Search

Background: Given sparse relevant data, the aim of this study was to determine whether Helicobacter pylori infection, including cytotoxin-associated gene-A (CagA) producing strains, is associated with dementia in type 2 diabetes (T2DM)., Methods: Longitudinal data from 1115 participants in the community-based Fremantle Diabetes Study Phase I (mean age 64.0 years, 48.0 % males; 38.0 % H. pylori seronegative, 24.3 % H. pylori seropositive/CagA seronegative, and 37.7 % H. pylori/CagA seropositive at baseline) were analyzed., Results: During up to 19 years of follow-up, 50.3 % and 83.5 % of participants without and with incident dementia, respectively, died. In Cox proportional hazards models, H. pylori/CagA seropositivity (hazard ratio (95 % CI) 1.68 (1.15, 2.46), P = 0.008), but not H. pylori seropositivity/CagA seronegativity (P = 0.541) was an independent predictor of incident dementia, but neither H. pylori seropositivity/CagA seronegativity nor H. pylori/CagA seropositivity were significant predictors in competing risks models (P ≥ 0.280)., Conclusions: Although CagA seropositivity in T2DM may have a contributory etiologic role in the risk of dementia, this may be through its association with reduced cardiovascular/all-cause mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To examine whether prior gestational diabetes mellitus (GDM) is associated with prevalent coronary heart disease (CHD), cerebrovascular disease (CeVD) and peripheral arterial disease (PAD), and all-cause mortality, in community-based women with type 2 diabetes., Methods: Baseline prevalences of CHD/CeVD/PAD/prior GDM were determined in 718 females (mean ± SD age 65.5 ± 11.9 years) from the Fremantle Diabetes Study Phase II. Deaths between baseline (2008-2011) and end-2016 were ascertained. Cox regression identified predictors of mortality with GDM as a candidate variable., Results: Compared to the 673 women without GDM, the 39 (5.4 %) with prior GDM were younger, more likely Aboriginal, smokers and obese, had longer diabetes duration and higher HbA 1c levels, and were more dyslipidemic (P ≤ 0.046). Prevalences of CHD (24.6 versus 23.1 %), CeVD (7.5 % versus 2.6 %) and PAD (27.5 % versus 23.7 %) were not significantly different in those without versus with prior GDM (P ≥ 0.35). There were 116 deaths (16.2 %) during 6.8 ± 1.6 years of follow-up. Age, Aboriginal ethnicity, marital status, current smoking, heart rate, estimated glomerular filtration rate, CHD and PAD were independently associated with all-cause mortality (P ≤ 0.023); GDM status did not add to the most parsimonious model (P = 0.62)., Conclusions: Prior GDM does not increase CVD risk or all-cause mortality in women with type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data relating to the effects of metformin-associated vitamin B12 deficiency on the risk of distal symmetrical polyneuropathy (DSPN) and megaloblastic anaemia in well-characterised community-based cohorts., Aims: To assess inter-relationships between metformin therapy, vitamin B12 deficiency assessed using serum active B12 concentrations, and DSPN and anaemia in 1492 Fremantle Diabetes Study Phase 2 (FDS2) participants with type 2 diabetes., Methods: Prevalence rates of vitamin B12 deficiency (total <80 pmol/L, active <23 pmol/L) and borderline deficiency (total ≥80 and ≤200 pmol/L, active ≥23 and ≤35 pmol/L) were determined using baseline sera. The relationship between vitamin B12 status and both DSPN and anaemia was assessed using multivariable analyses., Results: Most FDS2 participants (94.4%) were vitamin B12 replete (total serum concentration >200 pmol/L, active >35 pmol/L), 2.0% were deficient (total <80 pmol/L, active <23 pmol/L) and the remainder (3.6%) borderline. Although metformin treatment increased the odds of deficiency (4.2%, 3.1% borderline) in a dose-dependent fashion (odds ratio (95% confidence interval) 39.4 (4.90-316) for >2000 mg daily compared with no treatment; P < 0.001), there was no significant association between vitamin B12 status and DSPN, anaemia (haemoglobin ≤130 g/L males, ≤120 g/L females), haemoglobin concentration or mean corpuscular volume (P ≥ 0.147). Metformin increased the likelihood of anaemia, especially at high doses, independent of vitamin B12 deficiency., Conclusions: Since nutritional sources likely attenuate metformin-associated vitamin B12 malabsorption and its clinical sequelae in developed countries such as Australia, there is no need for routine/opportunistic serum vitamin B12 screening in metformin-treated patients., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Background: There is a paucity of contemporary data on the prevalence and prognostic significance of cardiac autonomic neuropathy (CAN) from community-based cohorts with type 2 diabetes assessed using gold standard methods. The aim of this study was to assess these aspects of CAN in the longitudinal observational Fremantle Diabetes Study Phase II (FDS2)., Methods: FDS2 participants were screened at baseline using standardised cardiovascular reflex tests (CARTs) of heart rate variation during deep breathing, Valsalva manoeuvre and standing. CAN (no/possible/definite) was assessed from the number of abnormal CARTs. Multinomial regression identified independent associates of CAN status. Cox proportional hazards modelling determined independent baseline predictors of incident heart failure (HF) and ischaemic heart disease (IHD), and all-cause mortality., Results: Of 1254 participants assessed for CAN, 86 (6.9%) were outside CART age reference ranges and valid CART data were unavailable for 338 (27.0%). Of the remaining 830 (mean age 62.3 years, 55.3% males, median diabetes duration 7.3 years), 51.0%, 33.7% and 15.3% had no, possible or definite CAN, respectively. Independent associates of definite CAN (longer diabetes duration, higher body mass index and resting pulse rate, antidepressant and antihypertensive therapies, albuminuria, distal sensory polyneuropathy, prior HF) were consistent with those reported previously. In Kaplan-Meier analysis, definite CAN was associated with a lower likelihood of incident IHD and HF versus no/possible CAN (P < 0.001) and there was a graded increase in all-cause mortality risk from no CAN to possible and definite CAN (P < 0.001). When CAN category was added to the most parsimonious models, it was not a significant independent predictor of IHD (P ≥ 0.851) or HF (P ≥ 0.342). Possible CAN (hazard ratio (95% CI) 1.47 (1.01, 2.14), P = 0.046) and definite CAN (2.42 (1.60, 3.67), P < 0.001) increased the risk of all-cause mortality versus no CAN., Conclusions: Routine screening for CAN in type 2 diabetes has limited clinical but some prognostic value., (© 2024. The Author(s).)

The applicability of a UK-validated genetic risk score (GRS) was assessed in 158 participants in the Fremantle Diabetes Study Phase II diagnosed between 20 and <40 years of age with type 1 or type 2 diabetes or latent autoimmune diabetes of adults (LADA). For type 1 versus type 2/LADA, the area under the receiver operating characteristic curve (AUC) was highest for serum C-peptide (0.93) and lowest for the GRS (0.66). Adding age at diagnosis and body mass index to C-peptide increased the AUC minimally (0.96). The GRS appears of modest diabetes diagnostic value in young Australians., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Objective: To assess whether there are clusters of people with type 2 diabetes with distinct temporal profiles of lung function changes and characteristics., Research Design and Methods: Group-based trajectory modeling (GBTM) identified groups of participants with type 2 diabetes from the community-based observational Fremantle Diabetes Study Phase II (FDS2) who had at least two biennial measurements of forced expiratory volume in 1 s as a percentage of predicted (FEV1%pred) over 6 years. Independent associates of group membership were assessed using multinomial regression., Results: Of 1,482 potential FDS2 participants, 1,074 (72.5%; mean age, 65.2 years; 45.5% female; median diabetes duration, 8.0 years) were included in the modeling. The best fitting GBTM model identified four groups categorized by FEV1%pred trajectory: high (19.5%; baseline FEV1%pred, 106.5 ± 9.5%; slope 0%/year), medium (47.7%; FEV1%pred, 87.3 ± 8.7%; slope, -0.32%/year), low (25.0%; baseline FEV1%pred, 68.9 ± 9.8%; slope, -0.72%/year), and very low (7.9%; baseline FEV1%pred, 48.8 ± 9.6%; slope, -0.68%/year). Compared with the high group, the other groups were characterized by nonmodifiable and modifiable risk factors associated with lung function decline in the general population (including ethnicity, marital status, smoking, obesity, coronary heart disease, and chronic respiratory disease). The main, diabetes-specific, significant predictor of group membership was a higher HbA1c in the very low group. There was a graded increase in mortality from 6.7% in the high group to 22.4% in the very low group., Conclusions: Measurement of lung function in type 2 diabetes could help optimize clinical management and improve prognosis, including addressing glycemic control in those with a very low FEV1%pred., (© 2024 by the American Diabetes Association.)

Context: Macrovascular outcomes in type 2 diabetes have improved over recent decades. There are scant equivalent distal symmetric polyneuropathy (DSPN) data., Objective: This work aimed to characterize temporal changes in DSPN prevalence and incidence rates (IRs) in community-based Australians., Methods: An observational study was conducted among an urban population. Participants included individuals with type 2 diabetes from the Fremantle Diabetes Study phases I (FDS1; n = 1296 recruited 1993-1996) and II (FDS2; n = 1509 recruited 2008-2011). Main outcome measures included Michigan Neuropathy Screening Instrument (MNSI) clinical grading., Results: DSPN prevalence by 8-point MNSI was 30.8% (FDS1) and 58.9% (FDS2; P < .001), and by 6-point (excluding foot appearance) and 2-point (biothesiometry alone) MNSI was 37.5% and 35.7% (P = .336), and 33.8% and 38.7% (P = .011), respectively. Given between-phase changes in appearance assessment, 8-point MNSI data were not analyzed further. In multivariable analysis, FDS2 vs FDS1 participation was associated with 6-point (odds ratio (95% CI) 0.68 (0.56-0.83); P < .001) but not 2-point (0.90 (0.74-1.11); P = .326) MNSI DSPN prevalence. Four-year DSPN IRs (95% CI) for 6-point MNSI were 13.6 (12.0-15.4) and 17.6 (15.9-19.4)/100 person-years in FDS1 and FDS2, respectively (IR ratio [IRR] 1.31 [1.12-1.55]; P < .001), and for 2-point MNSI were 13.9 (12.3-15.8) and 7.4 (16.3-8.6/100 person-years; IRR 0.53 [0.43-0.64]; P < .001). FDS2 vs FDS1 independently predicted incident DSPN for 6-point (hazard ratio [95% CI] 1.25 [1.06-1.48]; P = .009) and 2-point (0.42 [0.33-0.55]; P < .001) MNSI., Conclusion: DSPN prevalence was lower or equivalent in FDS2 vs FDS1, and its incidence was greater or lower, in multivariable models depending on the MNSI features used., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Aims: To examine the relationships between glycaemia and treatment complexity over 6 years in well-characterized community-based people with type 2 diabetes., Materials and Methods: Fremantle Diabetes Study Phase II participants who had type 2 diabetes with glycated haemoglobin (HbA1c) and blood glucose-lowering therapy (BGLT) data over 6 years were included. Group-based multi-trajectory modelling identified combined HbA1c/BGLT trajectory subgroups for diabetes durations of ≤1.0 year (Group 1; n = 160), >1.0 to 10.0 years (Group 2; n = 382;) and >10.0 years (Group 3; n = 357). Multinomial regression was used to identify baseline associates of subgroup membership., Results: The optimum numbers of trajectory subgroups were three in Group 1 (low, medium, high) and four in Groups 2 and 3 (low, low/high medium, high). Each low trajectory subgroup maintained a mean HbA1c concentration of <53 mmol/mol (<7.0%) on lifestyle measures, or monotherapy (Group 3). All five medium subgroups had stable HbA1c trajectories at <58 mmol/mol (<7.5%) but required increasing oral BGLT, or insulin (Group 3, high medium). The Group 1 high subgroup showed a falling then increasing HbA1c with steady progression to insulin. The high subgroups in Groups 2 and 3 showed stable HbA1c profiles at means of approximately 64 mmol/mol (8.0%) and 86 mmol/L (10.0%), respectively, on insulin. Non-Anglo Celt ethnicity, central obesity and hypertriglyceridaemia were strongly associated with Group 1 high subgroup membership. Younger age at diagnosis and central obesity were independent associates of the most adverse HbA1c trajectories in Groups 2 and 3., Conclusions: These data demonstrate diabetes duration-dependent heterogeneity in glycaemic and treatment profiles and related clinical and laboratory variables, which have implications for management., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)