Comparison of two methods for the detection of urinary iodine used in epidemiological studies.

Two methods for the determination of iodine in urine or serum based on the Sandell-Kolthoff reaction were compared. The first was an autoanalyser method (AAII, Technicon) where the mineralisation takes place in a continuous flow manner. This procedure was used at the Department of Clinical Chemistry of the University Hospital of Berne (Switzerland) from 1968 until 1993. The second method was evaluated and adapted in our own laboratory. Each sample and the iodate-standards are mineralised in a Pyrex glass tube and the decolorisation reaction takes place in a 96-well-microtiter plate which was read by a PC-controlled photometer at 405 nm. This method, with a detection limit of 0.1 micromol/l showed good analytical recovery (90 to 110%) and a low imprecision (intra-assay coefficient of variation (CV) of 5% and an inter-assay CV of 7.5%). In contrast to the autoanalyser method, the microtiter plate-method is suitable both for series up to 24 samples (3-fold) and for single samples. A comparison of 87 samples in the range of 0.1 to 60 micromol/l which were measured with both Sandell-Kolthoff based methods showed no obvious discrepancy. These two methods showed a good agreement for the determination of urinary iodine. This guarantees that the results of earlier epidemiological studies can be compared with recent studies performed in our and many other laboratories.

Iodine supply in different geographical areas of Switzerland: comparison between rural and urban populations in the Berne and the Ticino regions.

OBJECTIVE: We studied the question of possible regional differences of iodine intake in the population of rural and urban areas north and south of the Alps. DESIGN: Transversal study. SETTING: Six different regions from northern (Canton Berne) and southern Switzerland (Canton Ticino). SUBJECTS: For each region 30 individuals were studied. RESULTS: While significant differences of urinary iodine between some regions were found (range from 79 microg iodine/g creatinine in Chiasso to 130 microg iodine/g creatinine in the Maggia Valley), no significant differences between rural and urban populations of north and south of Switzerland were observed. Mild iodine deficiency affected 35%, moderate iodine deficiency 12% and severe iodine deficiency 0.6% of the total population investigated. CONCLUSIONS: 49% of this population showed at least mild or moderate iodine deficiency. The mean urinary iodine was just at the lower recommended limits. Significant differences were found between individual regions (such as Chiasso and the Valley of Maggia), but not generally between rural and urban areas in the north and south of the Alps.

Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A.

Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an i.v. bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 x 150 micrograms rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1-5) in the two patients were 9.6 +/- 1.3 and 9.2 +/- 1.2 mmol/l, respectively, and fell to 4.4 +/- 0.4 and 5.1 +/- 0.5 mmol/l on treatment days 8-10. Fasting insulin (2950 +/- 450 and 690 +/- 125 pmol/l), C-peptide (2217 +/- 183 and 1317 +/- 235 pmol/l) and proinsulin control levels (125 +/- 35 and 66 +/- 0 pmol/l) also decreased by approximately 65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent.

Insulin-like growth factor-I improves glucose and lipid metabolism in type 2 diabetes mellitus.

Hyperglycemia, hyperinsulinemia, and insulin resistance cause vascular disease in type 2 diabetes mellitus. Dietary treatment alone often fails and oral drugs or insulin enhance hyperinsulinemia. In previous studies, an intravenous bolus of recombinant human insulin-like growth factor-I (rhIGF-I) caused normoglycemia in insulin-resistant diabetics whereas rhIGF-I infusions lowered insulin and lipid levels in healthy humans, suggesting that rhIGF-I is effective in insulin-resistant states. Thus, eight type 2 diabetics on a diet received on five treatment days subcutaneous rhIGF-I (2 x 120 micrograms/kg) after five control days. Fasting and postprandial glucose, insulin, C-peptide, proinsulin, glucagon, triglyceride, insulin-like growth factor-I and -II, and growth hormone levels were determined. RhIGF-I administration increased total IGF-I serum levels 5.3-fold above control. During the control period mean (+/- SD) fasting glucose, insulin, C-peptide, and total triglyceride levels were 11.0 +/- 4.3 mmol/liter, 108 +/- 50 pmol/liter, 793 +/- 250 pmol/liter, and 3.1 +/- 2.7 mmol/liter, respectively, and decreased during treatment to a nadir of 6.6 +/- 2.5 mmol/liter, 47 +/- 18 pmol/liter, 311 +/- 165 pmol/liter, and 1.6 +/- 0.8 mmol/liter (P < 0.01), respectively. Postprandial areas under the glucose, insulin, and C-peptide curve decreased to 77 +/- 13 (P < 0.02), 52 +/- 11, and 60 +/- 9% (P < 0.01) of control, respectively. RhIGF-I decreased the proinsulin/insulin ratio whereas glucagon levels remained unchanged. The magnitude of the effects of rhIGF-I correlated with the respective control levels. Since rhIGF-I appears to improve insulin sensitivity directly and/or indirectly, it may become an interesting tool in type 2 diabetes and other states associated with insulin resistance.

Insulin-like growth factors in lysosomal storage disease.

Recent data indicate that insulin-like growth factor II (IGF II) and lysosomal enzymes bind to a common receptor. We measured serum IGF I and II levels in 16 patients with various lysosomal storage disorders. The IGF serum concentrations were normal as long as no marked liver disease was present. Under these conditions no direct interconnection between the lysosomal system and the serum IGF levels was found.

Polar surface distribution of type II insulin-like growth factor receptor in rat hepatocytes.

We describe the distribution of type II insulin-like growth factor receptors among canalicular (cLPM) and basolateral (bLPM) subfractions of rat liver plasma membranes (LPM). BLPM bound 3 times more 125I-IGF II than cLPM. The number of receptors was (1.3 +/- 0.15) X 10(-12) mol/mg in bLPM, and (0.4 +/- 0.17) X 10(-12) mol/mg in cLPM. Insulin-like growth factor II (IGF II) was 10 times more potent than insulin-like growth factor I (IGF I) in displacing 125I-IGF II from both basolateral and canalicular binding sites. Insulin did not interfere with binding of 125I-IGF II in either LPM preparations. Our findings point to an asymmetrical hepatocellular distribution of type II IGF receptors, thus extending the concept of surface polarization of hepatocytes to growth promoting hormone receptors.