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Biomedical subjects

E Larger

Publications and source records attributed to E Larger.

At least 19 recordsLinked to original sources
PubMed2006

Postprandial glycaemia: a plea for the frequent use of delta postprandial glycaemia in the treatment of diabetic patients.

Postprandial hyperglycaemia is a phenomenon often neglected by patients as well as doctors. While patients only voluntarily measure morning and preprandial capillary glycaemia, physicians do not encourage the measurement of anything further. The specific role of postprandial hyperglycaemia in the determination of late diabetes complications, such as micro- and macroangiopathy, remains controversial. It is however undeniable that the postprandial glycaemic excursion plays an important role in total hyperglycaemia reflected by an increase in glycated haemoglobin. The postprandial glycaemia measurement or, more appropriately, the postprandial glycaemic excursion (the difference between postprandial and preprandial glycaemia, also called the postprandial delta glycaemia), is important to measure and there are specific tools to correct it when abnormal. Postprandial delta glycaemia should lie between 30 and 50 mg/dl. It is thus suggested to measure it not necessarily on a daily basis, but when it is expected that the glycaemic couple, or "pre-postprandial couple", is high. The specific tools for treatment of postprandial hyperglycaemia can be dietetic (carbohydrate quantity reduction or ingestion of fiber-rich and/or low glycaemic index foods) or medicinal. Among the specific medicinal treatments are the alpha-glucosidase-inhibitors (which can be used for both type 1 and type 2 diabetic patients), glinides and fast-acting insulins. Rather than first treating fasting and interprandial hyperglycaemia, as has been commonly done by physicians, the authors recommend the simultaneous treatment of pre-, inter- and postprandial hyperglycaemia. The optimal time at which to evaluate postprandial glycaemia is approximately 1 h and 15 minutes for type 1 and type 2 diabetic patients.

Blood Glucose↗
PubMed2005

Weight gain and insulin treatment.

This review presents recent data on weight gain when on insulin treatment in type 1 and type 2 diabetic patients. In both types of diabetes, the excess weight gain with intensified insulin therapy compared with conventional insulin or sulfonylurea remains modest: 2.6 kg over 7.5 years in the Stockholm study (type 1 diabetic patients) and 1.7 kg when compared to glibenclamide over 10 years in the UKPDS (type 2 diabetic patients). Patients who gain the most weight after insulin initiation are those who: (1) had the worst metabolic control before the intensification of treatment, (2) had the greater weight loss prior to insulin initiation, and (3) in the case of patients with type 1 diabetes, have a family history of type 2 diabetes. This suggests that most of the weight gain observed after the insulin initiation is a "catch-up" weight re-gain. There is no evidence that weight gain after insulin therapy initiation is associated with a deterioration in the lipid profile or arterial hypertension or an excess risk for cardiovascular events, contrary to common beliefs. All clinical studies performed to date with the insulin analogue detemir have shown that this analogue is associated with lesser weight gain than NPH insulin. There is no explanation yet for these intriguing results. If confirmed on the long-term, this favourable effect on weight might be an interesting feature of this new insulin analogue.

Age of Onset↗
PubMed2005

Transfer of diabetes from prediabetic NOD mice to NOD-SCID/SCID mice: association with pancreatic insulin content.

Splenocytes from prediabetic female NOD mice can transfer diabetes to NOD-SCID mice. Whereas the kinetics of disease transfer was shown to be a function of the age of donor splenocytes, information is scarce as to how the stage of autoimmune disease, as evaluated by pancreatic insulin content, is related to the diabetogenic potency of splenic T-cells. We therefore determined individual diabetes transfer times after an i. v. injection of splenocytes from prediabetic NOD mice of different ages into female NOD-SCID mice in relation to the diabetes incidence in NOD donor mice and their pancreatic insulin contents. Three groups (n = 8) of NOD mice aged 5, 11, and 17 weeks (wk) underwent splenectomy and hemipancreatectomy. After that, 10x10 (6) splenocytes either pooled from all donor NOD mice of the different age groups or individually from single donor mice were transferred to groups of four 6-week-old NOD-SCID mice, respectively, in two sets of experiments. Insulin was extracted from the resected hemipancreas, and the insulin content was determined by a RIA. Diabetes in the NOD-SCID cohort occurred after a mean time of 126 days after transfer of pooled splenocytes from 5-week-old NODs, after 68 days (transfer from 11-week-old NODs), and after a mean time of 43 days (transfer from 17-week-old NODs, 5 vs. 11 wk: p < 0.02, 11 vs. 17 wk: p < 0.001). Individual time to diabetes positively correlated with diabetes transfer times in NOD-SCID recipients (p < 0.0001) in the 17-week-old NOD mice, confirming previous diabetes transfer studies in hemi-pancreatectomized NOD mice. Furthermore, individual insulin concentrations in 17-week-old NOD mice also positively correlated to diabetes transfer times in recipient mice (p < 0.0001). No such correlations for these parameters were seen for the 5 and 11-week-old NOD mice (time to diabetes: 11 wk, p = 0.14, 5 wk, p = 0.75; insulin content: 11 wk, p = 0.81, 5 wk, p = 0.14). These data suggest that destructive T-cell activity increases during the course of islet autoimmunity. The immune response seems to be programmed for beta-cell destruction just before diabetes onset. This is the only time that pancreatic insulin content predicts the impending onset of diabetes.

Animals↗
PubMed2001

[Tissular toxicity of glucose and therapeutic perspectives].

Vascular endothelial cells are the main victims of chronic hyperglycaemia. In these cells glucose uptake is directly proportional to the glucose concentration in the medium. Excessive intracellular glucose concentration increases the production of free radicals. Free radicals directly activate 4 biochemical pathways which are involved in the pathogenesis of chronic diabetic complications: the hexosamine pathway, the polyol pathway, the advanced glycation endproducts pathway and the activation of protein kinase C. A precapillary vasodilatation is consequent to the developed pseudo-hypoxia, which provides a haemodynamic basis for diabetic microangiopathy. New specific inhibitors of each of these pathways are studied in clinical trials. Based on these pathophysiological observations, a new treatment strategy is proposed for diabetic microangiopathy.

Antioxidants↗
PubMed2001

[Prediction, screening and treatment of renal complications of diabetes].

Diabetic nephropathy is a glomerular disease, which causes most of premature mortality observed in diabetic patients. The risk of diabetic nephropathy is not entirely accounted for by diabetes duration and control. Diagnosis has been improved by sensitive assays for urinary albumin (microalbuminuria). Treatment relies up on early and liberal use of several antihypertensive agents. Among them, angiotensin I converting enzyme inhibitors rank first, because of their efficacy.

Adult↗
PubMed2001

[Mycobacterium kansasii skin infection at insulin injection sites].

BACKGROUND: Insulin injection sites rarely become infected. We report a case of Mycobacterium kansasii infection at the sites of insulin injection. CASE REPORT: An 84-year-old woman with insulin-dependent diabetes consulted for lesions on the anterior aspect of the thighs. She had papulonodules at the sites of insulin injection. These lesions progressed to hard fibrinonecrotic ulcerations with a raised erythematous border. There were no enlarged nodes locally. Laboratory tests were normal. Bacteriological samples were negative at direct examination. Histology was not specific. The biopsy cultures finally found an atypical mycobacteria, Mycobacterium kansasii. The clinical course was favorable with clarithromycin alone. DISCUSSION: Only 35 cases of Mycobacterium kansasii skin infections have been reported in the literature. This is the first case observed in a diabetic subject and the first treated with clarithromycin alone. This case illustrates the potential, though exceptional, risk of insulin bottle contamination by an environmental germ.

Aged↗
PubMed2001

[Insulin sensitivity, blood pressure and cardiovascular diseases].

Essential hypertension is one of the main components of the insulin resistance syndrome. Blood pressure levels are especially critical for the cardiovascular prognosis of patients with diabetes. However, whether the relationship between blood pressure levels and insulin sensitivity is causal, or just an association, remains debatable. In this study, this relationship is explored through the data of currently available clinical trials.

Blood Pressure↗
PubMed2001

[Insulin and weight gain: myth or reality?].

Most patients with type 2 diabetes gain weight when treated with insulin. Weight gain is observed when insulin is introduced after oral agents have failed, but also when insulin is introduced shortly after the diagnosis of diabetes. The mechanisms of this weight gain are incompletely understood, but reduction of energy lost by glucosuria and reduction of energy needed for glucose production are main determinants. The same reasons apply to the weight gain observed at the beginning of treatment with sulfonylureas, even though patients usually gain less weight with sulfonyulreas than with insulin. In the UKPDS, at 10 years of the study, patients treated with insulin gained 2 kg more, i.e. 2.5% of the average weight of patients included in the trial, than patients treated with sulfonylureas. The reasons of the excess of weight gain with insulin as compared with sulfonylureas remain unclear. Patients with type 2 diabetes treated with insulin gain weight only during the first 2-3 years after insulin introduction. The weight stabilizes thereafter. Type 2 diabetes usually remains unknown for years before diagnosis and patients may lose weight during this long period of time preceding diagnosis. It is hypothesized that the weight gain observed after the introduction of insulin may simply correspond to the reexpression of the physiologically controlled body weight.

Diabetes Mellitus, Type 2↗
PubMed2000

[Is diabetes mellitus a sufficient condition to suspect hemochromatosis?].

Genetic Hemochromatosis (GH) is a highly prevalent autosomal recessive disorder, which outcome has been dramatically improved by early phlebotomy. Attempts to screen for the disease, using biological and genetic approaches, are currently under evaluation. Diabetes mellitus often complicates GH. However, as it occurs late in the course of the disease, in most cases when cirrhosis is already present, its usefulness for the screening of GH seems reduced. Diabetes mellitus, when isolated, appears also as a poor predictor of hemochromatosis. Indeed, the risk of being carrier of the disease is not increased in diabetic patients compared with non diabetic sujects. This risk is however highly enhanced by the co-existence of cirrhosis. Thus, in the face of a newly diagnosed diabetes mellitus, the search for hemochromatosis must be performed only when it associates with cirrhosis or with other evocative clinical conditions.

Diabetes Complications↗
PubMed1999

[Type 1 diabetes mellitus].

POSITIVE DIAGNOSIS: Among the various diseases leading to chronic hyperglycemia, type 1 diabetes mellitus is distinctive by the presence of specific autoantibodies. The common from of type 1 diabetes mellitus is insulin-dependant diabetes, but type 1 diabetes may also present as non-insulin-dependent. In order to predict insulin-dependence and screen for associated autoimmune diseases, search for autoantibodies is required in all patients with diabetes, whatever the clinical presentation. COMPLEX PATHOPHYSIOLOGY: Diabetes mellitus is a multifactorial disease implicating of environmental and genetic factors leading to breakdown immune tolerance. LONG PRECLINICAL PHASE: Chronic hyperglycemia is preceded by a long preclinical phase during which the only observable anomalies result from activation of the immune system. With the development of simplified techniques for detecting autoantibodies, it would be reasonable to foresee large-scale screening. ONGOING SECONDARY PREVENTION TRIALS: The goal is to prevent the development of chronic hyperglycemia by intervening early, during the infraclinical phase, in patients with signs of immune activation. AT THE TIME OF DIAGNOSIS: When diabetes is discovered, intensive insulin therapy helps preserve residual insulin secretion and guarantees better long-term metabolic control.

Chronic Disease↗
PubMed1998

Mutation screening in 18 Caucasian families suggest the existence of other MODY genes.

Maturity-onset diabetes of the young (MODY) is a heterogeneous subtype of non-insulin-dependent diabetes mellitus characterised by early onset, autosomal dominant inheritance and a primary defect in insulin secretion. To date five MODY genes have been identified: hepatocyte nuclear factor-4 alpha (HNF-4alpha/MODY1/TCF14) on chromosome 20q, glucokinase (GCK/MODY2) on chromosome 7p, hepatocyte nuclear factor-1 alpha (HNF-1alpha/MODY3/TCF1) on chromosome 12q, insulin promoter factor-1 (IPF1/MODY4) on chromosome 13q and hepatocyte nuclear factor-1 beta (HNF-1beta/MODY5/TCF2) on chromosome 17cen-q. We have screened the HNF-4alpha, HNF-1alpha and HNF-1beta genes in members of 18 MODY kindreds who tested negative for glucokinase mutations. Five missense (G31D, R159W, A161T, R200W, R271W), one substitution at the splice donor site of intron 5 (IVS5nt + 2T-->A) and one deletion mutation (P379fsdelT) were found in the HNF-1alpha gene, but no MODY-associated mutations were found in the HNF-4alpha and HNF-1beta genes. Of 67 French MODY families that we have now studied, 42 (63%) have mutations in the glucokinase gene, 14 (21%) have mutations in the HNF-1alpha gene, and 11 (16%) have no mutations in the HNF-4alpha, IPF1 and HNF-1beta genes. Eleven families do not have mutations in the five known MODY genes suggesting that there is at least one additional locus that can cause MODY.

Adult↗