Feasibility of prevention of type 2 diabetes in low- and middle-income countries.

Type 2 diabetes is a leading cause of global mortality and morbidity. Nearly 80% of individuals with diabetes live in low- and middle-income countries (LMICs), where nearly half of those with the condition remain undiagnosed. The majority of known cases have sub-optimal clinical outcomes. Moreover, large populations with impaired glucose tolerance and/or impaired fasting glucose contribute to the rapid increase in type 2 diabetes. Globally, priority should be given to limit the population with diabetes, especially in LMICs, alongside actions to optimise the care of people diagnosed with diabetes. Primary prevention studies in LMICs have generated evidence to show the efficacy and scalability of strategies to fully prevent or delay the development of diabetes in high-risk groups. However, these are mainly limited to certain countries in Asia, particularly China and India. The studies have indicated that prevention policies are effective in populations with a high risk of type 2 diabetes, and they also have long-term benefits, not only for the risk of type 2 diabetes but also for the risk of associated metabolic disorders, such as CVDs. For the effective conduct of national programmes, innovative mechanisms must be implemented, such as the use of information technology, joint efforts of multiple teams implementing similar programmes, and involvement of governmental and non-governmental partnerships. Continuous monitoring and long-term studies are required to assess the utility of these programmes. The effectiveness of such programmes in LMICs has not been proven over the longer term, except in China. Despite the available evidence, the feasibility of prevention strategies for type 2 diabetes in LMICs at population level remains an enigma. There remain challenges in the form of cultural, societal and economic constraints; insufficient infrastructure and healthcare capacity; and the non-fully elucidated natural history and determinants of type 2 diabetes in LMICs.

Normalization of impaired glucose tolerance after kidney transplantation is associated with improved ß-cell function.

Our previous study revealed that over 50% of recipients with pretransplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with ß-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). ß-Cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2 and DI increased significantly after transplantation in the improved group (P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min OGTT plasma glucose levels (both P < 0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = -0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in ß-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant ß-cell function. Improvements in BUN after transplantation were associated with improvements in ß-cell function.NEW & NOTEWORTHY In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in ß-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant ß-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus.

Test and Treat for Prediabetes: A Review of the Health Effects of Prediabetes and the Role of Screening and Prevention.

The term prediabetes describes blood glucose levels above the normal range but below the threshold to diagnose type 2 diabetes. Several population health initiatives encourage a test and treat approach for prediabetes. In this approach, screening and identification of individuals with prediabetes should be followed by prompt referral to structured lifestyle modification programs or pharmacologic interventions that have been shown to prevent or delay the progression to type 2 diabetes in clinical trials. Here we provide a critical review of evidence for this test and treat approach by examining health outcomes associated with prediabetes and the availability and effectiveness of lifestyle modification approaches that target prediabetes. We also describe current limitations to the reach and uptake of evidence-based treatment options for prediabetes. Finally, we highlight lessons learned from identifying and labeling other preconditions to consider challenges and opportunities that may arise with increasing awareness of prediabetes as part of routine preventive care.

Association of prediabetes with clinical outcomes in patients with chronic coronary syndrome: a post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials.

BACKGROUND: There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes. METHODS: This is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7-6.4% [40-47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof. RESULTS: Overall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1-4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95-2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29-2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15-10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years. CONCLUSIONS: In patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years. Trial Registration NCT01471522, BioLINCC ID 13936.

Cancer risk following onset of type 2 diabetes in New Zealanders with impaired glucose tolerance over 25 years: a matched prospective cohort study.

BACKGROUND: In people with prediabetes, the link between developing type 2 diabetes (T2D) and cancer risk among those with impaired glucose tolerance (IGT) remains uncertain. We examined this association in IGT individuals from primary care in South and West Auckland, New Zealand, spanning 1994-2019, assessing 5- and 10-year cancer risks. METHODS: Study cohorts were extracted from the Diabetes Care Support Service in Auckland, New Zealand, linking it with national registries for death, cancer, hospital admissions, pharmaceutical claims, and socioeconomic status. We compared cancer risks in individuals with IGT newly diagnosed with or without T2D within a 1-5-year exposure window. Employing tapered matching and landmark analysis to address potential confounding effects, we formed comparative IGT cohorts. Weighted Cox regression models were then employed to assess the association between T2D onset and 5- and 10-year cancer risks. RESULTS: The study included 26,794 patients with IGT, with 629 newly diagnosed with T2D within 5 years and 13,007 without such a diagnosis. Those progressing to T2D had similar 5-year cancer risk but significantly higher 10-year risk (HR 1.35; 95% CI 1.09-1.68). This association was stronger in older individuals, the socioeconomically deprived, current smokers, those with worse metabolic measures, and lower renal function. Patients with IGT of NZ European ethnicity had lower 10-year cancer risk. CONCLUSIONS: T2D diagnosis influences cancer risk in individuals with IGT. Developing risk scores for high-risk IGT individuals and implementing cancer screening and structured diabetes prevention, especially in deprived or minority ethnic populations, is essential.

Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity.

Obesity is commonly linked with white adipose tissue (WAT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic complications associated with obesity. To improve metabolic and cardiovascular health, countering these inflammatory and oxidative signaling processes is crucial. Offering potential in this context, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by nitro-fatty acids (NO2-FA) promote diverse anti-inflammatory signaling and counteract oxidative stress. Additionally, we previously highlighted that nitro-oleic acid (NO2-OA) preferentially accumulates in WAT and provides protection against already established high fat diet (HFD)-mediated impaired glucose tolerance. The precise mechanism accounting for these protective effects remained largely unexplored until now. Herein, we reveal that protective effects of improved glucose tolerance by NO2-OA is absent when Nrf2 is specifically ablated in adipocytes (ANKO mice). NO2-OA treatment did not alter body weight between ANKO and littermate controls (Nrf2fl/fl) mice on both the HFD and low-fat diet (LFD). As expected, at day 76 (before NO2-OA treatment) and notably at day 125 (daily treatment of 15 mg/kg NO2-OA for 48 days), both HFD-fed Nrf2fl/fl and ANKO mice exhibited increased fat mass and reduced lean mass compared to LFD controls. However, throughout the NO2-OA treatment, no distinction was observed between Nrf2fl/fl and ANKO in the HFD-fed mice as well as in the Nrf2fl/fl mice fed a LFD. Glucose tolerance tests revealed impaired glucose tolerance in HFD-fed Nrf2fl/fl and ANKO compared to LFD-fed Nrf2fl/fl mice. Notably, NO2-OA treatment improved glucose tolerance in HFD-fed Nrf2fl/fl but did not yield the same improvement in ANKO mice at days 15, 30, and 55 of treatment. Unraveling the pathways linked to NO2-OA's protective effects in obesity-mediated impairment in glucose tolerance is pivotal within the realm of precision medicine, crucially propelling future applications and refining novel drug-based strategies.

Current type 2 diabetes guidelines: Individualized treatment and how to make the most of metformin.

Evidence-based guidelines provide the premise for the delivery of quality care to preserve health and prevent disabilities and premature death. The systematic gathering of observational, mechanistic and experimental data contributes to the hierarchy of evidence used to guide clinical practice. In the field of diabetes, metformin was discovered more than 100 years ago, and with 60 years of clinical use, it has stood the test of time regarding its value in the prevention and management of type 2 diabetes. Although some guidelines have challenged the role of metformin as the first-line glucose-lowering drug, it is important to point out that the cardiovascular-renal protective effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were gathered from patients with type 2 diabetes, the majority of whom were treated with metformin. Most national, regional and international guidelines recommend metformin as a foundation therapy with emphasis on avoidance of therapeutic inertia and early attainment of multiple treatment goals. Moreover, real-world evidence has confirmed the glucose-lowering and cardiovascular-renal benefits of metformin accompanied by an extremely low risk of lactic acidosis. In patients with type 2 diabetes and advanced chronic kidney disease (estimated glomerular filtration rate 15-30 mL/min/1.73m2), metformin discontinuation was associated with an increased risk of cardiovascular-renal events compared with metformin persistence. Meanwhile, it is understood that microbiota, nutrients and metformin can interact through the gut-brain-kidney axis to modulate homeostasis of bioactive molecules, systemic inflammation and energy metabolism. While these biological changes contribute to the multisystem effects of metformin, they may also explain the gastrointestinal side effects and vitamin B12 deficiency associated with metformin intolerance. By understanding the interactions between metformin, foods and microbiota, healthcare professionals are in a better position to optimize the use of metformin and mitigate potential side effects. The United Kingdom Prospective Diabetes Study and the Da Qing Diabetes Prevention Program commenced 40 years ago provided the first evidence that type 2 diabetes is preventable and treatable. To drive real-world impact from this evidence, payors, practitioners and planners need to co-design and implement an integrated, data-driven, metformin-based programme to detect people with undiagnosed diabetes and prediabetes (intermediate hyperglycaemia), notably impaired glucose tolerance, for early intervention. The systematic data collection will create real-world evidence to bring out the best of metformin and make healthcare sustainable, affordable and accessible.

Frequency of prediabetes in individuals with increased adiposity and metabolically healthy or unhealthy phenotypes.

AIMS: To utilize the estimated glucose disposal rate (eGDR) index of insulin sensitivity, which is based on readily available clinical variables, namely, waist circumference, hypertension and glycated haemoglobin, to discriminate between metabolically healthy and unhealthy phenotypes, and to determine the prevalence of prediabetic conditions. METHODS: Non-diabetic individuals (n = 2201) were stratified into quartiles of insulin sensitivity based on eGDR index. Individuals in the upper quartiles of eGDR were defined as having metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW) or metabolically healthy obesity (MHO) according to their body mass index, while those in the lower quartiles were classified as having metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW) and metabolically unhealthy obesity (MUO), respectively. RESULTS: The frequency of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and IFG + IGT status was comparable among the MHNW, MHOW and MHO groups, while it increased from those with MUNW status towards those with MUOW and MUO status. As compared with participants with MHNW, the odds ratio of having IFG, IGT, or IFG + IGT was significantly higher in participants with MUOW and MUO but not in those with MUNW, MHOW and MHO, respectively. CONCLUSIONS: A metabolically healthy phenotype is associated with lower frequency of IFG, IGT, and IFG + IGT status across all body weight categories.

The real-life management of glucose homeostasis abnormalities in pediatric onco-hematological diseases: data from a national survey.

Glycemic abnormalities are a frequent finding in pediatric oncological patients, both during treatment and after its discontinuation. Moreover, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG) and diabetes mellitus (DM) are not rarely diagnosed in non-oncological hematological diseases. To explore the current pediatric Italian approach to the diagnosis and the management of the glycemic alterations in this clinical setting and, thus, to identify and enforce current clinical needs, we submitted an online 23-items survey to all the Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers, and surveys were descriptively analyzed. Thirty-nine AIEOP centers were involved in the study. In 2021, among 75278 children and adolescents affected by an oncological or a hematological disease, 1.2 and 0.65% developed DM, while IGT or IFG were widespread in 2.3 and 2.8%, respectively. The main causes of DM were the use of corticosteroids in patients with cancer and the iron overload in patients with thalassemia. Venous fasting plasma glycemia was the most used tool to detect glycemic abnormalities. The performance of oral glucose tolerance test (OGTT) was extremely limited, except when IFG occurred. Despite the diagnosis of DM, ∼45% of patients with cancer and 30% of patients with one hematological disease did not receive an appropriate treatment. In the other cases, insulin was the drug of first choice. Emerging technologies for diabetes care (glucose sensors and insulin pumps) are not largely used yet. The results of our study support the standardization of the care of the glycemic abnormalities during or after onco-hematologic diseases in the pediatric age. Despite the scarce data in pediatric literature, proper guidelines are needed.

Long-term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered-matched landmark analysis over 25 years.

INTRODUCTION: We aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years. METHODS: Tapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5- and 10-year IR of dementia was estimated by weighted Cox models. RESULTS: The onset of T2D was significantly associated with the 10-year IR of dementia, especially in the socioeconomically deprived, those of non-NZ European ethnicity, those currently smoking, and patients with higher metabolic measures. DISCUSSION: Our findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds. HIGHLIGHTS: Increased dementia incidence rate links with T2D onset in people with IGT. Significant incidence varied by ethnicity, socioeconomic status, and health factors. Results emphasize the diabetes manage and socioeconomic factors on dementia risk. Secondary analysis highlights the key role of vascular health in dementia prevention.

Elevated remnant cholesterol and atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study.

AIMS/HYPOTHESIS: Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. This association is not well studied in individuals with diabetes, who are often included in clinical trials of remnant cholesterol-lowering therapy. We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of ASCVD in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol. METHODS: We included 4569 white Danish individuals with diabetes (58% statin users) nested within the Copenhagen General Population Study (2003-2015). The ASCVDs peripheral artery disease, myocardial infarction and ischaemic stroke were extracted from national Danish health registries without losses to follow-up. Remnant cholesterol was calculated from a standard lipid profile. RESULTS: During up to 15 years of follow-up, 236 individuals were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischaemic stroke and 498 with any ASCVD. Multivariable adjusted HR (95% CI) per doubling of remnant cholesterol was 1.6 (1.1, 2.3; p=0.01) for peripheral artery disease, 1.8 (1.2, 2.5; p=0.002) for myocardial infarction, 1.5 (1.0, 2.1; p=0.04) for ischaemic stroke, and 1.6 (1.2, 2.0; p=0.0003) for any ASCVD. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischaemic stroke and 1.6-fold for any ASCVD. Excess risk explained by elevated remnant cholesterol and low-grade inflammation was 14% and 8% for peripheral artery disease, 26% and 16% for myocardial infarction, 34% and 34% for ischaemic stroke, and 24% and 18% for any ASCVD, respectively. LDL-cholesterol did not explain excess risk, as it was not higher in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol. CONCLUSIONS/INTERPRETATION: Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes. Remnant cholesterol and low-grade inflammation explained substantial excess risk of ASCVD conferred by diabetes. Whether remnant cholesterol should be used as a treatment target remains to be determined in randomised controlled trials.

The role of postprandial thermogenesis in the development of impaired glucose tolerance and type II diabetes.

Accounting for 5%-15% of total daily energy expenditure, postprandial thermogenesis (PPT) refers to an acute increase in resting metabolic rate (RMR) in the hours after eating. This is largely explained by the energy costs of processing the macronutrients of a meal. Most individuals spend the majority of the day in the postprandial state, thus over one's lifetime even minor differences in PPT may possess true clinical significance. In contrast to RMR, research indicates that PPT may be reduced in the development of both prediabetes and type II diabetes (T2D). The present analysis of existing literature has found that this impairment may be exaggerated in hyperinsulinemic-euglycemic clamp studies compared with food and beverage consumption studies. Nonetheless, it is estimated that daily PPT following carbohydrate consumption alone is approximately 150 kJ lower among individuals with T2D. This estimate fails to consider protein intake, which is notably more thermogenic than carbohydrate intake (20%-30% vs. 5%-8%, respectively). Putatively, dysglycemic individuals may lack the insulin sensitivity required to divert glucose toward storage-a more energy-taxing pathway. Accordingly, the majority of findings has associated an impaired PPT with a reduced "obligatory" energy output (i.e., the energy costs associated with nutrient processing). More recently, it has been reported that "facultative" thermogenesis [e.g., the energy costs associated with sympathetic nervous system (SNS) stimulation] may also contribute to any impairment in PPT among individuals with prediabetes and T2D. Further longitudinal research is required to truly ascertain whether meaningful changes in PPT manifest in the prediabetic state, before the development of T2D.

Machine learning-based models to predict one-year mortality among Chinese older patients with coronary artery disease combined with impaired glucose tolerance or diabetes mellitus.

PURPOSE: An accurate prediction of survival prognosis is beneficial to guide clinical decision-making. This prospective study aimed to develop a model to predict one-year mortality among older patients with coronary artery disease (CAD) combined with impaired glucose tolerance (IGT) or diabetes mellitus (DM) using machine learning techniques. METHODS: A total of 451 patients with CAD combined with IGT and DM were finally enrolled, and those patients randomly split 70:30 into training cohort (n = 308) and validation cohort (n = 143). RESULTS: The one-year mortality was 26.83%. The least absolute shrinkage and selection operator (LASSO) method and ten-fold cross-validation identified that seven characteristics were significantly associated with one-year mortality with creatine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and chronic heart failure being risk factors and hemoglobin, high density lipoprotein cholesterol, albumin, and statins being protective factors. The gradient boosting machine model outperformed other models in terms of Brier score (0.114) and area under the curve (0.836). The gradient boosting machine model also showed favorable calibration and clinical usefulness based on calibration curve and clinical decision curve. The Shapley Additive exPlanations (SHAP) found that the top three features associated with one-year mortality were NT-proBNP, albumin, and statins. The web-based application could be available at https://starxueshu-online-application1-year-mortality-main-49cye8.streamlitapp.com/ . CONCLUSIONS: This study proposes an accurate model to stratify patients with a high risk of one-year mortality. The gradient boosting machine model demonstrates promising prediction performance. Some interventions to affect NT-proBNP and albumin levels, and statins, are beneficial to improve survival outcome among patients with CAD combined with IGT or DM.

Effect of onset of type 2 diabetes on risks of cardiovascular disease and heart failure among new Zealanders with impaired glucose tolerance over 25 years: tapered-matched landmark analysis.

BACKGROUND: This study aimed to examine the association between the incident onset of T2DM and 5- and 10-year risks of CVD and HF in people with IGT identified in primary care in South and West Auckland, New Zealand (NZ) between 1994 and 2019. METHODS: We compared CVD and HF risks in patients with IGT and with/without T2D newly diagnosed within the exposure window (1-5 years). Tapered matching and landmark analysis (to account for immortal bias) were used to control for potential effects of known confounders. RESULTS: Among 26,794 patients enrolled with IGT, 845 had T2D newly diagnosed within 5 years from enrolment (landmark date) and 15,452 did not have T2D diagnosed. Patients progressing to T2D (vs. those not progressing) had a similar 5-year risk for CVD (hazard ratio 1.19; 95% CI 0.61-2.32) but significantly higher 10-year risk of CVD (2.45(1.40-4.29)), 5-year risk of HF (1.94(1.20-3.12)) and 10-year risk of HF (2.84(1.83-4.39). The association between the onset of T2D and risk of 10-year risk of CVD, 5-year and 10-year risk of HF was more likely among men, the socioeconomically deprived, those currently smoking, patients with higher metabolic measures and/or those with lower renal function. Patients of NZ European ethnicity had a lower 10-year risk of CVD. CONCLUSIONS: The study suggests that the diagnosis of T2D mediates the risk of CVD and HF in people with IGT. The development of risk scores to identify and better manage individuals with IGT at high risk of T2D is warranted.

Neuropathy in prediabetes.

Diabetic neuropathies are the most frequent complications of diabetes, contributing to high morbidity, excess mortality, reduced quality of life, and increased healthcare costs. Prediabetes is characterised by glucose levels within an intermediate range above normoglycaemia yet below the diagnostic threshold for diabetes. In 2021, 10.6% and 6.2% of adults worldwide were estimated to have impaired glucose tolerance and impaired fasting glucose, respectively, the majority of whom are unaware of having prediabetes. Evidence has accumulated suggesting that prediabetes is a predictor of cardiovascular disease (CVD) and increased mortality. The past 2 decades have witnessed an extensive debate, particularly among diabetologists and neurologists, as to whether prediabetes is associated with peripheral neuropathy. In this review, we elaborate on the current evidence, particularly from population-based studies supporting an increased risk of distal sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in people with prediabetes. Moreover, we discuss whether lifestyle interventions showing efficacy in preventing or delaying the transition from prediabetes to diabetes in persons with prediabetes may also exert favourable effects on the development and progression of DSPN and CAN. This review should help in raising the awareness of and translating the current knowledge on neuropathies in people with prediabetes into clinical practice and public health. The current recommendation that adults who are overweight or obese should be screened for prediabetes and referred to or offered preventive interventions should ultimately culminate in preventing not only CVD but also prediabetic neuropathy.

Dairy Product Consumption and Incident Prediabetes in the Australian Diabetes, Obesity, and Lifestyle Study With 12 Years of Follow-Up.

BACKGROUND: Investigating modifiable risk factors for the early stages of the development of type 2 diabetes is essential for effective prevention. Some studies show protective associations between dairy and prediabetes; however, associations are heterogeneous by the type and fat content of dairy foods. OBJECTIVE: To examine the relationship between the consumption of dairy, including different types of dairy products and risk of prediabetes. METHODS: The study included 4891 participants with normal glucose tolerance (aged 49.0 ± 12.3 y, 57% female) of the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study, a longitudinal population-based study. Dairy intake was measured at baseline using a food frequency questionnaire. Prediabetes at the 5-y and 12-y follow-ups was defined according to the WHO criteria as fasting plasma glucose levels of 110-125 mg/dL or 2-h plasma glucose levels of 140-199 mg/dL. Associations were analyzed using Poisson regression, adjusted for social demographics, lifestyle behaviors, a family history of diabetes, and food group intake. RESULTS: In total, 765 (15.6%) incident cases of prediabetes were observed. The mean intake of dairy foods was 2.4 ± 1.2 servings/d, mostly consisting of low-fat milk (0.70 ± 0.78 servings/d) and high-fat milk (0.47 ± 0.72 servings/d). A higher intake of high-fat dairy (RRservings/d: 0.92; 95% CI: 0.85, 1.00), high-fat milk (0.89; 95% CI: 0.80, 0.99), and total cheese (0.74; 95% CI: 0.56, 0.96) was associated with a lower risk of prediabetes. Low-fat milk intake was associated nonlinearly with prediabetes risk. Low-fat dairy foods, total milk, yogurt, low-fat cheese, and ice cream were not associated with prediabetes risk. CONCLUSION: In this large Australian cohort, protective associations were found for high-fat dairy types, whereas neutral associations were seen for low-fat dairy types. Studies with more detail on sugar content of types of dairy foods and products eaten with dairy foods (e.g., cereals or jam), and studies into potential causal mechanisms of the health effects of dairy intake are required.

Unmasking a silent killer: Prevalence of diagnosed and undiagnosed diabetes mellitus among people living with HIV in rural South Africa.

OBJECTIVES: To document the prevalence of impaired glucose tolerance (IGT) and undiagnosed diabetes mellitus (DM) and to identify factors associated with undiagnosed DM in people living with HIV (PLWH). METHODS: Cross-sectional study performed at Ndlovu Medical Center, Limpopo, South Africa including PLWH aged ≥18 years. Between August and November 2017, 356 HIV-positive participants were included. Information was collected on socio-demographics, DM symptoms and risk factors for DM. IGT and DM were diagnosed using random plasma glucose and/or HbA1c. Factors associated with undiagnosed DM were assessed by comparing participants with newly diagnosed DM to participants without DM. RESULTS: IGT was diagnosed in 172 (48.3%) participants. Twenty-nine (8.1%) participants met the definition of DM, of whom 17 (58.6%) were newly diagnosed. Compared to participants without DM, participants with DM were on average 5 years older, were more likely to have a positive family history for DM, were less physically active and had higher systolic blood pressure, body mass index and waist circumference. Factors associated with undiagnosed DM included age ≥45 years (odds ratio [OR] = 3.59) and physical inactivity (OR = 3.17). CONCLUSIONS: The prevalence of IGT and DM among PLWH is high and more than half of DM cases were undiagnosed. Regular screening for DM in PLWH is recommended, especially in an ageing population with additional cardiovascular disease risk factors.

Prevalence of glucose metabolism disorders and its association with left atrial remodelling before and after catheter ablation in patients with atrial fibrillation.

AIMS: To investigate the exact prevalence of glucose metabolism disorders, and their impact on left atrial (LA) remodelling and reversibility in patients with atrial fibrillation (AF). METHODS AND RESULTS: We examined 204 consecutive patients with AF who underwent their first catheter ablation (CA). Oral glucose tolerance test was used to evaluate glucose metabolism disorders in 157 patients without known diabetes mellitus (DM). Echocardiography was performed before and 6 months after CA. Oral glucose tolerance test identified abnormal glucose metabolism in 86 patients [11 with newly diagnosed DM, 74 with impaired glucose tolerance (IGT) and 1 with impaired fasting glucose (IFG)]. Ultimately, 65.2% of patients had abnormal glucose metabolism. Diabetes mellitus group had the worst LA reservoir strain and LA stiffness (both P < 0.05), while there was no significant difference in baseline LA parameters between normal glucose tolerance (NGT) group and IGT/IFG group. The prevalence of LA reverse remodelling (≥15% decrease in the LA volume index at 6 months after CA) was significantly higher in NGT group compared with IGT/IFG and DM group (64.1 vs. 38.6 vs. 41.5%, P = 0.006). Both DM and IFG/IGT carry a significant risk of lack of LA reverse remodelling independent of baseline LA size and AF recurrence. CONCLUSION: Approximately 65% of patients with AF who underwent their first CA had abnormal glucose metabolism. Patients with DM had significantly impaired LA function compared with non-DM patients. Impaired glucose tolerance/IFG as well as DM carries significant risk of unfavourable LA reverse remodelling. Our observations may provide valuable information regarding the mechanisms and therapeutic strategies of glucose metabolism-related AF.

Cystic fibrosis related diabetes (CFRD) in the era of modulators: A scoping review.

Cystic fibrosis-related diabetes (CFRD) is a common complication of CF that increases in incidence as patients age. Poor glycemic control has been shown to negatively impact lung function and weight, resulting in higher risk of recurrent pulmonary exacerbations. With the advent of highly effective modulator therapies (HEMT), patients with CF are living longer and healthier lives. Consequently, CFRD and its microvascular complications are rising in prominence, becoming one of the most urgent clinical concerns. As HEMT were developed with the primary focus of improving pulmonary outcomes, it is not clear from the original phase III studies what the short- or long-term benefits of modulators might be on CFRD development and trajectory. In this review, we will examine the pathophysiology of CFRD, summarize and synthesize the available evidence of HEMT impact on CFRD and describe the emerging research needs in this field.

Are HOMA-IR and HOMA-B good predictors for diabetes and pre-diabetes subtypes?

BACKGROUND: To investigate the association between the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Homeostasis Model Assessment of Beta-cell function (HOMA-B) with the incidence of diabetes and pre-diabetes subtypes. METHODS: A total of 3101 normoglycemic people aged 20-70 years were included in the 6-year follow-up study. Multinomial logistic regression was used to calculate the incidence possibility of isolated Impaired Fasting Glucose (iIFG), isolated Impaired Glucose Tolerance (iIGT), Combined impaired fasting glucose & impaired glucose tolerance (CGI), and Diabetes Mellitus (DM) per standard deviation (SD) increment in HOMA-IR and HOMA-B in the crude and multivariable model. RESULTS: In the multivariate model, an increase in one SD change in HOMA-IR was associated with a 43, 42, 75, and 92% increased risk of iIFG, iIGT, CGI, and DM, respectively. There was a positive correlation between the increase in HOMA-B and the incidence of iIGT; however, after adjusting the results for metabolic syndrome components, it was inversely correlated with the incidence of iIFG [Odds Ratio = 0.86(0.75-0.99)]. CONCLUSIONS: HOMA-IR is positively correlated with diabetes and pre-diabetes subtypes' incidence, and HOMA-B is inversely correlated with the incidence of iIFG but positively correlated with iIGT incidence. However, none of these alone is a good criterion for predicting diabetes and pre-diabetes.