Bernard Vandeleene

Urinary proteins and red blood cell membrane negative charges in diabetes mellitus.

The nature and origin of proteinuria in diabetes mellitus have been investigated by measuring the urinary excretion of seven specific proteins of low (beta 2-microglobin, retinol-binding protein) or high molecular weight (albumin, transferrin, hemopexin and IgG). Using the Alcian Blue binding test, we also measured negative charges on red blood cell (RBC) membrane which according to recent studies might mirror the glomerular polyanion charge. A group of 190 diabetics was examined, including 90 patients with type I diabetes, 23 type II diabetics treated with diet and/or hypoglycaemic agents and 77 longstanding type II diabetics requiring insulin therapy. With the exception of beta 2-microglobulin all proteins measured were excreted in the urine of diabetics in significantly higher amounts than in controls. The assay of transferrin proved the most sensitive (58% positive) followed by albumin (49%), IgG (34%), hemopexin (28%) and retinol-binding protein (26%). Practically the same ranking was obtained when only type I diabetics were considered. RBC membrane negative charges were diminished in diabetics and negatively correlated with the urinary excretion of albumin (r = -0.61, n = 190). RBC charges were also negatively correlated with other urinary proteins of high molecular mass (r between - 0.5 and - 0.2) but presented no relation with urinary beta 2-microglobulin or retinol-binding protein. The loss of RBC charges in diabetics most likely reflects the concomitant depletion of the glomerular polyanion responsible for the increased glomerular leakage of high molecular mass plasma proteins. The preferential increase in transferrin excretion together with the progressive rise in the urinary excretion of IgG lead us to postulate that the loss of glomerular polyanion in diabetes is accompanied, from the early stage, by a progressive decrease in the size-selectivity of the glomerular filter. The urinary excretion of retinol-binding protein was weakly correlated with albuminuria (r = 0.26, n = 186). Eight % of diabetics showed an elevation of urinary retinol-binding protein without evidence of microalbuminuria, which clearly demonstrates that a proximal tubular impairment can occur independently of the glomerular alterations in the course of diabetic nephropathy.

Allergic contact dermatitis caused by isobornyl acrylate in Freestyle® Libre, a newly introduced glucose sensor

Glucose sensors, such as FreeStyle® Libre, are innovative medical devices developed for diabetes patients as a replacement for classic glucose meters, ensuring continuous glucose monitoring without the disadvantage of regular skin finger pricks.

Treatment of systemic hypertension in insulin-treated diabetes mellitus with rilmenidine.

The effects of a new alpha 2 agonist (S 3341 or rilmenidine) on blood pressure (BP), glycemic control, lipid metabolism and renal function were investigated during a 16-week open study in 29 insulin-treated diabetic patients with mild to moderate hypertension. There were 17 men and 12 women aged 50.9 +/- 2.2 years (mean +/- standard error of the mean). Duration of diabetes and insulin therapy was 218 +/- 24 and 143 +/- 30 months. After 2 weeks of placebo, systolic and diastolic BP was 165 +/- 3 and 97 +/- 0.5 mm Hg, respectively (supine). Rilmenidine (S 3341) given alone at daily doses of 1 or 2 mg according to the clinical response led to a prompt and sustained decrease of systolic and diastolic BP (159 +/- 4 and 88 +/- 1 mm Hg after 2 weeks; 149 +/- 3 and 85 +/- 1 mm Hg after 12 weeks; p less than 0.01). Seventeen patients (59%) had normal BP (systolic BP less than 160; diastolic BP less than 90 mm Hg, supine) after 12 weeks of S 3341. Diuretics were associated with S 3341 for the nonresponders at week 12; this led to normalization of BP in 90% of the patients at the end of the study. Glycemic control was assessed by home glucose monitoring (5 determinations/1 day per week), 24-hour glucosuria and postprandial plasma glucose at the outpatient clinic (n = 7) as well as by the measurement of the glycosylated hemoglobin. None of these parameters was significantly affected by S 3341.(ABSTRACT TRUNCATED AT 250 WORDS)

Red Blood Cell Electric Charge and Microalbuminuria in Diabetes mellitus

Prof. R. Lauwerys, Faculté de Médecine, Clos Chapelle-aux-Champs 30, B-1200 Bruxelles (Belgium) Dear Sir, The glomerular filtration barrier is both sizeand charge-selective. Fixed anionic sites within the glomerular basement membrane and on the epithelial cell coat appear to be the basis of the charge selectivity. This charge barrier restricts the passage across the filter of polyanionic macromolecules such as serum albumin [1]. Recently, it has been reported that in children with nephrotic syndrome, a reduction of membrane-negative charge as measured by the binding of the cationic dye, alcian blue (AB), can be detected in red blood cells (RBC) similar to that observed histologically on the glomerular capillary wall in nephrotic patients [2]. The validity of these results has been questioned [3, 4]. However, in rats chronically exposed to cadmium, a well-known nephro-toxin, we have been able to demonstrate, with the AB binding test, a relation between the decrease of membranenegative charges in RBC and in renal glomeruli and the intensity of the cadmium-induced albuminuria. Furthermore, in cadmium workers a significant decrease of RBC charge was also found which on the average paralleled both the cadmium body burden and albumin excretion [5]. An increased urinary excretion of albumin which is not detectable with conventional tests of proteinuria (microalbuminuria) is an early manifestation of diabetic nephropathy [6]. The initial rate of albumin leakage is due to an enhanced glomerular filtration. Impaired tubular reabsorption of albumin can be excluded because the latter would be associated with an increased urinary excretion of low molecular weight proteins [7] which is not always the case in diabetic nephropathy [8]. Two mechanisms have been suggested as an explanation for the increase filtration of albumin in diabetics: hemodynamic changes in the renal microcirculation [9] which have been linked to rheological changes [10] or a loss of fixed negative charges in the glomerular capillary 250-ι

Cross-reactivity of insulin analogs with the Diasorin Liaison insulin assay.

Insulin or insulin secretagogue treatment of diabetes mellitus remains the most common cause of hypoglycemia (1). The measurement of circulating concentrations of insulin is therefore part of the workup and management of hypoglycemic disorders, as recently indicated by the clinical practice guideline of the Endocrine Society (1). The awareness about the specific detection abilities of an insulin assay for insulin and insulin analogs is mandatory for the evaluation of potential factitious insulin-induced hypoglycemia. Previous reports have already determined the cross-reactivities to insulin analogs of some automated insulin assays (2–4). Such data have not yet been published for the Liaison insulin automated immunoassay. The aim of our study was therefore to evaluate the crossreactivity of the Liaison insulin assay (Diasorin, Saluggia, Italy) with some insulin analogs currently used for the treatment of diabetic patients. The Liaison insulin assay format is an immunometric assays using monoclonal antibodies with a chemiluminescence based method and is calibrated using the international reference standard NIBSC 66/304. The observed coefficients of variation for this assay in our laboratory are 25.4%, 5.3% and 9.1% at 0.7, 15 and 22 mUI/mL, respectively. The evaluation of cross-reactivity was performed with three different recombinant insulin analogs: lispro (Humalog ; Eli Lilly and Company), aspart (NovoRapid 300 FlexPen ; Novo Nordisk Pharmaceuticals), and glargine (Lantus ; Aventis Pharmaceuticals). The insulin analogs having a concentration of 100 kIU/L were diluted with a 10 g/L bovine serum albumin solution (BSA; Sigma Aldrich, St. Louis, MO, USA) or with insulin depleted serum (Sunnylab, Sittingbourne, UK) to reach final insulin concentra-

Treatment of hypertension in diabetic patients.

Hypertension, common in diabetic patients, worsens not only the risk of cardiovascular complications, but also that of microangiopathic complications (nephropathy, retinopathy) of diabetes mellitus. It is thus important to ensure the perfect control of even mild hypertension in diabetic patients. However, treatment sometimes becomes difficult given that certain categories of antihypertensive drugs interfere with blood glucose control and/or lipid metabolism, interfere with the symptomatology of hypoglycemia, or promote orthostatic hypotension, a complication of autonomic neuropathy. A study was undertaken to determine the effects of rilmenidine, administered for 16 weeks, in 29 diabetic patients treated with insulin and experiencing mild-to-moderate hypertension (supine diastolic blood pressure, 96.7 +/- 0.5 mmHg). Administered as single-drug therapy, rilmenidine rapidly normalized blood pressure (systolic blood pressure, less than 160 mmHg; diastolic blood pressure, no more than 90 mmHg--supine) in 17 patients; this persisted throughout the trial period. Addition of a diuretic after 12 weeks in the remaining 12 patients led to normalization of blood pressure in nine additional patients. Blood glucose control (evaluated at home by weekly blood glucose measurements and by glycosylated hemoglobin levels) was unaffected by treatment. Plasma levels of cholesterol (total, high-density lipoprotein and low-density lipoprotein), triglycerides and proteinuria (or microalbuminuria) showed no change during the course of the trial. In conclusion, rilmenidine offers an effective and safe treatment for mild-to-moderate hypertension in diabetic patients treated with insulin and does not interfere with their blood glucose control.

An Unusual Cause of Factitious Mineralocorticoid Excess

The presence of hypokalaemia in hypertensive patient must prompt a search for increased mineralocorticoid activity. We describe and discuss the observation of a patient with biological markers of hypermineralocorticoidism, despite low plasma and urinary aldosterone levels, and suppressed plasma renin activity. This typical syndrome of apparent mineralocorticoid excess was secondary, in our patient, to prolonged administration of a mineralocorticoid-containing nasal spray.

Syndrome de Werner avec complications inhabituelles

This case of Werner syndrome proved highly interesting because of severe insulinoresistant diabetes, various complications, myelofibrosis progressing as an acute myeloid leukemia. Recent concepts about the syndrome are commented upon.

Comparaison de l'insuline humaine semi-synthétique et de l'insuline porcine chez des patients diabétiques avec ou sans anticorps anti-insuline circulants.

SummaryThe effects of semi-synthetic human insulin (IHSS) and monocomponent porcine insulin (IPMC) were compared in a double blind study carried out in 9 totally insulin dependent diabetic patients in hospital. Short-acting preparations of these insulins were administered subcutaneously 4 times per day at an identical dose in each subject. Plasma glucose and plasma free insulin were measured 28 times on the 3rd day of each insulin treatment. At none of the 28 time points were the mean plasma glucose and free insulin levels significantly different. In the 5 patients without or with only a low titer of anti-insulin antibodies (AIA —), the mean circadian glycemia was markedly higher (under IHSS or IPMC) and the glycemic fluctuations were more pronounced (with IPMC) than in the 4 other subjects with a higher titer of anti-insulin antibodies (AIA +). This observation could be explained by a reduced half-life of circulating insulin in patients AIA —, leading to low levels of plasma free insulin, and, thus, to g...