Is There an Association Between Metformin Exposure and Frailty?

Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality, and utilization in older adults. Frailty and type 2 diabetes mellitus share similar pathophysiological mechanisms which metformin may target. The purpose of this study was to determine whether exposure to metformin is associated with frailty in veterans. This is a cross-sectional study of veterans 65 years and older with type 2 diabetes who were screened for frailty between January 2016 and August 2017. We constructed a 44-item Frailty Index including multiple variables using a deficit accumulation framework. After adjustment for covariates, the association was calculated using binomial logistic regression models with frailty status as the outcome variable, and metformin exposure as the independent variable. Patients were 98.3% male and 56.7% White with a mean age of 72.9 ( SD = 6.8) years. The proportion of robust, prefrail and frail patients was 2.9% ( n = 22), 46.7 % ( n = 356) and 50.5% ( n = 385), respectively. In binomial logistic regression, exposure to metformin was associated with lower risk for frailty, adjusted odds ratio (OR) = .55 (95% confidence interval [CI] = .39–.77), p ≤ .001. This study shows that exposure to metformin was associated with lower risk for frailty in community-dwelling veterans.

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Associations between Serum Betaine, Methyl-Metabolizing Genetic Polymorphisms and Risk of Incident Type 2 Diabetes: A Prospective Cohort Study in Community-Dwelling Chinese Adults

Nutrients ◽

10.3390/nu14020362 ◽

2022 ◽

Vol 14 (2) ◽

pp. 362

Author(s):

Xiaoting Lu ◽

Rongzhu Huang ◽

Shuyi Li ◽

Aiping Fang ◽

Yuming Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Genetic Polymorphisms ◽

Lower Risk ◽

Methylenetetrahydrofolate Reductase ◽

Community Dwelling ◽

Cox Proportional Hazards Model ◽

Chinese Adults ◽

Baseline Serum ◽

Mthfr A1298c

Previous studies have explored associations between betaine and diabetes, but few have considered the effects of genes on them. We aimed to examine associations between serum betaine, methyl-metabolizing genetic polymorphisms and the risk of type 2 diabetes in Chinese adults. This prospective study comprised 1565 subjects aged 40–75 without type 2 diabetes at baseline. Serum betaine was measured by high-performance liquid chromatography tandem mass spectrometry. Genotyping of methyl-metabolizing genes was detected by Illumina ASA-750K arrays. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median of 8.9 years of follow-up, 213 participants developed type 2 diabetes. Compared with participants in the lowest quartile of serum betaine, those in the highest quartile had lower risk of type 2 diabetes, adjusted HRs (95%CIs) was 0.46 (0.31, 0.69). For methylenetetrahydrofolate reductase (MTHFR) G1793A (rs2274976) and MTHFR A1298C (rs1801131), participants carrying 1793GA + AA and 1298AC + CC had lower risk of type 2 diabetes. Interactions of serum betaine and genotype of MTHFR G1793A and MTHFR A1298C could be found influencing type 2 diabetes risk. Our findings indicate that higher serum betaine, mutations of MTHFR G1793A and A1298C, as well as the joint effects of them, are associated with lower risk of type 2 diabetes.

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Is there an association between ageist attitudes and frailty?

BMC Geriatrics ◽

10.1186/s12877-019-1357-y ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Douglas Salguero ◽

Juliana Ferri-Guerra ◽

Nadeem Y. Mohammed ◽

Dhanya Baskaran ◽

Raquel Aparicio-Ugarriza ◽

...

Keyword(s):

Older Adults ◽

Logistic Regression ◽

Multinomial Logistic Regression ◽

Frailty Index ◽

Cross Sectional Study ◽

Community Dwelling ◽

Outcome Variable ◽

Cross Sectional ◽

Logistic Regression Models ◽

Frailty Status

Abstract Background Frailty is defined as a state of vulnerability to stressors that is associated with higher morbidity, mortality and healthcare utilization in older adults. Ageism is “a process of systematic stereotyping and discrimination against people because they are old.” Explicit biases involve deliberate or conscious controls, while implicit bias involve unconscious processes. Multiple studies show that self-directed ageism is a risk factor for increased morbidity and mortality. The purpose of this study was to determine whether explicit ageist attitudes are associated with frailty in Veterans. Methods This is a cross-sectional study of Veterans 50 years and older who completed the Kogan’s Attitudes towards Older People Scale (KAOP) scale to assess explicit ageist attitudes and the Implicit Association Test (IAT) to evaluate implicit ageist attitudes from July 2014 through April 2015. We constructed a frailty index (FI) of 44 variables (demographics, comorbidities, number of medications, laboratory tests, and activities of daily living) that was retrospectively applied to the time of completion of the KAOP and IAT. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multinomial logistic regression models with frailty status (robust, prefrail and frail) as the outcome variable, and with KAOP and IAT scores as the independent variables. Age, race, ethnicity, median household income and comorbidities were considered as covariates. Results Patients were 89.76% male, 48.03% White, 87.93% non-Hispanic and the mean age was 60.51 (SD = 7.16) years. The proportion of robust, pre-frail and frail patients was 11.02% (n = 42), 59.58% (n = 227) and 29.40% (n = 112) respectively. The KAOP was completed by 381 and the IAT by 339 participants. In multinomial logistic regression, neither explicit ageist attitudes (KAOP scale score) nor implicit ageist attitudes (IAT) were associated with frailty in community dwelling Veterans after adjusting for covariates: OR = .98 (95% CI = .95–1.01), p = .221, and OR:=.97 (95% CI = .37–2.53), p = .950 respectively. Conclusions This study shows that neither explicit nor implicit ageist attitudes were associated with frailty in community dwelling Veterans. Further longitudinal and larger studies with more diverse samples and measured with other ageism scales should evaluate the independent contribution of ageist attitudes to frailty in older adults.

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IMPACT OF AN INTENSIVE MULTIDOMAIN LIFESTYLE INTERVENTION ON DEFICIT ACCUMULATION FRAILTY INDICES

Innovation in Aging ◽

10.1093/geroni/igz038.2874 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S781-S781

Author(s):

Felicia Simpson ◽

Nicholas M Pajewski ◽

Alain M Bertoni ◽

Frank Ingram ◽

Barbara M Nicklas ◽

...

Keyword(s):

Type 2 Diabetes ◽

Lifestyle Intervention ◽

Frailty Index ◽

Biological Aging ◽

Controlled Clinical Trial ◽

Deficit Accumulation ◽

Dietary Counseling ◽

Two Indices ◽

Over Time

Abstract Background: Type 2 diabetes and obesity increase accumulation of health deficits over time and may accelerate biological aging. It is unknown whether multidomain lifestyle interventions can mitigate against this. Methods: Within a large, randomized controlled clinical trial of intensive lifestyle intervention (ILI) including caloric restriction, increased physical activity, dietary counseling, and risk factor monitoring compared with diabetes support and education (DSE) we examined the trajectory of frailty across 8 years. We used two complementary frailty index (FI) definitions, one modeled on work in the Systolic Blood Pressure Intervention Trial; the other including additional deficits related to aging with obesity and type 2 diabetes mellitus. Differences between intervention groups and the consistency of these across clinical subgroups were assessed with re-randomization tests. Results: Data from 4859 adults (45-76 years at baseline, 59% female) were analyzed. Random assignment to ILI was associated with lower FI scores throughout 8 years of follow-up (p<0.001), over which time mean differences between intervention groups averaged 5.8% and 5.4% for the two indices. At year 8, the percentages of participants categorized as frail (FI>0.21) were lower among ILI (39.8% and 54.5%) compared with DSE (42.7% and 60.9%) for the two indices (both p<0.001). Intervention benefits were relatively greater for individuals who were older, not obese, and without history of cardiovascular disease at baseline. Conclusions: Eight years of multidomain lifestyle intervention slows the accumulation of health deficits over time in overweight or obese adults with type 2 diabetes.

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Meal frequency and incidence of type 2 diabetes: a prospective study

British Journal Of Nutrition ◽

10.1017/s0007114521003226 ◽

2021 ◽

pp. 1-6

Author(s):

Xiaowen Wang ◽

Yonghua Hu ◽

Li-Qiang Qin ◽

Jia-Yi Dong

Keyword(s):

Type 2 Diabetes ◽

Lower Risk ◽

Dietary Habits ◽

Community Dwelling ◽

Meal Frequency ◽

Incident Type ◽

Incident Type 2 Diabetes ◽

A Prospective Study ◽

Baseline Bmi

Abstract Dietary habits play an important role in the development of obesity and type 2 diabetes. However, evidence on association between diet frequency and type 2 diabetes was limited and inconclusive. We aimed to examine the association between meal frequency and risk of type 2 diabetes. The cohort study used data from China Health and Retirement Longitudinal Study of 8874 community-dwelling people aged over 45 years. Participants were classified as eating two meals per day, three meals per day and four meals per day. Multiple Poisson regression models were used to examine risk of 4-year incident type 2 diabetes among people who ate more or less than three meals per day compared with people who ate three meals per day. We documented 706 type 2 diabetes cases during follow-up. After adjustment for known risk factors for type 2 diabetes, except for BMI, participants who ate four meals per day were at a lower risk of type 2 diabetes than those who ate three meals per day (relative risk(RR) = 0·73 (0·58, 0·92)). After further adjustment for baseline BMI, the association was slightly attenuated but remained statistically significant (RR = 0·76 (0·60, 0·97)). Subgroup analysis showed that the fully adjusted RR of type 2 diabetes for people eating four meals per day were 0·66 (0·48, 0·91) and 0·93 (0·65, 1·34) among those had a BMI < 25 and ≥ 25 kg/m2, respectively. Eating four meals per day, compared with eating three meals per day was associated with lower risk of developing type 2 diabetes in a Chinese population, particularly in those with a BMI < 25 kg/m2.

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Eight Year Changes in Multimorbidity and Frailty in Adults with Type 2 Diabetes Mellitus: Associations with Cognitive and Physical Function and Mortality

The Journals of Gerontology Series A ◽

10.1093/gerona/glab342 ◽

2021 ◽

Author(s):

Mark A Espeland ◽

Jamie Nicole Justice ◽

Judy Bahnson ◽

Joni K Evans ◽

Medha Munshi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Physical Function ◽

Frailty Index ◽

Biological Aging ◽

Older Individuals ◽

Deficit Accumulation ◽

Increased Risk

Abstract Background Indices of multimorbidity and deficit accumulation (i.e. frailty indices) have been proposed as markers of biological aging. If true, changes in these indices over time should predict downstream changes in cognition and physical function, and mortality. Methods We examined associations that 8-year changes in 1) a multimorbidity index comprised of nine chronic diseases and 2) a frailty index (FI) based on deficit accumulation in functional, behavioral, and clinical characteristics had with subsequent measures of cognitive and physical function over 10 years. We drew data from 3841 participants in the Look AHEAD clinical trial. They were aged 45-76 years at baseline and at risk for accelerated biological aging due to overweight/obesity and type 2 diabetes mellitus. Results 1501 (39%) of the cohort had 8-year increases of one among the nine diseases tracked in the multimorbidity index and 868 (23%) had increases of >2. Those with greatest increases in multimorbidity tended to be older individuals, males, and non-Hispanic whites. Greater FI increases tended to occur among individuals who were older, non-Hispanic white, heavier, and who had more baseline morbidities. Changes in multimorbidity and FI were moderately correlated (r=0.26; p<0.001). Increases in both multimorbidity and FI were associated with subsequently poorer composite cognitive function and 400m walk speed and increased risk for death (all p<0.001). Conclusions Accelerated biological aging, as captured by multimorbidity and frailty indices, predicts subsequent reduced function and mortality. Whether intensive lifestyle interventions generally targeting multimorbidity and FI reduce risks for downstream outcomes remains to be seen.

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Association between frailty and risk of fall among diabetic patients

Endocrine Connections ◽

10.1530/ec-20-0405 ◽

2020 ◽

Vol 9 (10) ◽

pp. 1057-1064

Author(s):

Xiaojie Wang ◽

Zhiyuan Chen ◽

Ziyi Li ◽

Bo Chen ◽

Yong Qi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Frailty Index ◽

Epidemiological Studies ◽

Vulnerable Groups ◽

Diabetic Patients ◽

Balance Performance ◽

Deficit Accumulation ◽

Increased Risk ◽

Risk Of Fall

Background Several epidemiological studies have demonstrated the risk factors for fall, while few studies investigated the association between frailty and risk of fall in diabetic patients aged ≥45 years. Methods In this multicity observational study, participants with type 2 diabetes aged ≥45 years were enrolled. Frailty status was measured by a frailty index (FI) of deficit accumulation. We used multivariable regression models to examine the relationship between frailty and fall in diabetic patients, and further investigated the associations between frailty and fall in varied subgroups. Results A total of 2049 participants with type 2 diabetes were identified in our study. Our results showed a per-s.d. and a per-0.01 increment of FI were associated with an increased risk of fall, with a fully adjusted OR of 1.89 (95% CI: 1.50, 2.38), 1.06 (95% CI: 1.04, 1.09), respectively. The effects were magnified when frailty was considered as dichotomous, with an OR of 3.08 (95% CI: 2.18, 4.34). In further subgroup analyses, we found that the females, the older, rural residents, individuals with no sitting toilet, people with poor balance performance and those in poor health status were susceptible to fall. Especially, for the risk of fall in the older, a per-s.d. increase of FI corresponded to an OR of 2.46 (95% CI: 1.68, 3.62). When frailty was regarded as a binary variable, the effect increased to 4.62 (95% CI: 2.54, 8.38) in the older subgroup. Conclusion Frailty was associated with a higher risk of fall in people with type 2 diabetes, and the effects were higher in vulnerable groups. This evidence suggested that more attention should be paid to vulnerable groups for fall prevention.

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Effect of the Age at Menarche and Menopause Status Interaction on Type 2 Diabetes: The Henan Rural Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz328 ◽

2020 ◽

Vol 105 (3) ◽

pp. e139-e147 ◽

Cited By ~ 1

Author(s):

Lulu Zhang ◽

Yuqian Li ◽

Xiaokang Dong ◽

Wen Zhou ◽

Chongjian Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Interaction Effect ◽

Lower Risk ◽

Significant Interaction ◽

Age At Menarche ◽

Homa Index ◽

Significant Interaction Effect ◽

Multiple Variables ◽

Menarche Age

Abstract Purpose The aims of this study were to evaluate the effect of age at menarche (AM) on type 2 diabetes mellitus (T2DM) and to assess whether the fasting plasma glucose (FPG) and homeostasis model assessment (HOMA) index responses to AM and menopause status interact in Chinese rural adults. Methods A cross-sectional, population-based study including 23 138 participants was performed. Logistic regression and multivariable linear regression were performed to investigate the relationship between AM and glucose status. Generalized linear model was used to calculate the interaction term of AM and menopause status on FPG and the HOMA index. Interaction plot was used to interpret the significant interaction effect. Results Women in the later menarche age group (≥18 years) had a 17.7% lower risk of T2DM (95% confidence interval [CI]: 0.712-0.951, P = .008), after adjusting for multiple variables. Further adjustment for body mass index (BMI) completely attenuated this association (odds ratio = 0.884, 95% CI: 0.764-1.024, P = .099). A significant interaction effect of AM and menopause status on T2DM (P = .004) was observed. The adverse effects of menopausal status on FPG and HOMA-2 of insulin resistance decreased with increasing menarche age, and the age ranges were limited to <18 and 9 to 19 years, respectively. Conclusions Later menarche was associated with a lower risk of T2DM, and the association appears to be mediated by BMI. More importantly, the adverse effect of menopause status on T2DM was decreased along with increasing menarche age.

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Less Advanced Stages of Colon Cancer in Patients with Type 2 Diabetes Mellitus: an Unexpected Finding?

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0031-1299704 ◽

2012 ◽

Vol 120 (04) ◽

pp. 224-228 ◽

Cited By ~ 4

Author(s):

J. Nagel ◽

S. Bücker ◽

M. Wood ◽

R. Stark ◽

B. Göke ◽

...

Keyword(s):

Diabetes Mellitus ◽

Colorectal Cancer ◽

Type 2 Diabetes ◽

Colon Cancer ◽

Type 2 Diabetes Mellitus ◽

Logistic Regression ◽

Regression Analysis ◽

Lower Risk ◽

Advanced Stages

AbstractEpidemiological studies have found an increased risk for colon cancer and faster disease progression in patients with type 2 diabetes mellitus (T2DM). We aimed to determine whether patients with T2DM are diagnosed with more advanced stages of colorectal cancer, i. e., metastasized disease (UICC III and IV), at the time of diagnosis, since such a finding may have an impact on future guidelines for patients with T2DM.A cross-sectional analysis of colorectal cancer patients was performed. Stages at diagnosis in patients with (18.0%) or without (82%) T2DM were compared using logistic regression analysis to correct for confounders.Patients with T2DM were older, more obese, and more often male (each p<0.05). Unexpectedly, patients with T2DM had a lower risk for metastasized disease at diagnosis (p=0.023). Correction for age, gender, BMI, smoking and aspirin intake in a multiple logistic regression analysis did not change the result (OR=0.57, p=0.037). When looking at individual cancer stages rather than collapsed categories, there was a trend for less advanced stages in patients with T2DM (p=0.093). Excluding stage I because of potential screening bias due to the introduction of (insurance-covered) colonoscopy screening improved model fit, and confirmed less advanced cancer stages (p=0.0246).Possibly because of earlier detection, patients with T2DM may be at lower risk for advanced stages of colon cancer at diagnosis. Further studies are warranted to confirm our results and to investigate the impact of closer medical surveillance in patients with type 2 diabetes mellitus.

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