Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion.

Studies of bortezomib in patients with relapsed multiple myeloma (MM) suggested that bortezomib may be active even in the presence of adverse prognostic factors. We therefore evaluated 62 patients with relapsed/refractory MM who were treated with single-agent bortezomib, and addressed the question whether or not the negative prognostic impact of unfavorable cytogenetic abnormalities may be overcome by bortezomib. By interphase fluorescence in situ hybridization (FISH), a deletion of chromosome 13q14 [del(13q14)] was present in 33 patients (53%). Overall response rates to bortezomib were similar in patients with and without del(13q14) (45 versus 55%; P=0.66), and rates of complete remission (CR) near CR were also not different between the two patient populations (18 versus 14%). Three patients had a t(4;14)(p16;q32) in addition to del(13q14), and all of them had a >50% paraprotein reduction. Median duration of response was 12.3 months in patients with del(13q14) compared with 9.3 months in patients with normal 13q-status (P=0.25), and survival was also not different between the two patient populations. Patients not benefiting from single-agent bortezomib were characterized by the combined presence of a del(13q14) and low serum albumin (median survival 4.6 months). Our results provide evidence for remarkable activity of bortezomib in MM with del(13q14). Patients who do not respond to bortezomib and consecutively have short time to treatment failure and overall survival can be identified by low serum albumin in addition to del(13q14) and should be considered for bortezomib combinations.

Basal and stimulated plasma levels of pancreatic amylin indicate its co-secretion with insulin in humans.

Amylin is a 37-amino acid pancreatic polypeptide, probably involved in the pathophysiology of Type 2 (non-insulin-dependent) diabetes mellitus. We have determined amylin in human plasma by extraction-based radioimmunoassay (Sep-Pak C18). Of 23 healthy control subjects plasma amylin was determined as 11.9 +/- 3.5 ng/l. Of 27 patients with Type 2 diabetes receiving insulin the amylin levels were lower, and in 16 patients with Type 2 diabetes on oral medication they were higher than in the control subjects; 8.2 +/- 4.4 ng/l (p less than 0.01) vs 18.8 +/- 9.9 ng/l (p less than 0.05). In 14 Type 1 (insulin-dependent) diabetic patients we found extremely low mean amounts of amylin: 2.9 +/- 1.9 ng/l (p less than 0.002). Thus, basal amylin appears to be associated with the capacity to release insulin. An oral glucose load stimulated the release of amylin, this was more pronounced in patients with Type 2 diabetes than in healthy subjects. An excellent correlation of mean amylin with mean insulin concentrations was obtained (r = 0.949). In patients with Type 2 diabetes amylin was reduced congruent to decreases in C-peptide during a hyperinsulinaemic, euglycaemic glucose clamp experiment (r = 0.971 for linear correlation between C-peptide levels and amylin). We conclude, that amylin and insulin are co-secreted in humans, and that the amylin release is under feedback-control by insulin.

Metabolic effects of isradipine versus hydrochlorothiazide in diabetes mellitus.

Most antihypertensive drugs have negative effects on metabolic control in diabetic patients. Calcium antagonists have been widely used in antihypertensive treatment of diabetics, although a possible influence on glucose tolerance, insulin secretion, and insulin action is unknown. Therefore, the effect of the calcium antagonist isradipine on glucose tolerance and insulin secretion (75 g oral glucose tolerance test) and on peripheral and hepatic insulin action (euglycemic clamp) was evaluated in 11 type II diabetic patients. All patients were treated with placebo or isradipine for 8 weeks (double-blind, crossover design). A second group of six diabetic patients received a thiazide diuretic, hydrochlorothiazide, according to the same protocol. Systolic blood pressure was significantly lowered after isradipine and hydrochlorothiazide compared with placebo (127 +/- 3 versus 139 +/- 6 mm Hg and 129 +/- 4 versus 142 +/- 4, respectively; p less than 0.05). Fasting blood glucose (190 +/- 21 versus 152 +/- 15 mg/dl; p less than 0.01), glucose levels, basal and glucose-stimulated insulin levels were significantly higher after hydrochlorothiazide compared with placebo but remained unchanged after calcium antagonist treatment. Basal hepatic glucose production and peripheral insulin resistance were significantly elevated after hydrochlorothiazide compared with placebo or calcium antagonist therapy. These data indicate that the calcium antagonist isradipine has no effect on glucose tolerance, insulin secretion, and insulin action in type II diabetic patients and might therefore be a useful drug for antihypertensive treatment in diabetes mellitus. However, diuretic treatment can lead to impairment of metabolic control and reduction of insulin action in type II diabetes mellitus.

[The value of fructosamine in hemodialysis patients]. / Die Wertigkeit von Fructosamin bei Hämodialysepatienten.

Fructosamine is thought to be an alternative diabetic long term parameter to HbAlc. A possible advantage of fructosamine is the shorter half life of this parameter. Therefore changes in the metabolic control of diabetes can be evaluated faster. However, daily variations of protein concentrations limit the clinical usefulness of fructosamine, especially in patients on hemodialysis, where we see variations in total protein- and albumin concentration during dialysis. Due to these limitations we studied the clinical usefulness of a new fructosamine assay in 38 patients with chronic renal failure. Fructosamine values, total protein, albumin, blood glucose and creatinine were measured before and after three hours hemodialysis treatment as well as glycosylated hemoglobin. Before dialysis HbA1c correlated with HbA1c after dialysis (r = 0.99), which documents the usefulness of glycosylated hemoglobin in patients on hemodialysis. Fructosamine before dialysis shows a correlation with fructosamine values after dialysis of r = 0.77. After correction with total protein the correlation was r = 0.95, also after correction with albumin. Fructosamine values before and after dialysis correlated excellently (r = 0.95). Fructosamine values before and after dialysis can only be compared after correction with total protein or with albumin.

[Diurnal variations of fructosamine in patients with type II diabetes mellitus]. / Tageszeitliche Schwankungen von Fructosamin bei Patienten mit Typ-II-Diabetes mellitus.

During the last years fructosamine has been presented as a measurement of diabetic long term control, particularly a shorter half life of fructosamine was seen as an advantage over HbAlc (half life of fructosamine: 16 days, half life of HbAlc: 28 days). Due to diurnal variations of fructosamine levels especially in dependence of variations of the albumin-and protein concentrations the interpretation of this parameter was somewhat limited. Recently a new colorimetric fructosamine-assay was developed. We investigated the diurnal variations of fructosamine in 28 patients with type II diabetes. Fructosamine, glucose, albumin, total protein and creatinine were measured at the times towards 3, 6, 9, 12 a.m. and 3, 6, 9, and 12 p.m. In relation to the 6 a.m. fructosamine value (= 100%) the fructosamine levels showed a daily variation from -4% at 3 a.m. to +11% at 9 a.m. Correcting fructosamine levels with total protein or with albumin reduced the variations to -1% to +6% or -3% to +9%. Daily profiles of the new fructosamine assay show a daily variation which can be minimized by correcting with protein-or with albumin concentrations. For clinical routine the daily variations especially of the corrected fructosamine levels are neglectible.