Reduced Risk Of Type 2 Diabetes Research Articles

Loneliness, Discrimination, Stress, and Type 2 Diabetes Risk in Young Adults

IntroductionThe aim of this study was to determine the associations between type 2 diabetes (T2D) or prediabetes and loneliness and related social experiences in young adults, a population at increasingly high risk of T2D. MethodsThis was a cross-sectional analysis using data from adults ages 18-35 enrolled in the All of Us Research Program. Exposures included loneliness, social support, discrimination, neighborhood social cohesion, and stress, measured by standardized surveys. The main outcome was T2D or prediabetes by self-report or linked health record. Logistic regression determined odds of T2D/prediabetes for each survey measure, adjusting for age, sex, race or ethnicity, income, and family history. Latent class analysis (LCA) evaluated clustering of social experiences. Data was collected from 2018-2022 and analyzed May 2023-June 2024. ResultsThe cohort included 14,217 young adults (28.2 ± 4.4 years; 70.3% (n=9,792) women; 64.1% (n=9,111) White, 10.6% (n=1,506) Hispanic, 5.7% (n=806) Black, 9.1% (n=1,299) multiracial). Overall, 5.5% (n=777) had either prediabetes or T2D. The two highest loneliness quartiles were associated with increased odds of prediabetes/T2D (Q3: OR 1.42 [95% CI 1.15-1.76]; Q4: 1.75 [95% CI 1.43-2.16]). Greater stress and discrimination and lower social support and neighborhood social cohesion were also associated with increased odds of prediabetes/T2D. LCA revealed three distinct phenotypes, with elevated odds of prediabetes/T2D in the two with the most adverse social profiles (OR 2.32 [95% CI 1.89-2.84] and OR 1.28 [95% CI 1.04-1.58]). ConclusionsLoneliness and related experiences are strongly associated with T2D and prediabetes in young adults. Whether these factors could be leveraged to reduce T2D risk should be investigated.

Testosterone and the prevention of type 2 diabetes mellitus: therapeutic implications from recent trials.

Type 2 diabetes (T2D) is increasing to epidemic proportions and frequently associated with obesity and a low serum testosterone concentration in men. This review valuates recent randomized controlled trials (RCTs) investigating the effect of testosterone treatment on glycemic control and T2D prevention. The 2-year Testosterone for the Prevention of Type 2 diabetes Trial (T4DM) study showed that in men aged 50 years and over with visceral obesity and impaired glucose tolerance, testosterone treatment on the background of a lifestyle intervention reduced T2D risk by 40%. The Testosterone Effects on Atherosclerosis Progression in Aging Men and Testosterone Trials demonstrated modest improvements in insulin sensitivity and body composition. However, the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men trial found no significant glycemic benefits over 2 years. Recent data from the Diabetes Prevention Program Outcome Study support the cost efficacy and durability of metformin. In men at high risk of T2D, treatment with testosterone prevents the disease; however, there are caveats to its use and other approaches may be more applicable. Differences in trial designs, age groups, and outcome measures contribute to varying results. HbA1C is a suboptimal outcome measure. Future research should explore potential synergies between testosterone and GLP-1 receptor agonists in T2D management, while considering cost-effectiveness.

The Other Side of the Perfect Cup: Coffee-Derived Non-Polyphenols and Their Roles in Mitigating Factors Affecting the Pathogenesis of Type 2 Diabetes.

The global prevalence of type 2 diabetes (T2D) is 10.5% among adults in the age range of 20-79 years. The primary marker of T2D is persistent fasting hyperglycemia, resulting from insulin resistance and β-cell dysfunction. Multiple factors can promote the development of T2D, including obesity, inflammation, and oxidative stress. In contrast, dietary choices have been shown to prevent the onset of T2D. Oatmeal, lean proteins, fruits, and non-starchy vegetables have all been reported to decrease the likelihood of T2D onset. One of the most widely consumed beverages in the world, coffee, has also demonstrated an impressive ability to reduce T2D risk. Coffee contains a diverse array of bioactive molecules. The antidiabetic effects of coffee-derived polyphenols have been thoroughly described and recently reviewed; however, several non-polyphenolic molecules are less prominent but still elicit potent physiological actions. This review summarizes the effects of select coffee-derived non-polyphenols on various aspects of T2D pathogenesis.

Joint B Vitamin Intake and Type 2 Diabetes Risk: The Mediating Role of Inflammation in a Prospective Shanghai Cohort.

Type 2 diabetes (T2D) is a global and complex public health challenge, and dietary management is acknowledged as critical in its prevention. Recent studies have highlighted the involvement of micronutrients in T2D pathophysiology; our study aims to assess the association between B vitamin intake and T2D risks and the mediating role of inflammation. In a prospective cohort design, data on B vitamins intake, including thiamine (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), folate (B9), and cobalamin (B12), was obtained using a validated food frequency questionnaire (FFQ), and blood inflammatory biomarkers were analyzed according to standard protocol in the local hospitals at baseline from 44,960 adults in the Shanghai Suburban Adult Cohort and Biobank (SSACB). Incident T2D cases were identified according to a physician's diagnosis or medication records from the electronic medical information system. We employed logistic and weighted quantile sum regression models to explore the associations of single and combined levels of B vitamins with T2D and mediation analyses to investigate the effects of inflammation. Negative correlations between B vitamins and T2D were observed in the single-exposure models, except for B3. The analyses of joint exposure (B1, B2, B6, B9, and B12) also showed an inverse association (OR 0.80, 95% CI 0.71 to 0.88), with vitamin B6 accounting for 45.58% of the effects. Further mediation analysis indicated a mediating inflammatory impact, accounting for 6.72% of the relationship. Dietary intake of B vitamins (B1, B2, B6, B9, B12) was associated with a reduced T2D risk partially mediated by inflammation in Shanghai residents.

Combined associations of visceral adipose tissue and adherence to a Mediterranean lifestyle with T2D and diabetic microvascular complications among individuals with prediabetes

BackgroundIt’s unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes.Methods11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as “Mediterranean food consumption,” “Mediterranean dietary habits,” and “Physical activity, rest, social habits, and conviviality.” Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors.ResultsOver a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71–0.98) and 31% for incident DMC (0.69, 0.56–0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72–7.49) and incident any DMC (1.79, 1.36–2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08–0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC.ConclusionHigh adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT’s risk partly. The Mediterranean lifestyle’s adaptability to diverse populations suggests promise for preventing T2D.

Higher habitual intakes of flavonoids and flavonoid-rich foods are associated with a lower incidence of type 2 diabetes in the UK Biobank cohort

AimTo examine the associations of a diet high in flavonoid-rich foods, as reflected by a “Flavodiet Score” (FDS), the major individual food contributors to flavonoid intake, and flavonoid subclasses with type 2 diabetes (T2D) risk in the UK Biobank cohort.Materials and methodsFlavonoid intakes were estimated from ≥2 dietary assessments among 113,097 study participants [age at enrolment: 56 ± 8 years; 57% female] using the U.S Department of Agriculture (USDA) databases. Multivariable Cox proportional hazards models were used to investigate associations between dietary exposures and T2D.ResultsDuring 12 years of follow-up, 2628 incident cases of T2D were identified. A higher FDS (compared to lower [Q4 vs. Q1]), characterised by an average of 6 servings of flavonoid-rich foods per day, was associated with a 26% lower T2D risk [HR: 0.74 (95% CI: 0.66–0.84), ptrend = <0.001]. Mediation analyses showed that lower body fatness and basal inflammation, as well as better kidney and liver function partially explain this association. In food-based analyses, higher intakes of black or green tea, berries, and apples were significantly associated with 21%, 15%, and 12% lower T2D risk. Among individual flavonoid subclasses, 19–28% lower risks of T2D were observed among those with the highest, compared to lowest intakes.ConclusionsA higher consumption of flavonoid-rich foods was associated with lower T2D risk, potentially mediated by benefits to obesity/sugar metabolism, inflammation, kidney and liver function. Achievable increases in intakes of specific flavonoid-rich foods have the potential to reduce T2D risk.

Adipose Tissue Insulin Resistance in South Asian and Nordic Women after Gestational Diabetes Mellitus

South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1–3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs.

Genetic predisposition to bone mineral density and their health conditions in East Asians.

Osteoporosis, a condition defined by low BMD (typically < -2.5 SD), causes a higher fracture risk and leads to significant economic, social, and clinical impacts. Genome-wide studies mainly in Caucasians have found many genetic links to osteoporosis, fractures, and BMD, with limited research in East Asians (EAS). We investigated the genetic aspects of BMD in 86 716 individuals from the Taiwan Biobank and their causal links to health conditions within EAS. A genome-wide association study (GWAS) was conducted, followed by observational studies, polygenic risk score assessments, and genetic correlation analyses to identify associated health conditions linked to BMD. GWAS and gene-based GWAS studies identified 78 significant SNPs and 75 genes related to BMD, highlighting pathways like Hedgehog, WNT-mediated, and TGF-β. Our cross-trait linkage disequilibrium score regression analyses for BMD and osteoporosis consistently validated their genetic correlations with BMI and type 2 diabetes (T2D) in EAS. Higher BMD was linked to lower osteoporosis risk but increased BMI and T2D, whereas osteoporosis linked to lower BMI, waist circumference, hemoglobinA1c, and reduced T2D risk. Bidirectional Mendelian randomization analyses revealed that a higher BMI causally increases BMD in EAS. However, no direct causal relationships were found between BMD and T2D, or between osteoporosis and either BMI or T2D. This study identified key genetic factors for bone health in Taiwan, and revealed significant health conditions in EAS, particularly highlighting the genetic interplay between bone health and metabolic traits like T2D and BMI.

Child Opportunity Index and clinical characteristics at diabetes diagnosis in youth: type 1 diabetes versus type 2 diabetes

IntroductionAmong youth with type 1 diabetes (T1D), longitudinal poor glycemic control is associated with adverse socioeconomic conditions at the neighborhood level. Child Opportunity Index (COI), which encompasses measures of education,...

Effect of viral hepatitis on type 2 diabetes: A Mendelian randomization study.

The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.

Exploring the role of purinergic receptor P2RY1 in type 2 diabetes risk and pathophysiology: Insights from human functional genomics

ObjectiveHuman functional genomics has proven powerful in discovering drug targets for common metabolic disorders. Through this approach, we investigated the involvement of the purinergic receptor P2RY1 in type 2 diabetes (T2D). MethodsP2RY1 was sequenced in 9,266 participants including 4,177 patients with T2D. In vitro analyses were then performed to assess the functional effect of each variant. Expression quantitative trait loci (eQTL) analysis was performed in pancreatic islets from 103 pancreatectomized individuals. The effect of P2RY1 on glucose-stimulated insulin secretion was finally assessed in human pancreatic beta cells (EndoCβH5), and RNA sequencing was performed on these cells. ResultsSequencing P2YR1 in 9,266 participants revealed 22 rare variants, seven of which were loss-of-function according to our in vitro analyses. Carriers, except one, exhibited impaired glucose control. Our eQTL analysis of human islets identified P2RY1 variants, in a beta-cell enhancer, linked to increased P2RY1 expression and reduced T2D risk, contrasting with variants located in a silent region associated with decreased P2RY1 expression and increased T2D risk. Additionally, a P2RY1-specific agonist increased insulin secretion upon glucose stimulation, while the antagonist led to decreased insulin secretion. RNA-seq highlighted TXNIP as one of the main transcriptomic markers of insulin secretion triggered by P2RY1 agonist. ConclusionOur findings suggest that P2RY1 inherited or acquired dysfunction increases T2D risk and that P2RY1 activation stimulates insulin secretion. Selective P2RY1 agonists, impermeable to the blood–brain barrier, could serve as potential insulin secretagogues.

Ancestry-attenuated effects of socioeconomic deprivation on type 2 diabetes disparities in the All of Us cohort

BackgroundDiabetes is a common disease with a major burden on morbidity, mortality, and productivity. Type 2 diabetes (T2D) accounts for roughly 90% of all diabetes cases in the USA and has a greater observed prevalence among those who identify as Black or Hispanic.MethodsThis study aimed to assess T2D racial and ethnic disparities using the All of Us Research Program data and to measure associations between genetic ancestry (GA), socioeconomic deprivation, and T2D. We used the All of Us Researcher Workbench to analyze T2D prevalence and model its associations with GA, individual-level (iSDI), and zip code-based (zSDI) socioeconomic deprivation indices among participant self-identified race and ethnicity (SIRE) groups.ResultsThe study cohort of 86,488 participants from the four largest SIRE groups in All of Us: Asian (n = 2311), Black (n = 16,282), Hispanic (n = 16,966), and White (n = 50,292). SIRE groups show characteristic genetic ancestry patterns, consistent with their diverse origins, together with a continuum of ancestry fractions within and between groups. The Black and Hispanic groups show the highest levels of socioeconomic deprivation, followed by the Asian and White groups. Black participants show the highest age- and sex-adjusted T2D prevalence (21.9%), followed by the Hispanic (19.9%), Asian (15.1%), and White (14.8%) groups. Minority SIRE groups and socioeconomic deprivation, both iSDI and zSDI, are positively associated with T2D, when the entire cohort is analyzed together. However, SIRE and GA both show negative interaction effects with iSDI and zSDI on T2D. Higher levels of iSDI and zSDI are negatively associated with T2D in the Black and Hispanic groups, and higher levels of iSDI and zSDI are negatively associated with T2D at high levels of African and Native American ancestry.ConclusionsSocioeconomic deprivation is associated with a higher prevalence of T2D in Black and Hispanic minority groups, compared to the majority White group. Nonetheless, socioeconomic deprivation is associated with reduced T2D risk within the Black and Hispanic groups. These results are paradoxical and have not been reported elsewhere, with possible explanations related to the nature of the All of Us data along with SIRE group differences in access to healthcare, diet, and lifestyle.

You are What You Drink? How Associations Between Profiles of Beverage Consumption and Type 2 Diabetes Risk are Mediated by Biomarker Networks

BackgroundMultiple studies have independently investigated the associations of the consumption of individual beverage types and specific plasma biomarkers with the risk of type 2 diabetes (T2D). However, as individuals do not consume single beverage types exclusively and plasma biomarkers do not act in isolation, it remains unclear how patterns of beverage consumption and plasma biomarker networks associate both with each other and T2D risk. ObjectivesWe aimed to elucidate potential dietary determinants of T2D risk by defining a model that describes habitual beverage consumption profiles in relation to identified networks of circulating plasma biomarkers. MethodsThis study included 1,461 case and 1,568 control participants from case-control studies of T2D nested within the Nurses’ Health Study. Participants completed validated semiquantitative food frequency questionnaires that assessed habitual beverage consumption, and they provided blood samples from which 27 plasma biomarkers of cardiometabolic risk were identified. Common exploratory factor analysis (EFA) identified factors that separately described beverage consumption profiles and biomarker networks. Multivariable-adjusted regression elucidated the relationships between beverage and biomarker factors and T2D risk. ResultsEFA revealed five factors describing unique beverage consumption profiles and seven factors describing biomarker networks. The factor describing alcoholic beverage consumption was associated with a reduced risk of T2D (odds ratio [OR]: 0.50 [0.40, 0.64], P<0.001) mediated, in part, by the factor describing increased concentrations of adiponectin biomarkers (19.9% [12.0, 31.1] P = 0.004). The factor describing low-calorie sweetened beverage (LCSBs) consumption was associated with an increased risk of T2D (OR: 1.33 [1.03, 1.72], P = 0.021), and the factor describing lower concentrations of insulin-like growth factor binding proteins 1 and 2, and soluble leptin receptor, and increased leptin concentrations (P = 0.005). ConclusionsModerate alcohol consumption was associated with reduced T2D risk, mediated in part by increased circulating adiponectin. LCSB consumption was associated with both increased T2D risk and perturbed insulin-like growth factor and leptin signaling.

Partial substitution of red or processed meat with plant-based foods and the risk of type 2 diabetes

High consumption of red and processed meat has been associated with increased type 2 diabetes (T2D) risk. These kinds of diets are also environmentally unsustainable. We examined a modeled association between a partial substitution of red meat or processed meat with plant-based foods (legumes, vegetables, fruit, cereals, or a combination of these) and T2D risk among Finnish adults. We used pooled data from five Finnish cohorts (n = 41,662, 22% women, aged ≥ 25 years, 10.9 years median follow-up with 1750 incident T2D cases). Diet was assessed by a validated food frequency questionnaire. In the substitution models, 100 g/week of red meat or 50 g/week of processed meat were substituted with similar amounts of plant-based substitutes. Cohort-specific hazard ratios (HRs) were estimated by Cox proportional hazards multivariable model and pooled using a two-staged random-effects model. We observed small, but statistically significant, reductions in T2D risk in men when red or processed meat were partially substituted with fruits (red meat: HR 0.98, 95% CI 0.97–1.00, P = 0.049, processed meat: 0.99, 0.98–1.00, P = 0.005), cereals (red meat: 0.97, 0.95–0.99, P = 0.005, processed meat: 0.99, 0.98–1.00, P = 0.004) or combination of plant-based foods (only processed meat: 0.99, 0.98–1.00, P = 0.004) but not with legumes or vegetables. The findings of women were similar but not statistically significant. Our findings suggest that even small, easily implemented, shifts towards more sustainable diets may reduce T2D risk particularly in men.

Dairy foods and cardiometabolic diseases: an update and a reassessment of the impact of SFA.

Type 2 diabetes (T2D) and CVD are major causes of mortality and chronic morbidity. Whilst mortality from CVD has decreased they remain the largest cause of death in Europe and the prevalence of T2D is increasing rapidly. A consistent component of public health advice is to reduce intake of SFA to reduce CVD in particular, which implies limiting dairy food consumption. The prospective studies and randomised controlled trials included in this review show that for dairy foods at least, SFA are not consistently associated with CVD or T2D risk. For CVD the association with dairy foods is generally neutral despite dairy foods being the major source of SFA in many diets. This creates considerable doubt, at least for dairy foods, concerning the validity of the traditional diet-heart hypothesis which positively relates SFA intake to increased serum LDL-cholesterol and subsequent increased CVD. There is now emerging evidence to explain this which is highly relevant to dairy foods. These include the potentially counterbalancing effect of SFA-stimulated HDL-cholesterol and specific food matrix factors. In addition, SFA are associated with the less atherogenic large buoyant LDL particles and possible counterbalancing hypotensive effects of dairy proteins. Overall, dairy foods have either a neutral or beneficial association with CVD and T2D. Beneficial associations are seen for blood pressure and the reduced T2D risk linked to yoghurt consumption, a subject that needs urgent attention given the sharp rise in T2D prevalence in many countries.

The 18-month efficacy of an Intensive LifeStyle Modification Program (ILSM) to reduce type 2 diabetes risk among rural women: a cluster randomized controlled trial

BackgroundMany lifestyle interventions have demonstrated efficacy up to one-year follow-up, yet maintaining improvements at longer-term follow-up is a well-recognized worldwide challenge, especially in underserved areas. The purpose of this study is to compare the 18-month efficacy of an Intensive LifeStyle Modification Program to usual care in reducing the risk for type 2 diabetes (T2D) among women with a history of gestational diabetes mellitus (GDM).MethodsWe conducted a two-arm, cluster randomized controlled trial among women with a history of GDM in China. A total of 16 towns (clusters) in two distinct rural areas in south-central China were randomly selected (8 towns per area) and assigned (1:1) to the intervention (Intensive LifeStyle Modification Program) or control (usual care) group with stratification in the two rural areas. The strategies for maintaining intervention effects were used (including setting recursive goals and providing a supportive environment, etc.) under the guidance of social cognitive theory. The primary outcome was a change in T2D risk; secondary outcomes included glycemic, weight-related, behavioral, and psychological variables. All outcomes were collected at baseline, 6, and 18 months. All participants entered the intention-to-treat analysis. Data were analyzed via generalized estimation equation models (accounting for clusters) at the individual level, with subgroup analysis included in the model.ResultsThe sample included 320 women from 16 clusters (20 women per cluster). At 18 months, the intervention group demonstrated a significant improvement in T2D risk score, fasting blood glucose, body mass index (BMI), waist circumference, intention to eat low glycemic index food, perceived stress, quality of life in psychological and environmental domains, and social support over time (p < 0.05) based on the intention-to-treat analysis set. Subgroup analysis showed a significant interaction effect on T2D risk score in subgroups of different BMI, waist circumference, and blood glucose (p < 0.05).ConclusionsOver 18 months, the Intensive LifeStyle Modification Program reduced T2D risk among rural women with a history of GDM in China. Women who were overweight, had high abdominal adiposity, or had blood glucose intolerance benefited more from this intervention. This program serves as a potential diabetes prevention model for women with a history of GDM in low-resource settings worldwide.Trial registrationRegistered on Chinese Clinical Trial Registry (ChiCTR1800015023) on 1st March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25569

Primary care nurse practitioner practices to lower type 2 diabetes risks in women with a history of gestational diabetes mellitus

Women with a gestational diabetes mellitus (GDM) history have increased lifetime type 2 diabetes (T2D) risk, with 16 times greater risk 3 to 6 years after the pregnancy, compared with women without GDM. Offspring from diabetes-complicated pregnancies also face increased health risks. The study purpose was to describe the primary care practices of nurse practitioners (NPs) aimed at reducing T2D-related health risks in women with a history of GDM. Florida-licensed primary care NPs (n = 47) completed a 57-item online survey that included an 8-item scale about recommended practices to reduce T2D risks for women with GDM history. Descriptive statistics, Chi Square test, and Fisher exact test were conducted. Most (67%) participants "often/always" screened for T2D every 1-3 years per guidelines, but only 31.8% "often/always" advised about pregnancy planning/preconception T2D assessment. Compared with "none" or ≤2 hours of GDM care education, participants with >2 hours were more likely (p < .05) to "often/always" perform five recommended practices: 1) counsel about increased T2D risks; 2) educate about self-advocacy for T2D screening; 3) T2D screening every 1-3 years; 4) counsel about breastfeeding to reduce T2D risk; and 5) discuss postpartum weight loss and increased physical activity to lower T2D risk. Findings indicate inconsistent care practices and suggest that >2 hours of education about care of women with GDM history may increase primary care NPs performing recommended practices to reduce T2D risks and prevent health problems for women and future offspring. Nurse practitioner education is needed involving care of women with GDM history to mitigate risks for T2D.

Additive genetic effect of GCKR, G6PC2, and SLC30A8 variants on fasting glucose levels and risk of type 2 diabetes.

Impaired glucose tolerance is a major risk factor for type 2 diabetes (T2D) and several cardiometabolic disorders. To identify genetic loci underlying fasting glucose levels, we conducted an analysis of 9,232 individuals of European ancestry who at enrollment were either nondiabetic or had untreated type 2 diabetes. Multivariable linear mixed models were used to test for associations between fasting glucose and 7.9 million SNPs, with adjustment for age, body mass index (BMI), sex, significant principal components of the genotypes, and cryptic relatedness. Three previously discovered loci were genome-wide significant, with the lead SNPs being rs1260326, a missense variant in GCKR (p = 1.06×10-8); rs560887, an intronic variant in G6PC2 (p = 3.39×10-11); and rs13266634, a missense variant in SLC30A8 (p = 4.28×10-10). Fine mapping, genome-wide conditional analysis, and functional annotation indicated that the three loci were independently associated with fasting glucose. Each copy of an alternate allele at any of these three SNPs was associated with a reduction of 0.012 mmol/L in fasting glucose levels (p = 8.0×10-28), and this association was replicated in trans-ethnic analysis of 14,303 individuals (p = 2.2×10-16). The three SNPs were jointly associated with significantly reduced T2D risk, with an odds ratio (95% CI) of 0.93 (0.88, 0.98) per protective allele. Our findings implicate additive effects across pathophysiological pathways involved in type 2 diabetes, including glycolysis, gluconeogenesis, and insulin secretion. Since none of the individuals homozygous for the alternate alleles at all three loci has T2D, it might be possible to use a genetic predictor of fasting glucose levels to identify individuals at low vs. high risk of developing type 2 diabetes.

TIGER: The gene expression regulatory variation landscape of human pancreatic islets.

SUMMARYGenome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.

Incorporating Post-Cessation Weight-Control Coaching into Smoking Cessation Therapy to Reduce Type 2 Diabetes Risk.

Post-cessation weight gain (PCWG) facilitates short-term type 2 diabetes (T2D) risk in prediabetic smokers in the absence of complementary measures. In this shared decision-making-based non-randomized controlled trial, prediabetic smokers joined the Fight Tobacco and Stay Fit (FIT2) program or received usual care. The 16-week FIT2 program combined smoking cessation therapy with individualized coaching in diet and physical activity strategies for PCWG restriction (NCT01926041 at ClinicalTrials.gov). During a mean follow-up period of 1316 days, 217 participants (36.8%) developed T2D, and 68 (11.5%) regressed to normoglycemia. In the intention-to-treat analysis (n = 589), the FIT2 program was associated with a reduced T2D risk (HR, 0.58; 95% CI, 0.40–0.84) and a higher probability of regression to normoglycemia (HR, 1.91; 95% CI, 1.04–3.53) compared with usual care. The post-program quitters were at lower T2D risk (HR, 0.63; 95% CI, 0.44–0.92) and were more likely to regress to normoglycemia (HR, 1.83; 95% CI, 1.01–3.30) compared with the controls in the time-varying analysis (n = 532). We demonstrated that the FIT2 program was negatively associated with long-term T2D risk and positively associated with the probability of regression to normoglycemia compared with usual care. To prevent T2D development, we recommend simultaneously promoting smoking abstinence and lifestyle coaching for PCWG restriction.