Influence of endogenous and environmental factors on variations of serum lipoprotein (a) concentrations in a large population of insulin-treated diabetic patients.

Variations of serum Lp(a) concentrations were studied in a large population of insulin-treated diabetic patients in relation to the type of diabetes, insulin treatment and long-term complications. Lp(a) concentrations were measured by immunonephelometry in 740 diabetic patients [493 insulin-dependent diabetic (IDDM) patients and 247 insulin-treated Type 2 diabetic (ITD) patients]. Concentrations and distributions were compared with those of 128 non-diabetic controls. Correlations were investigated with lipidic and glycaemic parameters, daily lipid intake, body mass index (BMI), macrovascular and nephropathic complications, and insulin therapy. Both groups of insulin-treated patients (IDDM and ITD) displayed significantly higher Lp(a) concentrations when compared to controls. No relationship was found with macrovascular complications and nephropathy, except in IDDM patients in whom Lp(a) was elevated when creatinine concentration was above 120 mumol/L. Mean variations of Lp(a) were correlated with BMI and triglyceride variations in IDDM patients and only with triglycerides in ITD patients. These results suggest a direct and/or indirect (via serum triglycerides) potential role of exogenous insulin in the modulation of serum Lp(a) concentrations. BMI and lipid daily fat intake could be considered as additional modulating factors of Lp(a) serum concentrations in ITD patients.

Short-term intensive insulin therapy in insulin-requiring diabetes: effectiveness and factors predicting success.

Insulin-requiring diabetes (IRD) is a condition of permanent blood glucose imbalance which occurs despite a regulated diet and treatment with maximum doses of oral anti-diabetic drugs (glibenclamide 15 mg/d + metformin 1,700 mg/d). This report describes the results of a 2-year prospective study in 75 IRD patients treated to eliminate their insulin requirement. All had residual endogenous insulin secretion (REIS) (urinary C peptide > 80 micrograms/24 h and/or basal C peptide > 2.4 ng/ml) and were treated for 10 days by subcutaneous insulin infusion via a portable pump. REIS was measured, and insulin resistance was determined by an insulin tolerance test (ITT) to define their insulin sensitivity index (DG/G) before and after 10-day intensive therapy. The patients were monitored as outpatients, and the attempt at remission was considered to be a failure (F) or a success (S). Thirty of the 75 patients (40%) were in remission at 1 year, and 14/67 (21%) at 2 years. No clinical criterion differentiated successes from failures at 1 year, nor was the initial degree of blood glucose imbalance or the REIS predictive of the metabolic changes that occurred after insulin therapy. However, the drop in the insulin requirement (IR) (-26% for F and -39% for S, p < 0.05) and the increases in the DG/G index (+68 +/- 51% for F and 176 +/- 50% for S, p < 0.01) after insulin therapy were indicative of their condition 1 year later. Receiving operating characteristic curves showed that a 35% decrease in IR and an 80% increase in DG/G were indicative of a successful outcome at 1 year, with a specificity and sensitivity of about 70%. It is concluded that a decrease in daily IR and an increase in the DG/G index during insulin treatment are prognostic indicators of the course of insulin-requiring diabetics after temporary intensive insulin treatment.

Serum lipoprotein (a) concentrations in a population of 819 non-insulin-dependent diabetic patients.

Variations in serum Lp(a) concentrations were studied in a large population of non-insulin-dependent diabetic (NIDDM) patients in relation to long-term complications. Lp(a) concentrations were measured by immunonephelometry in 819 NIDDM subjects and compared with those of 128 controls. Correlations were investigated relative to plasma lipid and glycaemic parameters, body mass index (BMI) and macro- and microvascular complications. Mean absolute and relative variations of Lp(a) concentrations were studied in a subgroup of 245 patients over a one-year period. No significant differences were found between Lp(a) concentrations in NIDDM and control subjects. No relationship was evidenced with macrovascular and microvascular complications or glycaemic control. Mean relative Lp(a) variations were correlated with BMI and absolute and relative variations in triglyceridaemia. These results confirm the absence of any alterations of Lp(a) concentrations in a large cohort of NIDDM patients, either with or without micro- and macrovascular complications, but suggest a particular modulatory role for BMI and serum triglyceride variations.

[Insulin tolerance tests]. / Tests de tolérance à l'insuline.

Impaired sensitivity to insulin is a frequent clinical situation and interest in measuring sensitivity to insulin has greatly increased since Reaven described the X syndrome in 1988. This syndrome is an association of increased serum triglycerides, high blood pressure, low levels of HDL and insulin resistance; affected patients have an increased risk of coronary artery disease. Several methods have been described to measure insulin resistance. They rely on the effect of insulin on glucose metabolism. The euglycaemic clamp interprets the interactive feedback control between insulin and glucose. Insulin is infused to reach a constant serum insulin level, then glucose is administered at predetermined levels. The blood glucose level thus corresponds to hepatic production and insulin sensitivity is expressed as the amount of glucose infused in mg/kglmin. Metabolic glucose clearance is the relationship between glucose consumption and blood glucose level during the test. This method is reliable, reproducible and eliminates the errors related to insulinindependent metabolism. Steady state plasma glucose relies on drugs which suppress endogenous insulin secretion. Glucose and insulin are then infused at constant rates and the resulting glucose and insulin levels express insulin sensitivity. This method is technically difficult to handle and is used less often. Bergman's minimal model and the modified insulin tolerance test offer other more practical and global methods with particular indications. Each method has its advantages and disadvantages in terms of precision, cost and duration. The choice of a method is basically made as a function of the clinical or research needs.

Study of the rate of early glucose disappearance following insulin injection: insulin sensitivity index.

The euglycaemic hyperinsulinaemic glucose clamp is usually considered as the reference technique to evaluate insulin sensitivity. As it is an expensive and time-consuming tool, we therefore tried to validate a simple insulin tolerance test (ITT) (IV bolus of 0.1 IU/kg of regular insulin, with glucose sampling at -5, 0, 3, 5, 7, 10 and 15 min) and to demonstrate its usefulness. Insulin sensitivity was measured by DG/G0 ratio (G0 = initial glycaemia, DG is the variation between G0 and the glycaemia obtained at 15 min by the calculation of the regression plot). We confirmed the existence of a correlation between the glucose uptake (mg/kg per min) evaluated by glucose clamp and the DG/G0 index (r = 0.9, P < 0.01). There was no stimulation of hormonal counter regulation during the test. The ITT was significantly correlated both with fasting insulin (r = -0.43, P < 0.01), and post-glucose load insulin concentration (r = -0.67, P < 0.01); each measurement expressing insulin sensitivity. Four groups of patients with different insulin sensitivity: controls, NIDDM, gynoid and android obese subjects, were clearly separated by ITT. We showed that fasting glycaemia and DG/G0 were correlated (y = 2.63/x - 0.093; r = 0.82, P < 0.01). These results suggest that ITT could be an easy, quick and low cost method to evaluate insulin resistance in clinical practice and epidemiological studies.

Roles of LH and insulin resistance in lean and obese polycystic ovary syndrome.

OBJECTIVE: The relationship between insulin resistance and hyperandrogenism led us to study insulin resistance in polycystic ovary syndrome (PCOS) in order to determine its prevalence and pathogenesis. DESIGN: Blood samples were taken on the 8th day after menses commenced. PATIENTS: Sixty-one women with PCOS, 30 with normal weight (BMI < 25 kg/m2) (group 1) and 31 with obesity (BMI > 26 kg/m2) (group 2) were studied. They were divided also according to LH level: group A, low or normal LH (n = 23) and group B, high LH (n = 38). Twenty lean control women and 16 obese control women were studied. MEASUREMENTS: Serum LH, testosterone, free testosterone, dehydroepiandrosterone, sex-hormone binding globulin, androstenedione, and fasting insulin were measured. Insulin sensitivity was explored by the insulin tolerance test (ITT). ITT was performed by bolus i.v. insulin of 0.1 IU/kg. Blood glucose was measured before (-5,0) and after injection (3, 5, 7, 10, 15 minutes). Insulin sensitivity was given by the ratio of glycaemic variation to initial blood glucose (delta G/G index). RESULTS: delta G/G was correlated with other insulin resistance parameters, particularly fasting insulin r = 0.40, P < 0.01. The PCOS groups had the following insulin resistances (mean +/- SEM) compared to matched groups: delta G/G lean PCOS vs lead controls: 0.45 +/- 0.02 vs 0.61 +/- 0.01, P < 0.001; delta G/G obese PCOS vs obese controls: 0.32 +/- 0.02 vs 0.40 +/- 0.01, P < 0.02. Insulin resistance was higher in group A than in group B: delta G/G 0.29 +/- 0.02 vs 0.45 +/- 0.02, P < 0.001. The prevalence of insulin resistance was 63% in lean PCOS and 51% in obese PCOS. Positive correlations between delta G/G index and LH were found in group 1 and 2, respectively r = 0.45, P < 0.01 and r = 0.55, P < 0.01. CONCLUSION: PCOS was associated with a significant decrease of insulin sensitivity, independent of obesity. The correlation between LH and insulin sensitivity suggests a complementary action in PCOS.

[Lipoprotein (a) and diabetes: relationship based on 224 cases]. / Lipoprotéine (a) et diabète: relations à propos de 224 observations.

Recent studies have suggested that Lp(a) is implicated in the high incidence of coronary heart disease in diabetic subjects, but data are still controversial. We therefore studied the distribution of plasma Lp(a), assayed by radial immunodiffusion, in a group of 224 diabetics and compared them to 92 non diabetic controls. Besides plasma Lp(a), TG and glucose were evaluated in 16 insulin-requiring diabetic patients before and after 10 days of normoglycaemia. The distribution of plasma Lp(a), as usually skewed to the left, was not different either between diabetic subjects and controls or between Type 1 and Type 2 diabetic subjects. No significant correlation was observed between Lp(a) and glycaemic control expressed by HbA1c. The sequence of normoglycaemia did not affect plasma Lp(a), no significant correlation between the variations of glycaemia and Lp(a) levels and the variations of triglyceridaemia and Lp(a) levels were found. Thus our group of diabetic subjects has a similar distribution of Lp(a) to controls. Lp(a) concentrations do not seem to be affected by chronic hyperglycaemia or rapid normalisation of glycaemic levels. However there is a strong need of standardization of Lp(a) assay before any definitive conclusion. As we have so far no efficient treatment for lowering Lp(a) in daily clinical practice, the energetic care of other associated vascular risk factors is needed.

[Relationship between lipoprotein(a) and non-insulin-dependent diabetes in 602 patients]. / Relations entre lipoprotéine (a) et diabète non insulinodépendant chez 602 patients.

Lipoprotein (a) status has been evaluated in a population of 602 non insulin-dependent diabetics and compared to 74 healthy controls. There was no significant difference in concentration and no obvious influence of glycaemic, coronarian or renal status.

Remission of insulin requirement in late secondary failure to oral hypoglycemic agents (IRD): results at 24 months and analysis of predictive factors.

Over the last four years, we have done a prospective study of insulin requiring diabetes (IRD). We offered 59 patients insulin therapy during 10 to 14 days by means of continuous subcutaneous insulin injection with the help of a pump in order to maintain the patient under oral hypoglycemic agents (OHA). We divided our population into two characteristic groups and isolated parameters that were predictive of post-insulin therapy evolution by means of C peptide assays. In one group, in 50% of cases, endogenous insulin production appeared impaired and could not be restored by insulin therapy. The patients in this group suffered a renewed drug failure within 3 months. In the other group, 50% of cases, endogenous insulin production was preserved and the CP/blood glucose level ratio improved. On insulin treatment interruption, we observed a significantly improved fasting blood glucose level and we observed decreased insulin needs. The patients, who were probably insulin resistant, suffered only late failures or went into remission, often for longer than one year. The data bring us to the logical conclusion of IRD heterogeneity. Only some of these patients can benefit from temporary insulin therapy and the remission attempt should be limited to them.

High permanent plasma adrenaline levels: a marker of adrenal medullary disease in medullary thyroid carcinoma.

Increases in urinary, plasma and tumour adrenaline have been previously observed in MEN II patients with phaeochromocytoma. However, the sensitivity of adrenaline for early detection of adrenal medullary disease has not been accurately evaluated. Twenty-five patients with medullary thyroid carcinoma (MTC) histologically confirmed but without clinical or biological evidence of phaeochromocytoma have been studied. Medullary adrenal status was evaluated by adrenal CT-scan. MIBG scintigraphy, determination of urinary VMA, metanephrines and total catecholamine levels, measurement of nyctohemeral plasma adrenaline or noradrenaline concentrations (every 2 h during 24 h) and clonidine suppression test. Four of the 25 patients had evidence of adrenal medullary disease in view of the coexistence of CT-scan, MIBG scintigraphy and plasma adrenaline abnormalities. Moderate adrenal enlargement (unilateral, n = 3; bilateral, n = 1) was observed on scans together with a high adrenal MIBG uptake (bilateral, n = 4). Among the urinary parameters studied, a minor MN increase was observed in only one of the four patients. Plasma adrenaline levels were significantly (P less than 0.01) different from those of the other 21 patients (mean + SD 115 + 110 pmol/l). This plasma adrenaline increase is reproducible and not suppressed by clonidine. Unilateral adrenalectomy performed in one patient confirmed a phaeochromocytoma and induced normalization of plasma adrenaline levels. In contrast, the plasma noradrenaline levels of the four patients were not statistically different from those of the other 21 patients. These data suggest that persistent high plasma adrenaline levels may be selectively increased in MTC patients together with a moderate adrenal CT-scan enlargement and a high adrenal MIBG uptake, despite a normal urinary excretion of total catecholamines and catecholamines metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anesthesia for cesarean section and excision of pheochromocytoma caused by Sipple's syndrome]. / Anesthésie pour césarienne et exérèse d'un phéochromocytome dû au syndrome de Sipple.

A case of a 23-year-old primigravida with a tumour of the left adrenal gland and a medullary thyroid carcinoma is reported. Her blood pressure remained at about 100/60 mmHg throughout pregnancy. She was scheduled for elective Caesarean section combined with removal of both adrenal glands. Anaesthesia was carried out using 10 micrograms.kg-1 alfentanil, 5 mg.kg-1 thiopentone, 1.5 mg.kg-1 succinylcholine and 0.5 vol % enflurane. A single hypertensive crisis (190/100 mmHg) occurred intraoperatively, during dissection of the left adrenal gland. This responded well to 1 mg.min-1 phentolamine. The postoperative course was uneventful for both the mother and the child. Total thyroidectomy with block dissection of the lymph nodes was to be carried out within three weeks after the Caesarean section. Only two similar cases of multiple endocrine neoplasia associated with pregnancy have previously been published.

[Insulin-requiring diabetes]. / Le diabète insulinorequérant.

The insulinorequiring diabetes is a notion which deserves a clear definition, essentially clinical, because it covers a wide range of physiopathological situations. The progressive degradation of Diabetes type II means a progressive discrepancy of insulinosecretion and above all an increase of insulinoresistance. The noxious part of chronical hyperglycemia is at present well known. The present therapeutical prospects tend to delay or limit insulinotherapy, by trying to obtain remission of insulinorequiring and some attempt to give a combined treatment associating insulin and hypoglycemic drugs.