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Biomedical subjects

J F Gautier

Publications and source records attributed to J F Gautier.

At least 19 recordsLinked to original sources
PubMed2005

Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes.

Incretin hormones are defined as intestinal hormones released in response to nutrient ingestion, which potentiate the glucose-induced insulin response. In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide GIP, and glucagon-like peptide-1 GLP-1. GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. Their effect is mediated through their binding with specific receptors, though part of their biological action may also involve neural modulation. GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. As the insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide was a candidate as a therapeutic agent for this disease. A number of pharmacological strategies have been developed to provide continuous delivery of GLP-1 and to prevent degradation of GLP-1, including continuous administration of GLP-1, DPP-IV inhibitors and DPP-IV resistant GLP-1 analogues. Recent results of the most clinically advanced incretin mimetics confirmed their efficacy to improve glycemic control in type 2 diabetic patients. Further results are expected to confirm the efficacy/safety profile of these compounds, and to find their place in the therapeutic strategy of type 2 diabetes.

Diabetes Mellitus, Type 2↗
PubMed2005

Is capillary ketone determination useful in clinical practice? In which circumstances?

A new method is now available to measure capillary levels of 3-hydroxybutyrate (3HB), one of the three ketone bodies. It is a quantitative and enzymatic test that uses the same equipment as for home capillary blood glucose determination but with specific strips. In comparison to urine ketone test, there is no false negative or false positive results, it is highly correlate to standard automate assays and patients find it more acceptable. Clinical implementations of this new test begin to be reported. Some studies showed an advantage of ketonemia versus ketonuria measurement to detect and to treat diabetic ketoacidosis in the emergency room. In diabetic patients treated with continuous subcutaneous insulin infusion, ketonemia seems to be more relevant to detect lack of insulin. In the current care of patient with type 1 diabetes and especially in children blood ketone test is more effective than urine ketone test to prevent hospitalisation during sick days. For other situations such as diabetic pregnancy or type 2 diabetes, more data are needed to determine if capillary measurement of 3HB is really useful. This new test is easier and less unpleasant than doing urinary test but it is still far more expensive. Further clinical studies are needed to define whether self 3HB monitoring should substitute urinary test in outpatient care.

Biomarkers↗
PubMed2005

Subcutaneous insulin resistance successfully circumvented on long term by peritoneal insulin delivery from an implantable pump in four diabetic patients.

UNLABELLED: Extreme subcutaneous insulin resistance is a rare syndrome characterized by a severe resistance to subcutaneous (S/C) insulin together with persistence of normal or near normal intravenous (IV) insulin sensitivity. Its pathophysiology is unknown, although increased insulin degrading activity has been reported in the S/C adipose tissue fraction in some cases. Until now, proposed treatments have been disappointing. We report 4 cases who were successfully treated by intraperitoneal (IP) route. METHODS: The diagnosis of subcutaneous insulin resistance was based upon following combined conditions: resistance to hypoglycaemic action of subcutaneous insulin but normal or near normal sensitivity to IV or IP insulin. RESULTS: 4 patients among those followed by EVADIAC group met these criteria: 3 with type 1 diabetes (C peptide=0), the last one with unexplained non insulin-deficient diabetes (no anti-GAD antibodies, C peptide=5 ng/ml). All of them had been treated with subcutaneous insulin therapy without success despite huge doses (up to 4000 IU/day in two patients). The 3 type 1 diabetic patients presented with a history of repeated ketoacidosis episodes. A treatment of insulin mixed with aprotinin had been proposed to 2 patients without success. The IV insulin sensitivity was proved to be normal in two patients by euglycaemic clamp data. A skin biopsy was performed in 1 patient. An accumulation of insulin in the derma was revealed with no increase of degradation products of insulin. In these 4 patients, a dramatic improvement of diabetes control was obtained by IP insulin delivery from an implantable pump (HbA1c decrease by at least 3%). CONCLUSION: Although pathophysiology of the subcutaneous insulin resistance syndrome remains unexplained, our data show that intra-peritoneal insulin therapy from an implantable pump allows diabetes control in patients affected by this uncommon but severely disabling condition.

Adult↗
PubMed2004

[Physical activity as a therapeutic tool in type 2 diabetes: the rationale].

Physical exercise is an important component of type 2 diabetes mellitus management. Acute physical exercise, on a day by day basis, has a clear hypoglycaemic effect. Physical exercise, on a regular basis at a sufficient level, has numerous favourable effects: improvement of glycaemic control (HbA1c) and insulin sensitivity, decrease of visceral fat mass, increase of skeletal muscle mass, favourable effects on various cardiovascular risk factors (arterial pressure, HDL-cholesterol, triglycerides, etc.). However, precise characteristics of physical exercise to be advised in type 2 diabetic patients (type of exercise, frequency, intensity, etc.) are still a matter of debates, as well as lack of practical guidance in/or differences between the various current recommendations. The crucial point, however, remains their feasibility, as well as the lack of long term patient's motivation and compliance which may partly explain the current low level of physical exercise observed in type 2 diabetic patients.

Blood Glucose↗
PubMed2003

Marital status and family size of type 1 diabetic patients in a French cohort.

OBJECTIVE: To compare the marital status, the number of offspring and the cumulative incidence of type 1 diabetes in offspring of type 1 diabetic men and women. METHODS: From the database of patients attending our department, we reviewed the files of all the 352 subjects aged >=40 years with type 1 diabetes and compared male and female patients for whom age, age at diagnosis of diabetes, marital status, socio-economic status, number and age of offspring, diagnosed type 1 diabetes in the offspring could be obtained from patient's record and/or direct interview (86 males and 78 females). RESULTS: In this population, 73% of women and 81% of men were married or living a marital life (NS), and 35% of women versus 8% of men had no offspring (P<0.0001). The proportion of parents with 2 offspring or more was 43% in females and 61% in males (p=0.03) and was not related to the socio-economic status. The number of offspring with diagnosed type 1 diabetes was small (8/229) and did not show significant association with gender of the parent, with a cumulative incidence of 3.2 and 3.7% in offspring of type 1 diabetic mothers and fathers respectively. CONCLUSION: Type 1 diabetic women born before 1960 had fewer children than men. In this cohort, there was no difference in the cumulative incidence of type 1 diabetes in offspring of type 1 diabetic men and women despite reduced family size in women.

Adult↗
PubMed2002

Metabolic and immunogenetic prediction of long-term insulin remission in African patients with atypical diabetes.

AIMS: We aimed to characterize a cohort of 'atypical' diabetic patients of sub-Saharan African origin and to analyse possible determinants of long-term remission. METHODS: Over 6 years, we studied the clinical and therapeutic profile of 42 consecutive patients undiagnosed or untreated prior to inclusion presenting with cardinal features of diabetes mellitus. We measured insulin secretion and sensitivity at inclusion. Immunogenetic (anti-GAD, anti-ICA and HLA class II) markers of Type 1 diabetes were compared with a 90-non-diabetic unrelated adult African population. RESULTS: Twenty-one ketonuric patients (age 42 +/- 9 (sd) years; body mass index (BMI) 26 +/- 3 kg/m2) were initially insulin-treated (IT), and 21 non-ketonuric patients (age 38 +/- 8 years; BMI 26 +/- 5 kg/m2) had oral and/or diet therapy (NIT). Insulin could be discontinued in 47.6% (10/21) IT with adequate glycaemic control (HbA1c 6.7 +/- 1.3%), while insulin was secondarily started in 38.1% (8/21) NIT in expectation of better control. The initial basal (odds ratio (OR) 9.1, 95% confidence interval (CI) 1.3-64.4) and stimulated C-peptide (OR 8.17, 95% CI 1.5-44.1) were independently associated with remission. Insulin resistance was present in all the groups, more marked in the insulin-treated NIT. Anti-GAD antibodies and ICA were rare, but 38.1% IT vs. 1.1% controls had Type 1 diabetes HLA susceptibility haplotypes (P < 0.001) without significant difference between the subgroups. CONCLUSION: Prolonged discontinuation of insulin is frequent in African diabetic patients initially presenting with signs of insulinopenia. In our patients, long-term insulin therapy was not associated with immunogenetic markers of Type 1 diabetes. The initial measure of insulin secretion seemed a good predictor of long-term remission.

Acute Disease↗
PubMed2002

Diabetes in Africans. Part 2: Ketosis-prone atypical diabetes mellitus.

Diabetes is increasing with ageing and changes in lifestyle in populations of African ancestry as described in the first part of this review. Apart from classical type 1 and Type 2 diabetes, atypical presentations are observed in these populations, especially "tropical" and "ketosis-prone" atypical diabetes. Ketosis-prone atypical diabetes that has been classified by ADA as idiopathic Type 1 diabetes or Type 1b is the most common atypical form. It is characterised by an acute initial presentation with severe hyperglycaemia and ketosis, as classical Type 1 diabetes. In the subsequent clinical course after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. Metabolic studies showed a markedly blunted insulin secretory response to glucose, partially reversible with the improvement of blood glucose control. Variable levels of insulin resistance are observed, especially in obese patients. Pancreatic B-cell autoimmunity is an exceptional finding. Association with type 1 susceptibility HLA alleles is variable. The molecular mechanisms underlining the insulin secretory dysfunction are still to be understood and may involve gluco-lipotoxicity processes, glucagon dysregulation, effect of stress, or may be genetically determined. The present review summarises the available clinical and metabolic features and suggests some pathogenetic hypotheses and principles of management for the ketosis-prone atypical diabetes of the Africans.

Africa↗
PubMed2002

[Determinants and control of energy expenditure].

Obesity is a risk factor for many diseases including cardio-vascular disease, type 2 diabetes, and certain forms of cancer, among others. Obesity results from a chronic imbalance between calorie intake and energy expenditure. Genetic factors obviously play an important role in weight gain, but only in certain environments. The principal cause of the obesity epidemic is not clear: is obesity due to excessive food intake, a dynamic reduction in energy expenditure, or an association of these two factors? However, most obese subjects gain weight because of an inaptitude to adjust energy expenditure in response to excessive food intake. In this article, we review briefly the respective role of genes and environment in the development of obesity, then describe metabolic risk factors involved. Longitudinal studies conducted in Pima Indians have demonstrated that a relative decrease in basal metabolism, weak lipid oxidation in the fasting state, reduced spontaneous physical activity, and lower sympathetic nervous system activity are risk factors for obesity. Unlike our growing knowledge of food intake regulation, little is known about the control of energy expenditure. New discoveries should provide information on obesity susceptibility genes and increase the chances of developing new anti-obesity treatments.

Animals↗
PubMed2001

Effect of satiation on brain activity in obese and lean women.

OBJECTIVE: To investigate the response of the brains of women to the ingestion of a meal. RESEARCH METHODS AND PROCEDURES: We used measures of regional cerebral blood flow (rCBF), a marker of neuronal activity, by positron emission tomography to describe the functional anatomy of satiation, i.e., the response to a liquid meal in the context of extreme hunger (36-hour fast) in 10 lean (BMI < or = 25 kg/m(2); 32 +/- 10 years old, 61 +/- 7 kg; mean +/- SD) and 12 obese (BMI > or = 35 kg/m(2); 30 +/- 7 years old, 110 +/- 14 kg) women. RESULTS: In lean and obese women, satiation produced significant increases in rCBF in the vicinity of the prefrontal cortex (p < 0.005). Satiation also produced significant decreases in rCBF in several regions including the thalamus, insular cortex, parahippocampal gyrus, temporal cortex, and cerebellum (in lean and obese women), and hypothalamus, cingulate, nucleus accumbens, and amygdala (in obese women only; all p < 0.005). Compared with lean women, obese women had significantly greater increases in rCBF in the ventral prefrontal cortex and had significantly greater decreases in the paralimbic areas and in areas of the frontal and temporal cortex. DISCUSSION: This study indicates that satiation elicits differential brain responses in obese and lean women. It also lends additional support to the hypothesis that the paralimbic areas participate in a central orexigenic network modulated by the prefrontal cortex through feedback loops.

Adult↗
PubMed2001

Exercise training-induced triglyceride lowering negatively correlates with DHEA levels in men with type 2 diabetes.

OBJECTIVE: To investigate the effect of an exercise training program on lipid profile in correlation with DHEA level and body weight and body composition in type 2 diabetic men. DESIGN: Longitudinal, controlled clinical intervention study with exercise training consisting of an 8 week supervised program of aerobic exercise (75% VO(2) peak, 45 min), twice a week and intermittent exercise, once a week, on a bicycle ergometer. SUBJECTS: Sixteen men (age 45.4+/-7.2 y (mean+/-s.d.), HbA1c 8.15+/-1.7%, body mass index (BMI) 29.6+/-4.6 kg/m(2)) were randomly divided into two groups: trained group (n=8) and control group (n=8). MEASUREMENTS: Lipid, apo- and lipoprotein and DHEA concentrations. Cross-sectional areas of subcutaneous and visceral adipose tissue and mid-thigh muscle by magnetic resonance imaging. RESULTS: Training decreased visceral (153.25+/-38.55 vs 84.20+/-21.30 cm(2), P<0.001), subcutaneous (241.55+/-49.55 vs 198.00+/-39.99 cm(2), P<0.001) adipose tissue area and triglyceride levels (2.59+/-1.90 vs 1.79+/-1.08 nmol/l, P<0.05) and increased mid-thigh muscle cross-sectional area (148.30+/-36.10 vs 184.35+/-35.85 cm(2), P<0.001), and DHEA levels (11.00+/-3.10 vs 14.25+/-4.10 nmol/l, P<0.05) with no modification in body weight. Changes in triglycerides were negatively correlated with changes in DHEA (r=-0.81, P=0.03). This correlation was independent of changes in abdominal fat distribution. CONCLUSION: Training decreases abdominal fat depots, improves muscular mass and affects favourably triglyceride and DHEA levels. Changes in triglycerides and DHEA were inversely related.

Adipose Tissue↗
PubMed2001

Low acute insulin secretory responses in adult offspring of people with early onset type 2 diabetes.

The offspring of Pima Indians with early onset type 2 diabetes are at high risk for developing diabetes at an early age. This risk is greater among those whose mothers were diabetic during pregnancy. To define the metabolic abnormalities predisposing individuals in these high-risk groups to diabetes, we conducted a series of studies to measure insulin secretion and insulin action in healthy adult Pima Indians. In 104 normal glucose-tolerant subjects, acute insulin secretory response (AIR) to a 25-g intravenous glucose challenge correlated with the age at onset of diabetes in the mother (r = 0.23, P = 0.03) and, in multiple regression analyses, the age at onset of diabetes in the father (P = 0.02), after adjusting for maternal age at onset and after allowing for an interaction between these terms. In contrast, insulin action (hyperinsulinemic glucose clamp) did not correlate with the age at onset of diabetes in the parents. To determine whether early onset diabetes in the parents affected insulin secretion in the offspring across a range of glucose concentrations, responses to a stepped glucose infusion were measured in 23 subjects. Insulin secretion rates were lower in individuals whose mothers had developed diabetes before 35 years of age (n = 8) compared with those whose parents remained nondiabetic until at least 49 years of age (n = 15) (average insulin secretory rates: geometric mean [95% CI] 369 [209-652] vs. 571 [418-780] pmol/min, P = 0.007). Finally, the AIR was lower in individuals whose mothers were diabetic during pregnancy (n = 8) than in those whose mothers developed diabetes at an early age but after the birth of the subject (n = 41) (740 [510-1,310] vs. 1,255 [1,045-1,505] pmol/l, P < 0.02). Thus, insulin secretion is lower in normal glucose tolerant offspring of people with early onset type 2 diabetes. This impairment may be worsened by exposure to a diabetic environment in utero.

Adipose Tissue↗
PubMed2001

[Physical exercise and insulin sensitivity].

Physical exercise is known to be essential in the treatment of type 2 diabetes. An increased glucose uptake is evidenced during acute muscular exercise, over the post-exercise period, and following physical training. In this paper, we review metabolic and molecular aspects of physical exercise. We emphasize on the non-insulin dependent glucose transport induced by muscular contraction, which involves AMP-activated protein kinase. The discovery of this pathway is likely to open new therapeutic targets for type 2 diabetes.

Biological Transport↗