Anti-insulin antibodies and metabolic deterioration after interruption of continuous subcutaneous insulin infusion.
Explore the source record for details and available documents.
3-Hydroxybutyric Acid↗
Biomedical subjects
A J Scheen
Publications and source records attributed to A J Scheen.
Medical aspects of obesity.
Obesity poses a serious health hazard and its treatment is often disappointing. Major advances have been made during recent years in the understanding of body weight regulation, with the discovery of leptin, a protein produced by adipocytes and acting on the central nervous system to reduce food intake, and that of beta-3 adrenergic receptors and uncoupling proteins which contribute to stimulate energy expenditure. Numerous metabolic complications are associated with abdominal obesity and most of them, such as diabetes mellitus, dyslipidaemias and arterial hypertension, appear to be linked to insulin resistance and may be part of the socalled metabolic syndrome or syndrome X. While very-low-calorie diets are usually effective in the short-term, they cannot, in the long-term and for most patients, solve the problem of severe obesity. Pharmacological antiobesity treatment may include drugs that reduce food intake, drugs that increase energy expenditure and drugs that affect nutrient partitioning or metabolism. All of these pharmacological approaches have potential efficacy, but unfortunately serious limitations. This is also the case of mechanical means, such as intragastric balloons. Consequently, bariatric surgery may be considered as a valuable alternative therapy in well-selected patients with morbid obesity refractory to classical treatments. In conclusion, obesity is a chronic disease and should be treated as such with reasonable expectations.
Combined Modality Therapy↗
Impaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections.
The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk factors involved contrasts with the multitude of in vitro models focused on the metabolism and function of immune cells from diabetic patients. This review analyzes some of these models and their clinical relevance. The different levels of diabetes pathogenesis: genetic (Type 1), autoimmune (Type 1) and metabolic (Type 1 and Type 2) are responsible for immune abnormalities demonstrated in in vitro models. The participation of genetic and autoimmune factors has been mainly characterized on T lymphocyte function. The B8 DR3 haplotype is associated with several minor immunologic abnormalities in vitro. However, the high frequency of this haplotype in healthy individuals argues against its involvement in significant defects of antimicrobial immunity. Genetic deficiency of C4, present in 25% of Type 1 diabetic patients could, on the other hand, be responsible for opsonization defects against encapsulated pathogens. Several immunological abnormalities related to the autoimmune process preceding the onset of Type 1 diabetes mellitus, such as the depletion of memory CD4+ cells and the defective natural killer activity could transiently impair host defences against viral diseases. Several in vitro functional defects of the immune system have been correlated with the metabolic control of diabetic patients. This suggests the involvement of insulinopenia in some of the abnormalities observed. Insulinopenia-induced enzymatic defects have often been proposed to inhibit energy-requiring functions of phagocytes and lymphocytes. However, the relevance of this mechanism could be confined to patients with extremely severe metabolic abnormalities. The importance of systemic consequences of insulinopenia such as hyperglycaemia and ketosis has also been addressed. Usually, the defects induced in vitro by these factors are slight and require supraphysiologic concentrations of glucose or ketone bodies. Recent studies have shown abnormalities of signal transduction mechanisms in which insulinopenia itself and other factors such as circulating immune complexes could be involved. Despite numerous controversies, many in vitro studies of the immune cells of diabetic patients have demonstrated significant defects which bear quantitative similarities with abnormalities described in other immunodeficiency syndromes. Furthermore, several mechanisms have been proposed to link the different defects observed with the specific infections encountered in diabetic patients.
Autoimmunity↗
[Comments on the special issues on preventive medicine ].
Explore the source record for details and available documents.
France↗
[Metabolic syndrome: definitions and epidemiological data].
The metabolic syndrome is strongly related to visceral obesity and associated with a high risk of cardiovascular morbidity and mortality. Since the original description of Reaven in 1988, several working definitions have been proposed, especially by the World Health Organisation in 1998-99, the National Cholesterol Education Program (NCEP-ATP III) Expert Panel in the United States in 2001 and the European Group for the Study of Insulin Resistance (EGIR) in 2002. The present paper attempts at comparing these various definitions and at reporting epidemiological data both in North America and in Europe, especially in Belgium. The prevalence is generally higher in men than in women and strongly increases with age. Overall, one may estimate that around 20% of adults have a metabolic syndrome, which should therefore be considered as an important public health problem.
Albuminuria↗
[Alcohol, insulin sensitivity and diabetes].
The relationship between alcohol consumption and insulin resistance shows a U-shaped curve: insulin resistance is minimal in individuals with regular mild to moderate alcohol consumption and increases in both heavy drinkers and subjects without any alcohol consumption. These favourable metabolic effects on insulin sensitivity of moderate alcohol consumption may explain the significant reduction in the development of type 2 diabetes and the risk of cardiovascular complications reported in numerous epidemiological studies. This latter effect has also reported in patients with diabetes mellitus, although this observation remains controversial. However, alcohol consumption could increase the global risk of hypoglycaemia, both in the fasting state and after a meal (reactive hypoglycaemia) in both diabetic and nondiabetic subjects. These latter effects may result from a direct inhibition of gluconeogenesis, from a reduced secretion of counterregulatory hormones and/or from an alcohol-induced inappropriate behaviour.
Alcohol Drinking↗
[How I explore...the absolute cardiovascular risk at 10 years: from Framingham 1998 to SCORE 2003].
Prevention of cardiovascular diseases should primarily focus on high-risk individuals. In the absence of atherosclerosis manifestations, such persons may be screened by the calculation of the absolute risk of complications during the next ten years or extrapolated at the age of 60 years. This calculation is based upon the analysis of most important risk factors of atherosclerosis. The mode of calculation that prevailed for many years used the Framingham equation determining the absolute coronary risk (both morbidity and mortality) in the next 10 years: a risk equal or superior to 20% is considered as high and requiring specific intervention. The Third Joint Task Force of European and other Societies on cardiovascular disease prevention in clinical practice recently proposed a new mode of calculation (SCORE) based upon the absolute risk of cardiovascular (and not exclusively coronary) mortality (only fatal events and not morbidity): according to SCORE, the threshold of high risk has been set at a risk equal or superior to 5% in the next 10 years. The present article compares the two modes of calculation with their own advantages and disadvantages.
Cardiovascular Diseases↗
[Diabetes mellitus: an example of a well-considered disease. Introduction].
Explore the source record for details and available documents.
Diabetes Mellitus, Type 1↗
[The cost of type 2 diabetes: summary of the Cost of Diabetes in Europe-Type II study (CODE-2) and analysis of the situation in Belgium].
Type 2 diabetes mellitus is a common chronic disease whose economic impact on both patients and society is constantly increasing. "The Cost of Diabetes in Europe--Type 2 study" is the first coordinated attempt to measure total healthcare costs of type 2 diabetes mellitus in Europe. On average, 3% of the population with type 2 diabetes accounted for 5% of the total healthcare expenditure. Complications have a substantial impact on the costs of managing type 2 diabetes. The prevention of complications, especially cardiovascular disease, will potentially reduce overall healthcare expenditure.
Belgium↗
[Continuous subcutaneous insulin infusion with portable pumps].
Type I diabetes mellitus requires an exogenous supply of insulin that ideally mimics physiological insulin secretion. The treatment goal is to achieve normoglycaemia in order to prevent or delay chronic complications, while limiting the risk of hypoglycaemia. Numerous advances have been performed in the last 10 years, as far as nature of insulin formulations, home blood glucose monitoring devices and modes of insulin delivery. Among the latter, continuous subcutaneous insulin infusion (CSII) using portable pumps represents the most sophisticated treatment capable of best mimicking normal insulin secretion. Such treatment provides better glucose control and glucose stability as compared to conventional multiple injection insulin therapy. However, it is essential to respect well defined indications and to organize a structured management by a multidisciplinary team in order to get the best metabolic results. The present paper describes recommendations, advantages and limits as well as cost of CSII with portable pumps in type 1 diabetic patients.
Blood Glucose↗
[Pancreas transplantation in the management of diabetes].
Pancreas transplantation has now become an established option in the treatment of diabetic complications. It normalizes glucose metabolism, prevents, stabilizes and improves the evolution of diabetes-associated lesions. Improvements in surgical procedure and in immunosuppression have better defined its indications. Combined kidney-pancreas transplantation appears today as the best treatment for the diabetic patient with end stage renal disease. Isolated pancreas transplantation is reserved to non-uremic patients with severe diabetic complications or with hyperlabile glycaemic control and severe impairment of quality of life.
Diabetes Mellitus↗
[Obesity and type 2 diabetes].
Obesity is an epidemic disease associated with numerous cardiovascular risk factors as diabetes mellitus, dyslipidemia, hypertension. Insulin resistance seems to be an important promoter for the development of most of these abnormalities. Besides genetic background, obesity, especially abdominal adiposity, is by far the most important factor for the development of type 2 diabetes. The treatment of a diabetic obese subject begins with diet and regular physical activity, eventually with a psychological support. In case of failure of such lifestyle approach alone, addition of drug therapy should be considered. It may include pharmacological agents able to promote weight loss (orlistat, sibutramine, possibly rimonabant) and/or antihyperglycaemic compounds capable of reducing insulin resistance (metformin, glitazones, acarbose). In case of severe/morbid obesity complicated with type 2 diabetes not well controlled with medical means, bariatric surgery is the only treatment that can induce an important and sustained weight loss, associated with marked improvement of metabolic control and amelioration of overall prognosis.
Abdomen↗
[Prevention of type 2 diabetes: a new public health challenge].
Owing to the epidemics of type 2 diabetes, it is important to develop strategies of prevention of the disease. The first step should detect patients at risk, in function of simple anamnesis, clinical and biological criteria. Afterwards, those individuals should be encouraged to follow a prevention programme, which essentially comprises better lifestyle habits (diet and physical exercise), especially to prevent or correct weight excess. In at very high risk subjects, for instance because of moderately increased fasting or post-glucose load glucose levels, eventually in a context of family history of type 2 diabetes, a pharmacological approach could be considered. Various drugs (metformin, acarbose, glitazones, orlistat, inhibitors of the renin-angiotensin system) have proven their efficacy in reducing the incidence of type 2 diabetes, in particular in individuals with impaired glucose tolerance, with obesity and/or with arterial hypertension.
Diabetes Mellitus, Type 2↗
[Insulin sensitizers].
Insulin resistance has a genetic background and its phenotypic expression is triggered by fat diet, lack of physical activity and obesity. It provokes a stress on B cells, tends to increase blood glucose levels, is intimately associated with the metabolic syndrome and represents a major cardiovascular risk factor. Insulin resistance may be favourably influenced by simple life-style changes. If necessary, drugs may be prescribed, such as metformin, the first choice antidiabetic oral agent in overweight individuals, or thiazolidinediones (glitazones), new insulin sensitizers with promising effects. New molecules are currently developed, especially PPAR alpha/gamma or pan-agonists. Targeting insulin resistance has several objectives: reducing hyperglycaemia in type 2 diabetic patients, protecting B cells in order to prevent type 2 diabetes in at risk individuals and limiting the progressive metabolic deterioration in diabetic patients, finally, and perhaps most importantly, ameliorating the global cardiovascular prognosis.
Cardiovascular Diseases↗
[Towards a tripple oral therapy in the pharmacological treatment of type 2 diabetes?].
Type 2 diabetes is a complex disease combining several disturbances in various organs, especially a defect of insulin secretion by the pancreas, an increased production of glucose by the liver and a reduced insulin-mediated glucose uptake by the skeletal muscle. Each of these abnormalities can be, at least partially, reversed by a specific pharmacological approach, an agent promoting insulin secretion (sulphonylurea, glinide), metformin and a thiazolidinedione (glitazone), respectively. A triple oral therapy with "sulphonylurea (glinide)--metformin--glitazone", targeting simultaneously the three main metabolic abnormalities of type 2 diabetes, deserves special attention. Promising results have been observed in recent clinical trials as far as blood glucose control and some other cardiovascular risk factors are concerned. The precise place of such oral triple therapy remains to be specified, at a late stage to delay the shift to insulin or earlier in the natural history of the disease, to avoid the decline of the number and/or function of beta cells and the resulting metabolic deterioration.
Blood Glucose↗
[Insulin therapy in type 2 diabetes].
As compared to type 1 diabetes, type 2 diabetes usually requires insulin at a late stage, after secondary failure to oral antidiabetic drugs. However, it should be pointed out that insulin therapy should not be delayed in patients not well controlled on oral agents. Type 2 diabetic patients failing to oral antidiabetic medications need insulin. Nevertheless, insulin therapy in type 2 diabetic patients is less standardized than in those with type 1 diabetes. Several clinical trials tried to investigate what is the most appropriate initial insulin therapy in type 2 diabetic patients, with the main objectives of reaching almost normoglycaemia without increased risk of frequent or severe hypoglycaemic episodes. However, there is no agreement upon optimal mode of initiating insulin. The most important factors leading to adequate metabolic control are a global educational approach together with a intensified follow up, independently of the insulin regimen.
Blood Glucose↗
[Similar reduction in new cases of type 2 diabetes with angiotensin receptor blocker and ACE inhibitor: comparison of meta-analyses of prospective randomised trials].
This paper aims at comparing two meta-analyses of clinical trials having investigated the effect of the inhibition of the renin-angiotensin system either with an angiotensin converting enzyme inhibitor (ACEI) or with a selective angiotensin receptor blocker (ARB) on the incidence of new cases of type 2 diabetes mellitus in subjects with arterial hypertension or with congestive heart failure. The protection appears similar with ACEIs in six trials in a total of 24.623 patients (hazard ratio: 0.77; CI 95% 0.72-0.81; p < 0.00001 and with ARBs in five trials in a total of 14.344 patients (hazard ratio: 0.79; CI 95% 0.73-0.85; p < 0.00001). It is consistent whatever the comparator, a thiazide diuretic agent, a beta-blocker, a dihydropyridine calcium channel blocker or a placebo. The large ongoing ONTARGET controlled study will allow a direct comparison between an ACEI, ramipril, and an ARB, telmisartan, and will also investigate the potential benefit of a combined treatment with both drugs. The inhibition of the renin-angiotensin system should be considered among pharmacological strategies of prevention of type 2 diabetes mellitus.
Angiotensin-Converting Enzyme Inhibitors↗
[Hereditary hemochromatosis and diabetes mellitus: diagnostic approach and clinical evolution].
We report the characteristics of diabetes mellitus in 10 patients with a suspicion of hereditary hemochromatosis. The results of this personal series were compared to literature's data described in a recent article. Early diagnosis and treatment by phlebotomy can improve blood glucose control in the early stages of the disease. If diagnosis occurs later, when the patient already needs insulin therapy, diabetes will not be improved by phlebotomy anymore.
Adult↗