Correction: Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial.

[This corrects the article DOI: 10.1371/journal.pone.0269440.].

Healthcare Resource Utilization in Controlled Versus Uncontrolled Adults Living With Type 1 Diabetes in the South African Public Healthcare Sector.

OBJECTIVES: This study aimed to understand the cost implications of managing people living with type 1 diabetes mellitus in the South African public healthcare system. METHODS: A multicenter, noninterventional retrospective chart review study was performed. Data on healthcare resource consumption, demographics, risk factors, clinical history, and acute events were collected. Direct medical costs were collected over a 1-year period, stratified by controlled versus uncontrolled patients. In addition, the costs in people with controlled (glycated hemoglobin < 7%) versus uncontrolled glycated hemoglobin (≥ 7%) at time horizons of 1, 5, 10, and 25 years were modeled using the IQVIA Core Diabetes Model. RESULTS: The costs based on the retrospective chart review were $630 versus $1012 (controlled versus uncontrolled population). The modeled costs at various time horizons were as follows: at 1 year, $900 versus $1331; at 5 years, $4163 versus $6423; at 10 years, $7759 versus $16 481; and at 25 years, $16 969 versus $66 268. The largest cost in the controlled population was severe hypoglycemia requiring nonmedical assistance, severe hypoglycemia requiring medical assistance, and treatment costs. In the uncontrolled population, the largest cost was the cost of diabetic ketoacidosis, severe hypoglycemia requiring nonmedical assistance, severe hypoglycemia requiring medical assistance, and foot complications. CONCLUSIONS: Strict glycemic control reduces healthcare resource use overall. Patients in the controlled group still experienced high resource use related to hypoglycemic events. The introduction of a structured patient education program and analog insulins may result in less episodes of hypoglycemia and potential cost savings.

Health Care Resource Utilization in Adults Living With Type 1 Diabetes Mellitus in the South African Public Health Sector: Protocol for a 1-Year Retrospective Analysis With a 5-, 10-, and 25-Year Projection.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is less common than type 2 diabetes mellitus but is increasing in frequency in South Africa. It tends to affect younger individuals, and upon diagnosis, exogenous insulin is essential for survival. In South Africa, the health care system is divided into private and public health care systems. The private system is well resourced, whereas the public sector, which treats more than 80% of the population, has minimal resources. There are currently no studies in South Africa, and Africa at large, that have evaluated the immediate and long-term costs of managing people living with T1DM in the public sector. OBJECTIVE: The primary objective was to quantify the cost of health care resource utilization over a 12-month period in patients with controlled and uncontrolled T1DM in the public health care sector. In addition, we will project costs for 5, 10, and 25 years and determine if there are cost differences in managing subsets of patients who achieve glycemic control (hemoglobin A1c [HbA1c] <7%) and those who do not. METHODS: The study was performed in accordance with Good Epidemiological Practice. Ethical clearance and institutional permissions were acquired. Clinical data were collected from 2 tertiary hospitals in South Africa. Patients with T1DM, who provided written informed consent, and who satisfied the inclusion criteria were enrolled in the study. Data collection included demographic and clinical characteristics, acute and chronic complications, hospital admissions, and so on. We plan to perform a cost-effectiveness analysis to quantify the costs of health care utilization in the preceding 12 months. In addition, we will estimate projected costs over the next 10 years, assuming that study participants maintain their current HbA1c level. The cost-effectiveness analysis will be modeled using the IQVIA CORE Diabetes Model. The primary outcome measures are incremental quality-adjusted life years, incremental costs, incremental cost-effectiveness ratios, and incremental life years. RESULTS: Ethical clearance and institutional approval were obtained (reference number 200407). Enrollment began on February 9, 2021, and was completed on August 24, 2021, with 224 participants. A database lock was performed on October 29, 2021. The statistical analysis and clinical study report were completed in January 2022. CONCLUSIONS: At present, there are no data assessing the short- and long-term costs of managing patients with T1DM in the South African public sector. It is hoped that the findings of this study will help policy makers optimally use limited resources to reduce morbidity and mortality in people living with T1DM. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/44308.

Dyslipidemia in South African patients with hypothyroidism.

Background: Overt hypothyroidism leads to increased cardiovascular risk, primarily through effects the disorder has on lipids. Most studies investigating lipids in the setting of hypothyroidism, have been performed in predominantly Caucasians in North America and Europe. Different patterns and prevalence of dyslipidemia have been described; one study reporting dyslipidemia in 90% of patients with hypothyroidism. The prevalence of dyslipidemia in overt hypothyroidism among the ethnically diverse predominantly black South African population is unknown. Methodology: A retrospective case-control study evaluating lipid profiles of an ethnically diverse cohort of patients with overt hypothyroidism (TSH > 10 mIU/L) attending two academic hospitals in Johannesburg, South Africa from September 2006-September 2016. Patients with primary or secondary causes for dyslipidemia and those taking lipid-lowering therapy were excluded. Results: Two hundred and six patients with hypothyroidism were included and compared to 412 euthyroid controls matched for sex, ethnicity, and age. Most hypothyroid patients were female (n = 180;67.5 %). Median TSH was similar across all ethnic groups (p = 0.09). Median TC, TG and LDL-C were higher in hypothyroid patients (p < 0.01). Normal lipid profiles were found in 29.44 % of all hypothyroid patients. However, a greater proportion, 47 of 124 (37.90 %), black African patients with hypothyroidism had a normal lipid profile. Conclusion: Dyslipidemia is less common in black African patients with hypothyroidism. This is probably due to this population group being in an earlier stage of epidemiologic transition. Those with hypothyroidism were at greater overall cardiovascular risk based on TC/HDL-C ratio but did not reach high risk atherogenic profiles reported in previous studies.

Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial.

BACKGROUND: The ketogenic diet (KD) has been shown to result in body mass loss in people with disease as well as healthy people, yet the effect of the KD on thyroid function and metabolism are unknown. OBJECTIVE: We aimed to determine the effects of a KD, compared with an isocaloric high-carbohydrate low-fat (HCLF) diet, on resting metabolic rate and thyroid function in healthy individuals. DESIGN: Eleven healthy, normal-weight participants (mean(SD) age: 30(9) years) completed this randomized crossover-controlled study. For a minimum of three weeks on each, participants followed two isocaloric diets: a HCLF diet (55%carbohydrate, 20%fat, 25%protein) and a KD (15%carbohydrate, 60%fat, 25% protein), with a one-week washout period in-between. Importantly, while on the KD, the participants were required to remain in a state of nutritional ketosis for three consecutive weeks. Crossover analyses and linear mixed models were used to assess effect of diet on body mass, thyroid function and resting metabolic rate. RESULTS: Both dietary interventions resulted in significant body mass loss (p<0.05) however three weeks of sustained ketosis (KD) resulted in a greater loss of body mass (mean (95%CI): -2.9 (-3.5, -2.4) kg) than did three weeks on the HCLF diet (-0.4 (-1.0, 0.1) kg, p < 0.0001). Compared to pre-diet levels, the change in plasma T3 concentration was significantly different between the two diets (p = 0.003), such that plasma T3 concentration was significantly lower following the KD diet (4.1 (3.8, 4.4) pmol/L, p<0.0001) but not different following the HCLF diet (4.8 (4.5, 5.2) pmol/L, p = 0.171. There was a significant increase in T4 concentration from pre-diet levels following the KD diet (19.3 (17.8, 20.9) pmol/L, p < 0.0001), but not following the HCLF diet (17.3 (15.7, 18.8) pmol.L, p = 0.28). The magnitude of change in plasma T4 concentration was not different between the two diets (p = 0.4). There was no effect of diet on plasma thyroid stimulating hormone concentration (p = 0.27). There was a significantly greater T3:T4 ratio following the HCLF diet (0.41 (0.27, 0.55), p < 0.0001) compared to pre-diet levels but not following the KD diet (0.25 (0.12, 0.39), p = 0.80). CONCLUSIONS: Although the diets were isocaloric and physical activity and resting metabolic rate remained constant, the participants lost more mass after the KD than after the HCLF diet. The observed significant changes in triiodothyronine concentration suggest that unknown metabolic changes occur in nutritional ketosis, changes that warrant further investigation. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR201707002406306 URL: https://pactr.samrc.ac.za/.

Relationship between amino acid ratios and decline in estimated glomerular filtration rate in diabetic and non-diabetic patients in South Africa.

BACKGROUND: Diabetic kidney disease is a major complication resulting from type 1 and type 2 diabetes. Currently, the microalbuminuria test is used to monitor renal function; however, it does not detect albumin until progressive loss of renal function has occurred. OBJECTIVE: This study analysed the relationship between changes in amino acid ratios and estimated glomerular filtration rate (eGFR) decline in diabetic and non-diabetic patients. METHODS: Urine samples were collected from participants between February 2019 to April 2019 and analysed from November 2020 to January 2021. Diabetic (glycated haemoglobin > 6.4%) and non-diabetic patients (glycated haemoglobin ≤ 6.4%) from Chris Hani Baragwanath Hospital, South Africa, were further categorised based on the degree of renal function predicted by the eGFRs. Amino acids were quantified using tandem mass spectrometry to determine the concentrations and ratios of tyrosine/phenylalanine, ornithine/arginine, arginine/citrulline and citrulline/ornithine at different stages of the chronic kidney disease. RESULTS: Among diabetic patients, the tyrosine/phenylalanine ratio showed a statistically significant increase (p = 0.04) as the eGFR declined from stage 1 to stage 4; the ornithine/arginine ratio showed a strong negative correlation with eGFR. The citrulline/ornithine ratio differed between the diabetic and non-diabetic patients in stage 1 of chronic kidney disease. CONCLUSION: Amino acid ratios (ornithine/arginine and tyrosine/phenylalanine) are affected by the progression of diabetes and can be correlated to renal function. The citrulline/ornithine ratios differ between the studied groups in stage 1 of the disease and may be utilised to predict the onset of chronic kidney disease.

Zinc transporter 8 (ZnT8) autoantibody prevalence in black South African participants with type 1 diabetes.

BACKGROUND: Autoantibodies to ß-cell specific antigens are markers of type 1 diabetes. The most recently identified autoantibodies are targeted to the zinc transporter 8 (ZnT8) protein located in the membrane of ß-cell insulin secretory granules. The prevalence of ZnT8 autoantibodies in newly diagnosed participants with type 1 diabetes has been found to range from 33 to 80 %. Due to the lack of data on the immunological aetiology of type 1 diabetes in African populations, this study aimed to determine the prevalence of ZnT8 autoantibodies in black South Africans with type 1 diabetes and whether ZnT8 autoantibody positivity was associated with age at diagnosis and disease duration. METHODS: Participants with type 1 diabetes and controls were recruited from the greater Johannesburg area, South Africa. Positivity for ZnT8, GAD65 and IA2 autoantibodies was determined by ELISA. RESULTS: Participants with type 1 diabetes (n = 183) and controls (n = 49) were matched for age (29.1 ± 9.53 vs. 27.3 ± 7.29, respectively; p = 0.248). The mean age at diagnosis for participants with type 1 diabetes was 20.8 ± 8.46 years. The prevalence of ZnT8 autoantibody positivity was 17.5 % (32 of 183) in participants with type 1 diabetes with a median disease duration of 7.00 [2.00; 11.0] years. ZnT8 autoantibody prevalence in newly diagnosed participants (< 1 year duration) was 27.3 % (6 of 22). Logistic regression analysis found an association between ZnT8 autoantibody positivity and shorter disease duration (OR: 0.9 (0.81-1.00); p = 0.042). In addition, ZnT8 autoantibody positivity was significantly associated with an increased chance of being GAD65 (OR: 3.37 (1.10-10.3)) and IA2 (OR: 8.63 (2.82-26.4)) autoantibody positive. Multiple regression analysis found no association between ZnT8 autoantibody positivity and age at diagnosis. However, the presence of ≥ 2 autoantibodies was associated with a younger age at diagnosis of type 1 diabetes when compared to participants with ≤ 1 autoantibody (B = -5.270; p = 0.002). CONCLUSIONS: The presence of ZnT8 autoantibodies was not related to a younger age at diagnosis in black South African patients with type 1 diabetes. However, the greater the numbers of autoantibodies present in an individual the earlier the age at diagnosis. ZnT8 autoantibodies decline with disease duration in the black South African population.

Management of patients with diabetes and obesity in the COVID-19 era: Experiences and learnings from South and East Europe, the Middle East, and Africa.

The COVID-19 pandemic has had a major effect on healthcare during 2020. Current evidence suggests that, while individuals with diabetes and obesity are no more prone to SARS-CoV-2 infection than those without, the risk of hospitalisation if someone has diabetes or obesity and then contracts COVID-19 is three times higher - and 4.5 times higher if they have diabetes and obesity. We assembled a panel of experts from South and East Europe, the Middle East, and Africa to discuss the challenges to management of diabetes and obesity during and post the COVID-19 pandemic. The experience and learnings of this panel cover a heterogeneous patient population, wide range of clinical settings, healthcare organisations, disease management strategies, and social factors. We discuss the importance of timely and effective disease management via telemedicine, providing reassurance and guidance for patients unable or unwilling to visit healthcare settings at this time. We address the use of novel therapies and their role in managing diabetes and obesity during the pandemic, as well as the importance of controlling hypoglycaemia and preventing cardiovascular complications, particularly in vulnerable people. Finally, we consider post-COVID-19 management of diabetes and obesity, and how these learnings and experiences should impact upon future clinical guidelines.

A retrospective study correlating sonographic features of thyroid nodules with fine-needle aspiration cytology in a South African setting.

BACKGROUND: Thyroid nodules are prevalent worldwide. Detection rates are increasing because of the use of ultrasonography. Ultrasound has become the first-choice imaging modality in evaluating nodules. The decision to perform an US-guided fine-needle aspiration (FNA) is based on a nodule's sonographic features. Thus, it is essential to accurately risk stratify thyroid nodules so that they are appropriately referred for FNA. OBJECTIVES: The aim of this study was to correlate the ultrasound imaging features of thyroid nodules with FNA cytology and surgical histopathology results, and to risk stratify patients using the American Thyroid Association (ATA) classification for each imaging characteristic with the likelihood of the nodule being malignant. METHOD: Retrospective analysis of a thyroid ultrasound database at Chris Hani Baragwanath Academic Hospital, over the period 2015-2017. Frequencies and percentages were used to summarise the data. Univariate logistic regression analyses were used to assess the accuracy of sonographic features in predicting the histologically determined diagnosis for thyroid tumours. RESULTS: A total of 113 nodules underwent FNA, of which 104 were diagnostic. The best three ultrasound features that pose a higher risk for malignancy are absent halo, presence of microcalcifications and hypoechoic appearance. No single nodule feature is an absolute indicator for malignancy. There is a high agreement between ATA classification and cytopathology or histology when nodule features are grouped into clusters. Agreement between the ATA classification and cytopathology/histology was 86.7% with a kappa of 0.714. The agreement between the cytopathology FNA results and lobectomy histopathology was 98.8% with a kappa of 0.973. CONCLUSION: This study contributes to the paucity of data available for sub-Saharan Africa and provides reassurance that our results are consistent with international studies. The study confirms that the usage of a thyroid nodule classification system improves characterisation and increases accuracy in detecting thyroid malignancies, thus sparing many patients the morbidity of unnecessary thyroid surgery.

Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction.

The pituitary hormone, thyrotropin (TSH), is regarded as the primary biomarker for evaluating thyroid function and is useful in guiding treatment with levothyroxine for patients with hypothyroidism. The amplified response of TSH to slight changes in thyroid hormone levels provides a large and easily measured signal in the routine care setting. Laboratories provide reference ranges with upper and lower cutoffs for TSH to define normal thyroid function. The upper limit of the range, used to diagnose subclinical (mild) hypothyroidism, is itself a matter for debate, with authoritative guidelines recommending treatment to within the lower half of the range. Concomitant diseases, medications, supplements, age, gender, ethnicity, iodine status, time of day, time of year, autoantibodies, heterophilic antibodies, smoking, and other factors influence the level of TSH, or the performance of current TSH assays. The long-term prognostic implications of small deviations of TSH from the reference range are unclear. Correction of TSH to within the reference range does not always bring thyroid and other biomarkers into range and will not always resolve the patient's symptoms. Overt hypothyroidism requires intervention with levothyroxine. It remains important that physicians managing a patient with symptoms suggestive of thyroid disease consider all of the patient's relevant disease, lifestyle, and other factors before intervening on the basis of a marginally raised TSH level alone. Finally, these limitations of TSH testing mitigate against screening the population for the undoubtedly substantial prevalence of undiagnosed thyroid disease, until appropriately designed randomised trials have quantified the benefits and harms from this approach.

The effect of HIV infection on glycaemia and renal function in type 2 diabetic patients.

BACKGROUND: Infection with, and treatment of HIV is associated with effects on glycaemia and renal function. The purpose of this study was therefore to compare glycaemic control and albuminuria in HIV-positive and HIV-negative type 2 diabetic patients. MATERIALS AND METHODS: Diabetic patients with and without HIV infection were recruited from a diabetic clinic at Chris Hani Baragwanath Hospital in Soweto, South Africa. Data was collected on weight, height, HbA1c, fasting glucose, urine albumin:creatinine ratio, HIV status, CD4 counts, viral load and concomitant therapies. Multivariable regression analysis was used to isolate the determinants of fasting glucose and HbA1c levels and risk factors for albuminuria. RESULTS: Data were collected from 106 HIV-positive and 214 HIV-negative diabetics. All HIV infected subjects were receiving anti-retroviral therapy. The determinants of fasting glucose levels (log) were HIV infection (ß = 0.04, p = 0.01) and use of anti-hypertensive agents (ß = 0.07, p = 0.0006), whilst for HbA1c levels (log) they were HIV infection (ß = -0.03, p = 0.03), BMI (ß = 0.004, p = 0.0005), statin use (ß = 0.04, p = 0.002) and glucose levels (ß = 0.01, p<0.0005). In HIV-positive subjects, CD4 counts were negatively associated with glucose levels (ß = -0.0002, p = 0.03). The risk factors for albuminuria were (odds ratio [95% CIs]) dyslipidaemia (1.94 [1.09, 3.44], p = 0.02) and HbA1c levels (1.24 [1.12, 1.38], p<0.0001). DISCUSSION: These data suggest that glycaemic control is worse in type 2 diabetic subjects with HIV infection and that HbA1c underestimates glycaemia in these patients. Albuminuria was not associated with HIV-positivity. The negative relationship of CD4 counts with glucose levels may reflect viral removal and easing of the associated inflammatory response. It is possible that the association of statin and anti-hypertensive therapies with high HbA1c and glucose levels, respectively, is due to such therapies being given largely to subjects with poor glycaemic control.

Hypoparathyroidism Causing Seizures: When Epilepsy Does Not Fit.

A 24-year-old man presented to the Chris Hani Baragwanath Academic Hospital emergency department with recurrent seizures having previously been diagnosed with epilepsy from age 14. The biochemical investigations and brain imaging were suggestive of seizures secondary to hypocalcemia, and a diagnosis of idiopathic hypoparathyroidism was confirmed. After calcium and vitamin D replacement, the patient recovered well and is seizure free, and off antiepileptic therapy. This case highlights the occurrence of brain calcinosis in idiopathic hypoparathyroidism; the occurrence of acute symptomatic seizures due to provoking factors other than epilepsy; and the importance, in the correct clinical setting, of considering alternative, and sometimes treatable, causes of seizures other than epilepsy.

Implementation of POCT in the diabetic clinic in a large hospital.

AIM: Point-of-care testing (POCT) is gaining renewed interest, especially in resource-limiting primary health care, due to rise in prevalence of communicable and non-communicable diseases hence POCT needscontinuous appraisal. METHODS: Random glucose and glycated haemoglobin (HbA1c) were measured in 104 diabetic patients using standard laboratory multichannel analyzer 917. The utility of venous blood compared to capillary blood in measuring HbA1c was evaluated in a subset of 20 patients using a POCT device, DCA Vantage. Lastly, the POCT was validated against the laboratory multichannel analyser 917, in measurement of HbA1c in a second subset of 46 patients. RESULTS: Random blood glucose levels and HbA1c levels moderately correlated (r2 = 0.56; p < 0.0001). Random glucose tests showed that 41% of the patients had poor glycaemic control while HbA1c showed 74%. Venous and capillary blood in HbA1c showed strong correlation (r2 = 0.89440; p < 0.001. There was also strong correlation (r = 0.9802; p < 0.0001) in HbA1c measured using the DCA Vantage and the standard laboratory analyser, Multichannel Analyser 917. CONCLUSION: Venous or capillary blood can be used in POCT for HbA1c. POCT is ideal for monitoring glucose control and management of diabetes in resource-limited countries such as South Africa.