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Summary: This study evaluated mediators of fracture risk in postmenopausal women with type 1 (T1D) and type 2 diabetes (T2D), over a 15-year follow-up period. This study provides evidence that the increased fracture risk in women with T1D or T2D is partially explained by falls. Furthermore, a shorter reproductive lifespan in women with T1D contributes modestly to fracture risk in this cohort. Purpose(s): Skeletal fragility is associated with diabetes mellitus, while limited estrogen exposure during the reproductive years also predisposes to lower bone mass and higher fracture risk. We aimed to determine osteoporosis diagnosis, fall and fracture rates in women with type 1 (T1D) and type 2 (T2D) diabetes mellitus, and explore mediators of the diabetes-fracture relationship. Method(s): Prospective observational data drawn from the Australian Longitudinal Study in Women's Health (ALSWH) from 1996 to 2010. Women were randomly selected from the national health insurance database. Standardized data collection occurred at six survey time points, with main outcome measures being self-reported osteoporosis, incident fracture, falls, and reproductive lifespan. Mediation analyses were performed to elucidate relevant intermediaries in the diabetes-fracture relationship. Result(s): Exactly 11,313 women were included at baseline (T1D, n = 107; T2D, n = 333; controls, n = 10,873). A total of 885 new cases of osteoporosis and 1099 incident fractures were reported over 15 years. Women with T1D or T2D reported more falls and fall-related injuries; additionally, women with T1D had a shorter reproductive lifespan. While fracture risk was increased in women with diabetes (T1D: OR 2.28, 95% CI 1.53-3.40; T2D: OR 2.40, 95% CI 1.90-3.03), compared with controls, adjustment for falls attenuated the risk of fracture by 10% and 6% in T1D and T2D, respectively. In women with T1D, reproductive lifespan modestly attenuated fracture risk by 4%. Conclusion(s): Women with T1D and T2D have an increas

The rising global prevalence of obesity and diabetes, especially in youth, confers substantial metabolic consequences and increased mortality in affected individuals. While obesity is strongly tied to the development of insulin resistance and type 2 diabetes, emerging evidence shows that obesity rates are also increasing exponentially in those with type 1 diabetes, contributing to insulin resistance and cardiometabolic sequelae. In addition, both obesity and diabetes can exert adverse effects on female reproductive health independently, with the presence of both conditions likely to exacerbate reproductive dysfunction in this cohort. If the current trends in obesity and diabetes incidence persist, it is likely that more women will be at risk of obesity- and diabetes-related reproductive disorders. This review aims to describe the epidemiology and mechanisms of obesity in women with diabetes, and summarize current literature regarding reproductive disorders in diabetes and weight management strategies in this cohort.Copyright © 2021. Thieme. All rights reserved.

Background: Type 1 diabetes (T1D) is associated with reproductive dysfunction, particularly in the setting of poor metabolic control. Improvements in contemporary management ameliorate these problems, albeit at the cost of increased exogenous insulin and rising obesity, with emerging reproductive implications. Objective(s): To evaluate changes in body mass index (BMI) and the relationship between obesity, menstrual irregularity and polycystic ovary syndrome (PCOS) in young women with T1D, compared with controls. Method(s): Longitudinal observational study using data from the Australian Longitudinal Study in Women's Health of the cohort born in 1989-95, from 2013 to 2015. Three questionnaires administered at baseline and yearly intervals were used to evaluate self-reported menstrual irregularity, PCOS and BMI. Result(s): Overall, 15 926 women were included at baseline (T1D, n = 115; controls, n = 15 811). 61 women with T1D and 8332 controls remained at Year 2. Median BMI was higher in women with type 1 diabetes (25.5 vs 22.9 kg/m2, P <.001), where over half were overweight or obese (54.4% vs 32.9%, P <.001). Median BMI increased by 1.11 and 0.45 kg/m2, in the T1D and control groups, respectively. T1D was independently associated with an increased risk of menstrual irregularity (RR 1.22, 95% CI 1.02-1.46) and PCOS (RR 2.41, 95% CI 1.70-3.42). Obesity conferred a 4-fold increased risk of PCOS, compared to those with normal BMI (RR 3.93, 95% CI 3.51-4.42). Conclusion(s): Obesity is prevalent amongst women with T1D and may be a key contributor to the higher risk of menstrual irregularity and PCOS in this cohort, representing an important opportunity for prevention and intervention.Copyright © 2020 John Wiley & Sons Ltd

Reproductive dysfunction is a common but little studied complication of diabetes. The spectrum of reproductive health problems in diabetes is broad, and encompasses delayed puberty and menarche, menstrual cycle abnormalities, subfertility, adverse pregnancy outcomes, and potentially early menopause. Depending on the age at diagnosis of diabetes, reproductive problems can manifest early on in puberty, emerge later when fertility is desired, or occur during the climacteric period. Historically, women with type 1 diabetes have frequently had amenorrhoea and infertility, due to central hypogonadism. With the intensification of insulin therapy and improved metabolic control, these problems have declined, but do persist. Additional reproductive implications of contemporary diabetes management are now emerging, including polycystic ovary syndrome and hyperandrogenism, which are underpinned by insulin action on the ovary. The sharp rise in type 2 diabetes incidence in youth suggests that more women of reproductive age will encounter diabetes-related reproductive problems in their lifetimes. With an ever increasing number of young women living with diabetes, clinicians need to be aware of and equipped for the challenges of navigating reproductive health concerns across the lifespan.Copyright © 2020 Elsevier Ltd

Objectives: The detrimental effects of coeliac disease (CD) on bone health are well established. Individuals with CD have an increased risk of osteoporosis and fractures, but few studies have evaluated bone microarchitecture in CD. Our aim was to evaluate trabecular bone score (TBS) derived from DXA images, as an indirect assessment of bone microarchitecture in individuals with CD compared with controls. Method(s): TBS was obtained from 29 female participants who were diagnosed with CD at age <=55 years, 5 years after diagnosis(1), and from29 female controls without CD. There was no history of prior fracture in either group. Multiple linear regression was performed to evaluate associations between age, BMI, CD and menopausal status, and TBS. Result(s):Women in the CD group were five years younger (47.1+/-10.0 vs. 52.2+/-7.4 years, p=0.03). There were no significant differences in BMI (25.7+/-3.2 vs. 25.2+/-4.9 kg/m2, p=0.64), lumbar spine BMD (1.16+/-0.21 vs. 1.15+/-0.18 g/cm2, p=0.83), femoral neck BMD (0.96+/-0.12 vs. 0.92 +/-0.10 g/cm2, p=0.21) or menopausal status (54.8% vs. 75.9% postmenopausal, p=0.11) between groups. Individuals with CD had significantly lower TBS compared with controls (1.36+/-0.11 vs. 1.41+/-0.06, p=0.03), despite an 89.7% mucosal remission rate on duodenal biopsy, 5 years after CD diagnosis. 27.5% of the CD group demonstrated seropositivity to either tissue transglutaminase or deamidated gliadin peptide antibodies. Using a cutoff of 1.35, 45.2% of the CD group had TBS in the degraded range, compared with 13.8% of controls (p=0.01). TBS was negatively associated with both CD and postmenopausal status, but positively associated with lumbar spine BMD and BMI, suggesting neither BMD, nor menopausal status were responsible for the lower TBS in CD. Conclusion(s): We show, for the first time, women with CD had significantly lower TBS compared with older controls matched by BMI and BMD. Degraded TBS secondary to CD was present in half of CD patien

Background: Type 1 diabetes mellitus (T1DM) is associated with skeletal fragility. While previous meta-analyses have demonstrated an increased risk of fracture in individuals with T1DM, little is known about fracture risk in T1DM, in the absence of age-related confounders. Aim(s): To determine the risk of fracture in young and middle-aged adults with T1DM aged 18-50 years old. Design(s): Systematic review and meta-analysis. Data sources: Ovid MEDLINE, PubMed, EMBASE, EBM reviews and relevant conference abstracts. Study inclusion criteria: Studies of adults aged between 18-50 years with type 1 diabetes mellitus, with reported fracture outcomes. Primary outcomes: Incident or prevalent fracture. Result(s): Six studies were included in the meta-analysis. A total of 1724 fractures occurred in 35 925 patients with T1DM and 48 253 fractures occurred in 2 455 016 controls. RR for all fractures was 1.88 (95% CI 1.52-2.32, P <.001). Fifty-six hip fractures occurred among 34 707 patients with T1DM and 594 hip fractures occurred in 2 295 177 controls. The RR of hip fractures was 4.40 (95% CI 2.58-7.50, P <.001). Females and males with T1DM had a RR of 5.79 (95% CI 3.55-9.44, P <.001) and 3.67 (95% CI 2.10-6.41, P <.001), respectively. Conclusion(s): In the absence of age-related comorbidities, fracture risk remains significantly elevated in young and middle-aged adults with T1DM. Younger age does not mitigate against hip fracture risk in T1DM, and health professionals need to be aware of this risk. Further studies are needed to evaluate the mechanisms of fracture in T1DM.Copyright © 2018 John Wiley & Sons Ltd

The association between type 1 diabetes mellitus (T1DM) and bone health has garnered interest over the years. Fracture risk is known to be increased in individuals with T1DM, although bone health assessment is not often performed in the clinical setting. We describe the case of a 21-year-old male with longstanding T1DM with multilevel vertebral fractures on imaging, after presenting with acute back pain without apparent trauma. Dual-energy X-ray absorptiometry (DXA) revealed significantly reduced bone mineral density at the lumbar spine and femoral neck. Extensive investigations for other secondary or genetic causes of osteoporosis were unremarkable, apart from moderate vitamin D deficiency. High-resolution peripheral quantitative computed tomography and bone biospy revealed significant alterations of trabecular bone microarchitecture. It later transpired that the patient had sustained vertebral fractures secondary to unrecognised nocturnal hypoglycaemic seizures. Intravenous zoledronic acid was administered for secondary fracture prevention. Despite anti-resorptive therapy, the patient sustained a new vertebral fracture after experiencing another hypoglycaemic seizure in his sleep. Bone health in T1DM is complex and not well understood. There are significant challenges in the assessment and management of osteoporosis in T1DM, particularly in young adults, where fracture prediction tools have not been validated. Clinicians should be aware of hypoglycaemia as a significant risk factor for fracture in patients with T1DM.Copyright © 2018 The authors.

Background: Type 1 diabetes mellitus (T1DM) and coeliac disease (CD) have been independently associated with reduced bone mineral density (BMD) and increased fracture risk in adults1,2. Whilst poorer glycaemic control and increased microvascular complications3,4 have been described in patients with concomitant CD and T1DM (T1+CD), the literature examining bone health and its determinants in this cohort is limited. Objective(s): To evaluate associations of T1+CD with glycaemic control, microvascular disease and fractures, compared with T1DM alone. Method(s): We conducted a retrospective cross-sectional study of young adults with T1DM, who attended outpatient diabetes clinics at a tertiary referral centre between August 2016 to February 2017. Clinical information, radiological and biochemistry results were extracted from medical records. Patients with comorbid chronic kidney disease, glucocorticoid use, malignancy, hypogonadism and untreated hyperthyroidism were excluded. Result(s): 346 patients with T1DM only (median age 22 years) and 49 patients with T1+CD (median age 24 years) were included. Median age, gender distribution, BMI, glycated haemoglobin, total daily insulin dose, presence of microvascular complications and serum vitamin D levels were similar between groups. Subjects with T1+CD had a longer median duration of diabetes (14.0 vs 11.0 years; P = 0.01) and median duration of CD was 8 years. The adjusted risk of hypoglycaemia (>2 per week) was significantly greater for T1+CD (55.1% vs 27.7%, OR 3.28, P = .001, 95%CI 1.61-6.69). Vitamin D sufficiency was associated with a reduced risk of hypoglycaemia (OR 0.48, 95%CI 0.29-0.80; P = .005), but not fractures. Despite patients with T1+CD having a higher adjusted risk of fracture compared with T1DM alone(12.2% vs 3.5%; P < .05, OR 3.50, 95%CI 1.01-12.12), BMD was measured in only 6.1%. Conclusion(s): Young adults with T1+CD have significantly more hypoglycaemia and fractures. Recurrent hypoglycaemia may contribut

Background: Type 1 diabetes mellitus (T1D) is an emerging but underrecognised risk factor for osteoporosis. Patients with T1D have a 7-fold risk of fracture compared to controls1; importantly, this increased risk is present throughout the lifespan2. Multiple mechanisms, such as hypoinsulinaemia, osteoblast dysfunction and inflammation have been linked to impaired bone formation and defects in trabecular bone architecture 3,4,5. Case Report: We present a 21-year-old male with a 12-year history of T1D, who sustained extensive vertebral fractures in the setting of nocturnal hypoglycaemic seizures. Severe osteoporosis was diagnosed on Dualenergy X-ray Absorptiometry (DXA). Moderate vitamin D deficiency was identified in the absence of other comorbidities potentially contributing to bone fragility. Disturbance of trabecular architecture, including reduced numbers, thinning and reduced connectivity, consistent with diabetes-related bone pathology, was appreciated on imaging with highresolution peripheral quantitative computed tomography (HRpQCT), as well as on tetracycline-labelled bone biopsy. Discussion(s): This case illustrates multi-level vertebral fractures in an otherwise healthy and young patient with chronic T1D, and is the first case report to demonstrate T1D-related trabecular bone defects on both HR-pQCT and bone histomorphometry. Hypoglycaemia is a common adverse effect of insulin therapy; severe hypoglycaemia may lead to seizures, where muscle contractions during convulsions are forceful enough to cause vertebral fractures6. The majority of vertebral fractures in this population may be asymptomatic7, and a high index of clinical suspicion is required for diagnosis. Although there is increasing awareness of the association between impaired bone quality in T1D, guidelines for assessment of bone in T1D patients are lacking and additional research is necessary to identify and manage patients at high fracture risk. Disclosures: None.

Background: Both Type 1 diabetes mellitus (T1DM) and coeliac disease (CD) are independently associated with reduced bone mineral density (BMD) and increased fracture risk. Whilst poorer glycaemic control and increased microvascular complications have been described, the literature examining bone health and fractures in adults with concomitant T1DM and CD (T1DM + CD) is limited. Objective(s): To evaluate fracture prevalence and explore associations with glycaemic control, hypoglycaemia and microvascular disease in T1DM + CD compared with T1DM alone. Method(s): We conducted a retrospective cross-sectional study of young adults with T1DM, who attended diabetes clinics at a large tertiary referral centre between August 2016 and February 2017. Clinical information, radiological and biochemistry results were extracted from medical records. Patients with comorbid chronic kidney disease, glucocorticoid use, hypogonadism and untreated hyperthyroidism were excluded. Result(s): A total of 346 patients with T1DM alone (median age 23 years) and 49 patients with T1DM + CD (median age 24 years) were included. Median age, gender distribution, BMI, haemoglobin A1c, daily insulin dose and serum 25-hydroxyvitamin D levels were similar between groups. Higher adjusted fracture risk was observed in T1DM + CD compared with T1DM (12.2% vs 3.5%; OR 3.50, 95% CI 1.01-12.12, P =.01), yet BMD was only measured in 6% of patients. The adjusted risk of hypoglycaemia >=2/week was greater for T1DM + CD (55% vs 38%, OR 3.28, 95% CI 1.61-6.69, P =.001); however, this was not independently associated with fractures. Replete vitamin D (>= 50 nmol/L) was associated with less hypoglycaemia (OR 0.48, 95% CI 0.29-0.80; P =.005), but not with fractures. Conclusion(s): Coeliac disease status was independently associated with increased fracture prevalence in young adults with T1DM. Recurrent hypoglycaemia was also increased in T1DM + CD, although hypoglycaemia was not independently associated with fractures.