Effect of Diet Quality and Genetic Predisposition on Hemoglobin A and Type 2 Diabetes Risk: Gene-Diet Interaction Analysis of 357,419 Individuals.
Diabetes care
OBJECTIVE:To assess the interactions between diet quality and genetic predisposition to incident type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS:Between 2006 and 2010, 357,419 participants with genetic and complete dietary data from the UK Biobank were enrolled and prospectively followed up to 2017. The genetic risk score (GRS) was calculated on the basis of 424 variants associated with T2D risk, and a higher GRS indicates a higher genetic predisposition to T2D. The adherence to a healthy diet was assessed by a diet quality score comprising 10 important dietary components, with a higher score representing a higher overall diet quality. RESULTS:There were 5,663 incident T2D cases documented during an average of 8.1 years of follow-up. A significant negative interaction was observed between the GRS and the diet quality score. After adjusting for major risk factors, per SD increment in the GRS and the diet quality score was associated with a 54% higher and a 9% lower risk of T2D, respectively. A simultaneous increment of 1 SD in both the diet quality score and GRS was additionally associated with a 3% lower T2D risk due to the antagonistic interaction. In categorical analyses, a sharp reduction of 23% in T2D risk associated with a 1-SD increment in the diet quality score was detected among participants in the extremely high GRS group (GRS >95%). We also observed a strong negative interaction between the GRS and the diet quality score on the blood HbA level at baseline ( < 0.001). CONCLUSIONS:The adherence to a healthy diet was associated with more reductions in blood HbA levels and subsequent T2D risk among individuals with a higher genetic risk. Our findings support tailoring dietary recommendations to an individual's genetic makeup for T2D prevention.
10.2337/dc21-1051
Changes in Supplemental Nutrition Assistance Program Policies and Diabetes Prevalence: Analysis of Behavioral Risk Factor Surveillance System Data From 2004 to 2014.
Diabetes care
OBJECTIVE:Food insecurity is associated with diabetes. The Supplemental Nutrition Assistance Program (SNAP) is the largest U.S. government food assistance program. Whether such programs impact diabetes trends is unclear. The objective of this study was to evaluate the association between changes in state-level policies affecting SNAP participation and county-level diabetes prevalence. RESEARCH DESIGN AND METHODS:We evaluated the association between change in county-level diabetes prevalence and changes in the U.S. Department of Agriculture SNAP policy index-a measure of adoption of state-level policies associated with increased SNAP participation (higher value indicating adoption of more policies associated with increased SNAP participation; range 1-10)-from 2004 to 2014 using g-computation, a robust causal inference methodology. The study included all U.S. counties with diabetes prevalence data available from the Centers for Disease Control and Prevention's U.S. Diabetes Surveillance System. RESULTS:The study included 3,135 of 3,143 U.S. counties. Mean diabetes prevalence increased from 7.3% (SD 1.3) in 2004 to 9.1% (SD 1.8) in 2014. The mean SNAP policy index increased from 6.4 (SD 0.9) to 8.2 (SD 0.6) in 2014. After accounting for changes in demographic-, economic-, and health care-related variables and the baseline SNAP policy index, a 1-point absolute increase in the SNAP policy index between 2004 and 2014 was associated with a 0.050 (95% CI 0.042-0.057) percentage point lower diabetes prevalence per year. CONCLUSIONS:State policies aimed at increasing SNAP participation were independently associated with a lower rise in diabetes prevalence between 2004 and 2014.
10.2337/dc21-1203
The Mediterranean Diet and 2-Year Change in Cognitive Function by Status of Type 2 Diabetes and Glycemic Control.
Diabetes care
OBJECTIVE:To determine associations of a Mediterranean diet score (MeDS) with 2-year change in cognitive function by type 2 diabetes and glycemic control status and contrast it against other diet quality scores. RESEARCH DESIGN AND METHODS:We used data from the longitudinal Boston Puerto Rican Health Study ( = 913; 42.6% with type 2 diabetes at 2 years). Glycemic control at baseline was categorized as uncontrolled (hemoglobin A ≥7% [53 mmol/mol]) versus controlled. Two-year change in glycemic control was defined as stable/improved versus poor/declined. We defined MeDS, Healthy Eating Index, Alternate Healthy Eating Index, and Dietary Approaches to Stop Hypertension scores. Adjusted mixed linear models assessed 2-year change in global cognitive function score, executive and memory function, and nine individual cognitive tests. RESULTS:Higher MeDS, but no other diet quality score, was associated with higher 2-year change in global cognitive function in adults with type 2 diabetes (β ± SE = 0.027 ± 0.011; = 0.016) but not in those without ( = 0.80). Similar results were noted for Mini-Mental State Examination, word recognition, digit span, and clock drawing tests. Results remained consistent for individuals under glycemic control at baseline (0.062 ± 0.020; = 0.004) and stable/improved over 2 years (0.053 ± 0.019; = 0.007), but not for individuals with uncontrolled or poor/declined glycemic control. All diet quality scores were associated with higher 2-year memory function in adults without type 2 diabetes. CONCLUSIONS:Both adhering to a Mediterranean diet and effectively managing type 2 diabetes may support optimal cognitive function. Healthy diets, in general, can help improve memory function among adults without type 2 diabetes.
10.2337/dc19-0130
Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus.
Gut microbes
Biogeographic variations in the gut microbiota are pivotal to understanding the global pattern of host-microbiota interactions in prevalent lifestyle-related diseases. Pakistani adults, having an exceptionally high prevalence of type 2 diabetes mellitus (T2D), are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by bacterial 16S ribosomal RNA gene and fungal internal transcribed spacer (ITS) region amplicon sequencing and eubacterial qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide-binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis of the bacterial microbiota. Overall, urbanized Pakistanis' gut microbiota was similar to that of transitional or non-industrialized populations, depleted in and enriched in (dominated by the non-Westernized clades of ). The relatively high proportion of appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations, e.g., increased relative abundance of /, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for a more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.
10.1080/19490976.2022.2142009
Dose-Dependent Associations of Dietary Glycemic Index, Glycemic Load, and Fiber With 3-Year Weight Loss Maintenance and Glycemic Status in a High-Risk Population: A Secondary Analysis of the Diabetes Prevention Study PREVIEW.
Diabetes care
OBJECTIVE:To examine longitudinal and dose-dependent associations of dietary glycemic index (GI), glycemic load (GL), and fiber with body weight and glycemic status during 3-year weight loss maintenance (WLM) in adults at high risk of type 2 diabetes. RESEARCH DESIGN AND METHODS:In this secondary analysis we used pooled data from the PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) randomized controlled trial, which was designed to test the effects of four diet and physical activity interventions. A total of 1,279 participants with overweight or obesity (age 25-70 years and BMI ≥25 kg ⋅ m) and prediabetes at baseline were included. We used multiadjusted linear mixed models with repeated measurements to assess longitudinal and dose-dependent associations by merging the participants into one group and dividing them into GI, GL, and fiber tertiles, respectively. RESULTS:In the available-case analysis, each 10-unit increment in GI was associated with a greater regain of weight (0.46 kg ⋅ year; 95% CI 0.23, 0.68; < 0.001) and increase in HbA. Each 20-unit increment in GL was associated with a greater regain of weight (0.49 kg ⋅ year; 0.24, 0.75; < 0.001) and increase in HbA. The associations of GI and GL with HbA were independent of weight change. Compared with those in the lowest tertiles, participants in the highest GI and GL tertiles had significantly greater weight regain and increases in HbA. Fiber was inversely associated with increases in waist circumference, but the associations with weight regain and glycemic status did not remain robust in different analyses. CONCLUSIONS:Dietary GI and GL were positively associated with weight regain and deteriorating glycemic status. Stronger evidence on the role of fiber is needed.
10.2337/dc20-3092
Dietary carbohydrate intake and new-onset diabetes: A nationwide cohort study in China.
Metabolism: clinical and experimental
AIM:The association of carbohydrate intake with diabetes risk remains uncertain. We aimed to evaluate the prospective associations of the amount and types of carbohydrate intake with new-onset diabetes. METHODS:A total of 16,260 non-diabetic participants from the China Health and Nutrition Survey (CHNS) were included. Dietary intake was collected by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with self-reported physician diagnosed diabetes, or fasting plasma glucose ≥7.0 mmol/L or glycated hemoglobin ≥6.5% during the follow-up were defined having new-onset diabetes. RESULTS:During a median follow-up of 9 years (158,930 person-years), 1100 participants developed diabetes. Overall, there was a U-shaped association between percent of energy from carbohydrate intake and new-onset diabetes, with minimal risk at 49-56% of energy from total carbohydrate intake (quartile 2) (P for nonlinearity <0.001). Moreover, there was an L-shaped association between high-quality carbohydrate intake and new-onset diabetes (P for nonlinearity <0.001), and a J-shaped association of low-quality carbohydrate intake with new-onset diabetes (P for nonlinearity <0.001). Furthermore, there was an inverse association between the plant-based low-carbohydrate diet scores for low-quality carbohydrate and new-onset diabetes. However, a reversed J-shaped association was found between the animal-based low-carbohydrate diet scores for low-quality carbohydrate and new-onset diabetes (P for nonlinearity <0.001). CONCLUSIONS:There was a U-shape association between percent of total carbohydrate intake and new-onset diabetes, with the lowest risk at 49-56% carbohydrate intake. Our findings provide some evidence for the intake of high-quality carbohydrate, and the substitution of plant-based products for low-quality carbohydrate for primary prevention of diabetes.
10.1016/j.metabol.2021.154865
Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study.
Diabetes care
OBJECTIVE:Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. In this study we aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with risk of diabetic microvascular complications. RESEARCH DESIGN AND METHODS:This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS:Median serum 25(OH)D concentration was 40.7 nmol/L (interquartile range 27.5, 56.4). During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, in comparisons with participants with 25(OH)D <25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. CONCLUSIONS:Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications.
10.2337/dc22-0513
A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.
PLoS medicine
BACKGROUND:Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. METHODS AND FINDINGS:We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. CONCLUSIONS:These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.
10.1371/journal.pmed.1004221
Diet-Related Lipidomic Signatures and Changed Type 2 Diabetes Risk in a Randomized Controlled Feeding Study With Mediterranean Diet and Traditional Chinese or Transitional Diets.
Diabetes care
OBJECTIVE:Few trials studied the links of food components in different diets with their induced lipidomic changes and related metabolic outcomes. Thus, we investigated specific lipidomic signatures with habitual diets and modified diabetes risk by using a trial and a cohort. RESEARCH DESIGN AND METHODS:We included 231 Chinese with overweight and prediabetes in a randomized feeding trial with Mediterranean, traditional, or transitional diets (control diet) from February to September 2019. Plasma lipidomic profiles were measured at baseline, third month, and sixth month by high-throughput targeted liquid chromatography-mass spectrometry. Associations of the identified lipids with habitual dietary intakes were examined in another lipidomic database of a Chinese cohort (n = 1,117). The relationships between diet-induced changes of lipidomic species and diabetes risk factors were further investigated through both individual lipids and relevant modules in the trial. RESULTS:Out of 364 lipidomic species, 26 altered across groups, including 12 triglyceride (TAG) fractions, nine plasmalogens, four phosphatidylcholines (PCs), and one phosphatidylethanolamine. TAG fractions and PCs were associated with habitual fish intake while plasmalogens were associated with red meat intake in the cohort. Of the diet-related lipidomic metabolites, 10 TAG fractions and PC(16:0/22:6) were associated with improved Matsuda index (β = 0.12 to 0.42; PFDR < 0.030). Two plasmalogens were associated with deteriorated fasting glucose (β = 0.29 to 0.31; PFDR < 0.014). Similar results were observed for TAG and plasmalogen related modules. CONCLUSIONS:These fish- and red meat-related lipidomic signatures sensitively reflected different diets and modified type 2 diabetes risk factors, critical for optimizing dietary patterns.
10.2337/dc23-0314
Impact of dietary interventions on pre-diabetic oral and gut microbiome, metabolites and cytokines.
Nature communications
Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
10.1038/s41467-023-41042-x
Dietary Protein Sources, Mediating Biomarkers, and Incidence of Type 2 Diabetes: Findings From the Women's Health Initiative and the UK Biobank.
Diabetes care
OBJECTIVE:Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. RESEARCH DESIGN AND METHODS:We included 108,681 postmenopausal women without T2D at baseline from the Women's Health Initiative (WHI) (primary cohort) and 34,616 adults without T2D from the U.K. Biobank (UKB) (replication cohort). Cox proportional hazard models were used for estimation of protein-T2D associations. Mediation analysis was performed to assess the mediating roles of biomarkers in case-control studies nested in the WHI. RESULTS:In the WHI, 15,842 incident T2D cases were identified during a median follow-up of 15.8 years. Intake of animal protein was associated with increased T2D risk (hazard ratio in comparing the highest to the lowest quintile = 1.31 [95% CI 1.24-1.37]) and plant protein with decreased risk (0.82 [0.78-0.86]). Intakes of red meat, processed meat, poultry, and eggs were associated with increased T2D risk and whole grains with decreased risk. Findings from the UKB were similar. These findings were materially attenuated after additional adjustment for BMI. Substituting 5% energy from plant protein for animal protein was associated with 21% decreased T2D risk (0.79 [0.74-0.84]), which was mediated by levels of hs-CRP, interleukin-6, leptin, and SHBG. CONCLUSIONS:Findings from these two large prospective cohorts support the notion that substituting plant protein for animal protein may decrease T2D risk mainly by reducing obesity-related inflammation.
10.2337/dc22-0368
Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study.
PLoS medicine
BACKGROUND:The influence of overall lifestyle behaviors on diabetic microvascular complications remains unknown. In addition, the potential mediating biomarkers underlying the association is unclear. This study aimed to examine the associations of the combined lifestyle factors with risks of total and individual microvascular complications among patients with type 2 diabetes (T2D) and to explore the potential mediation effects of metabolic biomarkers. METHODS AND FINDINGS:This retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95% confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend ≤0.01). Further, the population-attributable fraction (95% CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle (<4 low-risk factors) ranged from 25.3% (10.0%, 39.4%) to 39.0% (17.7%, 56.8%). In addition, albumin, HDL-C, triglycerides, apolipoprotein A, C-reactive protein, and HbA1c collectively explained 23.20% (12.70%, 38.50%) of the associations between overall lifestyle behaviors and total diabetic microvascular complications. The key limitation of the current analysis was the potential underreporting of microvascular complications because the cases were identified via electronic health records. CONCLUSIONS:Adherence to overall healthy lifestyle behaviors was associated with a significantly lower risk of microvascular complications in patients with T2D, and the favorable associations were partially mediated through improving biomarkers of glycemic control, systemic inflammation, liver function, and lipid profile.
10.1371/journal.pmed.1004135