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Biomedical subjects

P Passa

Publications and source records attributed to P Passa.

At least 19 recordsLinked to original sources
PubMed1992

Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young.

Maturity-onset diabetes of the young (MODY), characterised by non-insulin-dependent diabetes mellitus (NIDDM) with an early age of onset, is a genetically heterogeneous disorder. In most MODY kindreds described in France, chronic hyperglycaemia is caused by mutations in the gene encoding pancreatic beta-cell and liver glucokinase (GCK). We here report the beta-cell secretory profiles of nine patients from four GCK-linked MODY kindreds. First-phase insulin secretion assessed by an intravenous glucose test was comparable in patients and seven controls. However, beta-cell secretory response to continuous glucose stimulus during a hyperglycaemic glucose clamp was significantly reduced: mean plasma insulin values of 12 (SD 7) vs 40 (11) mU/l (p = 0.0001) and mean plasma C-peptide values 1.20 (0.30) vs 2.61 (0.37) (p = 0.0001). This secretory profile is different from those for NIDDM with late age of onset or MODY not linked to GCK. Fasting plasma insulin and C-peptide in patients were inappropriately low in relation to concomitant plasma glucose level. Furthermore, during a hyperinsulinaemic euglycaemic clamp, endogenous insulin secretion at euglycaemia (5 mmol/l) was suppressed in patients but not in controls. These results suggest that mutant GCK may lead to chronic hyperglycaemia by raising the threshold of circulating glucose level which induces insulin secretion. These data provide the first demonstration of a primary pancreatic secretory defect associated with a form of NIDDM.

Adolescent↗
PubMed1992

Hyperinsulinemia, insulin resistance and essential hypertension.

Glucose intolerance and noninsulin-dependent diabetes are commonly associated with hypertension. Epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. When hypertensive patients whether obese or of normal weight are compared with matched normotensive control subjects, an increased plasma insulin response to a glucose challenge is consistently observed. Studies using insulin glucose clamp techniques in combination with tracer glucose infusion and indirect calorimetry have demonstrated that the insulin resistance in hypertensive subjects is located in muscles and restricted to glycogen synthesis. The relations between hyperinsulinemia and blood pressure do not prove that the relationship is a causal one. However, at least four mechanisms may link hyperinsulinemia with hypertension: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport and proliferation of vascular smooth muscle cells. Diuretics and beta-blockers may enhance insulin resistance, which is not affected by calcium antagonists, but decreased by the ACE inhibitor captopril. Weight reduction and regular physical exercise can improve insulin sensitivity and decrease blood pressure values. These nonpharmacological interventions should be more strongly recommended to diabetic and nondiabetic hypertensive patients.

Antihypertensive Agents↗
PubMed1992

Non-invasive identification of severe coronary artery disease in patients with long-standing diabetes mellitus.

OBJECTIVES: To detect severe coronary artery disease in asymptomatic middle-aged diabetic patients exposed to coronary artery disease risk factors. PATIENTS AND METHODS: Forty-four middle-aged patients (30 to 65 years of age) with a known duration of diabetes exceeding 10 years and at least one additional cardiovascular risk factor were studied. Patients were free of anginal chest pain and had a normal 12-lead ECG at rest. All patients underwent 24-hour ambulatory ECG, maximal bicycle exercise electrocardiography and intravenous dipyridamole thallium myocardial scintigraphy. If one of these 3 non-invasive tests revealed signs of myocardial ischaemia, a coronary angiography was performed. RESULTS: Non-invasive investigation yielded the diagnosis of myocardial ischaemia in 9/44 patients (20%). Six of the 9 patients had significant coronary artery stenoses (> 70% narrowing) and 5 exhibited severe triple-vessel disease. With dipyridamole thallium scintigraphy, the positive predictive value for diagnosis of coronary artery disease was optimal. CONCLUSION: In diabetic patients with additional coronary risk factors, periodical thorough clinical examination and resting ECG may fail to detect severe coronary disease. More sophisticated cardiovascular non-invasive tests should then be proposed as part of the periodical care of these patients.

Coronary Angiography↗
PubMed1979

[The effects of acebutolol on endocrine and metabolic reactions induced by acute hypoglycaemia. Study in normal subjects and in insulin-dependent diabetics (author's transl)].

Six normal subjects and six normotensive insulin-dependent diabetics underwent two insulin hypoglycaemia tests after administration for three days of either a placebo or of acebutolol--a cardioselective beta-blocker--at a dose of 400 mg per day. The order in which the tests were performed was decided by random selection. Acebutolol suppressed the tachycardia which occurred as a reaction to hypoglycaemia but did not interfere with other warning symptoms and signs. In both normal subjects and diabetics, acebutolol neither worsened the initial hypoglycaemia nor did it delay a return to normal values. The increase in lactate levels following hypoglycaemia was not reduced by acebutolol but free fatty acid rebound was suppressed. Hormonal responses (glucagon, cortisol, growth hormone) were unaffected by the beta-blocker. If they are confirmed by long term studies, these results would suggest that acebutolol is safer to use than non-cardioselective beta-blockers in the treatment of coronary insufficiency and of hypertension in diabetics exposed to the risk of hypoglycaemia.

Acebutolol↗
PubMed1979

[HbA1c: need of its dosage in diabetics (author's transl)].

HbA1c is the product of a slow, virtually irreversible reaction, occurring continuously throughout the 120 day life-span of the erythrocyte, between HbAo and glucose. It has been shown to represent the time-averaged blood glucose concentration of the preceeding 2 month period, and is independant of day to day fluctuations in the blood glucose concentration. HbA1c therefore acts as a biochemical marker and permits clinicans, by one test, to judge the quality of the diabetic control, in their patients.

Blood Glucose↗
PubMed1979

Influence of hepatic insufficiency in pharmacokinetics of drugs: example for an anthranilic diuretic.

Hepatic insufficiency is responsible for numerous modifications of drug metabolism and pharmacokinetics, because the liver is the most important organ for the transformation and, with the kidney, elimination of drugs. Pharmacokinetics of furosemide, an anthranilic diuretic, was compared in normal subjects and cirrhotics with hepatic insufficiency, after oral administration. In patients, we observed few modifications of the bioavailability. The total elimination of the drug was normal when the urinary excretion compensated a slight reduction in biliary secretion, but when this reduction was important the total clearance of furosemide decreased. In urine, the elimination time was lengthened, but the percentage of excretion was about the same as for normal subjects. The pharmacological effects were also modified for cirrhotics with decrease of sodium and water excretion, for the same blood concentration of drug as in controls. Also, we observed a shift between the salidiuretic effect and the blood concentration in patients, when there was an exact concordance of these times in control subjects. Two hypotheses have been proposed to explain this phenomenon: (1) modifications in hepatic metabolism or, (2) in drug protein binding.

Adult↗
PubMed1978

In vivo platelet kinetics in 31 diabetic patients. Correlation with the degree of vascular impairment.

In vivo platelet survival was estimated, in 31 diabetic patients, using 51Cr-labelled autologous platelets. A mathematical analysis attempted to measure the "potential" life span (senescence process) and the degree of a superimposed aleatory destruction (consumption process). The potential platelet life span in diabetics did not differ from normal values. However, excessive consumption was observed in one third of the studied cases, without correlation with the age of the patients, the clinical duration of diabetes, and the degree of vascular impairment. Thus, platelet kinetic studies did not provide presently useful indications, in a particular patient, regarding the prognosis of the vascular disease, and the justification of anti-aggregant therapy.

Blood Platelets↗
PubMed1978

[Familial idiopathic haemochromatosis with diabetes. Study of glucagon and growth hormone secretions (author's transl)].

In the course of familial idiopathic haemochromatosis with diabetes, after stimulation with arginine, the alpha cell responds perfectly to stimulation, in contrast to the case of chronic pancreatic diseases. After an oral glucose load, there is no reduction in plasma glucagon concentrations, and a paradoxal increase is sometimes seen. These results are quite similar to those reported in common diabetes. Secretion of growth hormone after an infusion of arginine and insulin hypoglycaemia seem to be significantly reduced in comparison with normal subjects and those suffering from common diabetes, paired and explored using the same protocol. This may perhaps explain the low degree of severity and slow course of associated vascular disease.

Adult↗
PubMed1978

Idiopathic hemochromatosis: linkage with HLA.

Forty-eight unrelated patients with idiopathic hemochromatosis were found to have a significantly higher frequency of three HLA antigens (A3, B7 and B14) than 591 healthy controls. A significant association between HLA haplotypes and disease segregations was demonstrated in 14 family studies. A recessive inheritance of a strongly A3-linked disease gene responsible for abnormal iron stores in the heterozygote state is postulated. The lod score value (4.415 for theta = 0.025) is compatible with this hypothesis. However, the excess of HLA-identical pairs of affected sibs does not exclude the possibility of a pseudo-recessiveness due to two codominant genes both HLA-linked. For the first time, a means of screening for high risk subjects is available and therefore offers the possibility of a preventive approach.

Genes, Dominant↗
PubMed1978

[Idiopathic hemochromatosis linkage with the HLA system (author's transl)].

Fourteen selected families containing two or more subjects suffering from idiopathic hemochromatosis and 34 unrelated cases have been studied for their HLA markers. A 3 was present in 75% of the unrelated cases vs 26% in the normal population (p less than 10(-8)). The frequencies of B 7 (38% vs 19%) and B 14 (23% vs 9%) were also increased (p lessthan 0,05). Inevitably, in most cases both antigens in the B locus were associated with A 3. Seven of nine affected sib pairs shared both HLA haplotypes, while two shared only one. Significant association between HLA haplotypes and diseases segregation has been demonstrated in family studies. These facts are consistent with the recessive inheritance of a strongly A 3 linked "disease" gene responsible for abnormal iron stores in the heterozygote state. This hypothesis would account for 64% of our present cases. Most of discordances (26%) were females who are physiologically protected, or children under 17 who might later develop the disease. The remaining 10% of disordant cases could be explained by crossing-over between "disease" gene and HLA loci or by an heterogeneity of the disease. This provides a method for screening for high risk subjects and perhaps an opportunity for anticipatory prevention.

Adolescent↗
PubMed1977

Glucagon secretion in diabetic patients with idiopathic haemochromatosis.

The aim of the present investigation was to determine in patients with idiopathic haemochromatosis whether diabetes is of the primary type or secondary to pancreatic injury due to iron deposition. For this purpose, plasma glucagon concentrations were determined following arginine infusion or an oral glucose load in eight patients with diabetes and idiopathic haemochromatosis. The enhanced glucagon response to arginine and the nonsuppressibility of glucagon secretion by oral glucose found in these patients were similar to the results found in the same tests performed in our previous series of patients with "idiopathic" diabetes and at variance with those reported by others in patients with chronic pancreatitis.

Adult↗