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Diabetes mellitus, prediabetes and the risk of Parkinson's disease: a systematic review and meta-analysis of 15 cohort studies with 29.9 million participants and 86,345 cases.
Aune, D, Schlesinger, S, Mahamat-Saleh, Y, Zheng, B, Udeh-Momoh, CT, Middleton, LT
European journal of epidemiology. 2023;38(6):591-604
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Diabetes mellitus and prediabetes may increase an individual’s risk for Parkinson’s disease (PD), however the research completed to date has been controversial. This meta-analysis of 15 observational studies with 86,345 individuals with PD aimed to update the research on PD risk for individuals with diabetes or prediabetes and determine possible reasons for the ambiguity of previous research. The results showed that compared to people without diabetes, those with, were at a 27% increased relative risk of PD and a 4% increase amongst those with prediabetes. Individuals with a history of complications alongside diabetes were at a higher risk than those without. It was concluded that the risk of developing PD is increased amongst individuals with diabetes. This study could be used by healthcare professionals to understand that individuals with diabetes may be at an increased risk for PD and should be monitored. However, as this is based on observational studies, there is a chance that PD increases the risk for diabetes and not the reverse.
Abstract
A diagnosis of diabetes mellitus and prediabetes has been associated with increased risk of Parkinson's disease (PD) in several studies, but results have not been entirely consistent. We conducted a systematic review and meta-analysis of cohort studies on diabetes mellitus, prediabetes and the risk of PD to provide an up-to-date assessment of the evidence. PubMed and Embase databases were searched for relevant studies up to 6th of February 2022. Cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between diabetes, prediabetes and Parkinson's disease were included. Summary RRs (95% CIs) were calculated using a random effects model. Fifteen cohort studies (29.9 million participants, 86,345 cases) were included in the meta-analysis. The summary RR (95% CI) of PD for persons with diabetes compared to persons without diabetes was 1.27 (1.20-1.35, I2 = 82%). There was no indication of publication bias, based on Egger's test (p = 0.41), Begg's test (p = 0.99), and inspection of the funnel plot. The association was consistent across geographic regions, by sex, and across several other subgroup and sensitivity analyses. There was some suggestion of a stronger association for diabetes patients reporting diabetes complications than for diabetes patients without complications (RR = 1.54, 1.32-1.80 [n = 3] vs. 1.26, 1.16-1.38 [n = 3]), vs. those without diabetes (pheterogeneity=0.18). The summary RR for prediabetes was 1.04 (95% CI: 1.02-1.07, I2 = 0%, n = 2). Our results suggest that patients with diabetes have a 27% increased relative risk of developing PD compared to persons without diabetes, and persons with prediabetes have a 4% increase in RR compared to persons with normal blood glucose. Further studies are warranted to clarify the specific role age of onset or duration of diabetes, diabetic complications, glycaemic level and its long-term variability and management may play in relation to PD risk.
2.
Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis.
Filippini, T, Wise, LA, Vinceti, M
Environment international. 2022;158:106920
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Cadmium is a toxic metal released in the environment after both natural and anthropogenic activities, particularly in contaminated and industrial areas devoted to smelting and refining of metals, and the manufacturing of batteries, coatings, or plastics. Exposure to cadmium may occur through occupational activities, smoking, food, and air pollution. The aim of this study was to provide updated literature on cadmium exposure and the risk of both type 2 diabetes and prediabetes, and to model the shape of these associations using a dose response approach. This study is a systematic review and meta-analysis of forty-two studies. Diabetes was investigated as an outcome in thirty-one studies, prediabetes in four studies, and both diabetes and prediabetes in seven studies. Results show that higher cadmium exposure was associated with increased risks of both diabetes and prediabetes. Diabetes risk increased linearly in studies using urinary cadmium concentrations, while disease risk increased only at the highest exposure levels when assessed using blood concentrations. The analysis for prediabetes also showed a linear increase in risk from low exposure, with a flattening effect at higher urinary cadmium concentrations. Authors conclude that their findings add to the available evidence on potential adverse health effects of environmental exposure to cadmium.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Cadmium exposure through diet, occupational exposure and smoking may increase the risk of type 2 diabetes in affected individuals.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Cadmium exposure might occur through occupational activities, food, air pollution, and smoking. Smokers, in particular, have higher blood cadmium concentrations than non-smokers. Food is the main transmission route for non-smokers, particularly cereals, vegetables, mollusks, and offal. Females and older adults are at a greater risk due to an increased risk of iron deficiency in these population groups, leading to increased absorption, as well as greater age-related bioaccumulation.
Furthermore, cadmium exposure has been associated with an increased risk of diabetes in a number of studies, as referenced in the present manuscript. However, the magnitude and shape of the correlation are uncertain.This systematic review and meta-analysis therefore investigates the relationship between exposure to cadmium and type 2 diabetes and prediabetes risk.
Methods
- The systematic review was conducted and reported in line with the PRISMA 2020 statement. Search strings related to the terms “cadmium” and “diabetes”, or “prediabetes state” in PubMed/MEDLINE, Web of Science and EMBASE databases were employed to search for relevant articles. Latest search date: 1 October 2021.
- Eligibility criteria included: studies evaluating cadmium exposure via biomarker levels with outcomes of interest being type 2 diabetes or prediabetes using WHO criteria and the American Diabetes Association; and reporting of relative risk estimates using the hazard ratio (HR), risk ratio (RR), or odds ratio (OR) with the corresponding 95% confidence interval (CIs). For inclusion in dose-response meta-analysis: reported effect estimates for all exposure categories along with dose in each category.
- Studies were assessed for risk of bias using theROBINS-E tool. Overall certainty of the evidence was assessed using the GRADE approach.
- The meta-analysis involved estimating RRs with corresponding 95% CIs from each study. Generalised least-squares regression with a random effects model and restricted maximum likelihood estimation were used. The highest versus lowest exposure categories were compared. The association between exposure and risk of diabetes or prediabetes was investigated using a one-stage dose-response meta-analysis. Sensitivity analyses were performed and heterogeneity between studies was assessed..
Results
- 42 eligible studies (case-control, cross-sectional, and cohort studies), ranging 65-34, 814 male and female adult participants, were identified investigating the association between cadmium exposure and risk of diabetes or prediabetes. Seven of the included studies were at overall high risk of bias; heterogeneity in the resulting meta-analyses was moderate to substantial. Sensitivity analyses indicated comparable results. Assessment with GRADE found no major inconsistency, indirectness or imprecision for either outcome.
- Comparing the highest versus lowest cadmium exposure concentrations associated with type 2 diabetes resulted in a RR of 1.24 (95% CI 0.96–1.59), RR 1.21 (CI 95% 1.00–1.45), and RR 1.47 (CI 95% 1.01–2.13) for blood, urinary, and toenail matrices, respectively. Concurrently, there was an elevated risk of prediabetes for cadmium levels in urine of RR 1.41 (95% CI: 1.15–1.73) and blood RR 1.38 (95% CI: 1.16–1.63), respectively.
- In the dose-response meta-analysis, a linear positive correlation between increasing urinary cadmium levels and diabetes risk was observed, with a RR 1.25 (95% CI 0.90–1.72) at concentration 2.0 µg/g of creatinine compared with no exposure. Conversely, for blood cadmium concentrations, the diabetes risk seemed to rise above 1 µg/L compared with no exposure. Moreover, prediabetes risk increased up to approximately 2 µg/g creatinine beyond which a plateau was reached with RR 1.40 (95% CI 1.12–1.76) at 2 µg/g creatinine.
- The meta-regression showed a negligible correlation between blood cadmium levels and diabetes risk. However, a positive yet imprecise association was found with increasing urinary cadmium concentrations. Similarly, no association was observed between blood cadmium concentrations and risk of prediabetes, whereas a positive relationship with urinary cadmium levels was observed. However, these findings were based on a limited cohort of studies.
Conclusions
- A positive linear correlation between cadmium concentration (measured in multiple matrices) and risk of both type 2 diabetes and prediabetes with a dose-response relationship (moderate-certainty evidence) were observed in this systematic review and meta-analysis. Diabetes risk increased linearly in studies using urinary cadmium concentrations, whereas disease risk increased only at the highest exposure levels when assessed using blood levels. The analysis for prediabetes also demonstrated a linear increase in risk from low exposure, which plateaued at higher urinary cadmium concentrations.
Clinical practice applications:
- To inform practitioners and clients of the risks of cadmium exposure in the diet, through occupational exposure, and through smoking.
- To motivate practitioners to educate themselves and their clients regarding the foods which may pose a higher risk of cadmium exposure (not reviewed in the present article).
- To advise clients on prediabetes and type 2 diabetes risk from cadmium exposure through smoking.
Considerations for future research:
- As cited by the authors, future studies could incorporate stratified analysis in specific subgroups, e.g., non-smokers, or could be restricted to prospective cohort studies with more sufficient data,
- Large-scale observational studies could be conducted investigating cadmium exposure in smokers versus non-smokers.
- Clinical trials could be performed to evaluate the effect of reduction or cessation of tobacco smoking on total body cadmium concentrations .
- Continuous surveillance of dietary cadmium exposure and other heavy metals should be prioritised to inform public health.
- Dietary interventions could assess the possibility to attenuate the risk of cadmium exposure.
Abstract
BACKGROUND Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association. OBJECTIVE To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association. DATA SOURCE After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes. STUDY ELIGIBILITY CRITERIA We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only. STUDY APPRAISAL AND SYNTHESIS METHODS Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model. RESULTS In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96-1.59), 1.21 (1.00-1.45), and 1.47 (1.01-2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15-1.73) and blood (RR = 1.38, 95% CI: 1.16-1.63). In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90-1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12-1.76) at 2 µg/g creatinine. LIMITATIONS AND CONCLUSIONS This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.
3.
Prevention of Type 2 Diabetes by Lifestyle Changes: A Systematic Review and Meta-Analysis.
Uusitupa, M, Khan, TA, Viguiliouk, E, Kahleova, H, Rivellese, AA, Hermansen, K, Pfeiffer, A, Thanopoulou, A, Salas-Salvadó, J, Schwab, U, et al
Nutrients. 2019;11(11)
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With Type 2 Diabetes growing globally this paper analyses whether T2D is preventable with lifestyle measures including diet. Seven RCTs were included for review with a total of 4090 participants, and 2466 incidents of T2D, and were chosen on the basis that the lifestyle interventions included both physical exercise and diet (typically Mediterranean Diet). They found that diet and lifestyle intervention reduced the risk of T2D by 47%. Sustained risk reduction was also found in follow-up studies up to 10 years later with participants maintaining improved blood glucose control. Lifestyle interventions may also reduce risk factors for cardiovascular disease. Weight reduction was considered a cornerstone of preventing T2D and adherence to lifestyle changes a key element in long term prevention. Dietary foods reviewed include processed meats, white rice and sugars which correlated highly with T2D whilst leafy greens, berries, wholegrains, legumes, dietary fibre and yoghurt correlate with a lower risk of T2D. Dietary patterns of skipping breakfast and snacking correlate higher with T2D. Different criteria for evaluating physical activity estimate that it reduces risk factors by 50%. In conclusion there is high evidence that lifestyle factors which optimise diet, increase physical activity and promote weight reduction are preventative factors for T2D and can be sustained long term.
Abstract
Prevention of type 2 diabetes (T2D) is a great challenge worldwide. The aim of this evidence synthesis was to summarize the available evidence in order to update the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy. We conducted a systematic review and, where appropriate, meta-analyses of randomized controlled trials (RCTs) carried out in people with impaired glucose tolerance (IGT) (six studies) or dysmetabolism (one study) to answer the following questions: What is the evidence that T2D is preventable by lifestyle changes? What is the optimal diet (with a particular focus on diet quality) for prevention, and does the prevention of T2D result in a lower risk of late complications of T2D? The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was applied to assess the certainty of the trial evidence. Altogether seven RCTs (N = 4090) fulfilled the eligibility criteria and were included in the meta-analysis. The diagnosis of incident diabetes was based on an oral glucose tolerance test (OGTT). The overall risk reduction of T2D by the lifestyle interventions was 0.53 (95% CI 0.41; 0.67). Most of the trials aimed to reduce weight, increase physical activity, and apply a diet relatively low in saturated fat and high in fiber. The PREDIMED trial that did not meet eligibility criteria for inclusion in the meta-analysis was used in the final assessment of diet quality. We conclude that T2D is preventable by changing lifestyle and the risk reduction is sustained for many years after the active intervention (high certainty of evidence). Healthy dietary changes based on the current recommendations and the Mediterranean dietary pattern can be recommended for the long-term prevention of diabetes. There is limited or insufficient data to show that prevention of T2D by lifestyle changes results in a lower risk of cardiovascular and microvascular complications.