Optimising Cardiometabolic Risk Factors in Pregnancy: A Review of Risk Prediction Models Targeting Gestational Diabetes and Hypertensive Disorders.

Cardiovascular disease, especially coronary heart disease and cerebrovascular disease, is a leading cause of mortality and morbidity in women globally. The development of cardiometabolic conditions in pregnancy, such as gestational diabetes mellitus and hypertensive disorders of pregnancy, portend an increased risk of future cardiovascular disease in women. Pregnancy therefore represents a unique opportunity to detect and manage risk factors, prior to the development of cardiovascular sequelae. Risk prediction models for gestational diabetes mellitus and hypertensive disorders of pregnancy can help identify at-risk women in early pregnancy, allowing timely intervention to mitigate both short- and long-term adverse outcomes. In this narrative review, we outline the shared pathophysiological pathways for gestational diabetes mellitus and hypertensive disorders of pregnancy, summarise contemporary risk prediction models and candidate predictors for these conditions, and discuss the utility of these models in clinical application.

Obesity, menstrual irregularity and polycystic ovary syndrome in young women with type 1 diabetes: A population-based study.

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: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Double Whammy of Obesity and Diabetes on Female Reproductive Health.

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.

Diabetes: a metabolic and reproductive disorder in women.

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.

Fracture risk in young and middle-aged adults with type 1 diabetes mellitus: A systematic review and meta-analysis.

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. AIMS: To determine the risk of fracture in young and middle-aged adults with T1DM aged 18-50 years old. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Recurrent vertebral fractures in a young adult: a closer look at bone health in type 1 diabetes mellitus.

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. LEARNING POINTS: Type 1 diabetes mellitus (T1DM) is a secondary cause of osteoporosis, characterised by reduced bone mass and disturbed bone microarchitecture.Hypoglycaemic seizures generate sufficient compression forces along the thoracic column and can cause fractures in individuals with compromised bone quality.Unrecognised hypoglycaemic seizures should be considered in patients with T1DM presenting with fractures without a history of trauma.Patients with T1DM have increased fracture risk and risk factors should be addressed. Evaluation of bone microarchitecture may provide further insights into mechanisms of fracture in T1DM.Further research is needed to guide the optimal screening and management of bone health in patients with T1DM.

Increased prevalence of fracture and hypoglycaemia in young adults with concomitant type 1 diabetes mellitus and coeliac disease.

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: To evaluate fracture prevalence and explore associations with glycaemic control, hypoglycaemia and microvascular disease in T1DM + CD compared with T1DM alone. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Prospective studies are required to determine the long-term impacts of CD on bone health and glycaemic control in patients with T1DM.