References of "Diabetes/Metabolism Research & Reviews"
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See detailEfficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus.
Scheen, André ULg; Charpentier, Guillaume; Ostgren, Carl Johan et al

in Diabetes/Metabolism Research & Reviews (2010), 26(7), 540-9

BACKGROUND: Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin ... [more ▼]

BACKGROUND: Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione). This 18-week, phase 3b, multicentre, double-blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase-4 inhibitors, saxagliptin and sitagliptin, in patients whose glycaemia was inadequately controlled with metformin. METHODS: Adult type 2 diabetes mellitus patients (N = 801) with glycated haemoglobin (HbA(1c)) 6.5-10% on stable metformin doses (1500-3000 mg/day) were randomized 1 : 1 to add-on 5 mg saxagliptin or 100 mg sitagliptin once daily for 18 weeks. The primary efficacy analysis was a comparison of the change from baseline HbA(1c) at week 18 in per-protocol patients. Noninferiority was concluded if the upper limit of the two-sided 95% confidence interval of the HbA(1c) difference between treatments was < 0.3%. RESULTS: The adjusted mean changes in HbA(1c) following the addition of saxagliptin or sitagliptin to stable metformin therapy were - 0.52 and - 0.62%, respectively. The between-group difference was 0.09% (95% confidence interval, - 0.01 to 0.20%), demonstrating noninferiority. Both treatments were generally well tolerated; incidence and types of adverse events were comparable between groups. Hypoglycaemic events, mostly mild, were reported in approximately 3% of patients in each treatment group. Body weight declined by a mean of 0.4 kg in both groups. CONCLUSIONS: Saxagliptin added to metformin therapy was effective in improving glycaemic control in patients with type 2 diabetes mellitus inadequately controlled by metformin alone; saxagliptin plus metformin was noninferior to sitagliptin plus metformin, and was generally well tolerated. [less ▲]

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See detailPulse pressure and cardiovascular autonomic neuropathy according to duration of type 1 diabetes.
Philips, Jean-Christophe ULg; Marchand, Monique ULg; Scheen, André ULg

in Diabetes/Metabolism Research & Reviews (2009)

BACKGROUND: To evaluate changes in pulse pressure (PP) and markers of cardiovascular autonomic neuropathy (CAN) according to duration of type 1 diabetes mellitus (T1DM). METHODS: This cross-sectional ... [more ▼]

BACKGROUND: To evaluate changes in pulse pressure (PP) and markers of cardiovascular autonomic neuropathy (CAN) according to duration of type 1 diabetes mellitus (T1DM). METHODS: This cross-sectional controlled study evaluated 159 diabetic patients during a 3-min posture test (standing-squatting-standing) with continuous measurement of systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure by a Finapres device. Arterial stiffness was indirectly assessed by PP and the slope of PP as a function of MBP calculated during the whole 3-min test. CAN was assessed by the expiration/inspiration pulse interval ratio (E/I R-R ratio) during deep breathing and by three indices measured during the squatting test. Patients were divided into four groups according to diabetes duration (<10 years, 11-20 years, 21-30 years and > 30 years from group 1 to group 4, respectively) and compared with age-matched non-diabetic subjects. RESULTS: PP progressively increased (p < 0.0001) and PP/MBP decreased (p < 0.0005) according to T1DM duration, whereas these parameters remained almost unchanged in age-matched control subjects. E/I ratio (p < 0.0001) and baroreflex gain (p < 0.0005) progressively decreased with T1DM duration. The parasympathetic index (squatting test vagal ratio-SqTv) significantly increased (p < 0.0001), whereas the sympathetic index (squatting test sympathetic ratio-SqTs) only tended to decrease (p = 0.12) according to diabetes duration. No such changes in CAN indices were observed in the non-diabetic population. CONCLUSIONS: PP increased according to T1DM duration in an age range where PP remained almost stable in controls, in agreement with accelerated arterial stiffening due to chronic hyperglycaemia. The baroreflex gain decreased and other indices of CAN also deteriorated with diabetes duration, more so indices reflecting parasympathetic rather than sympathetic dysfunction. [less ▲]

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See detailCirculating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose control.
Radermecker, Régis ULg; Renard, E; Scheen, André ULg

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 ▲]

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See detailAllergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues.
Radermecker, Régis ULg; Scheen, André ULg

in Diabetes/Metabolism Research & Reviews (2007), 23(5), 348-55

The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations ... [more ▼]

The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations. Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), and the use of insulin analogues, resulting from the alteration in the amino acid sequence of the native insulin molecule, may influence the immunogenicity and antigenicity of native insulin. Instead of increasing allergy reactions, CSII has been reported to represent a successful alternative treatment in diabetic patients presenting local or generalized allergy to insulin or other components (zinc, protamine) of conventional treatment. Most recent reports concern CSII-treated patients using short-acting insulin analogues (essentially insulin lispro), although the precise role of these insulin analogues remains unclear as allergy to them has also been described. Finally, data on antigenicity and immunogenicity of long-acting insulin analogues (glargine, detemir), which may mimic the basal insulin delivery with CSII, remain scarce at present. [less ▲]

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See detailThe kallikrein-kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity
Damas, Jacques ULg; Garbacki, Nancy ULg; Lefèbvre, P. J.

in Diabetes/Metabolism Research & Reviews (2004), 20(4, Jul-Aug), 288-297

The therapeutic use of angiotensin converting enzyme (ACE) inhibitors, at a large scale, in arterial hypertension has showed that these molecules can exert, beneficial effects on insulin sensitivity and ... [more ▼]

The therapeutic use of angiotensin converting enzyme (ACE) inhibitors, at a large scale, in arterial hypertension has showed that these molecules can exert, beneficial effects on insulin sensitivity and may reduce the occurrence of type 2 diabetes mellitus. One hypothesis explaining these effects of ACE inhibitors may relate to their capacity to interfere with bradykinin (BK) metabolism and action. BK may participate in the regulation of substrate utilization by, several tissues by improving blood flow and substrate delivery to the tissues and also by promoting translocation of glucose transporters. Moreover, BK has been shown to increase phosphorylation of insulin receptor and its cell substrates. BK also appears to improve the release of insulin. Furthermore, insulin may activate the kallikrein-kinin system, which consequently may increase its metabolic effects. However, in experimental diabetes mellitus, BK can participate to the inflammatory reaction leading to Langerhans islets destruction. In diabetes, whereas tissue kallikrein mRNA levels were reduced in several organs, an overexpression of kinin receptors, an increase in plasma levels of kininogens and kallikrein and an activation of the kinin system have all been reported. Lastly, kinins may be involved in the development of diabetic nephropathy. Reduction of kinin metabolism by ACE inhibitors might be involved in the beneficial effects exerted by these compounds in diabetic kidney functions. Copyright (C) 2004 John Wiley Sons, Ltd. [less ▲]

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See detailContinuous subcutaneous insulin infusion with short-acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and cost-effectiveness.
Radermecker, Régis ULg; Scheen, André ULg

in Diabetes/Metabolism Research & Reviews (2004), 20(3), 178-88

Portable insulin infusion devices are effective and safe insulin delivery systems for managing diabetes mellitus, especially type 1 diabetes. Rapidly absorbed insulin analogues, such as insulin lispro or ... [more ▼]

Portable insulin infusion devices are effective and safe insulin delivery systems for managing diabetes mellitus, especially type 1 diabetes. Rapidly absorbed insulin analogues, such as insulin lispro or insulin aspart, may offer an advantage over regular human insulin for insulin pumps. Several open-label randomised crossover trials demonstrated that continuous subcutaneous insulin infusion (CSII) with insulin lispro provided a better control of postprandial hyperglycaemia and a slightly but significantly lower glycated haemoglobin level, with lower daily insulin requirement and similar or even less hypoglycaemic episodes. A CSII study comparing insulin lispro and insulin aspart demonstrated similar results with the two analogues, and better results than those with regular insulin. Because these analogues have a quicker onset and a shorter duration of action than regular insulin, one might expect an earlier and greater metabolic deterioration in case of CSII interruption, but a more rapid correction of metabolic abnormalities after insulin boluses when reactivating the pump. These expectations were confirmed in randomised protocols comparing the metabolic changes occurring during and after CSII interruption of various durations when the pump infused either insulin lispro or regular insulin. The extra cost resulting from the use of CSII and insulin analogues in diabetes management should be compensated for by better metabolic control and quality of life. In conclusion, CSII delivering fast-acting insulin analogues may be considered as one of the best methods to replace insulin in a physiological manner by mimicking meal and basal insulin requirements, without higher risk of hypoglycaemia or ketoacidosis in well-educated diabetic patients. [less ▲]

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See detailAre all glitazones the same?
Van Gaal, Luc; Scheen, André ULg

in Diabetes/Metabolism Research & Reviews (2002), 18 Suppl 2

This supplement focuses on the benefits of targeting insulin resistance through therapy with a new class of oral antidiabetic agents, the thiazolidinediones (TZDs) or 'glitazones'. There are important ... [more ▼]

This supplement focuses on the benefits of targeting insulin resistance through therapy with a new class of oral antidiabetic agents, the thiazolidinediones (TZDs) or 'glitazones'. There are important differences between the three TZD class members that warrant discussion to enable physicians to make rational and informed therapeutic choices between the agents. Overall the TZDs appear to be similar in their effects on blood glucose, as all class members have demonstrated effective glycaemic control, both as monotherapy and in combination with sulphonylureas, metformin or exogenous insulin. The safety profiles of the three agents are more diverse, with what appear to be 'TZD class effects', (probably mediated via activation of peroxisome proliferator-activated receptor gamma [PPAR gamma]) and 'TZD-specific effects', which are unique to each agent and may be a consequence of differing chemical structures. While rosiglitazone and pioglitazone share some class effects with troglitazone, they have several characteristics that define them as unique agents. By tackling the control of type 2 diabetes through direct effects on insulin resistance, the TZDs represent an important new therapeutic tool for healthcare professionals. [less ▲]

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See detailThymic Expression of Insulin-Related Genes in an Animal Model of Autoimmune Type 1 Diabetes
Kecha-Kamoun, Ouafae; Achour, Imane; Martens, Henri ULg et al

in Diabetes/Metabolism Research & Reviews (2001), 17(2, Mar-Apr), 146-52

BACKGROUND: Insulin and multiple other autoantigens have been implicated in the pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against ... [more ▼]

BACKGROUND: Insulin and multiple other autoantigens have been implicated in the pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against insulin-secreting islet beta-cells remains obscure. The primary objective of the present study was to investigate the hypothesis that a defect in thymic central T-cell self-tolerance of the insulin hormone family could contribute to the pathophysiology of type 1 diabetes. This hypothesis was investigated in a classic animal model of type 1 diabetes, the Bio-Breeding (BB) rat. METHODS: The expression of the mammalian insulin-related genes (Ins, Igf1 and Igf2) was analysed in the thymus of inbred Wistar Furth rats (WF), diabetes-resistant BB (BBDR) and diabetes-prone BB (BBDP) rats. RESULTS: RT-PCR analyses of total RNA from WF, BBDP and BBDR thymi revealed that Igf1 and Ins mRNAs are present in 15/15 thymi from 2-day-old, 5-day-old and 5-week-old WF, BBDR and BBDP rats. In contrast, a complete absence of Igf2 mRNA was observed in more than 80% of BBDP thymi. The absence of detectable Igf2 transcripts in the thymus of BBDP rats is tissue-specific, since Igf2 mRNAs were detected in all BBDP brains and livers examined. Using a specific immunoradiometric assay, the concentration of thymic IGF-2 protein was significantly lower in BBDP than in BBDR rats (p<0.01). CONCLUSIONS: The present study suggests an association between the emergence of autoimmune diabetes and a defect in Igf2 expression in the thymus of BBDP rats. This tissue-specific defect in gene expression could contribute both to the lymphopenia of these rats (by impaired T-cell development) and the absence of central T-cell self-tolerance of the insulin hormone family (by defective negative selection of self-reactive T-cells). [less ▲]

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See detailAntiobesity pharmacotherapy in the management of type 2 diabetes.
Scheen, André ULg; Lefebvre, Pierre ULg

in Diabetes/Metabolism Research & Reviews (2000), 16(2), 114-24

Obesity is a well-known risk factor for the development of Type 2 diabetes mellitus. The management of the obese diabetic patient remains a challenge for the clinician but, in any case, weight reduction ... [more ▼]

Obesity is a well-known risk factor for the development of Type 2 diabetes mellitus. The management of the obese diabetic patient remains a challenge for the clinician but, in any case, weight reduction should be considered as a key objective. In this respect, several antiobesity drugs have demonstrated potential. However, while fenfluramine and dexfenfluramine have been shown to promote weight loss and to directly improve insulin sensitivity, being two mechanisms contributing to better blood glucose control in obese Type 2 diabetic patients, they were recently withdrawn due to safety problems. Sibutramine, a new selective norepinephrine and serotonin reuptake inhibitor, promotes weight loss by decreasing food intake, an effect which leads to a mild improvement (significant in patients losing > or =5% of initial body weight) of blood glucose control in obese diabetic patients. Similarly, orlistat, a selective gastrointestinal lipase inhibitor which increases faecal fat losses, enhances diet-induced weight reduction and improves both blood glucose control and vascular risk profile, especially dyslipidaemia, in obese Type 2 diabetic patients. Further studies are required to better identify good responders to pharmacotherapy and specify the role of antiobesity agents in the overall long-term management of obese subjects with Type 2 diabetes. Other novel pharmacological approaches deserve further consideration, for instance beta-3 agonists aiming to increase energy expenditure, drugs interfering with tumor necrosis factor-alpha (TNF-alpha) or free fatty acid release by the adipose tissue or agents that slow gastric emptying. However, until now, results regarding efficacy and/or safety have been disappointing or preliminary in humans. [less ▲]

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