insulin production. METHODS: Forty-eight recent onset type 1 diabetes patients were assigned subcutaneous injections of 0.2, 1.0 or 2.5 mg peptide DiaPep277 (n = 12 per dosage) at entry, and 1, 6 and 12 months, or four placebo injections (n = 12). The primary clinical endpoints were safety and efficacy (glucagon-stimulated C-peptide production at 6 and 12 months); secondary endpoints were HbA1c levels and daily insulin dose adjusted for body weight at 2, 6, 12 and 18 months. RESULTS: C-peptide levels decreased over time in all groups except the 2.5 mg-treated. The decrease in C-peptide production was less in treated patients versus placebo, mostly in the 2.5 mg group. HbA1c increased significantly in the 1.0 mg group and in the 2.5 mg group at 2 and 18 months, respectively. No differences were seen in daily insulin doses. One patient was withdrawn from the study possibly owing to a treatment-related adverse event. CONCLUSIONS: Multiple DiaPep277 peptide administration seems safe and may have a beneficial effect on C-peptide levels over time, but this finding is not supported by lower HbA1c levels or daily insulin requirement. Further investigation on a larger scale is warranted.

C-Peptide↗
PubMed2007

Economic aspects of diabetic foot care in a multidisciplinary setting: a review.

BACKGROUND: To evaluate the economic aspects of diabetic foot care in a multidisciplinary setting. METHOD: A review of the English language literature, published from 1966 to November 2005. RESULTS: The results of available studies on the cost-of-illness of diabetic foot problems are difficult to compare. Nevertheless trends concerning excess of costs, protraction in time of costs, positive correlation to severity of ulcer and/or peripheral vascular disease, contribution of in-hospital stay and length of stay, and the patient's own contribution to total costs, are obvious. Only a few cost-effectiveness and cost-utility studies are available. Most use a Markov based model to predict outcome and show an acceptable result on long-term. CONCLUSIONS: Diabetic foot problems are frequent and are associated with high costs. A multidisciplinary approach to diabetic foot problems has proved to be cost saving with regard to cost of treatment itself. Nevertheless, it remained unclear if these savings could offset the overall costs involved in implementing this kind of approach. The few studies that address this issue specifically all show an acceptable cost-effectiveness, but often the profit will be evident after some years only, because long-term costs are involved. Based on these data, policymakers should foresee sufficient reimbursement for preventive and early curative measures, and not only for 'salvage manoeuvres'.

Cost of Illness↗
PubMed2006

Monocytes from type 2 diabetic patients have a pro-inflammatory profile. 1,25-Dihydroxyvitamin D(3) works as anti-inflammatory.

The exact factors contributing to the pathogenesis of type 2 diabetes remain elusive. Lately, it was suggested that inflammation and activation of the innate immune system could be linked to type 2 diabetes pathogenesis and also to the development of common diabetic complications, mainly atherosclerosis. The aim of this study was to investigate the role of monocytes in this sub-clinical inflammatory state and test 1,25-dihydroxyvitamin D(3), the active form of Vitamin D, as an anti-inflammatory agent. For this purpose, monocytes from type 2 diabetic patients were compared to monocytes from healthy controls and type 1 diabetic patients. The expression profile of inflammatory markers in freshly isolated and immune-stimulated monocytes was measured by quantitative real-time RT-PCR. Type 2 diabetic patients showed significantly higher expression levels of TNF-alpha, IL-6, IL-1, IL-8, COX-2, ICAM-1 and B7-1 compared to controls and type 1 diabetic patients. 1,25-Dihydroxyvitamin D(3) was able to down-regulate the expression of TNF-alpha, IL-6, IL-1, and IL-8, confirming its immunomodulatory properties. From these data we concluded that monocytes from type 2 diabetic patients have a pro-inflammatory profile. In addition, 1,25-dihydroxyvitamin D(3) was able to modulate inflammation in these monocytes.

Adolescent↗
PubMed2006

Correlation between beta cell mass and glycemic control in type 1 diabetic recipients of islet cell graft.

Islet grafts can induce insulin independence in type 1 diabetic patients, but their function is variable with only 10% insulin independence after 5 years. We investigated whether cultured grafts with defined beta cell number help standardize metabolic outcome. Nonuremic C-peptide-negative patients received an intraportal graft with 0.5-5.0 x 10(6) beta cells per kilogram of body weight (kg BW) under antithymocyte globulin and mycophenolate mofetil plus tacrolimus. Metabolic outcome at posttransplant (PT) month 2 was used to decide on a second graft under maintenance mycophenolate mofetil/tacrolimus. Graft function was defined by C-peptide >0.5 ng/ml and reduced insulin needs, metabolic control by reductions in HbA(1c), glycemia coefficient of variation, and hypoglycemia. At PT month 2, graft function was present in 16 of 17 recipients of >2 x 10(6) beta cells per kg BW versus 0 of 5 with lower number. The nine patients with C-peptide >1 ng/ml and glycemia coefficient of variation of <25% did not receive a second graft; five of them were insulin-independent until PT month 12. The 12 others received a second implant; it achieved insulin-independence at PT month 12 when the first and second graft contained >2 x 10(6) beta cells per kg BW. Of the 20 recipients of at least one graft with >2 x 10(6) beta cells per kg BW, 17 maintained graft function and metabolic control up to PT month 12. At PT month 12, beta cell function in insulin-independent patients ranged around 25% of age-matched control values. Thus, 1-year metabolic control can be reproducibly achieved and standardized by cultured islet cell grafts with defined beta cell number.

Adolescent↗
PubMed2006

IL-12 contributes to allergen-induced airway inflammation in experimental asthma.

Lack of sufficient IL-12 production has been suggested to be one of the basic underlying mechanisms in atopy, but a potential role of IL-12 in established allergic airway disease remains unclear. We took advantage of a mouse model of experimental asthma to study the role of IL-12 during the development of bronchial inflammation. Administration of anti-IL-12p35 or anti-IL-12p40 mAb to previously OVA-sensitized BALB/c mice concomitantly with exposure to nebulized OVA, abolished both the development of bronchial hyperresponsiveness to metacholine as well as the eosinophilia in bronchoalveolar lavage fluid and peripheral blood. Anti-IL-12 treatment reduced CD4(+) T cell numbers and IL-4, IL-5, and IL-13 levels in the bronchoalveolar lavage fluid and the mRNA expression of IL-10, eotaxin, RANTES, MCP-1, and VCAM-1 in the lung. Anti-IL-12p35 treatment failed to show these effects in IFN-gamma knockout mice pointing to the essential role of IFN-gamma in IL-12-induced effects. Neutralization of IL-12 during the sensitization process aggravated the subsequent development of allergic airway inflammation. These data together with recent information on the role of dendritic cells in both the sensitization and effector phase of allergic respiratory diseases demonstrate a dual role of IL-12. Whereas IL-12 counteracts Th2 sensitization, it contributes to full-blown allergic airway disease upon airway allergen exposure in the postsensitization phase, with enhanced recruitment of CD4(+) T cells and eosinophils and with up-regulation of Th2 cytokines, chemokines, and VCAM-1. IFN-gamma-producing cells or cells dependent on IFN-gamma activity, play a major role in this unexpected proinflammatory effect of IL-12 in allergic airway disease.

Allergens↗
PubMed2006

The Vitamin D analogue TX 527 blocks NF-kappaB activation in peripheral blood mononuclear cells of patients with Crohn's disease.

Crohn's disease (CD) is an inflammatory disease characterized by the activation of the immune system in the gut. Since tumor necrosis factor (TNF-alpha) plays an important role in the initiation and perpetuation of intestinal inflammation in CD, we investigated whether TX 527 [19-nor-14,20-bisepi-23-yne-1,25(OH)(2)D(3)], a Vitamin D analogue, could affect peripheral blood mononuclear cells (PBMC) proliferation and exert an immunosuppressive effect on TNF-alpha production in CD patients, and whether this immunosuppressive action could be mediated by NF-kappaB down-regulation. TX 527 significantly decreased cell proliferation and TNF-alpha levels. On activation, NF-kappaB, rapidly released from its cytoplasmatic inhibitor (IKB-alpha), transmigrates into the nucleus and binds to DNA response elements in gene promoter regions. The activation of NF-kappaB, stimulated by TNF-alpha, and its nuclear translocation together with the degradation of IKB-alpha were blocked by TX 527. At the same time, NF-kappaB protein levels present in cytoplasmic extracts decreased in the presence of TNF-alpha and increased when PBMC were incubated with TX 527. The results of our studies indicate that TX 527 inhibits TNF-alpha mediated effects on PBMC and the activation of NF-kappaB and that its action is mediated by Vitamin D receptor (VDR), which is activated when the cells are stimulated with TX 527.

Adult↗
PubMed2006

IL-10- and IL-12-independent down-regulation of allergic sensitization by stimulation of CD40 signaling.

Interaction between CD154 (CD40 ligand) on activated T lymphocytes and its receptor CD40 has been shown to be critically involved in the generation of cell-mediated as well as humoral immunity. CD40 triggering activates dendritic cells (DC), enhances their cytokine production, up-regulates the expression of costimulatory molecules, and induces their maturation. It is unknown how stimulation of CD40 during sensitization to an airborne allergen may affect the outcome of allergic airway inflammation. We took advantage of a mouse model of allergic asthma and a stimulatory mAb to CD40 (FGK45) to study the effects of CD40-mediated DC activation on sensitization to OVA and subsequent development of OVA-induced airway inflammation. Agonistic anti-CD40 mAb (FGK45) injected during sensitization with OVA abrogated the development of allergic airway inflammation upon repeated airway challenges with OVA. Inhibition of bronchial eosinophilia corresponded with reduced Th2 cytokine production and was independent of IL-12, as evidenced by a similar down-regulatory effect of anti-CD40 mAb in IL-12 p40-deficient mice. In addition, FGK45 equally down-regulated allergic airway inflammation in IL-10-deficient mice, indicating an IL-10-independent mechanism of action of FGK45. In conclusion, our results show that CD40 signaling during sensitization shifts the immune response away from Th2 cytokine production and suppresses allergic airway inflammation in an IL-12- and IL-10-independent way, presumably resulting from enhanced DC activation during sensitization.

Animals↗
PubMed2006

Immune regulation of 25-hydroxyvitamin D-1alpha-hydroxylase in human monocytic THP1 cells: mechanisms of interferon-gamma-mediated induction.

CONTEXT: 25-Hydroxyvitamin D can be activated to 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] by the rate-limiting enzyme 1alpha-hydroxylase in cells of the immune system under control of immune stimuli, such as interferon-gamma (IFNgamma). In pathological situations, such as sarcoidosis, this can lead to systemic excess of 1,25(OH)(2)D(3) and hypercalcemia. OBJECTIVE: The aim of this study was to elucidate the intracellular pathways used by the immune system to tightly regulate 1,25(OH)(2)D(3) production in monocytes and macrophages. DESIGN: Human monocytic THP1-cells were differentiated and activated by IFNgamma and a secondary stimulus, such as lipopolysaccharide or phorbol myristate acetate. 1alpha-Hydroxylase mRNA levels were quantified by real-time RT-PCR. The involvement of different signaling pathways in the regulation of this enzyme was investigated using specific pharmacological inhibitors, whereas phosphorylation of signal transducer and activator of transcription 1alpha and CCAAT/enhancer binding protein beta was investigated by Western blotting. RESULTS: In undifferentiated monocytic THP1 cells, IFNgamma needs to be combined with a second stimulus, such as lipopolysaccharide, to induce 1alpha-hydroxylase. In contrast, in phorbol myristate acetate-differentiated THP1 macrophages, IFNgamma alone induces 1alpha-hydroxylase and to much higher levels. Many different signaling pathways need to be activated concurrently to allow immune-mediated 1alpha-hydroxylase up-regulation. We show involvement of the Janus kinase-signal transducer and activator of transcription, MAPK, and nuclear factor-kappaB pathways, with a crucial role for the transcription factor CCAAT/enhancer binding protein beta. Furthermore, histone remodeling involving histone deacetylases and histone acetylase p300 is required. CONCLUSION: The present findings indicate that IFNgamma-mediated 1,25(OH)(2)D(3) production, as observed in granulomatous diseases such as sarcoidosis, will take place only under conditions where the necessary other signaling pathways are also activated.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2006

CCL27 is a critical factor for the development of atopic dermatitis in the keratin-14 IL-4 transgenic mouse model.

The keratin-14 IL-4 transgenic (Tg) mouse model of atopic dermatitis (AD) is characterized by skin infiltration of T cells, early up-regulation of T(h)2 cytokines and late surge of T(h)1 cytokines. In the present study, we investigated the role of CCL27, a T cell skin-homing chemokine known to be elevated in sera of human AD patients, in disease development in our animal model of AD. The results showed that the mRNA and protein levels of CCL27 in the skin and serum were significantly increased in IL-4 Tg mice. The percentage of T cells expressing CCR10 in skin draining lymph nodes of IL-4 Tg mice was increased, consistent with the findings of >80% of skin-infiltrating T cells in Tg mice expressing CCR10. Chemotaxis transmigration assay demonstrated that CCL27 promotes a greater degree of migration of T cells in diseased Tg mice. Subcutaneous injection of neutralizing anti-CCL27 to IL-4 Tg mice with early skin lesions resulted in reduced clinical progression of inflammation, accompanied with decreased T cell and mast cell infiltration in the skin, and down-regulation of inflammatory cytokines. In conclusion, CCL27 and CCR10 interaction is important for the development of skin inflammation in our AD model.

Animals↗
PubMed2006

Hepatocellular neoplasms induced by low-number pancreatic islet transplants in autoimmune diabetic BB/Pfd rats.

It has been shown that combined high local hyperinsulinism and hyperglycemia after low-number islet transplantation into the livers of streptozotocin-diabetic rats lead to the development of hepatocellular neoplasms but a substantial cocarcinogenic effect of genotoxic streptozotocin could not be ruled out completely. Thus, we herein investigated this model in BB/Pfd rats (n = 805; nine experimental groups), which develop spontaneous autoimmune diabetes similar to human type 1 diabetes. After low-number islet transplantation (n = 450), the liver acini downstream of the islets show insulin-induced alterations: massive glycogen and/or fat accumulation, translocation of the insulin receptor, decrease in glucose-6-phosphatase activity, increase in expression of insulin-like growth factor (IGF)-I, IGF-II/mannose-6-phosphate receptor, insulin receptor substrate-1, Raf-1, and Mek-1, corresponding to clear cell preneoplastic foci of altered hepatocytes known from chemical hepatocarcinogenesis and identical to that in streptozotocin-diabetic Lewis rats. After 6 months, many altered liver acini progressed to other types of preneoplasias often accompanied by an overexpression of the glutathione-S transferase (placental form), IGF-I receptor, and transforming growth factor (TGF)-alpha. After 12 to 15 and 15 to 18 months, 52% and 100% of the animals showed one or multiple hepatocellular adenomas or hepatocellular carcinomas (HCCs), respectively. Conclusively, this study identifies combined hyperinsulinism and hyperglycemia as a carcinogenic mechanism for the development of HCCs in diabetic rats. Hepatocarcinogenesis is independent from additional genotoxic compounds (i.e., streptozotocin), but is primarily triggered by increased intracellular insulin signaling via pathways associated with cell growth and proliferation, such as the Ras-Raf-mitogen-activated protein kinase pathway and the IGF system, and secondarily involves other growth factors, such as TGF-alpha.

Animals↗
PubMed2006

Vitamin D resistance.

Vitamin D is a secosteroid of nutritional origin but can also be generated in the skin by ultraviolet light. After two hydroxylations 1,25-(OH)2 vitamin D avidly binds and activates the vitamin D receptor (VDR), a nuclear transcription factor, hereby regulating a large number of genes. The generation of VDR deficient mice has expanded the knowledge on vitamin D from a calcium-regulating hormone to a humoral factor with extensive actions. The effects of the vitamin D system on calcium and bone homeostasis are largely mediated by promoting active intestinal calcium transport via the induction of the epithelial calcium channel TRPV6. Although VDR is redundant in bone, it may regulate the differentiation and function of several bone cells. In skin, VDR expression in keratinocytes is essential in a ligand-independent manner for the maintenance of the normal hair cycle. Therefore, VDR but not vitamin D deficiency results in alopecia. Moreover, 1,25-(OH)2 vitamin D impairs the proliferation not only of keratinocytes but also of many cell types by regulating the expression of cell cycle genes, leading to a G1 cell cycle arrest. In addition, VDR inactivation in mice results in high renin hypertension, cardiac hypertrophy and thrombogenesis. Finally, a dual effect of vitamin D was observed in the immune system where it stimulates the innate immune system while tapering down excessive activation of the acquired immune system. Taken together, the vitamin D endocrine system not only regulates calcium homeostasis but affects several systems mainly by altering gene expression but also by ligand-independent actions.

Animals↗
PubMed2006

Increased peritoneal and endometrial gene expression of biologically relevant cytokines and growth factors during the menstrual phase in women with endometriosis.

OBJECTIVE: To examine differential messenger RNA (mRNA) expression of relevant cytokines, metalloproteases, growth and adhesion factors in endometrium and peritoneum from women with endometriosis when compared with women without the disease during menstrual and luteal phases of the cycle. DESIGN: Patients with endometriosis were compared with control patients. SETTING: University hospital. PATIENT(S): A total of 35 patients (20 patients during the luteal phase and 15 patients during the menstrual phase) were selected for this study on the basis of cycle phase and presence or absence of endometriosis. INTERVENTION(S): In this study, endometriosis was laparoscopically and histologically confirmed in 24 women with endometriosis of revised American Society for Reproductive Medicine (ASRM) stage I-II (n = 12) and revised ASRM stage III-IV (n = 12), and the presence of a normal pelvis was documented by laparoscopy in 11 control patients. The macroscopically normal peritoneum tissues were collected from lateral wall left or right, near the colon ascendens or descendens. MAIN OUTCOME MEASURE(S): The expression levels were determined as ratios between the target molecules and beta-actin as housekeeping gene. RESULT(S): In women with endometriosis, peritoneal mRNA levels of matrix metalloproteinase (MMP)-3, transforming growth factor-beta, interleukin (IL)-6, and intercellular adhesion molecule-1 and endometrial mRNA levels of MMP-3, tumor necrosis factor (TNF)-alpha, and IL-8 were significantly higher during the menstrual phase when compared with luteal phase. During the menstrual phase of the cycle, both endometrial expression of TNF-alpha, IL-8, and MMP-3 mRNA levels and peritoneal expression of transforming growth factor-beta, IL-6, and intercellular adhesion molecule-1 mRNA levels were significantly higher in women with endometriosis when compared with controls. Immunohistochemical staining confirmed the presence of TNF-alpha in peritoneum and endometrium in both women with endometriosis and controls. CONCLUSION(S): Increased endometrial and peritoneal cytokine mRNA expression during menstruation may contribute to a pelvic inflammatory microenvironment favoring the development of endometriosis.

Biomarkers↗
PubMed2006

Vitamin D and cancer.

1,25-dihydroxy Vitamin D [1,25-(OH)(2)D] exerts its effects via the vitamin D receptor (VDR) that belongs to the steroid/thyroid hormone receptor superfamily leading to gene regulation which results in various biological responses. Within the last two decades, the receptor has been shown to be present not only in classical target tissues such as bone, kidney and intestine but also in many other non-classical tissues. Besides the almost universal presence of VDRs, some cell types (e.g. keratinocytes, monocytes, bone, placenta) are capable of metabolizing 25-hydroxyvitamin D to 1,25(OH)(2)D by the enzyme 1alpha-hydroxylase (CYP27B1). The combined presence of 25(OH)D-1alpha-hydroxylase as well as the specific receptor in several tissues introduced the idea of a paracrine role for 1,25(OH)(2)D. Moreover, it has been demonstrated that 1,25(OH)(2)D can induce differentiation and inhibit proliferation of a wide variety of cell types. The molecular mechanisms behind this antiproliferative action is thoroughly explored but the whole picture is still difficult to understand. Important cell cycle regulators are involved such as cyclins, cyclin dependent kinases and their corresponding inhibitors as well as E2F transcription factors and accompanying pocket proteins. However the precise hierarchical structure of this wide diversity of actions of 1,25(OH)(2)D on genes influencing cell cycle progression is not firmly established nor do we understand which pathways are essential and which redundant. The antiproliferative action makes 1,25-(OH)(2)D and its analogs a possible therapeutic tool to treat hyperproliferative disorders, among which different types of cancer. This review focuses on the effects of 1,25(OH)(2)D and its analogs on cell proliferation, the results in in vivo experiments in Vitamin D deficient or resistant animals to cancer and the current epidemiological and intervention studies linking Vitamin D status or treatment and human cancer.

Animals↗
PubMed2006

Development and validation of the Economic Assessment of Glycemic Control and Long-Term Effects of diabetes (EAGLE) model.

BACKGROUND: The Economic Assessment of Glycemic control and Long-term Effects of diabetes (EAGLE) model was developed to provide a flexible and comprehensive tool for the simulation of the long-term effects of diabetes treatment and related costs in type 1 and type 2 diabetes. METHODS: EAGLE simulations are based on risk equations, which were developed using published data from several large studies including the Diabetes Control and Complications Trial, the United Kingdom Prospective Diabetes Study, and the Wisconsin Epidemiological Study of Diabetic Retinopathy. Risk equations for the probability of complications (including hypoglycemia, retinopathy, macular edema, end-stage renal disease, neuropathy, diabetic foot syndrome, myocardial infarction, and stroke) were based on regression analyses, using linear, exponential, and quadratic regression formulae. Subsequent cost calculations are made from the simulated event rates. Internal validation of the EAGLE model was completed by comparing simulated event rates with the published event rates used as the basis for the model. RESULTS: EAGLE provides microsimulations of virtual patient cohorts for type 1 and type 2 diabetes over n years in 1-year cycles. Complications include microvascular and macrovascular events and death, which are calculated over time as cumulative incidences. Glycosylated hemoglobin levels over time are simulated in relation to treatment regimen. Internal validation demonstrated that each mean event rate simulated by EAGLE overlapped with the published mean event (within a range of +/-10%). CONCLUSIONS: The EAGLE model is an evidence-based, internally valid tool for the assessment of the long-term effects of diabetes treatment and related costs.

Diabetes Complications↗
PubMed2006

Inhaled human insulin ((insulin human [rDNA origin]) Inhalation Powder) in diabetes mellitus.

Inhaled human insulin ((insulin human [rDNA origin]) Inhalation Powder) is a prandial insulin approved in the EU and the US for the treatment of adults with diabetes. Its glycaemic control is comparable to subcutaneous insulin in Type 1 and 2 diabetes, and has superior efficacy versus oral antidiabetic agents in Type 2 diabetes. Hypoglycaemia and mild-to-moderate cough are the main side effects. The treatment group differences in pulmonary function occur early, and are small, nonprogressive for up to 2 years and reversible following discontinuation. Patient-reported outcomes data displays higher diabetes treatment satisfaction, improvements in some quality-of-life scores, and treatment preference with inhaled human insulin versus traditional means. Availability of inhaled insulin may increase insulin acceptance and thus improve glycaemic control in patients with diabetes.

Administration, Inhalation↗
PubMed2006

Quantification of chemokines by real-time reverse transcriptase PCR: applications in type 1 diabetes.

Type 1 diabetes is a T-cell mediated autoimmune disease, characterized by the destruction of insulin-producing pancreatic beta-cells. This review will discuss the role of chemokines in the recruitment of immune cells leading to the pathology of this disease. There will be a focus on the quantification of chemokines and chemokine receptors by the recently developed real-time reverse transcriptase PCR technique. Today, this technique is in widespread use for analysis of chemokines in cells, tissues and tissue biopsies. The minute amount of tissue needed for analysis, as well as the very high sensitivity of this method, make it the method of choice for analysis of chemokines, which are often expressed at very low levels in target tissues. However, validation and optimization of the technique is of crucial importance for obtaining reliable results.

Animals↗