-
Diabetes & Metabolic Syndrome Jan 2024To assess the relationship between frailty phenotypes and the risk of MVD among prediabetics in two prospective cohorts.
BACKGROUND AND AIMS
To assess the relationship between frailty phenotypes and the risk of MVD among prediabetics in two prospective cohorts.
METHODS
The study included 66,068 and 226 participants with prediabetes from the UK Biobank (UKB) and Chinese Ocular Imaging Project (COIP) in Guangzhou, China, respectively. Frailty was evaluated using the Fried phenotype, which includes weight loss, fatigue, low grip strength, low physical activity, and slow walking pace. The outcome was incident microvascular diseases, including diabetic retinopathy, nephropathy, and neuropathy in UKB, and decline rate of retinal capillary density in COIP. Cox models were used to calculate hazard ratios (HRs) and 95 % confidential intervals (CIs), and mixed linear model was used to determine the β and 95 % CIs.
RESULTS
At baseline, 27,491 (41.6 %) and 3332 (5.0 %) prediabetics were classified as pre-frail and frail, respectively in UKB. During a median follow-up of 8.9 years, 3784 cases of incident microvascular diseases were identified. Pre-frailty and frailty were significantly associated with a higher risk of microvascular diseases (HR 1.21 [1.12, 1.30] for pre-frailty; HR 1.60 [1.42, 1.81] for frailty). Compared to no frailty, the adjusted HRs for frailty were 1.42 (0.73, 2.76) for retinopathy, 1.49 (1.31, 1.70) for nephropathy, and 2.37 (1.69, 3.33) for neuropathy. Fatigue and walking pace were the strongest mediators of frailty and microvascular diseases. In the COIP, the lowest handgrip strength group exhibited 62%-63 % faster annually decline in retinal capillary density compared with the highest group (all P<0.05).
CONCLUSIONS
Each frailty point is important for prediabetics because both pre-frailty and frailty phenotypes are strongly associated with an increased risk of microvascular diseases and its subtypes. Lower handgrip strength presents with faster decline in retinal capillary density.
Topics: Adult; Humans; Frailty; Prospective Studies; Prediabetic State; Hand Strength; Fatigue
PubMed: 38211481
DOI: 10.1016/j.dsx.2024.102942 -
Biomolecules Dec 2023In this study, we aimed to reveal the pro-inflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus...
In this study, we aimed to reveal the pro-inflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabetes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy participants. We measured the levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in the serum of the participants. ANOVA Bonferroni and Kruskal-Wallis Dunn tests were used to compare the inflammation markers and vitamin D levels between the groups. Based on covariance analysis with age, gender and BMI, the Vit D levels of the T2DM group were significantly lower ( < 0.003). Pro-inflammatory markers and CRP were significantly higher in prediabetic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In the T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the pro-inflammatory effects of Vit D deficiency and insufficiency in new-onset type 2 diabetes mellitus and prediabetes.
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Calcifediol; Interleukin-8; Tumor Necrosis Factor-alpha; Interleukin-6; NF-kappa B; Vitamin D; C-Reactive Protein; Mitogen-Activated Protein Kinases; Vitamins
PubMed: 38136648
DOI: 10.3390/biom13121778 -
Nature Dec 2023Diabetes is a leading cause of morbidity, mortality and cost of illness. Health behaviours, particularly those related to nutrition and physical activity, play a key...
Diabetes is a leading cause of morbidity, mortality and cost of illness. Health behaviours, particularly those related to nutrition and physical activity, play a key role in the development of type 2 diabetes mellitus. Whereas behaviour change programmes (also known as lifestyle interventions or similar) have been found efficacious in controlled clinical trials, there remains controversy about whether targeting health behaviours at the individual level is an effective preventive strategy for type 2 diabetes mellitus and doubt among clinicians that lifestyle advice and counselling provided in the routine health system can achieve improvements in health. Here we show that being referred to the largest behaviour change programme for prediabetes globally (the English Diabetes Prevention Programme) is effective in improving key cardiovascular risk factors, including glycated haemoglobin (HbA1c), excess body weight and serum lipid levels. We do so by using a regression discontinuity design, which uses the eligibility threshold in HbA1c for referral to the behaviour change programme, in electronic health data from about one-fifth of all primary care practices in England. We confirm our main finding, the improvement of HbA1c, using two other quasi-experimental approaches: difference-in-differences analysis exploiting the phased roll-out of the programme and instrumental variable estimation exploiting regional variation in programme coverage. This analysis provides causal, rather than associational, evidence that lifestyle advice and counselling implemented at scale in a national health system can achieve important health improvements.
Topics: Humans; Body Weight; Diabetes Mellitus, Type 2; Electronic Health Records; England; Exercise; Glycated Hemoglobin; Health Behavior; Health Promotion; Life Style; Lipids; National Health Programs; Prediabetic State; Primary Health Care
PubMed: 37968391
DOI: 10.1038/s41586-023-06756-4 -
American Journal of Physiology.... Oct 2023The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin...
The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin and/or exercise on fasting and postprandial insulin sensitivity in individuals with pre-diabetes and type 2 diabetes (T2D). Eight T2D adults (60 ± 4 yr) with overweight/obesity (32 ± 4 kg·m) under chronic metformin treatment (9 ± 6 yr; 1281 ± 524 mg·day) underwent four trials; ) taking their habitual metformin treatment (MET), ) substituting during 96 h their metformin medication by placebo (PLAC), ) placebo combined with 50 min bout of high-intensity interval exercise (PLAC + EX), and ) metformin combined with exercise (MET + EX). Plasma glucose kinetics using stable isotopes (6,6-H and [U-C] glucose), and glucose oxidation by indirect calorimetry, were assessed at rest, during exercise, and in a subsequent oral glucose tolerance test (OGTT). Postprandial glucose and insulin concentrations were analyzed as mean and incremental area under the curve (iAUC), and insulin sensitivity was calculated (i.e., MATSUDA and OGIS). During OGTT, metformin reduced glucose iAUC (i.e., MET and MET + EX lower than PLAC and PLAC + EX, respectively; = 0.023). MET + EX increased MATSUDA above PLAC (4.8 ± 1.4 vs. 3.3 ± 1.0, respectively; = 0.018) and OGIS above PLAC (358 ± 52 vs. 306 ± 46 mL·min·m, respectively; = 0.006). Metformin decreased the plasma appearance of the ingested glucose (R OGTT; MET vs. PLAC, -3.5; 95% CI -0.1 to -6.8 µmol·kg·min; = 0.043). Metformin combined with exercise potentiates insulin sensitivity during an OGTT in individuals with pre-diabetes and type 2 diabetes. Metformin's blood glucose-lowering effect seems mediated by decreased oral glucose entering the circulation (gut-liver effect) an effect partially blunted after exercise. Metformin is the most prescribed oral antidiabetic medicine in the world but its mechanism of action and its interactions with exercise are not fully understood. Our stable isotope tracer data suggested that metformin reduces the rates of oral glucose entering the circulation (gut-liver effect). Exercise, in turn, tended to reduce postprandial insulin blood levels potentiating metformin improvements in insulin sensitivity. Thus, exercise potentiates metformin improvements in glycemic control and should be advised to metformin users.
Topics: Adult; Humans; Metformin; Glucose; Prediabetic State; Insulin Resistance; Diabetes Mellitus, Type 2; Kinetics; Blood Glucose; Insulin
PubMed: 37584610
DOI: 10.1152/ajpendo.00118.2023 -
Adipocyte Dec 2023This systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-2020) standards. This was... (Meta-Analysis)
Meta-Analysis Review
METHODS
This systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-2020) standards. This was accomplished by searching clinical MeSH categories in MEDLINE with full texts, EMBASE, Web of Science, PubMed, Cochrane Library, Academic Search Complete, ICTRP and ClinicalTrial.gov. Reviewers examined all the findings and selected the studies that satisfied the inclusion criteria. The Downs and Black Checklist was used to assess for bias, followed by a Review Manager v5. A Forrest plot was used for the meta-analysis and sensitivity analysis. The protocol for this review was registered with PROSPERO CRD42022320252.
RESULTS
The clinical studies ( = 2) comprised 1065 patients with prediabetes and 1103 normal controls. The RAAS measurements were completed in the adipose tissue. The RAAS components, renin and aldosterone were higher in the prediabetic (PD) compared to the control [mean difference (MD) = 0.16, 95% CI 0.16 (-0.13, 0.45), = 0.25]. Furthermore, the PD group demonstrated higher triglycerides mean difference [MD = 7.84, 95% CI 7.84 (-9.84, 25.51), = 0.38] and increased BMI [MD = 0.13, 95% CI 0.13 (-0.74, 0.99), = 0.77] compared to the control. The overall quality of the studies was fair with a median score and range of 17 (16-18).
CONCLUSION
The current study highlights the relationship between increased BMI, RAAS and insulin resistance which is a predictor of prediabetes. The renin is slightly higher in the prediabetes group without any statistical significance, aldosterone is rather negatively associated with prediabetes which may be attributed to the use of anti-hypertensive treatment.
Topics: Humans; Aldosterone; Prediabetic State; Renin; Renin-Angiotensin System; Risk Factors; Adipose Tissue
PubMed: 37606270
DOI: 10.1080/21623945.2023.2249763 -
Cardiovascular Diabetology Aug 2023The atherogenic index of plasma (AIP) can reflect the burden of atherosclerosis. Hyperglycemia is one of the leading causes of atherosclerosis. However, the relationship...
BACKGROUND
The atherogenic index of plasma (AIP) can reflect the burden of atherosclerosis. Hyperglycemia is one of the leading causes of atherosclerosis. However, the relationship between AIP and prediabetes is rarely studied. Therefore, we aimed to explore the relationship between AIP and prediabetes.
METHODS
This retrospective cohort study recruited 100,069 Chinese adults at the Rich Healthcare Group from 2010 to 2016. AIP was calculated according to Log10 (triglyceride/high-density lipoprotein cholesterol) formula. Cox regression method, sensitivity analyses and subgroup analyses were used to examine the relationship between AIP and prediabetes. Cox proportional hazards regression with cubic spline functions and smooth curve fitting was performed to explore the non-linearity between AIP and prediabetes. The two-piece Cox proportional hazards regression model was used to determine the inflection point of AIP on the risk of prediabetes.
RESULTS
After adjusting for confounding covariates, AIP was positively associated with prediabetes (HR: 1.41, 95%CI: 1.31-1.52, P < 0.0001). The two-piecewise Cox proportional hazards regression model discovered that the AIP's inflection point was 0.03 (P for log-likelihood ratio test < 0.001). AIP was positively associated with the risk of prediabetes when AIP ≤ 0.03 (HR: 1.90, 95%CI: 1.66-2.16, P < 0.0001). In contrast, When AIP > 0.03, their association was not significant (HR: 1.04, 95%CI: 0.91-1.19, P = 0.5528).
CONCLUSION
This study shows that AIP was positively and non-linearly associated with the risk of prediabetes after adjusting for other confounding factors. When AIP ≤ 0.03, AIP was positively associated with the risk of prediabetes.
Topics: Adult; Humans; Atherosclerosis; East Asian People; Prediabetic State; Retrospective Studies; Risk Factors; Triglycerides; Cholesterol, HDL
PubMed: 37563588
DOI: 10.1186/s12933-023-01934-0 -
PloS One 2023This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and... (Review)
Review
AIMS
This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms.
METHODS
An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms.
RESULTS
Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of -8.129 (-12.175, -4.084) mg/dL and -0.134 (-0.304, -0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis.
CONCLUSION
CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS.
TRIAL REGISTRATION
PROSPERO (CRD42016042131).
Topics: Adult; Humans; Blood Glucose; Curcuma; Diabetes Mellitus, Type 2; Dietary Supplements; Glycated Hemoglobin; Metabolic Syndrome; Prediabetic State; Randomized Controlled Trials as Topic; Meta-Analysis as Topic; Systematic Reviews as Topic
PubMed: 37471428
DOI: 10.1371/journal.pone.0288997 -
The Journal of Clinical Endocrinology... Jul 2023People with type 2 diabetes (T2D) have higher risks of cancer incidence and death. (Meta-Analysis)
Meta-Analysis
CONTEXT
People with type 2 diabetes (T2D) have higher risks of cancer incidence and death.
OBJECTIVE
We aimed to evaluate the relationship between dietary and physical activity-based lifestyle intervention and cancer outcomes among prediabetes and T2D populations.
METHODS
We searched for randomized controlled trials with at least 24 months of lifestyle interventions in prediabetes or T2D populations. Data were extracted by pairs of reviewers and discrepancies were resolved by consensus. Descriptive syntheses were performed, and the risk of bias was assessed. Relative risks (RRs) and 95% CIs were estimated using a pairwise meta-analysis with both a random-effects model and a general linear mixed model (GLMM). Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework, and trial sequential analysis (TSA) was conducted to assess if current information is enough for definitive conclusions. Subgroup analysis was performed by glycemic status.
RESULTS
Six clinical trials were included. Among 12 841 participants, the combined RR for cancer mortality comparing lifestyle interventions with usual care was 0.94 (95% CI, 0.81-1.10 using GLMM and 0.82-1.09 using random-effects model). Most studies had a low risk of bias, and the certainty of evidence was moderate. TSA showed that the cumulative Z curve reached futility boundary while total number did not reach detection boundary.
CONCLUSION
Based on the limited data available, dietary and physical activity-based lifestyle interventions had no superiority to usual care on reducing cancer risk in populations with prediabetes and T2D. Lifestyle interventions focused on cancer outcomes should be tested to better explore their effects.
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Life Style; Exercise; Neoplasms
PubMed: 36869709
DOI: 10.1210/clinem/dgad123 -
Journal of Clinical Oncology : Official... Mar 2024Little is known about the prevalence of prediabetes and associated risk of cardiovascular events and chronic kidney disease (CKD) with this reversable condition in...
PURPOSE
Little is known about the prevalence of prediabetes and associated risk of cardiovascular events and chronic kidney disease (CKD) with this reversable condition in survivors.
METHODS
Prevalence of prediabetes (fasting plasma glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.4%) and diabetes was clinically assessed in 3,529 adults ≥5 years from childhood cancer diagnosis and 448 controls stratified by age. Cox proportional hazards regression estimated progression from prediabetes to diabetes, and risk of future cardiac events, stroke, CKD, and death.
RESULTS
Among survivors, median age 30 years (IQR, 18-65), and the prevalence of prediabetes was 29.2% (95% CI, 27.7 to 30.7) versus 18.1% (14.5 to 21.6) in controls and of diabetes was 6.5% (5.7 to 7.3) versus 4.7% (2.7 to 6.6). By age 40-49 years, more than half of the survivors had prediabetes (45.5%) or diabetes (14.0%). Among 695 survivors with prediabetes and longitudinal follow-up, 68 (10%; median follow-up, 5.1 years) progressed to diabetes. After adjustment for demographic factors and body composition, risk of progression was associated with radiation exposure to the pancreatic tail ≥10 Gy (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.8]) and total-body irradiation (4.4 [1.5 to 13.1]). Compared with survivors with normal glucose control, adjusting for relevant treatment exposures, those with prediabetes were at increased risk of future myocardial infarction (HR, 2.4 [95% CI, 1.2 to 4.8]) and CKD (2.9 [1.04 to 8.15]), while those with diabetes were also at increased risk of future cardiomyopathy (3.8 [1.4 to 10.5]) or stroke (3.4 [1.3 to 8.9]).
CONCLUSION
Prediabetes is highly prevalent in adult survivors of childhood cancer and independently associated with an increased risk of future cardiovascular and kidney complications. Prediabetes, a modifiable risk factor among childhood cancer survivors, represents a new target for intervention that may prevent subsequent morbidity and mortality.
Topics: Adult; Humans; Child; Middle Aged; Prediabetic State; Cancer Survivors; Neoplasms; Diabetes Mellitus; Risk Factors; Survivors; Renal Insufficiency, Chronic; Stroke
PubMed: 38091552
DOI: 10.1200/JCO.23.01005 -
Psychoneuroendocrinology Mar 2024The relationship between insulin-like growth factor-1 (IGF-1) and cognition has been studied in healthy individuals, but not extensively with regards to insulin... (Observational Study)
Observational Study
BACKGROUND
The relationship between insulin-like growth factor-1 (IGF-1) and cognition has been studied in healthy individuals, but not extensively with regards to insulin resistance and type 2 diabetes mellitus (T2DM). In this retrospective observational study, we investigated relationships of IGF-1 with memory and executive function across people with normoglycemia, prediabetes, and T2DM.
METHODS
Data from the Midlife in the United States (MIDUS) study were used. Episodic memory and executive function were assessed using the Brief Test of Adult Cognition by Telephone approximately 21.42 ± 12.10 months prior to measuring IGF-1 levels from a fasting blood sample. Normoglycemia was identified as individuals without a physician diagnosis of diabetes and glycated hemoglobin (HbA1c) ≤5.6%. Prediabetes was identified as those without a physician diagnosis of diabetes and HbA1c between 5.7%-6.4%. T2DM was identified as anyone with a physician diagnosis of diabetes, or HbA1c ≥6.5%, or anyone using an oral hypoglycemic medication. The associations were assessed using linear regressions controlling for age, sex, education, body mass index, C-reactive protein, HbA1c or homeostatic model of insulin resistance, MIDUS wave, exercise, smoking status, sleep quality, alcohol intake, oral hypoglycemic use, and insulin use.
RESULTS
The study included 1400 participants, which consisted of 583 normoglycemic (48.4% female, mean age 51.0 ± 12.2 years), 512 prediabetes (58.4% female, mean age 57.3 ± 11.8 years), and 305 T2DM participants (53.8% female, mean age 57.6 ± 11.5 years). Peripheral IGF-1 concentrations were lower (F = 28.29, p < 0.001) in people with prediabetes or T2DM, vs. normoglycemia. Participants with prediabetes or T2DM had lower episodic memory (F = 9.21, p < 0.001) and executive function (F = 20.29, p < 0.001) composite z-scores than people with normoglycemia. Higher IGF-1 concentrations were associated with better executive performance in individuals with prediabetes (β = 0.115 [0.028, 0.202], p = 0.010), but not in individuals with normoglycemia or T2DM. An interaction between IGF-1 and sex in predicting executive function was observed in the prediabetes group (β = -0.344, p = 0.042), where the relationship was weaker in females (β = 0.106 [-0.012, 0.224], p = 0.077) than males (β = 0.251 [0.123, 0.380], p < 0.001). No associations were seen between IGF-1 and memory.
CONCLUSION
The results suggest that peripheral IGF-1 concentrations may be related to executive function, and that the relationship may be sex-specific and dependent on diabetes status.
Topics: Male; Adult; Humans; Female; Middle Aged; Aged; Diabetes Mellitus, Type 2; Prediabetic State; Glycated Hemoglobin; Insulin-Like Peptides; Insulin Resistance; Insulin-Like Growth Factor I; Blood Glucose; Hypoglycemic Agents; Cognition
PubMed: 38198904
DOI: 10.1016/j.psyneuen.2023.106946