Browsing by Subject "GLYCEMIC CONTROL"

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  • Matthews, David R.; Paldanius, Päivi M.; Stumvoll, Michael; Han, Jackie; Bader, Giovanni; Chiang, YannTong; Proot, Pieter; Del Prato, Stefano (2019)
    Aims To ensure the integrity of the planned analyses and maximize the clinical utility of the VERIFY study results by describing the detailed concepts behind its statistical analysis plan (SAP) before completion of data collection and study database lock. The SAP will be adhered to for the final primary data analysis of the VERIFY trial. Materials and Methods Vildagliptin efficacy in combination with metformin for early treatment of T2DM (VERIFY) is an ongoing, multicentre, randomized controlled trial aiming to demonstrate the clinical benefits of glycaemic durability and glucose control achieved with an early combination therapy in newly-diagnosed type 2 diabetes (T2DM) patients. Results The SAP was initially designed at the study protocol conception phase and later modified, as reported here, in collaboration between the steering committee members, statisticians, and the VERIFY study leadership team. All authors were blinded to treatment allocation. An independent statistician has additionally retrieved and presented unblinded data to the independent data safety monitoring committee. An overview of the trial design with a focus on describing the fine-tuning of the analysis plan for the primary efficacy endpoint, risk of initial treatment failure, and secondary, exploratory and pre-specified subgroup analyses is provided here. Conclusion According to optimal trial practice, the details of the statistical analysis and data-handling plan prior to locking the database are reported here. The SAP accords with high-quality standards of internal validity to minimize analysis bias and will enhance the utility of the reported results for improved outcomes in the management of T2DM.
  • Strandberg, Arto Y.; Hoti, Fabian J.; Strandberg, Timo E.; Christopher, Solomon; Haukka, Jari; Korhonen, Pasi (2016)
    Background Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown. Objective To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland. Methods 23 751 individuals aged >= 40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years). Results 2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50) for detemir, and 0.55 (95% CI, 0.44-0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses. Conclusion In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.
  • Tynjälä, Anniina; Forsblom, Carol; Harjutsalo, Valma; Groop, Per-Henrik; Gordin, Daniel (2020)
    OBJECTIVE Type 1 diabetes is accompanied by a significant burden of cardiovascular disease (CVD), which is poorly explained by traditional risk factors. We therefore aimed to explore whether arterial stiffness estimated by the augmentation index (AIx) predicts mortality in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS After baseline examination comprising pulse wave analysis by applanation tonometry alongside assessment of traditional cardiovascular risk factors, 906 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study were followed up for a median of 8.2 years (interquartile range 5.7-9.7). Associations between baseline hemodynamics, including AIx, and all-cause mortality as well as a composite of cardiovascular and/or diabetes-related mortality were investigated using multivariable Cox regression models. RESULTS The 67 individuals who died during follow-up had higher baseline AIx (median 28% [interquartile range 21-33] vs. 19% [9-27];P<0.001) compared with those alive. This association was independent of conventional risk factors (age, sex, BMI, HbA(1c), estimated glomerular filtration rate [eGFR], and previous CVD event) in Cox regression analysis (standardized hazard ratio 1.71 [95% CI 1.10-2.65];P= 0.017) and sustained in a subanalysis of individuals with chronic kidney disease. Similarly, higher AIx was associated with the composite secondary end point of cardiovascular and diabetes-related death (N= 53) after adjustments for sex, BMI, eGFR, previous CVD event, and height (standardized hazard ratio 2.30 [1.38-3.83];P= 0.001). CONCLUSIONS AIx predicts all-cause mortality as well as a composite cardiovascular and/or diabetes-related cause of death in individuals with type 1 diabetes, independent of established cardiovascular risk factors.
  • Ahola, Aila J.; Saraheimo, Markku; Freese, Riitta; Forsblom, Carol; Mäkimattila, Sari; Groop, Per-Henrik; FinnDiane Study Grp (2017)
    Aims: Inflammation plays an important role in the pathogenesis of cardiovascular diseases. Diet, as a modifiable risk factor, may in turn impact systemic inflammation. We therefore assessed whether adherence to the dietary recommendations is associated with high-sensitivity C-reactive protein (hs-CRP) concentrations in type 1 diabetes. Methods: Cross-sectional data from 677 FinnDiane study participants (48% men, mean +/- standard deviation age 46 +/- 13 years) were included. Dietary intake was assessed with a self-administered questionnaire. A diet score, with higher values denoting better adherence to the recommendations, was calculated. Serum hs-CRP concentration was measured, and individuals with hs-CRP <1.0 mg/l, and hs-CRP > 3.0 but <10.0 mg/l were compared. Results: Men and women with high hs-CRP had higher BMI, waist circumference, and triglyceride concentration, but lower HDL-cholesterol concentration. Adjusted for BMI, mean diet score was higher in the low hs-CRP group, both in men (10.8 +/- 3.6 vs. 9.9 +/- 3.8, p = 0.023) and women (12.7 +/- 3.4 vs. 11.6 +/- 3.5, p = 0.021). After further adjustments with potential confounding factors, the difference remained significant only in men. Conclusions: A diet that more closely adheres to the dietary recommendations is associated with lower hs-CRP in men. A prudent diet may help reduce systemic inflammation in type 1 diabetes. (C) 2017 Elsevier B.V. All rights reserved.
  • Finndiane Study Grp (2018)
    Background and aims: In the general population, habitual coffee consumption is inversely associated with the metabolic syndrome, a syndrome that is rather common also in patients with type 1 diabetes. However, whether coffee intake is beneficially related to the metabolic syndrome also in type 1 diabetes, is not known. We, therefore, studied the potential association between coffee consumption and the metabolic syndrome in a large population of individuals with type 1 diabetes. Furthermore, we investigated whether coffee consumption is associated with insulin resistance (estimated glucose disposal rate, eGDR), kidney function (estimated glomerular filtration rate, eGFR), and low-grade chronic inflammation (high-sensitivity C-reactive protein, hsCRP). Methods and results: Data from 1040 participants in the Finnish Diabetic Nephropathy Study were included in these cross-sectional analyses. Metabolic syndrome was assumed if at least 3 of the following cardiovascular risk factors were present: central obesity, high blood pressure, low HDL-cholesterol concentration, high triglyceride concentration, and hyperglycaemia. Subjects were categorized based on self-reported daily coffee intake: non-consumers (= 1 cups/d <3), moderate (>= 3 cups/d <5), and high coffee consumption (>= 5 cups/d). In multivariable logistic regression analysis, moderate and high coffee consumption was associated with increased odds of the metabolic syndrome. Moreover, any level of coffee consumption was associated with increased risk of the blood pressure-component. An increasing trend was observed in the eGFR with increasing coffee consumption. Conclusions: In type 1 diabetes, high coffee intake is associated with the metabolic syndrome, and especially its blood pressure-component. (C) 2018 Published by Elsevier B.V.
  • Ahola, Aila J.; Radzeviciene, Lina; Zaharenko, Linda; Bulum, Tomislav; Skrebinska, Sabine; Prakapiene, Edita; Blaslov, Kristina; Roso, Vinko; Rovite, Vita; Pirags, Valdis; Duvnjak, Lea; Sokolovska, Jelizaveta; Verkauskiene, Rasa; Forsblom, Carol (2020)
    Aims: To investigate the association between depressive symptomatology and health markers in type 1 diabetes. Methods: Four countries from the InterDiane Consortium had adopted the Finnish Diabetic Nephropathy Study protocol, including the Beck Depression Inventory (BDI). Associations between depression symptomatology, diabetes complications (diabetic nephropathy, proliferative retinopathy, major adverse cardiovascular events [MACE]) and vascular risk factors (metabolic syndrome, body mass index, glycaemic control) were investigated. Results: In a sample of 1046 participants (Croatia n = 99; Finland n = 314; Latvia n = 315; Lithuania n = 318), 13.4% displayed symptoms of depression (BDI score 16) with no statistically significant difference in the prevalence of depression among the cohorts. The highest rates of diabetic nephropathy (37.1%) and proliferative retinopathy (36.3%) were observed in Lithuania. The rates of MACE and metabolic syndrome were highest in Finland. In joint analyses, individuals exhibiting depression symptomatology had higher HbA(1c) (79 vs. 72 mmol/mol, p <0.001) and higher triglyceride concentration (1.67 vs. 1.28 mmol/l, p <0.001), than those without. In the multivariable model, BDI score was positively associated with the presence of diabetic nephropathy, proliferative retinopathy, MACE, and metabolic syndrome and its triglyceride component. Moreover, BDI score was positively associated with the number of metabolic syndrome components, triglyceride concentration, and HbA(1c). Conclusions: Comorbid depression should be considered a relevant factor explaining metabolic problems and vascular outcomes. Causality cannot be inferred from this crosssectional study. (c) 2020 Elsevier B.V. All rights reserved.
  • But, Anna; De Bruin, Marie L.; Bazelier, Marloes T.; Hjellvik, Vidar; Andersen, Morten; Auvinen, Anssi; Starup-Linde, Jakob; Schmidt, Marjanka K.; Furu, Kari; de Vries, Frank; Karlstad, Oystein; Ekstrom, Nils; Haukka, Jari (2017)
    Aims/hypothesis The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. Methods National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. Results A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for 6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences. Conclusions/interpretation The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.
  • Laine, M. K.; Kujala, R.; Eriksson, J. G.; Kautiainen, H.; Sarna, S.; Kujala, U. M. (2017)
    Aims Regular physical activity plays a major role, in both prevention and treatment of type 2 diabetes. Less is known whether vigorous physical activity during young adulthood is associated with costs of diabetes medication in later life. The aim of this study is to evaluate this question. Methods The study population consisted of 1314 former elite-class athletes and 860 matched controls. The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Information on purchases of diabetes medication between 1995 and 2009 was obtained from the drug purchase register of the Finnish Social Insurance Institution. Results The total cost of diabetes medication per person year was significantly lower among the former endurance (mean 81 theta [95% CI 33-151 theta ]) and mixed group athletes (mean 272 theta [95% CI 181- 388 theta]) compared with the controls (mean 376 theta [95% CI 284- 485 theta]), (p <0.001 and p = 0.045, respectively). Of the former endurance athletes, 0.4% used insulin, while 5.2% of the controls used insulin (p = 0.018). Conclusions A career as former endurance, sprint, jumper or team game athlete seems to reduce the costs of diabetes medication in later life.
  • Finndiane Study Grp; Ahola, Aila J.; Harjutsalo, Valma; Forsblom, Carol; Pouwer, Francois; Groop, Per-Henrik (2021)
    OBJECTIVE To investigate the relationship between depression and diabetic nephropathy progression in type 1 diabetes. RESEARCH DESIGN AND METHODS Data from 3,730 participants without end-stage renal disease (ESRD) at baseline, participating in the Finnish Diabetic Nephropathy Study, were included. Depression was assessed in three ways. Depression diagnoses were obtained from the Finnish Care Register for Health Care. Antidepressant agent purchase data were obtained from the Drug Prescription Register. Symptoms of depression were assessed using the Beck Depression Inventory (BDI). Based on their urinary albumin excretion rate (AER), participants were classified as those with normal AER, microalbuminuria, and macroalbuminuria. Progression from normal AER to microalbuminuria, macroalbuminuria, or ESRD; from microalbuminuria to macroalbuminuria or ESRD; or from macroalbuminuria to ESRD, during the follow-up period, was investigated. RESULTS Over a mean follow-up period of 9.6 years, renal status deteriorated in 18.4% of the participants. Diagnosed depression and antidepressant purchases before baseline were associated with 53% and 32% increased risk of diabetic nephropathy progression, respectively. Diagnosed depression assessed during follow-up remained associated with increased risk of disease progression (32%). BDI-derived symptoms of depression showed no association with the progression, but the total number of antidepressant purchases modestly reduced the risk (hazard ratio 0.989 [95% CI 0.982-0.997]), P = 0.008). With the sample divided based on median age, the observations followed those seen in the whole group. However, symptoms of depression additionally predicted progression in those age
  • The FinnDiane Study Group; Ahola, Aila J.; Forsblom, Carol; Harjutsalo, Valma; Groop, Per-Henrik (2019)
    Aims Low-carbohydrate diet (LCD) has gained interest among individuals with diabetes as a means to manage glycaemia. We investigated the adherence to LCD in the Finnish Diabetic Nephropathy Study and whether carbohydrate restriction is associated with cardio-metabolic risk factors. Methods Cross-sectional data were available from 902 individuals with type 1 diabetes (44% men, age 47±13 years). Dietary data were collected twice with a 3-day diet record. Mean of the measurements was used. Carbohydrate intake 253 g/day or >48 E%). In the whole population, carbohydrate-to-fat ratio was calculated and its association with health variables was investigated. Results Higher carbohydrate-to-fat ratio was associated with higher blood glucose variability, higher blood pressure, lower HDL cholesterol concentration, and in men with lower waist-to-hip ratio. LCD adherence (n=69) was associated with lower BMI (25.6 vs. 27.8 kg/m2, p=0.030), lower variability of blood glucose measurements (0.38 vs. 0.45 mmol/l, p=0.030), and lower diastolic blood pressure (74 vs. 79 mmHg, p=0.048). Men reporting LCD had higher total (5.1 vs. 4.0 mmol/l, p=0.007) and non-HDL cholesterol (3.4 vs. 2.7 mmol/l, p=0.021). Women with LCD had higher HDL-cholesterol concentration (1.9 vs. 1.5 mmol/l, p=0.014). Conclusions Reduced blood glucose variability, related to LCD, could have clinical relevance to individuals with type 1 diabetes.
  • Ahola, Aila J.; Harjutsalo, Valma; Thomas, Merlin C.; Forsblom, Carol; Groop, Per-Henrik (2021)
    We investigated the association between diet and risk of hospitalisation for diabetic ketoacidosis (DKA) or hypoglycaemia in type 1 diabetes. Food records were used to assess dietary intake. Data on DKA and hypoglycaemia hospitalisations, within two years of dietary assessments, were obtained from registries. Analyses were conducted with and without macronutrient substitution. Data were available from 1391 participants, 28 (2.0%) and 55 (4.0%) of whom were hospitalised due to DKA or hypoglycaemia, respectively. In the adjusted model, self-reported alcohol intake was associated with increased (per 10 g: B=1.463, 95% CI=1.114-1.922, p=0.006; per E%: B=1.113, 95% CI=1.027-1.206, p=0.009), and fibre intake with reduced (per g/MJ: B=0.934, 95% CI=0.878-0.995, p=0.034) risk of DKA hospitalisation. Substituting carbohydrates for fats was associated with increased risk for hypoglycaemia hospitalisation (B=1.361, 95% CI=1.031-1.795, p=0.029), while substituting alcohol for carbohydrates (B=1.644, 95% CI=1.006-2.685, p=0.047) or proteins (B=2.278, 95% CI=1.038-4.999, p=0.040) increased the risk for DKA hospitalisation. In conclusion, refraining from alcohol intake is a preventable risk factor for DKA, while higher fibre intake seems rather protective. Increasing carbohydrate intake while decreasing that of fats, is associated with higher hypoglycaemia risk. Whether this is a cause or effect of hypoglycaemia remains to be established.
  • Ahola, Aila J.; Freese, Riitta; Mäkimattila, Sari; Forsblom, Carol; Groop, Per-Henrik; FinnDiane Study Grp (2016)
    Aims: Diet plays an important role in the management of type 1 diabetes. However, the association between dietary intake and health has not been extensively studied in this population. We studied the cross-sectional association between dietary factors, and selected vascular health markers and complications in type 1 diabetes. Methods: Data from 874 individuals with type 1 diabetes participating in the FinnDiane Study were included. Dietary intake was assessed using a self-reported questionnaire and a diet score, expressing the extent to which individuals adhered to the dietary recommendations, was calculated. Diet questionnaire was also used to reveal dietary patterns using factor analysis. Results: Seven factors with high degree of inter-correlation were formed; healthy, traditional, vegetable, sweets, modern, low-fat cheese, and fish and eggs. In multivariate models, higher diet score and healthy factor score were associated with better glycaemic control. Higher diet score was associated with higher, while sweets, and fish and eggs patterns were associated with lower systolic blood pressure. Healthy, sweets, and fish and eggs factors were additionally associated with lower diastolic blood pressure. Conclusions: Closer adherence to the dietary recommendations, and a diet high in fresh vegetables, fruits and berries, cooked vegetables, fish dishes, and yoghurt may be beneficial for the glycaemic control in type 1 diabetes. Moreover, a diet pattern with fish and eggs may have beneficial effects for blood pressure. (C) 2016 Published by Elsevier Inc.
  • Ahola, Aila J.; Lassenius, Mariann I.; Forsblom, Carol; Harjutsalo, Valma; Lehto, Markku; Groop, Per-Henrik (2017)
    Gram-negative bacteria-derived lipopolysaccharides (LPS) are associated with various negative health effects. Whether diet is associated with LPS, is an understudied phenomenon. We investigated the association between diet and serum LPS activity in 668 individuals with type 1 diabetes in the FinnDiane Study. Serum LPS activity was determined using the Limulus Amoebocyte Lysate assay. Diet was assessed with a food frequency questionnaire (FFQ) section of a diet questionnaire and a food record. The food record was used to calculate energy, macronutrient, and fibre intake. In a multivariable model, energy, macronutrient, or fibre intake was not associated with the LPS activity. Using factor analysis, we identified seven dietary patterns from the FFQ data ("Sweet", "Cheese", "Fish", "Healthy snack", "Vegetable", "Traditional", and "Modern"). In a multivariable model, higher factor scores of the Fish, Healthy snack, and Modern patterns predicted lower LPS activity. The validity of the diet questionnaire was also investigated. The questionnaire showed reasonable relative validity against a 6-day food record. The two methods classified participants into the dietary patterns better than expected by chance. In conclusion, healthy dietary choices, such as consumption of fish, fresh vegetables, and fruits and berries may be associated with positive health outcomes by reducing systemic endotoxaemia.
  • Wackström, Nanna; Koponen, Anne M.; Suominen, Sakari; Tarkka, Ina M.; Simonsen, Nina (2020)
    ABSTRACT Background: Physical activity (PA) is a key component in management of type 2 diabetes (T2D). Pain might be a barrier to PA especially among older adults with T2D, but surprisingly few studies have investigated the association between chronic pain and PA. Our aim was to evaluate the prevalence of chronic pain among older adults with T2D and to examine the association between chronic pain and PA while taking important life-contextual factors into account. Methods: Data of this register-based, cross-sectional study were collected in a survey among adults with T2D (n=2866). In the current study, only respondents aged 65?75 years were included (response rate 63%, n=1386). Data were analysed by means of descriptive statistics and multivariate logistic regression analysis. Results: In total, 64% reported chronic pain. In specific groups, e.g. women and those who were obese, the prevalence was even higher. Among respondents experiencing chronic pain, frequent pain among women and severe pain among both genders were independently associated with decreased likelihood of being physically active. Moreover, the likelihood of being physically active decreased with higher age and BMI, whereas it increased with higher autonomous motivation and feelings of energy. Among physically active respondents suffering from chronic pain, neither intensity nor frequency of pain explained engagement in exercise (as compared with incidental PA). Instead, men were more likely to exercise regularly as were those with good perceived health and higher autonomous motivation. Conclusions: The prevalence of chronic pain is high among older adults with T2D. This study shows that among those suffering from chronic pain, severe pain is independently and inversely associated with being physically active, as is frequent pain, but only among women. Moreover, the findings show the importance of autonomous motivation and health variables for both incidental PA and exercise among older adults with T2D experiencing chronic pain.
  • Finndiane Study Grp (2018)
    Aims/hypothesisThe aim of this study was to assess the potential dose-dependent effects of smoking on the risk of CHD, heart failure and stroke in individuals with type 1 diabetes.MethodsThe study included 4506 individuals with type 1 diabetes who were participating in the Finnish Diabetic Nephropathy (FinnDiane) study. Intensity of smoking was estimated by packs per day and cumulative smoking by pack-years. Cox regression analyses were used to estimate the risk of incident CHD, heart failure or stroke during follow-up.ResultsOne pack per day significantly increased the risk of incident CHD in current smokers compared with never smokers (HR 1.45 [95% CI 1.15, 1.84]), after adjustment for age, sex, HbA(1c), hypertension, duration of diabetes and BMI. The risk of CHD in former smokers was similar to the risk in never smokers. The risk of incident heart failure was 1.43 (95% CI 1.03, 1.97) in current smokers per one pack per day and 1.37 (95% CI 1.05, 1.77) in former smokers, while the risk of incident stroke was 1.70 (95% CI 1.26, 2.29) and 1.49 (95% CI 1.14, 1.93), respectively. After further adjustments for lipids, however, the difference in the risk of heart failure in current and former smokers was no longer significant. Cumulative smoking data were similar to smoking intensity data.Conclusions/interpretationThere is a dose-dependent association between smoking and cardiovascular disease in individuals with type 1 diabetes. In men in particular, the risk of incident stroke remains high even after smoking cessation and is increased in current and former smokers independently of other risk factors.
  • Paldanius, Päivi Maria (2020)
    Type 2 diabetes mellitus (T2DM) is a complex and progressive chronic disease characterised by elevating hyperglycaemia and as-sociated need to gradually intensify therapy in order to achieve and maintain glycaemic control. Treating hyperglycaemia with se-quential therapy is proposed to allow holistic assessment of the efficacy and risk-to-benefit ratio of each added component. How-ever, there is an array of evidence supporting the scientific rationale for using synergistic, earlier, modern drug combinations to achieve glycaemic goals, delay the deterioration of glycaemic control, and, therefore, potentially preserve or slow down the declin-ing β-cell function. Additionally, implementation of early combination(s) may lead to opportunities to combat clinical inertia and other hurdles to optimised disease management outcomes. This review aims to discuss the latest empirical evidence for long-term clinical benefits of this novel strategy of early combination in people with newly diagnosed T2DM versus the current widely-im-plemented treatment paradigm, which focuses on control of hyperglycaemia using lifestyle interventions followed by sequentially intensified (mostly metformin-based) monotherapy. The recent reported Vildagliptin Efficacy in combination with metfoRmin For earlY treatment of T2DM (VERIFY) study results have provided significant new evidence confirming long-term glycaemic durability and tolerability of a specific early combination in the management of newly diagnosed, treatment-naïve patients world-wide. These results have also contributed to changes in clinical treatment guidelines and standards of care while clinical imple-mentation and individualised treatment decisions based on VERIFY results might face barriers beyond the existing scientific evi-dence.
  • Vencio, Sergio; Manosalva, Juan P.; Mathieu, Chantal; Proot, Pieter; Lozno, Hernan Yupanqui; Paldanius, Päivi M. (2021)
    Background Patients with type 2 diabetes mellitus (T2DM) from Latin American countries face challenges in access to healthcare, leading to under-diagnosis, under-achievement of glycemic target, and long-term complications. Early diagnosis and treatment initiation are of paramount importance in this population due to the high prevalence of risk factors such as obesity and metabolic syndrome. The VERIFY study in patients with newly diagnosed T2DM (across 34 countries), assessed the normoglycemic durability (5 years), with early combination (EC) therapy approach versus the traditional stepwise approach of initiating treatment with metformin monotherapy (MET). Here we present the results from the VERIFY study for participants from eight countries in Latin America. Methods Newly diagnosed adult patients with T2DM, HbA1c 6.5-7.5% and body-mass index (BMI) of 22-40 kg/m(2) were enrolled. The primary endpoint was time to initial treatment failure (TF; HbA1c >= 7.0% at two consecutive scheduled visits 13 weeks apart). Time to second TF was evaluated when patients in both groups were receiving and failing on the vildagliptin combination. Safety and tolerability were also assessed for both treatment approaches during the study. Results A total of 537 eligible patients (female, 58.8%) were randomly assigned to receive either EC (n = 266) or MET (n = 271). EC significantly reduced the relative risk of time to initial TF by 47% versus MET [HR (95% CI) 0.53 (0.4, 0.7) p < 0.0001]. Overall, 46.4% versus 66.3% of patients achieved the primary endpoint in the EC and MET groups, with a median [interquartile range (IQR)] time to TF of 59.8 (27.5, not evaluable) and 33.4 (12.2, 60.1) months, respectively. The risk for time to second TF was 31% lower with EC (p < 0.0092). A higher proportion of patients receiving EC maintained durable HbA1c < 7.0%, < 6.5%, and < 6.0%. Both treatment approaches were well tolerated, and only 3.2% of participants discontinued the study due to adverse events. All hypoglycemic events (EC: n = 7 and MET: n = 3) were single, mild episodes and did not lead to study discontinuation. Conclusion Similar to the global population, long-term clinical benefits were achieved more frequently and without tolerability issues with EC versus standard-of-care MET in this Latin American sub-population. This study is registered with ClinicalTrials.gov, NCT01528254.
  • Teramo, Kari; Piñeiro-Ramos, José David (2019)
    Oxidative stress is responsible for microvascular complications (hypertension, nephropathy, retinopathy, peripheral neuropathy) of diabetes, which during pregnancy increase both maternal and fetal complications. Chronic hypoxia and hyperglycemia result in increased oxidative stress and decreased antioxidant enzyme activity. However, oxidative stress induces also anti-oxidative reactions both in pregnant diabetes patients and in their fetuses. Not all type 1 diabetes patients with long-lasting disease develop microvascular complications, which suggests that some of these patients have protective mechanisms against these complications. Fetal erythropoietin (EPO) is the main regulator of red cell production in the mother and in the fetus, but it has also protective effects in various maternal and fetal tissues. This dual effect of EPO is based on EPO receptor (EPO-R) isoforms, which differ structurally and functionally from the hematopoietic EPO-R isoform. The tissue protective effects of EPO are based on its anti-apoptotic, anti-oxidative, anti-inflammatory, cell proliferative and angiogenic properties. Recent experimental and clinical studies have shown that EPO has also positive metabolic effects on hyperglycemia and diabetes, although these have not yet been fully delineated. Whether the tissue protective and metabolic effects of EPO could have clinical benefits, are important topics for future research in diabetic pregnancies.
  • Tikkanen-Dolenc, Heidi; Waden, Johan; Forsblom, Carol; Harjutsalo, Valma; Thorn, Lena M.; Saraheimo, Markku; Elonen, Nina; Rosengård-Bärlund, Milla; Gordin, Daniel; Tikkanen, Heikki O.; Groop, Per-Henrik; FinnDiane Study Grp (2017)
    Aims/hypothesis Cardiovascular disease (CVD) is the most common cause of premature death and disability among patients with type 1 diabetes. Diabetic nephropathy accounts for the increased cardiovascular morbidity and mortality of these patients. We recently showed that the intensity of exercise predicts the incidence and progression of diabetic nephropathy in patients with type 1 diabetes. Little is known about the relationship between physical activity and CVD. Therefore, we studied how physical activity affects the risk of CVD events in patients with type 1 diabetes. Methods A 10 year follow-up study including 2180 type 1 diabetes patients from the nationwide multicentre Finnish Diabetic Nephropathy Study (FinnDiane). Leisure time physical activity (LTPA) was assessed by a previously validated self-report questionnaire. A CVD event was defined as a verified myocardial infarction, coronary procedure or stroke. Patients were analysed separately for the risk of developing a first ever CVD event and for the risk of a recurrent CVD event following a baseline event. Results A total of 206 patients had an incident CVD event during follow-up. A higher total LTPA and higher intensity, frequency and duration of activity were associated with a lower risk of incident CVD events. The observed association between exercise frequency and incident CVD remained significant when adjusted for classic risk factors. Exercise intensity also had a borderline effect on the recurrence-free time in patients with a major CVD event at baseline. Conclusion/interprelation This study suggests that exercise, particularly high frequency and high intensity exercise, may reduce the risk of CVD events in patients with type 1 diabetes.
  • Karjalainen, M.; Saltevo, J.; Tiihonen, M.; Haanpää, M.; Kautiainen, H.; Mäntyselkä, P. (2018)
    Background: The association between pain and diabetes in older people has been largely unexplored. The aim of this survey was to analyze the prevalence and characteristics of pain among Finnish men and women 65 or older with and without diabetes in primary care. Methods: All home-dwelling persons 65 years or older with diabetes (N = 527) and age and gender matched controls (N = 890) were identified from electronic patient records. Frequent pain was regarded as any pain experienced more often than once a week, and it was divided into pain experienced several times a week but not daily and pain experienced daily or continuously. The Numeric Rating Scale (0-10) (NRS) was used to assess the intensity and interference of the pain. Results: The number of subjects who returned the questionnaire was 1084 (76.5%). The prevalence of frequent pain in the preceding week was 50% among women without diabetes and 63% among women with diabetes (adjusted, p = 0.22). In men, the corresponding proportions were 42% without diabetes and 47% with diabetes (adjusted, p = 0.58). In both genders, depressive symptoms and the number of comorbidities were associated with pain experienced more often than once a week and with daily pain. Diabetes was not associated with pain intensity or pain interference in either women or men. Conclusions: Pain in older adults is associated with depressive symptoms and the number of comorbidities more than with diabetes itself.