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The investigators sought evidence-based criteria for identifying late-onset hypogonadism in men between the ages of 40 and 79 years on the basis of the association between symptoms and a low testosterone level. The data suggest that late-onset hypogonadism can be defined by the presence of at least three sexual symptoms with a total testosterone level of less than 11 nmol per liter and a free testosterone level of less than 220 pmol per liter. The data suggest that late-onset hypogonadism can be defined by the presence of at least three sexual symptoms with a total testosterone level of less than 11 nmol per liter and a free testosterone level of less than 220 pmol per liter. The clinical importance of an age-related reduction in the testosterone level 1 – 3 remains controversial. 4 , 5 Because of the uncertainty regarding the nature of testosterone deficiency in aging men, 6 – 9 recent guidelines have suggested that so-called late-onset hypogonadism be regarded as a clinical and biochemical state with advancing age, characterized by particular symptoms and a low level of serum testosterone. 10 , 11 However, few data on hypogonadism in aging men are available 4 , 8 , 12 because of the lack of evidence regarding the exact criteria for identifying testosterone deficiency in older men who do not have pathological hypogonadism. 6 , 13 Although a familiar array . . .

Prospective Study of C-Reactive Protein in Relation to the Development of Diabetes and Metabolic Syndrome in the Mexico City Diabetes Study Thang S. Han , MD, PHD 1 , Naveed Sattar , MD, PHD 2 , Ken Williams , MS 3 , Clicerio Gonzalez-Villalpando , MD 4 , Michael E.J. Lean , MD, FRCP 5 and Steven M. Haffner , MD, MPH 3 1 Addenbrooke’s Hospital, Cambridge University Medical School, Cambridge, U.K 2 University Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, U.K 3 Department of Medicine #7873, University of Texas Health Science Center at San Antonio, San Antonio, Texas 4 Center de Estudios in Diabetes, Mexico City, Mexico 5 Department of Human Nutrition, Glasgow Royal Infirmary, Glasgow, U.K Abstract OBJECTIVE —Recent evidence suggests that C-reactive protein (CRP) may predict development of diabetes in Caucasian populations. We evaluated CRP as a possible risk factor of the development of diabetes and metabolic syndrome in a 6-year study of 515 men and 729 women from the Mexico City Diabetes Study. RESEARCH DESIGN AND METHODS —Baseline CRP, indexes of adiposity, and insulin resistance (homeostasis model assessment [HOMA-IR]) were used to predict development of the metabolic syndrome, defined as including two or more of the following: 1 ) dyslipidemia (triglyceride ≥2.26 mmol/l or HDL cholesterol ≤0.91 mmol/l in men and ≤1.17 mmol/l in women; <35 and 40 mg/dl for men and women); 2 ) hypertension (blood pressure >140/90 mmHg or on hypertensive medication); or 3 ) diabetes (1999 World Health Organization criteria). RESULTS —At baseline, CRP correlated significantly ( P < 0.001) with all metabolic indexes in women, but less so in men. After 6 years, 14.2% of men and 16.0% of women developed the metabolic syndrome. Compared with tertile 1, women with CRP in the highest tertile had an increased relative risk of developing the metabolic syndrome by 4.0 (95% CI 2.0–7.9) and diabetes by 5.5 (2.2–13.5); these risks changed minimally after adjusting for BMI or HOMA-IR. The area under receiver-operating characteristic (ROC) curve for the prediction of the development of the syndrome was 0.684 for CRP, increasing to 0.706 when combined with BMI and to 0.710 for a complex model of CRP, BMI, and HOMA-IR. CONCLUSIONS —CRP was not a significant predictor of the development of the metabolic syndrome in men. Our data strongly support the notion that inflammation is important in the pathogenesis of diabetes and metabolic disorders in women. CRP, C-reactive protein HOMA-IR, homeostasis model assessment of insulin resistance ROC, receiver-operating characteristic Footnotes Address correspondence and reprint requests to Steven M. Haffner, Department of Medicine #7873, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. E-mail: haffner{at}uthscsa.edu . Received for publication 17 December 2001 and accepted in revised form 4 August 2002. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. DIABETES CARE

Key Words: obesity, type 2 diabetes, remission

To explore the factors (including knowledge and attitude) influencing the decision to follow a low-carbohydrate diet (LCD) or not in a sample of the UK population. An online questionnaire was distributed electronically to adults who had either followed LCD or not (February–December 2019). Demographics and self-reported “LCD-status” (current, past and non-follower) were collected. Multivariable linear regression was used with carbohydrate knowledge, dietary guideline agreement and theory of planned behaviour (TPB) constructs (all as predictors) to explain the intention to follow a LCD (outcome). Respondents (n = 723, 71% women, median age 34; 85% white-ethnicity) were either following (n = 170, 24%) or had tried a LCD in the preceding 3 months (n = 184, 25%). Current followers had lower carbohydrate knowledge scores (1–2 point difference, scale − 11 to 11) than past and non-followers. A majority of current LCD followers disagreed with the EatWell guide recommendations “Base meals on potatoes, bread, rice and pasta, or other starchy carbohydrates. Choose whole grains where possible” (84%) and “Choose unsaturated oils and spreads and eat in small amounts such as vegetable, rapeseed, olive and sunflower oils” (68%) compared to past (37%, 10%, respectively) and non-followers (16%, 8%, respectively). Weight-loss ranked first as a motivation, and the internet was the most influencial source of information about LCDs. Among LCD-followers, 71% reported ≥ 5% weight loss, and over 80% did not inform their doctor, nurse, or dietitian about following a diet. Approximately half of LCD followers incorporated supplements to their diets (10% used multivitamin/mineral supplements), despite the restrictive nature of the diet. TPB constructs, carbohydrate knowledge, and guideline agreement explained 60% of the variance for the intention to follow a LCD. Attitude (std-β = 0.60), perceived behavioural control (std-β = 0.24) and subjective norm (std-β = 0.14) were positively associated with the intention to follow a LCD, while higher knowledge of carbohydrate, and agreeing with national dietary guidelines were both inversely associated (std-β = − 0.09 and − 0.13). The strongest primary reason behind UK adults’ following a LCD is to lose weight, facilitated by attitude, perceived behavioural control and subjective norm. Higher knowledge about carbohydrate and agreement with dietary guidelines are found among people who do not follow LCDs.

Background Low-carbohydrate diets (LCD) are popular for weight loss but lack evidence about micronutrient sufficiency in real-life use. This study assessed the intake and biochemical status of selected micronutrients in people voluntarily following LCDs. Methods A cross-sectional study was conducted (2018-20) among 98 adults recruited as self-reporting either LCD ( n  = 49) or diets not restricting carbohydrates (controls; n  = 49). Diets were assessed using the 130-item EPIC-Norfolk food-frequency questionnaire. Red-blood-cell thiamine diphosphate (TDP) was measured for thiamine status using HPLC. Plasma magnesium, zinc, copper, and selenium were measured using inductively coupled plasma mass spectrometry. Between-group biomarker comparisons were conducted using ANCOVA and adjusted for age, sex, body mass index (BMI), and diabetes status. Results LCD-followers (26% male, median age 36 years, median BMI 24.2 kg/m 2 ) reported adhering to LCDs for a median duration of 9 months (IQR 4–36). The most followed LCD type was ‘their own variations of LCD’ (30%), followed by ketogenic (23%), ‘palaeolithic’ (15%), and Atkins diets (8%). Among controls, 41% were male (median age 27 years, median BMI 23 kg/m 2 ). Median macronutrient intakes for LCD vs control groups were carbohydrate 16%Energy (E) vs. 50%E; protein 25%E vs. 19%E; and fat 55%E vs 34%E (saturated fat 18%E vs. 11%E). Two-thirds of LCD followers (32/49) and half of the controls (24/49) reported some use of dietary supplements ( p  = 0.19). Among LCD-followers, assessing from food data only, 21 (43%) failed to meet the reference nutrient intake (RNI) for thiamine (vs.14% controls, p  = 0.002). When thiamine from supplementation (single- or multivitamin) was included, there appeared to be no difference in thiamine intake between groups. Still, red-blood-cell TDP was lower in LCD-followers than controls (407 ± 91 vs. 633 ± 234 ng/gHb, p  < 0.001). Three LCD-followers were thiamine-deficient (RBC thiamine < 275 ng/gHb) vs. one control. There were no significant differences in dietary intakes or plasma concentrations of magnesium, zinc, copper, and selenium between groups. Conclusions Following LCDs is associated with lower thiamine intake and TDP status than diets without carbohydrate restriction, incompletely corrected by supplement use. These data, coupled with a lack of RCT evidence on body weight control, do not support recommending LCDs for weight management without appropriate guidance and diet supplementation.

Aims Models are needed to quantify the economic implications of obesity in relation to health outcomes and health‐related quality of life. This report presents the structure of the Core Obesity Model (COM) and compare its predictions with the UK clinical practice data. Materials and methods The COM is a Markov, closed‐cohort model, which expands on earlier obesity models by including prediabetes as a risk factor for type 2 diabetes (T2D), and sleep apnea and cancer as health outcomes. Selected outcomes predicted by the COM were compared with observed event rates from the Clinical Practice Research Datalink‐Hospital Episode Statistics (CPRD‐HES) study. The importance of baseline prediabetes prevalence, a factor not taken into account in previous economic models of obesity, was tested in a scenario analysis using data from the 2011 Health Survey of England. Results Cardiovascular (CV) event rates predicted by the COM were well matched with those in the CPRD‐HES study (7.8–8.5 per 1000 patient‐years across BMI groups) in both base case and scenario analyses (8.0–9.4 and 8.6–9.9, respectively). Rates of T2D were underpredicted in the base case (1.0–7.6 vs. 2.1–22.7) but increased to match those observed in CPRD‐HES for some BMI groups when a prospectively collected prediabetes prevalence was used (2.7–13.1). Mortality rates in the CPRD‐HES were consistently higher than the COM predictions, especially in higher BMI groups. Conclusions The COM predicts the occurrence of CV events and T2D with a good degree of accuracy, particularly when prediabetes is included in the model, indicating the importance of considering this risk factor in economic models of obesity.

Patients with schizophrenia are more likely than the general population to develop diabetes, which contributes to a high risk of cardiovascular complications; individuals with schizophrenia are two to three times more likely to die from cardiovascular disease than the general population. The risk of diabetes, and hence cardiovascular disease, is particularly increased by some of the new atypical antipsychotic drugs. Individuals taking an atypical antipsychotic drug, particularly younger patients under 40 years of age (odds ratio 1.63, 95% CI 1.23-2.16), represent an underrecognized group at high risk of type 2 diabetes. The mechanisms responsible for antipsychotic-induced diabetes remain unclear. Hypotheses include these drugs' potential to cause weight gain, possibly through antagonism at the H(1), 5-HT(2A), or 5-HT(2C) receptors. Other mechanisms independent of weight gain lead to elevation of serum leptin and insulin resistance. Patients with psychoses have difficulties with diet and lifestyle interventions for diabetes and weight management. If hyperglycemia develops, withdrawal from antipsychotic medication will often be inappropriate, and a change to an atypical antipsychotic drug with lower diabetogenic potential should be considered, especially in younger patients. Management of psychoses should routinely include body weight and blood glucose monitoring and steps to promote exercise and minimize weight gain. Careful collaboration between the psychiatric and diabetology teams is essential to minimize the risk of diabetes in patients taking atypical antipsychotic medication and for effective management when it develops. This collaboration will also help minimize the already high risk of cardiovascular disease in individuals with schizophrenia.

There exist published literature for cardiovascular disease (CVD) risk monitoring in cancer survivors but the extent of monitoring in clinical oncology practice is unknown. We performed an interactive survey at a Royal College of Physicians conference (11 November 2016) attended by practitioners with an interest in late effects of cancer treatment and supplemented the survey with an audit among 32 lung cancer survivors treated at St Peter’s NHS Hospital in 2012–2016. Among the practitioners, 40% reported CVD risk monitoring performed at least annually, which is compatible with European Group for Blood and Marrow Transplantation Guidelines, but 31% indicated that monitoring was never performed. In contrast, 77% felt that at least an annual assessment was required (p<0.001). Corroborating these data, among the lung cancer survivors, 31% and 16% had lipids or glucose/HbA1C measured annually, and 28% and 31% had never had these tests performed since their cancer treatment. Alerting healthcare providers to review protocols may help reduce CVD after cancer treatments.

OBJECTIVE: To investigate the independent contributions of waist circumference, physical activity, and sedentary behavior on glycemia in South Asians living in Scotland. RESEARCH DESIGN AND METHODS: Participants were 1,228 (523 men and 705 women) adults of Indian or Pakistani origin screened for the Prevention of Type 2 Diabetes and Obesity in South Asians (PODOSA) trial. All undertook an oral glucose tolerance test, had physical activity and sitting time assessed by International Physical Activity Questionnaire, and had waist circumference measured. RESULTS: Mean ± SD age and waist circumference were 49.8 ± 10.1 years and 99.2 ± 10.2 cm, respectively. One hundred ninety-one participants had impaired fasting glycemia or impaired glucose tolerance, and 97 had possible type 2 diabetes. In multivariate regression analysis, age (0.012 mmol · L⁻¹ · year⁻¹ [95% CI 0.006-0.017]) and waist circumference (0.018 mmol · L⁻¹ · cm⁻¹ [0.012-0.024]) were significantly independently associated with fasting glucose concentration, and age (0.032 mmol · L⁻¹ · year⁻¹ [0.016-0.049]), waist (0.057 mmol · L⁻¹ · cm⁻¹ [0.040-0.074]), and sitting time (0.097 mmol · L⁻¹ · h⁻¹ · day⁻¹ [0.036-0.158]) were significantly independently associated with 2-h glucose concentration. Vigorous activity time had a borderline significant association with 2-h glucose concentration (-0.819 mmol · L⁻¹ · h⁻¹ · day⁻¹ [-1.672 to 0.034]) in the multivariate model. CONCLUSIONS: These data highlight an important relationship between sitting time and 2-h glucose levels in U.K. South Asians, independent of physical activity and waist circumference. Although the data are cross-sectional and thus do not permit firm conclusions about causality to be drawn, the results suggest that further study investigating the effects of sitting time on glycemia and other aspects of metabolic risk in South Asian populations is warranted.

Aims/hypothesisWeight reduction is fundamental for type 2 diabetes management and remission, but uncertainty exists over which diet type is best to achieve and maintain weight loss. We evaluated dietary approaches for weight loss, and remission, in people with type 2 diabetes to inform practice and clinical guidelines.MethodsFirst, we conducted a systematic review of published meta-analyses of RCTs of weight-loss diets. We searched MEDLINE (Ovid), PubMed, Web of Science and Cochrane Database of Systematic Reviews, up to 7 May 2021. We synthesised weight loss findings stratified by diet types and assessed meta-analyses quality with A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. We assessed certainty of pooled results of each meta-analysis using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) (PROSPERO CRD42020169258). Second, we conducted a systematic review of any intervention studies reporting type 2 diabetes remission with weight-loss diets, in MEDLINE (via PubMed), Embase and Cochrane Central Register of Controlled Trials, up to 10 May 2021. Findings were synthesised by diet type and study quality (Cochrane Risk of Bias tool 2.0 and Risk Of Bias In Non-randomised Studies – of Interventions [ROBINS-I]), with GRADE applied (PROSPERO CRD42020208878).ResultsWe identified 19 meta-analyses of weight-loss diets, involving 2–23 primary trials (n = 100–1587), published 2013–2021. Twelve were ‘critically low’ or ‘low’ AMSTAR 2 quality, with seven ‘high’ quality. Greatest weight loss was reported with very low energy diets, 1.7–2.1 MJ/day (400–500 kcal) for 8–12 weeks (high-quality meta-analysis, GRADE low), achieving 6.6 kg (95% CI −9.5, −3.7) greater weight loss than low-energy diets (4.2–6.3 MJ/day [1000–1500 kcal]). Formula meal replacements (high quality, GRADE moderate) achieved 2.4 kg (95% CI −3.3, −1.4) greater weight loss over 12–52 weeks. Low-carbohydrate diets were no better for weight loss than higher-carbohydrate/low-fat diets (high quality, GRADE high). High-protein, Mediterranean, high-monounsaturated-fatty-acid, vegetarian and low-glycaemic-index diets all achieved minimal (0.3–2 kg) or no difference from control diets (low to critically low quality, GRADE very low/moderate). For type 2 diabetes remission, of 373 records, 16 met inclusion criteria. Remissions at 1 year were reported for a median 54% of participants in RCTs including initial low-energy total diet replacement (low-risk-of-bias study, GRADE high), and 11% and 15% for meal replacements and Mediterranean diets, respectively (some concerns for risk of bias in studies, GRADE moderate/low). For ketogenic/very low-carbohydrate and very low-energy food-based diets, the evidence for remission (20% and 22%, respectively) has serious and critical risk of bias, and GRADE certainty is very low.Conclusions/interpretationPublished meta-analyses of hypocaloric diets for weight management in people with type 2 diabetes do not support any particular macronutrient profile or style over others. Very low energy diets and formula meal replacement appear the most effective approaches, generally providing less energy than self-administered food-based diets. Programmes including a hypocaloric formula ‘total diet replacement’ induction phase were most effective for type 2 diabetes remission. Most of the evidence is restricted to 1 year or less. Well-conducted research is needed to assess longer-term impacts on weight, glycaemic control, clinical outcomes and diabetes complications.