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Adherence to Mediterranean Diet and NAFLD in Patients with Metabolic Syndrome: The FLIPAN Study.
Montemayor, S, Mascaró, CM, Ugarriza, L, Casares, M, Llompart, I, Abete, I, Zulet, MÁ, Martínez, JA, Tur, JA, Bouzas, C
Nutrients. 2022;14(15)
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Non-alcoholic fatty liver disease (NAFLD) is characterised by fat deposition that is not linked to excessive alcohol intake. This condition is often linked to other health issues such as obesity, metabolic syndrome, type 2 diabetes and cardiovascular disease, and they share common diagnostic biomarkers. An unhealthy diet and lifestyle are also linked to the progression of NAFLD. Mediterranean diet is a predominantly plant-based diet that may have an association with lower risk and reduced severity of NAFLD. This multicentre, prospective, randomised controlled trial included one hundred and thirty-six NAFLD patients to analyse the effect of Mediterranean diet adherence on NAFLD in patients with metabolic syndrome. The NAFLD patients followed a personalised Mediterranean diet and physical activity interventions for six months. Individuals with greater adherence to the Mediterranean diet and physical activity interventions showed improvements in body mass index, body weight, waist circumference, blood pressure and intrahepatic fat content after six months of intervention. Healthcare professionals can use the results of this study to understand the benefits of adherence to the Mediterranean diet and physical activity interventions in reducing NAFLD severity and metabolic irregularities. However, due to the small sample size of this study, further robust studies are required to evaluate the benefits of different dietary strategies, the therapeutic value of different food items and the intervention duration required to achieve improvements in NAFLD and metabolic syndrome.
Abstract
Unhealthy diet is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). Previous studies showed the benefits of a Mediterranean diet (MedDiet) on Metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases, which usually have a pathophysiological relationship with NAFLD. To assess the effect of adherence to a MedDiet on NAFLD in MetS patients after lifestyle intervention, this multicentre (Mallorca and Navarra, Spain) prospective randomized trial, with personalized nutritional intervention based on a customized MedDiet, coupled with physical activity promotion was performed to prevent, and reverse NAFLD among patients with MetS. The current analysis included 138 patients aged 40 to 60 years old, Body Mass Index (BMI) 27-40 kg/m2, diagnosed with NAFLD using MRI, and MetS according to the International Diabetes Federation (IDF). A validated food frequency questionnaire was used to assess dietary intake. Adherence to Mediterranean diet by means of a 17-item validated questionnaire, anthropometrics, physical activity, blood pressure, blood biochemical parameters, and intrahepatic fat contents (IFC) were measured. The independent variable used was changes in MedDiet adherence, categorized in tertiles after 6 months follow-up. Subjects with high adherence to the MedDiet showed higher decreases in BMI, body weight, WC, SBP, DBP, and IFC. An association between improvement in adherence to the MedDiet and amelioration of IFC after 6-month follow-up was observed. High adherence to the MedDiet is associated with better status of MetS features, and better values of IFC.
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Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.
Zhu, L, She, ZG, Cheng, X, Qin, JJ, Zhang, XJ, Cai, J, Lei, F, Wang, H, Xie, J, Wang, W, et al
Cell metabolism. 2020;31(6):1068-1077.e3
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The novel coronavirus disease 2019 (COVID-19) is caused by infection from the newly emerged, highly contagious coronavirus SARS-CoV-2. The aim of this study was to analyse the association between plasma glucose levels and clinic outcomes in COVID-19 patients with type 2 diabetes (T2D). The study is a retrospective longitudinal, multi-centre study from a cohort of 7,337 COVID-19 cases enrolled among 19 hospitals. Results show that patients with pre-existing T2D received significantly more intensive integrated treatments to manage their symptoms of COVID-19 than the non-diabetic subjects. Furthermore, findings indicate that well-controlled blood glucose was associated with a markedly improved outcome of patients with COVID-19 and pre-existing T2D. Authors conclude that T2D is an important risk factor for COVID-19 progression and adverse endpoints, and well-controlled blood glucose is associated with a significant reduction in the composite adverse outcomes and death.
Abstract
Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors.
Merino, J, Jablonski, KA, Mercader, JM, Kahn, SE, Chen, L, Harden, M, Delahanty, LM, Araneta, MRG, Walford, GA, Jacobs, SBR, et al
Diabetes. 2020;69(1):112-120
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Individual risk of Coronary Artery Disease (CAD) and type 2 diabetes reflects the interplay between lifestyle behaviours acting on a backdrop of genetic predisposition. The aim of this study was to examine whether type 2 diabetes prevention strategies, either an intensive lifestyle intervention (ILS) or metformin treatment (MET), modify the association between CAD genetic risk and cardiometabolic risk factors (CRFs) in participants at high risk of type 2 diabetes. The study is a randomised controlled trial were participants were randomly allocated to one of the three groups; ILS (n = 1,079), MET (850 mg twice daily [n = 1,073]), or placebo (n = 1,082). Results indicate that there weren’t major significant differences in baseline characteristics, except for lower high-density lipoprotein and higher triglyceride in the placebo individuals compared with individuals assigned to MET or ILS. In fact, either an ILS or MET has a beneficial effect on 1-year change in different CRFs. Authors conclude that type 2 diabetes–preventive strategies for individuals at high risk of type 2 diabetes provide beneficial effects on CRFs regardless of CAD genetic risk profile.
Abstract
Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (P interaction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.
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The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE.
Lee, AK, Woodward, M, Wang, D, Ohkuma, T, Warren, B, Sharrett, AR, Williams, B, Marre, M, Hamet, P, Harrap, S, et al
The Journal of clinical endocrinology and metabolism. 2020;105(1)
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Type 2 diabetes is characterized by metabolic dysregulation resulting in an increased risk of cardiovascular disease The objectives of this study were: a. to determine whether weight change over 2 years was associated with subsequent cardiovascular outcomes and death in adults with diabetes, and b. to examine whether this association was modified by baseline body mass index (BMI), age, or type of glucose-lowering medications. This study is a large prospective study of adults with type 2 diabetes. One arm tested the effects of intensive glucose lowering versus standard glucose control. Whereas the second arm tested the effects of blood pressure-lowering medication versus a placebo. Results showed that that >10% weight loss was associated with >2 times higher risk of cardiovascular and all-cause mortality and was associated with 75% greater risk of major macrovascular events, compared with adults with stable weight. These associations were not significantly modified by metformin use, age, or baseline BMI. Authors conclude that unless patients specifically report lifestyle changes to lose weight, even modest weight loss may be a marker of declining health for which further clinical investigation is merited.
Abstract
CONTEXT Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. OBJECTIVE To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. DESIGN AND SETTING The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. RESULTS Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. CONCLUSIONS In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.
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Behaviour change, weight loss and remission of Type 2 diabetes: a community-based prospective cohort study.
Dambha-Miller, H, Day, AJ, Strelitz, J, Irving, G, Griffin, SJ
Diabetic medicine : a journal of the British Diabetic Association. 2020;37(4):681-688
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Type 2 Diabetes is considered a lifelong condition, but calorie restriction or weight loss can lead to complete remission. Patients newly diagnosed with Type 2 Diabetic may benefit from behavioural change over the long run. When Type 2 Diabetes is diagnosed early in the disease trajectory, it may increase the patient's motivation and make them more receptive to weight-loss interventions. This prospective cohort study included 865 newly diagnosed Type 2 diabetic patients from the ADDICTION Cambridge Trial, a pragmatic, parallel-group cluster randomised controlled trial. The study assessed the relationship between behaviour change and weight loss and the prospect of type 2 diabetes remission in the first year, following four years and after five years without intense dietary or lifestyle intervention in patients. 30% of the patients achieved diabetes remission at 5-year follow-up, with a significant likelihood of remission among those who achieved ≥ 10% weight loss in the first year of diagnosis. A self-reported change in intake of alcohol units was found to be the only consistent association between behaviour change and remission in this study. The role of behaviour change in the remission of diabetes requires further robust research. This study will help healthcare professionals understand the association between weight loss and remission in diabetic patients.
Abstract
AIM: To quantify the association between behaviour change and weight loss after diagnosis of Type 2 diabetes, and the likelihood of remission of diabetes at 5-year follow-up. METHOD We conducted a prospective cohort study in 867 people with newly diagnosed diabetes aged 40-69 years from the ADDITION-Cambridge trial. Participants were identified via stepwise screening between 2002 and 2006, and underwent assessment of weight change, physical activity (EPAQ2 questionnaire), diet (plasma vitamin C and self-report), and alcohol consumption (self-report) at baseline and 1 year after diagnosis. Remission was examined at 5 years after diabetes diagnosis via HbA1c level. We constructed log binomial regression models to quantify the association between change in behaviour and weight over both the first year after diagnosis and the subsequent 1-5 years, as well as remission at 5-year follow-up. RESULTS Diabetes remission was achieved in 257 participants (30%) at 5-year follow-up. Compared with people who maintained the same weight, those who achieved ≥ 10% weight loss in the first year after diagnosis had a significantly higher likelihood of remission [risk ratio 1.77 (95% CI 1.32 to 2.38; p<0.01)]. In the subsequent 1-5 years, achieving ≥10% weight loss was also associated with remission [risk ratio 2.43 (95% CI 1.78 to 3.31); p<0.01]. CONCLUSION In a population-based sample of adults with screen-detected Type 2 diabetes, weight loss of ≥10% early in the disease trajectory was associated with a doubling of the likelihood of remission at 5 years. This was achieved without intensive lifestyle interventions or extreme calorie restrictions. Greater attention should be paid to enabling people to achieve weight loss following diagnosis of Type 2 diabetes.
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Fasting blood glucose, glycaemic control and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.
Murtola, TJ, Vihervuori, VJ, Lahtela, J, Talala, K, Taari, K, Tammela, TL, Auvinen, A
British journal of cancer. 2018;118(9):1248-1254
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Studies have shown that people with diabetes mellitus have lower risk of developing prostate cancer compared with non-diabetics. Glucose metabolism (the process by which simple sugars found in food are processed and used to produce energy) may have an independent role in prostate cancer development and progression. The aim of this study was to investigate the associations between fasting blood glucose and glycaemic control and prostate cancer risk. The study recruited 80,144 men who were randomly assigned either to be screened with PSA at four-year intervals (the screening arm, 31,866 men) or to control arm with no intervention and followed through national registries (48,278 men). Results indicate an association between fasting blood glucose level and elevated prostate cancer risk. This association was more noticeable in the screening arm, and concerned both poorly and well-differentiated cancers. Furthermore, compared to the normoglycemic men, overall prostate cancer risk was elevated in diabetic, but not in pre-diabetic men. Authors conclude that diabetic fasting blood glucose level is associated with elevated prostate cancer risk in a population-based cohort of Finnish men.
Abstract
BACKGROUND Diabetic men have lowered overall risk of prostate cancer (PCa), but the role of hyperglycaemia is unclear. In this cohort study, we estimated PCa risk among men with diabetic fasting blood glucose level. METHODS Participants of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to laboratory database for information on glucose measurements since 1978. The data were available for 17,860 men. Based on the average yearly level, the men were categorised as normoglycaemic, prediabetic, or diabetic. Median follow-up was 14.7 years. Multivariable-adjusted Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for prostate cancer overall and separately by Gleason grade and metastatic stage. RESULTS In total 1,663 PCa cases were diagnosed. Compared to normoglycaemic men, those men with diabetic blood glucose level had increased risk of PCa (HR 1.52; 95% CI 1.31-1.75). The risk increase was observed for all tumour grades, and persisted for a decade afterwards. Antidiabetic drug use removed the risk association. Limitations include absence of information on lifestyle factors and limited information on BMI. CONCLUSIONS Untreated diabetic fasting blood glucose level may be a prostate cancer risk factor.
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Improvement of Nonalcoholic Fatty Liver Disease With Carnitine-Orotate Complex in Type 2 Diabetes (CORONA): A Randomized Controlled Trial.
Bae, JC, Lee, WY, Yoon, KH, Park, JY, Son, HS, Han, KA, Lee, KW, Woo, JT, Ju, YC, Lee, WJ, et al
Diabetes care. 2015;38(7):1245-52
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Non-alcoholic fatty liver disease (NAFLD) is recognized as the hepatic component of metabolic syndrome, and it is associated with insulin resistance independent of obesity and other metabolic components. Carnitine is a modulator of mitochondrial free fatty acid transport and oxidation, and several studies have demonstrated the antioxidant activity of carnitine in hepatocytes. The aim of this study was to evaluate the effects of carnitine-orotate complex in patients with NAFLD and diabetes. This study is a multicentre, randomised, double-blind, placebo-controlled trial. Patients were randomly assigned to receive carnitine-orotate complex or placebo during the 12-week treatment period. Results show that treatment with carnitine-orotate complex improves hepatic steatosis in patients with diabetes and NAFLD, and has a beneficial effect on glucose metabolism, particularly in relation to improvement of hepatic steatosis. Authors conclude that further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.
Abstract
OBJECTIVE We aimed to evaluate the effects of carnitine-orotate complex in patients with nonalcoholic fatty liver disease (NAFLD) and diabetes. RESEARCH DESIGN AND METHODS Eight hospitals in Korea participated in this randomized, controlled, double-blind trial of patients with diabetes and NAFLD. Seventy-eight patients were randomly assigned in a 1:1 ratio to receive carnitine-orotate complex (824 mg, three times daily) or matching placebo. The primary study outcome was decline in alanine aminotransferase (ALT) to the normal range. Secondary study outcomes were change in ALT, radiological hepatic steatosis, parameters for anthropometry, liver function, lipid profiles, and glycemic control. Hepatic steatosis was assessed using Hounsfield units on noncontrast computed tomography (CT) imaging with hepatic attenuation. RESULTS After 12 weeks of treatment, compared with placebo group, carnitine-orotate complex-treated participants had a significantly higher rate of normalization of serum ALT level (17.9% vs. 89.7%, P < 0.001). On hepatic CT analysis, participants treated with carnitine-orotate complex showed an increased liver attenuation index (0.74 ± 8.05 vs. 6.21 ± 8.96, P < 0.008). A significant decrease in HbA1c was observed in the carnitine-orotate complex group (-0.33 ± 0.82% [-3.6 ± 9.0 mmol/mol], P = 0.007), but no significant change was seen in the placebo group. CONCLUSIONS Treatment with carnitine-orotate complex improves serum ALT and may improve hepatic steatosis as assessed by CT in patients with diabetes and NAFLD. Further studies using more advanced magnetic resonance imaging and liver histology as an end point are needed to assess its efficacy in NAFLD.