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- Lind, Marcus, 1976, et al.
(författare)
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A systematic review of HbA1c variables used in the study of diabetic complications
- 2008
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Ingår i: Diabetes and Metabolic Syndrome: Clinical Research and Reviews. - : Elsevier BV. - 1871-4021. ; 2:4, s. 282-293
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The predictive power of different HbA1c variables is of importance in prognosis of diabetic complications, clinical guidelines, health-economical analyses and in the design of clinical trials of antidiabetic agents. The aim was to review the literature with regard to the HbA1c variables used, and determine how the predictive power of these relates to diabetic complications. Method: We reviewed 97 full-text articles on HbA1c and diabetic complications. Results: The most commonly used HbA1c variables were: the baseline value, the mean and the "updated" mean HbA1c. Other variables used were the logarithm of the updated mean, the standard deviation, the slope (annual average change), the initial decline (change during the first year), the final value, and the change in HbA1c between baseline and the fourth year. The updated mean, logarithm of the updated mean and mean HbA1c were found to have greater predictive power than baseline HbA1c. The slope, final value, S.D., initial decline and change of HbA1c did not add any further information. The predictive power of the mean or updated mean HbA1c became stronger with longer study lengths. There was a persistent effect over several years between HbA1c values and diabetic complications. Measurements of HbA1c varied from a single value to measurements each month. Conclusions: The use of a mean or the updated mean HbA1c is recommended in the study design. HbA1c values several years old also influence the prognosis of diabetic complications. The possibility of finding a true effect of an antidiabetic agent increases with longer study length. © 2008 Diabetes India.
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- Lind, Marcus, 1976, et al.
(författare)
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The effect of insulin lispro on glycemic control in a large patient cohort.
- 2009
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Ingår i: Diabetes technology & therapeutics. - : Mary Ann Liebert Inc. - 1520-9156 .- 1557-8593. ; 11:1, s. 51-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of rapid-acting insulin analogs and regular insulin differs considerably in countries throughout the world. We therefore studied how glycemic control has been affected by using insulin lispro in clinical practice over 5 years in 14 hospitals in Sweden. METHODS: We used a time period when most patients had not changed the basal insulin, but only the mealtime insulin. Accordingly the most recent years were not suitable since many patients had changed basal insulin from NPH to glargine or determir. We therefore analyzed the metabolic consequences on glycosylated hemoglobin (HbA1c) when changing from regular insulin to insulin lispro from 1997 and during the following 5 years. We studied 1,069 patients with diabetes taking NPH insulin as basal insulin and at least three daily injections of regular insulin, of whom 423 changed their mealtime insulin to insulin lispro and 646 controls who continued with regular insulin. RESULTS: Patients changing to insulin lispro on average decreased by 0.19% units more in HbA1c than those remaining on regular insulin. The effect was most pronounced in patients with high HbA1c even after controlling for regression to the mean. A beneficial effect of insulin lispro was also indicated since patients had the same level of HbA1c during a long period of time with regular insulin but then dropped when changing to insulin lispro. CONCLUSIONS: This study indicates that insulin lispro has had a beneficial and persisting effect on glycemic control when used in patients with diabetes on multiple daily injections of insulin in clinical practice.
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- Lind, Marcus, 1976, et al.
(författare)
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The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: An observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes.
- 2012
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Ingår i: Primary Care Diabetes. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 6:1, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To elucidate methodological questions in assessing the relationship between insulin treatment and cancer, since the risk of tumour growth generally increases with longer exposure time and higher dose of a growth promoting substance. METHODS: Continuous hazard functions for risk of breast and prostate cancer were estimated in relation to exposure of insulin glargine among diabetic patients included in the record system, Diab-Base, as well as in the general population in Sweden. RESULTS: In 7942 female diabetic patients, mean follow-up 7.0 years, 2014 patients initiated insulin glargine with a mean follow-up of 3.5 years. Among 11,613 men, mean follow-up 6.9 years, 2760 had a mean follow-up with glargine of 3.4 years. Risk of prostate cancer decreased significantly with longer exposure to insulin glargine (p=0.032), although average risk versus non-glargine was non-significantly higher (HR 1.37, 95% CI 0.78-2.39). The breast cancer risk did not change with longer exposure to insulin glargine (p=0.35) and the mean risk was similar for glargine and non-glargine (p=0.12). With higher dose of insulin glargine, there was an increase in risk of prostate (p=0.037) and breast cancer (p=0.019). In diabetics, the mean risk of prostate cancer was decreased (HR 0.68, 95% CI 0.59-0.79) but similar for breast cancer (HR 0.95, 95% CI 0.78-1.14) compared to the general population and did not change with longer diabetes duration (p=0.68 and p=0.53 respectively). CONCLUSIONS: Analysing continuous hazard functions for cancer risk in relation to exposure time to an antidiabetic agent is an important complementary tool in diabetes and cancer research.
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- Lind, M, et al.
(författare)
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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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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 53:6, s. 1093-1098
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Tidskriftsartikel (refereegranskat)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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- Lind, Marcus, 1976, et al.
(författare)
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The true value of HbA1c as a predictor of diabetic complications: simulations of HbA1c variables
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:2
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Lind, Marcus, 1976, et al.
(författare)
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Variability of INR and its relationship with mortality, stroke, bleeding and hospitalisations in patients with atrial fibrillation.
- 2012
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Ingår i: Thrombosis research. - : Elsevier BV. - 1879-2472 .- 0049-3848.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND - RATIONALE FOR STUDY: Atrial fibrillation is associated with an increased risk of stroke and mortality which is reduced by treatment with Warfarin. The most commonly used tool to assess the effectiveness of warfarin therapy is the time in therapeutic Range (TTR) of International Normalised Ratio (INR) 2.0-3.0. Our aim was to study whether INR variability, as assessed by the standard deviation of transformed INR (SDT(INR)) is more prognostically important than the TTR. METHODS AND RESULTS: We studied 19,180 patients with atrial fibrillation on warfarin therapy to evaluate the association of TTR and that of SDT(INR) with all-cause mortality, stroke, bleeding and hospitalisation. The SDT(INR) was more prognostically important than the TTR. One standard deviation (SD) higher of SDT(INR) had a hazard ratio (HR) of 1.59 (95% CI 1.52-1.66) of mortality compared with 1.18 (95% CI 1.13-1.24) for one SD lower of TTR. For the other 3 events the HR was also higher for the SDT(INR) than for the TTR (stroke 1.30 (95% CI 1.22-1.39) vs. 1.06 (95% CI 1.00-1.13), bleeding 1.27 (95% CI 1.20-1.35) vs. 1.07 (95% CI 1.01-1.14) , hospitalisation 1.47 (95% CI 1.45-1.49) vs. 1.13 (95% CI 1.10-1.15). When both metrics were included in the same analysis only the SDT(INR) was of significant predictive value. CONCLUSIONS: The SDT(INR) is a better predictor of mortality, stroke, bleeding and hospitalisation than the TTR in patients with atrial fibrillation receiving warfarin therapy.
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| 8. |
- Österbrand, Marcus, 1976, et al.
(författare)
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A method to predict the metabolic effects of changes in insulin treatment in subgroups of a large population based patient cohort.
- 2007
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 22:3, s. 151-7
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Tidskriftsartikel (refereegranskat)abstract
- This case-control study was designed to analyse predictors of the effects on HbA1c levels in 4001 type 1 and type 2 diabetic patients after changing their insulin treatment. Patients from 15 outpatient diabetic clinics were treated with basal insulin and multiple injections of short-acting insulin. The effects on HbA1c of changing from NPH insulin to insulin glargine as basal insulin were studied, compared to patients continuing with NPH insulin. The following possible predictors were examined with multiple regression analysis: age, sex, type and duration of diabetes, smoking, metformin use, insulin requirement, number of basal doses per day, BMI and HbA1c at baseline. The difference between the two regression functions yielded the effect of switching treatment to insulin glargine compared to continuing with NPH insulin. Male gender, low BMI and high baseline HbA1c levels were significant predictors for a greater decrease in HbA1c when changing to insulin glargine. For example, for men with a BMI of 25 and an HbA1c of 8.0%, there was a calculated mean benefit in HbA1c of 0.26 percentage points by changing to insulin glargine, whereas women with a BMI 30 had no benefit of such a change. Thus, changing to insulin glargine had best effect in male patients with low BMI. This is one of the first studies designed to find responders to insulin treatment. Analyses of predictors may prove useful in order to tailor insulin treatment in diabetic patients in clinical practice. The clinical effects need to be confirmed in other studies and randomised controlled trials.
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