| 1. |
- Ekman, Bertil, et al.
(författare)
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A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults
- 2002
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 147:1, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.
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| 2. |
- Ekman, Bertil, et al.
(författare)
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Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin–angiotensin–aldosterone system
- 2002
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 57:4, s. 473-479
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Tidskriftsartikel (refereegranskat)abstract
- objective To study the effects of individualized recombinant GH substitution, aiming at normal circulating IGF-I levels, in GH-deficient adults on blood pressure, the renin–angiotensin–aldosterone system (RAAS), natriuretic peptides and urine free cortisol.study design Open study with control group. The patients were titrated in dose steps of 0·17 mg GH/day every 6–8 weeks until an IGF-I level around the mean + 1 SD was attained (Tmax). After another month the dose was reduced by 0·17 mg (minimum dose 0·17 mg/day) to produce IGF-I levels at or slightly below the age-related mean (Tend), and this maintenance dose was held constant for 6 months.subjects Eighteen patients (11 males and seven females) with GH deficiency participated. For comparison we also prospectively evaluated 17 matched control subjects.measurements Blood pressure and heart rate, circulating levels of IGF-I, plasma renin activity (PRA), immunoreactive active renin (IRR), angiotensin II, aldosterone, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and 24-h urine aldosterone and urine free cortisol levels.results Blood pressure was unchanged by GH substitution but heart rate increased significantly (P < 0·03). PRA was elevated on the highest GH dose (Tmax) compared to baseline (P < 0·01), but returned to baseline and levels of controls at Tend. Four patients developed transient oedema and tended to have higher PRA levels than the rest of the subjects (P = 0·09). The circulating levels of IRR, angiotensin II, aldosterone, BNP and 24-h urine aldosterone and urine free cortisol levels were unchanged by GH substitution, and did not differ from the levels in the control subjects. Baseline ANP levels in the patients were lower than in the controls (P < 0·01), but increased after GH substitution (P < 0·01) to levels found in with the controls.conclusions We found no major changes of the variables in the circulating renin–angiotensin–aldosterone system and a normalization of atrial natriuretic peptide when an individualized dose of GH was titrated to near-normal IGF-I levels.
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| 3. |
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| 4. |
- Hedman, Christina, 1964-, et al.
(författare)
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Residual β-cell function more than glycemic control determines abnormalities of the insulin-like growth factor system in type 1 diabetes
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:12, s. 6305-6309
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Tidskriftsartikel (refereegranskat)abstract
- The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual β-cell function. Patients with hemoglobin A 1c (HbA 1c) less than 6% (reference range, 3.6-5.4%) were selected for the study. Twenty-two men and 24 women, aged 41.3 ± 13.8 yr (mean ± SD), with a diabetes duration of 17.8 ± 14.6 yr participated. Healthy controls (15 women and nine men), aged 41.3 ± 13.0 yr, were also studied. Overnight fasting serum samples were analyzed for HbA 1c, C peptide, free and total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3 proteolysis. HbA 1c was 5.6 ± 0.5% in patients and 4.4 ± 0.3% in controls. Total IGF-I was 148 ± 7 μg/liter in patients and 178 ± 9 μg/liter in controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated compared with control values. Patients with detectable C peptide (≥100 pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide level despite having identical average HbA 1c. IGFBP-3 proteolysis did not differ between patients and controls. Despite very good glycemic control, patients with type 1 diabetes and no endogenous insulin production have low free and total IGF-I. Residual β-cell function, therefore, seems more important for the disturbances in the IGF system than good metabolic control per se, suggesting that portal insulin delivery is needed to normalize the IGF system.
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| 5. |
- Hedman, Christina, 1964-, et al.
(författare)
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Treatment with insulin lispro changes the insulin profile but does not affect the plasma concentrations of IGF-I and IGFBP-1 in type 1 diabetes
- 2001
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 55:1, s. 107-112
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE IGF-I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF-I and IGFBP-1 than that seen during treatment with conventional human insulin (regular insulin).DESIGN AND PATIENTS Twelve patients with type 1 diabetes, age 47·8 ± 2·4 years (mean ± SEM), body mass index 26·5 ± 1·0 kg/m2, diabetes duration 30·5 ± 3·2 years participated in this open label randomized cross-over study. IGF-I and IGFBP-1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF-I was measured fasting while IGFBP-1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose.RESULTS Lispro gave a marked insulin peak of 135 ± 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0·01). Plasma IGF-I concentration was 78·8 ± 10·9 µg/l on lispro and 82·3 ± 10·5 µg/l on human regular insulin (not significant). AUC for IGFBP-1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0·006) but glycosylated haemoglobin (HbA1c) was 6·4 ± 0·2% on both therapies.CONCLUSIONS Our results indicate that the effect of lispro on IGF-I and IGFBP-1 in patients with type 1 diabetes does not differ from that of human regular insulin.
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| 6. |
- Lindström, Torbjörn, 1952-, et al.
(författare)
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The use of human ultralente is limited by great intraindividual variability in overnight plasma insulin profiles
- 2000
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; 60:5, s. 341-348
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to investigate the usefulness of human ultralente insulin as basal substitution overnight in patients with Type 1 diabetes treated with multiple insulin injection therapy by evaluating the free insulin and glucose profiles, the day-to-day variability and the impact of the time of injection. Methods: Ten patients with Type 1 diabetes and with good metabolic control (mean HbAlc 6.0%), treated with regular human insulin before breakfast, lunch and dinner and human ultralente (Ultratard«) before dinner or at bedtime, were studied. Plasma profiles of blood glucose and free insulin were measured on three occasions from 16.00 h until noon the next day. On two of these occasions Ultratard« was injected before dinner and once it was injected at bedtime in randomized order. Results: Injection of regular insulin before dinner resulted in a high insulin peak during the evening but no insulin peak was found that could be attributed to ultralente. The plasma concentration of free insulin at 03.00 h was 11.0▒1.9 mU/L and it slowly decreased to 6.4▒1.4 at 12.00 h after administration of ultralente at 17.00 h. There were no differences in the mean plasma insulin profiles compared to the other occasion when insulin was given at 17.00 h or at 22.00 h. On the other hand, the intra-individual day-to-day variability of mean insulin concentration during the night was considerable, often exceeding 50%. No differences were noted in the mean blood glucose profiles between the three occasions. Conclusion: Human ultralente insulin gives an insulin profile suitable for overnight substitution, but the great day-to-day variability limits its usefulness. It can be injected before dinner or at bedtime without any change in the insulin profile during the night.
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| 7. |
- Lindström, Torbjörn, 1952-, et al.
(författare)
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Use of a novel double-antibody technique to describe the pharmacokinetics of rapid-acting insulin analogs
- 2002
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 25:6, s. 1049-1054
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—To measure the contribution of bedtime intermediate-acting human insulin on the morning plasma insulin profiles after injection of the rapid-acting insulin analogs lispro and aspart in patients with type 1 diabetes.RESEARCH DESIGN AND METHODS—A total of 14 patients with type 1 diabetes, aged 35 ± 13 years (mean ± SD), participated in this single-blind, randomized crossover study. After taking their usual injection of human intermediate-acting insulin the night before, they were given insulin aspart or insulin lispro (10 units) before a standardized breakfast. The contribution of continuing absorption of the human insulin was measured using a monoclonal antibody not cross-reacting with insulin aspart or lispro, whereas the contribution of the analogs was estimated by subtraction after measurement of all plasma free insulin using an antibody cross-reacting equally with human insulin and both analogs.RESULTS—The correlation coefficient of the fasting free insulin concentrations measured with both insulin methods was 0.95. Fasting free insulin was 95 ± 25 pmol/l before administration of insulin aspart, when determined with enzyme-linked immunosorbent assay detecting only human insulin, and 71 ± 20 pmol/l before administration of insulin lispro (NS). Both insulin analogs gave marked peaks of free insulin concentrations, lispro at 40 ± 3 min and aspart at 55 ± 6 min after injection (P = 0.01). The later part of the profiles, from 4.5 to 5.5 h after injection, were similar and showed almost no contribution of the insulin analogs.CONCLUSIONS—The combination of insulin assays that detect human insulin only or both human insulin and analogs provides a new tool for studying insulin pharmacokinetics. Using this technique, we showed that 4.5 h after administration of the rapid-acting insulin analogs lispro and aspart, the free insulin levels are almost only attributable to the intermediate-acting insulin given at bedtime.
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| 8. |
- Löfgren, U B, et al.
(författare)
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Diabetes control in Swedish community dwelling elderly : More often tight than poor
- 2004
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 255:1, s. 96-101
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine glycaemic control in elderly patients with diabetes living in community dwelling. Design. Descriptive, cross-sectional and open. Prospective with regard to blood glucose. Setting. Community-dwelling in-patients. Subjects. From a total number of 351 patients in seven Swedish centres of community dwelling we identified and recruited all 45 patients with diabetes receiving treatment with insulin, and/or oral medication. Main outcome measures. Blood glucose was measured fasting, 2 h after breakfast, in the evening and at night, for three consecutive days. Results. Mean HbA1c was 5.9 ± 1.1% (range 3.6-8.6%). The patients were split in three HbA1c-groups for analysis: lower- (3.6-5.3%), middle-(5.4-6.3%) and higher-tertile (6.4-8.6%). The groups where similar with regard to age, time in community dwelling, ability to eat and move around independently, but body mass index was lower in the lower tertile (P < 0.003 and P < 0.04, compared with middle- and higher-tertiles). We recorded 14 episodes with blood glucose ≤4.0 mmol L-1 in eight patients. Blood glucose ≤4.0 mmol L-1 was mostly recorded during night (n = 8) or in the morning (n = 3). Conclusions. Swedish patients with diabetes in community dwelling are over- rather than undertreated and have low HbA1c levels. Despite very regular eating habits and near total compliance with medication, hypoglycaemias are frequent and possibly linked to malnutrition.
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| 9. |
- Olsson, PO, et al.
(författare)
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Combination-therapy with bedtime NPH insulin and sulphonylureas gives similar glycaemic control but lower weight gain than insulin twice daily in patients with type 2 diabetes
- 2002
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Ingår i: Diabetes & Metabolism. - : Elsevier Masson. - 1262-3636 .- 1878-1780. ; 28:4 Part 1, s. 272-277
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Tidskriftsartikel (refereegranskat)abstract
- Background: To study the effect on body weight and glycaemic control of two insulin treatment regimens in patients with Type 2 diabetes and moderate failure to oral hypoglycaemic agents. Methods: Sixteen patients treated with oral hypoglycaemic agents (6 men and 10 women) were included in this open-label, randomized, parallel group study. Their age was 62 ▒ 2 (mean ▒ SEM) years (range 44-79 years), body weight 71.3 ▒ 2.9 kg, body mass index (BMI) 24.6 ▒ 0.8 kg/m2. The patients were switched to insulin treatment with bedtime NPH insulin combined with daytime sulphonylurea (combination group) or twice daily injections of a premixed combination of regular human and NPH insulin (insulin twice daily group) with measurements as given below before and after 12 and 24 weeks of treatment. Results: HbA1c was lowered from 8.3 ▒ 0.3% to 7.0 ▒ 0.2% in the insulin twice daily group (p < 0.05) and from 8.3 ▒ 0.3% to 6.8 ▒ 0.5% in the combination group (p < 0.03, ns between treatment groups). Body weight increased from 71.7 ▒ 4.0 kg to 77.6 ▒ 4.4 kg in the insulin twice daily group (p < 0.001) and from 70.8 ▒ 4.6 kg to 72.7 ▒ 5.1 kg in the combination group (ns, p < 0.02 between groups). The dose of insulin at 24 weeks in the insulin twice daily group was 45.8 ▒ 4.2 U and 29.4 ▒ 5.4 U in the combination group (p = 0.03). Combination treatment reduced fasting and stimulated C-peptide levels. Conclusions: Both treatments improved glycaemic control to the same extent but the combination of bedtime NPH insulin and daytime sulphonylurea gave a very small increase of body weight over a 6 months period. We conclude that combination therapy is an attractive alternative when starting insulin treatment in patients with Type 2 diabetes as this is a critical period for weight gain in such patients.
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| 10. |
- Vrethem, Magnus, 1955-, et al.
(författare)
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Painful polyneuropathy in patients with and without diabetes : Clinical, neurophysiologic, and quantitative sensory characteristics
- 2002
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Ingår i: The Clinical Journal of Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0749-8047 .- 1536-5409. ; 18:2, s. 122-127
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study pain characteristics and peripheral nerve involvement in patients with painful diabetic and nondiabetic polyneuropathy in comparison with patients with nonpainful polyneuropathy. Patients and Methods: Fifty-five patients with polyneuropathy (37 with painful polyneuropathy, of whom 19 had diabetes and 18 had no diabetes, and 18 with painless polyneuropathy of different etiologies) were examined clinically using quantitative sensory tests and neurophysiology. Pain intensity and characteristics were analyzed by daily ratings on a 10-step verbal scale and by a questionnaire. Results: Most patients experienced pain of more than one character. There was no clear difference in character or duration of pain between patients with and without diabetes. The mean value of the daily rating of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetic patients. Thirty-two of the 37 patients with pain had paresthesias and/or dysesthesias, whereas only 7 of 18 patients without pain had paresthesias. Pain was always located in the feet, and, in most patients, also in the lower part of the legs. Some patients also experienced pain in the hands. Tactile sensibility, measured by quantitative tests, was more affected in both diabetic and nondiabetic patients with painful polyneuropathy compared with patients without pain (p = 0.02). Temperature, pain, and vibratory sensibility were equally affected in all patient groups. Nerve conduction velocity, amplitudes, and distal latency were equally affected in the pain group as compared with the control group, indicating that both thin and thick nerve afferents are affected in patients with painful as well as nonpainful polyneuropathy and that etiology has no clear impact on nerve involvement. Conclusions: Neuropathy pain was always located in the feet and more severe in diabetic patients compared with patients with neuropathy pain of other etiologies. The authors also found evidence for a greater tactile sensibility involvement in patients with neuropathy pain, irrespective of etiology, whereas other quantitative sensibility and neurography parameters were equally affected in all patient groups.
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