path: root/gnqa/paper1_eval/src/data/responses/aging/experts/03.json

{
    "created_at": "2024-05-31T20:36:11.762580Z",
    "data": {
        "amplify": false,
        "answer": "Yes, there is a direct association between aging and susceptibility to having diabetes. The risk of onset of type 2 diabetes increases with age, and most diabetic patients in certain regions are 40 years old or more. Additionally, aging is associated with changes in body composition and glucose tolerance, which can contribute to the development of diabetes.",
        "context": {
            "29e232a4-a580-411d-83a3-7ff6a4e8f0ad": [
                {
                    "document_id": "29e232a4-a580-411d-83a3-7ff6a4e8f0ad",
                    "text": "\n\nOur result provides a novel hypothesis on the mechanism for the connection between two aging-related diseases: Alzheimer's disease and type 2 diabetes."
                }
            ],
            "6e570a0b-a876-4263-b32f-cee85088756d": [
                {
                    "document_id": "6e570a0b-a876-4263-b32f-cee85088756d",
                    "text": "\n\nThere are two major factors that underlie these alarming projections.The first is T2D is associated with age, and Western populations are aging rapidly.The second major explanation is our lifestyles have changed dramatically in recent years.Epidemiological studies have identified strong T2D risk relationships for obesity, sedentary behavior [2][3][4], and diets rich in energy [5], processed carbohydrates [6], and animal fats [7].Collectively, these lifestyle factors impede the actions of insulin and raise hepatic glucose production, which can result in the diminution of endogenous insulin production and T2D.The strongest evidence for a causal relationship between adverse lifestyle behaviors and T2D comes from randomized controlled trials that show intensive lifestyle interventions involving structured exercise regimes which promote habitual physical activity (PA) and have a major beneficial impact on diabetes incidence in high-risk individuals [8,9]."
                },
                {
                    "document_id": "6e570a0b-a876-4263-b32f-cee85088756d",
                    "text": "\n\nEpidemiological studies examining the associations between lifestyle behaviors and diabetes risk have reached similar conclusions as the clinical trials described above.For example, the 14-year follow-up University of Pennsylvania Alumni Health Study [52] (n = 5,990 men aged 39-68 years) showed PA (leisure time physical activity [LTPA] expressed in kcal expended per week through walking, stair climbing, and sports) was inversely associated with the incidence of T2D.Incidence rates declined as energy expenditure rose from 500 through 3,500 kcal/week.The age-adjusted relative risk ratio (RR) of T2D was reduced by about 6% for each 500 kcal increment increase in PA energy expenditure."
                }
            ],
            "71172700-7bcc-42f5-9354-d8e9290e8743": [
                {
                    "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                    "text": "\n\nOverall, results were similar in analyses restricted to diabetes mellitus identified at baseline only, although the confidence interval included 1.These results suggest that diabetes mellitus is related to risk of AD in old age.These findings are consistent with the results of 2 large longitudinal cohort studies. 5,6In one study, 5 diabetes mellitus doubled the risk of AD during 2 years of follow-up in a sample of more than 6000 older persons from a defined cohort.The other study, 6 using data from about 2500 Japanese American men, found a similar result: diabetes mellitus approximately doubled the risk of AD.In contrast, 2 other longitudinal studies 7,8 did not  demonstrate a significant association between diabetes mellitus and incident AD, but in both, the results were in the direction of increased risk.Some, [9][10][11] but not all, 12 previous studies found that diabetes mellitus was related to change in cognitive function.One factor that may contribute to variability from study to study is that diabetes mellitus may be related to decline in some cognitive systems but not others.4][15] Although diabetes mellitus was related to level of global cognition and multiple cognitive domains at baseline, we found that diabetes mellitus was only related to decline in perceptual speed.The one study 12 that did not find a relation between diabetes mellitus and cognitive decline did not include a measure of perceptual speed."
                },
                {
                    "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                    "text": "COMMENT\n\nIn a cohort of more than 800 older persons, we found that diabetes mellitus sometime in the study was associated with an increased risk of developing AD during a mean of 5.5 years of observation.The risk of incident AD was 65% higher in those with diabetes mellitus than in those without it."
                },
                {
                    "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                    "text": "\n\nIn summary, these findings suggest that diabetes mellitus is associated with AD and decline in cognitive function in older persons.December 12, 2003."
                },
                {
                    "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                    "text": "DIABETES MELLITUS AND RISK OF AD\n\nDuring the follow-up evaluations, 151 persons developed AD, of whom 31 had diabetes mellitus.In a proportional hazards model adjusted for age, sex, and educational level, there was a 65% increase in the risk of developing AD in those with diabetes mellitus compared with those without diabetes mellitus (hazard ratio, 1.65; 95% confidence interval, 1.10-2.47).The cumulative hazard of AD over time, adjusted for age, sex, and educational level, is shown graphically in Figure 1 for typical participants with and without diabetes mellitus.Similar results were found in analyses with diabetes mellitus identified at baseline only (hazard ratio, 1.53; 95% confidence interval, 0.96-2.45)."
                }
            ],
            "77daf125-3e88-41fe-92fd-71a9ce9c6671": [
                {
                    "document_id": "77daf125-3e88-41fe-92fd-71a9ce9c6671",
                    "text": "\n\nAge. Age is another factor that has a considerable effect on outcomes in obesity and T2DM research.In humans, body weight increases with age and peaks at ~55 years in both men and women.Ageing per se is associated with a redistribution of both the fat-free mass and the fat mass, with the latter increase starting at ~30 years of age 129 .Intramuscular and intrahepatic fat are particularly increased in older persons, and this increase has been linked to insulin resistance 130 .Partially on the basis of these changes, ageing has been proposed to be an independent determinant of glucose tolerance, which progressively worsens with age 131,132 ."
                }
            ],
            "94e153f4-bc43-4e5b-99d4-6bb64ed24e4a": [
                {
                    "document_id": "94e153f4-bc43-4e5b-99d4-6bb64ed24e4a",
                    "text": "\n\nAge also plays a vital role in the onset of diabetes (Cowie & Eberhardt, 1995).In south-east Asia almost 97% diabetic patients are 40 years old or more (IDF Atlas, 2017).In Bangladesh, the reported age of diabetes is ≥40 years in 71% urban and 85% rural female, while in the case of male the proportion is 85.5% urban and 86.5% in rural population (IDF Atlas, 2017).The current study also pinpointed an exponential increase in the risk of onset of T2DM with the increase of age when 40 years was chosen as the reference (Table S4)."
                },
                {
                    "document_id": "94e153f4-bc43-4e5b-99d4-6bb64ed24e4a",
                    "text": "\n\nWhether age and stress variables are risk factors for type 2 diabetes incidence was assessed by multivariate logistic regression (Table S4).Subjects in the age groups of (40-60) and >60 years had 1.78× (p = .005)and 3.19× (p = .006)greater risk for type 2 diabetes respectively than group of <40 years.Overall, patients under stressful condition are more likely to develop T2DM than that of nonstressed respondent (p = .000).Moreover, when stress is divided into two groups-low stress and high stress, we found that both males (p = .000)and females (p = .000)with high stress were at high risk of diabetes mellitus, whereas the association between low stress and T2DM incidence was significant only among males (Male: p = .002;Female: p = .115).The distribution and association of the genotypes, age, and stress with T2DM have been summarized in Table 3 and Figure 3.There was no difference in T2DM incidence between CT (p = .030)and TT/CC (p = .034)genotype containing people who were in age group of 40-60 years (Table 3).In contrast, people who were more than 60 years old with CT genotype (OR = 4.636, p = .029)were more prone to T2DM than that of TT/CC genotype (OR = 3.714, p = .007)subjects (Table 3)."
                }
            ],
            "9c9cc0b3-5dde-4077-ae41-1410db9aeb24": [
                {
                    "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                    "text": "Research Gaps\n\nThere is a clear correlation of environmental influences to diabetes risk.Yet, the assembled experts agreed that hypothesis-driven research is needed to define direct causal relationships between specific environmental factors and pathophysiologies leading to diabetes.Research efforts need to address environmental etiologies of type 1 diabetes and determine their relative contribution to onset of autoimmunity and progression to symptomatic disease.Whether there is a direct causal role of the intestinal microbiota in pathogenesis of type 1 and type 2 diabetes and response to therapies needs to be determined.Public health interventions that successfully reduce the levels of consumption of energy-dense foods and/or reduce sedentary time and increase time spent in physical activity need to be evaluated to determine whether they can reduce type 2 diabetes incidence at a population level."
                }
            ],
            "afe6a42e-2c8b-4cfd-9334-157d1b9d15b6": [
                {
                    "document_id": "afe6a42e-2c8b-4cfd-9334-157d1b9d15b6",
                    "text": "\n\nIn sum, it is clear that multiple risk factors are involved in diabetes-associated cognitive decrements as well as in dementia in relation to diabetes 38 .On the basis of our assessment of the literature, it is also clear that there are still substantial knowledge gaps on how the risk factors interconnect, how the risk factors translate to potentially modifiable mechanisms and which genetic factors are involved."
                }
            ],
            "b21bbbce-b53f-416b-8378-b635f4270ace": [
                {
                    "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                    "text": "\n\nThe aim of this study was to investigate the association between age at natural menopause and risk of developing type 2 diabetes, and to assess whether this association is independent of potential intermediate risk factors for type 2 diabetes.Furthermore, we examined the role of endogenous sex hormone levels in the association between age at natural menopause and type 2 diabetes."
                },
                {
                    "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                    "text": "\n\nAims/hypothesis In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators.Methods We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study.Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature,  <40 years; early, 40-44 years; normal, 45-55 years; and late  menopause, >55 years [reference]).Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from Rotterdam Study visits.HRs and 95% CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens."
                },
                {
                    "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                    "text": "\nAims/hypothesis In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators.Methods We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study.Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature,  <40 years; early, 40-44 years; normal, 45-55 years; and late  menopause, >55 years [reference]).Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from Rotterdam Study visits.HRs and 95% CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens.Results During a median follow-up of 9.2 years, we identified 348 individuals with incident type 2 diabetes.After adjustment for confounders, HRs for type 2 diabetes were 3.7 (95% CI 1.8, 7.5), 2.4 (95% CI 1.3, 4.3) and 1.60 (95% CI 1.0, 2.8) for women with premature, early and normal menopause, respectively, relative to those with late menopause (ptrend <0.001).The HR for type 2 diabetes per 1 year older at menopause was 0.96 (95% CI 0.94, 0.98).Further adjustment for BMI, glycaemic traits, metabolic risk factors, C-reactive protein, endogenous sex hormone levels or shared genetic factors did not affect this association.Conclusions/interpretation Early onset of natural menopause is an independent marker for type 2 diabetes in postmenopausal women."
                },
                {
                    "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                    "text": "\n\nassociation and explore whether the timing of natural menopause can add value to diabetes prediction and prevention."
                }
            ],
            "d1449eee-d4ec-4886-87d1-835fb54a5f56": [
                {
                    "document_id": "d1449eee-d4ec-4886-87d1-835fb54a5f56",
                    "text": "\n\nAlthough drawing of definitive conclusions is difficult from these observational studies, their results suggest that young-onset type 2 diabetes is associated with a much more frequent occurrence of adverse macrovascular and microvascular outcomes and a more rapidly progressing severity of complications than is seen in type 1 diabetes or later-onset type 2 diabetes."
                },
                {
                    "document_id": "d1449eee-d4ec-4886-87d1-835fb54a5f56",
                    "text": "\n\nIn a study of the age-specific incidence of type 2 diabetes in the UK (a retrospective cohort study of patients with newly diagnosed type 2 diabetes between 1990 and 2010), the investigators reported a substantial increase in the proportion of people aged 40 years or younger at diagnosis"
                },
                {
                    "document_id": "d1449eee-d4ec-4886-87d1-835fb54a5f56",
                    "text": "\nThe prevalence of type 2 diabetes in adolescents and young adults is dramatically increasing.Similar to older-onset type 2 diabetes, the major predisposing risk factors are obesity, family history, and sedentary lifestyle.Onset of diabetes at a younger age (defined here as up to age 40 years) is associated with longer disease exposure and increased risk for chronic complications.Young-onset type 2 diabetes also affects more individuals of working age, accentuating the adverse societal effects of the disease.Furthermore, evidence is accumulating that young-onset type 2 diabetes has a more aggressive disease phenotype, leading to premature development of complications, with adverse effects on quality of life and unfavourable effects on long-term outcomes, raising the possibility of a future public health catastrophe.In this Review, we describe the epidemiology and existing knowledge regarding pathophysiology, risk factors, complications, and management of type 2 diabetes in adolescents and young adults."
                }
            ],
            "f53cd4d6-2d42-47e1-b58f-5bf8f2d65ef5": [
                {
                    "document_id": "f53cd4d6-2d42-47e1-b58f-5bf8f2d65ef5",
                    "text": "\n\nThe biological processes linking aging and disease risk are poorly understood.Still, aging is considered to date as one of the main factors responsible for several complex diseases including cancer, cardiovascular diseases, and diabetes."
                }
            ]
        },
        "data_source": [
            {
                "document_id": "29e232a4-a580-411d-83a3-7ff6a4e8f0ad",
                "section_type": "main",
                "text": "\n\nOur result provides a novel hypothesis on the mechanism for the connection between two aging-related diseases: Alzheimer's disease and type 2 diabetes."
            },
            {
                "document_id": "94e153f4-bc43-4e5b-99d4-6bb64ed24e4a",
                "section_type": "main",
                "text": "\n\nAge also plays a vital role in the onset of diabetes (Cowie & Eberhardt, 1995).In south-east Asia almost 97% diabetic patients are 40 years old or more (IDF Atlas, 2017).In Bangladesh, the reported age of diabetes is ≥40 years in 71% urban and 85% rural female, while in the case of male the proportion is 85.5% urban and 86.5% in rural population (IDF Atlas, 2017).The current study also pinpointed an exponential increase in the risk of onset of T2DM with the increase of age when 40 years was chosen as the reference (Table S4)."
            },
            {
                "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                "section_type": "main",
                "text": "\n\nOverall, results were similar in analyses restricted to diabetes mellitus identified at baseline only, although the confidence interval included 1.These results suggest that diabetes mellitus is related to risk of AD in old age.These findings are consistent with the results of 2 large longitudinal cohort studies. 5,6In one study, 5 diabetes mellitus doubled the risk of AD during 2 years of follow-up in a sample of more than 6000 older persons from a defined cohort.The other study, 6 using data from about 2500 Japanese American men, found a similar result: diabetes mellitus approximately doubled the risk of AD.In contrast, 2 other longitudinal studies 7,8 did not  demonstrate a significant association between diabetes mellitus and incident AD, but in both, the results were in the direction of increased risk.Some, [9][10][11] but not all, 12 previous studies found that diabetes mellitus was related to change in cognitive function.One factor that may contribute to variability from study to study is that diabetes mellitus may be related to decline in some cognitive systems but not others.4][15] Although diabetes mellitus was related to level of global cognition and multiple cognitive domains at baseline, we found that diabetes mellitus was only related to decline in perceptual speed.The one study 12 that did not find a relation between diabetes mellitus and cognitive decline did not include a measure of perceptual speed."
            },
            {
                "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                "section_type": "main",
                "text": "COMMENT\n\nIn a cohort of more than 800 older persons, we found that diabetes mellitus sometime in the study was associated with an increased risk of developing AD during a mean of 5.5 years of observation.The risk of incident AD was 65% higher in those with diabetes mellitus than in those without it."
            },
            {
                "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                "section_type": "main",
                "text": "\n\nIn summary, these findings suggest that diabetes mellitus is associated with AD and decline in cognitive function in older persons.December 12, 2003."
            },
            {
                "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                "section_type": "main",
                "text": "\n\nThe aim of this study was to investigate the association between age at natural menopause and risk of developing type 2 diabetes, and to assess whether this association is independent of potential intermediate risk factors for type 2 diabetes.Furthermore, we examined the role of endogenous sex hormone levels in the association between age at natural menopause and type 2 diabetes."
            },
            {
                "document_id": "6e570a0b-a876-4263-b32f-cee85088756d",
                "section_type": "main",
                "text": "\n\nThere are two major factors that underlie these alarming projections.The first is T2D is associated with age, and Western populations are aging rapidly.The second major explanation is our lifestyles have changed dramatically in recent years.Epidemiological studies have identified strong T2D risk relationships for obesity, sedentary behavior [2][3][4], and diets rich in energy [5], processed carbohydrates [6], and animal fats [7].Collectively, these lifestyle factors impede the actions of insulin and raise hepatic glucose production, which can result in the diminution of endogenous insulin production and T2D.The strongest evidence for a causal relationship between adverse lifestyle behaviors and T2D comes from randomized controlled trials that show intensive lifestyle interventions involving structured exercise regimes which promote habitual physical activity (PA) and have a major beneficial impact on diabetes incidence in high-risk individuals [8,9]."
            },
            {
                "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                "section_type": "main",
                "text": "Research Gaps\n\nThere is a clear correlation of environmental influences to diabetes risk.Yet, the assembled experts agreed that hypothesis-driven research is needed to define direct causal relationships between specific environmental factors and pathophysiologies leading to diabetes.Research efforts need to address environmental etiologies of type 1 diabetes and determine their relative contribution to onset of autoimmunity and progression to symptomatic disease.Whether there is a direct causal role of the intestinal microbiota in pathogenesis of type 1 and type 2 diabetes and response to therapies needs to be determined.Public health interventions that successfully reduce the levels of consumption of energy-dense foods and/or reduce sedentary time and increase time spent in physical activity need to be evaluated to determine whether they can reduce type 2 diabetes incidence at a population level."
            },
            {
                "document_id": "94e153f4-bc43-4e5b-99d4-6bb64ed24e4a",
                "section_type": "main",
                "text": "\n\nWhether age and stress variables are risk factors for type 2 diabetes incidence was assessed by multivariate logistic regression (Table S4).Subjects in the age groups of (40-60) and >60 years had 1.78× (p = .005)and 3.19× (p = .006)greater risk for type 2 diabetes respectively than group of <40 years.Overall, patients under stressful condition are more likely to develop T2DM than that of nonstressed respondent (p = .000).Moreover, when stress is divided into two groups-low stress and high stress, we found that both males (p = .000)and females (p = .000)with high stress were at high risk of diabetes mellitus, whereas the association between low stress and T2DM incidence was significant only among males (Male: p = .002;Female: p = .115).The distribution and association of the genotypes, age, and stress with T2DM have been summarized in Table 3 and Figure 3.There was no difference in T2DM incidence between CT (p = .030)and TT/CC (p = .034)genotype containing people who were in age group of 40-60 years (Table 3).In contrast, people who were more than 60 years old with CT genotype (OR = 4.636, p = .029)were more prone to T2DM than that of TT/CC genotype (OR = 3.714, p = .007)subjects (Table 3)."
            },
            {
                "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                "section_type": "main",
                "text": "\n\nAims/hypothesis In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators.Methods We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study.Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature,  <40 years; early, 40-44 years; normal, 45-55 years; and late  menopause, >55 years [reference]).Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from Rotterdam Study visits.HRs and 95% CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens."
            },
            {
                "document_id": "d1449eee-d4ec-4886-87d1-835fb54a5f56",
                "section_type": "main",
                "text": "\n\nAlthough drawing of definitive conclusions is difficult from these observational studies, their results suggest that young-onset type 2 diabetes is associated with a much more frequent occurrence of adverse macrovascular and microvascular outcomes and a more rapidly progressing severity of complications than is seen in type 1 diabetes or later-onset type 2 diabetes."
            },
            {
                "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                "section_type": "abstract",
                "text": "\nAims/hypothesis In this study, we aimed to examine the association between age at natural menopause and risk of type 2 diabetes, and to assess whether this association is independent of potential mediators.Methods We included 3639 postmenopausal women from the prospective, population-based Rotterdam Study.Age at natural menopause was self-reported retrospectively and was treated as a continuous variable and in categories (premature,  <40 years; early, 40-44 years; normal, 45-55 years; and late  menopause, >55 years [reference]).Type 2 diabetes events were diagnosed on the basis of medical records and glucose measurements from Rotterdam Study visits.HRs and 95% CIs were calculated using Cox proportional hazards models, adjusted for confounding factors; in another model, they were additionally adjusted for potential mediators, including obesity, C-reactive protein, glucose and insulin, as well as for levels of total oestradiol and androgens.Results During a median follow-up of 9.2 years, we identified 348 individuals with incident type 2 diabetes.After adjustment for confounders, HRs for type 2 diabetes were 3.7 (95% CI 1.8, 7.5), 2.4 (95% CI 1.3, 4.3) and 1.60 (95% CI 1.0, 2.8) for women with premature, early and normal menopause, respectively, relative to those with late menopause (ptrend <0.001).The HR for type 2 diabetes per 1 year older at menopause was 0.96 (95% CI 0.94, 0.98).Further adjustment for BMI, glycaemic traits, metabolic risk factors, C-reactive protein, endogenous sex hormone levels or shared genetic factors did not affect this association.Conclusions/interpretation Early onset of natural menopause is an independent marker for type 2 diabetes in postmenopausal women."
            },
            {
                "document_id": "6e570a0b-a876-4263-b32f-cee85088756d",
                "section_type": "main",
                "text": "\n\nEpidemiological studies examining the associations between lifestyle behaviors and diabetes risk have reached similar conclusions as the clinical trials described above.For example, the 14-year follow-up University of Pennsylvania Alumni Health Study [52] (n = 5,990 men aged 39-68 years) showed PA (leisure time physical activity [LTPA] expressed in kcal expended per week through walking, stair climbing, and sports) was inversely associated with the incidence of T2D.Incidence rates declined as energy expenditure rose from 500 through 3,500 kcal/week.The age-adjusted relative risk ratio (RR) of T2D was reduced by about 6% for each 500 kcal increment increase in PA energy expenditure."
            },
            {
                "document_id": "d1449eee-d4ec-4886-87d1-835fb54a5f56",
                "section_type": "main",
                "text": "\n\nIn a study of the age-specific incidence of type 2 diabetes in the UK (a retrospective cohort study of patients with newly diagnosed type 2 diabetes between 1990 and 2010), the investigators reported a substantial increase in the proportion of people aged 40 years or younger at diagnosis"
            },
            {
                "document_id": "afe6a42e-2c8b-4cfd-9334-157d1b9d15b6",
                "section_type": "main",
                "text": "\n\nIn sum, it is clear that multiple risk factors are involved in diabetes-associated cognitive decrements as well as in dementia in relation to diabetes 38 .On the basis of our assessment of the literature, it is also clear that there are still substantial knowledge gaps on how the risk factors interconnect, how the risk factors translate to potentially modifiable mechanisms and which genetic factors are involved."
            },
            {
                "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                "section_type": "main",
                "text": "DIABETES MELLITUS AND RISK OF AD\n\nDuring the follow-up evaluations, 151 persons developed AD, of whom 31 had diabetes mellitus.In a proportional hazards model adjusted for age, sex, and educational level, there was a 65% increase in the risk of developing AD in those with diabetes mellitus compared with those without diabetes mellitus (hazard ratio, 1.65; 95% confidence interval, 1.10-2.47).The cumulative hazard of AD over time, adjusted for age, sex, and educational level, is shown graphically in Figure 1 for typical participants with and without diabetes mellitus.Similar results were found in analyses with diabetes mellitus identified at baseline only (hazard ratio, 1.53; 95% confidence interval, 0.96-2.45)."
            },
            {
                "document_id": "d1449eee-d4ec-4886-87d1-835fb54a5f56",
                "section_type": "abstract",
                "text": "\nThe prevalence of type 2 diabetes in adolescents and young adults is dramatically increasing.Similar to older-onset type 2 diabetes, the major predisposing risk factors are obesity, family history, and sedentary lifestyle.Onset of diabetes at a younger age (defined here as up to age 40 years) is associated with longer disease exposure and increased risk for chronic complications.Young-onset type 2 diabetes also affects more individuals of working age, accentuating the adverse societal effects of the disease.Furthermore, evidence is accumulating that young-onset type 2 diabetes has a more aggressive disease phenotype, leading to premature development of complications, with adverse effects on quality of life and unfavourable effects on long-term outcomes, raising the possibility of a future public health catastrophe.In this Review, we describe the epidemiology and existing knowledge regarding pathophysiology, risk factors, complications, and management of type 2 diabetes in adolescents and young adults."
            },
            {
                "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                "section_type": "main",
                "text": "\n\nassociation and explore whether the timing of natural menopause can add value to diabetes prediction and prevention."
            },
            {
                "document_id": "80500e0d-0e39-4e46-bb60-8721f4f512c0",
                "section_type": "main",
                "text": "Clinical Factors Predicting Incidence of Diabetes\n\nIn both the MPP and Botnia studies, a family history of diabetes, an increased BMI, and increased levels of blood pressure and serum levels of triglycerides, apolipoprotein A-I, and liver enzymes were independent predictors of future type 2 diabetes (Table 1).In the MPP study, current smoking was also associated with a marked increase in the risk of diabetes.Impaired insulin secretion and action, particularly insulin secretion adjusted for insulin resistance (disposition index), were strong predictors of future diabetes.The presence of a first-degree family history of diabetes doubled the risk of the disease that was seen with an increased BMI (Fig. 2A) and a low disposition index (Fig. 2B)."
            },
            {
                "document_id": "92004cb7-4f79-4dde-a8e7-d1e93a253dc3",
                "section_type": "main",
                "text": "\n\nWe identified 164 (78%, >3:4) participants with evidence of age-related chronic disease or risk factors.One hundred eighteen study participants (56%) had evidence of diabetes or risk for diabetes: 15 (7%) had type 2 diabetes, 80 (38%) had prediabetes, and 23 (11%) had insulin resistance suggesting prediabetes risk (based on Quantose IR).Only 19 (9%) reported a history of type 2 diabetes or prediabetes.One hundred twentyfour participants (59%) had evidence of atherosclerotic disease or risk.Thirty-three (16%) had evidence of metabolic syndrome.Twenty-eight participants (13%) met a screening definition for NAFLD, and one had suspected NASH.Many participants had multiple overlapping conditions, including 29 with prediabetes and atherosclerotic disease or risk; 19 with prediabetes, atherosclerotic disease or risk, and metabolic syndrome; and 13 with insulin resistance and atherosclerotic disease or risk.When diabetes, prediabetes, and insulin resistance were considered as a group of diseases and conditions, 28 (11%) had all four of the common diseases and conditions (diabetes and diabetes risk, atherosclerosis or atherosclerosis risk, metabolic syndrome, and NAFLD).As expected, there was a strong effect of age on the prevalence of these conditions, with exception of NAFLD (Fig. 2)."
            },
            {
                "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                "section_type": "main",
                "text": "\n\nType 2 diabetes is a major risk factor for CVD, and it is unclear whether age at menopause is associated with risk of type 2 diabetes [3,4].Data from cross-sectional studies examining the association between age at menopause and type 2 diabetes are contradictory, with a few studies reporting no association and some other reporting higher odds of having type 2 diabetes with early onset of menopause [5][6][7].Recently, a nested case-cohort study reported that an increased risk of type 2 diabetes is associated with early onset of menopause, but it did not adjust for potential intermediate risk factors such as glucose metabolism, insulin or shared genetic factors [8].Menopause transition is associated with weight gain, an increase in visceral fat and impairment of glucose homeostasis, all of which are important risk factors for type 2 diabetes [9][10][11].However, no study has examined the role of postmenopausal hormone levels in the association between age of menopause and risk of type 2 diabetes.Although the available evidence is not persuasive and the mechanisms remain unclear, age of menopause might be associated with levels of endogenous sex hormones, which might affect the risk of type 2 diabetes in postmenopausal women [12][13][14][15][16][17].Therefore, it is not clear whether the observed association between early onset of menopause and risk of type 2 diabetes can be explained by differences in sex hormones levels in women who experience early vs late menopause."
            },
            {
                "document_id": "d1449eee-d4ec-4886-87d1-835fb54a5f56",
                "section_type": "main",
                "text": "Summary and future research directions\n\nAlthough it is tempting to extrapolate the disease course of type 2 diabetes in young people as just an earlier and more rapid form of type 2 diabetes in older adults, distinctive differences are evident.The young-onset phenotype has a stronger family history, a greater association with obesity, early loss of both first and second phases of insulin secretion alongside often severe insulin resistance, early onset and rapid progression of microvascular and macrovascular complications, and poor sustainability of responsiveness to oral glucose-lowering therapies, frequently neces sitating early introduction of insulin."
            },
            {
                "document_id": "756b902b-cbc7-40e8-84a5-9372221d83a4",
                "section_type": "abstract",
                "text": "\nBackground: Type 2 diabetes mellitus is an important risk factor for Alzheimer disease and is more prevalent in elderly minority persons compared with non-Hispanic white persons.Objective: To determine whether diabetes is related to a higher risk of mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer disease, in a multiethnic cohort with a high prevalence of diabetes."
            },
            {
                "document_id": "77daf125-3e88-41fe-92fd-71a9ce9c6671",
                "section_type": "main",
                "text": "\n\nAge. Age is another factor that has a considerable effect on outcomes in obesity and T2DM research.In humans, body weight increases with age and peaks at ~55 years in both men and women.Ageing per se is associated with a redistribution of both the fat-free mass and the fat mass, with the latter increase starting at ~30 years of age 129 .Intramuscular and intrahepatic fat are particularly increased in older persons, and this increase has been linked to insulin resistance 130 .Partially on the basis of these changes, ageing has been proposed to be an independent determinant of glucose tolerance, which progressively worsens with age 131,132 ."
            },
            {
                "document_id": "d1449eee-d4ec-4886-87d1-835fb54a5f56",
                "section_type": "main",
                "text": "\n\nThe prevalence of type 2 diabetes in adolescents and young adults is dramatically increasing.Similar to older-onset type 2 diabetes, the major predisposing risk factors are obesity, family history, and sedentary lifestyle.Onset of diabetes at a younger age (defined here as up to age 40 years) is associated with longer disease exposure and increased risk for chronic complications.Young-onset type 2 diabetes also affects more individuals of working age, accentuating the adverse societal effects of the disease.Furthermore, evidence is accumulating that young-onset type 2 diabetes has a more aggressive disease phenotype, leading to premature development of complications, with adverse effects on quality of life and unfavourable effects on long-term outcomes, raising the possibility of a future public health catastrophe.In this Review, we describe the epidemiology and existing knowledge regarding pathophysiology, risk factors, complications, and management of type 2 diabetes in adolescents and young adults."
            },
            {
                "document_id": "756b902b-cbc7-40e8-84a5-9372221d83a4",
                "section_type": "main",
                "text": "\n\nObjective: To determine whether diabetes is related to a higher risk of mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer disease, in a multiethnic cohort with a high prevalence of diabetes."
            },
            {
                "document_id": "756b902b-cbc7-40e8-84a5-9372221d83a4",
                "section_type": "main",
                "text": "\n\nOur results provide further support to the potentially important independent role of diabetes in the pathogenesis of AD.Diabetes may also be a risk factor for nonamnestic forms of MCI and cognitive impairment, but our analyses need to be repeated in a larger sample."
            },
            {
                "document_id": "756b902b-cbc7-40e8-84a5-9372221d83a4",
                "section_type": "main",
                "text": "\n\nBackground: Type 2 diabetes mellitus is an important risk factor for Alzheimer disease and is more prevalent in elderly minority persons compared with non-Hispanic white persons."
            },
            {
                "document_id": "ceab3d6d-62ca-459a-9a97-02a16d4dd193",
                "section_type": "main",
                "text": "Aetiological factors\n\nProspective studies suggest that the main pathophysiological defects leading to type 2 diabetes are insulin resistance and a relative insulin secretory defect.The main aetiological risk factors are age, obesity, family history, and physical inactivity.Dietary risk factors have recently emerged: risk is increased by high consumption of red and processed meat 13 and sugar-sweetened beverages, 14 and reduced by intake of fruit and vegetables, 15 some types of dairy products, 16 and some overall dietary patterns. 17Novel strategies to use quantifiable nutritional biomarkers are paving the way for more detailed understanding of the association between diet and diabetes.Although the heritability of type 2 diabetes is high (30e70%) and more than 60 genetic variants related with diabetes risk have now been identified, 18   even when combined into a genetic score, known genes contribute little to the prediction of diabetes.Phenotype-based risk models provide greater discrimination for diabetes, and the addition of genotypic information adds no more than 5e10% improvement in prediction.The current conclusion is that genetic variants provide insights into biological pathways and pathogenesis of diabetes, but not its prediction.It is likely that interactions between the environment/lifestyle and genetic factors provide the explanation for the risk of type 2 diabetes, but demonstrating such interaction is challenging.Encouraging research findings have recently shown higher absolute risk of diabetes associated with obesity at any level of genetic risk. 19evention and screening"
            },
            {
                "document_id": "195cace4-f298-4910-8b7c-c4e6f208cd35",
                "section_type": "main",
                "text": "Does a shared pathogenesis underlie both obesity and type 2 diabetes? Although the link between obesity and type 2 diabetes is widely held to involve two discrete lesions-obesityinduced insulin resistance and ␤-cell failure-both disorders may share an underlying defect.This \"unified field theory\" raises questions about whether defects favoring progressive weight gain and metabolic impairment also contribute to ␤-cell decompensation."
            },
            {
                "document_id": "893e83e6-05f4-4917-9dee-6ec2cb847def",
                "section_type": "abstract",
                "text": "\nThe worldwide explosion of the rates of diabetes and other metabolic diseases in the last few decades cannot be fully explained only by changes in the prevalence of classical lifestyle-related risk factors, such as physical inactivity and poor diet.For this reason, it has been recently proposed that other \"nontraditional\" risk factors could contribute to the diabetes epidemics.In particular, an increasing number of reports indicate that chronic exposure to and accumulation of a low concentration of environmental pollutants (especially the so-called persistent organic pollutants (POPs)) within the body might be associated with diabetogenesis.In this review, the epidemiological evidence suggesting a relationship between dioxin and other POPs exposure and diabetes incidence will be summarized, and some recent developments on the possible underlying mechanisms, with particular reference to dioxin, will be presented and discussed."
            },
            {
                "document_id": "92eb0c69-5e98-41aa-9084-506e7f223b1a",
                "section_type": "main",
                "text": "\n\nAlthough Alzheimer's disease is a chronic neurodegenerative disease, seemingly not related to DM, several studies support the fact DM and AD have a strong causal relationship [86].Alzheimer's disease is often referred to as \"type 3\" diabetes.In [87], authors delved into the relationship between DM and AD via semantic data mining.Following extensive analysis of several paper abstracts, they managed to identify genes related to both diseases.Efforts were also made to construct an interaction network in order to identify existing links (genes and molecules) in the network."
            },
            {
                "document_id": "516de7be-3cef-47ee-8338-199fb922bc6f",
                "section_type": "main",
                "text": "\n\nWhat these predisposing factors share is an ability to negatively impact the glucose homeostasis system through worsening of insulin resistance or to impair b-cell function.Superimposing these factors onto a genetically compromised glucose homeostasis system raises the risk of progressing to hyperglycemia.It is the rapid emergence of these disadvantageous environmental factors that is causing the worldwide diabetes epidemic.This concept of environmental changes promoting diabetes was highlighted many years ago by populations that rarely experienced type 2 diabetes, but then moved from a nomadic or farm existence to urban environments followed by an explosion of diabetes, typically with profound obesity: Pima Indians in the Southwest U.S., Saharan nomadic tribes, Australian Aborigines, and many others.Particularly dramatic were studies that showed reversal of the diabetes when they returned to their prior way of life (15).A recent example of this is the rapidly rising incidence of type 2 diabetes in China and India as people move from the country to cities-there is a 0.1-0.2%incidence of diabetes for rural farmers in China as opposed to well more than 5% for city dwellers.Perhaps the scariest example of this is children in the U.S. where the obesity statistics worsen yearly.As many as 20% of U.S. children are now obese, and they are developing all of the elements of the metabolic syndrome-insulin resistance, hypertension, hyperlipidemia, and glucose intolerance (16)."
            },
            {
                "document_id": "b21bbbce-b53f-416b-8378-b635f4270ace",
                "section_type": "main",
                "text": "Discussion\n\nIn this large population-based study of postmenopausal women free of type 2 diabetes at baseline, we showed that early onset of natural menopause is associated with an increased risk of type 2 diabetes, independent of potential intermediate risk factors for type 2 diabetes (including BMI, glucose and insulin levels) and of levels of endogenous sex hormones and SHBG.We also showed that shared genetic factors could not explain the association between age at natural menopause and risk of type 2 diabetes."
            },
            {
                "document_id": "29d09d03-fd2f-48b3-a020-ea574d583dc4",
                "section_type": "main",
                "text": "Diet, Nutrition, and Type 2 Diabetes\n\nObesity is pathophysiologically associated with the development of type II diabetes [199,200].Oxidative stress and inflammation, metabolic impairment and accelerated aging on both the micro-and macrocellular level contribute to the pathogenesis of metabolic diseases [201,202]."
            },
            {
                "document_id": "f53cd4d6-2d42-47e1-b58f-5bf8f2d65ef5",
                "section_type": "main",
                "text": "\n\nThe biological processes linking aging and disease risk are poorly understood.Still, aging is considered to date as one of the main factors responsible for several complex diseases including cancer, cardiovascular diseases, and diabetes."
            },
            {
                "document_id": "893e83e6-05f4-4917-9dee-6ec2cb847def",
                "section_type": "main",
                "text": "\n\nThe worldwide explosion of the rates of diabetes and other metabolic diseases in the last few decades cannot be fully explained only by changes in the prevalence of classical lifestyle-related risk factors, such as physical inactivity and poor diet.For this reason, it has been recently proposed that other \"nontraditional\" risk factors could contribute to the diabetes epidemics.In particular, an increasing number of reports indicate that chronic exposure to and accumulation of a low concentration of environmental pollutants (especially the so-called persistent organic pollutants (POPs)) within the body might be associated with diabetogenesis.In this review, the epidemiological evidence suggesting a relationship between dioxin and other POPs exposure and diabetes incidence will be summarized, and some recent developments on the possible underlying mechanisms, with particular reference to dioxin, will be presented and discussed."
            },
            {
                "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                "section_type": "main",
                "text": "\n\nIndependent of geography, the risk of developing type 2 diabetes is associated with low socioeconomic status.Low educational level increases risk by 41%, low occupation level by 31%, and low income level by 40% (16)."
            },
            {
                "document_id": "71172700-7bcc-42f5-9354-d8e9290e8743",
                "section_type": "main",
                "text": "\n\nBackground: Few prospective studies have assessed diabetes mellitus as a risk factor for incident Alzheimer disease (AD) and decline in cognitive function."
            },
            {
                "document_id": "f53cd4d6-2d42-47e1-b58f-5bf8f2d65ef5",
                "section_type": "main",
                "text": "Discussion\n\nBased on available data, it is still unclear if a faster rate of telomere attrition and the consequent premature cell senescence can be a cause or a consequence of type 2 diabetes 8 .Although telomere length in different cell types may better reflect specific diseases, tissue-specific aging, or cell-specific adaptations, several studies have shown not only a significant association between LTL shortening and T2D 10 , but also a correlation with time of onset, duration of disease and increasing number of diabetes related complications 6,[21][22][23] .Indeed, the attrition of this chromosome region seems to be attenuated in patients with well-controlled diabetes 24 .Therefore, telomere shortening in leukocytes may correspond to a similar shortening of telomeres in organs and tissues such as islet β-cells, which lead to premature senescence and subsequent impaired insulin secretion and glucose tolerance 25,26 .On the other hand, many studies show that physical activity seems to confer a beneficial effect on LTL maintenance in healthy and diseased elderly people 19,[27][28][29][30][31] ."
            }
        ],
        "document_id": "B627313B69829B6ACD923E8E6588A622",
        "engine": "gpt-4",
        "first_load": false,
        "focus": "api",
        "keywords": [
            "aging",
            "diabetes",
            "T2DM",
            "age",
            "susceptibility",
            "onset",
            "risk&factors",
            "incidence",
            "type&2&diabetes",
            "age-related&diseases"
        ],
        "metadata": [
            {
                "object": "The NeuroD1-Ala45Thr variation may itself have an important role in susceptibility to or be in disequilibrium with early-onset T2DM in Chinese. The Ala45Thr may affect the onset pattern of T2DM, i.e., early-onset but not late-onset T2DM in Chinese.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab839109"
            },
            {
                "object": "Data suggest that subjects with point mutation 3243A>G in mtRNA-LeuUUR develop MIDD maternally inherited diabetes and deafness; as compared to patients with T1DM type 1 diabetes mellitus or early-onset T2DM type 2 diabetes mellitus matched for sex, age, duration of diabetes, such MIDD patients have highest rate of osteoporosis.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab211558"
            },
            {
                "object": "The SORBS1 GG genotype of rs2281939 was associated with a higher risk of diabetes at baseline, an earlier onset of diabetes, and higher steady-state plasma glucose levels in the modified insulin suppression test. The minor allele T of rs2296966 was associated with higher prevalence and incidence of diabetes, an earlier onset of diabetes, and higher 2-h glucose during oral glucose tolerance test in Chinese patients.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab872946"
            },
            {
                "object": "The present study shows that elevated plasma levels of RBP4 were associated with diabetic retinopathy and vision-threatening diabetic retinopathy in Chinese patients with type 2 diabetes, suggesting a possible role of RBP4 in the pathogenesis of diabetic retinopathy complications. Lowering RBP4 could be a new strategy for treating type 2 diabetes with diabetic retinopathy .",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab851311"
            },
            {
                "object": "The mean age of Parkinsonism onset among LRRK2 G2385R carriers was 42.7 years old for early-onset compared to 74.3 for late-onset patients. LRRK2 G2385R mutation appears to be as prevalent among early-onset as late-onset patients.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab833283"
            },
            {
                "object": "Study shows nucleotide substitutions in CD101, the human homolog of a diabetes susceptibility gene in non-obese diabetic mouse, in patients with type 1 diabetes. The results raise the possibility that CD101 is a susceptibility gene for type 1 diabetes.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab750084"
            },
            {
                "object": "This study investigates the involvement of a 14-bp deletion polymorphism rs371194629 at the 3' untranslated region of HLA-G in the context of T1DM and age of onset.the deletion/deletion DEL/DEL genotype was found to be associated with an early age of onset P = 0.001, while the presence of the insertion allele INS was associated to a later age of onset of type I diabetes mellitus",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab944007"
            },
            {
                "object": "Data confirm the association between the FTO first intron polymorphism and the presence of type 2 diabetes mellitus in the Slavonic Czech population. The same variant is likely to be associated with development of chronic complications of diabetes mellitus, especially with diabetic neuropathy and diabetic kidney disease in either T2DM or both T1DM and T2DM.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab173943"
            },
            {
                "object": "Blockade of IL-27 significantly delayed the onset of diabetic splenocyte-transferred diabetes, while IL-27-treated diabetic splenocytes promoted the onset of autoimmune diabetes.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab103352"
            },
            {
                "object": "Polymorphism of eNOS G894T is not a risk factor for diabetic foot ulcer formation. T allele is a risk factor for diabetes, but T allele is not a risk factor for diabetic foot ulcer formation.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab604531"
            }
        ],
        "question": "Is there a direct association between aging and susceptibility to having diabetes?",
        "subquestions": null,
        "task_id": "B627313B69829B6ACD923E8E6588A622",
        "usage": {
            "chatgpt": 5686,
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            "gpt-4-turbo-preview": 2918
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    "document_id": "B627313B69829B6ACD923E8E6588A622",
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}