Biomedical subjects
Publications and source records attributed to P E Lins.
Explore the source record for details and available documents.
OBJECTIVE: A number of short-term studies using the continuous glucose monitoring system (CGMS) indicate that improved metabolic control can be observed in patients with type 1 diabetes when CGMS is applied in clinical practice. Data have also accumulated to suggest that spot measurements of glucose performed four times a day would not detect as much as 70% of all hypoglycaemic episodes registered by CGMS. When more frequent reference values were obtained however it was inferred that nighttime hypoglycaemia reported by CGMS may be spurious. As most assessments with CGMS have been utilizing abdominal subcutaneous tissue, we were interested to evaluate whether differences between blood glucose and sensor readings obtained from different sites exist. RESEARCH DESIGN AND METHODS: Two viscometric affinity glucose sensors, applicable to subcutaneous tissue of both forearm and abdomen, were inserted subcutaneously in 12 non-diabetic subjects. Sensors generated glucose data at 3 min intervals and venous blood glucose was determined in duplicates by HemoCue at 15-90 min intervals for 24 hours. Each subject consumed three carbohydrate-rich meals, performed an exercise test, and was observed during nocturnal bed-rest at the research center. RESULTS: The initial decrease of blood glucose during exercise was not fully detected by the sensors. Otherwise, no significant differences between sensor values and blood glucose were observed during day-time. During nocturnal bed-rest abdominal sensor values came approximately 20% lower than blood glucose (P<0.001) and forearm sensor readings. CONCLUSION: It is concluded that a difference between glucose values obtained from abdominal and forearm subcutaneous fat can be observed during nocturnal bed-rest in non-diabetics.
OBJECTIVE: To evaluate the accuracy of nocturnal continuous glucose monitoring by CGMS. RESEARCH DESIGN AND METHODS: A CGMS was inserted in 14 type 2 diabetic patients on combined oral and insulin therapy at altogether 15 occasions. During the second (48 hours) and third (72 hours) night of registration each subject was observed and plasma glucose was analysed seven times during the night by venous sampling and compared to CGMS. These venous values were not used for calibration of the sensor. Pairs of data were analysed using correlation coefficient, Bland-Altman graphs and Clarke Error Grid analysis. RESULTS: 32% of CGMS data did not meet the quality criteria for optimal accuracy and were excluded. A correlation coefficient of 0.80 (p < 0.0001) was seen after 48 hours and a lower coefficient of 0.33 (p = 0.0082) after 72 hours. Bland-Altman analyses demonstrated that the dispersion of the values around the mean of differences was wider after 72 hours as compared to after 48 hours. In the Clark Error Grid analysis 100% of data were within zones A and B after 48 hours, with 60% in zone A. After 72 hours only 44% were in zone A and 7% of data were in the clinically unacceptable zone D. CONCLUSION: The MiniMed Medtronic CGMS has acceptable nocturnal accuracy after 48 hours of registration, but the accuracy thereafter deteriorates with time, implicating that the CGMS thereafter may prove less useful for nocturnal monitoring.
Previous studies have shown that the relationship between gastrointestinal symptoms and gastric emptying is weak. Therefore the quantitative assessment of gastric emptying with a relatively simple, non-invasive test would be of considerable clinical value in insulin-treated diabetic patients to identify those with disturbed gastric emptying. The aim of this investigation was to evaluate the inter- and intra-subject variability of a paracetamol-pasta test in healthy subjects and in IDDM patients. Eighteen healthy subjects (8 women) with a mean age of 37 years (range 19-68) and 19 IDDM patients (10 women) with a mean age of 48 years (range 25-62) and mean duration of diabetes of 28 years (range 6-52) were studied on two occasions with an interval of 1 to 4 weeks. After an overnight fast the subjects ingested a standardized pasta meal mixed with 2 g paracetamol in a period of 15 min. Blood samples were drawn at regular intervals after meal intake and analysed for paracetamol (P) and blood glucose. The serum levels of P were significantly lower at 15 min in diabetic patients. The intra-subject coefficients of variation (CV%) of the areas under the serum paracetamol concentration-time curve (AUC) were almost identical in healthy and diabetic subjects, while the intra-subject CV of the P-Tmax was considerably lower in diabetic patients as well as markedly lower than the corresponding inter-subject CV. The inter-subject CVs of all parameters calculated were generally higher in diabetic patients. This study indicates that the assessment of paracetamol absorption kinetics during a paracetamol-pasta test is reproducible in healthy as well as in diabetic subjects. Diabetic patients with non-optimal glucose control and without a case history indicating gastroduodenal motor function disturbances achieve lower serum concentration of P at 15 min and generally display a higher inter-individual variability indicative of subclinical disturbances of gastric emptying in this group of patients.
The rat is commonly used to evaluate physiological responses of subcutaneous tissue to implanted devices. In vivo longevity of various devices and the biocompatibility of biomaterials depend on how adjacent tissue interacts. How closely the rat model predicts the human response has not been well characterized. The objective of this study was to compare rat and human subcutaneous foreign body responses by monitoring the biochemical environment at a polymer-tissue interface over 8 days using microdialysis. Polyamide microdialysis probes were implanted subcutaneously in humans and rats (n = 12). Daily microdialysis samples were analyzed for glucose, lactate, pyruvate, glycerol, and urea. Blood glucose was also monitored. Analyte concentrations differed significantly between rats and humans at the implant-tissue interface. There were also qualitative differences in the 8-day trends. For example, over 8 days, microdialysate glucose increased two- to fourfold in humans but decreased in rats (P < 0.001). This study reveals profound physiological differences at material-tissue interfaces in rats and humans and highlights the need for caution when extrapolating subcutaneous rat biocompatibility data to humans.
OBJECTIVE: Our aim was to distinguish beneficial effects of B-cell rest from other effects of correction of hyperglycaemia. For this purpose we used diazoxide which reversibly blocks insulin secretion. MATERIAL AND METHODS: Eight obese (age 53 +/- 1 yr: BMI 33 +/- 2 kg/m2: 4 females) type 2 diabetic patients with poor metabolic control (HbA1c 8.7 +/- 0.9% ref.<5.2%) were studied twice after a randomly ordered treatment period of five days of intensive i.v. insulin treatment alone or i.v. insulin with peroral diazoxide (300 mg/day, divided into 3 doses). The glycaemic control was not altered between the two treatment periods. Insulin secretion was measured in response to i.v. glucose and arginine. RESULTS: Insulin infusion was used to achieve close to identical degrees of glycaemia during the two treatment periods. Previous treatment with diazoxide was associated with a moderate 1.9 +/- 0.6 fold rise in insulin response to intravenous glucose (p=0.04) and 1.6 +/- 0.4 fold increased glucose potentiation of arginine-induced insulin secretion (GPAIS) (p=0.04). Conversely, after insulin alone there was no response to i.v. glucose and no change in GPAIS. CONCLUSIONS: Short-term diazoxide treatment improved important parameters of B-cell function and these effects could be dissociated from confounding effects of changes in glycaemia. Consequently, the results indicate beneficial effects of B-cell rest.
OBJECTIVE: To evaluate if insulin has a suppressive effect on the glucagon secretion stimulated by arginine in type 1 diabetes. RESEARCH DESIGN AND METHODS: The alpha-cell response to an i.v. bolus of arginine (150mgkg(-1)) followed by an infusion of arginine (10mgkg(-1)min(-1)) was studied in random order during either low dose infusion (LDT) or high dose infusion (HDT) of insulin in ten patients with type 1 diabetes. The blood glucose level was clamped at an arterialized level of 5mmoll(-1) by a variable infusion of glucose. Venous C-peptide, glucagon, growth hormone, and insulin were analyzed. RESULTS: The mean plasma concentration of insulin was four times higher during the HDT. The C-peptide level did not differ between the LDT and the HDT. During the LDT in response to arginine the blood glucose level increased from 5.0 to 5.8mmol l(-1) although the glucose infusion was markedly reduced, while no change was seen during the HDT. A significantly smaller increase in the glucagon levels during the HDT was seen (area under the curve of 413+/-45 vs 466+/-44pgml(-1)h(-1), P=0.03) while the growth hormone levels were almost identical. CONCLUSION: This study demonstrates that a high level of circulating insulin exerts an inhibitory effect on the glucagon response to arginine in type 1 diabetes. Thus, the suppressive effect of insulin on the glucagon release from the alpha-cell seems to be general and not only dependent on stimulation by hypoglycemia.
The glycaemic and hormonal responses to a hypoglycaemic event induced by an i.v. bolus of insulin was studied in seven type 1 diabetic patients treated first with continuous subcutaneous insulin infusion (CSII) and subsequently with continuous intraperitoneal insulin infusion (CIPII). Arterialised blood glucose and venous hormonal responses were analyzed. HbA1c was improved by CIPII. Although a regimen of a higher basal insulin infusion rate was applied during CIPII the basal peripheral venous insulin levels were lower. The i.v. bolus of insulin resulted in hypoglycaemia in both tests but was more pronounced during the CSII test expressed as a smaller area under the curve (AUC) for the first hour (13.0 +/- 2.3 vs. 13.7 +/- 1.2 mmol l(-1) h(-1), p=0.016, CSII vs. CIPII). The hypoglycaemia resulted in a significant and similar increase in the plasma levels of adrenaline, cortisol and growth hormone in both experiments. A significant increase in the glucagon level was only observed during CIPII. The incremental glucagon response was also significantly more pronounced in the CIPII test expressed as maximal responses (7.5 +/- 3.0 vs. 17.0 +/- 3.1 pg ml(-1), p =0.048, CSII vs. CIPII) as well as incremental AUC (5.1 +/- 12.0 vs. 44.4 +/- 13.2 pg ml(-1) h(-1), p =0.027, CSII vs. CIPII). It seems that CIPII in type 1 diabetic patients could improve the glucagon release to hypoglycaemia. This observation may contribute in explaining why CIPII is associated with a lower incidence of hypoglycaemia in spite of an improvement in metabolic control.
The aim of the study was to compare lispro (LP) and Insuman(R) (I) insulin in continuous subcutaneous insulin infusion (CSII) therapy with respect to blood glucose control as expressed by the standard deviation of blood glucose (SD(BG) ) and HbA(1c) and to monitor the well-being (WBQ) and treatment satisfaction (DTSQ) parameters during such treatment. Forty-one IDDM patients who had used CSII for at least 6 months participated in an open-label, randomized, cross-over, multicenter study for 4 months (2 months LP and 2 months I or vice versa). Boluses with LP were given 5 min before each meal and with I 30 min before each meal. During LP administration compared with I, the SD(BG) of all blood glucose values (3.6 mmol/l vs. 3.9 mmol/l, p=0.012), as well as the SD(BG) of the postprandial, blood glucose values (3.6 mmol/l vs. 4.0 mmol/l, p=0.006), were significantly reduced. The HbA(1c) was significantly lower during LP administration (7.4% vs. 7.6%, p=0.047). The incidence of hypoglycemic events per 30 days (capillary blood glucose<3.0 mmol/l and/or symptoms) did not significantly differ between LP and I (9.7 vs. 8.0 per month, p=0.23). The total amount of daily insulin was slightly but significantly lower with LP, compared to I (38.0 IU vs. 40.3 IU, p=0.004). There was no treatment effects of LP compared to I concerning WBQ and DTSQ. It is concluded that in CSII therapy LP is superior to I with respect to the stability of blood glucose control, a lower HbA(1c), a less insulin requirement without increasing the frequency of hypoglycemia.
We conducted a long-term clinical follow-up of 20 insulin-treated diabetic patients with the problem of repeated severe hypoglycaemic events, identified during 1982-1984. Furthermore, we investigated the reproducibility of a standardized insulin-infusion test among eight of these patients and 10 insulin-dependent diabetes mellitus patients without the problem of severe hypoglycaemia. At start of the follow-up, the patients were characterized, which revealed that proposed risk factors for severe hypoglycaemia were very common and that at least one predisposing factor was present in all patients. No fatal episode of hypoglycaemia occurred in this group of patients during the follow-up. Emergency visits due to hypoglycaemia decreased during the follow-up from 1.05 year(-1) in 1982-1984 to 0.42 year(-1) in 1992-1994 (P=0.024). No association to HbAlc was seen (P=0.11). A correlation with the change to multiple insulin regimen was seen with a incidence of 1.27 year(-1) before the change to 0.47 year(-1) after (P=0.003). The glucose response to an insulin-infusion test appeared reproducible among the patients with recurrent attacks of severe hypoglycaemia.
OBJECTIVES: To study effects of insulin-induced hypoglycaemia on the cardiac repolarization, using QT interval measurements, in patients with type 2 diabetes. DESIGN: Hypoglycaemia was induced by an i.v. insulin-infusion and blood glucose was clamped at 2.7 mmol L-1 for 60 min (T = 90-150 min) in two experiments, with (+GLIB) and without (-GLIB) glibenclamide. In a third experiment, with similar hyperinsulinaemia, glucose was clamped at a euglycaemic level (;5 mmol L-1). ECG was continuously recorded for arrhythmia-monitoring, and 12-lead ECGs were recorded at T = 0 and 150 min. QT intervals were measured, and we determined QT dispersion (difference between the maximum and the minimum QT interval) reflecting interlead variability of repolarization. SUBJECTS: Thirteen patients with type 2 diabetes, on combined insulin and glibenclamide treatment, were studied during hypoglycaemia, and eight of them participated in the euglycaemic experiment. RESULTS: No significant arrhythmias were seen during hypoglycaemia but the mean QT intervals and QT dispersion increased significantly (P < 0.001), with no differences between -GLIB and +GLIB. During the euglycaemic clamp all QT measurements remained unchanged. Serum potassium decreased significantly (P < 0.001) during all three clamps, but the decrease was more pronounced during hypoglycaemia. The change in potassium was not correlated to the degree of QT prolongation or QT dispersion. CONCLUSIONS: Significant changes in the repolarization of the heart can be seen during hypoglycaemia in patients with type 2 diabetes, indicating an increased risk of arrhythmia at low blood glucose levels.
AIM: To explore whether the lowering of insulin relates to changes in leptin following weight reduction after vertical banded gastroplasty (VBG) in seven grossly obese women (BMI 45.9 +/- 1.5 kg/m2). RESULTS: At 6-24 months after VBG, BMI was reduced to 31.3 +/- 0.9 kg/m2 (p < 0.018), leptin from 43 +/- 9 to 12 +/- 2 ng/ml (p < 0.018) and insulin from 172 +/- 19 to 71 +/- 2 pmol/l (p=0.018). The reduction in leptin correlated to the reduction in insulin (r = 0.94, p = 0.002) but not to that of BMI (r = 0.05, NS). CONCLUSION: Reduction in insulin seems more important for reduction in leptin than lowering of BMI, suggesting a close association between leptin and insulin in obese subjects.
AIMS: To evaluate the effect of adding insulin to sulphonylurea (SU) and the effect of SU withdrawal on glycaemic control in Type 2 diabetic patients who failed on treatment with SU alone. METHOD: One hundred and seventy-five patients were included in a placebo-controlled multicentre study. During phase I (4 months), premixed insulin was added to glibenclamide therapy; during phase II (1-4 months, depending on response) the insulin dose was fixed, while placebo or glibenclamide replaced the open SU therapy. Insulin sensitivity (KITT), beta-cell function (C-peptide) and metabolic control (HbA1c) were monitored. RESULTS: HbA1c improved from 9.65% to 7.23% (P < 0.0001) during phase I. A high HbA1c value (P < 0.0001) and a high KITT-value (P = 0.045) at baseline were associated with a beneficial response to combination treatment. During phase II, glycaemic control was unchanged in the control (glibenclamide) group. In the placebo group, after SU withdrawal, fasting blood glucose (FBG) increased by 10% or more within 4 weeks in 79% of the patients. Patients (67 of 112) with an FBG increase > or =40% during phase II were defined as 'SU responders' by protocol. In a multivariate analysis only a long duration of diabetes was associated with SU response. There were more GAD-antibody-positive patients among non-responders (18% vs. 4%, P = 0.0263). CONCLUSIONS: Poor glycaemic control in combination with preserved insulin sensitivity and lack of GAD antibodies predicts a beneficial response to combination therapy, which can be achieved in 75% of patients with SU failure.
Intensifying pharmacological therapy in patients with type 2 diabetes increases the risk of hypoglycemia and often requires the simultaneous use of more than one agent. Combining insulin and sulfonylurea is an effective and frequently used therapy in such patients. However, sulfonylurea derivatives have been shown to affect the release of glucagon, indicating a possible effect of such therapy on hormonal counterregulation to hypoglycemia. Thirteen patients receiving combined therapy were studied on two occasions: 1) after a wash-out period of glibenclamide (-GLIB), and 2) after resuming combined treatment for 6 months (+GLIB). We performed nonstep-wise, hyperinsulinemic hypoglycemic clamps using a constant i.v. insulin infusion and clamping blood glucose at 2.7 mmol/L (48 mg/dL) for 60 min. C Peptide levels were significantly higher during + GLIB, but no significant differences were seen in peripheral plasma insulin levels (+GLIB mean +/- SD, 70 +/- 17 mU/L vs. -GLIB, 75 +/- 14; P = 0.26). Epinephrine responses were similar in the two tests, but when glibenclamide was present the glucagon response was smaller, both the peak value (P = 0.016) and the incremental area under the curve (P = 0.011) as well as the total area under the curve (P = 0.016). These results suggest that intraislet insulin secretion is of importance for the alpha-cell responsiveness to hypoglycemia in these patients.
This study evaluated the effect of cisapride on glycaemic control, well-being and treatment satisfaction in insulin-dependent diabetes mellitus (IDDM) patients with documented moderate to severe glycaemic instability. Thirty-seven patients with glycaemic instability were included in a randomized, double-blind, placebo-controlled, cross-over study. Patients were instructed to take cisapride 10 mg q.i.d. or placebo tablets q.i.d. (15 to 30 min before each of the three main meals and before bedtime) for two periods of four weeks. The first treatment period was followed by a wash-out period of four weeks, with placebo treatment. Patients measured blood glucose with a glucometer before breakfast, lunch, dinner, 90 min after dinner and before bedtime every two days. After each treatment period, glucose data were collected from the glucometer to calculate the standard deviation (SDBG) of self-monitored blood glucose (SMBG). Questionnaires designed to measure well-being and treatment satisfaction were also completed initially and after each of the two treatment periods. There were no treatment effects of cisapride compared to placebo with respect to SDBG, mean glucose, percentage of extremes, number of hypoglycaemic episodes, insulin requirement, insulin variability, well-being, or treatment satisfaction. Cisapride 10 mg q.i.d. given for four weeks did not affect diabetic control or well-being and treatment satisfaction in a group of IDDM patients with glycaemic instability, i.e. a standard deviation of blood-glucose > 3.9 mmol/l.
This study was performed to determine whether metabolic and hormonal responses during moderate exercise differ between continuous intraperitoneal insulin infusion (CIPII) and continuous subcutaneous insulin infusion (CSII). In seven Type 1 diabetic patients, treatment was changed from CSII to CIPII. Prior to the change, these patients performed an ergometer exercise at 60% of VO2max for 40 min followed by a 200-min rest. About one year later, when the procedure was repeated during CIPII, HbA1c had improved from 8.5 to 7.1%. Arterial blood glucose, venous lactate and hormonal responses were analysed. Although a regimen with a higher basal insulin infusion rate was applied during the exercise test on CIPII, corresponding venous insulin levels were lower (28.0 +/- 2.2 vs. 48.1 +/- 7.9 pmol L-1, p = 0.04). Exercise caused a more marked decline in blood glucose during CIPII, with nadir blood glucose at the end of exercise (3.6 +/- 0.4 vs. 5.1 +/- 0.4 mmol L-1, p = 0.005). Both exercise tests yielded significant and similar increases in plasma levels of adrenaline, noradrenaline, cortisol and growth hormone. A significant rise in plasma glucagon (15.1 +/- 4.5 pg mL-1, p = 0.01) was observed during CIPII, but not during CSII (7.4 +/- 3.5, pg mL-1, n.s.). It is concluded that patients on CIPII should reduce their insulin infusion rate during exercise. CIPII appears to have favourable effects on counterregulatory capacity; in particular, a more prominent glucagon response to exercise may prove important.
BACKGROUND: The objective was to elicit whether hormonal responses to and subjective symptoms of hypoglycemia are modified during pregnancy in patients with insulin-dependent diabetes mellitus. METHODS: In ten type I diabetic women, hyperinsulinemic hypoglycemic clamps, with target arterial blood glucose content of 2.2 mmol/l, were performed during the third trimester of pregnancy and 5-13 months after delivery. The levels of arterial glucose and venous catecholamines, pituitary growth hormone, cortisol, glucagon, dehydroepiandrosterone and free insulin were assessed repeatedly. Subjective symptoms of hypoglycemia were recorded on a visual analog scale. The paired t-test and Wilcoxon signed rank test were used for statistical comparisons. RESULTS: Adrenaline and dehydroepiandrosterone increased during hypoglycemia on both occasions, but dehydroepiandrosterone disclosed a significantly different pattern of response during pregnancy (p=0.016). The cortisol increase was augmented during pregnancy (420+/-50 vs. 310+/-30 nmol/l non-pregnant, p=0.039), while the increase in pituitary growth hormone (hGH) was diminished (5.4+/-1.2 vs. 27.9+/-5.4 microg/l non-pregnant, p=0.001), but nevertheless the increase during pregnancy was significant (p=0.002). Three of the eight subjective symptoms of hypoglycemia recorded were less prominent during pregnancy, namely 'inability to concentrate' (p=0.03), 'headache' (p=0.01) and 'pounding heart' (p=0.03). CONCLUSIONS: Albeit some subjective symptoms were diminished during pregnancy, the study gives no evidence that, in diabetic patients, pregnancy per se impairs the counterregulatory response to hypoglycemia, with the exception of growth hormone. However, despite the suppressed basal growth hormone secretion in late pregnancy, the study disclosed a secretory response of this hormone at hypoglycemia.
OBJECTIVE: To study the effect of induced hypoglycaemia on serum levels of the placental hormones oestriol, human placental lactogen, placental growth hormone and progesterone in the third trimester of pregnancy. DESIGN: A prospective experimental investigation. SETTING: High risk pregnancy unit and diabetes research unit at Karolinska Institutet Danderyd Hospital, a university hospital. PARTICIPANTS: Ten women with insulin-dependent diabetes mellitus in the third trimester of pregnancy. METHODS: Venous blood samples were collected every 15 minutes for analyses of oestriol, progesterone, human placental lactogen and placental growth hormone, during the 150 min of a hyperinsulinaemic hypoglycaemic clamp, which maintained arterial blood-glucose level of about 2.2 mmol/l. MAIN OUTCOME MEASURES: Levels of analysed placental hormones during hypoglycaemia. RESULTS: A statistically significant increase was observed in placental growth hormone during hypoglycaemia (P < 0.0001), whereas the placental hormones progesterone, human placental lactogen and oestriol did not show changes of clinical significance. CONCLUSIONS: The increase in placental growth hormone indicates that the placenta is an endocrine organ which may take an active part in acute metabolic processes, such as here in the hormonal counterregulation of hypoglycaemia.