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  • 1.
    Abdelgadir, Moawia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Elbagir, Murtada
    Eltom, Mohamed
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The influence of glucose self-monitoring on glycaemic control in patients with diabetes mellitus in Sudan2006In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 74, no 1, 90-94 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Early Insulin Response and Insulin Sensitivity are Equally Important as Predictors of Glucose Tolerance after Correction for Measurement Errors2009In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 86, no 3, 219-224 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Calamia, Michael
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kidney injury molecule (KIM)-1 is associated with insulin resistance: Results from two community-based studies of elderly individuals2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 103, no 3, 516-521 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 4.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Wandell, Per E.
    Hedlund, Ebba
    Walldius, Goran
    Nordqvist, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Jungner, Ingmar
    Hammar, Niklas
    Country of birth-specific and gender differences in prevalence of diabetes in Sweden2013In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 100, no 3, 404-408 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 5.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Eliasson, B.
    Nilsson, P.M.
    Weiss, L.
    Gudbjörnsdottir, S.
    Microalbuminuria and risk factors in type 1 and type 2 diabetic patients2005In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 67, no 3, 258-66 p.Article in journal (Refereed)
    Abstract [en]

    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 (20–200μg/min) were elevated HbA1c 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 HbA1c, 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 HbA1c < 6.5% (21–48%), BP < 130/85mmHg (33–13%), cholesterol < 5mmol/l (48–46%), triglycerides < 1.7mmol/l (83–48%) and BMI < 25kg/m2 (50–18%), respectively.

    In conclusion, high HbA1c, 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.

  • 6.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nilsson, Peter M
    Eeg-Olofsson, Katarina
    Eliasson, Björn
    Gudbjörnsdottir, Soffia
    Effect of tight control of HbA1c and blood pressure on cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR)2009In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 86, no 1, 74-81 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To estimate hazard ratio (HR) of first incident fatal/non-fatal cardiovascular diseases (CVD) in female/male type 2 diabetic patients, with tight versus adverse control of HbA1c and blood pressure (BP) at baseline, age 30-70 years, no baseline CVD, followed for mean 5.7 years. METHODS: 2593 patients with tight control of HbA1c <7.5% and BP < or = 140/90 mmHg (median 6.5%/130/80 mmHg), and 2160 patients with adverse control 7.5-9.0%/141-190/91-110 mmHg (median 8.1%/155/85 mmHg). RESULTS: The hazard ratio (HR) for CVD with tight/adverse control was 0.67 (0.55-0.80; p<0.001), adjusting for age, sex, duration, hypoglycaemic treatment, smoking, BMI, lipid-lowering drugs, antihypertensive drugs, microalbuminuria. Adjusted HR for myocardial infarction, coronary heart disease, stroke and total mortality were 0.72 (0.56-0.92; p=0.01), 0.69 (0.55-0.86; p<0.001), 0.62 (0.45-0.84; p<0.001), 1.00 (0.72-1.39). The partial population-attributable risk percent for myocardial infarction, stroke and CVD was 23%, 33%, 29% if adverse HbA1c/BP control could be avoided, while 43%, 38%, 39% with overweight and smoking also avoided. Baseline lower BMI and absence of microalbuminuria were associated with tight control. CONCLUSION: Median difference of HbA1c/BP 1.6%/25/5 mmHg between tight and adverse control considerably reduced the risk of cardiovascular diseases. The findings call for a multi-factorial approach to improve HbA1c, BP, obesity, smoking, and microalbuminuria.

  • 7. Eeg-Olofsson, Katarina
    et al.
    Gudbjornsdottir, Soffia
    Eliasson, Bjorn
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    The triglycerides-to-HDL-cholesterol ratio and cardiovascular disease risk in obese patients with type 2 diabetes: An observational study from the Swedish National Diabetes Register (NDR)2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 106, no 1, 136-144 p.Article in journal (Refereed)
    Abstract [en]

    Aims: Assessing the association between BMI and risk of coronary heart disease (CHD), cardiovascular disease (CVD) and mortality in patients with type 2 diabetes, also with regard to higher or lower levels of the ratio triglycerides-to-HDL-cholesterol (TG:HDL). Methods: 54,061 patients with BMI >= 18.5 kg/m(2), mean age and duration 61.5 +/- 8 and 6.9 +/- 6 years, 59% males, 14% with CVD history, from the Swedish National Diabetes Register, followed for mean 4.8 years. Results: Adjusting at Cox regression for non-BMI-linked (age, sex, smoking, CVD history) and BMI-linked (blood lipids, blood pressure, HbA1c, albuminuria) covariates, hazard ratios (HR) for fatal/nonfatal CHD and CVD were mainly increased with prominent obesity (BMI >= 35 kg/m(2)), 1.19 (p = 0.01) and 1.17 (p = 0.009), compared to normal weight (BMI 18.5-24.9 kg/m(2)), although increased also with obesity (BMI 30-34.9 kg/m(2)), 1.34 and 1.30 (p < 0.001), when adjusting only for non-BMI-linked covariates. Stratifying by 75th percentile of TG: HDL, with normal weight and TG: HDL < 1.9 as reference, obese and prominently obese with TG: HDL >= 1.9 had considerably increased HR around 1.7 for fatal/nonfatal CHD and 1.6 for CVD (p < 0.001), while obese and prominently obese with TG: HDL < 1.9 only had HR 1.2-1.3 for CHD and CVD (p 0.003-<0.01). Conclusion: Obese T2D patients with high TG: HDL, associated with increased insulin resistance, had considerably increased risk of CHD and CVD.

  • 8.
    Eriksson, Jan W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Bodegard, Johan
    AstraZeneca Nordic Baltic, Sodertalje, Sweden..
    Nathanson, David
    Karolinska Inst, Unit Diabet Res, Div Internal Med, Dept Clin Sci & Educ, Stockholm, Sweden..
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden..
    Nyström, Thomas
    Karolinska Inst, Unit Diabet Res, Div Internal Med, Dept Clin Sci & Educ, Stockholm, Sweden..
    Norhammare, Anna
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Sulphonylurea compared to DPP-4 inhibitors in combination with metformin carries increased risk of severe hypoglycemia, cardiovascular events, and all-cause mortality2016In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 117, 39-47 p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 9.
    Granström, Therese
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Forsman, Henrietta
    Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden..
    Olinder, Anna Lindholm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Söder Sjukhuset, Sachs Children & Youth Hosp, Stockholm, Sweden.;Söder Sjukhuset, Karolinska Inst, Dept Clin Res & Educ, Stockholm, Sweden..
    Gkretsis, Dimitrios
    Dalarna Cty Hosp, Dept Ophthalmol, Falun, Sweden..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Granstam, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Vastmanland Cty Hosp, Dept Ophthalmol, Vasteras, Sweden..
    Leksell, Janeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Patient-reported outcomes and visual acuity after 12 months of anti-VEGF-treatment for sight-threatening diabetic macular edema in a real world setting2016In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 121, 157-165 p.Article in journal (Refereed)
    Abstract [en]

    Aims: To examine objective visual acuity measured with ETDRS, retinal thickness (OCT), patient reported outcome and describe levels of glycated hemoglobin and its association with the effects on visual acuity in patients treated with anti-VEGF for visual impairment due to diabetic macular edema (DME) during 12 months in a real world setting.

    Methods: In this cross-sectional study, 58 patients (29 females and 29 males; mean age, 68 years) with type 1 and type 2 diabetes diagnosed with DME were included. Medical data and two questionnaires were collected; an eye-specific (NEI VFQ-25) and a generic health-related quality of life questionnaire (SF-36) were used.

    Results: The total patient group had significantly improved visual acuity and reduced retinal thickness at 4 months and remains at 12 months follow up. Thirty patients had significantly improved visual acuity, and 27 patients had no improved visual acuity at 12 months. The patients with improved visual acuity had significantly improved scores for NEI VFQ-25 subscales including general health, general vision, near activities, distance activities, and composite score, but no significant changes in scores were found in the group without improvements in visual acuity.

    Conclusions: Our study revealed that anti-VEGF treatment improved visual acuity and central retinal thickness as well as patient-reported outcome in real world 12 months after treatment start.

  • 10.
    Gylfe, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Gilon, Patrick
    Glucose regulation of glucagon secretion2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 103, no 1, 1-10 p.Article, review/survey (Refereed)
    Abstract [en]

    Glucagon secreted by pancreatic alpha-cells is the major hyperglycemic hormone correcting acute hypoglycaemia (glucose counterregulation). In diabetes the glucagon response to hypoglycaemia becomes compromised and chronic hyperglucagonemia appears. There is increasing awareness that glucagon excess may underlie important manifestations of diabetes. However opinions differ widely how glucose controls glucagon secretion. The autonomous nervous system plays an important role in the glucagon response to hypoglycaemia. But it is clear that glucose controls glucagon secretion also by mechanisms involving direct effects on alpha-cells or indirect effects via paracrine factors released from non-alpha-cells within the pancreatic islets. The present review discusses these mechanisms and argues that different regulatory processes are involved in a glucose concentration-dependent manner. Direct glucose effects on the a-cell and autocrine mechanisms are probably most significant for the glucagon response to hypoglycaemia. During hyperglycaemia, when secretion from beta-and delta-cells is stimulated, paracrine inhibitory factors generate pulsatile glucagon release in opposite phase to pulsatile release of insulin and somatostatin. High concentrations of glucose have also stimulatory effects on glucagon secretion that tend to balance and even exceed the inhibitory influence. The latter actions might underlie the paradoxical hyperglucagonemia that aggravates hyperglycaemia in persons with diabetes.

  • 11.
    Hyllienmark, Lars
    et al.
    Dept. of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekberg, K.
    Dept. of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Lindström, P.
    Dept. of Neurology, Karolinska Institutet, Stockholm, Sweden.
    Abnormal cold perception in the lower limbs: a sensitive indicator for detection of polyneuropathy in patients with type 1 diabetes mellitus2009In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 85, no 3, 298-303 p.Article in journal (Refereed)
    Abstract [en]

    Diabetic peripheral neuropathy differs in type 1 and type 2 diabetes. The aim of this study was to evaluate how signs and symptoms of neuropathy correlated with defects in motor and sensory nerve conduction velocity (MCV and SCV) and sensory perception thresholds in patients with type 1 diabetes. MCV and SCV in peroneal and sural nerves and vibratory, warm and cold perception thresholds (VPT, WPT, CPT) were evaluated in the lower limbs of 127 patients (42+/-7.9 years old, duration of diabetes, 16+/-11 years and HbA1c, 7.7+/-1.4%). The results were compared with clinical findings (neuropathy impairment assessment, NIA) and sensory symptoms (neurological symptom assessment, NSA). Sensory symptoms were present in 24% of patients, 91% had at least one abnormal finding in the neurological examination and 84% had abnormal nerve conduction. The greatest deviation from normal was observed for CPT on the dorsum of the foot and peroneal MCV. NIA and NSA correlated with all electrophysiological measurements in the foot and big toe. It is concluded that clinical findings correlate well with electrophysiological abnormalities in patients with type 1 diabetic neuropathy. An elevated CPT for the foot was the most pronounced sensory defect.

  • 12.
    Ingelsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Effects of trans10cis12CLA-induced insulin resistance on retinol-binding protein 4 concentrations in abdominally obese men2008In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 82, no 3, e23-e24 p.Article in journal (Refereed)
    Abstract [en]

    In this randomized, placebo-controlled, double-blind study of 57 abdominally obese middle-aged men, conjugated linoleic acid (CLA) did not induce changes in retinol-binding protein 4 concentrations (RBP4), despite marked induced insulin resistance. Further, there were no associations between CLA-induced insulin resistance and changes in RBP4.

  • 13.
    Mayega, Roy William
    et al.
    Department of Epidemiology, Biostatistics, Makerere University School of Public Health, Kampala, Uganda.
    Guwatudde, David
    Department of Epidemiology, Biostatistics, Makerere University School of Public Health, Kampala, Uganda.
    Makumbi, Fredrick Edward
    Department of Epidemiology, Biostatistics, Makerere University School of Public Health, Kampala, Uganda.
    Nakwagala, Frederick Nelson
    Department of Internal Medicine, Mulago National Referral and Hospital, Kampala, Uganda.
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Tomson, Göran
    Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Ostenson, Claes-Göran
    Department of Molecular Medicine and Surgery, Endocrine and Diabetes Unit, Karolinska Institutet, Stockholm, Sweden.
    Comparison of fasting plasma glucose and haemoglobin A1c point-of-care tests in screening for diabetes and abnormal glucose regulation in a rural low income setting2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 104, no 1, 112-120 p.Article in journal (Refereed)
    Abstract [en]

    Aims

    Glycated haemoglobin (HbA1C) has been suggested to replace glucose tests in identifying diabetes and pre-diabetes. We assessed agreement between fasting plasma glucose (FPG) and HbA1C rapid tests in classifying abnormal glucose regulation (AGR), and their utility for preventive screening in rural Africa.

    Methods

    A population-based survey of 795 people aged 35–60 years was conducted in a mainly rural district in Uganda. FPG was measured using On-Call® Plus glucometers, and classified using World Health Organization (WHO) and American Diabetes Association (ADA) criteria. HbA1C was measured using A1cNow® kits and classified using ADA criteria. Body mass index and blood pressure were measured. Percentage agreement between the two tests was computed.

    Results

    Using HbA1C, 11.3% of participants had diabetes compared with 4.8% for FPG. Prevalence of HbA1C-defined pre-diabetes (26.4%) was 1.2 times and 2.5 times higher than FPG-defined pre-diabetes using ADA (21.8%) and WHO (10.1%) criteria, respectively. With FPG as the reference, agreement between FPG and HbA1C in classifying diabetes status was moderate (Kappa = 22.9; Area Under the Curve (AUC) = 75%), while that for AGR was low (Kappa = 11.0; AUC = 59%). However, agreement was high (over 90%) among negative tests and among participants with risk factors for type 2 diabetes (obesity, overweight or hypertension). HbA1C had more procedural challenges than FPG.

    Conclusions

    Although low in the general sample, agreement between HbA1C and FPG is excellent among persons who test negative with either test. A single test can therefore identify the majority at lower risk for type 2 diabetes. Nurses if trained can conduct these tests.

  • 14. Norberg, M
    et al.
    Stenlund, H
    Lindahl, B
    Andersson, C
    Eriksson, Jan W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Weinehall, L
    Work stress and low emotional support is associated with increased risk of future type 2 diabetes in women.2007In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 76, no 3, 368-77 p.Article in journal (Refereed)
    Abstract [en]

    A case-referent study nested within a population-based health survey investigated the associations between psychosocial stress, such as work stress and low emotional support, and future development of type 2 diabetes among occupationally working middle-aged men and women. All participants in a health survey conducted during 1989-2000 (n=33,336) in Umeå in northern Sweden, were included. We identified 191 cases, who were not diabetic initially but were diagnosed with type 2 diabetes after 5.4+/-2.6 years. Two age- and sex-matched referents were selected for each case. Multivariate logistic regression analyses and interaction effects between variables were evaluated. In women, passive or tense working situations were associated with future type 2 diabetes with odds ratios 3.6 (95% confidence interval 1.1-11.7) and 3.6 (1.0-13.3), respectively, and also low emotional support 3.0 (1.3-7.0). These associations were not seen in men. In women, they remained after adjustment for BMI, civil status and educational level, and there were also tendencies for interactions between work stress and low emotional support. In conclusion, work stress and low emotional support may increase the risk of type 2 diabetes in women, but not in men. These findings contribute to our understanding of psychosocial stress as potential risk factors for type 2 diabetes in a Swedish population.

  • 15.
    Nyström, Thomas
    et al.
    Karolinska Inst, Unit Diabet Res, Div Internal Med, Dept Clin Sci & Educ, Stockholm, Sweden..
    Bodegard, Johan
    AstraZeneca Nordic Baltic, Sodertalje, Sweden..
    Nathanson, David
    Karolinska Inst, Unit Diabet Res, Div Internal Med, Dept Clin Sci & Educ, Stockholm, Sweden..
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden..
    Norhammard, Anna
    Karolinska Inst, Dept Med, Cardiol Unit, Stockholm, Sweden.;Capio St Gorans Hosp, Stockholm, Sweden..
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Second line initiation of insulin compared with DPP-4 inhibitors after metformin monotherapy is associated with increased risk of all-cause mortality, cardiovascular events, and severe hypoglycemia2017In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 123, 199-208 p.Article in journal (Refereed)
    Abstract [en]

    Aims: The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i). Methods: All patients with T2D in Sweden who initiated second-line treatment with insulin or DPP-4i after metformin monotherapy during 2007-2014 identified in the Swedish Prescribed Drug Register were followed for outcome in the Cause of Death and National Patient Registers. Insulin and DPP-4i patients were matched 1: 1 using propensity-score matching. Comparisons between groups were performed using unadjusted Cox regression models. Additionally, multivariate adjusted survival models were used to test the results using the full population without matching. Results: Of 27,767 mono-metformin-treated patients, 55.7% started insulin and 44.3% a DPP-4i, and after matching both groups had 9278 patients each. Median follow-up (patients years) times were 3.84 (37,578) and 3.93 (37,983) for insulin and DPP-4i-groups, respectively. Insulin compared with DPP-4i was associated with higher risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia; adjusted HR (95% CI): 1.69 (1.45-1.96); 1.39 (1.21-1.61); and 4.35 (2.26-8.35), respectively. When performing multivariate adjusted analyses on the full population similar results were found. Conclusions: Initiation of insulin, compared with DPP-4i treatment, was associated with an increased risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia. Results from randomized trials will be important to elucidate causal relationships.

  • 16.
    Petersson, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Serum fatty acid composition and insulin resistance are independently associated with liver fat markers in elderly men2010In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 87, no 3, 379-384 p.Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the relationships of serum fatty acid (FA) composition and estimated desaturase activities with the liver fat marker alanine aminotransferase (ALT). METHODS: 546 Swedish elderly men of a population-based cohort participated in this cross-sectional study. FA composition was assessed in serum cholesterol esters to determine dietary fat quality (e.g. linoleic) and desaturation products (e.g. dihomo-gamma-linolenic acid). Desaturase indices, including stearoyl coenzymeA desaturase-1 (SCD-1), were calculated by FA product-to-precursor ratios. RESULTS: In linear regression analyses adjusting for lifestyle, abdominal obesity and insulin sensitivity, the dietary biomarker linoleic acid (n-6), but not n-3 FAs, was inversely related to ALT. Desaturation products including palmitoleic, oleic, gamma-linolenic and dihomo-gamma-linolenic acids, and Delta6-desaturase and SCD-1 indices were directly related to ALT (all p<0.05). After further adjustment for factors previously linked to fatty liver (i.e. serum lipids, adiponectin concentrations), SCD-1 index (p=0.004) and insulin resistance (p<0.0001) were independent determinants of ALT activity, whereas waist circumference, triglycerides, non-esterified FA and adiponectin were not. CONCLUSION: A low dietary intake of linoleic acid and elevated SCD-1 index may contribute to higher ALT activity in elderly men, even independently of obesity and insulin resistance.

  • 17.
    Thors Adolfsson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Walker-Engström, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Smide, Bibbi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wikblad, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Patient education in type 2 diabetes: A randomized controlled 1-year follow-up study2007In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 76, no 3, 341-350 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the impact of empowerment group education on type 2 diabetes patients’ confidence in diabetes knowledge, self-efficacy, satisfaction with daily life, BMI and glycaemic control compared with the impact of routine diabetes care on the same factors at a 1-year follow-up. In this randomized controlled trial, conducted at 7 primary care centres in central Sweden, 101 patients were randomly assigned either to empowerment group education (intervention group) or to routine diabetes care (control group). Out of these, 42 patients in the intervention group and 46 in the control group completed the 1-year follow-up. Before the intervention and at the 1-year follow-up, the patients answered a 27-item questionnaire, and weight, BMI and HbA1c were measured. The questionnaire comprised three domains: confidence in diabetes knowledge, self-efficacy and satisfaction with daily life. At 1-year follow-up, the level of confidence in diabetes knowledge was significantly higher in the intervention group than in the control group (p<0.05). No significant differences were found in self-efficacy, satisfaction with daily life, BMI and HbA1c between the intervention and control group.

    The empowerment group education did improve patients’ confidence in diabetes knowledge with maintained glycaemic control despite the progressive nature of the disease.

  • 18.
    Wahlberg, Jeanette
    et al.
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Ekman, Bertil
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Nystrom, Lennarth
    Umea Univ, Dept Publ Hlth & Clin Med, Epidemiol, Umea, Sweden..
    Hanson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Persson, Bengt
    Karolinska Inst, Div Pediat, Dept Women & Child Hlth, Stockholm, Sweden..
    Arnqvist, Hans J.
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Gestational diabetes: Glycaemic predictors for fetal macrosomia and maternal risk of future diabetes2016In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 114, 99-105 p.Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate how glucose levels at diagnosis of gestational diabetes (GDM) are associated with infant birth weight and long-term risk of manifest diabetes mellitus in the mother. Methods: In a case control study GDM pregnancies (n = 2085) were compared with non-GDM pregnancies matched for day of delivery and obstetric unit (n = 3792). GDM was defined as capillary blood glucose (cB-glucose) >9.0 mmol/l (plasma glucose >10.0 mmol/l) after a 75 g oral glucose tolerance test (OGTT). The GDM cohort were followed up 8.5-13.5 yrs after initial diagnosis with a questionnaire, answered by 1324 GDM women (65%). Results: GDM women had higher mean infant birth-weight compared with controls (3682 g vs. 3541 g, P < 0.001). In multiple linear regression analysis, birth weight was positively correlated to fasting cB-glucose at GDM diagnosis (P < 0.001), increased week of gestation (P < 0.001) and BMI before pregnancy (P < 0.003), while 2 h OGTT cB-glucose values >= 9.0 mmol/l were not related. Infants born to mothers with fasting cB-glucose >= 4.5 mmol/l had no increased mean birth-weight or macrosomia (>= 4500 g) compared to controls. In the follow up 334/1324 women (25%) of the GDM women had developed diabetes, 215 type 2 diabetes, 46 type 1 diabetes and 72 unclassified diabetes. In logistic regression fasting cB-glucose and 2 h OGTT cB-glucose at diagnosis of GDM as well as BMI >25 and origin outside Europe were risk factors for manifest diabetes. Conclusions: Fasting blood glucose at diagnosis of GDM gives important information besides 2 h OGTT glucose about pregnancy outcome and future risk for maternal diabetes.

  • 19. Wandell, Per E.
    et al.
    Carlsson, Axel C.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Gender differences and time trends in incidence and prevalence of type 2 diabetes in Sweden: A model explaining the diabetes epidemic worldwide today?2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 106, no 3, E90-E92 p.Article in journal (Refereed)
    Abstract [en]

    Gender differences in type 2 diabetes in Sweden were studied based on a literature search. The male predominance in 1940s (male/female ratio 1.2-1.4 in the ages 10-55 years) increased over time especially in the age 45-64 years with a male/female ratio up to 2.

  • 20.
    Zethelius, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Med Prod Agcy, Uppsala, Sweden..
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Comparison between indexes of insulin resistance for risk prediction of cardiovascular diseases or development of diabetes2015In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 110, no 2, 183-192 p.Article in journal (Refereed)
    Abstract [en]

    Aim: The predictive effect of various insulin resistance indexes for risk of cardiovascular diseases (CVD) or type 2 diabetes (T2DM) is still unclear. Methods: One thousand and forty-nine 71-years-old male subjects from the Swedish ULSAM study, mean follow-up 9 years. All subjects performed the euglycemic insulin clamp for M/I [glucose disposal/mean insulin], and 75-g oral glucose tolerance test for Ceder-IR: 1/glucose uptake rate/[mean glucose x log mean insulin]; Matsuda-IR: 1/10,000/square root [glucose0 x insulin0 x glucose120 x insulin120]; Belfiore-IR: 1/([glucose0 + glucose120]/normal mean glucose x [insulin0 + insulin120]/normal mean insulin)+1); and HOMA-IR: [glucose0 x insulin0]/22.5. Results: Bland-Altman plots showed best agreement between M/I versus Belfiore-IR and Ceder-IR with mean difference near zero, -0.21 to -0.46, while -0.68 to -0.77 for the other indexes. ISI-Ceder was the strongest predictor for incident nonfatal/fatal ischemic heart disease (CHD) or CVD at Cox regression in all subjects, and for incident T2DM at logistic regression in 1024 subjects with no baseline T2DM, with significantly higher hazard ratios or odds ratios than with all other indexes, also with best model fit, after adjusting for clinical characteristics and the traditional cardiovascular risk factors, including metabolic syndrome for CVD risk. Conclusion: Ceder-IR performed strongest as independent predictor for incidences of CHD/CVD and T2DM.

  • 21.
    Zethelius, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eliasson, Björn
    Eeg-Olofsson, Katarina
    Svensson, Ann-Marie
    Gudbjörnsdottir, Soffia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    A new model for 5-year risk of cardiovascular disease in type 2 diabetes, from the Swedish National Diabetes Register (NDR)2011In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 93, no 2, 276-284 p.Article in journal (Refereed)
    Abstract [en]

    AIM:

    We assessed the association between risk factors and cardiovascular disease (CVD) in an observational study of type 2 diabetes patients from the Swedish National Diabetes Register.

    METHODS:

    A derivation sample of 24,288 patients, aged 30-74 years, 15.3% with previous CVD, baseline 2002, 2488 CVD events when followed for 5 years until 2007. A separate validation data set of 4906 patients, baseline 2003, 522 CVD events when followed for 4 years.

    RESULTS:

    Adjusted hazard ratios at Cox regression for fatal/nonfatal CVD were: onset-age 1.59, diabetes duration 1.55, total-cholesterol-to-HDL-cholesterol ratio 1.20, HbA1c 1.12, systolic BP 1.09, BMI 1.07 (1 SD increase in natural log continuous variables); males 1.41, smoker 1.35, microalbuminuria 1.27, macroalbuminuria 1.53, atrial fibrillation 1.50, previous CVD 1.98 (all p<0.001 except BMI p=0.0018). All 12 variables were used to elaborate an equation for 5-year CVD risk in the derivation dataset: mean 5-year risk 11.9±8.4%. Calibration in the validation dataset was adequate: ratio predicted 4-year risk/observed rate 0.97. Discrimination was sufficient: C statistic 0.72, sensitivity 51% and specificity 78% for top quartile.

    CONCLUSION:

    This CVD risk model from a large observational study of patients in routine care showed adequate calibration and discrimination, and can be useful for clinical practice.

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