Emma J. Hamilton

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes

Aims  To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes.

Incidence and predictors of hospitalization for bacterial infection in community-based patients with type 2 diabetes: the fremantle diabetes study.

Background The few studies that have examined the relationship between diabetes and bacterial infections have utilized administrative databases and/or have had limited/incomplete data including recognized infection risk factors. The aim of this study was to determine the incidence and associates of bacterial infection severe enough to require hospitalization in well-characterized community-based patients with type 2 diabetes. Methods and Findings We studied a cohort of 1,294 patients (mean±SD age 64.1±11.3 years) from the longitudinal observational Fremantle Diabetes Study Phase I (FDS1) and 5,156 age-, gender- and zip-code-matched non-diabetic controls. The main outcome measure was incident hospitalization for bacterial infection as principal diagnosis between 1993 and 2010. We also examined differences in statin use in 52 FDS1 pairs hospitalized with pneumonia (cases) or a contemporaneous non-infection-related cause (controls). During 12.0±5.4 years of follow-up, 251 (19.4%) patients were hospitalized on 368 occasions for infection (23.7/1,000 patient-years). This was more than double the rate in matched controls (incident rate ratio (IRR) (95% CI), 2.13 (1.88–2.42), P<0.001). IRRs for pneumonia, cellulitis, and septicemia/bacteremia were 1.86 (1.55–2.21), 2.45 (1.92–3.12), and 2.08 (1.41–3.04), respectively (P<0.001). Among the diabetic patients, older age, male sex, prior recent infection-related hospitalization, obesity, albuminuria, retinopathy and Aboriginal ethnicity were baseline variables independently associated with risk of first hospitalization with any infection (P≤0.005). After adjustment for these variables, baseline statin treatment was not significant (hazard ratio (95% CI), 0.70 (0.39–1.25), P = 0.22). Statin use at hospitalization for pneumonia among the case-control pairs was similar (23.1% vs. 13.5%, P = 0.27). Conclusions The risk of severe infection is increased among type 2 diabetic patients and is not reduced by statin therapy. There are a number of other easily-accessible sociodemographic and clinical variables that could be used to optimize infection-related education, prevention and management in type 2 diabetes.

Effect of continuous positive airway pressure therapy on sexual function and serum testosterone in males with type 2 diabetes and obstructive sleep apnoea

There have been no studies of the effect of continuous positive airway pressure (CPAP) therapy on erectile dysfunction (ED) and serum testosterone in men with type 2 diabetes and obstructive sleep apnoea (OSA), a patient group at increased risk of ED and hypogonadism. The aim of this study was to determine whether CPAP improves sexual and gonadal function in males with type 2 diabetes and a pre‐CPAP apnoea–hypopnoea index >15/h.

Prevalence and prognosis of a low serum testosterone in men with type 2 diabetes: the Fremantle Diabetes Study Phase II.

Because published studies have usually involved imprecise assays and selected patients with limited additional data and follow‐up, the consequences of a low serum testosterone in diabetes are unclear. This study assessed the prevalence, associates and prognosis of a low testosterone in community‐dwelling men with type 2 diabetes.

Influence of Premature Mortality on the Link Between Type 2 Diabetes and Hip Fracture: The Fremantle Diabetes Study

Context: Studies of hip fracture complicating diabetes have not considered the effect of premature mortality. Objective: The aim of our study was to determine influence of the competing risk of death on the association between type 2 diabetes and hip fracture. Design: The study was designed as a longitudinal observational study. Setting: The study setting was an urban community. Patients: Participants included 1291 patients with type 2 diabetes (mean age 64.0 years) and 5159 matched residents without diabetes. Main Outcome Measures: Primary outcome measures were incident hip fracture hospitalizations and deaths. Hip fracture risk was assessed using proportional hazards and competing risk regression modeling. Results: During a mean of 14.1 years of follow-up, the incidence rate ratio for first hip fracture hospitalization in participants with vs without diabetes was 1.33 [95% confidence interval (CI), 1.05 to 1.68; P = 0.013]. Type 2 diabetes was associated with a cause-specific hazard ratio (csHR) for hip fracture of 1.50 (95% CI, 1.19 to 1.89; P < 0.001) and a subdistribution hazard ratio (sdHR) of 1.21 (95% CI, 0.96 to 1.52; P = 0.11) after adjustment for age, sex, and comorbidities. In patients with diabetes, significant csHRs for incident hip fracture were male sex (protective), body mass index (protective), insulin use, and renal impairment. These variables, with increasing age, also had significant sdHRs. Conclusions: The diabetes-associated risk of hip fracture is attenuated after allowing for the competing risk of death. Risk factors for hip fracture in diabetes were those in reported in general population studies plus insulin use.

Prevalence, risk factors and sequelae of Staphylococcus aureus carriage in diabetes: the Fremantle Diabetes Study Phase II

AIMS To determine the prevalence and associates of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) carriage in community-based diabetes, and their relationship to hospitalization with S. aureus infection. METHODS A cross-sectional subset of 660 Fremantle Diabetes Study Phase II patients (mean±SD age 65.1±11.5years, 53.1% males) had nasal/axillary swabs as part of biennial review. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured in 358 patients. Those with positive swabs were invited back for a repeat swab. Hospitalizations with S. aureus infections were ascertained from validated data linkage. Multiple logistic regression was used to identify associates of carriage, and Cox proportional hazards modelling was used to determine predictors of subsequent hospitalization. RESULTS 258 patients (39.1%) were positive for S. aureus and eight (3.1%) carried MRSA. S. aureus carriage was independently associated with being married/in a de facto relationship and inversely with older age and being born overseas (P≤0.043). Repeat swabs in 137 patients (53.1% of those with an initially positive swab) grew S. aureus in 113 (82.5%). Five of eight MRSA-positive patients were re-swabbed, and four were MRSA-positive. Independent predictors of hospitalization with staphylococcal infection after the initial swab were S. aureus carriage (hazard ratio (95% CI) 5.42 (1.49-19.79)), prior hospitalization with S. aureus (4.84 (1.19-19.63)) and Aboriginality (7.20 (1.91-27.17) (P≤0.027). Serum 25(OH)D was not associated with S. aureus carriage or subsequent hospitalization. CONCLUSIONS S. aureus and MRSA carriage in our patients was consistent with previous general population studies. There were no diabetes-specific risk factors. Persistent colonization may underlie the increased risk of hospitalization with S. aureus.

Circulating osteocalcin is unrelated to glucose homoeostasis in adults with type 1 diabetes

AIMS To assess the relationship between total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC) and a range of markers of glucose homeostasis in type 1 diabetes. METHODS One hundred and eight community-based Caucasian adults (53 males, 55 females) without a history of osteoporosis and with a mean±SD age 39.1±15.1years and median [inter-quartile range] type 1 diabetes duration of 14.3 [6.6-20.4] years participated in a cross-sectional study of bone health. Fasting serum glucose and HbA1c, and serum tOC, ucOC, total adiponectin and procollagen type 1N-terminal propeptide (P1NP) were measured using validated assays, and daily insulin dose and estimated glucose disposal rate (eGDR) were calculated. Multiple linear regression was used to determine independent associates of markers of glucose homoeostasis (HbA1c, fasting serum glucose, daily insulin dose, eGDR and serum total adiponectin). RESULTS In sex-adjusted multivariable regression analyses, ln(serum P1NP) was independently and inversely associated with ln(HbA1c) and ln(serum adiponectin) (P≤0.013). Other associations included those between ln(serum vitamin D) and ln(HbA1c) (inversely), daily insulin dose (inversely) and eGDR (positively) (P≤0.035), as well as an inverse relationship between overweight by waist circumference and ln(serum adiponectin) (P<0.001). Ln(serum tOC) and ln(serum ucOC) were not independently associated with any glucose homoeostasis marker. CONCLUSIONS These data from well characterized community-based adults with type 1 diabetes do not suggest that there is a role for osteocalcin in the potentially complex interplay between the skeleton and energy homoeostasis in type 1 diabetes.

Risk and associates of incident hip fracture in type 1 diabetes: The Fremantle Diabetes Study

AIMS To determine the relative risk of incident hip fracture in patients with type 1 diabetes and matched controls, to examine baseline associates of incident hip fracture in the patients with type 1 diabetes, and to compare hip fracture rates in age- and sex-matched patients with type 1 versus type 2 diabetes. METHODS Longitudinal observational study of 121 adults with type 1 diabetes (mean ± SD age 43.0 ± 15.5 years, 59.5% male) and 484 age- and sex-matched adults without diabetes. Age and sex matching was possible for 93 pairs of type 1 and type 2 participants. The main outcome measure was incident hip fracture hospitalisation. RESULTS During a mean ± SD 14.5 ± 5.8 years of follow-up, the incidence rate ratio for first hip fracture hospitalisation in type 1 participants versus residents without diabetes was 6.39 (95% CI 1.94-22.35, P < .001). In Cox proportional hazards modelling, type 1 diabetes was associated with cause-specific hazard ratio (csHR) for hip fracture of 7.11 (2.45-20.64, P < .001) after age and sex adjustment. Hip fracture in type 1 participants was associated with older age, osteoporosis treatment, depressive symptoms, ethnicity, systolic blood pressure, serum HDL-cholesterol, albuminuria and serum adiponectin (P ≤ 0.047); associations remained for the first three of these variables after adjustment for age and body mass index (P ≤ 0.025). The csHR for incident hip fracture was 5.32 (1.12-25.37, P = .036) for type 1 versus 2 diabetes. CONCLUSIONS Hip fracture risk is markedly elevated in type 1 diabetes compared with age and sex-matched individuals without diabetes and with type 2 diabetes from the same population.

A ten-year prospective study of bone mineral density and bone turnover in males and females with type 1 diabetes.

Context In a previous community-based, cross-sectional study, males with type 1 diabetes (T1D) had lower bone mineral density (BMD) than did matched people without diabetes but females with T1D had normal BMD. Objective To determine whether BMD in the males continued to decline, the neutral effect of T1D on BMD in females persisted, and whether temporal BMD changes reflected changes in bone turnover markers. Design Longitudinal observational study. Setting Urban community. Patients Forty-eight of the original 102 original cross-sectional study participants (20 males, 28 females) of mean age 42.0 years and median diabetes duration 14.6 years at baseline who were restudied a mean of 10.3 years later. Main Outcome Measures BMD at total hip, femoral neck, lumbar spine (L1 to L4), and distal forearm. Biochemical bone turnover markers. Results After adjustment for age, body mass index (BMI), and renal function, there was no temporal change in BMD at the hip or forearm in the males (P ≥ 0.12), but lumbar spine BMD increased (P = 0.009). Females exhibited no statistically significant change in BMD in similar multivariable models that also included postmenopausal status, except a mild increase at the forearm (P = 0.046). Age- and sex-related changes in bone turnover markers paralleled those in general population studies. Conclusions There is a reduction in BMD in males with T1D that occurs early in the course of the disease but then stabilizes. BMD in females with T1D remains similar to that expected for age, BMI, and postmenopausal status.