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- Lind, M, et al.
(author)
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The shape of the metabolic memory of HbA(1c): re-analysing the DCCT with respect to time-dependent effects.
- 2010
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 53:6, s. 1093-1098
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: We determined the shape of the metabolic memory of HbA(1c) and its contribution to retinopathy, as well as the importance of reducing HbA(1c) to prevent progression of retinopathy. METHODS: The relative risk contribution of HbA(1c) values at different points in time to current progression of retinopathy was determined in the DCCT patients. RESULTS: HbA(1c) 2 to 3 years earlier had the greatest relative risk contribution to current progression of retinopathy. HbA(1c) up to 5 years earlier made a greater contribution than current values, while values from 8 years earlier still had an important impact. When HbA(1c) had been at 8% for a long period and was subsequently lowered to 7%, the salutary effects did not begin to appear until 2 to 3 years after lowering. The hazard function for a constant level of HbA(1c) increased with time. The numbers needed to treat when reducing HbA(1c) from 8.3% to 8% from diagnosis was estimated to be 1,688 for the first 3 years and 13 for the period 9 to 12 years. Survival functions when reducing HbA(1c) from 8% to 7% show that pre-study glycaemic control dominates the effect on progression of retinopathy during the first years of a trial. CONCLUSIONS/INTERPRETATION: The most harmful effect of hyperglycaemia on progression of retinopathy in type 1 diabetes initially increases, but declines after roughly 5 years. The salutary effect of reducing HbA(1c) accelerates with time and becomes greater in clinical practice than has been previously understood. Clinical trials should preferably be designed for long periods or include patients with low previous glycaemic exposure to distinguish trial effects from those of the metabolic memory.
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- Anderson, J., et al.
(author)
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Effect on glycemic control by short- and long-term use of continuous glucose monitoring in clinical practice
- 2011
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In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 5:6, s. 1472-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: In Sweden, patients with diabetes mellitus frequently receive short-term (<3 months) continuous glucose monitoring (CGM) to study glucose patterns or long-term CGM to treat poor glycemic control or severe hypoglycemia. The effects of CGM on glycemic control in clinical practice in relation to indication and duration of use has not been completely studied. METHODS: Patients with diabetes, among which 99% were diagnosed as type 1, receiving CGM at 10 outpatient clinics in Sweden were studied retrospectively. Long-term use of CGM was defined as >/= 3 months use of CGM and short-term as <3 months. A control group matched on start date and date of latest value 3 months after the start was selected for both long- and short-term groups. RESULTS: In 34 long-term users of CGM, over a mean follow-up of 1.1 years, the adjusted mean difference of hemoglobin A1c (HbA1c) compared with controls (n = 408) was -0.76 (95% confidence interval -1.17; -0.33, p < .001). Long-term users with indications for high HbA1c (n = 15) had a reduction of 1.2% in HbA1c from 10.1 to 8.9% (p = .003), whereas patients with hypoglycemia as their indication (n = 16) decreased by 0.3% (p = .17). Nonsevere hypoglycemic events decreased in long-term users within the same follow-up period (p = .004). Short-term users showed no statistically significant improvement in HbA1c compared with controls at 1.1 years (n = 41), p = .85 or at 2.6 years (n = 43), p = .19. CONCLUSION: Long-term CGM use was associated with improved glycemic control in clinical practice and a reduction in nonsevere hypoglycemic events, whereas short-term use had no effect on HbA1c. The effect on glycemic control varied by indication.
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- Choong, FX, et al.
(author)
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Real-time optotracing of curli and cellulose in live Salmonella biofilms using luminescent oligothiophenes
- 2016
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In: NPJ biofilms and microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 2, s. 16024-
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Journal article (peer-reviewed)abstract
- Extracellular matrix (ECM) is the protein- and polysaccharide-rich backbone of bacterial biofilms that provides a defensive barrier in clinical, environmental and industrial settings. Understanding the dynamics of biofilm formation in native environments has been hindered by a lack of research tools. Here we report a method for simultaneous, real-time, in situ detection and differentiation of the Salmonella ECM components curli and cellulose, using non-toxic, luminescent conjugated oligothiophenes (LCOs). These flexible conjugated polymers emit a conformation-dependent fluorescence spectrum, which we use to kinetically define extracellular appearance of curli fibres and cellulose polysaccharides during bacterial growth. The scope of this technique is demonstrated by defining biofilm morphotypes of Salmonella enterica serovars Enteritidis and Typhimurium, and their isogenic mutants in liquid culture and on solid media, and by visualising the ECM components in native biofilms. Our reported use of LCOs across a number of platforms, including intracellular cellulose production in eukaryotic cells and in infected tissues, demonstrates the versatility of this optotracing technology, and its ability to redefine biofilm research.
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- Fahlén, M, et al.
(author)
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Megestrol acetate may stimulate the production of insulin-like growth factor 1 in breast tissues of women with breast cancer
- 2013
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In: Hormone molecular biology and clinical investigation. - : Walter de Gruyter GmbH. - 1868-1891 .- 1868-1883. ; 13:3, s. 51-4
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Journal article (peer-reviewed)abstract
- In women with breast cancer who were treated with either continuous tamoxifen alone or sequential tamoxifen followed by megestrol acetate (MA), we demonstrated significant positive associations between the breast tumor estrogen receptor (ER) and an increase in serum sex hormone-binding globulin (SHBG) during tamoxifen treatment. We interpreted this as “ER uniformity” in different tissues, e.g., breast, liver. No other associations with ER were found. In the same study, the breast tumor progesterone receptor (PR) was determined. Our aim was to see if there were any associations between PR and endocrine changes during MA treatment.The breast tumor PR before treatment and serum insulin-like growth factor I (∂IGF-1), steroids, steroid-binding proteins, and insulin before and during treatment were measured in 17 postmenopausal women with breast cancer who were treated sequentially with tamoxifen 40 mg/day followed by MA 160 mg/day in alternating 3-month periods.During MA treatment periods, the levels of IGF-1 and insulin increased significantly, whereas the levels of androgens, SHBG, corticosteroid-binding globulin, and cortisol decreased significantly. Significant positive correlations were found between the PR content and increments in ∂IGF-1 but not between PR and any other endocrine change.PR expression in human liver is very weak, but malignant and normal breast tissues secrete considerable amounts of growth hormone and IGF-1 in vitro and in vivo. This activity is stimulated by progestogens. The association between PR and ∂IGF-1 may therefore reflect a direct PR-mediated action of MA on malignant and normal human breast tissues in vivo.
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- Fahlén, M, et al.
(author)
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Optimization of basal insulin delivery in Type 1 diabetes: a retrospective study on the use of continuous subcutaneous insulin infusion and insulin glargine.
- 2005
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In: Diabetic medicine : a journal of the British Diabetic Association. - : Wiley. - 0742-3071. ; 22:4, s. 382-6
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Journal article (peer-reviewed)abstract
- AIMS: To compare the effects on glycaemic control after using continuous subcutaneous insulin infusion (CSII) or insulin glargine. METHODS: Data were obtained from 17 diabetes outpatient clinics in Sweden, employing the same diabetes data management system. Type 1 diabetic patients using multiple dose injections were included prior to starting on either CSII (n = 563) or glargine (n = 513). The median duration of therapy was 25 months for CSII and 6 months for glargine. The comparison between the treatment modalities was carried out by multiple regression analysis and logistic regression analysis in an attempt at reducing the influence of confounding factors. RESULTS: The mean HbA1c decrease was 0.59 +/- 1.19% for CSII and 0.20 +/- 1.07% for glargine (P < 0.001, when assessed by logistic regression). An additional 0.1% lower HbA1c would be expected if glargine had been optimized with basal insulin 40-60% of the daily dose. The more pronounced effect of CSII was achieved with a lower daily dosage of insulin. In a multiple regression analysis with a change of HbA1c as the dependent variable, the following variables were significant: choice of treatment (P < 0.001), HbA1c prior to treatment (P < 0.001) and BMI prior to treatment (P < 0.01). CONCLUSION: Both regimes improved metabolic control, but CSII resulted in significantly higher reduction in HbA1c than after insulin glargine treatment, particularly in those individuals who had higher levels of HbA1c at baseline.
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- Lind, Marcus, 1976, et al.
(author)
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The true value of HbA1c as a predictor of diabetic complications: simulations of HbA1c variables
- 2009
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:2
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Journal article (peer-reviewed)abstract
- Aim The updated mean HbA1c has been used in risk estimates of diabetic complications, but it does not take into account the temporal relationship between HbA1c and diabetic complications. We studied whether the updated mean HbA1c underestimated the risk of diabetic complications. Method Continuous HbA1c curves for 10,000 hypothetical diabetes patients were simulated over an average of 7 years. Simulations were based on HbA1c values encountered in clinical practice. We assumed that each short time interval of the continuous HbA1c curves had a long-lasting effect on diabetic complications, as evidenced by earlier studies. We tested several different HbA1c variables including various profiles, e.g. different duration, of such a long-lasting effect. The predictive power of these variables was compared with that of the updated mean HbA1c. Results The predictive power of the constructed HbA1c variables differed considerably compared to that of the updated mean HbA1c. The risk increase per standard deviation could be almost 100% higher for a constructed predictor than the updated mean HbA1c. Conclusions The importance of good glycemic control in preventing diabetic complications could have been underestimated in earlier hallmark studies by not taking the time-dependent effect of HbA1c into account.
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