[Microalbuminuria and diabetic nephropathy. Detection and correlation with other degenerative complications]. / Microalbuminurie et néphropathie diabétique. Dépistage et corrélations avec les autres complications dégénératives.

The prevalence of microalbuminuria and persistent proteinuria was studied in a population of 801 diabetic patients (535 with type II and 266 with type I diabetes). Urinary albumin excretion rate (AER) was measured on morning samples by laser nephelometry. Normoalbuminuria, as defined, in the absence of contaminated urine, by an albumin: creatinine (A/C) ratio below 2, was found in 551 patients, microalbuminuria (NC greater than or equal to 2 with AER below 200 mg/l) in 190 patients and persistent proteinuria (AER greater than or equal to 200 mg/l) in 60 patients. Microalbuminuria was present in 48 (18 p. 100) IDDM patients and 142 NIDDM patients. In IDDM patients, AER increased with the duration of the disease with no apparent influence of age at the onset. The prevalence of hypertension was 25 p. 100 and 61 p. 100 in IDDM patients with microalbuminuria and macroproteinuria respectively versus 10 p. 100 in patients with normoalbuminuria. This prevalence increased in NIDDM patients from 39.3 p. 100 with normoalbuminuria to 40.8 p. 100 and 76.2 p. 100 with microalbuminuria or macroproteinuria respectively. Proliferative retinopathy in type I and type II patients with normal AER was 7.4 p. 100 and 1.2 p. 100 respectively increasing to 15.2 p. 100 and 8.9 p. 100 with microalbuminuria and 27.8 p. 100 and 23.1 p. 100 with macroproteinuria. The prevalence of coronary disease increased from 4 to 10.4 p. 100 in patients with type I diabetes and microalbuminuria. The prevalence of cardiac failure increased from 1.5 to 2.1 p. 100 in type I diabetics and from 3.2 to 7.8 p. 100 in type II diabetics in the presence of microalbuminuria. Patients with microalbuminuria had increased levels of glycosylated hemoglobin A 1C but statistical difference was only obtained for patients with type II diabetes. Routine analysis of AER in diabetics allows early detection of diabetic nephropathy and emphasizes the need for tight metabolic and blood pressure control. Hypertension can be detrimental to nephropathy but might also initiate renal lesions in NIDDM patients.

[C-peptide assays of the urine and plasma at baseline and under stimulation with glucagon in healthy subjects and diabetics]. / Dosages du C-peptide urinaire et plasmatique de base et sous stimulation par le glucagon chez des sujets sains ou diabétiques.

Urinary (CPU) and plasma C peptide values at baseline (CP0) and under stimulation with glucagon were determined in healthy subjects (n = 17) and in insulin-dependent (IDD, n = 45) and non insulin-dependent (NIDD, n = 32) diabetics. A significant difference in the parameters of insulin secretion (x? SD) was found on the one hand between the IDD group (CPU = 5.58 +/- 5.58 nmol/24 h; CP = 0.14 +/- 0.08 nmol/l; maximum C peptide value after stimulation (CPmax) = 0.33 +/- 0.31 nmol/l; C peptide delta (delta CP) = 0.14 +/- 0.14 nmol/l; area under the curve (A) = 5.00 +/- 4.84) and the NIDD group (CPU = 15.47 +/- 8.22 nmol/24 h; CP = 0.64 +/- 0.28 nmol/l; CPmax = 1.14 +/- 0.44 nmol/l; delta CP = 0.50 +/- 0.31 nmol/l; A = 17.5 +/- 5.86) and on the other hand between the IDD group and the control group (CPU = 18.20 +/- 8.40 nmol/24 h; CP = 0.41 +/- 0.11 nmol/l; CPmax = 1.00 +/- 0.31 nmol/l; delta CP = 0.69 +/- 0.20 nmol/l; A = 17.10 +/- 4.45). As regards the NIDD group, only the fasting C peptide and delta C peptide values were significantly different from those found in the control group. The significance of each parameter of insulin secretion was also studied. There was a correlation between the values of C peptidaemia before and after stimulation with glucagon. However, the correlation between plasma C peptide and urinary C peptide values was mediocre, probably because of the numerous variability factors which intervene in the urinary excretion of C peptide.

[Restoration of insulin sensitivity after correction of hypokalemia due to chronic tubulopathy in a diabetic patient]. / Normalisation de la sensibilité a l'insuline après correction d'une hypokaliémie par tubulópathie chronique chez une patiente diabétique.

In a type II diabetic patient presenting with chronic hypokaliemia secondary to a selective renal tubulopathy, insulin sensitivity was explored three times during a euglycemic hyperinsulinemic clamp procedure at two rates of insulin infusion: 1 and 10 mU/kg/min: once before treatment of hypokaliemia and once after successful correction of hypokaliemia with indomethacine or spironolactone. During insulin infusion, a 20% dextrose solution was infused by a Biostator in order to maintain the patient's glycemia at 90 mg/dl. Amounts of glucose infused during the last 20 min of each 2 hour insulin infusion were (at 1 and 10 m/kg/min respectively): before treatment (K+ = 2.7 mmol/l): 2.4 and 8.4 mg/kg/min; after spironolactone (K+ = 3.9 mmol/l): 3.3 and 15.4 mg/kg/min; after indomethacine (K+ = 3.7 mmol/l): 5 and 19 mg/kg/min after stopping drugs (K+ = 2.9 mmol/l): 2.5 and 5.3 mg/kg/min. These data suggest that potassium metabolism plays a critical role in the mechanisms of insulin sensitivity.

[Cushing's syndrome caused by ectopic production of CRF by a medullary carcinoma of the thyroid body]. / Syndrome de Cushing secondaire à la production ectopique de CRF par un carcinome médullaire du corps thyroïde.

A 58-yr-old man presented a Cushing's syndrome gradually developed for two years, and a cervical tumor. Urinary free cortisol and 17-hydroxy-corticosteroids were elevated and non suppressible under high dose dexamethasone (8 mg a day X 2 days). Plasma calcitonin (7,200 pg/ml), CEA (803 ng/l), beta LPH (624 pg/ml), and CRF (29 pg/ml) were elevated. Total thyroidectomy revealed a medullary carcinoma of the thyroid. Postoperatively the Cushing's syndrome disappeared and plasma CRF became undetectable although plasma calcitonin remained elevated. One out of 3 CRF antisera tested for immunocytology was positive in 10 to 30% of the cells. In tumor extract, CRF (RIA) concentration was 4.75 ng/g. There was no detectable ACTH in the tumor by biochemical as well as immunocytochemical method. In the present report, the next evidences are--for the first time--simultaneously present to demonstrate an ectopic secretion of CRF by a medullary thyroid carcinoma: presence of CRF in systemic blood being undetectable after surgery; cure of the clinical and biological features of Cushing's syndrome after thyroidectomy; characterization of CRF immunoreactivity in tumor. Taken together, the radioimmunological and the immunocytochemical data suggest the production of several molecular forms of CRF.

The 24-h cortisol secretory pattern in Cushing's syndrome.

The 24-h plasma cortisol profile was obtained at 20-min intervals in 18 patients with Cushing's syndrome (10 with Cushing's disease, 5 with adrenal adenoma, 2 with ectopic ACTH secretion and 1 of questionable aetiology). The mean cortisol level was maximum in the case of ectopic ACTH secretion. The coefficient of variation of cortisol levels was subnormal in all except 2 subjects. Periodogram calculations, providing a best-fit curve (B F C) for each profile, showed that the existence of a significant baseline variation is a frequent feature. In certain cases, it is compatible with the persistence of a true circadian rhythm (2 patients with Cushing's disease; 1 patient with adrenal adenoma). The alteration of plasma cortisol pulsatility is much more pronounced in patients with adrenal adenoma than in patients with Cushing's disease. This is consistent with the hypothesis of a predominantly tonic secretion blunting the episodic hormone release. In 9 patients with Cushing's disease, the plasma cortisol pattern was suggestive of a combination of episodic cortisol release under CRF control and of continuous cortisol secretion due to constant stimulation from an autonomous ACTH source. Two cases were possibly of hypothalamic origin, as suggested by the presence of enhanced cortisol pulsatility and of a normal circadian amplitude. The analysis of the 24-h profile of plasma cortisol in Cushing's syndrome contributes to our understanding of the physiopathological mechanisms underlying this disorder and may help the diagnosis of its aetiology.

Regulation of peripheral plasma somatostatin like immunoreactivity in type I diabetes: role of the degree of metabolic control.

We have determined peripheral venous somatostatin like immunoreactivity (SLI) levels in 11 normal subjects (blood glucose--BG--: 4.4 +/- 0.1 mM; ketone bodies--KB--: 90 +/- 12 microM; plasma free fatty acids--FFA --: 340 +/- 42 microM), 4 Biostator controlled insulin dependent diabetics (BG: 5.4 +/- 0.2 mM; FFA: 418 +/- 38 microM; KB: 226 +/- 41 microM) and 7 poorly controlled ketotic diabetics (BG: 10.8 +/- 1.3 mM; FFA: 915 +/- 19 microM; KB: 2490 +/- 576 microM). SLI was determined again after 48 to 96 hours of intravenous insulin infusion for the 7 ketotic diabetics and after transient interruption of insulin infusion for the Biostator controlled diabetics. Relative to normal subjects ketotic diabetics had elevated SLI levels (29.7 +/- 5.9 vs 13.5 +/- 1.8 ng/L, p less than 0.01) whereas biostator-controlled patient had near to normal values (20.4 +/- 6.4 ng/L, p greater than 0.30). Transient arrest of insulin infusion in the Biostator controlled diabetics resulted only in a mild metabolic deterioration (BG: 12.8 +/- 2.1 mM; FFA: 640 +/- 146 microM; KB: 950 +/- 163 microM) without a significant rise of SLI. Intravenous insulin infusion in the initially ketotic patients decreased BG and KB in each subject (p less than 0.01) but decreased FFA (1097 +/- 170 to 453 +/- 74 microM, p less than 0.05) and SLI (34.0 +/- 12.0 to 9.8 +/- 2.4 ng/L, p less than 0.05) only in 4 patients whereas both FFA (737 +/- 107 to 725 +/- 25 microM) and SLI (27.6 +/- 4.7 to 20.3 +/- 4.7 ng/L) levels remained stable in the other 3. These results suggest that SLI levels in type I diabetics are dependent the degree of metabolic control and could be related to the variations of FFA concentrations.