| 11. |
- Cervin, Camilla, et al.
(författare)
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Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes
- 2008
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 57:5, s. 1433-1437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Latent autoimmune diabetes in adults (LADA) is often considered a slowly progressing subtype of type 1 diabetes, although the clinical picture more resembles type 2 diabetes. One way to improve classification is to study whether LADA shares genetic features with type 1 and/or type 2 diabetes. RESEARCH DESIGN AND METHODS-To accomplish this we studied whether LADA shares variation in the HLA locus or INS VNTR and PTPN22 genes with type I diabetes or the TCF7L2 gene with type 2 diabetes in 361 LADA, 718 type 1 diabetic, and 1,676 type 2 diabetic patients, as well as 1,704 healthy control subjects from Sweden and Finland. RESULTS-LADA subjects showed, compared with type 2 diabetic patients, increased frequency of risk for the HLA-DQB1 *0201/*0302 genotype (27 vs. 6.9%; P < 1 X 10(-6)), with similar frequency as with type I diabetes (36%). In addition, LADA subjects showed higher frequencies of protective HLA-DQB1 *0602(3)/X than type I diabetic patients (8.1 vs. 3.2%, P = 0.003). The AA genotype of rs689, referring to the class I allele in the INS VNTR, as well as the CT/TT genotypes of rs2476601 in the PTPN22 gene, were increased both in type 1 diabetic (P = 3 X 10(-14) and P = 1 X 10(-10), respectively) and LADA (P = 0.001 and P = 0.002) subjects compared with control subjects. Notably, the frequency of the type 2 diabetes-associated CT/TT genotypes of rs7903146 in the TCF7L2 were increased in LADA subjects (52.8%; P = 0.03), to the same extent as in type 2 diabetic subjects (54.1%, P = 3 X 10(-7)), compared with control subjects (44.8%) and type I diabetic subjects (43.39%). CONCLUSIONS-LADA shares genetic features with both type I (HLA, INS VNTR, and PTPN22) and type 2 (TCF7L2) diabetes, which justifies considering LADA as an admixture of the two major types of diabetes.
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| 12. |
- Dahlin, Lars B., et al.
(författare)
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Improved metabolic control using glucose monitoring systems leads to improvement in vibration perception thresholds in type 1 diabetes patients
- 2020
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 57:4, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Few studies have examined how improved metabolic control might influence vibration perception thresholds (VPTs). The aim of this study was to evaluate if improved HbA1c can influence vibration thresholds in adults with type 1 diabetes (T1DM). Methods: VPTs were investigated at six frequencies (4–125 Hz) using VibroSense Meter in the sole of the foot at two occasions in 159 T1DM patients, at the heads of the first and fifth metatarsal bones, i.e. MTH1 and MTH5, respectively. The participants were divided into three groups: group A: HbA1c improved by more than 1 mmol/mol (n = 95), group B: HbA1c deteriorated by more than 1 mmol/mol (n = 48) and group C: HbA1c unchanged (± 1 mmol/mol) (n = 16) compared to baseline. Results: In group A, the mean z-score, reflecting the combined effect of all VPTs, improved being lower at the follow-up than at the baseline [0.2 (− 0.3 to 1.2) vs. −0.1 (− 0.7 to 0.8), p = 0.00002]. VPTs improved at 4 and 64 Hz at both MTH1 (metatarsal head 1) and MTH5. The VPTs at 125 Hz frequency improved at MTH5, but not at MTH1. No significant differences were seen in group B or group C. Conclusions: Lower HbA1c and lower VPTs in T1DM patients were associated with improved VPT, suggesting a reversible effect on nerve function by improved metabolic control.
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| 13. |
- Ekman, Linnéa, et al.
(författare)
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Diagnostic contribution of multi-frequency vibrometry to detection of peripheral neuropathy in type 1 diabetes mellitus compared with nerve conduction studies
- 2024
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Aim The aim was to assess the use of multi-frequency vibrometry (MFV) in detecting diabetic peripheral neuropathy (DPN) in type 1 diabetes in comparison to nerve conduction studies (NCS) and neurothesiometer (NT). Our objectives were to examine how VPTs correlated with NCS parameters, evaluate the efficacy of MFV in distinguishing DPN as well as to investigate whether MFV procedure could be based on fewer frequencies.Methods Adults with type 1 diabetes with previous MFV examinations were recruited at Skane University Hospital in Malmo, Sweden, between 2018 and 2020. Participants were examined regarding nerve function in the lower limbs through MFV, NT and NCS.Results A total of 66 participants (28 women and 38 men) with a median age of 50 (39 to 64) years were included in the study. Through NCS assessment, 33 participants (50%) were diagnosed with DPN. We found negative correlations between VPTs and all NCS parameters, where the strongest correlation was found between sural nerve amplitude and the 125 Hz frequency of MFV. A combination of four frequencies, two low (4 and 8 Hz) and two high (125 and 250 Hz), showed the highest classification efficacy (AUC 0.83, 95% CI 0.73-0.93).Conclusion We conclude that a strong correlation exists between the sural nerve amplitude and the VPTs at 125 Hz and that VPT testing with MFV can be focused on only four frequencies instead of seven, thus shortening test time, to distinguish DPN in the lower limb.
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| 14. |
- Ekman, Linnea, et al.
(författare)
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Normative values of the vibration perception thresholds at finger pulps and metatarsal heads in healthy adults
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Aims To establish normative values of vibration perception thresholds (VPTs), using multi-frequency vibrometry at finger pulps and at metatarsal heads of the foot in healthy adults. We also aimed to investigate factors that could potentially affect VPTs such as age, sex, height, weight, foot- or handedness and skin temperature. Methods VPTs were examined in 924 healthy and randomly selected subjects in the southern Sweden (mean 46 years; 628 women and 296 men). Inclusion criterias were adult subjects (>18 years) in considerable health without diabetes mellitus or other nerve affecting disorders. VPTs were measured at the finger pulps of index and little finger, as well as the first and fifth metatarsal heads of the foot, through multi-frequency vibrometry using the VibroSense Meter® I device. Patient characteristics were recorded and skin temperature was measured before assessment of VPTs. Results We present normative values of VPTs for a large population of both male and female subjects in various ages. VPTs detoriated as age increased (0.09-0.59 dB per year; p<0.001), i.e. progressing with normal aging. Increasing skin temperature affected VPTs in finger pulps, but not at metatarsal heads, with -0.2 to -1.6 dB, i.e. vibration perception improved with higher temperatures. Height was only found to affect the VPTs of metatarsal heads (250 Hz: 0.42 dB per cm). Sex, weight and handedness did not affect the VPTs. Conclusion We investigated the normative values of VPTs and presented affecting factors as age, skin temperature and height. With these results, VPT testing through multi-frequency vibrometry is enabled to be used in a clinical practice as a diagnostic tool when investigating neuropathy and other neurological disorders.
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| 15. |
- Elgzyri, Targ, et al.
(författare)
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Healing below the ankle is possible in patients with diabetes mellitus and a forefoot gangrene
- 2021
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Ingår i: SAGE Open Medicine. - : Sage Publications. - 2050-3121. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Forefoot gangrene in patients with diabetes is a severe form of foot ulcers with risk of progress and major amputation. No large cohort studies have examined clinical characteristics and outcome of forefoot gangrene in patients with diabetes. The aim was to examine clinical characteristics and outcome of forefoot gangrene in patients with diabetes admitted to a diabetic foot centre. Methods: Patients with diabetes and foot ulcer consecutively presenting were included if they had forefoot gangrene (Wagner grade 4) at initial visit or developed forefoot gangrene during follow-up at diabetic foot centre. Patients were prospectively followed up until final outcome, either healing or death. The median follow-up period until healing was 41 (3-234) weeks. Results: Four hundred and seventy-six patients were included. The median age was 73 (35-95) years and 63% were males. Of the patients, 82% had cardiovascular disease and 16% had diabetic nephropathy. Vascular intervention was performed in 64%. Fifty-one patients (17% of surviving patients) healed after auto-amputation, 150 after minor amputation (48% of surviving patients), 103 had major amputation (33% of surviving patients) and 162 patients deceased unhealed. Ten patients were lost at follow-up. The median time to healing for all surviving patients was 41 (3-234) weeks; for auto-amputated, 48 (10-228) weeks; for minor amputated, 48 (6-234) weeks; and for major amputation, 32 (3-116) weeks. Conclusion: Healing without major amputation is possible in a large proportion of patients with diabetes and forefoot gangrene, despite these patients being elderly and with extensive co-morbidity.
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| 16. |
- Enhörning, Sofia, et al.
(författare)
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Plasma copeptin and the risk of diabetes mellitus.
- 2010
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Ingår i: Circulation. - 1524-4539. ; 121:19, s. 51-2102
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited. METHODS AND RESULTS: We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001). CONCLUSIONS: Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation.
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| 17. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 18. |
- Glans, Forouzan, et al.
(författare)
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Immigrants from the Middle-East have a different form of Type 2 diabetes compared with Swedish patients.
- 2008
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Ingår i: Diabetic Medicine: A journal of the British Diabetic Association. - : Wiley. - 1464-5491. ; 25:3, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To compare the clinical characteristics of Type 2 diabetes (T2DM) between immigrants from the Middle-East and Swedish patients. METHODS: The study group included 450 consecutive patients with T2DM, 379 Swedish-born aged 61 +/- 12 years and 71 patients originally from the Middle-East aged 50 +/- 11 years from the diabetes clinic of Malmo University Hospital. RESULTS: Onset of diabetes had occurred 12 years earlier in the Middle-East immigrants compared with the Swedish-born patients (43 +/- 10 vs. 55 +/- 12 years, P < 0.001). Immigrants had lower fasting serum C-peptide [0.7 (0.1-2.6) vs. 0.9 (0.1-4.0) nmol/l, P = 0.013], lower homeostasis model assessment (HOMA)-beta[1.7 (0.1-9.1) vs. 2.7 (0.1-59.0), P = 0.010], lower HOMA-IR [0.4 (0.02-1.19) vs. 0.4 (0.01-2.8), P = 0.005] than the Swedish group. A first-degree family history of diabetes was reported in 61% of immigrants, compared with 47% of Swedish-born (P = 0.022). CONCLUSIONS: Immigrants from the Middle-East have an earlier onset, stronger family history and more rapid decline of pancreatic B-cell function than Swedish patients, suggesting that they have a different form of T2DM compared with Swedish patients.
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| 19. |
- Guey, Lin T., et al.
(författare)
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Power in the Phenotypic Extremes: A Simulation Study of Power in Discovery and Replication of Rare Variants
- 2011
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Ingår i: Genetic Epidemiology. - : Wiley. - 0741-0395. ; 35:4, s. 236-246
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Tidskriftsartikel (refereegranskat)abstract
- Next-generation sequencing technologies are making it possible to study the role of rare variants in human disease. Many studies balance statistical power with cost-effectiveness by (a) sampling from phenotypic extremes and (b) utilizing a two-stage design. Two-stage designs include a broad-based discovery phase and selection of a subset of potential causal genes/variants to be further examined in independent samples. We evaluate three parameters: first, the gain in statistical power due to extreme sampling to discover causal variants; second, the informativeness of initial (Phase I) association statistics to select genes/variants for follow-up; third, the impact of extreme and random sampling in (Phase 2) replication. We present a quantitative method to select individuals from the phenotypic extremes of a binary trait, and simulate disease association studies under a variety of sample sizes and sampling schemes. First, we find that while studies sampling from extremes have excellent power to discover rare variants, they have limited power to associate them to phenotype-suggesting high false-negative rates for upcoming studies. Second, consistent with previous studies, we find that the effect sizes estimated in these studies are expected to be systematically larger compared with the overall population effect size; in a well-cited lipids study, we estimate the reported effect to be twofold larger. Third, replication studies require large samples from the general population to have sufficient power; extreme sampling could reduce the required sample size as much as fourfold. Our observations offer practical guidance for the design and interpretation of studies that utilize extreme sampling. Genet. Epidemiol. 35: 236-246, 2011. (c) 2011 Wiley-Liss, Inc.
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| 20. |
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