Browsing by Subject "type 1"

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  • The FinnDiane Study Group; Jansson Sigfrids, Fanny; Stechemesser, Lars; Dahlström, Emma H.; Forsblom, Carol M.; Harjutsalo, Valma; Weitgasser, Raimund; Taskinen, Marja Riitta; Groop, Per Henrik (2022)
    Objectives: We studied apolipoprotein C-III (apoC-III) in relation to diabetic kidney disease (DKD), cardiovascular outcomes, and mortality in type 1 diabetes. Methods: The cohort comprised 3966 participants from the prospective observational Finnish Diabetic Nephropathy Study. Progression of DKD was determined from medical records. A major adverse cardiac event (MACE) was defined as acute myocardial infarction, coronary revascularization, stroke, or cardiovascular mortality through 2017. Cardiovascular and mortality data were retrieved from national registries. Results: ApoC-III predicted DKD progression independent of sex, diabetes duration, blood pressure, HbA1c, smoking, LDL-cholesterol, lipid-lowering medication, DKD category, and remnant cholesterol (hazard ratio [HR] 1.43 [95% confidence interval 1.05–1.94], p = 0.02). ApoC-III also predicted the MACE in a multivariable regression analysis; however, it was not independent of remnant cholesterol (HR 1.05 [0.81–1.36, p = 0.71] with remnant cholesterol; 1.30 [1.03–1.64, p = 0.03] without). DKD-specific analyses revealed that the association was driven by individuals with albuminuria, as no link between apoC-III and the outcome was observed in the normal albumin excretion or kidney failure categories. The same was observed for mortality: Individuals with albuminuria had an adjusted HR of 1.49 (1.03–2.16, p = 0.03) for premature death, while no association was found in the other groups. The highest apoC-III quartile displayed a markedly higher risk of MACE and death than the lower quartiles; however, this nonlinear relationship flattened after adjustment. Conclusions: The impact of apoC-III on MACE risk and mortality is restricted to those with albuminuria among individuals with type 1 diabetes. This study also revealed that apoC-III predicts DKD progression, independent of the initial DKD category.
  • Tynjälä, Anniina; Forsblom, Carol; Groop, Per-Henrik; Gordin, Daniel; Harjutsalo, Valma (Helsingin yliopisto, 2020)
    The fact that individuals with type 1 diabetes (T1D) are at greater risk for cardiovascular disease and premature death, can only partly be explained by traditional risk factors. Interestingly, T1D is accompanied by arterial stiffening that correlates with microvascular and macrovascular complications. The aim of this study was to find out whether arterial stiffness predicts all-cause mortality in individuals with T1D. Augmentation index (AIx), a measure of arterial pulse wave reflections, is used to estimate stiffness in the resistance arteries and can be determined non-invasively from pulse wave analysis by applanation tonometry. The data consisted of 906 individuals with T1D from the FinnDiane Study that have been examined for arterial stiffness, cardiovascular risk factors and diabetic complications at baseline between 2001 and 2015. After a median follow-up of 8.2 (5.7-9.7) years, 67 individuals had died according to mortality data from Statistics Finland. They had higher baseline AIx (28 [21-33] vs. 19 [9-27] %, P < 0.001) compared to those alive. This association was independent of related risk factors (age, sex, BMI, HbA1c, triglycerides, renal function and past cardiovascular events) in Cox regression analysis (hazard ratio 1.042 [1.007-1.078], P = 0.017). Arterial stiffness estimated by AIx independently predicted all-cause mortality in T1D. Promising pharmacological agents counteracting arterial stiffness include inhibitors of the renin-angiotensin-aldosterone system and sodium-glucose co-transporter 2, and research data on their effect in individuals with T1D is constantly growing. Our finding suggests that detecting early arterial stiffening individuals with T1D could be useful in targeting a more aggressive treatment for high-risk individuals.
  • FinnDiane Study Grp; Eriksson, Marika; Summanen, Paula; Gordin, Daniel; Forsblom, Carol; Shams, Sara; Liebkind, Ron; Tatlisumak, Turgut; Putaala, Jukka; Groop, Per-Henrik; Martola, Juha; Thorn, Lena M. (2021)
    Introduction Cerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain's vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes. Research design and methods For this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33-45) years; 53% female; diabetes duration 21.6 (18.2-30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score). Results In type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20-61) vs 20 (20-35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20-65) vs 20 (20-35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts. Conclusions Presence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.
  • Claesson, Tor-björn; Putaala, Jukka; Shams, Sara; Salli, Eero; Gordin, Daniel; Liebkind, Ron; Forsblom, Carol; Summanen, Paula A.; Tatlisumak, Turgut; Groop, Per-Henrik; Martola, Juha; Thorn, Lena M. (2020)
    Background and purpose: Degenerative change of the corpus callosum might serve as a clinically useful surrogate marker for net pathological cerebral impact of diabetes type 1. We compared manual and automatic measurements of the corpus callosum, as well as differences in callosal cross-sectional area between subjects with type 1 diabetes and healthy controls. Materials and methods: This is a cross-sectional study on 188 neurologically asymptomatic participants with type 1 diabetes and 30 healthy age- and sex-matched control subjects, recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent clinical work-up and brain MRI. Callosal area was manually measured and callosal volume quantified with FreeSurfer. The measures were normalized using manually measured mid-sagittal intracranial area and volumetric intracranial volume, respectively. Results: Manual and automatic measurements correlated well (callosal area vs. volume: rho = 0.83, p <0.001 and mid-sagittal area vs. intracranial volume: rho = 0.82, p <0.001). We found no significant differences in the callosal measures between cases and controls. In type 1 diabetes, the lowest quartile of normalized callosal area was associated with higher insulin doses (p = 0.029) and reduced insulin sensitivity (p = 0.033). In addition, participants with more than two cerebral microbleeds had smaller callosal area (p = 0.002). Conclusion: Manually measured callosal area and automatically segmented are interchangeable. The association seen between callosal size with cerebral microbleeds and insulin resistance is indicative of small vessel disease pathology in diabetes type 1.
  • TRIGR Investigators; Hakola, Leena; Erlund, Iris; Cuthbertson, David; Miettinen, Maija E.; Autio, Reija; Nucci, Anita M.; Härkönen, Taina; Honkanen, Jarno; Vaarala, Outi; Hyöty, Heikki; Knip, Mikael; Krischer, Jeffrey P.; Niinistö, Sari; Virtanen, Suvi M. (2021)
    Background Circulating fatty acids have been linked to development of type 1 diabetes. Objectives To study the prospective associations of serum fatty acids with the risk of islet autoimmunity in high-risk children. Methods A nested case-control selection was carried out within the TRIGR cohort, which included infants with HLA (DQB1 or DQA1)-conferred disease susceptibility and a first-degree relative with type 1 diabetes, born between 2002 and 2007 in 15 countries and followed-up until 2017. The present study included 244 case children positive for at least two islet autoantibodies (ICA, IAA, GADA, and IA-2A) and two control children were matched for country and age. Proportions of 26 serum fatty acids at cord blood and at 6, 12, and 18 months of age were assessed using gas-chromatography. Results The average proportions of the following fatty acids were associated with an increased risk of islet autoimmunity, adjusted for sex, HLA risk, and maternal type 1 diabetes: pentadecanoic acid (15:0) (OR 3.41: 95% CI 1.70, 6.85), heptadecanoic acid (iso 17:0) (2.64: 1.62, 4.28) and (anteiso 17:0) (2.27: 1.39, 3.70), stearic acid (18:0) (23.8: 2.32, 244.6), and conjugated linoleic acid (18:2n-7) (2.60: 1.47, 4.59). Breastfeeding and not having maternal type 1 diabetes were positively associated with levels of the above-mentioned fatty acids. N-3 fatty acids were not consistently associated with islet autoimmunity. Conclusions We found direct associations of pentadecanoic acid, heptadecanoic acid, stearic acid, and conjugated linoleic acid with the risk of islet autoimmunity. Further studies are needed to understand the complex role of fatty acids in the development of type 1 diabetes.