Inhibiteurs du cotransporteur du glucose SGLT rénal pour traiter le diabète de type 2

in Revue Médicale Suisse (2011), 7(306), 1621-1629

Diabète et autocontrôle

in Revue de l'Association Belge du Diabète (2011), 54(2), 18-21

What makes tight glycemic control tight? The impact of variability and nutrition in two clinical studies.

in Journal of Diabetes Science and Technology (2010), 4(2), 284-98

INTRODUCTION: Tight glycemic control (TGC) remains controversial while successful, consistent, and effective protocols remain elusive. This research analyzes data from two TGC trials for root causes of ... [more ▼]

INTRODUCTION: Tight glycemic control (TGC) remains controversial while successful, consistent, and effective protocols remain elusive. This research analyzes data from two TGC trials for root causes of the differences achieved in control and thus potentially in glycemic and other outcomes. The goal is to uncover aspects of successful TGC and delineate the impact of differences in cohorts. METHODS: A retrospective analysis was conducted using records from a 211-patient subset of the GluControl trial taken in Liege, Belgium, and 393 patients from Specialized Relative Insulin Nutrition Titration (SPRINT) in New Zealand. Specialized Relative Insulin Nutrition Titration targeted 4.0-6.0 mmol/liter, similar to the GluControl A (N = 142) target of 4.4-6.1 mmol/liter. The GluControl B (N = 69) target was 7.8-10.0 mmol/liter. Cohorts were matched by Acute Physiology and Chronic Health Evaluation II score and percentage males (p > .35); however, the GluControl cohort was slightly older (p = .011). Overall cohort and per-patient comparisons (median, interquartile range) are shown for (a) glycemic levels achieved, (b) nutrition from carbohydrate (all sources), and (c) insulin dosing for this analysis. Intra- and interpatient variability were examined using clinically validated model-based insulin sensitivity metric and its hour-to-hour variation. RESULTS: Cohort blood glucose were as follows: SPRINT, 5.7 (5.0-6.6) mmol/liter; GluControl A, 6.3 (5.3-7.6) mmol/liter; and GluControl B, 8.2 (6.9-9.4) mmol/liter. Insulin dosing was 3.0 (1.0-3.0), 1.5 (0.5-3), and 0.7 (0.0-1.7) U/h, respectively. Nutrition from carbohydrate (all sources) was 435.5 (259.2-539.1), 311.0 (0.0-933.1), and 622.1 (103.7-1036.8) kcal/day, respectively. Median per-patient results for blood glucose were 5.8 (5.3-6.4), 6.4 (5.9-6.9), and 8.3 (7.6-8.8) mmol/liter. Insulin doses were 3.0 (2.0-3.0), 1.5 (0.8-2.0), and 0.5 (0.0-1.0) U/h. Carbohydrate administration was 383.6 (207.4-497.7), 103.7 (0.0-829.4), and 207.4 (0.0-725.8) kcal/day. Overall, SPRINT gave approximately 2x more insulin with a 3-4x narrower, but generally non-zero, range of nutritional input to achieve equally TGC with less hypoglycemia. Specialized Relative Insulin Nutrition Titration had much less hypoglycemia (<2.2 mmol/liter), with 2% of patients, compared to GluControl A (7.7%) and GluControl B (2.9%), indicating much lower variability, with similar results for glucose levels <3.0 mmol/liter. Specialized Relative Insulin Nutrition Titration also had less hyperglycemia (>8.0 mmol/liter) than groups A and B. GluControl patients (A+B) had a approximately 2x wider range of insulin sensitivity than SPRINT. Hour-to-hour variation was similar. Hence GluControl had greater interpatient variability but similar intrapatient variability. CONCLUSION: Protocols that dose insulin blind to carbohydrate administration can suffer greater outcome glycemic variability, even if average cohort glycemic targets are met. While the cohorts varied significantly in model-assessed insulin resistance, their variability was similar. Such significant intra- and interpatient variability is a further significant cause and marker of glycemic variability in TGC. The results strongly recommended that TGC protocols be explicitly designed to account for significant intra- and interpatient variability in insulin resistance, as well as specifying or having knowledge of carbohydrate administration to minimize variability in glycemic outcomes across diverse cohorts and/or centers. [less ▲]

Management of blood glucose in patients with stroke.

in Diabètes & Métabolism (2010), 36S3

Stroke is a leading cause of death worldwide and the most common cause of long-term disability amongst adults, more particularly in patients with diabetes mellitus and arterial hypertension. Increasing ... [more ▼]

Stroke is a leading cause of death worldwide and the most common cause of long-term disability amongst adults, more particularly in patients with diabetes mellitus and arterial hypertension. Increasing evidence suggests that disordered physiological variables following acute ischaemic stroke, especially hyperglycaemia, adversely affect outcomes. Post-stroke hyperglycaemia is common (up to 50% of patients) and may be rather prolonged, regardless of diabetes status. A substantial body of evidence has demonstrated that hyperglycaemia has a deleterious effect upon clinical and morphological stroke outcomes. Therefore, hyperglycaemia represents an attractive physiological target for acute stroke therapies. However, whether intensive glycaemic manipulation positively influences the fate of ischaemic tissue remains unknown. One major adverse event of management of hyperglycaemia with insulin (either glucose-potassium-insulin infusions or intensive insulin therapy) is the occurrence of hypoglycaemia, which can also induce cerebral damage. Novel insights into post-stroke hyperglycaemia management have been derived from continuous glucose monitoring systems (CGMS). This article aims: 1) to describe the adverse effects of hyperglycaemia following acute ischaemic stroke and the risk associated with iatrogenic hypoglycaemia; 2) to summarise the evidence from current glucose-lowering treatment trials; and 3) to show the usefulness of CGMS in both non-diabetic and diabetic patients with acute stroke. [less ▲]

Addition of incretin therapy to metformin in type 2 diabetes.

in Lancet (2010), 375(9724), 1410-2

Strategies pour eviter l'inertie et la non-observance dans les essais cliniques.

in Revue Médicale de Liège (2010), 65(5-6), 246-9

Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia ... [more ▼]

Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia and to combat patient's non compliance, two pitfalls that may hinder the demonstration of the therapeutic efficacy of the drug. Clinical inertia may be limited by titration, forced or optional, driven by therapeutic targets, or by the use, if necessary, of rescue medications. Compliance may be verified by "pill count". This simple technique allows to exclude non compliant patients when they are detected during the placebo run-in period before randomisation or not to take into account patients with poor compliance in the final evaluation by using a statistical analysis restricted to individuals who have strictly adhered to the study protocol ("per protocol analysis"). Self-monitoring and patient's empowerment in the treatment also contribute to improve drug compliance. Clinicians may take advantage of these approaches derived from clinical trials to improve their daily practice. [less ▲]

ézétimibe (Ezetrol®) chez le patient diabétique

in Revue Médicale de Liège (2009), 64(12), 606-611

L’ézétimibe (Ezetrol®) inhibe sélectivement l’absorption intestinale du cholestérol et des phytostérols apparentés. Son mécanisme d’action résulte en un effet hypocholestérolémiant synergique en ... [more ▼]

L’ézétimibe (Ezetrol®) inhibe sélectivement l’absorption intestinale du cholestérol et des phytostérols apparentés. Son mécanisme d’action résulte en un effet hypocholestérolémiant synergique en combinaison avec une statine, inhibant la synthèse hépatique de cholestérol, ce qui a conduit à la commercialisation d’une combinaison fixe ézétimibe-simvastatine (Inegy®). L’ézétimibe a été plus spécifiquement étudié chez les personnes avec un diabète de type 2 qui sont confrontées à un risque cardio-vasculaire particulièrement élevé. Le but de cet article est de présenter les avancées et les particularités en ce qui concerne l’utilisation de l’ézétimibe dans la population diabétique de type 2. [less ▲]

Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose control.

in Diabetes/Metabolism Research & Reviews (2009)

The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence, but not completely suppressed, the development of anti-insulin antibodies (IAs ... [more ▼]

The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence, but not completely suppressed, the development of anti-insulin antibodies (IAs). Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), continuous peritoneal insulin infusion (CPII) and more recently inhaled insulin administration, appear to significantly increase circulating levels of immunoglobulin G (IgG) anti-IAs in diabetic patients. However, the increase is usually moderate and mostly transient as compared to previous observations with poorly purified animal insulin preparations. The clinical impact of these circulating anti-IAs remains unclear. Nevertheless, several studies have suggested that antibodies could retard insulin action, leading to a worsening of postprandial hyperglycaemia and/or serve as a carrier, thus leading to unexpected hypoglycaemia. CPII may be associated with more marked and sustained increase in IAs levels, possibly related to the use of an unstable insulin and the formation of immunogenic aggregates of insulin. The possible clinical consequences of these high levels of IAs remain to be evaluated because a low-glucose morning syndrome or severe insulin resistance with ketone bodies production have been reported in some cases. In conclusion, even if CSII and CPII may promote the development of circulating IAs, this increase does not lead to immunological insulin resistance, compared to that previously described with animal non-purified insulin preparations, and seems to have only marginal influence on blood glucose control or complications in most diabetic patients. [less ▲]

Estimation of GFR by different creatinine- and cystatin-C-based equations in anorexia nervosa.

in Clinical Nephrology (2009), 71(5), 482-91

Background: Patients with anorexia nervosa (AN) are at high risk of renal failure. Glomerular filtration rate (GFR) is overestimated when estimated by the creatinine-based equations. We have studied the ... [more ▼]

Background: Patients with anorexia nervosa (AN) are at high risk of renal failure. Glomerular filtration rate (GFR) is overestimated when estimated by the creatinine-based equations. We have studied the accuracy and precision of cystatin C-based equations. Method: 27 AN patients were included. GFR was measured with the chromium-51-ethylenediaminetetraacetate (51Cr-EDTA) method. We have compared the accuracy and precision of creatinine-based equations (MDRD and Cockcroft) with those of different new cystatin C-based equations. Results: The creatinine-based equations overestimate measured GFR, especially the MDRD study equation. All the cystatin C-based equations also overestimate measured GFR. The Cockcroft and Gault formula and the cystatin C-based equation published by Rule have the best accuracy and precision, but these last performances remain unsatisfactory. Conclusion: Both creatinine and cystatin C-based equations strongly overestimate measured in patients with AN. [less ▲]

What makes TGC protocols “T” (tight)? An analysis of data from 2 studies

in Proc 9th Annual Diabetes Technology Meeting (DTM2009) (2009)