Interaction Between Primary Hyperlipidemias and Type 2 Diabetes: Therapeutic Implications.

There is a gap of knowledge about the clinical and pathophysiological implications resulting from the interaction between primary hyperlipidemias and type 2 diabetes (T2D). Most of the existing evidence comes from sub-analyses of cohorts; scant information derives from randomized clinical trials. The expected clinical implications of T2D in patients with primary hyperlipidemias is an escalation of their already high cardiovascular risk. There is a need to accurately identify patients with this dual burden and to adequately prescribe lipid-lowering therapies, with the current advancements in newer therapeutic options. This review provides an update on the interactions of primary hyperlipidemias, such as familial combined hyperlipidemia, familial hypercholesterolemia, multifactorial chylomicronemia, lipoprotein (a), and type 2 diabetes.

The association between breakfast frequency and diabetes incidence in middle-aged women: Results from the MTC study.

BACKGROUND AND AIMS: Breakfast consumption could have a synchronizer role in chronobiological functions. Across observational studies, the assessment of breakfast frequency consumption is heterogeneous, therefore consensus on the relation between of weekly frequency of breakfast consumption and the risk of diabetes is unclear. We examined the relation between weekly breakfast frequency consumption and the incidence of diabetes in middle-age women. METHODS AND RESULTS: Since baseline (2006-2008) we prospectively followed 71,373 women from the Mexican Teachers' Cohort. Participants were classified according to breakfast consumption frequency of 0, 1-3, 4-6, or 7 days/week. Diabetes was identified by self-report and clinical-administrative databases. We used Cox proportional hazards multivariable models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for breakfast frequency and diabetes adjusting for covariates. Stratified analyses were performed for age, birth weight, ethnicity, and physical activity. We identified 3613 new diabetes cases between baseline and 2014. The prevalence of daily breakfast consumers was 25%. The median follow-up was 2.2 years, interquartile range 1.8-3.8 years. Relative to women who skipped breakfast, those who consumed breakfast every day had a 12% lower risk of diabetes (multivariable HR = 0.88; 95% CI 0.78, 0.99; p-trend = 0.0018). One additional day per week of breakfast was associated with a lower risk of diabetes (HR = 0.98; 95% CI 0.97, 0.99). In stratified analysis, the observed inverse relation appeared to be stronger in women aged ≥40 years and in indigenous women. CONCLUSIONS: Breakfast frequency was inversely associated with the incidence of diabetes independently of lifestyle factors. Regular breakfast consumption may be a potential component of diabetes prevention.

Long-Term Adherence to the Mediterranean Diet Reduces 20-Year Diabetes Incidence: The ATTICA Cohort Study (2002-2022).

This study aimed to evaluate the association between adherence to the Mediterranean diet and the 20-year incidence of type II diabetes mellitus (T2DM) among adults from the ATTICA study. This study involved a prospective cohort of 3042 men and women recruited at baseline from the Attica region in Greece. Sociodemographic, anthropometric, lifestyle, and clinical characteristics were evaluated at baseline and follow-up examinations; adherence to the Mediterranean diet was assessed through the MedDietScore (range 0-55); four Mediterranean diet trajectories were identified (i.e., increasing, decreasing, and sustained high and sustained low adherence levels). For the present analysis, data from 2000 individuals with complete information were used (age 43 ± 13 years; 49% men). Over the 20-year period, 26.3% (95%CI 24.4%, 28.3%) of participants developed T2DM; men exhibited a 1.5-times higher incidence compared to women (p < 0.001). Individuals consistently close to the Mediterranean diet throughout the studied period had an improved glycemic and lipidemic profile (at baseline and at 10-y follow-up) (all p-values < 0.001) and showed a 21% reduction in their 20-year risk of developing T2DM compared to those who were consistently away (RR = 0.79, 95%CI 0.47, 0.86). A long-term adherence to the Mediterranean diet is protective against the onset of T2DM and, therefore, could be incorporated in public health actions for the prevention of the disease.

Habitual intake of iron, copper, and zinc and the risk of type 2 diabetes in a prospective cohort: The CAVAS (Cardiovascular Disease Association Study).

BACKGROUND AND AIMS: Unlike iron, evidence of the association between dietary copper and zinc intake and type 2 diabetes (T2D) risk is limited. This study aimed to examine the prospective associations of dietary intake of iron (total, plant-based, and animal-based), copper, and zinc with T2D risk among adults aged ≥40 years. METHODS AND RESULTS: For 16,666 participants, dietary intakes (baseline, cumulative average, and most recent) of iron, copper, and zinc were calculated from repeated food frequency questionnaires; a modified Poisson regression model with a robust error estimator was conducted. In men, positive associations between T2D and baseline dietary intake of Cu and Zn, cumulative average dietary intake of Fe (total and animal-based), Cu and Zn, and most recent dietary intake of Fe (total, plant-based, and animal-based), Cu, and Zn [most recent diet: for total Fe, IRR(95%CI) = 1.93 (1.41-2.64); for plant-based Fe, 1.56 (1.15-2.11); for animal-based Fe, 1.44 (1.09-1.90); for Cu, 3.17 (2.33-4.30); for Zn, 2.18 (1.64-2.89)] were observed, where as in women, there were positive associations of only cumulative average dietary Zn intake and most recent dietary intake of plant-based Fe, Cu, and Zn [most recent diet: for plant-based Fe, 1.30 (1.01-1.68); for Cu, 1.62 (1.27-2.08); for Zn, 2.07 (1.61-2.66)]. CONCLUSION: Dietary intakes of iron (total, plant-based, and animal-based), copper, and zinc may be positively associated with T2D risk. These positive associations are predominantly observed in most recent diet and appear to be stronger compared to baseline and cumulative average diet.

Organic food consumption and the incidence of type 2 diabetes mellitus in the Danish Diet, Cancer and Health cohort.

AIM: To investigate the association between organic food consumption and the incidence of type 2 diabetes mellitus. METHODS: Among 41,286 cohort participants, aged 50-65 years, organic food consumption of vegetables, fruits, dairy products, eggs, meat, and cereal products, was summarized into an organic food score evaluated as never, low, medium and high consumption and as continuous intake. During follow-up, 4,843 cases were identified in the National Diabetes Register. Organic food consumption was associated to the disease incidence in Cox regression models. RESULTS: Organic food consumption was linearly associated with a lower incidence of type 2 diabetes mellitus (Women, HR: 0.94, 95% CI: 0.89-1.00, Men, HR: 0.95, 95% CI: 0.90-1.00). Organic food consumption frequency, compared to never consumption, showed HRs below 1.00 for both women (medium intake HR: 0.96, 95% CI: 0.84-1.10, high intake HR: 0.88, 95% CI: 0.74-1.05) and men (low intake, HR: 0.95, 95% CI: 0.85-1.05, medium intake, HR: 0.92, 95% CI: 0.83-1.03, high intake, HR: 0.89, 95% CI: 0.75-1.05) but were not statistically significant. Similar patterns were observed with consumption of the specific organic food groups for women, but not for men. CONCLUSIONS: Organic food consumption was associated with a suggested lower incidence of type 2 diabetes mellitus.

Retention and outcomes of National Diabetes Prevention Program enrollees and non-enrollees with prediabetes: The University of Michigan experience.

AIMS: To evaluate retention and outcomes of insured adults with prediabetes who enrolled or did not enroll in National Diabetes Prevention Programs (NDPPs). METHODS: Between 2015 and 2019, 776 University of Michigan employees, dependents, and retirees with prediabetes and overweight or obesity enrolled in one-year NDPPs. RESULTS: Enrollees attended a median of 18 sessions. Median retention was 38 weeks. Retention was associated with older age, greater initial weight loss, and physical activity. At both 1- and 2-years, body mass index, triglycerides, and HbA1c were significantly improved among enrollees. After adjusting for age group, sex, and race, the odds of developing diabetes based on HbA1c ≥6.5 % was 40 % lower at 1-year and 20 % lower at 2-years, and the odds of self-reported diabetes was 57 % lower at 1-year and 46 % lower at 2-years in enrollees compared to non-enrollees. Enrollees who disenrolled before completing the core curriculum had higher odds and enrollees who completed the NDPP had lower odds of developing diabetes that non-enrollees. CONCLUSIONS: In this population with prediabetes, NDPP retention was generally good, risk factors were improved, and diabetes was delayed or prevented for up to two years.

The healthy beverage index is not associated with insulin resistance, prediabetes and type 2 diabetes risk in the Rotterdam Study.

PURPOSE: Whether beverage quality affects changes in glycaemic traits and type 2 diabetes (T2D) risk is unknown. We examined associations of a previously developed Healthy Beverage Index (HBI) with insulin resistance, and risk of prediabetes and T2D. METHODS: We included 6769 participants (59% female, 62.0 ± 7.8 years) from the Rotterdam Study cohort free of diabetes at baseline. Diet was assessed using food-frequency questionnaires at baseline. The HBI included 10 components (energy from beverages, meeting fluid requirements, water, coffee and tea, low-fat milk, diet drinks, juices, alcohol, full-fat milk, and sugar-sweetened beverages), with a total score ranging from 0 to 100. A higher score represents a healthier beverage pattern. Data on study outcomes were available from 1993 to 2015. Multivariable linear mixed models and Cox proportional-hazards regression models were used to examine associations of the HBI (per 10 points increment) with two measurements of HOMA-IR (a proxy for insulin resistance), and risk of prediabetes and T2D. RESULTS: During follow-up, we documented 1139 prediabetes and 784 T2D cases. Mean ± SD of the HBI was 66.8 ± 14.4. Higher HBI score was not associated with HOMA-IR (ß: 0.003; 95% CI - 0.007, 0.014), or with risk of prediabetes (HR: 1.01; 95% CI 0.97, 1.06), or T2D (HR: 1.01; 95% CI 0.96, 1.07). CONCLUSION: Our findings suggest no major role for overall beverage intake quality assessed with the HBI in insulin resistance, prediabetes and T2D incidence. The HBI may not be an adequate tool to assess beverage intake quality in our population.

Lifestyle Intervention in NAFLD: Long-Term Diabetes Incidence in Subjects Treated by Web- and Group-Based Programs.

BACKGROUND: Behavioral programs are needed for prevention and treatment of NAFLD and the effectiveness of a web-based intervention (WBI) is similar to a standard group-based intervention (GBI) on liver disease biomarkers. OBJECTIVE: We aimed to test the long-term effectiveness of both programs on diabetes incidence, a common outcome in NAFLD progression. METHODS: 546 NAFLD individuals (212 WBI, 334 GBI) were followed up to 60 months with regular 6- to 12-month hospital visits. The two cohorts differed in several socio-demographic and clinical data. In the course of the years, the average BMI similarly decreased in both cohorts, by 5% or more in 24.4% and by 10% or more in 16.5% of cases available at follow-up. After excluding 183 cases with diabetes at entry, diabetes was newly diagnosed in 48 cases during follow-up (31 (16.6% of cases without diabetes at entry) in the GBI cohort vs. 17 (9.7%) in WBI; p = 0.073). Time to diabetes was similar in the two cohorts (mean, 31 ± 18 months since enrollment). At multivariable regression analysis, incident diabetes was significantly associated with prediabetes (odds ratio (OR) 4.40; 95% confidence interval (CI) 1.97-9.81; p < 0.001), percent weight change (OR 0.57; 95% CI 0.41-0.79; p < 0.001) and higher education (OR 0.49; 95% CI 0.27-0.86; p = 0.014), with no effect of other baseline socio-demographic, behavioral and clinical data, and of the type of intervention. The importance of weight change on incident diabetes were confirmed in a sensitivity analysis limited to individuals who completed the follow-up. CONCLUSION: In individuals with NAFLD, WBI is as effective as GBI on the pending long-term risk of diabetes, via similar results on weight change.

Long-term air pollution exposure and diabetes risk in American older adults: A national secondary data-based cohort study.

Type 2 diabetes is a major public health concern. Several studies have found an increased diabetes risk associated with long-term air pollution exposure. However, most current studies are limited in their generalizability, exposure assessment, or the ability to differentiate incidence and prevalence cases. We assessed the association between air pollution and first documented diabetes occurrence in a national U.S. cohort of older adults to estimate diabetes risk. We included all Medicare enrollees 65 years and older in the fee-for-service program, part A and part B, in the contiguous United States (2000-2016). Participants were followed annually until the first recorded diabetes diagnosis, end of enrollment, or death (264, 869, 458 person-years). We obtained annual estimates of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and warm-months ozone (O3) exposures from highly spatiotemporally resolved prediction models. We assessed the simultaneous effects of the pollutants on diabetes risk using survival analyses. We repeated the models in cohorts restricted to ZIP codes with air pollution levels not exceeding the national ambient air quality standards (NAAQS) during the study period. We identified 10, 024, 879 diabetes cases of 41, 780, 637 people (3.8% of person-years). The hazard ratio (HR) for first diabetes occurrence was 1.074 (95% CI 1.058; 1.089) for 5 µg/m3 increase in PM2.5, 1.055 (95% CI 1.050; 1.060) for 5 ppb increase in NO2, and 0.999 (95% CI 0.993; 1.004) for 5 ppb increase in O3. Both for NO2 and PM2.5 there was evidence of non-linear exposure-response curves with stronger associations at lower levels (NO2 ≤ 36 ppb, PM2.5 ≤ 8.2 µg/m3). Furthermore, associations remained in the restricted low-level cohorts. The O3-diabetes exposure-response relationship differed greatly between models and require further investigation. In conclusion, exposures to PM2.5 and NO2 are associated with increased diabetes risk, even when restricting the exposure to levels below the NAAQS set by the U.S. EPA.

The association of specific types of vegetables consumption with 10-year type II diabetes risk: Findings from the ATTICA cohort study.

BACKGROUND: The present study aimed to investigate the association between vegetable consumption, in total as well as per type/category, and 10-year type-2 diabetes mellitus (T2DM) incidence. METHODS: The ATTICA study was conducted during 2001-2012 in 3042 apparently healthy adults living in Athens area, Greece. A detailed biochemical, clinical, and lifestyle evaluation was performed; vegetable consumption (total, per type) was evaluated through a validated semi-quantitative food frequency questionnaire. After excluding those with no complete information of diabetes status or those lost at the 10-year follow-up, data from 1485 participants were used for the current analysis. RESULTS: After adjusting for several participants' characteristics, including overall dietary habits, it was observed that participants consuming at least 4 servings/day of vegetables had a 0.42-times lower risk of developing T2DM (hazard ratio [HR] = 0.42; 95% confidence interval [CI] = 0.29-0.61); the benefits of consumption were greater in women (HR = 0.29; 95% CI = 0.16-0.53) compared to men (HR = 0.56; 95% CI = 0.34-0.92). Only 33% of the sample consumed vegetables 4 servings/day. The most significant associations were observed for allium vegetables in women and for red/orange/yellow vegetables, as well as for legumes in men. CONCLUSIONS: The intake of at least 4 servings/day of vegetables was associated with a considerably reduced risk of T2DM, independently of other dietary habits; underlying the need for further elaboration of current dietary recommendations at the population level.

Upper arm length and knee height are associated with diabetes in the middle-aged and elderly: evidence from the China Health and Retirement Longitudinal Study.

OBJECTIVE: To determine if limb lengths, as markers of early life environment, are associated with the risk of diabetes in China. DESIGN: We performed a cohort analysis using data from the China Health and Retirement Longitudinal Study (CHARLS), and multivariable-adjusted Cox proportional hazard regression models were used to examine the associations between baseline limb lengths and subsequent risk of diabetes. SETTING: The CHARLS, 2011-2018. PARTICIPANTS: The study confined the eligible subject to 10 711 adults aged over 45 years from the CHARLS. RESULTS: During a mean follow-up period of 6·13 years, 1358 cases of incident diabetes were detected. When controlling for potential covariates, upper arm length was inversely related to diabetes (hazard ratio (HR) 0·95, 95 % CI (0·91, 0·99), P = 0·028), and for every 1-cm difference in knee height, the risk of diabetes decreased by about 4 % (HR 0·96, 95 % CI (0·93, 0·99), P = 0·023). The association between upper arm length and diabetes was only significant among females while the association between knee height and diabetes was only significant among males. In analyses stratified by BMI, significant associations between upper arm length/knee height and diabetes only existed among those who were underweight (HR 0·91, 95 % CI (0·83, 1·00), P = 0·049, HR 0·92, 95 % CI (0·86, 0·99), P = 0·031). CONCLUSIONS: Inverse associations were observed between upper arm length, knee height and the risk for diabetes development in a large Asian population, suggesting early life environment, especially infant nutritional status, may play an important role in the determination of future diabetes risk.

Association of pancreatitis with risk of diabetes: analysis of real-world data.

Introduction: Diabetes is a major cause of disease burden with considerable public health significance. While the pancreas plays a significant role in glucose homeostasis, the association between pancreatitis and new onset diabetes is not well understood. The purpose of this study was to examine that association using large real-world data. Materials and methods: Utilizing the IBM® MarketScan® commercial claims database from 2016 to 2019, pancreatitis and diabetes regardless of diagnostic category, were identified using International Classification of Diseases, Tenth Revision [ICD-10] codes. We then performed descriptive analyses characterizing non-pancreatitis (NP), acute pancreatitis (AP), and chronic pancreatitis (CP) cohort subjects. Stratified Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of diabetes across the three clinical categories. Results: In total, 310,962 individuals were included in the analysis. During 503,274 person-years of follow-up, we identified 15,951 incident diabetes cases. While men and women had higher incidence rates of CP and AP-related diabetes, the rates were significantly greater in men and highest among individuals with CP (91.6 per 1000 persons-years (PY)) followed by AP (75.9 per 1000-PY) as compared to those with NP (27.8 per 1000-PY). After adjustment for diabetes risk factors, relative to the NP group, the HR for future diabetes was 2.59 (95% CI: 2.45-2.74) (P<0.001) for the CP group, and 2.39 (95% CI: 2.30-2.48) (P<0.001) for the AP group. Conclusion: Pancreatitis was associated with a high risk of diabetes independent of demographic, lifestyle, and comorbid conditions.

Fasting plasma glucose and HbA1c levels predict the risk of type 2 diabetes and diabetic retinopathy in a Thai high-risk population with prediabetes.

Introduction: The incidences of diabetes and diabetic retinopathy (DR) in Thai high-risk individuals with prediabetes have not been identified. This study compared diabetes and DR incidences among people at risk with different glycemic levels, using fasting plasma glucose (FPG) and hemoglobin A1C (HbA1c). Materials and methods: A historical cohort study estimating risk of type 2 diabetes and DR was conducted among outpatients, using FPG and HbA1c measurements at recruitment and monitored for ≥5 years. High-risk participants (defined as having metabolic syndrome or atherosclerotic cardiovascular disease) were categorized by glycemic level into 4 groups: 1) impaired fasting glucose (IFG)-/HbA1c- (FPG <110 mg/dl; HbA1c < 6.0%); 2) IFG+/HbA1c- (FPG 110-125 mg/dl; HbA1c < 6.0%); 3) IFG-/HbA1c+ (FPG <110 mg/dl; HbA1c 6.0%-6.4%); and 4) IFG+/HbA1c+ (FPG 110-125 mg/dl; HbA1c 6.0%-6.4%). The incidences of type 2 diabetes mellitus (T2DM) and DR were obtained and estimated using Kaplan-Meier analysis. Cox regression models explored hazard ratios (HRs). Results: We recruited 8,977 people at risk (metabolic syndrome, 89.9%; atherosclerotic cardiovascular disease, 16.9%). The baseline cohort consisted of 1) IFG-/HbA1c- (n = 4,221; 47.0%); 2) IFG+/HbA1c- (n = 1,274; 14.2%); 3) IFG-/HbA1c+ (n = 2,151; 24.0%); and 4) IFG+/HbA1c+ (n = 1,331; 14.8%). Their 5-year T2DM incidences were 16.0%, 26.4%, 30.8%, and 48.5% (p < 0.001). The median DR follow-up was 7.8 years (interquartile range, 7.0-8.4 years). The DR incidences were 0.50, 0.63, 1.44, and 2.68/1,000 person-years (p < 0.001) for IFG-/HbA1c-, IFG+/HbA1c-, IFG-/HbA1c+, and IFG+/HbA1c+, respectively. Compared with IFG-/HbA1c-, the multivariable-adjusted HRs (95% CI) for incident diabetes were 1.94 (1.34-2.80), 2.45 (1.83-3.29), and 4.56 (3.39-6.15) for IFG+/HbA1c-, IFG-/HbA1c+, and IFG+/HbA1c+, respectively. As for incident DR, the corresponding HRs were 0.67 (0.08-5.76), 4.74 (1.69-13.31), and 5.46 (1.82-16.39), respectively. Conclusion: The 5-year incidence of T2DM in Thai high-risk participants with prediabetes was very high. The incidences of diabetes and DR significantly increased with higher degrees of dysglycemia. High-risk people with FPG 110-125 mg/dl and HbA1c 6.0%-6.4% were more likely to develop T2DM and DR. Such individuals should receive priority lifestyle and pharmacological management.

Consumption of different animal-based foods and risk of type 2 diabetes: An umbrella review of meta-analyses of prospective studies.

We performed an umbrella review of dose-response meta-analyses of prospective studies reporting the incidence of type 2 diabetes associated with the consumption of animal-based foods. A systematic search was conducted in PubMed, Web of Science, Scopus, and Embase according to PRISMA. Thirteen meta-analyses are included in the study providing 175 summary risk ratio estimates. The consumption of 100 g/day of total or red meat, or 50 g/day of processed meat, were associated with an increased risk; RR and 95 % CI were respectively 1.20, 1.13-1.27; 1.22, 1.14-1.30 and 1.30, 1.22-1.39. White meat (50 g/day) was associated with an increased risk, but of lesser magnitude (RR 1.04, 95 % CI 1.00-1.08). A risk reduction was reported for 200 g/day of total dairy (RR 0.95, 95 % CI 0.92-0.98) or low-fat dairy (RR 0.96, 95 % CI 0.92-1.00) or milk (RR 0.90, 95 % CI 0.83-0.98), or 100 g/day of yogurt (RR 0.94, 95 % CI 0.90-0.98). No association with diabetes risk was reported for fish or eggs. In conclusions animal-based foods have a different association with diabetes risk. To reduce diabetes risk the consumption of red and processed meat should be restricted; a moderate consumption of dairy foods, milk and yogurt, can be encouraged; moderate amounts of fish and eggs are allowed.

The Long-Term Effects of Non-Pharmacological Interventions on Diabetes and Chronic Complication Outcomes in Patients With Hyperglycemia: A Systematic Review and Meta-Analysis.

Objective: This study aimed at examining the long-term effects of non-pharmacological interventions on reducing the diabetes incidence among patients with prediabetes and chronic complications events among patients with hyperglycemia (pre-diabetes and diabetes) by performing a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: PubMed, MEDLINE, EMBASE, the Cochrane Library, and the Web of Science Core Collection were searched for studies published between January 1990 and November 2021, looking for RCTs to evaluate the effects of non-pharmacological interventions on preventing the incidence of diabetes and chronic complications in comparison with medical therapy, placebo, or usual diabetes care. Two independent reviews extracted relevant data and quality assessment. Any discrepancies were resolved by a third reviewer. Results: In total, 20 articles involved 16 RCTs (follow-up ranged from 2 to 30 years) were included. Pooled analysis of intervention studies demonstrated clearly that non-pharmacological interventions have a significant effect on reducing the diabetes events in patients with prediabetes (RR 0.62; 95% CI 0.54, 0.71). Pooled analysis of extended follow-up studies showed that non-pharmacological interventions could effectively reduce the diabetes incidence in patients with prediabetes (RR 0.78; 95% CI 0.63, 0.96). Meta-regression and subgroup analysis indicates that the diabetes incidence of the long-term group (duration > 3 years) was clearly reduced by 0.05% compared with the relatively short-term group (duration ≤ 3 years). The incidence of microvascular complications in patients with hyperglycemia was effectively lowered by non-pharmacological interventions (RR 0.60; 95% CI 0.43, 0.83). Conclusion: Non-pharmacological interventions have a long-term effect on reducing the diabetes incidence among prediabetic patients and effectively preventing microvascular complications on hyperglycemia. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/.

A comparative study on the incidence of type 1 diabetes mellitus between children of North African migrants and Italian children in Emilia-Romagna region, Italy.

In the last few decades, many studies have reported an increasing global incidence of type 1 diabetes. Studies on migrant populations have underlined the importance of both environmental and genetic factors. AIMS: Evaluate the incidence of type 1 diabetes in North African vs Italian children aged 0-14 years from 1 January 2015, to 31st December 2018, in Emilia-Romagna region, Italy. METHODS: Clinical and epidemiological data about childhood onset type 1 diabetes in Emilia Romagna region were retrospectively collected by the regional centers of pediatric diabetology and matched using 3 different data sources. RESULTS: 365 new cases were diagnosed. Total cumulative incidence was 15.4/100,000/year. North African cases showed a cumulative incidence of 53.8/100,000/year, statistically significant compared to cumulative incidence of the Italian cases alone 13.1/100,000/year (p value < 0.001). The annual incidence did not differ in the 4 years for both groups.  Conclusion: The incidence of type 1 diabetes in the pediatric age (0 14 years) was significantly higher in the North African population than in the Italian one, suggesting that a mix of genetic and environmental factors may have caused the increase in newly diagnosed cases. WHAT IS KNOWN: • The incidence of type 1 diabetes largely varies worldwide. • Study on immigrants helped to better understand the interplay role between genetics and environment. WHAT IS NEW: • This is the first study focused on the incidence of children and adolescents of North African migrants in Italy. • The incidence of children and adolescents of North African migrants in Emilia Romagna region, Italy, seems to be higher than that reported in the host countries, and, above all, than that reported in highest-incidence countries in Europe and in the world.

Hyperglycaemic disorders associated with PCSK9 inhibitors: a real-world, pharmacovigilance study.

AIMS: While genetic and biological studies indicated a potential association between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and hyperglycaemia, real-world data are limited. Therefore, we sought to investigate this association using the FDA adverse event reporting system (FAERS). METHODS AND RESULTS: The FAERS database (2015-2020) was retrospectively queried to characterize reporting of hyperglycaemic adverse events (AEs) with PCSK9i. Disproportionality analyses were performed using the adjusted reporting odds ratio (adj.ROR), and the lower bound of the information component (IC) 95% credibility interval (IC025 > 0 is deemed significant). Among 7 295 624 eligible patients, 71 748 reports of evolocumab and 15 976 of alirocumab were identified. Compared to the full database, PCSK9i treatment was associated with increased reporting of hyperglycaemic AEs [n = 1841, adj.ROR = 1.14 (1.07-1.22), IC025 = 0.13]. Hyperglycaemic AEs were primarily mild hyperglycaemia [n = 1469, adj. ROR = 1.48 (1.36-1.62), IC025 = 0.51] rather than diabetes [n = 372, adj. ROR = 0.67 (0.60-0.74), IC025 = -0.90]. Among PCSK9i agents, evolocumab, but not alirocumab, was associated with hyperglycaemic AEs [n = 1587, adj. ROR = 1.24 (1.15-1.32), IC025 = 0.20; n = 254, adj. ROR = 0.73 (0.60-0.88), IC025 = -0.38, respectively]. Hyperglycaemic AEs were reported more often with PCSK9i compared to ezetimibe [adj.ROR = 1.99 (1.35-2.94)], and less often compared to statins [adj.ROR = 0.26 (0.25-0.28)]. Notably, hyperglycaemic AEs were reported more frequently by diabetic than by non-diabetic patients (P < 0.001), mostly occurred within 6 months of treatment and were reversible upon drug discontinuation. CONCLUSION: In a real-world setting, PCSK9i treatment was associated with increased reporting of mild hyperglycaemia, but not diabetes. While initial monitoring is warranted, the favourable glycaemic safety profile compared to statins supports their essential role in the management of lipid disorders.

Knockout of the Amino Acid Transporter SLC6A19 and Autoimmune Diabetes Incidence in Female Non-Obese Diabetic (NOD) Mice.

High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19+/+ and NOD.Slc6a19-/- mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41-1.42; Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19+/+ and NOD.Slc6a19-/- mice, respectively (ratio 1.1, 95% confidence interval 0.6-2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.

Dairy Consumption and 3-Year Risk of Type 2 Diabetes after Myocardial Infarction: A Prospective Analysis in the Alpha Omega Cohort.

Population-based studies suggest a role for dairy, especially yogurt, in the prevention of type 2 diabetes (T2D). Whether dairy affects T2D risk after myocardial infarction (MI) is unknown. We examined associations of (types of) dairy with T2D incidence in drug-treated, post-MI patients from the Alpha Omega Cohort. The analysis included 3401 patients (80% men) aged 60-80 y who were free of T2D at baseline (2002-2006). Dairy intakes were assessed using a validated food-frequency questionnaire. Incident T2D was ascertained through self-reported physician diagnosis and/or medication use. Multivariable Cox models were used to calculate Hazard ratios (HRs) and 95% confidence intervals (CI) for T2D with dairy intake in categories and per 1-standard deviation (SD) increment. Most patients consumed dairy, and median intakes were 264 g/d for total dairy, 82 g/d for milk and 41 g/d for yogurt. During 40 months of follow-up (10,714 person-years), 186 patients developed T2D. After adjustment for confounders, including diet, HRs per 1-SD were 1.06 (95% CI 0.91-1.22) for total dairy, 1.02 (0.88-1.18) for milk and 1.04 (0.90-1.20) for yogurt. Associations were also absent for other dairy types and in dairy categories (all p-trend > 0.05). Our findings suggest no major role for dairy consumption in T2D prevention after MI.

Irrational beliefs trigger depression and anxiety symptoms, and associated with increased inflammation and oxidative stress markers in the 10-year diabetes mellitus risk: the ATTICA epidemiological study.

PURPOSE: To investigate the combined role of irrational beliefs, anxiety and depression in the 10-year incidence of type 2 diabetes, and the underlying effect of biochemical, and socio-behavioural factors. METHODS: Within the context of the ATTICA cohort study (2002-2012), 853 participants without evidence of CVD [453 men (45 ± 13 years) and 400 women (44 ± 18 years)] underwent psychological evaluation through the Irrational Beliefs Inventory (IBI) (range 0-88), the Zung Self-Rating-Depression-Scale (ZDRS) and the State-Trait-Anxiety-Inventory (STAI). Diagnosis of diabetes at follow-up examination was based on the criteria of the American Diabetes Association (ADA). RESULTS: Mean IBI score was 53 ± 10 in men and 51 ± 11 in women (p = 0.68). Participants with high irrational beliefs who also had anxiety symptoms had a 93% excess risk of developing diabetes during the 10-year follow-up (Hazard Ratio 1.93; 95%CI 1.34, 2.78) as compared to those without anxiety. Moreover, diabetes risk was 73% higher among individuals with high levels of irrational beliefs and depression as compared to those where depression was absent (1.73; 1.21, 2.46). Lower education status, family history of diabetes, hypercholesterolemia, high BMI, as well as tumor necrosis factor and total antioxidant capacity were revealed as mediating risk factors related to the tested associations. CONCLUSION: Irrational beliefs among apparently healthy adults trigger depression and anxiety symptomatology, and through the increased inflammation and oxidative stress profile, were associated with increased diabetes risk. This observation moves psychological research a step forward in supporting and guiding primary prevention of mental health and metabolic conditions.