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Environmental risk factors of type 2 diabetes-an exposome approach.
Beulens, JWJ, Pinho, MGM, Abreu, TC, den Braver, NR, Lam, TM, Huss, A, Vlaanderen, J, Sonnenschein, T, Siddiqui, NZ, Yuan, Z, et al
Diabetologia. 2022;(2):263-274
Abstract
Type 2 diabetes is one of the major chronic diseases accounting for a substantial proportion of disease burden in Western countries. The majority of the burden of type 2 diabetes is attributed to environmental risks and modifiable risk factors such as lifestyle. The environment we live in, and changes to it, can thus contribute substantially to the prevention of type 2 diabetes at a population level. The 'exposome' represents the (measurable) totality of environmental, i.e. nongenetic, drivers of health and disease. The external exposome comprises aspects of the built environment, the social environment, the physico-chemical environment and the lifestyle/food environment. The internal exposome comprises measurements at the epigenetic, transcript, proteome, microbiome or metabolome level to study either the exposures directly, the imprints these exposures leave in the biological system, the potential of the body to combat environmental insults and/or the biology itself. In this review, we describe the evidence for environmental risk factors of type 2 diabetes, focusing on both the general external exposome and imprints of this on the internal exposome. Studies provided established associations of air pollution, residential noise and area-level socioeconomic deprivation with an increased risk of type 2 diabetes, while neighbourhood walkability and green space are consistently associated with a reduced risk of type 2 diabetes. There is little or inconsistent evidence on the contribution of the food environment, other aspects of the social environment and outdoor temperature. These environmental factors are thought to affect type 2 diabetes risk mainly through mechanisms incorporating lifestyle factors such as physical activity or diet, the microbiome, inflammation or chronic stress. To further assess causality of these associations, future studies should focus on investigating the longitudinal effects of our environment (and changes to it) in relation to type 2 diabetes risk and whether these associations are explained by these proposed mechanisms.
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Clinical efficacy of capsules containing standardized extract of Bauhinia forficata Link (pata-de-vaca) as adjuvant treatment in type 2 diabetes patients: A randomized, double blind clinical trial.
Tonelli, CA, de Oliveira, SQ, Silva Vieira, AAD, Biavatti, MW, Ritter, C, Reginatto, FH, Campos, AM, Dal-Pizzol, F
Journal of ethnopharmacology. 2022;:114616
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Bauhinia forficata Link, is a Brazilian native plant and popularly known as pata-de-vaca ("paw-of-cow"). The tea prepared with their leaves has been extensively used in the Brazilian traditional practices for the diabetes treatment. The aim of the present study was to investigate the effect of capsules containing granules of a standardized extract of B. forficata leaves as adjuvant treatment on the glycemic control of patients with type-2 diabetes melitus. MATERIALS AND METHODS A double-blind, randomized clinical trial using capsules containing granules prepared by wet granulation of a standardized extract from B. forficata leaves as adjuvant treatment, was conducted. 92 patients aged 18-75 years from an outpatient clinic with type-2 diabetes were randomly assigned by a simple randomization scheme, in a 1:1 ratio to receive capsules of B. forficata or placebo for four months. The capsules used contain 300 mg of standardized extract from B. forficata leaves, yielding 2% of total flavonoid content per capsule. Primary outcome was glycated hemoglobin levels and fasting plasma glucose at 4 months. Possible harms were also determined. RESULTS The findings showed that at 4 months, the mean fasting plasma glucose levels and glycated hemoglobin were both significantly lower in the B. forficata group than in the placebo group. CONCLUSION The present study suggests that the adjunctive use of capsules containing standardized extract of B. forficata can add to regular oral anti-diabetics in the metabolic and inflammatory control of type-2 diabetes patients.
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Incidence and predictors of chronic kidney disease in type-II diabetes mellitus patients attending at the Amhara region referral hospitals, Ethiopia: A follow-up study.
Ahmed, MA, Ferede, YM, Takele, WW
PloS one. 2022;(1):e0263138
Abstract
BACKGROUND Chronic kidney disease (CKD) is the severest form of kidney disease characterized by poor filtration. The magnitude of chronic kidney disease is trending upward in the last few years linked with the rapidly escalating cases of non-communicable chronic diseases, particularly diabetes mellitus. However, little is known about when this problem may occur, the incidence as well as predictors of chronic kidney disease among type-II diabetes mellitus patients. Thus, this study was conducted to determine the incidence, time to the occurrence, and predictors of chronic kidney disease in type-II diabetic patients attending the Amhara region referral hospitals, Ethiopia. METHODS A retrospective follow-up study was conducted involving 415 participants with type-II diabetes mellitus that enrolled in the chronic follow-up from 2012 to 2017. Multivariable shared Frailty Weibull (Gamma) survival model was employed considering the hospitals as a clustering variable. Model fitness was checked by both the Akaike information criteria (AIC) and log-likelihood. Factors having a p-value of ≤0.2 in the bi-variable analysis were considered to enter the multivariable model. Variables that had a p-value of <0.05 with its corresponding 95% confidence level were deemed to be significant predictors of chronic kidney disease. RESULTS The overall cumulative incidence of chronic kidney disease was 10.8% [95%; CI: 7.7-14.0%] with a median occurrence time of 5 years. The annual incidence rate was 193/10,000 [95%; CI: 144.28-258.78]. Having cardiovascular disease/s [AHR = 3.82; 95%CI: 1.4470-10.1023] and hypercholesterolemia [AHR = 3.31; 95% CI: 1.3323-8.2703] were predictors of chronic kidney disease. CONCLUSION One out of every ten diabetic patients experienced chronic kidney disease. The median time to develop chronic kidney disease was five years. Hypercholesterolemia and cardiovascular diseases have escalated the hazard of developing CKD. Thus, health promotion and education of diabetic patients to optimize cholesterol levels and prevent cardiovascular disease is recommended to limit the occurrence of this life-threatening disease.
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Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial.
Abildgaard, J, Johansen, MY, Skov-Jeppesen, K, Andersen, LB, Karstoft, K, Hansen, KB, Hartmann, B, Holst, JJ, Pedersen, BK, Ried-Larsen, M
Medicine and science in sports and exercise. 2022;(1):38-46
Abstract
INTRODUCTION/PURPOSE The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D. METHODS Persons with T2D were randomized to either a 12-month lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin, N-terminal propeptide of type-I procollagen, reflecting bone formation, and carboxyterminal collagen I crosslinks, reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up. RESULTS From baseline to follow-up, s-propeptide of type-I procollagen increased by 34% (95% confidence interval [CI], 17%-50%), serum-carboxyterminal collagen I crosslink by 36% (95% CI, 1%-71%), and s-osteocalcin by 31% (95% CI, 11-51%) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. Bone mineral density was unaffected by the intervention (ΔBMD, 0.1%; 95% CI, -1.1% to 1.2%). CONCLUSIONS A 12-month intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.
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Mechanisms of action of SGLT2 inhibitors and their beneficial effects on the cardiorenal axis.
Gronda, E, Lopaschuk, GD, Arduini, A, Santoro, A, Benincasa, G, Palazzuoli, A, Gabrielli, D, Napoli, C
Canadian journal of physiology and pharmacology. 2022;(2):93-106
Abstract
Large clinical studies conducted with sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and heart failure with reduced ejection fraction have demonstrated their ability to achieve both cardiac and kidney benefits. Although there is huge evidence on SGLT2i-mediated clinical benefits both in diabetic and non-diabetic patients, the pathophysiological mechanisms underlying their efficacy are still poorly understood. Some favorable mechanisms are likely due to the prompt glycosuric action which is associated with natriuretic effects leading to hemodynamic benefits as well as a reduction in glomerular hyperfiltration and renin-angiotensin-aldosterone system activation. In addition to the renal mechanisms, SGLT2i may play a relevant role in cardiorenal axis protection by improving the cardiomyocyte metabolism, by exerting anti-fibrotic and anti-inflammatory actions, and by increasing cardioprotective adipokine expression. New studies will be needed to better understand the specific molecular mechanisms that mediate the SGLT2i favorable effects in patients suffering diabetes. Our aim is to first discuss about the molecular mechanisms underlying the cardiovascular benefits of SGLT2i in each of the main organs involved in the cardiorenal axis. Furthermore, we update on the most recent clinical trials evaluating the beneficial effects of SGLT2i in treatment of both diabetic and non-diabetic patients suffering heart failure.
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Personal Activity Intelligence e-Health Program in People with Type 2 Diabetes: A Pilot Randomized Controlled Trial.
Coombes, JS, Keating, SE, Mielke, GI, Fassett, RG, Coombes, BK, O'Leary, KP, Cox, ER, Burton, NW
Medicine and science in sports and exercise. 2022;(1):18-27
Abstract
INTRODUCTION Innovative strategies are needed to enable people with type 2 diabetes (T2D) to self-manage physical activity (PA). Personal Activity Intelligence (PAI) is a new metric that uses the heart rate response to PA to inform the user as to whether they are doing enough PA to reduce the risk of premature mortality. The PAI score reflects PA over the previous 7 d with the goal to maintain a score ≥100. The aim of this study was to investigate the feasibility, acceptability, and efficacy of the PAI e-Health Program in people with T2D. METHODS Thirty participants with T2D who were not meeting PA guidelines were randomly assigned to 12 wk of either 1) PAI e-Health Program or 2) PA attention control. The PAI e-Health Program consisted of receiving a wrist-worn heart rate monitor and an app with the PAI metric, and attending 4 × 2 h·wk-1 sessions of exercise and counseling. Feasibility and acceptability of the program were evaluated by achievement of a PAI score ≥100 and participant feedback. Efficacy was determined from changes in glycemic control, cardiorespiratory fitness, exercise capacity (time-on-test), body composition, sleep time, and health-related quality of life. RESULTS Program participants in the PAI e-Health Program had a mean ± SD PAI score of 119.7 ± 60.6 and achieved ≥100 PAI on 56.4% of the days. The majority of participants (80%) intended to continue to use PAI monitoring. Compared with control, the PAI group significantly improved their exercise capacity (mean difference, 95% confidence interval) (63 s, 17.9-108.0 s), sleep time (67.2 min, 7.2-127.1 min), total percent body fat (-1.3%, -2.6% to -0.1%), and gynoid fat percent (-1.5%, -2.6 to -0.5). CONCLUSIONS The PAI e-Health Program is feasible, acceptable, and efficacious in people with T2D.
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Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney Disease.
Waijer, SW, Sen, T, Arnott, C, Neal, B, Kosterink, JGW, Mahaffey, KW, Parikh, CR, de Zeeuw, D, Perkovic, V, Neuen, BL, et al
Clinical journal of the American Society of Nephrology : CJASN. 2022;(2):251-259
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Abstract
BACKGROUND AND OBJECTIVES Clinical trials in nephrology are enriched for patients with micro- or macroalbuminuria to enroll patients at risk of kidney failure. However, patients with normoalbuminuria can also progress to kidney failure. TNF receptor-1, TNF receptor-2, and kidney injury marker-1 (KIM-1) are known to be associated with kidney disease progression in patients with micro- or macroalbuminuria. We assessed the value of TNF receptor-1, TNF receptor-2, and KIM-1 as prognostic biomarkers for CKD progression in patients with type 2 diabetes and normoalbuminuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS TNF receptor-1, TNF receptor-2, and KIM-1 were measured using immunoassays in plasma samples from patients with type 2 diabetes at high cardiovascular risk participating in the Canagliflozin Cardiovascular Assessment Study trial. We used multivariable adjusted Cox proportional hazards analyses to estimate hazard ratios per doubling of each biomarker for the kidney outcome, stratified the population by the fourth quartile of each biomarker distribution, and assessed the number of events and event rates. RESULTS In patients with normoalbuminuria (n=2553), 51 kidney outcomes were recorded during a median follow-up of 6.1 (interquartile range, 5.8-6.4) years (event rate, 3.5; 95% confidence interval, 2.6 to 4.6 per 1000 patient-years). Each doubling of baseline TNF receptor-1 (hazard ratio, 4.2; 95% confidence interval, 1.8 to 9.6) and TNF receptor-2 (hazard ratio, 2.3; 95% confidence interval, 1.5 to 3.6) was associated with a higher risk for the kidney outcome. Baseline KIM-1, urinary albumin-creatinine ratio, and eGFR were not associated with kidney outcomes. The event rates in the highest quartile of TNF receptor-1 (≥2992 ng/ml) and TNF receptor-2 (≥11,394 ng/ml) were 5.6 and 7.0 events per 1000 patient-years, respectively, compared with 2.8 and 2.3, respectively, in the lower three quartiles. CONCLUSIONS TNF receptor-1 and TNF receptor-2 are associated with kidney outcomes in patients with type 2 diabetes and normoalbuminuria. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629.
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Dietary calcium intake in relation to type-2 diabetes and hyperglycemia in adults: A systematic review and dose-response meta-analysis of epidemiologic studies.
Hajhashemy, Z, Rouhani, P, Saneei, P
Scientific reports. 2022;(1):1050
Abstract
Several epidemiological studies investigated the relation of Ca intake with type 2 diabetes mellitus (T2DM), but there were inconsistencies in their findings. So, we conducted a systematic review and dose-response meta-analysis to quantify the relation of dietary Ca intake with the risk of T2DM/hyperglycemia in adults. A systematic search was conducted up to May 2021, in MEDLINE (Pubmed), Web of Science (WOS), Scopus electronic databases and Google Scholar, for epidemiological studies that investigated the relation of dietary Ca intake (as the exposure) and T2DM/hyperglycemia (as the outcome) in adults, without restriction in publication date and language. Finally, 8 cohort and 9 cross-sectional studies were included in the analysis. The body of evidence was assessed by the GRADE approach. Combining effect sizes from prospective cohort studies included 255,744 general adult population illustrated that highest level of dietary Ca intake, compared to lowest category, was related to an 18% reduced risk of T2DM (RR: 0.82; 95% CI 0.74-0.92). Based on linear dose-response analysis (including 255,744 healthy individuals and 13,531 patients with T2DM), each 300, 600 and 1000 mg/day increment in dietary Ca intake was respectively associated to 7, 14 and 23% reduced risk of T2DM. There was a steeper reduction in risk of T2DM when dietary Ca intake increased from low levels to 750 mg/day. Nevertheless, meta-analysis of cross-sectional studies revealed an inverse significant association between dietary Ca intake and T2DM/hyperglycemia only in the female population (OR: 0.66; 95% CI 0.50-0.88). This meta-analysis illustrated an inverse association between dietary Ca intake and risk of T2DM in general adult populations in prospective cohort studies, in a dose-response manner. It seems that increasing dietary Ca intake from low levels to around 750 mg/day was inversely related to risk of T2DM. In cross-sectional studies, an inverse relation between dietary Ca intake and T2DM/hyperglycemia was found only in females.
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Delivering the Diabetes Remission Clinical Trial (DiRECT) in primary care: Experiences of healthcare professionals.
Rehackova, L, Taylor, R, Lean, M, Barnes, A, McCombie, L, Thom, G, Brosnahan, N, Leslie, WS, Sniehotta, FF
Diabetic medicine : a journal of the British Diabetic Association. 2022;(3):e14752
Abstract
OBJECTIVE The Diabetes Remission Clinical Trial (DiRECT) used a formula total diet replacement programme followed by structured weight loss maintenance to induce and sustain weight loss and remission of type 2 diabetes (T2D) in 36% of participants after 2 years. Nurses and dietitians delivering DiRECT in 22 primary care practices in Tyneside and Scotland provided behavioural support to participants. Participant experiences with DiRECT highlighted the key role of support by healthcare professionals (HCPs). We evaluated HCPs' experiences with DiRECT. RESEARCH DESIGN AND METHODS Healthcare professionals delivering DiRECT were interviewed at 12 months, while general practices (GPs) were sent an implementation questionnaire. The interviews were analysed thematically. The questionnaires were analysed using frequencies and a narrative synthesis. RESULTS Healthcare professionals representing 11 of 22 intervention practices were interviewed and 10 of 22 GPs completed questionnaires. HCPs' initial concerns over perceived potential negative intervention effects, particularly withdrawing anti-diabetes and anti-hypertensive medications, were barriers to engagement. Trust of HCPs towards the research team and perceived credibility of the study facilitated engagement and adoption. Ongoing support by research dietitians was key to the management of participants. Involvement in DiRECT inspired more focus on behaviour modification in the treatment of other people living with T2D in routine practice. CONCLUSIONS Diabetes Remission Clinical Trial was considered highly appropriate for the management of T2D in primary care when supported by trained dietitians. Addressing limitations, including varying training needs of HCPs may improve intervention scale-up and tailoring to clinical contexts.
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Duodenal-Jejunal Bypass Liner for the management of Type 2 Diabetes Mellitus and Obesity: A Multicenter Randomized Controlled Trial.
Ruban, A, Miras, AD, Glaysher, MA, Goldstone, AP, Prechtl, CG, Johnson, N, Chhina, N, Al-Najim, W, Aldhwayan, M, Klimowska-Nassar, N, et al
Annals of surgery. 2022;(3):440-447
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Abstract
OBJECTIVE The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation. SUMMARY BACKGROUND DATA This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery. METHODS In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months. RESULTS There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group. CONCLUSIONS The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions. TRIAL REGISTRATION ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.