Effect of prior gestational diabetes on the risk of cardiovascular disease and death in women with type 2 diabetes: The Fremantle Diabetes Study Phase II.

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 HbA1c 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.

Engagement of medication users in the development and implementation of digital medication adherence technologies: a multi-stakeholder study.

BACKGROUND: This study aims to create a comprehensive framework for the development and implementation of digital medication adherence technologies (DMATech), focusing on critical stages where engagement of medication users (MU) is considered meaningful, i.e. adds significant value, as agreed upon by participating stakeholders. METHODS: Through a literature review and expert consensus, a framework was outlined covering key DMATech development and implementation phases and steps. An in-person workshop with MU representatives and adherence experts, using the Nominal Group Technique, further refined these stages for MU engagement. RESULTS: The DMATech framework included three phases: 'Innovation,' 'Research and Development,' and 'Launch and Implementation,' each encompassing multiple steps. The workshop, attended by five MU representatives and nine adherence experts, identified critical stages for MU input including context analysis, ideation, proof of concept, prototype creation, DMATech's iteration, critical evaluation, healthcare implementation, real-world assessment, and improvement. Nevertheless, there was a divergence of consensus regarding the importance of MUs engagement in regulatory, financial, and marketing aspects. CONCLUSIONS: This study provides a holistic framework for DMATech development and implementation and underscores the necessity of MU engagement at various stages. Modes of MU engagement cannot be generalized; a case-by-case evaluation of engagement strategies is essential.

Increasing Access To Perinatal Mental Health Care: The Perinatal Psychiatry Access Program Model.

Perinatal psychiatry access programs offer a scalable approach to building the capacity of perinatal professionals to identify, assess, and treat mental health conditions. Little is known about access programs' implementation and the relative merits of differing approaches. We conducted surveys and semistructured interviews with access program staff and reviewed policy and procedure documents from the fifteen access programs that had been implemented in the United States as of March 2021, when the study was conducted. Since then, the number of access programs has grown to thirty state, regional, or national programs. Access programs implemented up to five program components, including telephone consultation with a perinatal psychiatry expert, one-time patient-facing consultation with a perinatal psychiatry expert, resource and referral to perinatal professionals or patients, trainings for perinatal professionals, and practice-level technical assistance. Characterizing population-based intervention models, such as perinatal psychiatry access programs, that address perinatal mental health conditions is a needed step toward evaluating and improving programs' implementation, reach, and effectiveness.

Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II.

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.

Pulmonary Function Trajectories Over 6 Years and Their Determinants in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

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.

Use of a type 1 genetic risk score for classification of diabetes type in young Australian adults: the Fremantle Diabetes Study Phase II.

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.

Individual and Collective Forms of Stigma Resistance: Pathways Between HIV and Sex Work Stigma and Viral Suppression Among Female Sex Workers in the Dominican Republic.

Intersecting forms of stigma including both HIV and sex work stigma have been known to impede HIV prevention and optimal treatment outcomes among FSW. Recent research has indicated that intersectional stigma can be resisted at the community and individual level. We assessed pathways between HIV stigma, sex work stigma, social cohesion and viral suppression among a cohort of 210 FSW living with HIV in the Dominican Republic. Through Poisson regression we explored the relationship between HIV outcomes and internalized, anticipated and enacted HIV and sex work stigma, and resisted sex work stigma. We employed structural equation modeling to explore the direct effect of various forms of stigma on HIV outcomes, and the mediating effects of multi-level stigma resistance including social cohesion at the community level and occupational dignity at the individual level. 76.2% of FSW were virally suppressed and 28.1% had stopped ART at least once in the last 6 months. ART interruption had a significant negative direct effect on viral suppression (OR = 0.26, p < 0.001, 95% CI: 0.13-0.51). Social cohesion had a significant positive direct effect on viral suppression (OR = 2.07, p = 0.046, 95% CI: 1.01-4.25). Anticipated HIV stigma had a significant negative effect on viral suppression (OR = 0.34, p = 0.055, 95% CI: 0.11-1.02). This effect was mediated by the interaction between cohesion and dignity which rendered the impact of HIV stigma on viral suppression not significant. Findings demonstrate that while HIV stigma has a negative impact on viral suppression among FSW, it can be resisted through individual and collective means. Results reinforce the importance of community-driven, multi-level interventions.

Temporal Trends in Distal Symmetric Polyneuropathy in Type 2 Diabetes: The Fremantle Diabetes Study.

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.

Serum vitamin B12, distal symmetrical polyneuropathy and anaemia in type 2 diabetes: the Fremantle Diabetes Study Phase 2.

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.

The relationship between glycated haemoglobin and blood glucose-lowering treatment trajectories in type 2 diabetes: The Fremantle Diabetes Study Phase II.

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.

The Relationship between Pulmonary Artery Pressure and Mortality in Type 2 Diabetes: A Fremantle Diabetes Study Phase II and National Echocardiographic Database of Australia Data Linkage Study.

An elevated estimated right ventricular systolic pressure (eRVSP) identified on echocardiography is present in one-third of individuals with type 2 diabetes, but its prognostic significance is unknown. To assess the relationship between eRVSP and mortality, prospective data from 1732 participants in the Fremantle Diabetes Study Phase II were linked with the National Echocardiographic Database of Australia. Of this cohort, 416 (mean age 70.6 years, 47.4% males) had an eRVSP measured and 381 (91.4%) had previously confirmed type 2 diabetes. Receiver- operating characteristic analysis of the relationship between eRVSP and all-cause mortality was conducted. Survival analyses were performed for participants with type 2 diabetes diagnosed before first measured eRVSP (n = 349). Cox regression identified clinical and echocardiographic associates of all-cause mortality. There were 141 deaths (40.4%) during 2348 person-years (mean ± SD 6.7 ± 4.0 years) of follow-up. In unadjusted Kaplan-Meier analysis, mortality rose with higher eRVSP (log-rank test, p < 0.001). In unadjusted pairwise comparisons, eRVSP >30 to 35, >35 to 40, and >40 mmHg had significantly increased mortality compared with eRVSP ≤ 30 mmHg (p = 0.025, p = 0.001, p < 0.001, respectively). There were 50 deaths in 173 individuals (29.1%) with eRVSP ≤ 30 mmHg, and 91 in 177 (51.4%) with eRVSP > 30 mmHg (log-rank test, p < 0.001). In adjusted models including age, Aboriginal descent, Charlson Comorbidity Index ≥ 3 and left heart disease, eRVSP > 30 mmHg predicted a two-fold higher all-cause mortality versus ≤ 30 mmHg. An eRVSP > 30 mmHg predicts increased all-cause mortality in type 2 diabetes. Where available, eRVSP could inform type 2 diabetes outcome models.

The Clinical Relevance of Diabetes Distress versus Major Depression in Type 2 Diabetes: A Latent Class Analysis from the Fremantle Diabetes Study Phase II.

BACKGROUND: The nosological position and clinical relevance of the concept of diabetes distress (DD) are uncertain. The aim of this study was to use latent class analysis (LCA) to categorise classes of people with type 2 diabetes and to compare their characteristics. METHODS: Data from 662 participants in the longitudinal observational Fremantle Diabetes Study Phase II were analysed. LCA identified latent subgroups based on individual responses to the Patient Health Questionnaire-9, the Generalised Anxiety Disorder Scale, and the 5-item Problem Areas in Diabetes Scale. RESULTS: Four classes were identified: Class 1 (65.7%, no symptoms), Class 2 (14.0%, DD), Class 3 (12.6%, subsyndromal depression (SSD)), and Class 4 (7.6%, major depression (MD)). Multinomial regression analysis with Class 1 as reference showed significant associations between the DD class and Southern European and Asian ethnic background, HbA1c, and BMI. The SSD class was significantly associated with HbA1c, cerebrovascular disease, and coronary heart disease (CHD). The MD class had significant associations with age (inversely), Southern European ethnic background, HbA1c, BMI, and CHD. In conclusion, LCA identified a pure DD group comprising 14.0% of participants. The only variable uniquely associated with the DD class was Asian ethnic background. CONCLUSION: Although identification of DD may have some utility in assessing the psychological wellbeing of individuals with type 2 diabetes, it adds little to the assessment of depressive disorder and its significant clinical sequalae.

Protocol for an economic evaluation of scalable strategies to improve mental health among perinatal women: non-specialist care delivered via telemedicine vs. specialist care delivered in-person.

BACKGROUND: Perinatal depression affects an estimated 1 in 5 women in North America during the perinatal period, with annualized lifetime costs estimated at $20.6 billion CAD in Canada and over $45.9 billion USD in the US. Access to psychological treatments remains limited for most perinatal women suffering from depression and anxiety. Some barriers to effective care can be addressed through task-sharing to non-specialist providers and through telemedicine platforms. The cost-effectiveness of these strategies compared to traditional specialist and in-person models remains unknown. This protocol describes an economic evaluation of non-specialist providers and telemedicine, in comparison to specialist providers and in-person sessions within the ongoing Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) trial. METHODS: The economic evaluation will be undertaken alongside the SUMMIT trial. SUMMIT is a pragmatic, randomized, non-inferiority trial across five North American study sites (N = 1,226) of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a behavioural activation treatment for perinatal depressive and anxiety symptoms. The primary economic evaluation will be a cost-utility analysis. The outcome will be the incremental cost-effectiveness ratio, which will be expressed as the additional cost required to achieve an additional quality-adjusted life-year, as assessed by the EuroQol 5-Dimension 5-Level instrument. A secondary cost-effectiveness analysis will use participants' depressive symptom scores. A micro-costing analysis will be conducted to estimate the resources/costs required to implement and sustain the interventions; healthcare resource utilization will be captured via self-report. Data will be pooled and analysed using uniform price and utility weights to determine cost-utility across all trial sites. Secondary country-specific cost-utility and cost-effectiveness analyses will also be completed. Sensitivity analyses will be conducted, and cost-effectiveness acceptability-curves will be generated, in all instances. DISCUSSION: Results of this study are expected to inform key decisions related to dissemination and scale up of evidence-based psychological interventions in Canada, the US, and possibly worldwide. There is potential impact on real-world practice by informing decision makers of the long-term savings to the larger healthcare setting in services to support perinatal women with common mental health conditions.

Temporal trends in chronic complications of diabetes by sex in community-based people with type 2 diabetes: the Fremantle Diabetes Study.

BACKGROUND: Whether recent reductions in cardiovascular disease (CVD) events and mortality in type 2 diabetes apply equally to both sexes is largely unknown. The aim of this study was to characterize temporal changes in CVD events and related outcomes in community-based male and female Australian adults with type 2 diabetes or without known diabetes. METHODS: Participants from the longitudinal observational Fremantle Diabetes Study Phases I (FDS1; n = 1291 recruited 1993-1996) and II (FDS2; n = 1509 recruited 2008-2011) and four age-, sex- and postcode-matched individuals without diabetes (FDS1 n = 5159; FDS2 n = 6036) were followed for first myocardial infarction, stroke, heart failure hospitalization, lower extremity amputation, CVD death and all-cause mortality. Five-year incidence rates (IRs) for males versus females in FDS1 and FDS2 were calculated, and IR ratios (IRRs) derived. RESULTS: The FD1 and FDS2 participants were of mean age 64.0 and 65.4 years, respectively, and 48.7% and 51.8% were males. For type 2 diabetes, IRRs for all endpoints were 11-62% lower in FDS2 than FDS1 for both sexes. For participants without diabetes, IRRs were 8-56% lower in FDS2 versus FDS1 apart from stroke in females (non-significantly 41% higher). IRRs for males versus females across FDS phases were not significantly different for participants with type 2 diabetes or those without diabetes (P-values for male * FDS2 interaction ≥ 0.0.083 adjusted for age). For risk factors in participants with type 2 diabetes, greater improvements between FDS1 and FDS2 in smoking rates in males were offset by a greater reduction in systolic blood pressure in females. CONCLUSIONS: The incidence of chronic complications in Australians with type 2 diabetes and without diabetes has fallen similarly in both sexes over recent decades, consistent with comparably improved overall CVD risk factor management.

Pregnancy outcomes of women with cardiac disease.

OBJECTIVE: To determine and predict the maternal and neonatal outcomes of pregnancies occurring in patients with cardiac disease. METHOD: This retrospective review included 147 pregnancies identified from antenatal, delivery, and nursery records. Information concerning the nature and severity of the pre-existing cardiac disease, comorbidities, risk scores, obstetric or cardiac complications, and pregnancy outcomes were collected. The data were analyzed using SPSS Windows version 22. RESULTS: In all, 111 (73.5%) of the cohort had acquired heart disease and 4 (2.7%) of patients belonged to WHO class IV, in which pregnancy is not recommended. Additionally, 12 (8.1%) were categorized as being at significant risk of having a cardiac complication. The proportion of patients that had maternal and perinatal mortality was 6 (4.0%) and 7 (4.8%), respectively. The WHO and CARPREG scoring systems were reliably able to predict cardiac events (P < 0.01). Mothers who received preconception counseling had significantly fewer occurrences of cardiac and obstetric events than those who did not. CONCLUSION: Cardiac disease in pregnancy in women managed at our center was most often an acquired disease. The baseline risk assessment scores accurately predicted the likelihood of adverse cardiac outcomes.

Comparative mortality and its determinants in community-based people with type 1 diabetes: the Fremantle Diabetes Study Phase I.

INTRODUCTION: The aim of this study was to compare mortality in community-based Australians with type 1 diabetes (T1D), without diabetes, or with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The longitudinal observational Fremantle Diabetes Study Phase I (FDS1) T1D cohort, matched people without diabetes from the FDS1 catchment area, and matched FDS1 participants with T2D were followed up from entry (1993-1996) to death/end-2017. Mortality rates (MRs) and mortality rate ratios (MRRs) were calculated. Cox regression models identified independent determinants of death. RESULTS: Of 121 participants with T1D and 484 age/sex/postcode-matched people without diabetes (pooled mean±SD age 43.1±15.3 years, 59.2% men), 55 (45.5%, MR 25.7 (95% CI 19.4 to 33.5)/1000 person-years) and 88 (18.2%, MR 8.5 (95% CI 6.8 to 10.4)/1000 person-years), respectively, died during 12 541 person-years of follow-up (MRR 3.04 (95% CI 2.13 to 4.31), p<0.001). Among participants with T1D, diagnosis at age 18-27 years and baseline HbA1c, urinary albumin:creatinine ratio, and retinopathy were independent predictors of death (p≤0.011). Twenty-five FDS1 participants died from cardiovascular disease (MR 11.7 (95% CI 7.6 to 17.3)/1000 person-years) vs 28 residents without diabetes (MR 2.7 (95% CI 1.8 to 3.9)/1000 person-years; MRR (95% CI) 4.34 (2.43, 7.73) (p<0.001). There were 93 FDS1 participants with T1D who were age/sex matched with an FDS1 participant with T2D and 53 (57.0%) and 37 (39.8%), respectively, died (p=0.027). In pooled Cox regression analysis, T1D was not a determinant of mortality (HR 1.18 (95% CI 0.71 to 1.97), p=0.523). CONCLUSIONS: T1D substantially increases the risk of death, especially when diagnosed in late adolescence/young adulthood. Diabetes type does not influence mortality after adjustment for key confounding variables.

Group-Based Trajectory Modelling of Changes in Mobility over Six Years in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

To investigate temporal changes in mobility in community-based people with type 2 diabetes, Fremantle Diabetes Study Phase II (FDS2) data were analysed. The baseline assessment included the Timed Up and Go (TUG) test, which was repeated biennially for up to six years. Group-based trajectory modelling (GBTM) identified TUG trajectory groups in participants with ≥2 tests. Independent associates of group membership were assessed using multinomial regression. Of 1551 potential FDS2 participants, 1116 (72.0%; age 64.9 ± 11.0 years, 45.6% female) were included in the modelling. The best-fitting GBTM model identified two groups with linear, minimally changing trajectories (76.2% and 19.4% of participants; baseline TUG times 8 ± 2 and 12 ± 3 s, respectively), and a third (4.5%; baseline TUG 17 ± 5 s) with a TUG that increased over time then fell at Year 6, reflecting participant attrition. Both slower groups were older, more likely to be female, obese, and had greater diabetes-associated complications and comorbidities. Almost one-quarter of the FDS2 cohort had clinically relevant mobility impairment that persisted or worsened over six years, was multifactorial in origin, and was associated with excess late withdrawals and deaths. The TUG may have important clinical utility in assessing mobility and its consequences in adults with type 2 diabetes.

Serum bicarbonate concentration and the risk of death in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIMS: To examine whether all-cause mortality is independently associated with serum bicarbonate concentration below the laboratory reference interval in a representative, well-characterised community-based cohort of people with type 2 diabetes. METHODS: 1478 FDS2 participants with type 2 diabetes (mean age 65.8 years, 51.6% males, median diabetes duration 9.0 years) from the longitudinal, observational Fremantle Diabetes Study Phase II (FDS2) were followed from study entry to death or end-2016. Independent associates of a low baseline serum bicarbonate (< 22 mmol/L) were determined using multiple logistic regression. The role of important covariates in influencing the association between bicarbonate and mortality was assessed by a stepwise Cox regression approach. RESULTS: A low serum bicarbonate was associated with increased all-cause mortality in unadjusted analysis (hazard ratio (HR) 1.90 (95% confidence limits (CL) 1.39, 2.60 per mmol/L). Mortality remained significantly associated with low serum bicarbonate (HR 1.40 (95% CL 1.01, 1.94) per mmol/L) in a Cox regression model with adjustment for factors associated with mortality but not low serum bicarbonate, but inclusion of estimated glomerular filtration rate categories rendered the association non-significant (HR 1.16 (95% CL 0.83, 1.63) per mmol/L). CONCLUSIONS: A low serum bicarbonate is not an independent prognostic marker in people with type 2 diabetes but it may be a manifestation of the pathway between the development of impaired renal function and death.