Timing of minor and major amputation in patients with diabetes-related foot ulceration admitted to two public tertiary referral hospitals in Australia.

BACKGROUND: There is limited information regarding the number of patients with diabetes-related foot ulceration (DFU) who receive minor or major amputation, and how quickly these amputations occur. This study aimed to identify the incidence of index minor and major amputation among inpatients with DFU over 4 years, and where amputation occurred during the patient's index DFU-related admission, investigate prognostic factors. METHODS: The incidence of index minor and major amputation, and the admission sequence during which amputation occurred were identified from DFU-related admissions to two public hospitals during 2014-2018. Where minor or major amputation occurred during the patient's index DFU-related admission, prognostic factors were investigated using logistic regression. RESULTS: DFU-related hospital admissions were required by 564 patients. The incidence of minor amputation over 4 years was 34% (n = 193). The incidence of minor amputation during the patient's index DFU-related admission was 28% (n = 155), which was associated with requiring revascularisation (odds ratio [OR] 2.33, 95% CI 1.53-3.55, P < 0.001). The incidence of major amputation over 4 years was 8% (n = 45). The incidence of major amputation during the patient's index DFU-related admission was 6% (n = 31), which was associated with having more comorbidities (OR 1.58, 95% CI 1.10-2.26, P = 0.01) and receiving care for a mental health condition (OR 3.85, 95% CI 1.48-10.01, P = 0.006). CONCLUSION: Most amputations occurred during the patient's index DFU-related hospital admission. Major amputation during a patient's index admission was associated with more comorbidities and mental health conditions.

Myocardial fibrosis in Type 2 Diabetes is associated with functional and metabolomic parameters.

AIMS: To identify biomarkers of cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) using cardiovascular magnetic resonance (CMR) and to identify associations between functional status, metabolomic profile and myocardial fibrosis. METHODS: In this prospective case control study, patients (n = 49) with T2DM without significant coronary artery disease, and matched controls (n = 18) underwent CMR, cardiopulmonary exercise testing, and plasma metabolomic analyses. RESULTS: Patients with T2DM (n = 49, median [interquartile range] age 61 [56-63] years, 61% male, diabetes duration 11 [7-20] years), historical HbA1c 7.6% (60 mmol/mol) (6.9-8.6) and matched controls (n = 18) were examined. Study patients had increased myocardial extracellular volume (ECV) (26.9 [23.8-30.0] vs 23.4 [22.4-25.5) %, p < 0.001). Increased ECV was associated with male sex (p = 0.04), time with T2DM (p = 0.02), reduced peak VO2 (R2 = 0.48, p = 0.01), increased circulating choline (p = 0.002) and cysteamine (p = 0.002) both of which were also associated with reduced peak VO2 (p < 0.025 and 0.014 respectively). CONCLUSIONS: Patients with well-controlled T2DM without significant coronary disease exhibit focal and diffuse myocardial fibrosis and diffuse myocardial fibrosis is associated with reduced exercise tolerance and metabolites. Plasma metabolites may provide mechanistic insights into diffuse myocardial fibrosis, and cardiopulmonary fitness.

Young adult onset type 2 diabetes versus type 1 diabetes: Progression to and survival on renal replacement therapy.

BACKGROUND: Young-onset type 2 diabetes is an aggressive disease characterized by development of diabetic complications, including nephropathy, early in the disease course. However, within the cohort of young-onset type 1 and type 2 diabetes there are limited comparative data regarding progression to ESKD requiring renal replacement therapy or renal-related death (RRT/RRD). METHODS: Probabilistic linkage of data from the RPAH Diabetes Centre, National Death Index and Australian and New Zealand Dialysis and Transplant Registry was undertaken. Cumulative Incidence Competing Risk and Cox Proportional Hazards Modelling approaches were utilized to examine progression to ESKD in young-onset type 1 and type 2 diabetes (age of diagnosis 15-35 years). FINDINGS: Unadjusted incidence rates (95% CI) of RRT/RRD in young-onset type 1 and type 2 diabetes were 3.1 (2.3-4.0) and 4.6 (3.7-5.7) per 1000 person years respectively. After adjustment for gender, ethnicity and duration of diabetes, the HR (95% CI) of RRT/RRD in young-onset type 2 diabetes was 2.0 (1.4-2.9). The HR remained higher after further adjustment for first available cholesterol, HbA1c and systolic blood pressure but not BMI. For those who progressed to RRT, prognosis was similar irrespective of diabetes type; cumulative incidence of mortality was 40% in both young-onset type 1 and type 2 diabetes after 6 years of dialysis. INTERPRETATION: Progression to RRT/RRD is greater in young-onset type 2 diabetes than in young-onset type 1 diabetes. The increased progression is associated with increased BMI. However, once ESKD is reached, individuals with young-onset type 1 and type 2 diabetes do equally poorly.

Secular Trends in Information Communications Technology: Access, Use, and Attitudes of Young and Older Patients With Diabetes.

BACKGROUND: Advances in information communications technology (ICT) provide opportunities for enhanced diabetes care. Knowledge of the more acceptable communication modalities in patients of different ages will help to inform the direction of future innovations. METHODS: An anonymous ICT survey (examining access and use of mobile phones, computers, tablets, and the Internet and attitudes toward e-mail, Web-based consultations, and online peer-support) was conducted at the Royal Prince Alfred Hospital Diabetes Centre in Sydney, Australia. Survey deployment occurred during 4-month periods in 2012 and 2017. Respondents were stratified by current age (<40 or ≥40 years). RESULTS: A total of 614 unselected patients (20% with type 1 diabetes, 55% with type 2 diabetes, 13% with gestational diabetes mellitus, and 12% with an undisclosed type of diabetes) completed the survey. Access to ICT increased from 89% in 2012 to 97% in 2017. The most commonly owned device was a mobile phone (87% ownership in 2017). Increase in mobile Internet usage in the <40 years of age subgroup was significant (P = 0.04). Significant increases in Internet access and smartphone feature use were observed in patients aged ≥40 years (P ≤0.001 for all). Overall use of short message service (SMS, or text messaging) was high (90 and 80% for ages <40 and ≥40 years, respectively). Use of digital applications was low, even among the young (45% in 2017). Comfort with online consultations (40%) and support groups (32%) was also low. CONCLUSION: Access to and acceptance and use of ICT is high, especially in those <40 years of age; however, the greatest increases were seen in those aged ≥40 years. High penetrance of mobile phones and text messaging in all age-groups would suggest that innovations involving an SMS platform have the greatest potential to enhance diabetes care.

Maternal vs paternal diabetes: The parental history is different in younger onset versus older onset type 2 diabetes.

BACKGROUND: A number of previous studies exploring family history of type 2 diabetes have reported a predominance of maternal diabetes. These studies have not explicitly compared parental history of diabetes across the spectrum of disease onset from youth to later adulthood. METHODS: Family history data from 11,467 patients with type 2 diabetes were extracted from the RPA Diabetes Centre database. Parental histories of diabetes were compared across a range of age of diagnosis strata (15-<30, 30-<40, 40-<50, 50-<60 and 60-<70 years). For the young-onset group (diagnosed between 15 and 30 years of age), associations between parental history of diabetes and the presence of cardio-metabolic risk factors and diabetic complications were also explored. RESULTS: For the total cohort and within each age of diagnosis strata, more individuals reported maternal history than paternal history of diabetes. The young-onset group demonstrated the highest prevalence of any parental history of diabetes (60.7%), the highest combined maternal and paternal history (15.8%) and the smallest differential between maternal (25.1%) and paternal (19.7%) history of diabetes. Within the young-onset group, no significant association between parental history and cardio-metabolic risk factors or diabetic complications were identified after a median of 15.0 years of diabetes exposure. CONCLUSION: Overall, our results demonstrate a consistent maternal excess of diabetes which could be consistent with an underlying epigenetic effect. However, the differential between maternal and paternal history is significantly lower in the young-onset group. Earlier emergence of type 2 diabetes may therefore reflect a different interaction and impact of genetic and environmental factors.

Data collection on retinopathy as a public health tool: The Hubble telescope equivalent of looking back in time.

OBJECTIVE: To test whether the rate of diabetic retinopathy development in a population calculated from the prevalence of retinopathy and duration of diabetes can be used to assess their prior glycemic control. RESEARCH DESIGN AND METHODS: 9281 patients with type 2 diabetes (T2DM) were grouped by duration of diabetes and plotted against the % of retinopathy in each band. The slope was used to calculate retinopathy development/year (RD/y). We correlated the RD/y with updated HbA1c within groups of different ethnicity, age of diabetes onset, year of the eye examination, socio-economic status and fluency in English. RESULTS: Differences in ethnicity, age of diabetes onset and year of the eye examination affect RD/y to a degree predictable from their respective updated HbA1c. No such relationship with updated HbA1c was evident when a factor has no apparent effect on RD/y. CONCLUSIONS: This relationship between prevalence of retinopathy and duration of diabetes can be used to assess future retinopathy burden. Perhaps more intriguing, the camera can be reversed to allow an estimate of prior glycemic control of a population from its retinopathy prevalence. Health care organizations can use this method to project future needs and to assess adequacy of prior glycemic control.

An Inverse Relationship Between Age of Type 2 Diabetes Onset and Complication Risk and Mortality: The Impact of Youth-Onset Type 2 Diabetes.

OBJECTIVE: This study compared the prevalence of complications in 354 patients with T2DM diagnosed between 15 and 30 years of age (T2DM15-30) with that in a duration-matched cohort of 1,062 patients diagnosed between 40 and 50 years (T2DM40-50). It also examined standardized mortality ratios (SMRs) according to diabetes age of onset in 15,238 patients covering a wider age-of-onset range. RESEARCH DESIGN AND METHODS: Complication status was assessed according to a standard protocol and extracted from our electronic database. Survival status was ascertained by data linkage with the Australian National Death Index. SMRs were calculated in comparison with the background Australian population and analyzed according to age of onset. RESULTS: After matching for duration, despite their younger age, T2DM15-30 had more severe albuminuria (P = 0.004) and neuropathy scores (P = 0.003). T2DM15-30 were as commonly affected by metabolic syndrome factors as T2DM40-50 but less frequently treated for hypertension and dyslipidemia (P < 0.0001). An inverse relationship between age of diabetes onset and SMR was seen, which was the highest for T2DM15-30 (3.4 [95% CI 2.7-4.2]). SMR plots adjusting for duration show that for those with T2DM15-30, SMR is the highest at any chronological age, with a peak SMR of more than 6 in early midlife. In contrast, mortality for older-onset groups approximates that of the background population. CONCLUSIONS: The negative effect of diabetes on morbidity and mortality is greatest for those diagnosed at a young age compared with T2DM of usual onset. These results highlight the growing imperative to direct attention toward young-onset T2DM and for effective interventions to be applied before middle age.

Ethnic specific differences in survival of patients with type 2 diabetes: analysis of data collected from an Australian multi-ethnic cohort over a 25 year period.

AIMS: To examine the survival of patients with type 2 diabetes from 7 ethnic groups, living in the shared environment of an Australian city. METHODS: Hazard ratio of death (HR) after diagnosis of diabetes was compared between Anglo-Celtic (n=5433), Indigenous Australian (n=439), Pacific Islander (n=354), Mediterranean (n=3138), Arabic (n=768), Indian (n=702) and Chinese (n=1632) patients who live in metropolitan Sydney. Mortality was ascertained by data-linkage with the Australian National Death Index. The modulating effects of glycaemic control, diabetes/vascular complications and risk factors, year of diabetes diagnosis and duration of diabetes on ethnic differences were analysed by Cox regression. Socio-economic status and competence in English were also examined. RESULTS: There were significant differences in survival between the ethnic groups; the Indigenous Australians had the highest HR for death (2.3, 95% CI 1.7-3.0) and the Chinese the lowest (0.4, 95% CI 0.4-0.5). The survival of the Anglo-Celtics (HR 1) was surprisingly poorer than for Indian (0.6, 95% CI 0.5-0.8), Arab (0.7, 95% CI 0.6-0.8) and Mediterranean groups (0.8, 95% CI 0.7-0.9). Prevalence of smoking and albuminuria were strongly associated with HR. The better survival of Chinese and Arab and the worse survival of Indigenous Australians remained after adjustment of risk factors. Need for an interpreter was a favourable risk factor for survival. CONCLUSIONS: Ethnicity is a significant determinant of survival in type 2 diabetes and this is substantially but not completely mediated by smoking and vascular risk factors. The favourable impact associated with less competence in English may represent a Healthy-migrant effect.

Long-term complications and mortality in young-onset diabetes: type 2 diabetes is more hazardous and lethal than type 1 diabetes.

OBJECTIVE: To evaluate long-term clinical outcomes and survival in young-onset type 2 diabetes (T2DM) compared with type 1 diabetes (T1DM) with a similar age of onset. RESEARCH DESIGN AND METHODS: Records from the Royal Prince Alfred Hospital Diabetes Clinical Database, established in 1986, were matched with the Australian National Death Index to establish mortality outcomes for all subjects until June 2011. Clinical and mortality outcomes in 354 patients with T2DM, age of onset between 15 and 30 years (T2DM15-30), were compared with T1DM in several ways but primarily with 470 patients with T1DM with a similar age of onset (T1DM15-30) to minimize the confounding effect of age on outcome. RESULTS: For a median observation period of 21.4 (interquartile range 14-30.7) and 23.4 (15.7-32.4) years for the T2DM and T1DM cohorts, respectively, 71 of 824 patients (8.6%) died. A significant mortality excess was noted in T2DM15-30 (11 vs. 6.8%, P = 0.03), with an increased hazard for death (hazard ratio 2.0 [95% CI 1.2-3.2], P = 0.003). Death for T2DM15-30 occurred after a significantly shorter disease duration (26.9 [18.1-36.0] vs. 36.5 [24.4-45.4] years, P = 0.01) and at a relatively young age. There were more cardiovascular deaths in T2DM15-30 (50 vs. 30%, P < 0.05). Despite equivalent glycemic control and shorter disease duration, the prevalence of albuminuria and less favorable cardiovascular risk factors were greater in the T2DM15-30 cohort, even soon after diabetes onset. Neuropathy scores and macrovascular complications were also increased in T2DM15-30 (P < 0.0001). CONCLUSIONS: Young-onset T2DM is the more lethal phenotype of diabetes and is associated with a greater mortality, more diabetes complications, and unfavorable cardiovascular disease risk factors when compared with T1DM.

Long-term efficacy of metformin therapy in nonobese individuals with type 2 diabetes.

OBJECTIVE: The U.K. Prospective Diabetes Study (UKPDS) has demonstrated that metformin is as effective as sulfonylureas in obese subjects and is associated with less weight gain, fewer hypoglycemic episodes, and better cardiovascular outcomes. It is hence the pharmacological therapy of choice in this subgroup. However, a gap in our present knowledge is the long-term response to metformin in nonobese individuals. In this study, we compared metformin therapy in normal, overweight, and obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A database of patients treated at a referral center in Sydney, Australia, were analyzed. Patients with type 2 diabetes and complete HbA(1c) (A1C) data and treated with metformin or sulfonylurea monotherapy for at least three visits before receiving dual oral therapy were included (n = 644). Analysis by BMI and the type of oral agent was performed. Individuals were categorized as normal, overweight, or obese (BMI <25, 25-29.9, and >/=30 kg/m(2), respectively). RESULTS: There were no differences between the initial, follow-up, and last A1C between the three metformin-treated groups. The duration of successful glycemic control with metformin monotherapy in the normal and overweight individuals and their incidences of diabetes-related complications for the entire duration of follow-up were not inferior to those of the obese individuals. The nonobese patients performed better regardless of the type of oral hypoglycemic agent used. CONCLUSIONS: We conclude that metformin is at least as efficacious in normal and overweight individuals as it is in those who are obese. Our study provides evidence-based data to support metformin use in nonobese individuals with type 2 diabetes.