How to provide a structured clinical assessment of a patient with overweight or obesity.

With the increasing prevalence of overweight and obesity worldwide, there is a reciprocal increase in the global economic burden and ill-health from obesity-related chronic diseases. Primary healthcare services have a role to play in ensuring early detection of weight issues and in directing patients towards evidence-based care to slow this progression. Research shows that many people with obesity are motivated to lose weight and want their clinician to initiate a conversation about weight management and treatment options. However, this conversation rarely occurs and there is a significant delay in treatment, resulting in an increased burden on the individual, healthcare system and society. In this paper, the components and rationale for the clinical assessment of adult patients with overweight or obesity, including anthropometric measurements and pathology tests, are described. Recommendations to ascertain the potential factors influencing the development of obesity in the patient, such as lifestyle factors (diet and physical activity) and mental health, are also provided. The potential sequelae of obesity that may be present and the necessary assessments for diagnosis are also addressed. These assessments are vital to ensure the patient is referred to the appropriate allied health services and/or specialists.

Effect of a low glycaemic index diet in gestational diabetes mellitus on post-natal outcomes after 3 months of birth: a pilot follow-up study.

A low glycaemic index (LGI) diet during pregnancy complicated by gestational diabetes mellitus (GDM) may offer benefits to the mother and infant pair beyond those during pregnancy. We aimed to investigate the effect of an LGI diet during pregnancy complicated with GDM on early post-natal outcomes. Fifty-eight women (age: 23-41 years; mean ± SD pre-pregnancy body mass index: 24.5 ± 5.6 kg m(-2) ) who had GDM and followed either an LGI diet (n = 33) or a conventional high-fibre diet (HF; n = 25) during pregnancy had a 75-g oral glucose tolerance test and blood lipid tests at 3 months post-partum. Anthropometric assessments were conducted for 55 mother-infant pairs. The glycaemic index of the antenatal diets differed modestly (mean ± SD: 46.8 ± 5.4 vs. 52.4 ± 4.4; P < 0.001), but there were no significant differences in any of the post-natal outcomes. In conclusion, an LGI diet during pregnancy complicated by GDM has outcomes similar to those of a conventional healthy diet. Adequately powered studies should explore the potential beneficial effects of LGI diet on risk factors for chronic disease.

The efficacy of bariatric surgery performed in the public sector for obese patients with comorbid conditions.

OBJECTIVE: To determine the efficacy of bariatric surgery in the public sector for the treatment of complicated obesity. DESIGN, SETTING AND PARTICIPANTS: A longitudinal observational study of obese participants with comorbid conditions, aged 21-73 years, who underwent publicly funded bariatric surgery. Data were extracted from clinical databases (1 October 2009 to 1 September 2013) and recorded at seven time points. Participants are from an ongoing public obesity program. MAIN OUTCOME MEASURES: Postoperative weight loss and partial or full resolution of: type 2 diabetes mellitus (T2DM), hypertension (HTN), dyslipidaemia and obstructive sleep apnoea (OSA). RESULTS: The 65 participants in the cohort lost a mean weight of 22.6 kg (SD, 9.5 kg) by 3 months, 34.2.kg (SD, 20.1 kg) by 12 months and 39.9 kg (SD, 31.4 kg) by 24 months (P < 0.001). Body mass index (BMI) decreased from a preoperative mean of 48.2 kg/m(2) (SD, 9.5 kg/m(2)) to 35.7 kg/m(2) (SD, 7.7 kg/m(2)) by 24 months (P < 0.001). Full resolution of comorbid conditions by 18 months (P < 0.001) was achieved by almost half of those with baseline T2DM, nearly two-thirds with HTN and three-quarters of those with OSA, with continued improvements beyond 24 months. CONCLUSIONS: Bariatric surgery performed in the public sector is efficacious in the treatment of obese patients with comorbid conditions. Our findings parallel similar studies suggesting that there is equal benefit in publicly funded and privately performed procedures. This study highlights that obese patients reliant on public health care maintain sufficient intrinsic motivation in the absence of payment and supposed value-driven incentive. Improved access to bariatric surgery in the public sector can justifiably reduce the health inequities for those most in need.

Cost-effectiveness analysis of recruitment strategies in a large diabetes prevention trial conducted across two sites in Sydney, Australia.

BACKGROUND: Diabetes prevention trials require large samples and community-based recruitment, which can be protracted and expensive. We analysed the cost-effectiveness of recruitment strategies used in a randomised placebo-controlled supplement trial in adults with prediabetes and overweight or obesity conducted in Sydney, Australia. METHODS: Recruitment strategies included advertising through local radio stations and newspapers, television news coverage, online advertising and editorials, advertising in and referral from primary care settings, university- and hospital-based advertising, and attending or hosting local events. For each strategy, the number of expressions of interest, screenings booked, and randomised participants were collated. The percentage contribution from each strategy, overall cost, and cost per participant were calculated. RESULTS: Of 4498 expressions of interest, 551 (12%) were eligible for onsite screening and 401 (9%) were randomised. Recruitment costs totalled AU$218,501, averaging AU$545 per participant. The recruitment strategy was recorded for 49% who expressed interest in the trial, and for 75% randomised into the trial. From these data, advertising on local radio stations was the most cost-effective strategy, contributing 46% of participants at AU$286 per participant, then advertising in and referral from primary care settings (57 participants [19%], AU$1438 per participant). The least cost-effective strategy was television news coverage, which was not targeted to the Sydney-based audience, contributing only six participants (AU$10,000 per participant). CONCLUSION: Radio advertising and recruitment through healthcare were the most effective recruitment strategies in this trial. Recruitment strategies should be location-specific and appropriate for the target population, prioritising low-effort high-yield strategies. Trial investigators should seek opportunities for free advertising.

Intensive Lifestyle Intervention for Remission of Early Type 2 Diabetes in Primary Care in Australia: DiRECT-Aus.

OBJECTIVE: We aimed to assess whether remission of type 2 diabetes (T2D) could be achieved with a low-energy total diet replacement (TDR) in an Australian primary care setting. RESEARCH DESIGN AND METHODS: Individuals aged 20-65 years with T2D duration up to 6 years, BMI >27.0 kg/m2, and not treated with insulin were prescribed a 13-week low-energy TDR (Optifast; Nestlé Health Science) followed by 8-week structured food reintroduction and 31-week supported weight maintenance. The primary outcome was T2D remission at 12 months. RESULTS: A total of 155 participants comprised the intention-to-treat population. At 12 months, T2D remission was achieved in 86 (56%) participants, with a mean adjusted weight loss of 8.1% (95% CI 7.2-9.1). Two serious adverse events requiring hospitalization related to the study intervention were reported. CONCLUSIONS: At 12 months T2D remission was achieved for one in two Australian adults in a primary care setting.

Corrigendum: Kidney disease in adults with Prader-Willi syndrome: international cohort study and systematic literature review.

[This corrects the article DOI: 10.3389/fendo.2023.1168648.].

Changes in Prediabetes Status Among Adults During a 6-Month Randomized Placebo-controlled Supplement Trial With Nutrition and Lifestyle Counselling and 6-Month Follow-up.

OBJECTIVES: In this work, we present an exploratory within-trial analysis of the changing prevalence of prediabetes in response to nutrition and lifestyle counselling provided as part of a randomized placebo-controlled supplement trial with follow-up. We aimed to identify factors associated with changing glycemia status. METHODS: Participants (n=401) in this clinical trial were adults with a body mass index (BMI) of ≥25 kg/m2 and prediabetes (defined by the American Diabetes Association as a fasting plasma glucose [FPG] of 5.6 to 6.9 mmol/L or a glycated hemoglobin [A1C] of 5.7% to 6.4%) within 6 months before trial entry. The trial consisted of a 6-month randomized intervention with 2 dietary supplements and/or placebo. At the same time, all participants received nutrition and lifestyle counselling. This was followed by a 6-month follow-up. Glycemia status was assessed at baseline and at 6 and 12 months. RESULTS: At baseline, 226 participants (56%) met a threshold for prediabetes, including 167 (42%) with elevated FPG and 155 (39%) with elevated A1C. After the 6-month intervention, the prevalence of prediabetes decreased to 46%, driven by a reduction in prevalence of elevated FPG to 29%. The prevalence of prediabetes then increased to 51% after follow-up. Risk of prediabetes was associated with older age (odds ratio [OR], 1.05; p<0.01), BMI (OR, 1.06; p<0.05), and male sex (OR, 1.81; p=0.01). Participants who reverted to normoglycemia had greater weight loss and lower baseline glycemia. CONCLUSIONS: Glycemia status can fluctuate over time and improvements can be gained from lifestyle interventions, with certain factors associated with a higher likelihood of reverting to normoglycemia.

Kidney disease in adults with Prader-Willi syndrome: international cohort study and systematic literature review.

Background: Prader-Willi syndrome (PWS) is a rare, complex, genetic disorder characterized by hyperphagia, hypotonia, delayed psychomotor development, low muscle mass and hypothalamic dysfunction. Adults with PWS often have obesity, hypertension and type 2 diabetes mellitus (DM2), known risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Early symptoms of CVD and CKD may be masked by intellectual disability and inability to express physical complaints. Furthermore, kidney diseases are often asymptomatic. Therefore, renal and cardiovascular disease might be missed in patients with PWS. Microalbuminuria is an early sign of microvascular damage in the kidneys and other vascular beds. Therefore, we screened our adult PWS cohort for the presence of elevated urinary albumin and (micro)albuminuria. Methods: We retrospectively collected anthropometric measurements, blood pressure, medical history, medication use, urine dipstick and biochemical measurements form electronic patient files. In addition, we performed a systematic literature review on kidney disease in PWS. Results: We included 162 adults with genetically confirmed PWS (56% male, median age 28 years), of whom 44 (27%) had DM2. None had known CVD. All subjects had normal estimated glomerular filtration rate (eGFR) according to non-PWS reference intervals. Elevated urinary albumin or (micro)albuminuria was present in 28 (18%); 19 out of 75 (25%) had an increased urinary albumin-to-creatinine ratio (UACR) and 10 out of 57 (18%) had an increased urinary protein-to-creatinine ratio. Elevated urinary albumin was present at a young age (median age 26 (IQR 24-32) years) and was associated with an significantly higher BMI and LDL-cholesterol levels and higher prevalence of DM2, hypertension and dyslipidemia than those with normal UACR (p=0.027, p=0.019, p<0.001, p<0.001, p=0.011 and respectively). Conclusion: Upon screening, one in every five adults with PWS had increased urinary albumin or (micro)albuminuria, early signs of microvascular disease. All had normal eGFR, according to non-PWS reference intervals, and none had a formal diagnosis of CVD. As muscle mass is low in PWS, creatinine levels and eGFR may be spuriously normal. Urinalysis in this patient group can be used as a screening tool for microvascular (kidney) disease. We propose an algorithm for the detection and management of microvascular disease in adults with PWS.

The Australian Obesity Management Algorithm: A simple tool to guide the management of obesity in primary care.

Obesity is a complex and multifactorial chronic disease with genetic, environmental, physiological and behavioural determinants that requires long-term care. Obesity is associated with a broad range of complications including type 2 diabetes, cardiovascular disease, dyslipidaemia, metabolic associated fatty liver disease, reproductive hormonal abnormalities, sleep apnoea, depression, osteoarthritis and certain cancers. An algorithm has been developed (with PubMed and Medline searched for all relevant articles from 1 Jan 2000-1 Oct 2021) to (i) assist primary care physicians in treatment decisions for non-pregnant adults with obesity, and (ii) provide a practical clinical tool to guide the implementation of existing guidelines (summarised in Appendix 1) for the treatment of obesity in the Australian primary care setting. MAIN RECOMMENDATIONS AND CHANGES IN MANAGEMENT: Treatment pathways should be determined by a person's anthropometry (body mass index (BMI) and waist circumference (WC)) and the presence and severity of obesity-related complications. A target of 10-15% weight loss is recommended for people with BMI 30-40 kg/m2 or abdominal obesity (WC > 88 cm in females, WC > 102 cm in males) without complications. The treatment focus should be supervised lifestyle interventions that may include a reduced or low energy diet, very low energy diet (VLED) or pharmacotherapy. For people with BMI 30-40 kg/m2 or abdominal obesity and complications, or those with BMI > 40 kg/m2 a weight loss target of 10-15% body weight is recommended, and management should include intensive interventions such as VLED, pharmacotherapy or bariatric surgery, which may be required in combination. A weight loss target of > 15% is recommended for those with BMI > 40 kg/m2 and complications and they should be referred to specialist care. Their treatment should include a VLED with or without pharmacotherapy and bariatric surgery.

Effect of severe compared with moderate energy restriction on physical activity among postmenopausal female adults with obesity: a prespecified secondary analysis of the Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity (TEMPO) Diet randomized controlled Trial.

BACKGROUND: An under-explored strategy for increasing physical activity is the dietary treatment of obesity, but empirical evidence is lacking. OBJECTIVES: We aimed to compare the effects of weight loss via severe as opposed to moderate energy restriction on physical activity over 36 mo. METHODS: A total of 101 postmenopausal female adults (45-65 y, BMI 30-40 kg/m2, <180 min/wk of structured exercise) were randomly assigned to either 12 mo of moderate energy restriction (25%-35% of energy requirement) with a food-based diet, or a severe intervention involving 4 mo of severe energy restriction (65%-75% of energy requirement) with a total meal replacement diet, followed by 8 mo of moderate energy restriction. Physical activity was encouraged, but no tailored or supervised exercise prescription was provided. Physical activity was assessed with an accelerometer worn for 7 d before baseline (0 mo) and 0.25, 1, 4, 6, 12, 24, and 36 mo after intervention commencement. RESULTS: Compared with the moderate group, the severe group exhibited greater mean: total volume of physical activity; duration of moderate-to-vigorous-intensity physical activity (MVPA); duration of light-intensity physical activity; step counts, as well as lower mean duration of sedentary time. All these differences (except step counts) were apparent at 6 mo [e.g., 1006 metabolic equivalent of task (MET)-min/wk; 95% CI: 564, 1449 MET-min/wk for total volume of physical activity], and some were also apparent at 4 and/or 12 mo. There were no differences between groups in the 2 other outcomes investigated (self-efficacy to regulate exercise; and proportion of participants meeting the WHO's 2020 Physical Activity Guidelines for MVPA). When the analyses were adjusted for weight at each time point, the differences between groups were either attenuated or abolished. CONCLUSIONS: Among female adults with obesity, including a dietary component to reduce excess body weight-notably one involving severe energy restriction-could potentially enhance the effectiveness of physical activity interventions.This trial was registered at www.anzctr.org.au as ACTRN12612000651886.

Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study.

CONTEXT: Prader-Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia, and hyperphagia. Hormone deficiencies such as hypogonadism, hypothyroidism, and growth hormone deficiency are common. The combination of hypotonia, low physical activity, and hypogonadism might lead to a decrease in bone mass and increase in fracture risk. Moreover, one would expect an increased risk of scoliosis due to hypotonia and low physical activity. OBJECTIVE: To study the prevalence and risk factors for skeletal problems (reduced bone mineral density, fractures, and scoliosis) in adults with PWS. METHODS: We retrospectively collected patient characteristics, medical history, medication, biochemical measurements, dual-energy X-ray absorptiometry scans, and spinal X-rays and reviewed the current literature. RESULTS: We included 354 adults with PWS (median age 31 years; 43% males), of whom 51 (14%) had osteoporosis (T-score below -2.5) and 143 (54%) had osteopenia (T-score -1 to -2.5). The most prevalent modifiable risk factors for osteoporosis were hypogonadism, insufficient dairy intake, sedentary lifestyle, and corticosteroid use. Male sex was associated with osteoporosis (P = .005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and nonvertebral fractures in 59 (17%). Scoliosis was present in 263 (80%), but no modifiable risk factors were identified. CONCLUSION: Besides scoliosis, osteoporosis is common in adults with PWS. Based on the literature and the risk factors for osteoporosis found in our cohort, we provide practical clinical recommendations to avoid skeletal complications in these vulnerable patients.

The Carbohydrate Threshold in Pregnancy and Gestational Diabetes: How Low Can We Go?

The original nutrition approach for the treatment of gestational diabetes mellitus (GDM) was to reduce total carbohydrate intake to 33-40% of total energy (EI) to decrease fetal overgrowth. Conversely, accumulating evidence suggests that higher carbohydrate intakes (60-70% EI, higher quality carbohydrates with low glycemic index/low added sugars) can control maternal glycemia. The Institute of Medicine (IOM) recommends ≥175 g/d of carbohydrate intake during pregnancy; however, many women are consuming lower carbohydrate (LC) diets (<175 g/d of carbohydrate or <40% of EI) within pregnancy and the periconceptual period aiming to improve glycemic control and pregnancy outcomes. This report systematically evaluates recent data (2018-2020) to identify the LC threshold in pregnancy in relation to safety considerations. Evidence from 11 reports suggests an optimal carbohydrate range of 47-70% EI supports normal fetal growth; higher than the conventionally recognized LC threshold. However, inadequate total maternal EI, which independently slows fetal growth was a frequent confounder across studies. Effects of a carbohydrate intake <175 g/d on maternal ketonemia and plasma triglyceride/free fatty acid concentrations remain unclear. A recent randomized controlled trial (RCT) suggests a higher risk for micronutrient deficiency with carbohydrate intake ≤165 g/d in GDM. Well-controlled prospective RCTs comparing LC (<165 g/d) and higher carbohydrate energy-balanced diets in pregnant women are clearly overdue.

Hyponatremia in Children and Adults with Prader-Willi Syndrome: A Survey Involving Seven Countries.

In Prader-Willi syndrome (PWS), conditions that are associated with hyponatremia are common, such as excessive fluid intake (EFI), desmopressin use and syndrome of inappropriate antidiuretic hormone (SIADH) caused by psychotropic medication. However, the prevalence of hyponatremia in PWS has rarely been reported. Our aim was to describe the prevalence and severity of hyponatremia in PWS. In October 2020, we performed a retrospective study based on the medical records of a large cohort of children and adults with PWS from seven countries. Among 1326 patients (68% adults), 34 (2.6%) had at least one episode of mild or moderate hyponatremia (125 ≤ Na < 135 mmol/L). The causes of non-severe hyponatremia were often multi-factorial, including psychotropic medication in 32%, EFI in 24% and hyperglycemia in 12%. No obvious cause was found in 29%. Seven (0.5%) adults experienced severe hyponatremia (Na < 125 mmol/L). Among these, five recovered completely, but two died. The causes of severe hyponatremia were desmopressin treatment for nocturnal enuresis (n = 2), EFI (n = 2), adrenal insufficiency (n = 1), diuretic treatment (n = 1) and unknown (n = 1). In conclusion, severe hyponatremia was very rare but potentially fatal in PWS. Desmopressin treatment for nocturnal enuresis should be avoided. Enquiring about EFI and monitoring serum sodium should be included in the routine follow-ups of patients with PWS.

Hypogonadism in Adult Males with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion.

Prader-Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.

Hypogonadism in Women with Prader-Willi Syndrome-Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion.

Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.

Attitudes and Approaches to Use of Meal Replacement Products among Healthcare Professionals in Management of Excess Weight.

Meal replacement product-based diets are an effective weight loss intervention used in the management of obesity. Historically, these diets have been underutilised by HealthCare Professionals (HCPs). An online survey of mixed methods design was distributed to HCPs to capture current perceptions and prescribing patterns of meal replacement products (MRPs) in the management of overweight and obesity. A total of 303 HCPs working in weight management across Australia began the survey and 197 (65%) completed it. While over 70% of HCPs have prescribed MRP currently or in the past, MRPs are only prescribed to a median 7% of patients seeking weight management treatment. Qualitative analysis identified potential barriers to MRP prescription, which include experience with patient non-compliance, perceived poor long-term weight loss durability and safety concerns regarding the product and its use as a total meal replacement program. Safety concerns are centred on the perceived risk of weight cycling and its potential negative psychological impact. MRP prescription is 66% more likely to occur if HCPs had formal training in the use of MRPs relative to those who did not, with a relative risk (RR) of 1.7 (95% CI 1.4, 2.0). This study highlights the potential barriers to the prescription of MRPs, which are centred around safety concerns. This also indicates that formal training may enhance the likelihood of prescribing MRPs, suggesting that once HCPs have a comprehensive understanding of the products and the evidence behind their use, their prescription is likely to be increased.

Hypoglycemia in cystic fibrosis during an extended oral glucose tolerance test.

BACKGROUND: Hypoglycemia in cystic fibrosis (CF), in the absence of glucose-lowering therapies, has long been identified as an important issue in the management of CF. There is currently still no unifying hypothesis for its etiology. AIM: The aims of this study were to perform a 3-h oral glucose tolerance test (OGTT) in participants with CF and (1) document glucose, insulin, glucagon, glucagon-like-peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) release patterns within varying glucose tolerance groups during the OGTT; (2) determine the prevalence of hypoglycemic during the OGTT; and (3) define any association between hypoglycemia and patterns of insulin, glucagon, GLP-1, and GIP release. METHODS: Eligible participants attending an adult CF clinic completed a 3-h OGTT. Hypoglycemia on OGTT was defined as mild (glucose 3.4-3.9 mmol/L), moderate (glucose 3.1-3.3 mmol/L), and severe (glucose ≤ 3 mmol/L). Hormones were measured at fasting, 30, 60, 120, and 180 min. RESULTS: Twenty-four participants completed the study, of which 7 had normal glucose tolerance, 12 had abnormal glucose tolerance, and 5 had cystic fibrosis related diabetes (CFRD). All participants had a delayed insulin response compared with normative data. All glucose tolerance groups showed appropriate and similar suppression of fasting glucagon. Four participants (17%) had mild hypoglycemic, three (13%) had moderate hypoglycemic, and eight (33%) had severe hypoglycemic. No participant with CFRD demonstrated hypoglycemic. Of the 19 participants without CFRD, 15 (79%) experienced hypoglycemic. Participants with hypoglycemic had greater peak glucose and insulin responses than those that did not have hypoglycemic, and this approached significance (p = .0625 for glucose and p = .0862 for insulin). No significant mean differences between GLP-1 and GIP release were found. There was no relationship between hypoglycemic and modulator therapy. CONCLUSION: Postprandial hypoglycemic was unmasked by the extension of an OGTT to 3 h. Delayed and abnormal insulin release, and ineffective counter-regulatory action of glucagon may have a role in its etiology.

Urine dipsticks are not accurate for detecting mild ketosis during a severely energy restricted diet.

BACKGROUND: Detection of the mild ketosis induced by severely energy-restricted diets may be a clinically useful way to monitor and promote dietary adherence. Mild ketosis is often assessed using urine dipsticks, but accuracy for this purpose has not been tested. OBJECTIVE: To determine the accuracy of urine dipsticks to detect mild ketosis during adherence to a severely energy-restricted diet. METHODS: Two hundred and sixty three (263) fasting urine and 263 fasting blood samples were taken from 50 women (mean [standard deviation, SD] age 58.0 [4.3] years and body mass index 34.3 [2.4] kg/m2) before and at six time points during or for up to 10 weeks after 16 weeks of severe energy restriction, achieved with a total meal replacement diet. The amount of ketones (acetoacetate) in the urine was classified as '0 (Negative)', '+/- (Trace)', '+ (Weak)' or '++ (Medium)' by urine dipsticks (Ketostix, Bayer). The concentration of ketones (ß-hydroxybutyrate) in the blood was measured with our reference method, a portable ketone monitor (FreeStyle Optium, Abbott). The diagnostic accuracy of the urine dipsticks was assessed from the percent of instances when a person was actually 'in ketosis' (as defined by a blood ß-hydroxybutyrate concentration at or above three different thresholds) that were also identified by the urine dipsticks as being from a person in ketosis (the percent 'true positives' or sensitivity), as well as the percent of instances when a person was not in ketosis (as defined by the blood monitor result) was correctly identified as such with the urine dipstick (the percent 'true negatives' or specificity). Thresholds of ≥0.3mM, ≥0.5mM or ≥1.0mM were selected, because mean blood concentrations of ß-hydroxybutyrate during ketogenic diets are approximately 0.5mM. Sensitivity and specificity were then used to generate receiver operating characteristic curves, with the area under these curves indicating the ability of the dipsticks to correctly identify people in ketosis (1 = perfect results, 0.5 = random results). RESULTS: At threshold blood ß-hydroxybutyrate concentrations of ≥0.3mM, ≥0.5mM and ≥1.0mM, the sensitivity of the urine dipsticks was 35%, 52% and 76%; the specificity was 100%, 97% and 78%; and the area under the receiver operating characteristic curves was 0.67, 0.74 and 0.77, respectively. These low levels of sensitivity mean that 65%, 48% or 24% of the instances when a person was in ketosis were not detected by the urine dipsticks. CONCLUSION: Urine dipsticks are not an accurate or clinically useful means of detecting mild ketosis in people undergoing a severely energy-restricted diet and should thus not be recommended in clinical treatment protocols. If monitoring of mild ketosis is indicated (eg, to monitor or help promote adherence to a severely energy-restricted diet), then blood monitors should be used instead.

Effects of α-Cyclodextrin on Cholesterol Control and Hydrolyzed Ginseng Extract on Glycemic Control in People With Prediabetes: A Randomized Clinical Trial.

Importance: Effective strategies for preventing type 2 diabetes are needed. Many people turn to complementary medicines, but there is little well-conducted scientific evidence to support their use. Objective: To assess the efficacy of α-cyclodextrin for cholesterol control and that of hydrolyzed ginseng for glycemic control in people with prediabetes and overweight or obesity. Design, Setting, and Participants: This 6-month double-blind, placebo-controlled, randomized clinical trial, with a 2 × 2 factorial design, was conducted between July 2015 and October 2018 at 2 locations in Sydney, Australia. Eligible participants were aged 18 years or older, had a body mass index (weight in kilograms divided by height in meters squared) of 25 or higher, and had prediabetes within 6 months of study entry according to the American Diabetes Association guidelines. Data analysis was performed from May to August 2019. Interventions: Participants were randomized to 1 of 4 groups to take active or placebo versions of each supplement (α-cyclodextrin plus hydrolyzed ginseng, α-cyclodextrin plus placebo, placebo plus hydrolyzed ginseng, or placebo plus placebo) for 6 months. All participants received dietetic advice for weight loss. Main Outcomes and Measures: The primary outcomes were the differences in total cholesterol and fasting plasma glucose between groups after 6 months. The primary analysis used the intention-to-treat principle. Multiple predetermined subsample analyses were conducted. Results: A total of 401 participants were eligible for the study (248 women [62%]; mean [SD] age, 53.5 [10.2] years; mean [SD] body mass index, 34.6 [6.2]). One hundred one patients were randomized to receive α-cyclodextrin plus hydrolyzed ginseng, 99 were randomized to receive α-cyclodextrin plus placebo, 101 were randomized to receive placebo plus hydrolyzed ginseng, and 100 were randomized to receive placebo plus placebo. For 200 participants taking α-cyclodextrin compared with 201 participants taking placebo, there was no difference in total cholesterol after 6 months (-1.5 mg/dL; 95% CI, -6.6 to 3.5 mg/dL; P = .51). For 202 participants taking hydrolyzed ginseng compared with 199 participants taking placebo, there was no difference in fasting plasma glucose after 6 months (0.0 mg/dL; 95% CI, -1.6 to 1.8 mg/dL; P = .95). Use of α-cyclodextrin was associated with constipation (16 participants vs 4 participants; P = .006) and cough (8 participants vs 1 participant; P = .02). Use of hydrolyzed ginseng was associated with rash and pruritus (13 participants vs 2 participants; P = .006). Only 37 of 401 participants (9.2%) experienced these adverse events. Conclusions and Relevance: Although they are safe for use, there was no benefit found for either α-cyclodextrin for cholesterol control or hydrolyzed ginseng for glycemic control in people with prediabetes and overweight or obesity. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614001302640.