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1.
  • Agardh, Carl-David, et al. (author)
  • The prognostic value of albuminuria for the development of cardiovascular disease and retinopathy: a 5-year follow-up of 451 patients with type 2 diabetes mellitus
  • 1996
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 32:1-2, s. 35-44
  • Journal article (peer-reviewed)abstract
    • The aim of the present study was to evaluate the risk for vascular morbidity or death and retinopathy in relation to urinary albumin concentration. To that end, we performed a 5-year follow-up study of all type 2 diabetic patients attending the outpatient-clinic. A total of 444 (98.4%) out of 451 adult patients initially studied were evaluated for the degree of retinopathy and levels of HbA1c blood pressure, serum creatinine and urinary albumin. Vascular morbidity and causes of death were registered by one and the most severe event only. Forty-seven patients developed atherosclerotic vascular disease, i.e. myocardial infarction (n = 19), cerebrovascular disease (n = 20), or amputation (n = 8), and 42 died. The observed annual mortality rate was 22.1/1000 compared to an expected rate of 13.6/1000 for the general population with corresponding age and sex. Urinary albumin concentration was found to be a prognostic marker for the development of vascular disease and death in patients treated with insulin at baseline (P < 0.01), whereas this was not the case in patients treated with diet and/or oral agents at baseline. However, insulin treatment per se was not associated with an increased mortality or mortality or morbidity. Urinary albumin concentration was not correlated with incidence or progression of retinopathy regardless of type of diabetes treatment. In conclusion, this study showed that albuminuria was a prognostic factor for vascular morbidity and death in type 2 diabetic patients treated with insulin but not in patients treated with diet or oral agents. Furthermore, albuminuria was not a predictor for incidence or progression of retinopathy.
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4.
  • Karlson, Björn, et al. (author)
  • Influence of intensified insulin regimen on quality of life and metabolic control in insulin-dependent diabetes mellitus
  • 1994
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 25:2, s. 111-115
  • Journal article (peer-reviewed)abstract
    • Seventy-eight non-randomized patients with IDDM, aged 33.8 +/- 9.6 years (mean +/- S.D.), with a duration of diabetes of 16.6 +/- 9.5 years and a HbA1c level of 8.0% +/- 1.5 at baseline were included in the study. The effects of a change from a 3-dose insulin regimen using conventional syringes to a treatment mode using 4 injections per day with a pen injector on metabolic control, perceived distress from diabetes on everyday life and correspondence between expectations and experiences of treatment during a 1-year trial were assessed. The experience measures were registered at baseline and after 3 and 12 months, respectively. HbA1c levels were measured every 3 months. Neither the metabolic control nor the body mass index or rate of hypoglycemic episodes changed during the study period. However, the patients experienced a decreased distress from diabetes, which appeared during the first 3 months and remained unchanged thereafter. The expectations of advantages from the intensified insulin therapy were generally high and were mostly either fulfilled or exceeded by experiences. We conclude that multiple insulin injection therapy, under routine treatment conditions, is subjectively preferable to patients and has favourable effects on their quality of life although something more is required in order to also achieve an improvement of metabolic control.
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5.
  • Samuelsson, Ulf, 1951-, et al. (author)
  • Islet autoantibodies in the prediction of diabetes in school children
  • 2001
  • In: Diabetes Research and Clinical Practice. - 1872-8227 .- 0168-8227. ; 51:1, s. 51-57
  • Journal article (peer-reviewed)abstract
    • In 1987 serum was collected from 1031 non-diabetic schoolchildren in the Southeast area of Sweden with the aim of evaluating islet autoantibody status (ICA, GADA and IA2-ab) in the prediction of diabetes in schoolchildren. The clinical development of Type 1 diabetes in the children was assessed in 1994 and 1997. The combination of ICA, GADA and IA2-ab were found in four subjects whereas six had two and 35 children one of these antibodies. After 10 years, six of the 1031 children had developed clinical diabetes and five of these six children were positive for islet antibodies. Two were positive for all three antibodies, two were positive for ICA and GADA, and one was positive for GADA. Among the individual autoantibodies, ICA showed the highest positive predictive value (29%) whereas the predictive value for the combination of two autoantibodies was highest for GADA and ICA (40%). Thus, GADA and ICA measurements may be a rational approach to detect schoolchildren at risk for developing diabetes.
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6.
  • Tallroth, Gustav, et al. (author)
  • The influence of different insulin regimens on quality of life and metabolic control in insulin-dependent diabetics
  • 1989
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 6:1, s. 37-43
  • Journal article (peer-reviewed)abstract
    • Administration of insulin with premeal boluses of short-acting insulin using a new injection device (Novopen) was compared with a conventional three times daily injection regimen regarding aspects of quality of life and metabolic control in insulin-dependent diabetes mellitus (IDDM). Eighteen C-peptide-negative patients with IDDM (16 men, two women, aged 31.0 ± 7.4 years, duration of diabetes 13.0 ± 4.6 years; mean ± SD) participated in the study. All patients had been treated with three daily insulin injections for at least 1 year prior to the study. The patients were randomized into two groups. Group A started a 3-month treatment period with premeal injections of short-acting insulin and intermediate-acting insulin at bedtime. This period was followed by another 3 months using the initial three times daily injection regimen. Group B completed the study in the reverse order. Quality of life was assessed by using questionaires and personal interviews by the same clinical psychologist. Metabolic control was assessed by measuring the levels of glycosylated hemoglobin. The results show that both treatment groups experienced a general improvement in mood and well-being during the period with multiple insulin injection treatment. Furthermore, during the periods of insulin pen treatment, an increased experience of freedom and less dependence on fixed meal times were noted. Overall metabolic control, insulin dosage, body weight, and number of hypoglycemic episodes did not changes during the study. It is concluded that metabolic control, safety, and number of hypoglycemic episodes using premeal doses of short-acting insulin using Novopen were not different from those seen during conventional treatment. However, the experienced effects and consequences on quality of life during this treatment regimen were generally more positive with an increased feeling of freedom and improvement in mood.
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7.
  • Andersson, P. O., et al. (author)
  • Pen injection and change in metabolic control and quality of life in insulin dependent diabetes mellitus
  • 1997
  • In: Diabetes Research and Clinical Practice. - 0168-8227 .- 1872-8227. ; 36:3, s. 169-172
  • Journal article (peer-reviewed)abstract
    • A second follow-up of metabolic control and quality of life in insulin dependent diabetes mellitus (IDDM) patients who had switched 3 years before from syringe to multiple pen injection treatment, was carried out. A total of 73 consecutive outpatients were enrolled in the initial follow-up study in 1988, 1 year after their changeover to insulin pen, with their metabolic control and quality of life examined. The present study concerns the reexamination of 65 of them in 1990. Their HbA(1c) level was recorded yearly, already from 1987, on. After an enhancement of metabolic control in 1988, exhibited primarily by patients with fewer syringe injections before pen treatment, control up to 1990 was found to have regressed to about baseline level or to have gradually declined. Patients who perceived their ability to self-test blood glucose to have decreased exhibited the least satisfactory course of metabolic control. This is seen to indicate that maintaining self-testing in multiple injection insulin treatment is a very real challenge to this regimen.
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8.
  • Boquist, Lennart, et al. (author)
  • Mitochondrial changes and associated alterations induced in mice by streptozotocin administered in vivo and in vitro.
  • 1987
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 3:4, s. 179-190
  • Journal article (peer-reviewed)abstract
    • Isolated mouse liver mitochondria incubated with streptozotocin showed decreased rate and extent of Ca2+ uptake, and, dependent on the concentration of streptozotocin and the addition of alpha-ketoglutarate, glutamate, fluorocitrate or guanosine 5'-triphosphate, the retention of Ca2+ was either increased or decreased. Similar observations were made in liver mitochondria incubated with succinyl-CoA. In mitochondria isolated from the kidneys and islets of mice injected with streptozotocin, with and without additional injections of glucose and/or glucagon, the rate and extent of Ca2+ uptake were reduced and the release of accumulated Ca2+ was stimulated. Electron microscopy and X-ray microanalysis showed dislocation of Ca2+-containing precipitates from the mitochondria to the cytosol, and stereology disclosed increased mitochondrial volume in the B cells of streptozotocin-treated mice. State 3 and state 4 respiration with NAD-linked substrates was inhibited, but succinate oxidation was unaffected, in mitochondria isolated from the kidneys of mice treated with streptozotocin. In the kidneys of streptozotocin-injected mice, the concentration of succinyl-CoA was increased, that of citrate and guanosine 5'-triphosphate was decreased, that of glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-diphosphate was unaffected, and the metabolite concentration ratios suggested increased mitochondrial [NAD+]/[NADH] ratio and decreased cytoplasmic [NAD+]/[NADH] ratio. It is suggested as a new hypothesis that the cytotoxicity and the diabetogenicity of streptozotocin are dependent on inhibited citric acid cycle enzyme activity (primarily that of succinyl-CoA synthetase and citrate synthetase) with altered metabolite concentrations, leading to impairment of the mitochondrial uptake of Ca2+ and the activation of the pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases.
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9.
  • Hanås, Ragnar, et al. (author)
  • Side effects and indwelling times of subcutaneous catheters for insulin injections : a new device for injecting insulin with a minimum of pain in the treatment of insulin-dependent diabetes mellitus
  • 1990
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 10:1, s. 73-83
  • Journal article (peer-reviewed)abstract
    • For 2 months we observed side-effects and indwelling times when using a subcutaneous catheter (Insuflon, Viggo AB, Sweden) for insulin injections. This method is used by approximately 600 children and adolescents with IDDM in Sweden today. 22 children and adolescents aged 4–19 years with a diabetes duration of 4.0 ± 3.0 (mean ± SD) years participated. Their HbA1c was 5.8 ± 1.0%. All used 4–6 dosages of insulin per day. The catheter was placed subcutaneously in the abdominal wall, and replaced by parents when home tests showed increased blood or urine glucose, when the child experienced pain or when skin changes were observed. The 22 patients used 239 catheters with a mean time between changing catheters of 4.8 ± 2.2 (range 0.5 – 17) days (= 1147 catheter days). Noted side effects were (% of catheter days): fixation problems, 5.6%; minor infection/irritation (= redness > 1 mm), 5.6%; pain, 2.8%; sore skin from plastic wings, 2.4%; itching/dry skin, 2.0%; eczema from band-aid, 1.7%; blocked catheter/injection needle, 1.6%; leakage of insulin, 1.3%, transient lipohypertrophies, 1.1%; hematoma/blood in catheter, 0.8%, and moist skin, 0.3%. No major infections requiring surgical or antibiotic treatment occurred. In conclusion, the use of indwelling insulin catheters seems to be a safe method to lessen the pain of insulin injections with a low frequency of side effects. The long-term metabolic control was not altered in this group of well-controlled children. We therefore find that we can recommend the use of indwelling catheters to children and adolescents who have difficulties with injections because of needle phobia or pain, particularly when using MIT.
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10.
  • Hedbrant, Johan, et al. (author)
  • Särimner : a computer model of diabetes physiology for education of physicians and patients.
  • 1991
  • In: Diabetes Research and Clinical Practice. - 0168-8227 .- 1872-8227. ; 14:2, s. 113-122
  • Journal article (peer-reviewed)abstract
    • Often diabetic patients have developed their skills by some trial-and-error-like training over a long period of time. To minimize this inconvenience we have made a mathematical model to facilitate diabetes education. The model consists of a number of blocks involved in diabetes physiology: digestion, blood (transport), pancreas, injected insulin absorption, liver, muscles, kidneys, metabolism and insulin sensitivity. The model serves as a demonstration object and the user can change meals, exercise and injections and see the resulting blood glucose level. A more experienced user can search for further explanations of different phenomena deeper in the physiology of the model. The model does not solve any problem for the user, but creates a learning situation in which the user, led by his own curiosity, successively increases his experience of diabetes physiology. Särimner is implemented as an easy-to-use menu driven computer program for IBM PC-clones with Hercules, EGA or VGA graphics.
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11.
  • Karlsson, Maria, et al. (author)
  • Determination of mRNA expression for IFN-γ and IL-4 in lymphocytes from children with IDDM by RT-PCR technique
  • 1998
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 40:1, s. 21-30
  • Journal article (peer-reviewed)abstract
    • Insulin-dependent diabetes mellitus (IDDM) is characterized by infiltration of T-lymphocytes in the islets of Langerhans. Antigens are presented to Th-lymphocytes which can be divided into Th1- and Th2-lymphocytes, producing interferon-γ (IFN-γ) and interleukin-4 (IL-4) respectively. The aim of our study was to determine the messenger-RNA (mRNA) for these cytokines by RT-PCR in antigen-stimulated lymphocytes from children with newly diagnosed IDDM. The expression of mRNA for IL-4, and to a lesser degree IFN-γ, is increased in lymphocytes stimulated with tetanus toxoid (TT). Loss of activity after freezing and thawing could be compensated for, by increased amplification, while the use of EDTA or sodium heparin in the blood samples did not influence the results. In a pilot application, the lymphocytes from children with newly diagnosed IDDM were stimulated with a peptide of glutamic acid decarboxylase (GAD) (a.a. 247–279) known to have a similar aminoacid sequence as the Coxsackie B virus (a.a. 32–47). Increased IFN-γ mRNA could be seen in two out of four children, whereas IL-4 showed a less pronounced mRNA expression. No increased mRNA expression for IFN-γ and IL-4 could be seen in healthy HLA-matched controls. Further studies are needed to confirm whether increased IFN-γ mRNA in Th1-like lymphocytes stimulated with this specific GAD-peptide play a role in the cell-mediated immune response seen in children early after the onset of IDDM.
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12.
  • Karlsson, Maria G. E., 1971-, et al. (author)
  • The ABBOS-peptide from bovine serum albumin causes an IFN-γ and IL-4 mRNA response in lymphocytes from children with recent onset of type 1 diabetes
  • 2000
  • In: Diabetes Research and Clinical Practice. - 0168-8227 .- 1872-8227. ; 47:3, s. 199-207
  • Journal article (peer-reviewed)abstract
    • The ABBOS-peptide from bovine serum albumin (BSA) in cow’s milk has been suggested to initiate the autoimmune process against the β-cells leading to type 1 diabetes. The aim of this study was to elucidate if the ABBOS-peptide is a possible trigger of type 1 diabetes. The cytokines IL-4 and IFN-γ were determined at the level of transcription as mRNA in lymphocytes, stimulated with the ABBOS-peptide. Sixteen children with newly diagnosed type 1 diabetes were compared with 10 healthy controls matched for the diabetes associated HLA-type DR3/4. Antibodies to bovine serum albumin (BSA), insulin antibodies (IA), and antibodies against islet cells (ICA) were determined, as well as serum C-peptide. Increased mRNA expression for IFN-γ and/or IL-4 could be observed in lymphocytes from 13/16 children with recent onset of diabetes after in vitro stimulation with the ABBOS-peptide. Low expression of IFN-γ mRNA was associated with high secretion of C-peptide, whereas a positive relationship could be observed between expression of IL-4 mRNA and insulin antibodies. Expression of IFN-γ and/or IL-4 mRNA was also detected in lymphocytes from 6/10 healthy controls. ABBOS may have a role as a reactive epitope in the upregulation of the autoimmune process against the β-cells but ABBOS does not seem to cause any specific Th1 response. An increased mRNA expression could also be seen in lymphocytes from healthy controls. Thus, the ABBOS-peptide might just cause or reflect an unspecific immune activity.
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13.
  • Saduaskaite-Kühne, Vaiva, 1970-, et al. (author)
  • Severity at onset of childhood type 1 diabetes in countries with high and low incidence of the condition
  • 2002
  • In: Diabetes Research and Clinical Practice. - 0168-8227 .- 1872-8227. ; 55:3, s. 247-254
  • Journal article (peer-reviewed)abstract
    • Severity of Type 1 diabetes mellitus (DM) at presentation was compared between south-east Sweden and Lithuania where incidence of childhood Type 1 diabetes is three times lower than in Sweden. New cases of diabetes at age 0–15 years from August 1995 to March 1999 in south-east Sweden and from August 1996 to August 2000 in Lithuania were included. Symptoms and clinical characteristics at diagnosis were recorded. Data about the close environment were collected using questionnaires. Lithuanian children were diagnosed in a more severe condition, mean pH 7.30 and HbA1c 11.5% compared with mean pH 7.36 and HbA1c 9.7% in Swedish children (P<0.0001). More Lithuanian than Swedish children were diagnosed in ketoacidosis (pH≤7.2, hyperglycaemia and ketonuria), 21.3 versus 7.3% (P<0.0001). Only 4.6% of Swedish children and 1.0% of Lithuanian children had no symptoms (P=0.007). Children in families with at least one first degree relative with diabetes (12.2% in Sweden and 8.4% in Lithuania, NS) had laboratory values at diagnosis closer to normal than sporadic cases in either country. Factors predicting ketoacidosis in Sweden were an unemployed mother and absence of infections in the 6 months before diagnosis. In Lithuania it was younger age and mother with less education. Additional educational activities for doctors are needed in countries with low incidence to reduce prevalence of ketoacidosis at onset.
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  • Abdelgadir, Moawia, et al. (author)
  • The influence of glucose self-monitoring on glycaemic control in patients with diabetes mellitus in Sudan
  • 2006
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 74:1, s. 90-94
  • Journal article (peer-reviewed)abstract
    • Objective: To investigate the influence of self-monitoring of glucose on the glycaemic control in Sudanese diabetic subjects. Subjects and methods: A group of 193 consecutive type 2 and type I diabetic subjects (95 men, 98 women) were studied. In 104 subjects with type 2 diabetes fasting blood glucose was measured using a glucose meter and blood was obtained for serum glucose measurement in the laboratory. In the remaining 89 diabetic subjects random blood glucose was measured using the same glucose meter and a whole blood sample was drawn for laboratory assessment of HbA1c. Data on self-monitoring and other clinical and personal characteristics were recorded. Results: More than 75% of either type I and type 2 diabetic patients never self-monitored blood or urine glucose. In type 2 diabetic subjects self-monitoring of blood or urine glucose was not related to glycaemic control. In type I diabetic subjects, however, self-monitoring of blood glucose was significantly associated with better glycaemic control, as assessed by HbA1c (P = 0.02) and blood glucose at clinic visits (P < 0.0001), and similar associations were found for urine glucose self-monitoring (P = 0.04 and 0.02) respectively. Neither glycaemic control nor glucose self-monitoring was associated with education level. Conclusions: Self-monitoring of blood glucose was not found to be associated to better glycaemic control in Sudanese subjects with type 2 diabetes. In contrast, self-monitoring of both blood and urine glucose was significantly associated with glycaemic control in subjects with type I diabetes. Self-monitoring of urine glucose could be useful where measurement of blood glucose is not available or affordable.
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17.
  • Afghahi, Henri, 1966, et al. (author)
  • The association between long-term glycemic control and all-cause mortality is different among older versus younger patients with diabetes mellitus and maintenance hemodialysis treatment.
  • 2022
  • In: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 191
  • Journal article (peer-reviewed)abstract
    • Knowledge about association between glycated hemoglobin (HbA1c) and risk of all-cause mortality in patients with diabetes mellitus on maintenance hemodialysis (HD)-treatment is sparse. The study aims to investigate association between HbA1c and all-cause mortality in patients with diabetes and maintenance HD-treatment, separately for two age groups- above and below 75years.2487 patients (mean age 66years, 66% men) were separated in two age groups: ≤75years (n=1810) and>75years (n=677) and followed up between 2008 and 2018. Hazard ratios (HR) and 95% confidence intervals (CI) for associations between HbA1c and all-cause mortality were calculated using Cox-regression-models.1295 (52%) patients died and 473 (70%) among the patients above 75years old. In the multivariate analysis, HbA1c5-6% was used as reference. In patients≤75years old, only increased HbA1c>9.7%, HR2.03(CI1.43-2.89) was associated with increased risk of all-cause mortality. In patients>75years, HbA1c≤5%, HR1.67(CI1.16-2.40); HbA1c6.9-7.8%, HR1.41(CI1.03-1.93) and HbA1c8.7-9.7%, HR1.79 (CI1.08-2.96) were associated with increased risk of all-cause mortality.We found a J-shaped association between HbA1c and mortality only in diabetic HD-patients>75years. This probably indicates that in an old population of diabetic HD-patients, both intensive glucose control and hyperglycemia could be harmful and associated with higher risk of death.
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  • Amsberg, Susanne, et al. (author)
  • Experience from a behavioural medicine intervention among poorly controlled adult type 1 diabetes patients
  • 2009
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 84:1, s. 76-83
  • Journal article (peer-reviewed)abstract
    • Aim To describe experience from a behavioural medicine intervention among poorly controlled adult type 1 diabetes patients, in terms of feasibility, predictors and associations of improved glycaemic control. Methods Data were collected on 94 poorly controlled adult type 1 diabetes patients who were randomised to a study evaluating the effects of a behavioural medicine intervention. Statistics covered descriptive and comparison analysis. Backward stepwise regression models were used for predictive and agreement analyses involving socio-demographic and medical factors, as well as measures of diabetes self-efficacy (DES), diabetes locus of control (DLOC), self-care activities (SDSCA), diabetes-related distress (Swe-PAID-20), fear of hypoglycaemia (HFS), well-being (WBQ), depression (HAD) and perceived stress (PSS). Results The participation rate in the study was 41% and attrition was 24%. Of those patients actually participating in the behavioural medicine intervention, 13% withdrew. From the regression models no predictors or associations of improvement in HbA1c were found. Conclusions The programme proved to be feasible in terms of design and methods. However, no clear pattern was found regarding predictors or associations of improved metabolic control as the response to the intervention. Further research in this area is called for.
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20.
  • Andersen, Gregers Stig Tig, et al. (author)
  • The DEXLIFE study methods : identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals
  • 2014
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 106:2, s. 383-389
  • Journal article (peer-reviewed)abstract
    • The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes.
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21.
  • Andersson, Tobias, 1976, et al. (author)
  • Mortality trends and cause of death in patients with new-onset type 2 diabetes and controls: A 24-year follow-up prospective cohort study.
  • 2018
  • In: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 138, s. 81-89
  • Journal article (peer-reviewed)abstract
    • Our aim was to assess causes of death and temporal changes in excess mortality among patients with new-onset type 2 diabetes in Skaraborg, Sweden.Patients from the Skaraborg Diabetes Register with prospectively registered new-onset type 2 diabetes 1991-2004 were included. Five individual controls matched for sex, age, geographical area and calendar year of study entry were selected using population records. Causes of deaths until 31 December 2014 were retrieved from the Cause of Death Register. Adjusted excess mortality among patients and temporal changes of excess mortality were calculated using Poisson models. Cumulative incidences of cause-specific mortality were calculated by competing risk regression.During 24years of follow-up 4364 deaths occurred among 7461 patients in 90,529 person-years (48.2/1000 person-years, 95% CI 46.8-49.7), and 18,541 deaths in 479,428 person-years among 37,271 controls (38.7/1000 person-years, 38.1-39.2). The overall adjusted mortality hazard ratio was 1.47 (p<.0001) among patients diagnosed at study start 1991 and decreased by 2% (p<.0001) per increase in calendar year of diagnosis until 2004. Excess mortality was mainly attributed to endocrine and cardiovascular cause of death with crude subdistributional hazard ratios of 5.06 (p<.001) and 1.22 (p<.001).Excess mortality for patients with new-onset type 2 diabetes was mainly attributed to deaths related to diabetes and the cardiovascular system, and decreased with increasing year of diagnosis 1991-2004. Possible explanations could be temporal trends of earlier diagnosis due to lowered diagnostic thresholds and intensified diagnostic activities, as well as improved treatment.
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  • Bennet, Louise, et al. (author)
  • Country of birth modifies the association of fatty liver index with insulin action in Middle Eastern immigrants to Sweden
  • 2015
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 110:1, s. 66-74
  • Journal article (peer-reviewed)abstract
    • Aims: Non-alcohol fatty liver disease (NAFLD) is a strong risk factor for insulin resistance and type 2 diabetes. The prevalence of NAFLD varies across populations of different ethnic backgrounds but the prevalence in Middle Eastern populations, which are at high risk of type 2 diabetes, is largely unknown. Using fatty liver index (FLI) as a proxy for NAFLD the aim was to calculate the odds of NAFLD (FLI >= 70) given country of origin and further to investigate the associations between ISI and FLI. Methods: In 2010-2012 we conducted a population-based study of individuals aged 30-75 years born in Iraq or Sweden, in whom anthropometrics, fasting blood samples and oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors characterized. Results: A higher proportion of Iraqis (N = 1085) than Swedes (N = 605) had a high probability of NAFLD (FLI >= 70, 32.5 vs. 22.6%, p < 0.001, age-and sex-adjusted data) and ISI was more severely impaired (70.7 vs. 95.9%, p < 0.001). Independently of traditional risk factors for NAFLD, being born in Iraqi increased the risk of FLI >= 70 (OR 1.59: 95% CI 1.15, 2.20). Furthermore, country of birth presented a stronger association between ISI and FLI >= 70 in Iraqis than in Swedes (P-interaction = 0.019). Conclusions: Our data indicate that immigrants from Iraq are at higher risk of NAFLD. The finding that country of birth modifies the relationship of FLI with ISI, suggests that liver fat may be a stronger determinant of impaired insulin action and increased risk of type 2 diabetes in Iraqis than in Swedes.
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24.
  • Bennet, Louise, et al. (author)
  • Ethnic differences in the contribution of insulin action and secretion to type 2 diabetes in immigrants from the Middle East compared to native Swedes
  • 2014
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 105:1, s. 79-87
  • Journal article (peer-reviewed)abstract
    • Aims: We investigated insulin action (insulin sensitivity index, ISI) and insulin secretion (oral disposition indices, DIo) and studied metabolic, demographic and lifestyle-related risk factors for type 2 diabetes and insulin action, in the largest non-European immigrant group to Sweden, immigrants from Iraq and native Swedes.Methods: Population-based, cross-sectional study conducted 2010-2012 including residents 30-75 years of age born in Iraq or Sweden, in whom oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors were characterized.Results: In Iraqis compared to Swedes, ISI was more impaired (76.9 vs. 102.3, p < .001) whereas corrected insulin response CIR was higher (226.6 vs. 188.6, p = .016). However, insulin secretion was inadequate given the substantial insulin resistance, as indicated by lower DIo indices in Iraqis than in Swedes (DIo 12,712.9 vs. 14,659.2, p < .001). The crude ethnic difference in ISI was not offset by traditional risk factors like waist circumference, body mass index or family history of diabetes. In Iraqis, ISI conveyed somewhat higher odds of type 2 diabetes than in Swedes (odds ratio OR 0.98, 95% CI 0.97-0.99) vs. OR 0.95, 0.92-0.99), as indicated by an interaction between country of birth and ISI (P-interaction = .044).Conclusion: This study reports ethnic differences in the contribution of insulin action to type 2 diabetes. Our data suggests that the impaired insulin action observed in immigrants from the Middle East to Sweden is not fully explained by established risk factors.(C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
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25.
  • Beraki, Åsa, et al. (author)
  • Increase in physical activity is associated with lower HbA1c levels in children and adolescents with type 1 diabetes : results from a cross-sectional study based on the Swedish pediatric diabetes quality registry (SWEDIABKIDS)
  • 2014
  • In: Diabetes Research and Clinical Practice. - Clare, Ireland : Elsevier. - 0168-8227 .- 1872-8227. ; 105:1, s. 119-125
  • Journal article (peer-reviewed)abstract
    • Aims: To evaluate the associations between physical activity (PA) and metabolic control, measured by glycated hemoglobin (HbA1c), in a large group of children and adolescents with type 1 diabetes.Methods: Cross-sectional analysis of data from 4655 patients, comparing HbA1c values with levels of physical activity. The data for the children and adolescents were obtained from the Swedish pediatric diabetes quality registry, SWEDIABKIDS. The patients were 7-18 years of age, had type 1 diabetes and were not in remission. Patients were grouped into five groups by frequency of PA.Results: Mean HbA1c level was higher in the least physically active groups (PA0: 8.8% +/- 1.5 (72 +/- 16 mmol/mol)) than in the most physically active groups (PA4: 7.7% +/- 1.0 (60 +/- 11 mmol/mol)) (p < 0.001). An inverse dose-response association was found between PA and HbA1c (beta: -0.30, 95%CI: -0.34 to -0.26, p < 0.001). This association was found in both sexes and all age groups, apart from girls aged 7-10 years. Multiple regression analysis revealed that the relationship remained significant (beta: -0.21, 95% CI: -0.25 to -0.18, p < 0.001) when adjusted for possible confounding factors.Conclusions: Physical activity seems to influence HbA1c levels in children and adolescents with type 1 diabetes. In clinical practice these patients should be recommended daily physical activity as a part of their treatment.
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26.
  • Berglund, Lars, 1955-, et al. (author)
  • Early Insulin Response and Insulin Sensitivity are Equally Important as Predictors of Glucose Tolerance after Correction for Measurement Errors
  • 2009
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 86:3, s. 219-224
  • Journal article (peer-reviewed)abstract
    • Aims: We estimated measurement error (ME) corrected effects of   insulin sensitivity (M/I), from euglycaemic insulin clamp, and insulin   secretion, measured as early insulin response (EIR) from oral glucose   tolerance test (OGTT), on fasting plasma glucose, HbA1c and type 2   diabetes longitudinally and cross-sectional.   Methods: : In a population-based study (n = 1128 men) 17 men made   replicate measurements to estimate ME at age 71 years. Effect of 1 SD   decrease of predictors M/I and EIR on longitudinal response variables   fasting plasma glucose (FPG) and HbA1c at follow-ups up to 11 years,   were estimated using uncorrected and ME-corrected (with the regression   calibration method) regression models.   Results: : Uncorrected effect on FPG at age 77 years was larger for M/I   than for EIR (effect difference 0.10 mmol/l, 95% CI 0.00;0.21), while   ME-corrected effects were similar (0.02 mmol/l, 95% CI -0.13;0.15   mmol/l). EIR had greater ME-corrected impact than M/I on HbA1c at age   82 years (-0.11%, -0.28; -0.01%).   Conclusions: : Due to higher ME effect of EIR on glycaemia is   underestimated as compared with M/I. By correcting for ME valid   estimates of relative contributions of insulin secretion and insulin   sensitivity on glycaemia are obtained.
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27.
  • Carlsson, Axel C., et al. (author)
  • Country of birth-specific and gender differences in prevalence of diabetes in Sweden
  • 2013
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 100:3, s. 404-408
  • Journal article (peer-reviewed)abstract
    • Objective: The aim was to investigate country or region of birth-specific prevalence and gender differences of diabetes in residents in Sweden, using Swedish-born men and women as referent. Methods: The Apolipoprotein MOrtality RISk (AMORIS) cohort was used (184,000 men and 151,453 women) aged between 20 and 80 years, with data from the CALAB laboratory, Stockholm, 1985-1996. Diabetes was defined as fasting glucose >= 7.0 mmol/L or a hospital diagnosis of diabetes. Country of birth was obtained by linkage to Swedish Censuses 1970-1990. Standardized prevalence rate ratios (SPRR) with 95% confidence intervals (95% CI) were estimated. Results: Five groups of women and one group of men had a significantly higher prevalence than Swedish-born (based on SPRR): women born in Iraq (6.0 (95% CI 1.3-28.9)), North Africa (6.9 (95% CI 3.1-15.3)), South Asia (3.1 (95% CI 1.0-10.0)), Syria (5.3 (95% CI 1.8-16.0)), Turkey (3.7 (95% CI 1.2-10.9)) and men born in other Middle Eastern countries (2.3 (95% CI 1.0-5.5)). Swedish-born men had a higher age-standardized prevalence of diabetes (3.9%) than Swedish born women ( 2.5%). A higher prevalence among men was also seen in other Western countries. In contrast, a higher age-standardized prevalence among women was observed in immigrants from Turkey (8.9% vs. 3.1%, p < 0.001), Syria (13.1% vs. 4.0%, p = 0.002), and North Africa (16.8% vs. 6.6%, p < 0.001). Conclusion: Female immigrants to Sweden from Iraq, North Africa, South Asia, Syria, and Turkey have an increased prevalence of diabetes of substantial public health concern.
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28.
  • Carlsson, Axel C, et al. (author)
  • Kidney injury molecule (KIM)-1 is associated with insulin resistance : results from two community-based studies of elderly individuals
  • 2014
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 103:3, s. 516-21
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.
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29.
  • Carlsson, Björn, 1958, et al. (author)
  • Differences in associations between HSD11B1 gene expression and metabolic parameters in subjects with and without impaired glucose homeostasis
  • 2010
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 88:3, s. 252-258
  • Journal article (peer-reviewed)abstract
    • Aims: Animal studies indicate a role for 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) in the development of obesity. The association to glucose homeostasis is less clear. We investigated the relationship between HSD11B1 mRNA levels in adipose tissue and in skeletal muscle and anthropometric and metabolic measurements in humans with and without impaired glucose homeostasis. Methods: Twelve obese subjects with impaired glucose homeostasis (MetS+) and 12 obese controls (MetS-) received a Very Low Calorie Diet for 16 weeks and adipose tissue biopsies, blood samples and measurements were obtained. In a second cohort, skeletal muscle biopsies, blood samples and measurements were obtained from 18 subjects with type 2 diabetes (T2DM) and 17 subjects with normal glucose tolerance (NGT). Gene expression was measured by DNA microarray in both studies. Results: HSD11B1 mRNA levels were reduced during diet, and anthropometric measurements and metabolic parameters were associated with HSD11B1 mRNA levels in the MetS-group. However, in the MetS+ group these associations were lost or in opposite direction. This difference was also observed in skeletal muscle between T2DM and NGT. Conclusions: HSD11B1 mRNA levels are associated with metabolic parameters and anthropometric measurements in subjects with normal glucose homeostasis but not in subjects with impaired glucose homeostasis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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30.
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31.
  • Cederholm, Jan, et al. (author)
  • Microalbuminuria and risk factors in type 1 and type 2 diabetic patients
  • 2005
  • In: Diabetes Res Clin Pract. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 67:3, s. 258-66
  • Journal article (peer-reviewed)abstract
    • A prospective study of normoalbuminuric diabetic patients was performed between 1997 and 2002 on 4097 type 1 and 6513 type 2 diabetic patients from the Swedish National Diabetes Register (NDR); mean study period, 4.6 years. The strongest independent baseline risk factors for the development of microalbuminuria (20-200 microg/min) were elevated HbA(1c) and diabetes duration in both types 1 and 2 diabetic patients. Other risk factors were high BMI, elevated systolic and diastolic BP in type 2 patients, and antihypertensive therapy in type 1 patients. A subsequent larger cross-sectional study in 2002 showed that established microalbuminuria was independently associated with HbA(1c), diabetes duration, systolic BP, BMI, smoking and triglycerides in types 1 and 2 diabetic patients, and also with HDL-cholesterol in type 2 patients. Relatively few types 1 and 2 patients with microalbuminuria achieved treatment targets of HbA(1c) < 6.5% (21-48%), BP < 130/85 mmHg (33-13%), cholesterol < 5 mmol/l (48-46%), triglycerides < 1.7 mmol/l (83-48%) and BMI < 25 kg/m(2) (50-18%), respectively. In conclusion, high HbA(1c), BP and BMI were independent risk factors for the development of microalbuminuria in types 1 and 2 diabetic patients. These risk factors as well as triglycerides, HDL-cholesterol and smoking were independently associated with established microalbuminuria. Treatment targets were achieved by a relatively few patients with microalbuminuria.
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32.
  • Ceriello, Antonio, et al. (author)
  • Diabetes as a case study of chronic disease management with a personalized approach: The role of a structured feedback loop
  • 2012
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 98:1, s. 5-10
  • Research review (peer-reviewed)abstract
    • As non-communicable or chronic diseases are a growing threat to human health and economic growth, political stakeholders are aiming to identify options for improved response to the challenges of prevention and management of non-communicable diseases. This paper is intended to contribute ideas on personalized chronic disease management which are based on experience with one major chronic disease, namely diabetes mellitus. less thanbrgreater than less thanbrgreater thanDiabetes provides a pertinent case of chronic disease management with a particular focus on patient self-management. Despite advances in diabetes therapy, many people with diabetes still fail to achieve treatment targets thus remaining at risk of complications. Personalizing the management of diabetes according to the patients individual profile can help in improving therapy adherence and treatment outcomes. This paper suggests using a six-step cycle for personalized diabetes (self-)management and collaborative use of structured blood glucose data. E-health solutions can be used to improve process efficiencies and allow remote access. Decision support tools and algorithms can help doctors in making therapeutic decisions based on individual patient profiles. Available evidence about the effectiveness of the cycles constituting elements justifies expectations that the diabetes management cycle as a whole can generate medical and economic benefit.
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33.
  • Cos, X., et al. (author)
  • Impact on guidelines : the general practitioner point of view
  • 2020
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 166
  • Journal article (peer-reviewed)abstract
    • Primary care physicians are uniquely placed to offer holistic, patient-centred care to patients with T2DM. While the recent FDA-mandated cardiovascular outcome trials offer a wealth of data to inform treatment discussions, they have also contributed to increasing complexity in treatment decisions, and in the guidelines that seek to assist in making these decisions. To assist physicians in avoiding treatment inertia, Primary Care Diabetes Europe has formulated a position statement that summarises our current understanding of the available T2DM treatment options in various patient populations. New data from recent outcomes trials is contextualised and summarised for the primary care physician. This consensus paper also proposes a unique and simple tool to stratify patients into 'very high' and 'high' cardiovascular risk categories and outlines treatment recommendations for patients with atherosclerotic cardiovascular disease, heart failure and chronic kidney disease. Special consideration is given to elderly/frail patients and those with obesity. A visual patient assessment tool is provided, and a comprehensive set of prescribing tips is presented for all available classes of glucose-lowering therapies. This position statement will complement the already available, often specialist-focused, T2DM treatment guidelines and provide greater direction in how the wealth of outcome trial data can be applied to everyday practice.
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34.
  • Dahlin, E, et al. (author)
  • Impaired vibrotactile sense at low frequencies in fingers in autoantibody positive and negative diabetes.
  • 2013
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 100:2, s. 46-50
  • Journal article (peer-reviewed)abstract
    • Vibration thresholds in index and little finger pulps in subjects with autoantibody [GADA, IA-2A and/or ICA] positive and negative diabetes 20 years after diagnosis were higher than in age-matched controls at low frequencies (8 and 16Hz), irrespective of HbA1c values, indicating selective impairment of Meissner's corpuscles and/or their innervating axons.
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35.
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36.
  • Dorkhan, Mozhgan, et al. (author)
  • Differences in effects of insulin glargine or pioglitazone added to oral anti-diabetic therapy in patients with type 2 diabetes What to add-Insulin glargine or pioglitazone?
  • 2008
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 82, s. 340-345
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: While metformin is the first line treatment in type 2 diabetes, the best way to escalate therapy is not always clear, particularly whether to add one or two oral agents or to introduce insulin. METHODS: Thirty-six patients inadequately controlled on metformin and sulfonylurea/meglitinide were randomized to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Insulin was up-titrated to achieve fasting plasma glucose <6mmol/l. Pioglitazone was increased to 45mg/day after 16 weeks if HbA1c>6.2%. beta-Cell function and insulin sensitivity were assessed by measuring insulin, proinsulin and adiponectin, and in a subgroup using a combined glucagon-stimulated C-peptide test and insulin tolerance test (GITT). Lipids and natriuretic peptides were measured at start and end of study. RESULTS: The reduction in HbA1c was slightly greater in the insulin glargine group and used as co-variate when analysing other variables. The effect on beta-cell function was more favourable with insulin glargine measured by proinsulin (42+/-48 to 19+/-16, p=0.01 vs. 36+/-26 to 27+/-16 p=0.04) while the improvement in insulin sensitivity measured by adiponectin (7.5+/-3.7 to 15+/-10, p<0.01 vs. 8.7+/-4 to 7.6+/-3, p=0.04) and HDL cholesterol (1.10+/-0.24 to 1.24+/-0.3, p<0.01 vs. 1.08+/-0.35 to 1.04+/-0.33, ns) (all p between groups <0.01) was more favourable in pioglitazone group. Pioglitazone caused significant increase in natriuretic peptides (BNP pmol/l 6.6+/-5.2 to 13.7+/-16.1, p=0.04 vs. 8.8+/-11.6 to 8.6+/-10.6, ns, p between groups 0.028). CONCLUSIONS: The results demonstrate characteristic differences in the effects of insulin glargine vs. pioglitazone on measures of beta-cell function and insulin sensitivity as well as cardiac load.
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37.
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38.
  • Ekelund, Magnus, et al. (author)
  • Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus
  • 2012
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 97:3, s. 394-398
  • Journal article (peer-reviewed)abstract
    • Aims: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM). Methods: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months. Results: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p = 0.00016 after adjustment for age and ethnicity). Conclusions: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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39.
  • Eltom, Mohamed A., et al. (author)
  • Increasing prevalence of type 2 diabetes mellitus and impact of ethnicity in north Sudan
  • 2018
  • In: Diabetes Research and Clinical Practice. - : ELSEVIER IRELAND LTD. - 0168-8227 .- 1872-8227. ; 136, s. 93-99
  • Journal article (peer-reviewed)abstract
    • Background: Diabetes mellitus constitutes a global health threat, with increasing burden of disease in low and middle-income countries witnessing ongoing epidemiological transition including Sudan.Aims: To study the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes and determine the relationship to gender, age, waist circumference, body mass index, residence and ethnicity among the adult population in north Sudan.Methods: A cross-sectional, population-based study in Northern State and River Nile State using random multi-stage cluster sampling targeting 5376 participants from 14 localities divided into 60 urban and 40 rural clusters. In each cluster, 60 households were studied. Blood glucose level and anthropometric measurements were recorded and a questionnaire containing demographic data was obtained from each participant.Results: The prevalence of T2DM among participants was 18.7% and prediabetes was 12.9%. Among people living with T2DM, 694(71.0%) were known cases of T2DM, whereas 284 (29.0%) were newly diagnosed cases. The significant associated risk factors for T2DM included urban residence (AOR 1.23, 95% CI 1.09-1.41), age above 60 years (AOR 4.77, 95% CI 4.04-5.63), obese BMI (AOR 1.26, 95% CI 1.03-1.55) and central obesity (AOR 1.39, 95% CI 1.14-1.68). Compared to indigenous population, individuals of Egyptian descents (AOR 1.28, 95% CI 1.04-1.57) and mixed origin (AOR 1.24, 95% CI 1.04-1.48) had increased risk of T2DM.Conclusion: The prevalence of T2DM and prediabetes in north Sudan have increased significantly since 1996 with variations between ethnicities which showed to be an independent risk factor for T2DM. Health authorities are recommended to set plans to meet the health needs of these communities.
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40.
  • Ericsson, Hans, et al. (author)
  • The glucokinase activator AZD6370 decreases fasting and postprandial glucose in type 2 diabetes mellitus patients with effects influenced by dosing regimen and food
  • 2012
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 98:3, s. 436-444
  • Journal article (peer-reviewed)abstract
    • Aims: To investigate the pharmacodynamics, pharmacokinetics and safety of the glucokinase activator AZD6370 after 1 day of administration under fed and fasted conditions in patients with type 2 diabetes mellitus (T2DM). less thanbrgreater than less thanbrgreater thanMethods: This was a two-part study. In Part A, patients received a single oral dose of AZD6370 (20, 60 or 180 mg) or placebo in the fasted or fed states (both n = 8). In Part B, patients (n = 8) received placebo and a total dose of AZD6370 180 mg given in one, two or four divided doses. Plasma glucose, insulin and C-peptide changes versus placebo were assessed. less thanbrgreater than less thanbrgreater thanResults: AZD6370 provided dose-dependent reductions in plasma glucose of up to 30% versus placebo in both fasted and fed patients (p andlt; 0.001 at 60 and 180 mg doses). Insulin secretion increased with dose, but absolute increases were relatively small in the fasted versus fed state (0-4 h). Dosing AZD6370 twice or four-times over 1 day gave a smoother 24-h glucose profile than single-dose. AZD6370 was rapidly absorbed. Pharmacokinetics of AZD6370 were dose-independent and unaffected by food. AZD6370 was generally well tolerated. less thanbrgreater than less thanbrgreater thanConclusions: AZD6370 produced dose-dependent glucose reductions and increased glucose-stimulated insulin secretion in patients with T2DM.
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41.
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42.
  • Eriksson, J., et al. (author)
  • Metformin or SGLT2 inhibitor as 1st line treatment of type 2 diabetes? Design and interim results of the SMARTEST trial
  • 2023
  • In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 197:Supl. 1
  • Journal article (other academic/artistic)abstract
    • Background: Metformin is generally recommended as 1 st line medication in T2D. However, there is no compelling evidence of its superiority in preventing diabetes complications. SGLT2 inhibitors prevent cardiovascular mortality, heart failure and renal impairment in T2D patients at high cardiovascular risk.Aim: To assess whether an SGLT2 inhibitor is superior to metformin in preventing organ complications and premature death in early-stage T2D.Method: The SMARTEST study (SGLT2 inhibitor or Metformin As standaRd Treatment of Early Stage Type 2 diabetes) is a registry-based trial in primary care. Participants are included via on-site or video visits at 31 centers across Sweden; T2D <4 yr; drugnaïve (currently 31%) or montherapy; no cardiorenal diseases. Randomizaton 1:1, open label metformin (individualized dose) or dapagliflozin 10 mg/day. Diet, exercise and other medications are stipulated according to national guidelines. Patients are followed 2–6 yrs.Endpoints are collected using NDR and the national Patient Registry. The study will close when 844 primary endpoint events have occurred, giving 90% power to detect a HR of 0.8 for dapagliflozin vs metformin. Primary composite endpoint: time to death, myocardial infarction, stroke, heart failure or appearance/progression of microvascular complications (retinopathy, nephropathy, diabetic foot lesions). Other endpoints include: need for insulin therapy; blood pressure, BMI, HbA1c, PROM and health economy.Results: From late 2019 until May 2022 1100 patients are included. 38% are females, mean age is 60 years and HbA1c 46.5 mmol/mol (6.4%). So far, the primary endpoint event rate is 11/100 patient years (PY), whereas 7/100 PY was estimated from previous data. Nephropathy and foot-at-risk had high rates (6 and 3/100 PY) but MACE was rare (1/100 PY). The recruitment target is 2700 participants, expected by end 2023.Conclusion: Final results are expected in 2025 and can challenge or, equally important, reinforce the current metformin paradigm in early T2D. Event rates are higher than previously recognized for nephropathy and diabetic foot problems but lower for MACE.
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43.
  • Eriksson, Jan W., et al. (author)
  • Sulphonylurea compared to DPP-4 inhibitors in combination with metformin carries increased risk of severe hypoglycemia, cardiovascular events, and all-cause mortality
  • 2016
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 117, s. 39-47
  • Journal article (peer-reviewed)abstract
    • Aims: There are safety concerns related to sulphonylurea treatment. The objective of this nationwide study was to compare the risk of cardiovascular disease (CVD), all-cause mortality and severe hypoglycemia in patients with type 2 diabetes (T2D) starting second-line treatment with either metformin + sulphonylurea or metformin + dipeptidyl peptidase-4 inhibitor (DPP-4i). Methods: All patients with T2D in Sweden who initiated second-line treatment with metformin + sulphonylurea or metformin + DPP-4i during 2006-2013 (n = 40,736 and 12,024, respectively) were identified in this nationwide study. The Swedish Prescribed Drug Register and the Cause of Death and National Patient Registers were used, and Cox survival models adjusted for age, sex, fragility, prior CVD, and CVD-preventing drugs were applied to estimate risks of events. Propensity score adjustments and matching methods were used to test the results. Results: Of 52,760 patients; 77% started metformin + SU and 23% metformin + DPP-4i. Crude incidences for severe hypoglycemia, CVD, and all-cause mortality in the SU cohort were 2.0, 19.6, and 24.6 per 1000 patient-years and in the DPP-4i cohort were 0.8, 7.6, and 14.9 per 1000 patient-years, respectively. Sulphonylurea compared with DPP4i was associated with higher risk of subsequent severe hypoglycemia, fatal and nonfatal CVD, and all-cause mortality; adjusted HR (95% CI): 2.07 (1.11-3.86); 1.17 (1.01-1.37); and 1.25 (1.02-1.54), respectively. Results were confirmed by additional propensity-adjusted and matched analyses. Among the SU drugs, glibenclamide had the highest risks. Conclusions: Metformin + SU treatment was associated with an increased risk of subsequent severe hypoglycemia, cardiovascular events, and all-cause mortality compared with metformin + DPP4i. Results from randomized trials will be important to elucidate causal relationships.
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44.
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45.
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46.
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47.
  • García-Calzón, Sonia, et al. (author)
  • DNA methylation partially mediates antidiabetic effects of metformin on HbA1c levels in individuals with type 2 diabetes
  • 2023
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 202
  • Journal article (peer-reviewed)abstract
    • Aims: Despite metformin being used as first-line pharmacological therapy for type 2 diabetes, its underlying mechanisms remain unclear. We aimed to determine whether metformin altered DNA methylation in newlydiagnosed individuals with type 2 diabetes.Methods and Results: We found that metformin therapy is associated with altered methylation of 26 sites in blood from Scandinavian discovery and replication cohorts (FDR < 0.05), using MethylationEPIC arrays. The majority (88%) of these 26 sites were hypermethylated in patients taking metformin for similar to 3 months compared to controls, who had diabetes but had not taken any diabetes medication. Two of these blood-based methylation markers mirrored the epigenetic pattern in muscle and adipose tissue (FDR < 0.05). Four type 2 diabetes-associated SNPs were annotated to genes with differential methylation between metformin cases and controls, e.g., GRB10, RPTOR, SLC22A18AS and TH2LCRR. Methylation correlated with expression in human islets for two of these genes. Three metformin-associated methylation sites (PKNOX2, WDTC1 and MICB) partially mediate effects of metformin on follow-up HbA1c levels. When combining methylation of these three sites into a score, which was used in a causal mediation analysis, methylation was suggested to mediate up to 32% of metformin's effects on HbA1c.Conclusion: Metformin-associated alterations in DNA methylation partially mediates metformin's antidiabetic effects on HbA1c in newly-diagnosed individuals with type 2 diabetes.
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48.
  • Gauffin, Emilia, et al. (author)
  • Plasma mid-regional pro-atrial natriuretic peptide predicts cardiovascular events in patients with type 2 diabetes independently of subclinical organ damage
  • 2021
  • In: Diabetes Research and Clinical Practice. - : ELSEVIER IRELAND LTD. - 0168-8227 .- 1872-8227. ; 182
  • Journal article (peer-reviewed)abstract
    • Aim: The aim of this study was to investigate the association between plasma MR-proANP and cardiovascular disease (CVD) in a middle-aged population with type 2 diabetes. Methods: MR-proANP was measured in 690 patients with type 2 diabetes participating in the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes-a Prospective Study in Primary Care). The outcome variables were incident major adverse cardiovascular events (MACE) and all-cause mortality. Patients were followed using the national Swedish Cause of Death Registry and the Inpatient Register. Results: During the mean follow-up period of 10.8 years, MACE occurred in 111 patients and 102 patients died. The hazard ratio for an increment of MR-proANP of 1 pmol/l adjusted for sex, age, current smoking, previous CVD, HbA1c, serum cholesterol, eGFR, systolic blood pressure, C-reactive protein, aortic pulse wave velocity, left ventricular mass and intima media thickness in the carotid arteries was 1.007 (95% CI 1.000-1.013, P = 0.042) for MACE and 1.008 (95% CI 1.001-1.014, P = 0.017) for all-cause mortality. Conclusions: Elevated MR-proANP levels predict an increased risk for MACE and all-cause mortality in patients with type 2 diabetes independently of CVD risk factors and markers for subclinical organ damage. (c) 2021 Elsevier B.V. All rights reserved.
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49.
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50.
  • Glans, Forouzan, et al. (author)
  • Evaluation of the effects of exercise on insulin sensitivity in Arabian and Swedish women with type 2 diabetes.
  • 2009
  • In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 85, s. 69-74
  • Journal article (peer-reviewed)abstract
    • AIMS: The purpose of this study was to evaluate the effects of exercise on cardio-respiratory fitness and insulin sensitivity in sedentary, overweight Arabian and Swedish women with type 2 diabetes. METHODS: Eighteen Arabian and 14 Swedish women participated in a supervised 6-month resistance training and aerobic program of moderate intensity. Insulin sensitivity and VO(2max) were measured at entry to the study and after 3 and 6 months training. RESULTS: After 6 months exercise, insulin sensitivity (M-value) increased (2.7+/-1.4mgkg(-1)min(-1) vs. 3.4+/-2mgkg(-1)min(-1), p<0.05) in all patients and accounted for by an increase in non-oxidative glucose metabolism (0.3+/-1.1mgkg(-1)min(-1) vs. 1.5+/-1.5mgkg(-1)min(-1), p<0.005) with no significant difference between the ethnic groups. Notably, significant improvement in HbA1c was only seen in the Swedish patients who achieved greater exercise intensity (73.3+/-4.8% vs. 63.3+/-5.2% of maximum heart rate, p<0.005). No changes were observed regarding VO(2max) or lipid profile in either group. CONCLUSIONS: Although a 6-month exercise intervention of moderate intensity in Arabian and Swedish patients with type 2 diabetes can improve insulin sensitivity it is hampered by the metabolic inflexibility of switching between oxidation of glucose or fat.
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