Biomedical subjects
Publications and source records attributed to M Kollind.
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AIMS: To test whether a bedtime dose of diazoxide can improve daytime beta-cell function without side-effects in Type 2 diabetes. METHODS: A double-blind randomized study was performed in 27 Type 2 diabetic subjects (17 male, 10 female) who were treated with bedtime insulin and metformin. Subjects received either bedtime diazoxide, 100 mg, or placebo for 9 weeks. Duplicate C-peptide glucagon tests were performed before and in the last days of intervention. RESULTS: No side-effects of diazoxide were detected. Treatment with diazoxide did not incur any increase in bedtime insulin. C-peptide responses to glucagon tended to increase: 0.15 +/- 0.06 nmol/l vs. -0.01 +/- 0.04 nmol/l for placebo, P < 0.06 for difference. Corresponding effects on insulin were 66.2 +/- 41.7 pmol/l for diazoxide vs. -84.2 +/- 51.5 for placebo, P < 0.03. Treatment with diazoxide decreased fasting glucagon levels by 41% vs. placebo, P < 0.03. Glycated haemoglobin (HbA1c) levels were not affected, whereas levels of blood glucose post breakfast were higher during diazoxide (1.34 +/- 0.43 mmol/l, P < 0.01 vs. placebo). CONCLUSIONS: Bedtime treatment with diazoxide in Type 2 diabetic subjects on bedtime insulin and metformin has no significant side-effects, does not increase bedtime insulin supplementation, tends to ameliorate beta-cell function but fails to improve metabolic control.
OBJECTIVE: To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment. STUDY DESIGN: Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998. RESULTS: When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture. CONCLUSION: Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO.
The aim of the present study was to evaluate the effect of the alpha 2-adrenoceptor antagonist idazoxan on hormonal responses and hypoglycaemia symptoms in patients with insulin-dependent (Type 1) diabetes mellitus. Six male Type 1 diabetic patients were studied with and without intravenous infusion of idazoxan. Hypoglycaemia was induced by an intravenous infusion of insulin (100 mU.kg-1.h-1), together with a glucose clamp, to obtain an arterialised venous blood glucose level of 2.3 mmol/l. Idazoxan was given at a dose of 295 micrograms/kg. Venous blood samples were obtained for analyses of free insulin, growth hormone (GH), glucagon and catecholamines. Symptoms were scored on a visual-analogue rating scale. Areas under the curves with and without idazoxan were respectively 22.4 +/- 7.0 vs 33.0 +/- 9.6 micrograms.l-1.h (p = 0.17) for GH, 4.1 +/- 1.1 vs 2.4 +/- 0.9 nmol.l-1h (p < 0.05) for adrenaline, 5.6 +/- 0.9 vs 1.3 +/- 0.5 nmol.l-1.h (p < 0.05) for noradrenaline and 51 +/- 38 vs -40 +/- 11 ng.l-1.h (p < 0.05) for glucagon. Sweating and palpitations were more pronounced during idazoxan infusion than during the control test. It is concluded that idazoxan increases catecholamine and glucagon responses as well as some of the warning signals of hypoglycaemia in Type 1 diabetic patients, whereas the GH response seems less affected by idazoxan.
The aim of the present study was to compare the day-to-day variations of the insulin sensitivity in male and female Type 1 diabetic patients and to assess the insulin sensitivity in the follicular and luteal phases of the menstrual cycle. Ten male and 20 female Type 1 diabetic patients participated in the study. The insulin sensitivity was assessed by the insulin (0.4 mU kg-1 min-1)-glucose/(4.5 mg kg-1 min-1)-infusion test (IGIT). In 5 of the female patients, a simultaneous i.v. influsion of somatostatin (100 micrograms h-1) was given (SIGIT). Each patient was studied twice, with 2 weeks separating the two tests. The day-to-day variations of the insulin sensitivity were almost identical in the male and female patients, the coefficients of variation being 13% in both groups. In 15 of the female patients, ovulation occurred. In these women, the mean blood-glucose levels between 120 and 240 min after the onset of the IGIT/SIGIT were 9.8 +/- 1.1 mmol l-1 in the follicular phase and 10.3 +/- 1.0 mmol l-1 in the luteal phase, n.s. (95% confidence interval for the difference (luteal-follicular) -0.8-1.9 mmol l-1). Although the present study cannot exclude minor changes of insulin sensitivity during the menstrual cycle, our results suggest that the changes of the metabolic control during the menstrual cycle, experienced by many women with Type 1 diabetes, are largely attributable to mechanisms other than variations of insulin sensitivity.
The effect of acute mental stress on insulin sensitivity was evaluated in ten IDDM patients, studied on two occasions (test day and control day) in random order and separated by a period of 1-3 weeks. Mental stress was evoked by a modified filmed version of Stroop's CWT for 20 min. On the control day, the patients were resting quietly during the corresponding period. Insulin sensitivity was estimated by an insulin (0.4 mU.kg-1 x min-1)-glucose (4.5 mg.kg-1 x min-1)-infusion test (IGIT) for 6.5 h. Mental stress evoked significant responses for adrenaline, cortisol and GH, their respective peak values being 0.27 +/- 0.05 nmol/l, 426 +/- 27 nmol/l and 7.6 +/- 1.8 micrograms/l, as well as increases in systolic and diastolic blood pressure and pulse rate The steady-state blood glucose levels, i.e. the mean blood glucose levels 3-6.5 h after the start of the IGIT, were significantly higher after stress, compared with those on the control day, 10.6 +/- 1.5 vs 8.7 +/- 1.4 mmol/l, p = 0.01, demonstrating impairment of the insulin sensitivity by mental stress. It is concluded that acute mental stress induces a state of insulin resistance in IDDM patients, which can be demonstrated by an IGIT to appear 1 h after maximal stress and to last more than 5 h.
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The aim of the study described here was to evaluate the standard deviation (SD) as a measure of blood-glucose variability in IDDM patients under 'normal life' conditions. One hundred IDDM patients performed self-monitoring of blood glucose (SMBG) five times every 2 days for 4 weeks. From these records the following measurements were calculated for each patient: the standard deviation of all blood-glucose values (SDBG), the M-value, the percentage of values < 3 and > 15 mmol l-1 (PE), and the mean, absolute difference of consecutive blood-glucose values (MAD), a novel measure of blood-glucose variability, also taking into consideration the succession of the values. Before the study the patients as well as their physicians were asked to estimate the blood-glucose stability of the patient, using a five-category scale of statements. The patients recorded an average of 64 (range: 32-70) SMBG values. The SDBG was normally distributed with a mean of 3.9 +/- 1.0 mmol l-1. There was a highly significant correlation between the SDBG and the other measures of blood-glucose variability (p = 0.0001, r > 0.8). It appeared that the variation of the SMBG values recorded before dinner contributed to the total glucose variability to a great extent. There was a poor agreement between the subjective estimations of the blood-glucose stability made by the patients and the physicians and the objective measures of the blood-glucose variability. It is concluded that the SD provides an accurate and easily available estimate of blood-glucose variability in IDDM patients practising home blood-glucose monitoring.
The purpose of this study was to evaluate the effectiveness of the warm-air box method on the arterialization of venous blood during euglycaemia and hypoglycaemia. Six healthy male volunteers were studied using an i.v. infusion of insulin (144 mU.kg-1.h-1). Arterial blood glucose was clamped at the baseline level for the first 30 min and subsequently reduced to 3.2 and to 2.5 mmol/lf or 20 min. At each stage, including prior to insulin infusion, arterial, arterialized venous (heating the hand in a warm-air box set to 55-60 degrees C), venous and capillary blood samples were taken simultaneously for analyses of blood glucose and oxygen saturation (not for capillary blood). The oxygen saturations in arterialized blood were approximately 3% below the arterial values. The arterial-arterialized difference of blood glucose was about 0.1 mmol/l (the 95% confidence interval: from -0.19 to 0.41 mmol/l), which tended to correlate with the difference in oxygen saturations between the arterial and arterialized blood samples (r = 0.25, p = 0.08). During the test the forearm venous blood oxygen saturation increased by 9% and the arteriovenous difference in blood glucose ranged from 0.2 to 0.5 mmol/l which correlated significantly with the difference in oxygen saturations (r = 0.48, p less than 0.001). Capillary glucose was similar to the arterialized value. Rectal temperature was stable during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
A five-year follow-up, by means of a personal interview, was performed on patients below the age of 40 years with acute chest pain without obvious organic cause (n = 64). They had been consecutively admitted to the emergency unit over a period of 8 weeks, and had all been subjected to a thorough medical and psychosocial investigation with feedback soon after the initial consultation (investigation patient group, IP). For comparison, a non-investigation patient (NIP) group (n = 51) was recruited over a period of 8 separate weeks. Half of the patients in each group reported at the follow-up that they continued to suffer from chest pain. Compared to normal subjects, they reported more depression. This means that the initial research programme performed in the investigation group had no sustained therapeutic effect compared to routine care at the emergency unit. Tension, anxiety and number of consultations with a physician, as reported in the initial investigation, were negatively correlated with the outcome at follow-up. We conclude that acute chest pain without obvious organic cause in young adults is a condition with an excellent prognosis in strictly physical terms. However, a high proportion of the patients continue to suffer from chest pain for several years, and many of them continue to be consumers of medical resources. We therefore suggest that therapeutic programmes should be developed, particularly for those who report psychological symptoms and those with a history of many consultations with physicians.
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Eight male patients with insulin-dependent diabetes mellitus (IDDM) without residual beta-cell function were studied on two occasions in random order. In one experiment hypoglycemia was induced by a constant rate iv infusion of insulin (0.034 U/kg/h) during 150 minutes. At the other occasion an identical infusion of insulin was given, but this time euglycemia was maintained by a variable iv infusion of glucose. Plasma levels of free insulin were almost identical during the two experiments indicating that insulin clearance is not influenced by hypoglycemia in patients with IDDM.
Clinical symptoms were studied in 69 consecutive patients below the age of 40 years who were attending the emergency unit because of unexplained chest pain. In a structured interview a few weeks after the emergency visit, only one-third of the patients reported that they believed in the doctor's diagnosis; they believed in a psychological or cardiac origin of the pain more often than the doctors. The chest pain was most often described as oppressive and/or stabbing. In 95% of cases it was central or left-sided. Associated symptoms were commonly reported, breathlessness being most commonly reported by two-thirds of the patients, followed by dizziness, palpitation and numbness/tingling. Mental symptoms such as tiredness, anxiety and tension were frequently reported. On the basis of the background literature the aetiology is discussed. We conclude that immediate symptom analysis, including psychosomatic symptoms, particularly breathing problems, is of central importance.
In an attempt to clarify whether circulating insulin per se exerts an inhibitory effect on the hormonal responses to hypoglycemia, with special emphasis on glucagon secretion, nine healthy volunteers were exposed to low dose (244 pmol/kg.h) and high dose (1034 pmol/kg.h) iv insulin infusions for 3 h on two separate occasions. A close to identical arterial hypoglycemia of about 3.4 mmo/L was obtained in both tests by glucose clamping during the high dose test. The corresponding glucose concentration in the venous blood was significantly lower in the high dose test (2.5 +/- 0.1 vs. 3.0 +/- 0.1 mmol/L; P less than 0.01), while the plasma free insulin level was 4 times higher in the high dose test (897 +/- 50 vs. 208 +/- 14 pmol/L). Plasma glucagon was elevated in both experiments, but its rise was reduced during the high dose test after 1 h, yielding an incremental area under the glucagon curve that was significantly smaller than that obtained during the low dose test (213 +/- 70 vs. 348 +/- 81 ng/L.h; P less than 0.05). The plasma adrenaline, noradrenaline, GH, C-peptide, pancreatic polypeptide, and somatostatin profiles were similar in the two tests. We conclude that an inhibitory effect of circulating insulin on the glucagon response to hypoglycemia can be demonstrated in normal man during an infusion of insulin yielding a plasma concentration of about 900 pmol/L. The responses of other hormones studied are not significantly influenced by the circulating insulin level.
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The effect of cyclic somatostatin on circulating insulin levels was studied in eight patients with insulin-dependent diabetes mellitus (IDDM). The study was performed after an overnight fast when their subcutaneous depots of insulin had been depleted during i.v. insulin substitution for 18 hours. A constant rate i.v. insulin infusion (0.4 mU/kg/min) was given for 240 min and somatostatin was co-infused between 60-120 min (100 micrograms/h) and 180-240 min (250 micrograms/h) respectively. Plasma insulin, blood glucose and hematocrit were measured at 15 min intervals. Hematocrit fell from 41.7 to 38.3% during the study period. Somatostatin increased the plasma insulin levels, corrected for the changes of hematocrit, by approximately 8% in the low dose (P less than 0.05) as well as in the high dose (P less than 0.05) period. It is concluded that somatostatin interferes with the clearance of insulin thereby increasing the circulating plasma insulin levels in IDDM patients without residual insulin secretion.
Insulin resistance was assessed after an intravenous infusion of adrenaline (50 ng.kg-1.min-1) or saline (control study) given between 08.00 and 08.30 hours in nine patients with Type 1 (insulin-dependent) diabetes mellitus. The blood glucose level during a somatostatin (100 micrograms/h)-insulin (0.4 mU.kg-1.min-1)-glucose (4.5 mg.kg-1.min-1)-infusion-test performed between 10.30 and 14.30 hours served as an indicator of the total body insulin resistance. Blood glucose was maintained around 7 mmol/l between 08.00 and 10.30 hours by a constant infusion of regular insulin (0.57 mU.kg-1.min-1) and a variable infusion of a 20% glucose solution. The infusion of adrenaline raised plasma adrenaline to 2.7 +/- 0.3 nmol/l (mean +/- SEM) at the end of the infusion; thereafter it returned to its basal level within 30 min. The plasma levels of free insulin, glucagon, cortisol and growth hormone were similar in the adrenaline and the control studies from 08.00 to 14.30 hours. In comparison with the control study the infusion of adrenaline decreased the need for intravenous glucose significantly over the initial 2 h. Furthermore, during the somatostatin-insulin-glucose infusion test the blood glucose rose significantly (p less than 0.05) over the initial 2 h; thereafter no significant differences between the two studies were seen. It is concluded that a short term infusion of adrenaline, resembling the adrenergic hormone response to hypoglycaemia, induces a diabetogenic effect which subsides within 6 h after omission of the adrenaline infusion.
Insulin resistance was assessed after a hypoglycemia induced by insulin (1.5 mU X kg-1 X min-1) between 7 and 8 a.m. in 10 well-insulinized patients with insulin-dependent diabetes mellitus (IDDM). Blood glucose levels during a somatostatin (100 micrograms X h-1)-insulin (0.4 mU X kg-1 X min-1)-glucose (4.5 mg X kg-1)-infusion test (SIGIT) performed between 11 a.m. and 3 p.m. served as an indicator of total body insulin resistance. Plasma epinephrine, growth hormone, and cortisol increased in response to hypoglycemia, while blunted responses of glucagon were simultaneously registered. At the start of the subsequent SIGIT, blood glucose and plasma-free insulin concentrations were similar to those obtained in the control study without preceding hypoglycemia, and at this point all counter-regulatory hormones had returned to basal. During the SIGIT close to identical levels of plasma-free insulin and counter-regulatory hormones were registered, despite which a significant hyperglycemia was seen 2 hours after the start of the SIGIT when preceded by hypoglycemia. In a separate study, the SIGIT was shown to have a good reproducibility in IDDM patients. We conclude that hypoglycemia evokes a state of insulin resistance for several hours, as demonstrated by elevated blood glucose levels during a somatostatin-insulin-glucose-infusion test.