Metformin revisited: A critical review of the benefit-risk balance in at-risk patients with type 2 diabetes.
SCHEEN, André ; Paquot, Nicolas
in Diabètes & Métabolism (2013)
Metformin is unanimously considered a first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of numerous ... [more ▼]
Metformin is unanimously considered a first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of numerous contraindications that could lead to an increased risk of lactic acidosis. Various observational data from real-life have shown that many diabetic patients considered to be at risk still receive metformin and often without appropriate dose adjustment, yet apparently with no harm done and particularly no increased risk of lactic acidosis. More interestingly, recent data have suggested that type 2 diabetes patients considered at risk because of the presence of traditional contraindications may still derive benefit from metformin therapy with reductions in morbidity and mortality compared with other glucose-lowering agents, especially sulphonylureas. The present review analyzes the benefit-risk balance of metformin therapy in special populations, namely, patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, congestive heart failure, renal impairment or chronic kidney disease, hepatic dysfunction and chronic respiratory insufficiency, all conditions that could in theory increase the risk of lactic acidosis. Special attention is also paid to elderly patients with type 2 diabetes, a population that is growing rapidly, as older patients can accumulate several comorbidities classically considered contraindications to the use of metformin. A review of the recent scientific literature suggests that reassessment of the contraindications of metformin is now urgently needed to prevent physicians from prescribing the most popular glucose-lowering therapy in everyday clinical practice outside of the official recommendations. [less ▲]Detailed reference viewed: 11 (0 ULg)
Diabète et Ramadan : représentations et pratiques de santé des patients et des soignants et intérêts de l'éducation thérapeutique du patient
; ; et al
in Diabètes & Métabolism (2012), 38(2), 47-48Detailed reference viewed: 19 (2 ULg)
Campagnes de sensibilisation au dépistage du diabète de type 2 dans les pharmacies. Comparaison de deux approches : glycémie capillaire et grille Findrisc
; ; et al
in Diabètes & Métabolism (2012), 38(2), 7Detailed reference viewed: 17 (2 ULg)
Etat des lieux des pratiques en éducation thérapeutique dans les institutions hospitalières en provinces de Liège et de Luxembourg
Degrange, Sophie ; ; Legrand, Catherine et al
in Diabètes & Métabolism (2012), 38(2), 51Detailed reference viewed: 35 (15 ULg)
Etat des lieux des pratiques en éducation thérapeutique des médecins généralistes dans la Grande Région
Pétré, Benoît ; Degrange, Sophie ; Legrand, Catherine et al
in Diabètes & Métabolism (2012), 38(2), 51Detailed reference viewed: 24 (18 ULg)
Vitamin D and type 2 diabetes mellitus: Where do we stand?
CAVALIER, Etienne ; DELANAYE, Pierre ; et al
in Diabètes & Métabolism (2011), 37(4), 265-72
AIMS: In-vitro and observational studies have established a link between vitamin D deficiency and different type 2 diabetes outcomes (insulin resistance, insulin secretion, glucose intolerance). Although ... [more ▼]
AIMS: In-vitro and observational studies have established a link between vitamin D deficiency and different type 2 diabetes outcomes (insulin resistance, insulin secretion, glucose intolerance). Although the number of randomized controlled trials vs placebo is small, vitamin D (VTD) has been shown to prevent increases in glucose concentration and insulin resistance, enhance insulin sensitivity and reduce systolic blood pressure in type 2 diabetic patients. METHODS: In this review, we have focused on the potential mechanisms that might explain the association between VTD and type 2 diabetes mellitus (T2DM). We have also evaluated the different epidemiological and observational studies on the topic, as well as the various interventional studies. RESULTS: Although the in vitro studies appear to be promising in explaining the link between VTD metabolism and T2DM, the results of in vivo studies are conflicting. This could be related to differences in their methodological approaches. CONCLUSION: Although more studies are needed to confirm the role of VTD in the treatment of T2DM, there is nevertheless enough evidence at this time to suggest a need to maintain 25-OH vitamin D levels in T2DM patients around 30ng/mL over the course of a year. [less ▲]Detailed reference viewed: 53 (7 ULg)
Squatting, a posture test for studying cardiovascular autonomic neuropathy in diabetes.
PHILIPS, Jean-Christophe ; MARCHAND, Monique ; SCHEEN, André
in Diabètes & Métabolism (2011), 37(6), 489-496
Cardiovascular autonomic neuropathy (CAN) is a frequent complication of diabetes mellitus, which is associated with increased morbidity and mortality. It involves both the parasympathetic and sympathetic ... [more ▼]
Cardiovascular autonomic neuropathy (CAN) is a frequent complication of diabetes mellitus, which is associated with increased morbidity and mortality. It involves both the parasympathetic and sympathetic nervous systems, and may be diagnosed by classical dynamic tests with measurements of heart rate (HR) and/or arterial blood pressure (BP). An original squat test (1-min standing, 1-min squatting, 1-min standing) was used with continuous monitoring of HR and BP, using a Finapres((R)) device. This active test imposes greater postural stress than the passive head-up tilt test, and provokes large changes in BP and HR that can be analyzed to derive indices of CAN. In healthy subjects, squatting is associated with BP increases and HR decreases (abolished by atropine: SqTv index), whereas the squat-stand transition is accompanied by a deep but transient drop in BP associated with sympathetic-driven tachycardia (abolished by propranolol: SqTs index). In diabetic patients with CAN, BP increases are accentuated during squatting whereas reflex bradycardia is reduced. When standing from squatting position, the fall in BP tends to be more pronounced and orthostatic hypotension more prolonged, while reflex tachycardia is markedly dampened. The baroreflex gain, similar to that calculated during pharmacological testing with vasodilator/vasopressor agents, can be derived by plotting pulse intervals (R-R) against systolic BP levels during the biphasic response following the squat-stand transition. The slope, which represents baroreflex sensitivity, is significantly reduced in patients with CAN. This discriminatory index allows study of the natural history of CAN in a large cohort of diabetic patients. [less ▲]Detailed reference viewed: 10 (0 ULg)
Haemodynamic changes during a squat test, pulsatile stress and indices of cardiovascular autonomic neuropathy in patients with long-duration type 1 diabetes.
PHILIPS, Jean-Christophe ; MARCHAND, Monique ; SCHEEN, André
in Diabètes & Métabolism (2011)
AIM: Cardiovascular autonomic neuropathy (CAN) and pulsatile stress are considered to be independent cardiovascular risk factors. This study compared haemodynamic changes during an active orthostatic test ... [more ▼]
AIM: Cardiovascular autonomic neuropathy (CAN) and pulsatile stress are considered to be independent cardiovascular risk factors. This study compared haemodynamic changes during an active orthostatic test in adult patients with type 1 diabetes (T1DM), using low versus high RR E/I ratios as a marker of CAN. METHODS: A total of 20 T1DM patients with low RR E/I ratios were compared with 20 T1DM patients with normal RR E/I ratios, matched for gender (1/1 ratio), age (mean: 46years) and diabetes duration (22-26years); 40 matched healthy subjects served as controls. All subjects were evaluated by continuous monitoring of arterial blood pressure (Finapres((R))) and heart rate using a standardized posture test (1-min standing, 1-min squatting, 1-min standing), thus allowing calculation of baroreflex gain. RESULTS: Compared with controls, T1DM patients showed lower RR E/I ratios, reduced baroreflex gains, higher pulsatile stress (pulse pressurexheart rate), greater squatting-induced pulse pressure rises, orthostatic hypotension and reduced reflex tachycardia. Compared with T1DM patients with preserved RR E/I ratios, T1DM patients with low RR E/I ratios showed reduced post-standing reflex tachycardia and baroreflex gain, and delayed blood pressure recovery, but no markers of increased pulsatile stress. Interestingly, decreased baroreflex gain was significantly associated with both pulsatile stress and microalbuminuria. CONCLUSION: The use of RR E/I ratios to separate T1DM patients allows the detection of other CAN markers during an orthostatic posture test, but with no significant differences in pulsatile stress or microalbuminuria. In this context, squatting-derived baroreflex gain appears to be more informative. [less ▲]Detailed reference viewed: 19 (1 ULg)
DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials.
in Diabètes & Métabolism (2011)
Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that ... [more ▼]
Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials. [less ▲]Detailed reference viewed: 15 (0 ULg)
Education on sensor-augmented pump use improves glucose control in type-1 diabetic patients.
Thielen, Vinciane ; ; et al
in Diabètes & Métabolism (2010)Detailed reference viewed: 34 (1 ULg)
Central nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia.
in Diabètes & Métabolism (2010), 36S3
Recent evidence suggests that the brain has a key role in the control of energy metabolism, body fat content and glucose metabolism. Neuronal systems, which regulate energy intake, energy expenditure, and ... [more ▼]
Recent evidence suggests that the brain has a key role in the control of energy metabolism, body fat content and glucose metabolism. Neuronal systems, which regulate energy intake, energy expenditure, and endogenous glucose production, sense and respond to input from hormonal and nutrient-related signals that convey information regarding both body energy stores and current energy availability. In response to this input, adaptive changes occur that promote energy homeostasis and the maintenance of blood glucose levels in the normal range. Defects in this control system are implicated in the link between obesity and type 2 diabetes mellitus. The central nervous system may be considered the conductor of an orchestra involving many peripheral organs involved in these homeostatic processes. However, the brain is mainly a glucose-dependent organ, which can be damaged by both hypoglycaemia and hyperglycaemia. Hypoglycaemia unawareness is a major problem in clinical practice and is associated with an increased risk of coma. Stroke is another acute complication associated with diabetes mellitus, especially in elderly people, and the control of glucose level in this emergency situation remains challenging. The prognosis of stroke is worse in diabetic patients and both its prevention and management in at-risk patients should be improved. Finally, chronic diabetic encephalopathies, which may lead to cognitive dysfunction and even dementia, are also recognized. They may result from recurrent hypoglycaemia and/or from chronic hyperglycaemia leading to cerebral vascular damage. Functional imaging is of interest for exploring diabetes-associated cerebral abnormalities. Thus, the intimate relationship between the brain and diabetes is increasingly acknowledged in both research and clinical practice. [less ▲]Detailed reference viewed: 12 (0 ULg)
Attempt to improve glucose control in type 2 diabetic patients by education about real-time glucose monitoring.
Thielen, Vinciane ; Scheen, André ; et al
in Diabètes & Métabolism (2010), 36(3), 240-3
The effectiveness of a specific educational programme involving the use of a real-time glucose-sensor system (Guardian RT) to improve glucose control was investigated in patients with poorly controlled ... [more ▼]
The effectiveness of a specific educational programme involving the use of a real-time glucose-sensor system (Guardian RT) to improve glucose control was investigated in patients with poorly controlled type 2 diabetes despite insulin therapy. Ten patients participated in a randomized crossover study comparing two 3-month periods, during which glucose levels were monitored by either self-monitoring of blood glucose (SMBG) alone or by Guardian RT (restricted to 1 week per month) in addition to SMBG. Only four of the enrolled patients completed both periods, while dropouts were mainly due to technical difficulties in using the device. All six patients who completed the first 3-month period showed a reduction in glycated haemoglobin (HbA(1c)) level whatever the mode of glucose monitoring (study effect). A further reduction in HbA(1c) level was observed in two of the three patients using the Guardian RT during the second period. Less frequent symptomatic hypoglycaemic episodes were noted during the 3-month period with the device in the four patients who completed both study periods. These limited, but promising, results of this pilot study appear to justify the initiation of a larger study to assess the use of a real-time glucose sensor in carefully selected patients with type 2 diabetes. [less ▲]Detailed reference viewed: 14 (0 ULg)
Management of blood glucose in patients with stroke.
Radermecker, Régis ; Scheen, André
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 ▲]Detailed reference viewed: 30 (5 ULg)
Continuous glucose monitoring reduces both hypoglycaemia and HbA1c in hypoglycaemia-prone type 1 diabetic patients treated with a portable pump.
Radermecker, Régis ; Saint-Remy, Annie ; Scheen, André et al
in Diabètes & Métabolism (2010), 36(5), 409-13
AIM: This study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and ... [more ▼]
AIM: This study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and presenting with frequent hypoglycaemic episodes. METHODS: Thirteen patients with type 1 diabetes (diabetes duration: 25+/-15 years; CSII duration: 5.5+/-7.0 years), with more than six recorded capillary blood glucose (CBG) values <60 mg/dL, according to their metres for the past 14 days, were offered the permanent use of a CGM device (Guardian RT((R)), Medtronic) plus ongoing self-monitoring of blood glucose (SMBG) for 12 weeks, followed by a 12-week crossover period of SMBG only, or vice versa. Glucose control, determined by recorded 14-day CBG values <60 mg/dL and HbA(1c) levels, and quality of life according to the Diabetes Quality of Life (DQOL) questionnaire, were assessed at baseline, and after 12- and 24-week follow-ups. RESULTS: Four patients withdrew from the study during the first period (of whom three were using CGM). In the nine study completers, the number of low CBG values decreased significantly from 13.9+/-9.2 to 7.6+/-6.8 (P=0.011) when patients used CGM, in either the initial or final trial period, while a decrease in HbA(1c) from 8.3+/-0.7 to 7.7+/-0.6% (P=0.049) was also observed, in contrast to the absence of any significant differences during the SMBG-only period. DQOL scores were also essentially unaffected. CONCLUSION: This pilot observational study supports the hypothesis that CGM use can significantly improve overall glucose control while reducing hypoglycaemic episodes in hypoglycaemia-prone type 1 diabetic patients treated by CSII. [less ▲]Detailed reference viewed: 33 (3 ULg)
Bariatric surgery in patients with Type 2 diabetes: benefits, risks, indications and perspectives.
Scheen, André ; De Flines, Jenny ; De Roover, Arnaud et al
in Diabètes & Métabolism (2009), 35(6 Pt 2), 537-43
Obesity plays a key role in the pathophysiology of type 2 diabetes (T2DM), and weight loss is a major objective, although difficult to achieve with medical treatments. Bariatric surgery has proven its ... [more ▼]
Obesity plays a key role in the pathophysiology of type 2 diabetes (T2DM), and weight loss is a major objective, although difficult to achieve with medical treatments. Bariatric surgery has proven its efficacy in obtaining marked and sustained weight loss, and is also associated with a significant improvement in glucose control and even diabetes remission. Roux-en-Y gastric bypass appears to be more effective in diabetic patients than the restrictive gastroplasty procedure. This may be explained not only by greater weight reduction, but also by specific hormonal changes. Indeed, increased levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) may lead to improved beta-cell function and insulin secretion as well as reduced insulin resistance associated with weight loss. The presence of T2DM in obese individuals is a further argument to propose bariatric surgery, and even more so when diabetes is difficult to manage by medical means and other weight-related complications may occur. Bariatric surgery is associated with a better cardiovascular prognosis and reduced mortality, even though acute and long-term complications are present. The observation that surgical rerouting of nutrients triggers changes in the release of incretin hormones that, in turn, ameliorate the diabetic state in the absence of weight loss has led to the recent development of innovative surgical procedures. Thus, bariatric surgery may be said to be progressing towards so-called 'metabolic surgery', which merits further evaluation in patients with T2DM within a multidisciplinary approach that involves both surgeons and endocrinologists. [less ▲]Detailed reference viewed: 32 (1 ULg)
Relation entre la progression des marqueurs de la neuropathie autonome cardiaque et de la rigidité artérielle en fonction de la durée du diabète de type 1.
PHILIPS, Jean-Christophe ; MARCHAND, Monique ; SCHEEN, André
in Diabètes & Métabolism (2008), 34(suppl), 1109Detailed reference viewed: 6 (2 ULg)
Abnormal glucose metabolism in patients treated with antipsychotics.
Scheen, André ;
in Diabètes & Métabolism (2007), 33(3), 169-75
Second-generation (atypical) antipsychotic medications are of great benefit to a wide variety of people with psychiatric disorders, especially patients with schizophrenia. However, one constellation of ... [more ▼]
Second-generation (atypical) antipsychotic medications are of great benefit to a wide variety of people with psychiatric disorders, especially patients with schizophrenia. However, one constellation of adverse effects is an increased risk of obesity, diabetes, and metabolic syndrome. Increasing numbers of reports concerning impaired glucose tolerance, diabetes, and ketoacidosis have raised concerns about a possible association between abnormal glucose metabolism and treatment with atypical antipsychotics, although the question is still debated because of the presence of many confounding factors. A close relationship between drug-induced weight gain and risk of diabetes has been reported, emphasizing the role of insulin resistance. However, some cases of diabetes developed independently of weight gain, rather rapidly and possibly progressing to ketoacidosis, thus arguing for a severe impairment of insulin secretion. Another debated question is whether diabetes risk is a class action or a differential action. Although not fully scientifically proven yet, available evidence suggests that clozapine and olanzapine have a higher propensity to induce diabetes and metabolic syndrome compared with other atypical antipsychotic drugs, risperidone and quetiapine. Despite more limited available data, amisulpride, aripiprazole and ziprazidone showed less likelihood of precipitating diabetes. Interestingly, reversibility of drug-related diabetes has been reported with aripiprazole. The choice of atypical antipsychotic medication for a specific patient depends on many factors, but the likelihood of developing diabetes should become an important consideration. When prescribing an atypical antipsychotic, a commitment to careful baseline screening and follow-up monitoring is essential in order to mitigate the risk of developing diabetes and associated complications. [less ▲]Detailed reference viewed: 21 (2 ULg)
Staphylococcus aureus endocarditis in a diabetic woman treated by continuous subcutaneous insulin infusion.
Legrand, Delphine ; Radermecker, Régis ; Stassen, Marie-José et al
in Diabètes & Métabolism (2007), 33(1), 79-81Detailed reference viewed: 16 (1 ULg)
Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion?
in Diabètes & Métabolism (2005), 31 Spec No 2
Elderly people are more glucose intolerant and insulin resistant than young individuals, and many of them will develop type 2 diabetes. It remains, however, controversial whether this decrease in function ... [more ▼]
Elderly people are more glucose intolerant and insulin resistant than young individuals, and many of them will develop type 2 diabetes. It remains, however, controversial whether this decrease in function is due to an inevitable consequence of "biological aging" or due to environmental or lifestyle variables. Indeed, increased adiposity/altered fat distribution, decreased fat free mass/abnormal muscle composition, poor dietary habits and physical inactivity all contribute to reduce insulin sensitivity. Insulin resistance in elderly people appears to predominate in skeletal muscle, whereas hepatic glucose output seems to be almost unaffected. Several abnormalities in islet beta-cell and insulin secretion were also pointed out in elderly people such as increased amyloid deposition and decreased amylin secretion, impaired insulin secretion pulsatility, decreased insulin sensitivity of pancreatic beta-cells to insulinotropic gut hormones and diminished insulin response to non-glucose stimuli such as arginine. Controversial results were reported concerning the effects of aging on absolute insulin secretion in response to oral or intravenous glucose. However, insulin secretion appears to decrease with age, with significantly diminished beta-cell sensitivity and acute insulin response to glucose, provided it is analyzed relative to concomitant decreased insulin sensitivity. Thus, there is an interplay between decreased insulin secretion and increased insulin resistance that largely explains the abnormal glucose metabolism seen in elderly. Weight loss, especially reduction of abdominal adiposity, and increased physical activity may contribute to improve insulin sensitivity and glucose tolerance, and prevent the development of type 2 diabetes in elderly people. [less ▲]Detailed reference viewed: 33 (0 ULg)
Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms.
in Diabètes & Métabolism (2004), 30(6), 498-505
The inhibition of the renin-angiotensin system (RAS) with either angiotensin converting enzyme inhibitors (ACEIs) or AT1 angiotensin receptor blockers (ARBs) consistently and significantly reduces the ... [more ▼]
The inhibition of the renin-angiotensin system (RAS) with either angiotensin converting enzyme inhibitors (ACEIs) or AT1 angiotensin receptor blockers (ARBs) consistently and significantly reduces the incidence of type 2 diabetes in patients with hypertension or congestive heart failure. The mechanisms underlying this protective effect appear to be complex and may involve an improvement of both insulin sensitivity and insulin secretion. These two effects may result, at least in part, from the well known effects of these pharmacological agents on the vascular system on the one hand, on the ionic balance on the other hand. Indeed, the vasodilation induced by ACEIs or ARBs could improve the blood circulation in skeletal muscles, thus favouring peripheral insulin action, but also in the pancreas, thus promoting insulin secretion. Preserving cellular potassium and magnesium pools by blocking the aldosterone effects could also improve both cellular insulin action and insulin secretion. However, besides these classical effects, new mechanisms have been recently suggested. A direct effect of the inhibition of angiotensin and/or of the enhancement of bradykinin on various steps of the insulin cascade signalling has been described as well an increase in GLUT4 glucose transporters after RAS inhibition. Furthermore, it has been demonstrated that angiotensin II inhibits adipogenic differentiation of human adipocytes via A1 receptors and, therefore, it has been hypothesised that RAS blockade may prevent diabetes by promoting the recruitment and differentiation of adipocytes. Finally, some lipophilic ARBs appear to induce PPAR-gamma activity in the adipose tissue. Hence, the protection against type 2 diabetes observed after RAS inhibition may be partially linked to a thiazolidinedione-like effect. In conclusion, numerous physiological and biochemical mechanisms could explain the protective effect of RAS inhibition against the development of type 2 diabetes in individuals with arterial hypertension or congestive heart failure. What might be the main mechanism in the overall protection effect of ACEIs or ARBs remains an open question. [less ▲]Detailed reference viewed: 22 (3 ULg)