Hyperparathyroidism Jaw Tumor Syndrome, an Unforeseen Diagnosis.

Asymptomatic primary hyperparathyroidism (PHPT) is often missed in developing nations due to limited formal healthcare exposure and biochemical screening programs. Many patients are thus only diagnosed once symptomatic. We present a 32-year-old female who developed bony protrusions in her jaw during pregnancy, resulting in a stillbirth. Three months later, during a dental consultation for worsening toothache, jaw abnormalities were detected. Radiological studies revealed bilateral mandibular radiolucent lesions, and bone biopsy confirmed histological features consistent with a brown tumor. These findings raised concerns about underlying PHPT, which was confirmed with a markedly elevated parathyroid hormone level in the presence of significant hypercalcemia. Further examination revealed impaired renal function, normal urine calcium excretion, and bilateral nephrocalcinosis. Low bone mineral density was measured with dual-energy X-ray absorptiometry, and conventional radiology identified additional low-density bony lesions in keeping with brown tumors. A parathyroid MIBI confirmed the presence of a singular parathyroid adenoma. A vague but possible family history, the patient's young age, and the severe renal and skeletal involvement prompted genetic testing. A cell division cycle 73 (CDC73) pathogenic variant, in keeping with primary hyperparathyroidism jaw tumor syndrome, was identified.

Pregnancy and diabetic ketoacidosis: fetal jeopardy and windows of opportunity.

Background: Diabetic ketoacidosis (DKA) during pregnancy poses significant risks to both the mother and fetus, with an increased risk of fetal demise. Although more prevalent in women with Type I diabetes (T1D); those with Type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) can also develop DKA. A lack of information about DKA during pregnancy exists worldwide, including in South Africa. Objective: This study examined the characteristics and outcomes associated with DKA during pregnancy. Methods: The study took place between 1 April 2020 and 1 October 2022. Pregnant women with DKA, admitted to Tygerberg Hospital's Obstetric Critical Care Unit (OCCU) were included. Maternal characteristics, precipitants of DKA, adverse events during treatment, and maternal-fetal outcomes were examined. Results: There were 54 episodes of DKA among 47 women. Most DKA's were mild and occurred in the third trimester. Pregestational diabetes dominated (31/47; 60%), with 47% having T1D and 94% requiring insulin. Seven women (7/47, 15%; T2D:6, T1D:1) had two episodes of DKA during the same pregnancy. Most women (32/47; 68%) were either overweight or obese. Yet, despite the T2D phenotype, biomarkers indicated that auto-immune diabetes was prevalent among women without any prior history of T1D (6/21; 29%). Twelve women (26%) developed gestational hypertension during pregnancy, and 17 (36%) pre-eclampsia. Precipitating causes of DKA included infection (14/54; 26%), insulin disruption (14/54; 26%) and betamethasone administration (10/54; 19%). More than half of the episodes of DKA involved hypokalemia (35/54, 65%) that was associated with fetal death (P=0.042) and hypoglycemia (28/54, 52%). Preterm birth (<37 weeks' gestation) occurred in 85% of women. No maternal deaths were recorded. A high fetal mortality rate (13/47; 28%) that included 11 spontaneous intrauterine deaths and two medical terminations, was observed. Conclusion: Women with DKA have a high risk of fetal mortality as well as undiagnosed auto-immune diabetes. There is a strong link between maternal hypokalemia and fetal loss, suggesting an opportunity to address management gaps in pregnant women with DKA.

Early postpartum HbA1c after hyperglycemia first detected in pregnancy-Imperfect but not without value.

BACKGROUND: South African women of childbearing age are disproportionally affected by obesity and at significant risk of Type 2 Diabetes Mellitus (T2DM). Unless pregnant, they do not readily undergo screening for T2DM. With a local focus on improved antenatal care, hyperglycemia is often first detected in pregnancy (HFDP). This may erroneously be attributed to Gestational Diabetes Mellitus (GDM) in all without considering T2DM. Glucose evaluation following pregnancy is essential for early detection and management of women with T2DM in whom persistent hyperglycemia is to be expected. Conventional testing with an oral glucose tolerance test (OGTT) is cumbersome, prompting investigation for alternate solutions. AIM: To compare the diagnostic performance of HbA1c to the current gold standard OGTT in women with HFDP 4-12 weeks post-delivery. METHODS: Glucose homeostasis was assessed with OGTT and HbA1c in 167 women with HFDP, 4-12 weeks after delivery. Glucose status was based on American Diabetes Association criteria. RESULTS: Glucose homeostasis was assessed at 10 weeks (IQR 7-12) after delivery. Of the 167 participants, 52 (31%) had hyperglycemia, which was comprised of 34 (20%) prediabetes and 18 (11%) T2DM. Twelve women in the prediabetes subgroup had diagnostic fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG), but in two-thirds of the patients (22/34) only one time point proved diagnostic. The FPGs and the 2hPGs of six women with HbA1c-based T2DM were both within the prediabetes diagnostic range. According to the HbA1c measurements, 85% of 52 participants with gold standard OGTT defined hyperglycemia (prediabetes and T2DM) as well as 15 of 18 women with postpartum persistent T2DM were correctly classified. According to FPG, 15 women with persistent hyperglycemia would have been missed (11 with prediabetes and four with T2DM; 29%). When compared to an OGTT, a single HbA1c of 6.5% (48mmol/mol) postpartum demonstrated a sensitivity of 83% and specificity of 97% for the identification of T2DM. CONCLUSION: HbA1c may improve access to postpartum testing in overburdened clinical settings where the required standards of OGTT cannot be guaranteed. HbA1c is a valuable test to detect women who will benefit most from early intervention but cannot unequivocally replace OGTT.

Nutritional deficiency in South African adults scheduled for bariatric surgery.

Background: Globally, there is a rising trend in obesity, known to increase morbidity and mortality. Metabolic surgery and adequate weight loss decrease mortality but may worsen pre-existing nutrient deficiencies. Most data on pre-existing nutritional deficiencies in the population undergoing metabolic surgery is from the developed world, where an extensive micronutrient assessment is achievable. In resource-constrained environments, the cost of a comprehensive micronutrient assessment must be weighed against the prevalence of nutritional deficiencies and the potential harm if one or more nutritional deficiencies are missed. Methods: This cross-sectional study investigated the prevalence of micronutrient and vitamin deficiencies in participants scheduled to undergo metabolic surgery in Cape Town, South Africa, a low-middle income country. 157 participants were selected and 154 reported on; who underwent a baseline evaluation from 12 July 2017 to 19 July 2020. Laboratory measurements were conducted, including vitamin B12 (Vit B12), 25-hydroxy vitamin D (25(OH)D), folate, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), thyroxine (T4), ferritin, glycated haemoglobin (HbA1c), magnesium, phosphate, albumin, iron, and calcium. Results: Participants were predominantly female, aged 45 years (37-51), with a preoperative BMI of 50.4 kg/m2 (44.6-56.5). A total of 64 individuals had Type 2 diabetes mellitus (T2D), with 28 undiagnosed cases at study entry (18% of study population). 25(OH)D deficiency was most prevalent (57%), followed by iron deficiency (44%), and folate deficiency (18%). Other deficiencies (vitamin B12, calcium, magnesium, phosphate) were rarely encountered and affected ≤1% of participants. Folate and 25(OH)D deficiency were related to obesity classification, with a higher prevalence in participants with a BMI ≥40 kg/m2 (p <0.01). Conclusion: A higher prevalence of some micronutrient deficiencies was noted compared with data from similar populations in the developed world. The minimum baseline/preoperative nutrient evaluation in such populations should include 25(OH)D, iron studies, and folate. Additionally, screening for T2D is recommended. Future efforts should seek to collate broader patient data on a national scale and include longitudinal surveillance after surgery. This may provide a more holistic picture of the relationship between obesity, metabolic surgery and micronutrient status inform more appropriate evidence-based care.

Pathology-supported genetic testing for the application of breast cancer pharmacodiagnostics: family counselling, lifestyle adjustments and change of medication.

BACKGROUND: Pathology-supported genetic testing (PSGT) enables transitioning of risk stratification from the study population to the individual. RESEARCH DESIGN AND METHODS: We provide an overview of the translational research performed in postmenopausal breast cancer patients at increased risk of osteoporosis due to aromatase inhibitor therapy, as the indication for referral. Both tumor histopathology and blood biochemistry levels were assessed to identify actionable disease pathways using whole exome sequencing (WES). RESULTS: The causes and consequences of inadequate vitamin D levels as a modifiable risk factor for bone loss were highlighted in 116 patients with hormone receptor-positive breast cancer. Comparison of lifestyle factors and WES data between cases with vitamin D levels at extreme upper and lower ranges identified obesity as a major discriminating factor, with the lowest levels recorded during winter. Functional polymorphisms in the vitamin D receptor gene contributed independently to therapy-related osteoporosis risk. In a patient with invasive lobular carcinoma, genetic counseling facilitated investigation of the potential modifying effect of a rare CDH1 variant co-occurring with BRCA1 c.66dup (p.Glu23ArgfsTer18). CONCLUSION: Validation of PSGT as a three-pronged pharmacodiagnostics tool for generation of adaptive reports and data reinterpretation during follow-up represents a new paradigm in personalized medicine, exposing significant limitations to overcome.

Access to care for low trauma hip fractures in South Africa.

RATIONALE: Early surgery is recommended for hip fractures. MAIN RESULT: In this study only one-third of subjects with hip fractures were admitted within 24 h of the fracture, and surgery was delayed beyond 48 h in the majority. SIGNIFICANCE: These findings highlight the need to improve access to care for hip fracture subjects. PURPOSE: There is limited data on the timing of admission and surgery following a low trauma hip fracture (HF) in South Africa (SA). METHODS: A prospective, observational study was conducted at public and private hospitals in three provinces, Gauteng (GP), KwaZulu-Natal (KZN) and the Western Cape (WC), in SA to determine time from fracture to admission and from admission to surgery in patients presenting with low trauma HF. Associations with delayed admission and surgery were explored using logistic regression. RESULTS: The median age of the 1996 subjects was 73 years (IQR 63-81 years), the majority were women (1346, 67%) and 1347 (67%) were admitted to the public hospitals. In one-third of subjects (661, 33%), admission was delayed to beyond 24 h after the fracture. There was a significantly longer time to admission in public compared to private hospitals (21 h [IQR 10.0-48.5] versus 6 h [IQR 3.3-14.1], p < 0.001), in subjects < 65 years, the WC and when admission occurred on a weekday. Surgery was delayed beyond 48 h in the majority (1272, 69%) of subjects and was significantly longer in public compared to private hospitals (130 h [IQR 62.6-212.4] versus 45.4 h [IQR 24.0-75.5], p < 0.001), in KZN, and when admission occurred after hours. CONCLUSION: The burden of HFs is higher at public hospitals in SA, where there is a significant delay in admission after a fracture and surgery after admission. This highlights the need for a review of HF care pathways, resources and policies.

Hyperglycemia First Detected in Pregnancy in South Africa: Facts, Gaps, and Opportunities.

This review contextualizes hyperglycemia in pregnancy from a South-African perspective. It aims to create awareness of the importance of hyperglycemia in pregnancy in low-middle-income countries. We address unanswered questions to guide future research on sub-Saharan African women with hyperglycemia first detected in pregnancy (HFDP). South African women of childbearing age have the highest prevalence of obesity in sub-Saharan Africa. They are predisposed to Type 2 diabetes (T2DM), the leading cause of death in South African women. T2DM remains undiagnosed in many African countries, with two-thirds of people living with diabetes unaware. With the South African health policy's increased focus on improving antenatal care, women often gain access to screening for non-communicable diseases for the first time in pregnancy. While screening practices and diagnostic criteria for gestational diabetes mellitus (GDM) differ amongst geographical areas in South Africa (SA), hyperglycemia of varying degrees is often first detected in pregnancy. This is often erroneously ascribed to GDM, irrespective of the degree of hyperglycemia and not overt diabetes. T2DM and GDM convey a graded increased risk for the mother and fetus during and after pregnancy, with cardiometabolic risk accumulating across the lifespan. Resource limitations and high patient burden have hampered the opportunity to implement accessible preventative care in young women at increased risk of developing T2DM in the broader public health system in SA. All women with HFDP, including those with true GDM, should be followed and undergo glucose assessment postpartum. In SA, studies conducted early postpartum have noted persistent hyperglycemia in a third of women after GDM. Interpregnancy care is advantageous and may attain a favourable metabolic legacy in these young women, but the yield of return following delivery is suboptimal. We review the current best evidence regarding HFDP and contextualize the applicability in SA and other African or low-middle-income countries. The review identifies gaps and shares pragmatic solutions regarding clinical factors that may improve awareness, identification, diagnosis, and management of women with HFDP.

FRAX-based fracture probabilities in South Africa.

The hip fracture rates in South Africa were used to create ethnic-specific FRAX® models to facilitate fracture risk assessment. INTRODUCTION: The aim of this study was to develop FRAX models to compute the 10-year probability of hip fracture and major osteoporotic fracture and assess their potential clinical application. METHODS: Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for the White, Black African, Coloured and Indian population of South Africa. Age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women to determine fracture probabilities at a femoral neck T score of -2.5 SD, or those equivalent to a woman with a prior fragility fracture. Fracture probabilities were compared with those from selected countries. RESULTS: Probabilities were consistently higher in Indian than in Coloured men and women, in turn, higher than in Black South Africans. For White South Africans, probabilities were lower than in Indians at young ages up to the age of about 80 years. When a BMD T score of -2.5 SD was used as an intervention threshold, FRAX probabilities in women age 50 years were approximately 2-fold higher than in women of the same age but with an average BMD and no risk factors. The increment in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T score of -2.5 SD was no longer a risk factor. Probabilities equivalent to women with a previous fracture rose with age and identified women at increased risk at all ages. CONCLUSIONS: These FRAX models should enhance accuracy of determining fracture probability amongst the South African population and help guide decisions about treatment.

Prevalence of Sarcopenia in Older South African Patients Following Surgery for Fragility Fractures of the Hip.

INTRODUCTION: Geriatric patients with a fragility fracture of the hip (FFH) are especially prone to sarcopenia with poor functional outcomes and quality of life. We assessed the prevalence of sarcopenia in older South African patients with FFH. Risk factors for sarcopenia were also investigated. MATERIALS AND METHODS: From August 1 to November 30, 2018, all older patients with FFH were invited to participate. Sarcopenia was diagnosed based on the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Handgrip strength (HGS) and muscle strength were assessed. Muscle quantity was determined by dual-energy X-ray absorptiometry. Demographic information was collected, and 25-hydroxyvitamin D (25[OH]D) status was determined. RESULTS: Of the 100 hip fracture cases, 65 were enrolled, and 52% (34/65) were sarcopenic (women: 62%; men: 38%). HGS accurately identified sarcopenia (sensitivity and specificity: 100%). Patients >80 years of age had a prevalence of sarcopenia twice (18/21 [83%]) that of younger patients (18/44 [36%]). Women with sarcopenia were smaller than those without (weight: p < 0.001; height: p < 0.001; body mass index: p = 0.018). Low 25(OH)D was almost universally present, with median 25(OH)D levels significantly lower in the patients with sarcopenia (27 nmol/L [interquartile range {IQR}: 20-39] vs. 40 nmol/L [IQR: 29-53]). Several risk factors, including advanced age; female sex; a smaller body size, especially among women; limited physical activity; and low 25(OH)D levels, were identified. DISCUSSION: The accuracy of HGS testing in this cohort underscores EWGSOP2's recommendation that muscle strength is key to sarcopenia. Further study and follow-up are required to determine the clinical relevance of sarcopenia among FFH patients. CONCLUSION: The prevalence of sarcopenia in our FFH population is high. Sarcopenia is associated with poor patient outcomes following surgical intervention. Orthopaedic surgeons should therefore be cognizant of the presentation and associated risk of sarcopenia as our patient populations age.

Utility of in-hospital post-delivery fasting plasma glucose to predict postpartum glucose status in women with hyperglycaemia first detected in pregnancy: A prospective cohort study.

BACKGROUND: Women with hyperglycaemia first detected in pregnancy (HFDP), including those with gestational diabetes mellitus (GDM), should undergo a glucose evaluation 4-12 weeks after delivery. Globally, suboptimal postpartum return rates limit the opportunity to intervene in women with sustained hyperglycaemia and pragmatic solutions should be sought to bridge this gap. OBJECTIVE: To assess the utility of postpartum in-hospital glucose evaluation to predict the outcome of the oral glucose tolerance test (OGTT) performed 4-12 weeks after delivery. METHODS: The study was performed prospectively at Tygerberg Hospital, Cape Town, South Africa. Women with HFDP, classified as GDM based on the modified National Institute for Health and Care Excellence criteria, who delivered between November 2018 and June 2019 were included in the study. Fasting plasma glucose (FPG) was performed 24-72 hours after delivery (t1) in the postnatal ward, provided glucose lowering medication was discontinued at delivery. An OGTT 4-12 weeks postpartum (t2) was scheduled for the total cohort. We compared glucose values and glucose categories at t1 and t2 and evaluated antenatal characteristics of women who returned, compared to the group that was lost to follow-up. RESULTS: In-hospital post-delivery glucose assessment (t1) was performed in 115 women. Glucose levels were significantly lower at t1 compared to antenatal diagnostic values (t0) and assessment at t2. Of the fourteen women with hyperglycaemia at t2, none had abnormal fasting glucose concentrations at t1. Women with HFDP who fulfilled criteria for overt diabetes at t0, all (24/115) had normal fasting glucose levels at t1 except for IFG in one (1/24). The antenatal characteristics of women with HFDP who returned at t2, were similar to the women who did not return. CONCLUSION: Based on this study, in-hospital fasting glucose 24-72 hours postpartum cannot replace the OGTT 4-12 weeks postpartum. Pragmatic solutions for low postpartum return rates in women with HFDP should be pursued.

CYP19A1 rs10046 Pharmacogenetics in Postmenopausal Breast Cancer Patients Treated with Aromatase Inhibitors: One-year Follow-up.

BACKGROUND: Significant individual variation in bone loss associated with aromatase inhibitors (AIs) emphasizes the importance of identifying postmenopausal breast cancer patients at high risk for this adverse effect. The study explores the clinical relevance of genetic variation in the Cytochrome P450 19A1 (CYP19A1) gene in a subset of South African patients during the first year of taking AIs for estrogen receptor (ER)-positive breast cancer. METHODS: The study population consisted of ER-positive breast cancer patients on AIs, followed in real-life clinical practice. Body mass index was measured and bone mineral density (BMD) was determined at baseline and at month 12. CYP19A1 genotyping was performed using real-time polymerase chain reaction analysis of rs10046, extended to Sanger sequencing and whole exome sequencing in 10 patients with more than 5% bone loss at month 12 at the lumbar spine. RESULTS: After 12 months of AI treatment, 72 patients had completed BMD and were successfully genotyped. Ten patients (14%) experienced more than 5% bone loss at the lumbar spine over the study period. Genotyping for CYP19A1 rs10046 revealed that patients with two copies of the A-allele were 10.79 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase at the lumbar spine, compared to patients with the GA or GG genotypes (CI of 1.771- 65.830, p=0.01). None of the 34 patients without lumbar spine bone loss at month 12 were homozygous for the functional CYP19A1 polymorphism. At the total hip region, patients with the AA genotype were 7. 37 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase (CI of 1.101- 49.336, p=0.04). CONCLUSION: Homozygosity for the CYP19A1 rs10046 A-allele may provide information, in addition to clinical and biochemical factors that may be considered in risk stratification to optimize bone health in postmenopausal breast cancer women on AIs. Further investigation is required to place the clinical effect observed for a single CYP19A1 gene variant in a genomic context.

Evidence to support the classification of hyperglycemia first detected in pregnancy to predict diabetes 6-12 weeks postpartum: A single center cohort study.

AIMS: Diagnostic criteria for type 2 diabetes mellitus (T2DM) applied to women with gestational diabetes mellitus (GDM) may predict postpartum T2DM but requires validation. METHODS: Women with GDM aged ≥ 18-years were prospectively evaluated 6-12 weeks after delivery at Tygerberg Hospital, Cape Town, South-Africa (November 2015- December 2018). Glucose status at GDM diagnosis was categorized into i) International Association for Diabetes in Pregnancy Study Group (IADPSG) T2DM (fasting glucose ≥ 7 mmol/L and/or 2hr-glucose ≥ 11.1 mmol/L) or ii) modified National Institute for Care Excellence (NICE) GDM (fasting glucose ≥ 5.6 mmol/L-6.9 mmol/L and/or 2hr-glucose ≥ 7.8 mmol/L-11 mmol/L) and compared with postpartum OGTT. RESULTS: IADPSG T2DM and NICE GDM was present in 35% (n = 64) and 65% (n = 117) of the 181 women who completed the 8 ± 2 weeks postpartum evaluation respectively. Postpartum, the prevalence of T2DM and prediabetes was 26% (n = 47/181) and 15% (n = 28). Antenatal IADPSG T2DM categorization identified 31/47 women with postpartum T2DM (sensitivity 75%; specificity 48%). All of the modified NICE GDM category women who developed T2DM (n = 16/117) had elevations of both fasting and 2hr-glucose values antenatally. CONCLUSION: The utility of the IADPSG T2DM criteria to predict T2DM postpartum is confirmed. Women with both fasting and 2hr-glucose values above GDM cut-offs emerged as another high-risk category.

Observations on Glucose Excursions With the Use of a Simple Protocol for Insulin, Following Antenatal Betamethasone Administration.

Aims: Pregnant women with diabetes often require preterm delivery. Antenatal betamethasone reduces perinatal morbidity and mortality, but induces hyperglycemia. The primary objective was to observe glucose excursions and determine the preliminary safety of a protocol for subcutaneous insulin following betamethasone administration in an antenatal ward. Material and Methods: This retrospective study included all women with diabetes who received betamethasone due to anticipated preterm delivery. Glucose excursions were evaluated in the fasting state and 2-h postprandial. Blood glucose values ≥14mmol/L or ≤3.5mmol/L were regarded as unacceptable hyper- and hypoglycemia respectively. Events over the first 96 h were documented. Results: This study spanned 52 months and included fifty-nine women. Eleven episodes of defined hypoglycemia occurred in six women, all receiving insulin therapy, but none after a corrective dose of insulin. No serious hypoglycemic incident was reported. Seventeen women experienced hyperglycemic incidents almost entirely (47/56) within 48 h of betamethasone administration, most often postprandially (34/56) and in 85% of episodes, preceded by pre-prandial values >9 mmol/L (29/34). 14 (82.4%) of these women were receiving background insulin therapy. No case with gestational diabetes encountered defined hyperglycemia. Conclusions: This small study demonstrated preliminary safety of the protocol. Enhanced surveillance is necessary for 72 h after initiation of betamethasone.

Baseline bone health status in multi-ethnic South African postmenopausal breast cancer patients at initiation of aromatase inhibitor therapy: A descriptive study.

INTRODUCTION: Osteoporosis (OP) risk factor assessment and bone mineral density (BMD) testing are frequently omitted at baseline in aromatase inhibitor (AI) studies, which may lead to misinterpretation of AI associated bone loss. The present study describes bone health of South African postmenopausal women of predominantly Mixed Ancestry, prior to AI treatment. METHODS: This descriptive baseline study, nested in a prospective AI cohort study, included postmenopausal women with endocrine sensitive breast cancer, aged 50 to 80 years. A baseline questionnaire documented demographic-, medical-, lifestyle- and fracture history. Body weight was assessed clinically, and body composition and BMD measured via dual energy absorptiometry (DXA). Data was analysed in STATA 14 using descriptive and inferential statistics. RESULTS: 101 participants were recruited, with a mean age of 61±7 years. Nearly a third (n = 32) of women at baseline fulfilled global criteria for bone protection (BMD T-score ≥-2SD (n = 18); BMD T-score -1.5SD to < -2SD with risk factors (n = 14). Lower body weight, body mass index (BMI), fat mass index and lean mass index were significantly associated with the participants with a BMD measurement in keeping with a diagnosis of OP (p <0.001). Low vitamin D was present in 93% of the cohort tested (n = 95), whilst deficient vitamin D status (<20ng/ml) was documented in 52 women (55%). CONCLUSIONS: In this study, a third of postmenopausal women considered for AI therapy fulfilled international criteria for bone protective pharmacological intervention. This emphasizes the need for clinical risk and BMD assessment in postmenopausal breast cancer patients at baseline. Body composition and bone health associations highlight bone fragility associated with lower body weight.

ADSC-conditioned media elicit an ex vivo anti-inflammatory macrophage response.

Obesity-associated inflammatory mechanisms play a key role in the pathogenesis of metabolic-related diseases. Failure of anti-inflammatory control mechanisms within adipose tissue and peripheral blood mononuclear cells (PBMCs) have been implicated in disease progression. This study investigated the efficacy of allogeneic adipose tissue-derived mesenchymal stem cells conditioned media (ADSC-CM) to counteract persistent inflammation by inducing an anti-inflammatory phenotype and cytokine response within PBMCs derived from patients with and without metabolic syndrome. Forty six (n=46) mixed ancestry females (18 - 45 years) were subdivided into a) healthy lean (HL) (n=10) (BMI < 25 kg/m2), b) overweight/obese (OW/OB) (BMI ≥ 25 kg/m2, < 3 metabolic risk factors) (n=22) and c) metabolic syndrome (MetS) (visceral adiposity , ≥ 3 metabolic risk factors) (n=14) groups. Body composition (DXA scan), metabolic (cholesterol, HDL, LDL, triglycerides, blood glucose) and inflammatory profiles (38-Plex cytokine panel) were determined. PBMCs were isolated from whole blood and treated ex vivo with either i) autologous participant-derived serum ii) ADSCs-CM or iii) a successive treatment regime. The activation status (CD11b+) and intracellular cytokine (IL6, IL10, TNFa) expression were determined in M1 (CD68+CD206-CD163-) and M2 (CD68+CD163+ CD206+) macrophage populations using flow cytometry. ADSC-CM treatment, promoted a M2 macrophage phenotype and induced IL10 expression, this was most pronounced in the OW/OB group. This response is likely mediated by multiple complementing factors within ADSC-CM, yet to be identified. This study is the first to demonstrate the therapeutic potential of ADSC-CM to restore the inflammatory balance in immune compromised obese individuals.

Evidence for the utility of antenatal HbA1c to predict early postpartum diabetes after gestational diabetes in South Africa.

Aim To evaluate antenatal HbA1c at diagnosis and in the 4 weeks preceding delivery to predict early postpartum diabetes mellitus (DM) in women with Gestational Diabetes Mellitus (GDM). Methods Seventy-eight women with GDM were prospectively assessed. The ability of HbA1c at GDM diagnosis (t1) and in the 4 weeks preceding delivery (t2) to predict DM 6-12 weeks after delivery was investigated. Glucose assessment was performed between November 1, 2015, and November 1, 2016 at Tygerberg Hospital (TH), Cape Town, South Africa (SA). Individuals with known pre-existing diabetes were excluded. Results HbA1c of 6.2% (44 mmol/mol) and 6.5% (48 mmol/mol) at t1 predicted DM with sensitivities of 95% and 90% and specificities of 62% and 70% respectively. At t2 the best cut-off for HbA1c, in accordance with t1, was also 6.2% (44 mmol/mol; sensitivity 92%, specificity 56%). Nineteen of the 29 women with suspected pre-gestational DM had HbA1c levels ≥ 6.5% (48 mmol/mol) at t1. The increased risk for postpartum DM with HbA1c ≥ 6.2% (44 mmol/mol) was four-fold (OR 3.97 CI 2.08-7.59p < 0.001) at t1 and five-fold (OR 5.08 CI 1.60-16.25 p = 0.006) at t2. Conclusion HbA1c lower than 6.5% (48 mmol/mol) predicts postpartum DM in women with GDM. HbA1c can serve as instrument to improve postpartum follow-up.

Prevalence and predictive factors of early postpartum diabetes among women with gestational diabetes in a single-center cohort.

OBJECTIVE: To determine the prevalence of diabetes at 6-12 weeks postpartum among women with gestational diabetes mellitus (GDM), and to identify prenatal postpartum diabetes predictors. METHODS: In the present prospective cohort study, glucose statuses of consecutive women newly diagnosed with hyperglycemia during pregnancy were evaluated at 6-12 weeks postpartum between November 1, 2015, and November 1, 2016, at Tygerberg Hospital, Cape Town, South Africa. Women with known diabetes were excluded. RESULTS: There were 78 patients included; 36 (46%) patients had abnormal postpartum glucose values (21 [27%] diabetes; 15 [19%] pre-diabetes) and 29 (37%) had overt diabetes in pregnancy. In univariate analyses, GDM diagnosis before 24 weeks of pregnancy (P<0.001), degree of hyperglycemia at diagnosis (P=0.001), need for insulin (P=0.001), glycosylated hemoglobin (HbA1c) in the month preceding delivery (P=0.006), older than 36 years (P=0.039), family history of diabetes (P=0.048), and preterm labor (P=0.039) were risk factors for postpartum diabetes. Multivariate analyses confirmed family history of diabetes (OR 7.45, 95% CI 1.05-52.76; P=0.044), HbA1c at diagnosis (OR 5.33, 95% CI 2.25-12.60; P<0.001), and age (OR 8.8, 95% CI 1.35-58.45; P=0.023), as robust predictors of diabetes after GDM. CONCLUSION: The high prevalence of diabetes supports early postpartum oral glucose tolerance testing. Several women had undiagnosed diabetes. The risk factors identified could be useful for prenatal risk stratification.

Randomized cross-over trial comparing the diagnosis of gestational diabetes by oral glucose tolerance test and a designed breakfast glucose profile.

OBJECTIVE: To compare a glucose test based on a standardized, designed breakfast to the 75-g oral glucose tolerance test (OGTT), comparing venous and capillary glucose values for the diagnosis of gestational diabetes mellitus (GDM). METHODS: The present prospective, randomized, cross-over trial enrolled patients at high risk of developing GDM who were attending the High-Risk Antenatal Clinic of Tygerberg Hospital, Cape Town, South Africa, between March 1 and December 31, 2015. Patients were randomized to initial testing with either the OGTT or a designed breakfast glucose profile (DBGP) glucose test before the alternate test was performed 1 week later; no dietary or other interventions were applied in the intervening period. Venous and capillary fasting and 2-hour glucose values were measured and were compared between the OGTT and DBGP, and between OGTT and laboratory venous samples. RESULTS: There were 51 patients included in the study. The fasting and 2-hour capillary glucose values from the OGTT correlated significantly with the laboratory venous samples (P<0.001 at both time intervals). The 2-hour capillary glucose values from the DBGP demonstrated a satisfactory correlation with those from the OGTT (P<0.001). CONCLUSIONS: The DBGP provided a sufficiently accurate alternate test for the diagnosis of GDM; it warrants further investigation.

Systemic Factors During Metabolic Disease Progression Contribute to the Functional Decline of Adipose Tissue-Derived Mesenchymal Stem Cells in Reproductive Aged Females.

It is known that advanced metabolic disorders such as type 2 diabetes compromise the functional and regenerative capacity of endogenous adipose-tissue resident stem cells (ADSCs). It is, however, still unclear at which stage of disease progression ADSCs become compromised and whether systemic factors contribute to their functional decline. It was therefore hypothesized that inflammatory changes in the systemic microenvironment during distinct stages of disease progression negatively affect the functional capacity of ADSCs. A total of forty-seven (n = 47) black African reproductive aged females (32 ± 8 years; mean ± SD) were included in this study and subdivided into: (a) healthy lean (C; body mass index, BMI ≤ 25 kg/m2), (b) healthy overweight/obese (OB; BMI ≥ 25 kg/m2), (c) obese metabolic syndrome (MetS; BMI ≥ 30 kg/m2), and (d) type 2 diabetes mellitus (T2DM; previously diagnosed and on treatment) groups. Participants underwent anthropometric assessments and a DXA scan to determine their body composition and adipose indices. Each persons' systemic metabolic- (cholesterol, HDL, LDL, triglycerides, and blood glucose) and inflammatory profiles (CRP, SDF1α, TNFα, IL6, IL8, IL10, and IFNy) were also evaluated. Participant-derived serum was then used to treat an ADSC cell line in vitro and its effect on viability (MTT-based assay), proliferation (BrdU), migration (wound healing assay), and osteogenic differentiation assessed. When exposed to serum derived from overweight/obese individuals (with or without metabolic syndrome), both the proliferative and migratory responses of ADSCs were less pronounced than when exposed to healthy control serum. Serum IL6 concentrations were identified as a factor influencing the proliferation of ADSCs, suggesting that long-term disruption to the systemic cytokine balance can potentially disrupt the proliferative responses of ADSCs. Obese participant-derived serum (with and without metabolic syndrome) furthermore resulted in lipid accumulation during osteogenic differentiation. This study, therefore demonstrated that systemic factors in obese individuals, regardless of the presence of metabolic syndrome, can be detrimental to the multifunctional properties of ADSCs.