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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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Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer's disease: a cross-sectional study of middle-aged adults from the broader New York City area.
Mosconi, L, Walters, M, Sterling, J, Quinn, C, McHugh, P, Andrews, RE, Matthews, DC, Ganzer, C, Osorio, RS, Isaacson, RS, et al
BMJ open. 2018;8(3):e019362
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Alzheimer’s disease (AD) is the most common form of dementia, affecting nearly 34 million people worldwide. It has been estimated that one in every three cases of AD may be attributable to diet and lifestyle factors. The aim of this study was to investigate the effects of lifestyle and vascular-related risk factors for AD. Researchers studied the brain scans of 116 healthy adults aged 30-60 years. They collected information on factors related to lifestyle, such as diet, physical activity and intellectual enrichment. They also looked at markers for vascular risk such as body mass index (BMI), cholesterol and homocysteine, as well as cognitive function. The researchers found that a Mediterranean-style diet and good insulin sensitivity were both associated with a healthier brain structure. A better score for intellectual enrichment and lower BMI were both associated with better cognition. They concluded that adopting a Mediterranean-style diet and maintaining a healthy weight might reduce the risk of developing AD.
Abstract
OBJECTIVE To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults. DESIGN Cross-sectional, observational. SETTING Broader New York City area. Two research centres affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. PARTICIPANTS We studied 116 cognitively normal healthy research participants aged 30-60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition. RESULTS Adherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: βs≥0.26, insulin sensitivity βs≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (βs≥0.25 P≤0.001), as were those between overweight and lower cognition (βs≥-0.22, P≤0.01). CONCLUSIONS In cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.
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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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Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: The EverExt study.
Pizzuti, L, Marchetti, P, Natoli, C, Gamucci, T, Santini, D, Scinto, AF, Iezzi, L, Mentuccia, L, D'Onofrio, L, Botticelli, A, et al
Scientific reports. 2017;7(1):10597
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Literature shows that hyperglycaemia is amongst the most common grade 3 or 4 drug-related adverse events in breast cancer patients. The aim of the study was to investigate the role of anthropometrics and biomarkers of glucose metabolism on treatment outcomes in advanced breast cancer patients. The study is an observational study that recruited 102 postmenopausal women, aged at least 18 years, who were diagnosed with advanced breast cancer and treated with everolimus and exemestane. Results indicate a significant trend towards increasing fasting glucose and decreasing BMI in the overall study population. Furthermore, significant evidence also shows that lower levels of fasting glucose is associated with better outcomes. Authors conclude that their study showed a predictive role of fasting glucose and BMI on treatment outcomes, longer progression free survival and clinical benefit rates (percentage of patients with shrinking tumours or stable disease for at least 6 months).
Abstract
Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms.
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Timing of food intake predicts weight loss effectiveness.
Garaulet, M, Gómez-Abellán, P, Alburquerque-Béjar, JJ, Lee, YC, Ordovás, JM, Scheer, FA
International journal of obesity (2005). 2013;37(4):604-11
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As obesity is a multifactorial disease, dietary interventions must take into account a range of physiological and psychological variables. There is emerging evidence linking energy regulation to the circadian clock, emphasizing that the timing of eating may play a role in weight regulation. The aim of this study was to evaluate the role of food timing in weight loss effectiveness among 420 overweight or obese participants during a 20-week weight loss treatment. Participants were grouped as either early or late eaters for consuming their main meal, and their energy intake, expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied. In this study, those who ate their main meal late lost significantly less weight than early eaters. The findings of this study indicate that timing of food intake relates to long-term weight loss effectiveness in humans. These findings may help in developing therapeutic strategies for weight loss that incorporates the timing of food consumption with the traditional energy balance and macronutrient composition.
Abstract
BACKGROUND There is emerging literature demonstrating a relationship between the timing of feeding and weight regulation in animals. However, whether the timing of food intake influences the success of a weight-loss diet in humans is unknown. OBJECTIVE To evaluate the role of food timing in weight-loss effectiveness in a sample of 420 individuals who followed a 20-week weight-loss treatment. METHODS Participants (49.5% female subjects; age (mean ± s.d.): 42 ± 11 years; BMI: 31.4 ± 5.4 kg m(-2)) were grouped in early eaters and late eaters, according to the timing of the main meal (lunch in this Mediterranean population). 51% of the subjects were early eaters and 49% were late eaters (lunch time before and after 1500 hours, respectively), energy intake and expenditure, appetite hormones, CLOCK genotype, sleep duration and chronotype were studied. RESULTS Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups. Nevertheless, late eaters were more evening types, had less energetic breakfasts and skipped breakfast more frequently that early eaters (all; P<0.05). CLOCK rs4580704 single nucleotide polymorphism (SNP) associated with the timing of the main meal (P=0.015) with a higher frequency of minor allele (C) carriers among the late eaters (P=0.041). Neither sleep duration, nor CLOCK SNPs or morning/evening chronotype was independently associated with weight loss (all; P>0.05). CONCLUSIONS Eating late may influence the success of weight-loss therapy. Novel therapeutic strategies should incorporate not only the caloric intake and macronutrient distribution - as is classically done - but also the timing of food.