[Physiopathology of post-prandial hyperglycemia].
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Glucose↗
Biomedical subjects
N Paquot
Publications and source records attributed to N Paquot.
[Type 1 diabetes and celiac disease].
Celiac disease is more prevalent in type 1 diabetic patients than in the general population. The exact reason for this association remains unknown. Two hypotheses are taken into consideration: either a common genetic background or an immune response against Langerhans islets triggered by celiac disease. This review presents recent data about this association and its consequences in clinical practice.
Celiac Disease↗
[PPAR-gamma receptors, new therapeutic target in metabolic and cardiovascular diseases].
PPARs ("Peroxisome Proliferator-Activated Receptors") belong to a superfamily of nuclear receptors with several isoforms, among which PPAR-alpha mainly located in the liver and PPAR-gamma mainly located in the adipose tissue. These receptors are considered as major pharmacological targets since the discovery of their activation by specific agonists, which lead to various favourable metabolic effects. Improvement of lipid profile by fibrates is explained by the activation of liver PPAR-alpha receptors. However, PPAR-gamma receptors have focused most fundamental and clinical research in recent years after the demonstration of their activation by thiazolidinediones (pioglitazone, rosiglitazone), a new class of antidiabetic agents. Beyond their effects on insulin sensitivity, glitazones exert pleiotropic effects that may result in cardiovascular protection in high risk patients. It has been recently demonstrated that certain angiotensin AT1 receptor blockers (sartans) can also exert a partial agonist activity on PPAR-gamma. Among the molecules of this class, telmisartan appears to exert this effect at the lower concentrations. Thus, PPAR-y, as common pharmacological target, may, at least partially, explain some of the effects observed with both thiazolidinediones and inhibitors of the renin-angiotensin system, in particular the improvement in insulin sensitivity (in particular via an increase in adiponectin levels), the protection against type 2 diabetes, the reduction in arterial blood pressure and the prevention of cardiovascular complications. There is currently a major interest from the pharmaceutical industry in the development of new molecules able to activate both PPAR-alpha and PPAR-gamma.
Cardiovascular Diseases↗
[Insulin detemir (Levemir)].
Insulin detemir (Levemir) is a soluble long acting human insulin analogue acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged metabolic effect (up to 24 hours) with low variability. Indeed, in patients with type 1 or type 2 diabetes mellitus, insulin detemir has a more predictable, protracted and consistent effect, with less intrapatient variability in glycaemic control (particularly fasting plasma glucose levels), compared with NPH (Neutral Protamine Hagedorn) insulin. Insulin detemir, is at least as effective as NPH insulin in maintaining overall glycaemic control, with a lower risk of nocturnal hypoglycaemia. It also provides the additional benefit of less body weight gain as compared to other basal insulins. Levemir, presented in cartridges for the pen device NovoPen 3 and administered preferably at bedtime (if necessary morning and evening), is a promising new option for basal insulin therapy in diabetic patients, especially those on a basal-bolus scheme.
Diabetes Mellitus↗
[Hematochromatosis and diabetes].
Nowadays, haemochromatosis is often diagnosed when the patient is monosymptomatic. Diabetes is frequently the first expression of the disease. So, it is important to know the clinical and biologic characteristics to evoke diagnosis as early as possible. Uncommon presentations request systematic screening.
Asthenia↗
[Blood glucose control and prevention of microangiopathy and macroangiopathy in type 2 diabetes].
Even if type 2 diabetes is a complex disease combining hyperglycaemia and various other metabolic abnormalities. Reduction of chronic hyperglycemia, assessed by glycated haemoglobin (HbA1c), allows the prevention or the delay of vascular complications. Evidence-based medicine already provided numerous data regarding the risk of microangiopathy, especially retinopathy and nephropathy but also neuropathy. The evidence is less obvious as far as macroangiopathy, especially coronary artery disease, is concerned. This observation should encourage a global approach of the type 2 diabetic patient, taking into account all vascular risk factors. It also provides further arguments in favour of alternative therapeutic modalities, such as the use of hypoglycaemic agents that improve postprandial hyperglycaemia and/or insulin resistance. This latter approach appears to be promising in view of the favourable results with metformin in the United Kingdom Prospective Diabetes Study. It should be confirmed in large prospective ongoing clinical trials with new insulin sensitizers like thiazolidinediones.
Blood Glucose↗
[Prevention of cardiovascular disease in type 2 diabetes].
It is estimated that 80% of individuals with type 2 diabetes die of cardiovascular diseases. Several factors account for the accelerated atherosclerosis present in diabetic patients. These include hyperglycaemia, dyslipidaemia, hypertension and prothrombotic state. Hypoglycaemic agents, statin or fibrates that improve dyslipidaemia, anti-hypertensive agents, aspirin and healthy lifestyle can modify these factors and have been shown to reduce morbidity and mortality caused by coronary heart disease in diabetic patients. It was recently demonstrated that a multifactorial intervention on modifiable risk factors of cardiovascular disease in type 2 diabetic patients dramatically reduces the incidence of cardiovascular events. Thus, an intensified intervention aimed at multiple risk factors should be recommended in patients with type 2 diabetes.
Cardiovascular Diseases↗
[Prevention of hypoglycemia in patients with type 1 diabetes].
Hypoglycaemia is the most common metabolic disorder in type 1 diabetic patients. It is rarely dangerous, but significantly alters the quality of life and hinders the achievement of "normoglycaemia". Even if hypoglycaemia is impossible to be avoided, both its frequency and severity may be reduced if patients follow several practical recommendations. After having defined hypoglycaemia, we shall briefly describe its pathophysiology and its main causes in type 1 diabetic patients. Afterwards, the different approaches of prevention of hypoglycaemia will be discussed. We will particularly stress the need to revise the glycaemic target in high-risk patients, the role of optimising insulin therapy, the valuable help of blood glucose monitoring, the critical support of diet adjustments, and the appropriate management in case of physical activity. There is no doubt that patient's education plays a crucial role in such a strategy that aims at preventing severe hypoglycaemia in type 1 diabetic individuals.
Diabetes Mellitus, Type 1↗
[Adiponectin: a new adipocytokine].
Adipose tissue is not simply a store of excess energy, but also secretes a variety of proteins into circulating blood that influence systemic metabolism. These include tumor necrosis factor (TNF-alpha), plasminogen activator inhibitor type 1 (PAI-1), leptin, resistine and adiponectin. These are collectively known as adipocytokines. Adiponectin (also referred to as AdipoQ, Acrp 30, apM1 or GBP28) is a novel adipose-specific protein. A recent genome study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome on chromosome 3q27, where the adiponectin gene is located. Adiponectin is a peculiar adipocytokine because in contrast to the markedly increased levels of many others, as leptin or TNF-alpha, its level is reduced in obesity and type 2 diabetes. The administration of thiazolidinediones, which are synthetic PPARs-gamma ligands, significantly increases the plasma adiponectin concentrations, an effect that could improve insulin sensitivity. Thus, the administration of adiponectin may provide a novel treatment modality for insulin resistance and type 2 diabetes.
Adiponectin↗
[How I explore ... the risk of a patient developing type 2 diabetes].
Both the prevalence and the incidence of type 2 diabetes are increasing rapidly. Effective prevention measures, including lifestyle or drug prescription, have been recently reported. It is thus important to detect at risk individuals in order to provide appropriate diet and exercise recommendations or even pharmacological treatment. We summarize the most useful indices based on anamnesis, clinical examination and biological assays that can help to detect subjects at high risk of progression towards type 2 diabetes.
Comorbidity↗
[Postprandial hyperglycemia. I. Physiopathology, clinical consequences and dietary management].
Postprandial hyperglycaemia depends on the amount and type of ingested carbohydrates and/or the degree of inhibition of hepatic glucose output following a meal. The kinetics of carbohydrate absorption is directly influenced by the type of food (carbohydrates with variable glycaemic indices, fibre content of the meal) and by the speed of gastric emptying. Hepatic glucose output is remarkably inhibited by insulin and strongly stimulated by glucagon. It remains abnormally high after a meal in diabetic patients because of insufficient portal insulin concentrations, hepatic insulin resistance and/or hyperglucagonaemia. In diabetic patients, postprandial hyperglycaemia contributes to the aggravation of chronic hyperglycaemia, and thus to the increase of glycated haemoglobin levels. Furthermore, it has been recently demonstrated that postprandial hyperglycaemia increases the cardiovascular risk, even in nondiabetic subjects, probably by inducing endothelial dysfunction. Appropriate dietary counselling plays a key-role in the control of postprandial hyperglycaemia. Generally speaking, it includes a selection of carbohydrates with low glycaemic index and a higher fibre intake. Pharmacological interventions may also be considered when necessary.
Absorption↗
[Postprandial hyperglycemia. II. Pharmacological approaches].
Besides dietary approaches, various pharmacological means have been recently developed in order to better control postprandial hyperglycaemia. This objective may be obtained: 1) by slowing down the intestinal absorption of carbohydrates; 2) by insuring a better insulin priming soon after the meal; and 3) by inhibiting post-prandial glucagon secretion or action. Some hormones (amylin, glucagon-like peptide-1) can slow gastric emptying while alpha-glucosidase inhibitors (acarbose, miglitol) retard intestinal digestion and resorption of complex carbohydrates. A more physiological post-meal profile of insulin may be obtained in type 2 diabetes by using new insulin secretagogues of the glinide family (repaglinide, nateglinide) with an earlier and shorter insulinotropic action or, mainly in type 1 diabetes but also in type 2 diabetes, by using short-acting insulin analogues (lispro. Asp B28) or inhated insulin the action of which is faster than that of subcutaneous insulin. Post-prandial glucagon secretion can be inhibited by amylin. GLP-1 or insulin while other glucagon antagonists are currently in development.
Diabetes Mellitus, Type 1↗
[Sports nutrition].
All nutrition recommendations for athletes must be based on current scientific data and the needs of athletes as individuals. Exercise performance may be improved by adequate food intake. Adequate energy intake needs to be consumed during times of high-intensity training to maintain body weight and maximize the training effect. Carbohydrates are important to maintain blood-glucose and replace muscle glycogen. During exercise, carbohydrates must be provided at the rate of 30 to 60 g per h. Fat intake should not be restricted. No vitamin and mineral supplements should be required if an athlete is consuming adequate energy from a variety of foods. Deshydratation decreases exercise performance. Two hours before exercise 400 to 600 ml of fluid should be consumed and during exercise 150 to 350 ml of fluid every 15 to 20 min. After exercise, the dietary goal is to provide adequate energy and carbohydrate to replace muscle glycogen and ensure rapid recovery.
Dehydration↗
[Beneficial effects of physical activity on cardiovascular risk factors].
Numerous observational (epidemiological surveys) or interventional (controlled trials) studies demonstrated that regular physical activity increases insulin sensitivity in normal subjects and decreases insulin resistance in patients with obesity and/or type 2 diabetes. These favourable effects are at least partially linked to a reduction in abdominal fat mass. This results in a significant improvement of lipid profile, with a decrease in the concentrations of total cholesterol, LDL cholesterol and triglycerides, associated with an increase of HDL cholesterol level. Such favourable metabolic effects related to regular physical activity probably explain the better cardiovascular prognosis observed in regularly exercising subjects as compared to sedentary individuals. These observations should motivate any practitioner to promote endurance physical exercise in every subject, especially in individuals at high cardiovascular risk.
Cardiovascular Diseases↗
[How I explore ... the different forms of sugar diabetes: clinical and biological differental diagnosis].
Owing to the increasing prevalence of diabetes mellitus and the various aspects of this disease, we present a practical approach which allows the clinician to more easily differentiate type 1 diabetes, type 2 diabetes and secondary diabetes of pancreatic origin, i.e. the most common forms of diabetes mellitus. Such an approach uses simple diagnostic criteria, based upon both clinical characteristics (family history, personal history, clinical presentation) and biological markers (C-peptide, autoantibodies,...). A right diagnosis should allow to optimize the management of the diabetic patient.
Biomarkers↗
Assessment of postprandial hepatic glycogen synthesis from uridine diphosphoglucose kinetics in obese and lean non-diabetic subjects.
BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic glycogen synthesis remains unknown. AIM: To determine whether postprandial hepatic glycogen synthesis is decreased in obese patients compared to lean subjects. METHODS: Lean and obese subjects with impaired glucose tolerance were studied over 4h after ingestion of a glucose load. Hepatic uridine diphosphoglucose kinetics were assessed using 13C-galactose infusion, with monitoring of urinary acetaminophen-glucuronide isotopic enrichment to estimate hepatic glycogen kinetics. RESULTS: Estimated net hepatic glycogen synthesis amounted to 18.6 and 22.6% of the ingested load in lean and obese subjects, respectively. CONCLUSION: Postprandial hepatic glycogen metabolism is not impaired in non-diabetic obese subjects.
Adult↗
Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man.
AIMS: This study was undertaken to determine the effects of a short-term dexamethasone treatment on hepatic sensitivities to insulin and glucagon. METHODS: Eleven healthy subjects were studied during one or several of four protocols. In all protocols, somatostatin was infused continuously to inhibit pancreatic hormone secretion. In protocol 1, basal insulin was infused over 300 min while glucagon was infused at a rate of 0.5 mg/kg(-1)/min(-1)during 180 min, then at a rate of 1.5 ng/kg(-1)/min(-1)during 150 min. In protocol 2, the same experiment was performed after a 2 day treatment with 8 mg/day dexamethasone. In protocol 3, the two-step glucagon infusion was performed during insulin infusion at a rate aimed to reproduce the hyperinsulinemia observed during protocol 2. In protocol 4, continuous basal insulin and low glucagon (0.5 mg/kg(-1)/min(-1)) were infused over 330 min. RESULTS: In protocol 1, plasma glucose rose transiently by 2.0 +/- 0.3 mmol/l when the glucagon rate was increased and glucose production increased by 1.4 +/- 0.5 micromol/kg(-1)/min(-1). In protocol 2, the insulin infusion rate (1.85 +/- 0.36 nmol/kg(-1)/min(-1)) required to maintain glycemia was 3.3-fold higher than during protocol 1. Glucagon-induced stimulation of glycemia (by 1.47 +/- 0.5 mmol/l) and endogenous glucose production (by 0.8 +/- 0.3 micromol/kg(-1)/min(-1)) were blunted, but not abolished. In protocol 3, endogenous glucose production was suppressed by 75% by hyperinsulinemia and was not stimulated when the glucagon infusion rate was increased. In protocol 4, endogenous glucose production did not change significantly with time. CONCLUSION: These results indicate that high dose glucocorticoids induce a marked hepatic insulin resistance. Stimulation of glucose production by hyperglucagonemia was maintained in spite of hyperinsulinemia which can be attributed to either hepatic insulin resistance and/or increased hepatic glucagon sensitivity.
Adult↗
No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients.
Inhibition of tumor necrosis factor (TNF)-alpha results in a marked increase in insulin sensitivity in obese rodents. We investigated the influence of a TNF antagonist [Ro 45-2081, a recombinant fusion protein that consists of the soluble TNF-receptor (p55) linked to the Fc portion of human IgG1] on insulin sensitivity of patients with android obesity. Seven patients (five women and two men; mean +/- SD age, 41 +/- 4 yr; body mass index, 36.1 +/- 4.7 kg/m2; waist to hip ratio, 0.99 +/- 0.11) were studied (three patients with normal glucose tolerance and four patients with impaired glucose tolerance or mild diabetes; all were hyperinsulinemic). Each patient underwent two consecutive euglycemic hyperinsulinemic glucose-clamp tests: 48 h after injection of placebo and 48 h after a single i.v. injection of 50 mg Ro 45-2081. In both tests, steady-state plasma glucose and insulin levels were similar. Insulin-mediated glucose disposal (2.23 +/- 0.74 vs. 2.38 +/- 0.99 mg/kg(-1) x min(-1)) and glucose metabolic clearance rate (2.28 +/- 0.85 vs. 2.48 +/- 1.03 mL/kg(-1) x min(-1)) were similar after placebo and after the drug. Indirect calorimetry showed no difference in substrate oxidation rates between the two experimental conditions. In conclusion, under the conditions of this study, no improvement in insulin sensitivity was observed in obese insulin-resistant patients following a single i.v. administration of a recombinant TNF receptor: Fc fusion protein.
Adult↗