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Biomedical subjects

R Prager

Publications and source records attributed to R Prager.

At least 19 recordsLinked to original sources

Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus.

PURPOSE: To investigate whether serum levels of lipid peroxides measured as thiobarbituric-acid-reactive substances (TBARS) differ in type I and type II diabetic patients, whether serum levels correlate with late sequelae of diabetes, and whether serum levels of free vitamin E correlate with levels of lipid peroxidation by-products. PATIENTS AND METHODS: The relationship among lipids, glycosylated hemoglobin A1c (HbA1c), lipid peroxides measured as TBARS, and free vitamin E was determined in 158 patients. Fifteen of the 77 patients with type I diabetes and 39 of the 81 patients with type II diabetes had clinically apparent peripheral vascular disease or coronary artery disease, or both. RESULTS: Compared with control subjects, serum levels of TBARS were found to be significantly elevated (P < 0.001) in diabetic patients, and type II diabetic patients had significantly higher levels (P < 0.001) than type I patients. Both type I and type II diabetic patients with good metabolic control (HbA1c < 6.5%) had significantly lower (P < 0.005) TBARS levels than patients with poor metabolic control, but all groups had higher levels than the control group. Type II patients with angiopathy had significantly higher levels of TBARS than patients without angiopathy. Free vitamin E levels in control subjects and diabetic patients did not differ statistically. CONCLUSION: Serum levels of TBARS were significantly increased in all patients suffering from diabetes mellitus, whereby TBARS levels did not depend on the total amount of circulating lipids. It can be suggested that the enhanced lipidperoxidation is contributed to an increased formation of free radicals in diabetes mellitus.

Adult

Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source.

A summer outbreak of severe gastroenteritis followed by haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura in a nursery school and kindergarten is described. Sandwiches prepared with green butter made with contaminated parsley were the likely vehicle of infection. The parsley originated from an organic garden in which manure of pig origin was used instead of artificial fertilizers. Clonally identical verotoxinogenic Citrobacter freundii were found as causative agents of HUS and gastroenteritis and were also detected on the parsley.

Adult

Intravenous calcitriol normalizes insulin sensitivity in uremic patients.

Recent studies suggest that secondary hyperparathyroidism and/or vitamin D deficiency are responsible for the insulin resistance in chronic renal failure. We investigated the effect of a 12-week intravenous treatment with 1,25 dihydroxycholecalciferol on glucose metabolism in 10 hemodialysis patients compared with 10 healthy control subjects by the frequently-sampled intravenous glucose tolerance test, analyzed with the minimal model technique. Compared to control subjects, the uremic patients featured elevated levels of parathyroid hormone (432 +/- 60 vs. 41 +/- 4 ng/liter, P < 0.001), insulin resistance (insulin sensitivity index, SI: 4.9 +/- 0.8 vs. 9.5 +/- 0.9 min-1/(microU/ml), P < 0.002), increased posthepatic insulin delivery (6.48 +/- 2.48 vs. 2.73 +/- 3.14 nmol/liter in 4 hr, P < 0.001) and a reduced C-peptide fractional clearance (0.033 +/- 0.004 vs. 0.085 +/- 0.009 min-1, P < 0.0002). Following treatment with 1,25 dihydroxycholecalciferol, the parathyroid hormone levels decreased significantly to 237 +/- 30 ng/liter (P < 0.05), the insulin sensitivity index (SI: 9.6 +/- 2.2, P < 0.05) reached a value similar to that of control subjects, and posthepatic insulin delivery decreased to 4.63 +/- 0.83 nmol/liter in 4 hr (P < 0.01), while all the other parameters remained unchanged. In summary, uremic patients with secondary hyperparathyroidism were found to be severely insulin resistant and hyperinsulinemic. Intravenous vitamin D treatment led to a significant reduction of parathyroid hormone levels and to a complete normalization of insulin sensitivity in the hemodialysis patients. Thus, intravenous 1,25 dihydroxycholecalciferol improves insulin resistance in uremic patients, acting per se or by reducing secondary hyperparathyroidism.

Adult

A program to reduce onset distress in unselected type I diabetic patients: effects on psychological variables and metabolic control.

This paper reports the results of a prospective controlled trial of a program addressing reduction of onset distress and better future adaptation in adults who were enrolled at the time of diagnosis of type I diabetes mellitus. Patients were assigned randomly to either standard intensive treatment and patient education with the distress reduction program (N = 10) or to standard intensive treatment and patient education without this program (N = 13). Prospective follow-up of patients with multiple validated measures of treatment outcome showed less anxious coping behavior, less depression and less denial at the 9-month follow-up and less denial at the 15-month follow-up in the group with the distress reduction program, but no differences in metabolic control between the two groups at any time. We conclude that our program has a positive impact on the crisis at diabetes onset; the lower denial in the treatment group may lead to improved regimen adherence in the long term.

Adaptation, Psychological

Effects of captopril treatment versus placebo on renal function in type 2 diabetic patients with microalbuminuria: a long-term study.

We evaluated the renal effect of long-term antihypertensive treatment (12 months) with the angiotensin-converting enzyme inhibitor captopril compared to placebo in 15 type 2 diabetic patients with microalbuminuria. The patients were randomly allocated to captopril (n = 9) or placebo (n = 6). After 1-year therapy no significant decrease in blood pressure was demonstrated with captopril (139 +/- 17/80 +/- 9 versus 138 +/- 13/76 +/- 6 mmHg) or placebo (138 +/- 9/75 +/- 6 versus 135 +/- 14/79 +/- 10 mmHg). Only in a small hypertensive subgroup (n = 4) treated with captopril did we find a significant reduction in blood pressure (154 +/- 2/88 +/- 1 versus 142 +/- 7/78 +/- 5 mmHg, P < 0.05). The urinary albumin excretion rate did not change significantly either in the captopril group (95.6 mg/24 h, 25th percentile 138.4, 75th percentile 25.1; versus 127.8 mg/24 h, 25th percentile 29.3, 75th percentile 222) or in the placebo group (99.2 mg/24 h, 25th percentile 58.5, 75th percentile 125.8; versus 120.9 mg/24 h, 25th percentile 62.1, 75th percentile 179.7). There were also no alterations in renal blood flow or filtration rate. In the hypertensive subgroup treated with captopril a reduction in urinary albumin excretion rate after 3 and 6 months of treatment was observed (captopril 73.4 versus 24 and 41 mg/24 h, P < 0.05), but not after 12 months. Triglyceride and cholesterol levels remained constant before and after treatment while glycosylated hemoglobin decreased significantly after 12 months captopril (7.8 +/- 0.9 versus 6.9 +/- 0.7 mg%, P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Long-term treatment with nifedipine reduces urinary albumin excretion and glomerular filtration rate in normotensive type 1 diabetic patients with microalbuminuria.

The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n = 8; dosage 30 mg/day) or placebo (n = 7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q1/Q3 in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90), P < 0.02; 12 months 39 (15/79), P < 0.05). GFR was significantly decreased by nifedipine treatment (baseline 157 +/- 15, 6 months 122 +/- 8, 12 months 111 +/- 47 ml/min; P < 0.05, mean +/- SEM), whereas RPF remained constant. Nifedipine treatment did not influence systolic (baseline 121 +/- 7, 12 months 124 +/- 2 mmHg, mean +/- SEM) or diastolic (baseline 72 +/- 2, 12 months 74 +/- 3 mmHg) arterial blood pressure. With placebo treatment no significant alterations of UAER, GFR, RPF and arterial blood pressure were observed. Metabolic control was constant throughout the whole study period. Thus, 1 year's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Psychological moderator variables and metabolic control in recent onset type 1 diabetic patients--a two year longitudinal study.

The relationships between psychosocial adjustment and subsequent glycaemic control were prospectively examined in forty-three adult patients during the first 2 yr after onset of type 1 diabetes mellitus. Decreasing depression was the single psychosocial parameter that changed over time. No correlations were found between the decrease in HbA1c levels and psychological variables at 8- and 16-month follow-ups. Global and specific coping features such as high control attitude, low coping anxiety and low emotional attribution correlated significantly with the decrease in HbA1c levels at the 2-yr follow-up, whereas stressful life events, depression, state-trait anxiety did not correlate. In a regression analysis coping explained 22% variance of the 2 yr decrease in HbA1c levels. We conclude that coping is a better predictor for metabolic control than emotional adaptation and life events. Metabolic control might deteriorate with prolonged stage of the disease being a first sign for psychophysiological coping exhaustion.

Adaptation, Psychological

Expression and plasmid transfer of genes coding for the fimbrial antigen F107 in porcine Escherichia coli strains.

Expression of the fimbrial antigen F107 of porcine E. coli strains on agar plates was achieved by microaerobic cultivation. For part of the strains of some types, addition of alizarin yellow and eosin to the agar medium proved to be necessary. Some of these strains reacted distinctly positive only when the small colonies growing between the larger ones on alizarin-yellow agar were tested. The fimbrial antigen of the Swiss strain 107/86 was provisionally designated the F107ab variant and that of the Hungarian strain 2134P and the Czech strain 8813, the F107ac variant. The F107 genetic determinants were found to be often linked with those encoding haemolysin production and are frequently carried by plasmids.

Animals

Increased levels of circulating islet amyloid polypeptide in patients with chronic renal failure have no effect on insulin secretion.

To elucidate the metabolism of islet amyloid polypeptide (IAPP) with respect to a possible renal elimination we investigated IAPP levels in 20 lean, nondiabetic patients with renal failure maintained on chronic hemodialysis (HD) and in 20 healthy controls. The basal levels of IAPP were significantly higher in uremic patients than in controls (15.1 +/- 3.2 vs. 3.2 +/- 0.2 pM, P < 0.001) suggesting renal excretion of IAPP. To investigate the impact of chronically elevated levels of endogenous IAPP on insulin secretion and insulin sensitivity, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed in a subset of patients on hemodialysis and in age-matched healthy controls (C) and obese patients with normal (NGT) and with impaired glucose tolerance (IGT). Insulin sensitivity index (SI) was 8.7 +/- 1.5 in C (P < 0.05 vs. NGT, P < 0.01 vs. IGT), 5.4 +/- 0.9 in HD (P < 0.05 vs. IGT), 3.1 +/- 1.0 in NGT, and 2.0 +/- 0.5 in IGT. First phase insulin secretion was increased in patients on HD compared with those of several control groups. The results of this study therefore indicate a renal route of metabolism of IAPP. Increased endogenous circulating IAPP levels over a long period of time do not lead to a decrease in insulin release in patients on HD and do not cause the insulin resistance commonly seen in obesity and diabetes. Increased levels of circulating IAPP therefore are not likely to be a pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM).

Adult

Antihypertensive efficacy of cilazapril 2.5 and 5.0 mg once-daily versus placebo on office blood pressure and 24-hour blood pressure profile.

In a double-blind, randomized, multicenter study the antihypertensive efficacy of cilazapril 5.0 and 2.5 mg once daily vs. placebo was examined on 180 ambulatory hypertensive subjects with supine diastolic office blood pressure (OBP) > or = 95 and < or = 115 mm Hg: a 4-week, single-blind, placebo period was followed by a 4-week double-blind treatment period. At the beginning and end of the latter, OBP measurements and ambulatory 24-h BP monitoring (ABPM) were both carried out on two different days (3 +/- 1), whereby each time two 24-h BP recordings were made using SpaceLabs 90202. Measurements were made every 30 min, and actual waking and sleeping phase evaluation was done using diary entries. White coat hypertensive patients were excluded by the ambulatory BP (ABP) inclusion criterion: mean diastolic 24-h BP > or = 85 mm Hg, or frequency of measurements > 90 mm Hg > or = 35%. One-hundred eighty patients were included in the study. Safety was evaluated in 170 of these patients, and efficacy on OBP in 162. Twenty-four-hour BP recordings that were amenable to analysis were available in the case of 146 patients (average age 56 +/- 10 years, 56 women, 90 men). The results of the main target variable for OBP, namely responder rates, were in the three treatment groups: placebo, 39.6%; cilazapril 2.5 mg, 55.6%; and cilazapril 5.0 mg, 65.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Apolipoprotein (a) levels in patients with type 1 diabetes mellitus are unrelated to metabolic control or vascular disease.

Increased serum levels of lipoprotein (a) have been found to be an independent risk factor for coronary heart disease. The major protein constituents of lipoprotein (a) are apolipoprotein B 100 und apolipoprotein (a) (apo(a)). We determined the serum levels of apo(a) and several lipid (cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoproteins A, A1 and B) and glycaemic (HbA1c, fasting blood glucose) parameters in 40 patients with type 1 diabetes mellitus and in 103 age- and sex-matched control subjects. The median serum levels of apo(a) were significantly increased in the type 1 diabetic patients (142.7 vs. 80.0 U/L; P = 0.03), whilst HDL, LDL-cholesterol, and apolipoprotein A, A1 and B levels were lower (P < 0.01). No significant correlation was found between parameters of metabolic control and apo(a) levels. After subdivision of the diabetic patients according to different stages of diabetic nephropathy (DN), determined by urinary albumin excretion, significant relationships were found between DN and triglycerides (P = 0.04), LDL (P = 0.03) and apolipoprotein B (P = 0.008, Kruskal-Wallis test) levels. Apo(a) levels were significantly higher than normal values in patients without DN (P < 0.05), but unrelated to the degree of DN. Patients with diabetic macroangiopathy had significant higher levels of cholesterol (P = 0.0001), triglycerides (P = 0.026), LDL (P = 0.0003), and apoB (P = 0.002) than patients without. Apo(a) levels were unrelated to diabetic macroangiopathy. The significantly elevated levels of apo(a) even in patients without DN or macroangiopathy are noteworthy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Haemostatic abnormalities persist despite glycaemic improvement by insulin therapy in lean type 2 diabetic patients.

Diabetes mellitus is associated with disturbances of the hemostatic system, which might contribute to the development of diabetic vascular disease. We investigated the effect of metabolic improvement by insulin therapy on the haemostatic system in 61 patients with type 2 diabetes mellitus and secondary sulfonylurea failure compared with 45 healthy control subjects matched for age, sex and BMI. Median age was 65, median diabetes duration 10 years. Median HbA1c (10%) and fructosamine (4.0 mM) levels were elevated before induction of therapy and decreased significantly within 6 months of insulin treatment to 7.5% and 3.0 mM, respectively (p < 0.0001). Compared with control subjects, median plasma levels of fibrinogen (317 vs 286 mg/dl), coagulation factor VII activity (1.1 vs 0.89 U/l), von Willebrand factor (1.6 vs 1.3 U/l), D-dimer (105 vs 86 micrograms/l), protein C:Ag (1.24 vs 0.95 U/l), total protein S:Ag (1.15 vs 0.91 U/l), and antithrombin III activity (1.17 vs 1.08 U/l) were significantly elevated. Levels of free protein S were not different from control values. No significant decline of coagulation parameters could be recorded during insulin therapy. Patients with diabetic vasculopathy had higher levels of D-dimer than those without (133 vs 76 micrograms/l before, 109 vs 88 micrograms/l during therapy), whereas the other haemostatic parameters were not different. Our data indicate a significant activation of the coagulation system in diabetic patients with secondary failure to sulfonylurea drugs, with signs of a prethrombotic state and endothelial cell disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Phase-specific function of denial in type 1 diabetic patients after disease onset].

In a longitudinal study we examined 43 patients with type 1 diabetes one week after onset as well as 8 and 24 month later in order to analyze the psychological role of denial processes in correlation to metabolic functions. Only depression decreased over the studied period while coping and denial remained stable. However, the adaptive function of denial after onset with low anxiety, good coping and few complaints became maladaptive over the first two years and the correlation of denial with a centripetal kinship behavior loosened. The destructive effect of denial was indicated only by delayed requests for assistance while no correlation could be shown for phase-specific internal restructuring of the psychological function of denial to compliance and metabolic control.

Adaptation, Psychological

Beta-cell hypersecretion and not reduced hepatic insulin extraction is the main cause of hyperinsulinemia in obese nondiabetic subjects.

Obesity is characterized by peripheral hyperinsulinemia, for which either beta-cell hypersecretion, diminished hepatic insulin extraction, or both may be responsible. To clarify this issue, we investigated insulin secretion and hormone hepatic extraction in 18 nondiabetic obese patients (body mass index [BMI], 39 +/- 1.3 kg/m2) and 18 healthy, lean control subjects (BMI, 21.3 +/- 0.7 kg/m2). Body fat distribution was calculated by measuring the waist to hip ratio (WHR). A highly reduced tissue insulin sensitivity (2.4 +/- 0.5 v 9.5 +/- 1.5 10(4).min-1/[microU/mL], P > .0005) and glucose effectiveness, ie, glucose's ability to stimulate its own disappearance at basal insulin (16 +/- 2 v 30 +/- 3 10(3).min-1, P > .005), were found in the overweight subjects compared with the controls. The basal (76 +/- 14 v 37 +/- 4 pmol/L/min) and total (377,848 +/- 5,562 v 16,864 +/- 1,850 pmol/L) prehepatic insulin secretion and the basal (15 +/- 2 v 7 +/- 0.7 pmol/L/min) and total (8,286 +/- 2,009 v 2,840 +/- 210 pmol/L) posthepatic insulin delivery were significantly higher in the overweight subjects compared with the controls (P < .005), whereas the mean hepatic insulin extraction did not differ (77.8% +/- 2.6% v 79.5% +/- 2.6%). A significant inverse correlation was found between the hepatic insulin extraction and the WHR (r = .5, P > .04), signifying the importance of fat distribution in insulin metabolism. The obese patients were subdivided into two subgroups according to their glucose tolerance; eight patients exhibited a normal tolerance and the remaining 10 were intolerant.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen

Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery.

OBJECTIVE: Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of beta-cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure. SUBJECTS: We studied 16 patients with pHPT, before and 12 weeks after parathyroidectomy; eight of these patients were re-evaluated one year after surgery. The control group consisted of 18 healthy volunteers. DESIGN AND MEASUREMENTS: All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual. RESULTS: The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 +/- 0.5 vs 9.5 +/- 1.5 x 10(4)/min/(microU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 +/- 0.002 vs 0.03 +/- 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 +/- 4769 vs 16864 +/- 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85 +/- 2 vs 76 +/- 2%, P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6 +/- 1 x 10(4)/min/(microU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either. CONCLUSIONS: Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially ameliorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.

C-Peptide

[24-hour blood pressure changes in elderly people with isolated systolic hypertension, essential hypertension and normotension].

In order to evaluate circadian blood-pressure (BP) profile characteristics typical of old age, we compared circadian BP profile in elderly subjects with isolated systolic hypertension (ISH; greater than 160/less than 90 mmHg), essential hypertension (EH; diastolic BP greater than or equal to 95 mmHg), and normotension (N; less than 140/less than 90 mmHg). Each group consisted of 18 subjects, approximately matched in age and sex, (age range 60-82 years; mean age 67.5 years). Ambulatory 24-h BP-monitoring was carried out using a SpaceLabs 90202 with measurements made every 30 min. In ISH, causal systolic BP is higher and circadian systolic BP is lower than in EH (n.s.). Circadian diastolic BP is lower than in EH and higher than in N; both are statistically highly significant (p less than 0.001, u-test, Wilcoxon). The decrease during the resting period is 6 mmHg in EH and 17 mmHg in ISH. In ISH there is a considerable difference of 39 mmHg between casual BP and circadian 24-h BP, in contrast to N and to EH, and this is due to a particular hyperreactivity. This discrepancy is typical of old age and holds the danger of over-treatment, if only causal BP is taken into consideration.

Aged

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.

Adult

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.

Adult