path: root/gnqa/paper1_eval/src/data/responses/diabetes/experts/06.json

{
    "created_at": "2024-05-31T23:15:26.855315Z",
    "data": {
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        "answer": "There are primarily four types of diabetes: Type 1, Type 2, gestational diabetes, and diabetes due to specific causes. However, there are also subtypes within these broad categories, such as latent autoimmune diabetes of adults (LADA) and maturity onset diabetes of the young (MODY).",
        "context": {
            "1cebda9b-a727-4bfd-8521-cf61903235cc": [
                {
                    "document_id": "1cebda9b-a727-4bfd-8521-cf61903235cc",
                    "text": "\n\nThe prevalence of diabetes mellitus worldwide is sobering; the International Diabetes Federation estimates that 415 million people have diabetes mellitus, with 90% of these individuals having type 2 diabetes mellitus (T2DM) 1 .T2DM occurs when pancreatic β-cells fail to release enough insulin to meet the demands of insulin-responsive tissues, which safely store and metabolize glucose.Driven by both genetic and environmental risk factors, T2DM is a complex, multifactorial disorder.Although the increasing prevalence of T2DM is driven by changes in our environment and mirrors the increase in obesity, the greater concordance for T2DM found in monozygotic compared with dizygotic twins has long provided evidence for a genetic component in T2DM risk 2 ."
                }
            ],
            "4252d7ad-82de-480c-a801-9ed1c84fb968": [
                {
                    "document_id": "4252d7ad-82de-480c-a801-9ed1c84fb968",
                    "text": "\n\nIn the UK alone, nearly 1.8 million people are already recognized to have this disorder (consuming w5% of the total National Health Service budget), and the search is on to find the 'missing million' who are living with the condition but in whom the diagnosis has yet to be made. 3In the USA, the situation appears to be even more serious with some commentators predicting that one in every three Americans born in the year 2000 will go on to develop diabetes during their lifetime, bringing unprecedented costs in terms of healthcare dollars as well as human morbidity and mortality. 4The majority (w90%) of these cases will be type 2 in origin, reflecting a trend towards obesity and more sedentary lifestyles as the 'norm' rather than the exception in 'developed' societies.Indeed, the face of T2DM is changing, as a condition that was once considered the preserve of middle/old age is increasingly diagnosed in young adults and even children, reflecting the high rates of obesity (and, in particular, visceral adiposity) in these populations."
                }
            ],
            "4d3330eb-acd0-4f72-aadf-b056d3c8b389": [
                {
                    "document_id": "4d3330eb-acd0-4f72-aadf-b056d3c8b389",
                    "text": "\n\nTable 1 lists the various subtypes of diabetes based on the classification suggested by the ADA [4]."
                },
                {
                    "document_id": "4d3330eb-acd0-4f72-aadf-b056d3c8b389",
                    "text": "\n\nThe ADA lists four subtypes of diabetes based on the clinical symptoms at time of presentation, [4] namely, Type 1 diabetes, Type 2 diabetes (T2D), gestational diabetes, and diabetes due to specific causes (genetic defects causing deficient insulin secretion or action, diseases of pancreas, use of certain drugs such as steroids, thiazides among others).Of these, T2D is the most prevalent (close to 90% of all cases) and is the major cause of morbidity and mortality in both developed and developing nations [1].At times it is difficult to assign a patient to a particular subtype due to the difference in conditions associated with hyperglycemia at the time of diagnosis [4,7].For example, a lady diagnosed with gestational diabetes mellitus during pregnancy is highly susceptible to develop T2D later.Therefore, other than proper treatment during and post pregnancy, a regular follow-up is required for stratifying disease risk, and for timely management before progression to another subtype.It is clear that the classification of diabetes may not be as simple as just categorizing it into any one of the four given subtypes due to its miscellaneous nature.Every case needs to be considered at the time of presentation, on the basis of the risk factors or underlying cause of hyperglycemia, the clinical symptoms, and disease prognosis."
                }
            ],
            "588bca6b-82c0-4ac1-9c7e-dc09af1d49b0": [
                {
                    "document_id": "588bca6b-82c0-4ac1-9c7e-dc09af1d49b0",
                    "text": "Introduction\n\nGlobally, diabetes affects more than 400 million people (World Health Organization, 2016), with Type 1 (insulin-dependent) diabetes (T1D) accounting for up to 10 percent of cases (American Diabetes Association, 2009).In the United States, T1D occurs at a rate of 15-30 cases per 100,000 children aged 0-14 years annually (International Diabetes Foundation, 2017;Maahs et al., 2010), with similar prevalence in Canada, Europe, Australia, and New Zealand (Fig. 1) (Derraik et al., 2012;International Diabetes Foundation, 2017;Maahs et al., 2010).By contrast, the estimated incidence rate of T1D among Asians, South Americans, and Africans is below 15 cases per 100,000 children (Fig. 1) (International Diabetes Foundation, 2017;Maahs et al., 2010).The global incidence of T1D has been rising by 3-5% per annum over the past two decades, with a notable increase in children below 10 years of age (Diamond Project, 2006;Patterson et al., 2009)."
                }
            ],
            "770beab7-59a4-4bbe-94a5-79a965ab696a": [
                {
                    "document_id": "770beab7-59a4-4bbe-94a5-79a965ab696a",
                    "text": "Animal Models\n\n9.2% in women and 9.8% in men, with approximately 347 million people suffering from the disease worldwide in 2008 (Danaei et al., 2011).There are several different classifications of diabetes, the most common being type 1 and type 2 diabetes."
                },
                {
                    "document_id": "770beab7-59a4-4bbe-94a5-79a965ab696a",
                    "text": "\n\nType 2 diabetes is the most common type of diabetes with prevalence in the United Kingdom of around 4%.It is most commonly diagnosed in middle-aged adults, although more recently the age of onset is decreasing with increasing levels of obesity (Pinhas-Hamiel and Zeitler, 2005).Indeed, although development of the disease shows high hereditability, the risk increases proportionally with body mass index (Lehtovirta et al., 2010).Type 2 diabetes is associated with insulin resistance, and a lack of appropriate compensation by the beta cells leads to a relative insulin deficiency.Insulin resistance can be improved by weight reduction and exercise (Solomon et al., 2008).If lifestyle intervention fails, there are a variety of drugs available to treat type 2 diabetes (Krentz et al., 2008), which can be divided into five main classes: drugs that stimulate insulin production from the beta cells (e.g.sulphonylureas), drugs that reduce hepatic glucose production (e.g.biguanides), drugs that delay carbohydrate uptake in the gut (e.g.a-glucosidase inhibitors), drugs that improve insulin action (e.g.thiazolidinediones) or drugs targeting the GLP-1 axis (e.g.GLP-1 receptor agonists or DPP-4 inhibitors)."
                }
            ],
            "7d4a197e-3774-40a4-9897-ed7c71f213b6": [
                {
                    "document_id": "7d4a197e-3774-40a4-9897-ed7c71f213b6",
                    "text": "Introduction\n\nDiabetes impacts the lives of approximately 200 million people worldwide [1], with chronic complications including accelerated development of cardiovascular disease.Over 90% of cases are of type 2 diabetes (T2D), with the bulk of the remainder presenting with type 1 diabetes (T1D)."
                }
            ],
            "961f88ba-2090-4904-942c-f0e014bbe53f": [
                {
                    "document_id": "961f88ba-2090-4904-942c-f0e014bbe53f",
                    "text": "Classification of Diabetes\n\nOn the basis of insulin deficiency, diabetes can be classified into the following types as follows."
                }
            ],
            "9b93b4eb-98c2-403f-aea2-6b24399501b8": [
                {
                    "document_id": "9b93b4eb-98c2-403f-aea2-6b24399501b8",
                    "text": "| INTRODUCTION\n\nToday, more than 265 million people are affected across the world.It is estimated that by the year 2030 this number will reach 366 million people (about 4/4 percent of the world's population), and now the cause of death is more than 1.1 million per year (including 50% of the population under-70 years of age and 55% of women).On the other hand, given its negative effect on the economic growth of developing countries, it calls for universal mobilization to combat this disease (Bhattacharya, Dey, & Roy, 2007).Diabetes or diabetes mellitus is referred to as a heterogeneous group of metabolic disorders characterized by chronic hyperglycemia and carbohydrate, fat and protein metabolism disorders that result from a defect in the secretion of insulin, or impairment in its function, or both.Types of diabetes mellitus include type 1, type 2 diabetes and other kind of diabetes, but the two most common types of diabetes mellitus are type 1 and type 2, which are different in several aspects (Meshkani, Taghikhani, Mosapour et al., 2007).Type 1 diabetes has been identified with autoimmune destruction of pancreatic beta cells (insulin secreting cells) and accounts for about 5% of all diabetic people, while type 2 diabetes is a predominant disorder characterized by insulin resistance or a relative decline in insulin production, and accounts for about 90% of all types of diabetes mellitus (Meshkani, Taghikhani, Al-Kateb et al., 2007).Important factors that predispose a person to type 2 diabetes are multifactorial, including genetic factors and environments.However, its inheritance has certainly not been proven, but it is believed that first-degree relatives of diabetic patients have a higher chance to develop the disease.In this regard, recognizing gene polymorphisms of this disease seems to be necessary (Häring et al., 2014).Multiple genes have been studied in the pathogenesis of type 2 diabetes."
                }
            ],
            "9c9cc0b3-5dde-4077-ae41-1410db9aeb24": [
                {
                    "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                    "text": "CONCLUSIONS\n\nDiabetes is currently broadly classified as type 1, type 2, gestational, and a group of \"other specific syndromes. \"However, increasing evidence suggests that there are populations of individuals within these broad categories that have subtypes of disease with a well-defined etiology that may be clinically characterized (e.g., LADA, MODY).These developments suggest that perhaps, with more focused research in critical areas, we are approaching a point where it would be possible to categorize diabetes in a more precise manner that can inform individual treatment decisions."
                },
                {
                    "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                    "text": "Type 2 Diabetes\n\nIn the U.S., an estimated 95% of the nearly 30 million people living with diabetes have type 2 diabetes.An additional 86 million have prediabetes, putting them at high risk for developing type 2 diabetes (9).Among the demographic associations for type 2 diabetes are older age, race/ ethnicity, male sex, and socioeconomic status (9)."
                },
                {
                    "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                    "text": "Type 1 Diabetes\n\nBetween 2001 and 2009, there was a 21% increase in the number of youth with type 1 diabetes in the U.S. (7).Its prevalence is increasing at a rate of ;3% per year globally (8).Though diagnosis of type 1 diabetes frequently occurs in childhood, 84% of people living with type 1 diabetes are adults (9).Type 1 diabetes affects males and females equally (10) and decreases life expectancy by an estimated 13 years (11).An estimated 5-15% of adults diagnosed with type 2 diabetes actually have type 1 diabetes or latent autoimmune diabetes of adults (LADA) (12)."
                }
            ],
            "ab32e261-658c-4a8b-94fc-857826b29f5a": [
                {
                    "document_id": "ab32e261-658c-4a8b-94fc-857826b29f5a",
                    "text": "\n\nBackground Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous.A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis."
                }
            ],
            "b666545f-6a53-45de-8562-55d88fc6f7ee": [
                {
                    "document_id": "b666545f-6a53-45de-8562-55d88fc6f7ee",
                    "text": "\n\nDiabetes mellitus now affects ~8% of the world's adult population [1], including ~3 000 000 individuals in the UK (with a further 600 000 people affected but presently undiagnosed) [2].Of these cases, > 90% have Type 2 diabetes.Treatments of the complications of the disease, which range from stroke, blindness and kidney failure to lower limb amputations and cancer, presently consume ~10% of the National Health Service budget, some £14 bn per year [3].These figures are anticipated to increase further in the next 10 years, driven by increasingly sedentary lifestyles and increases in obesity; the collision between these 'environmental' factors and genetic susceptibility (see below) being the key underlying driver.Whilst existing treatments ameliorate the symptoms of the disease, notably hyperglyca-emia, none target the underlying molecular aetiology.In particular, no available treatments tackle the progressive and largely irreversible loss of insulin production [4] which, in the face of insulin resistance, underlies the progressive deterioration in glucose control.Reductions in b-cell mass [5,6] and dysfunction [7] both contribute to this gradual impairment in insulin release.Recent years have seen an increase in the view that the former may play a less important role than the latter, with a 2008 study by Rahier et al. [6] reporting that b-cell mass (and insulin content) in people with Type 2 diabetes was on average ~35% lower than that of healthy control subjects.However, this difference was only ~24% within 5 years of diagnosis, far below levels likely to lead to the symptoms of diabetes.Indeed, given our present inability to monitor b-cell mass prospectively over the course of the disease, it is conceivable that the differences observed post mortem between healthy individuals and those with Type 2 diabetes [5,6] may reflect an increased predisposition to diabetes in those born with a lower than average b-cell mass."
                }
            ],
            "b72eb0d1-50e3-4def-94bc-abf77891f519": [
                {
                    "document_id": "b72eb0d1-50e3-4def-94bc-abf77891f519",
                    "text": "INTRODUCTION\n\nType 2 diabetes (T2D) affects an estimated 425 million people worldwide, a number predicted to rise to 629 million by 2045 (1).The disease usually involves insulin resistance but is ultimately the result of pancreatic b cell failure, a sine qua non for disease development (2).In contrast, Type 1 diabetes (T1D) affects a smaller proportion of people with diabetes and is chiefly the result of pancreatic b cell destruction mediated by immune cells (3)."
                }
            ],
            "ba7298cd-4d19-4f98-9a2a-5fb625aa0068": [
                {
                    "document_id": "ba7298cd-4d19-4f98-9a2a-5fb625aa0068",
                    "text": "Introduction\n\nDiabetes is a complex and heterogeneous disease with a staggering global impact and the most recent estimates indicate 346 million people worldwide suffer from this disease (WHO Diabetes Fact sheet No. 312, 2011).Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, accounting for >90% of cases, and occurs when peripheral tissue insulin resistance accompanies insufficient b-cell insulin production.While >80% of diabetes deaths occur in low-and middle-income countries [1].India and China have the highest reported prevalence of diabetes with 65 and 98 million in 2013, respectively [2]."
                }
            ],
            "ceab3d6d-62ca-459a-9a97-02a16d4dd193": [
                {
                    "document_id": "ceab3d6d-62ca-459a-9a97-02a16d4dd193",
                    "text": "\n\nThe disease burden related to diabetes is high and rising in every country, fuelled by the global rise in the prevalence of obesity and unhealthy lifestyles.The latest estimates show a global prevalence of 382 million people with diabetes in 2013, expected to rise to 592 million by 2035.The aetiological classification of diabetes has now been widely accepted.Type 1 and type 2 diabetes are the two main types, with type 2 diabetes accounting for the majority (>85%) of total diabetes prevalence.Both forms of diabetes can lead to multisystem complications of microvascular endpoints, including retinopathy, nephropathy and neuropathy, and macrovascular endpoints including ischaemic heart disease, stroke and peripheral vascular disease.The premature morbidity, mortality, reduced life expectancy and financial and other costs of diabetes make it an important public health condition."
                },
                {
                    "document_id": "ceab3d6d-62ca-459a-9a97-02a16d4dd193",
                    "text": "\nThe disease burden related to diabetes is high and rising in every country, fuelled by the global rise in the prevalence of obesity and unhealthy lifestyles.The latest estimates show a global prevalence of 382 million people with diabetes in 2013, expected to rise to 592 million by 2035.The aetiological classification of diabetes has now been widely accepted.Type 1 and type 2 diabetes are the two main types, with type 2 diabetes accounting for the majority (>85%) of total diabetes prevalence.Both forms of diabetes can lead to multisystem complications of microvascular endpoints, including retinopathy, nephropathy and neuropathy, and macrovascular endpoints including ischaemic heart disease, stroke and peripheral vascular disease.The premature morbidity, mortality, reduced life expectancy and financial and other costs of diabetes make it an important public health condition."
                }
            ],
            "eaca0f25-4a6b-4c0e-a6df-12e25060b169": [
                {
                    "document_id": "eaca0f25-4a6b-4c0e-a6df-12e25060b169",
                    "text": "\n\nIntroduction: Is Type 2 Diabetes a Genetic Disorder?According to the World Health Organization (WHO), approximately 350 million people worldwide have diabetes, and this disorder is likely to be the seventh leading cause of death in 2030.Diabetes is an economic burden on healthcare systems, especially in developing countries (World Health Organization, 2013)."
                }
            ]
        },
        "data_source": [
            {
                "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                "section_type": "main",
                "text": "CONCLUSIONS\n\nDiabetes is currently broadly classified as type 1, type 2, gestational, and a group of \"other specific syndromes. \"However, increasing evidence suggests that there are populations of individuals within these broad categories that have subtypes of disease with a well-defined etiology that may be clinically characterized (e.g., LADA, MODY).These developments suggest that perhaps, with more focused research in critical areas, we are approaching a point where it would be possible to categorize diabetes in a more precise manner that can inform individual treatment decisions."
            },
            {
                "document_id": "ba7298cd-4d19-4f98-9a2a-5fb625aa0068",
                "section_type": "main",
                "text": "Introduction\n\nDiabetes is a complex and heterogeneous disease with a staggering global impact and the most recent estimates indicate 346 million people worldwide suffer from this disease (WHO Diabetes Fact sheet No. 312, 2011).Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, accounting for >90% of cases, and occurs when peripheral tissue insulin resistance accompanies insufficient b-cell insulin production.While >80% of diabetes deaths occur in low-and middle-income countries [1].India and China have the highest reported prevalence of diabetes with 65 and 98 million in 2013, respectively [2]."
            },
            {
                "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                "section_type": "main",
                "text": "Type 2 Diabetes\n\nIn the U.S., an estimated 95% of the nearly 30 million people living with diabetes have type 2 diabetes.An additional 86 million have prediabetes, putting them at high risk for developing type 2 diabetes (9).Among the demographic associations for type 2 diabetes are older age, race/ ethnicity, male sex, and socioeconomic status (9)."
            },
            {
                "document_id": "4d3330eb-acd0-4f72-aadf-b056d3c8b389",
                "section_type": "main",
                "text": "\n\nTable 1 lists the various subtypes of diabetes based on the classification suggested by the ADA [4]."
            },
            {
                "document_id": "ceab3d6d-62ca-459a-9a97-02a16d4dd193",
                "section_type": "main",
                "text": "\n\nThe disease burden related to diabetes is high and rising in every country, fuelled by the global rise in the prevalence of obesity and unhealthy lifestyles.The latest estimates show a global prevalence of 382 million people with diabetes in 2013, expected to rise to 592 million by 2035.The aetiological classification of diabetes has now been widely accepted.Type 1 and type 2 diabetes are the two main types, with type 2 diabetes accounting for the majority (>85%) of total diabetes prevalence.Both forms of diabetes can lead to multisystem complications of microvascular endpoints, including retinopathy, nephropathy and neuropathy, and macrovascular endpoints including ischaemic heart disease, stroke and peripheral vascular disease.The premature morbidity, mortality, reduced life expectancy and financial and other costs of diabetes make it an important public health condition."
            },
            {
                "document_id": "ceab3d6d-62ca-459a-9a97-02a16d4dd193",
                "section_type": "abstract",
                "text": "\nThe disease burden related to diabetes is high and rising in every country, fuelled by the global rise in the prevalence of obesity and unhealthy lifestyles.The latest estimates show a global prevalence of 382 million people with diabetes in 2013, expected to rise to 592 million by 2035.The aetiological classification of diabetes has now been widely accepted.Type 1 and type 2 diabetes are the two main types, with type 2 diabetes accounting for the majority (>85%) of total diabetes prevalence.Both forms of diabetes can lead to multisystem complications of microvascular endpoints, including retinopathy, nephropathy and neuropathy, and macrovascular endpoints including ischaemic heart disease, stroke and peripheral vascular disease.The premature morbidity, mortality, reduced life expectancy and financial and other costs of diabetes make it an important public health condition."
            },
            {
                "document_id": "4d3330eb-acd0-4f72-aadf-b056d3c8b389",
                "section_type": "main",
                "text": "\n\nThe ADA lists four subtypes of diabetes based on the clinical symptoms at time of presentation, [4] namely, Type 1 diabetes, Type 2 diabetes (T2D), gestational diabetes, and diabetes due to specific causes (genetic defects causing deficient insulin secretion or action, diseases of pancreas, use of certain drugs such as steroids, thiazides among others).Of these, T2D is the most prevalent (close to 90% of all cases) and is the major cause of morbidity and mortality in both developed and developing nations [1].At times it is difficult to assign a patient to a particular subtype due to the difference in conditions associated with hyperglycemia at the time of diagnosis [4,7].For example, a lady diagnosed with gestational diabetes mellitus during pregnancy is highly susceptible to develop T2D later.Therefore, other than proper treatment during and post pregnancy, a regular follow-up is required for stratifying disease risk, and for timely management before progression to another subtype.It is clear that the classification of diabetes may not be as simple as just categorizing it into any one of the four given subtypes due to its miscellaneous nature.Every case needs to be considered at the time of presentation, on the basis of the risk factors or underlying cause of hyperglycemia, the clinical symptoms, and disease prognosis."
            },
            {
                "document_id": "9b93b4eb-98c2-403f-aea2-6b24399501b8",
                "section_type": "main",
                "text": "| INTRODUCTION\n\nToday, more than 265 million people are affected across the world.It is estimated that by the year 2030 this number will reach 366 million people (about 4/4 percent of the world's population), and now the cause of death is more than 1.1 million per year (including 50% of the population under-70 years of age and 55% of women).On the other hand, given its negative effect on the economic growth of developing countries, it calls for universal mobilization to combat this disease (Bhattacharya, Dey, & Roy, 2007).Diabetes or diabetes mellitus is referred to as a heterogeneous group of metabolic disorders characterized by chronic hyperglycemia and carbohydrate, fat and protein metabolism disorders that result from a defect in the secretion of insulin, or impairment in its function, or both.Types of diabetes mellitus include type 1, type 2 diabetes and other kind of diabetes, but the two most common types of diabetes mellitus are type 1 and type 2, which are different in several aspects (Meshkani, Taghikhani, Mosapour et al., 2007).Type 1 diabetes has been identified with autoimmune destruction of pancreatic beta cells (insulin secreting cells) and accounts for about 5% of all diabetic people, while type 2 diabetes is a predominant disorder characterized by insulin resistance or a relative decline in insulin production, and accounts for about 90% of all types of diabetes mellitus (Meshkani, Taghikhani, Al-Kateb et al., 2007).Important factors that predispose a person to type 2 diabetes are multifactorial, including genetic factors and environments.However, its inheritance has certainly not been proven, but it is believed that first-degree relatives of diabetic patients have a higher chance to develop the disease.In this regard, recognizing gene polymorphisms of this disease seems to be necessary (Häring et al., 2014).Multiple genes have been studied in the pathogenesis of type 2 diabetes."
            },
            {
                "document_id": "b72eb0d1-50e3-4def-94bc-abf77891f519",
                "section_type": "main",
                "text": "INTRODUCTION\n\nType 2 diabetes (T2D) affects an estimated 425 million people worldwide, a number predicted to rise to 629 million by 2045 (1).The disease usually involves insulin resistance but is ultimately the result of pancreatic b cell failure, a sine qua non for disease development (2).In contrast, Type 1 diabetes (T1D) affects a smaller proportion of people with diabetes and is chiefly the result of pancreatic b cell destruction mediated by immune cells (3)."
            },
            {
                "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                "section_type": "main",
                "text": "Type 1 Diabetes\n\nBetween 2001 and 2009, there was a 21% increase in the number of youth with type 1 diabetes in the U.S. (7).Its prevalence is increasing at a rate of ;3% per year globally (8).Though diagnosis of type 1 diabetes frequently occurs in childhood, 84% of people living with type 1 diabetes are adults (9).Type 1 diabetes affects males and females equally (10) and decreases life expectancy by an estimated 13 years (11).An estimated 5-15% of adults diagnosed with type 2 diabetes actually have type 1 diabetes or latent autoimmune diabetes of adults (LADA) (12)."
            },
            {
                "document_id": "b666545f-6a53-45de-8562-55d88fc6f7ee",
                "section_type": "main",
                "text": "\n\nDiabetes mellitus now affects ~8% of the world's adult population [1], including ~3 000 000 individuals in the UK (with a further 600 000 people affected but presently undiagnosed) [2].Of these cases, > 90% have Type 2 diabetes.Treatments of the complications of the disease, which range from stroke, blindness and kidney failure to lower limb amputations and cancer, presently consume ~10% of the National Health Service budget, some £14 bn per year [3].These figures are anticipated to increase further in the next 10 years, driven by increasingly sedentary lifestyles and increases in obesity; the collision between these 'environmental' factors and genetic susceptibility (see below) being the key underlying driver.Whilst existing treatments ameliorate the symptoms of the disease, notably hyperglyca-emia, none target the underlying molecular aetiology.In particular, no available treatments tackle the progressive and largely irreversible loss of insulin production [4] which, in the face of insulin resistance, underlies the progressive deterioration in glucose control.Reductions in b-cell mass [5,6] and dysfunction [7] both contribute to this gradual impairment in insulin release.Recent years have seen an increase in the view that the former may play a less important role than the latter, with a 2008 study by Rahier et al. [6] reporting that b-cell mass (and insulin content) in people with Type 2 diabetes was on average ~35% lower than that of healthy control subjects.However, this difference was only ~24% within 5 years of diagnosis, far below levels likely to lead to the symptoms of diabetes.Indeed, given our present inability to monitor b-cell mass prospectively over the course of the disease, it is conceivable that the differences observed post mortem between healthy individuals and those with Type 2 diabetes [5,6] may reflect an increased predisposition to diabetes in those born with a lower than average b-cell mass."
            },
            {
                "document_id": "1cebda9b-a727-4bfd-8521-cf61903235cc",
                "section_type": "main",
                "text": "\n\nThe prevalence of diabetes mellitus worldwide is sobering; the International Diabetes Federation estimates that 415 million people have diabetes mellitus, with 90% of these individuals having type 2 diabetes mellitus (T2DM) 1 .T2DM occurs when pancreatic β-cells fail to release enough insulin to meet the demands of insulin-responsive tissues, which safely store and metabolize glucose.Driven by both genetic and environmental risk factors, T2DM is a complex, multifactorial disorder.Although the increasing prevalence of T2DM is driven by changes in our environment and mirrors the increase in obesity, the greater concordance for T2DM found in monozygotic compared with dizygotic twins has long provided evidence for a genetic component in T2DM risk 2 ."
            },
            {
                "document_id": "588bca6b-82c0-4ac1-9c7e-dc09af1d49b0",
                "section_type": "main",
                "text": "Introduction\n\nGlobally, diabetes affects more than 400 million people (World Health Organization, 2016), with Type 1 (insulin-dependent) diabetes (T1D) accounting for up to 10 percent of cases (American Diabetes Association, 2009).In the United States, T1D occurs at a rate of 15-30 cases per 100,000 children aged 0-14 years annually (International Diabetes Foundation, 2017;Maahs et al., 2010), with similar prevalence in Canada, Europe, Australia, and New Zealand (Fig. 1) (Derraik et al., 2012;International Diabetes Foundation, 2017;Maahs et al., 2010).By contrast, the estimated incidence rate of T1D among Asians, South Americans, and Africans is below 15 cases per 100,000 children (Fig. 1) (International Diabetes Foundation, 2017;Maahs et al., 2010).The global incidence of T1D has been rising by 3-5% per annum over the past two decades, with a notable increase in children below 10 years of age (Diamond Project, 2006;Patterson et al., 2009)."
            },
            {
                "document_id": "ab32e261-658c-4a8b-94fc-857826b29f5a",
                "section_type": "main",
                "text": "\n\nBackground Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous.A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis."
            },
            {
                "document_id": "770beab7-59a4-4bbe-94a5-79a965ab696a",
                "section_type": "main",
                "text": "Animal Models\n\n9.2% in women and 9.8% in men, with approximately 347 million people suffering from the disease worldwide in 2008 (Danaei et al., 2011).There are several different classifications of diabetes, the most common being type 1 and type 2 diabetes."
            },
            {
                "document_id": "eaca0f25-4a6b-4c0e-a6df-12e25060b169",
                "section_type": "main",
                "text": "\n\nIntroduction: Is Type 2 Diabetes a Genetic Disorder?According to the World Health Organization (WHO), approximately 350 million people worldwide have diabetes, and this disorder is likely to be the seventh leading cause of death in 2030.Diabetes is an economic burden on healthcare systems, especially in developing countries (World Health Organization, 2013)."
            },
            {
                "document_id": "4252d7ad-82de-480c-a801-9ed1c84fb968",
                "section_type": "main",
                "text": "\n\nIn the UK alone, nearly 1.8 million people are already recognized to have this disorder (consuming w5% of the total National Health Service budget), and the search is on to find the 'missing million' who are living with the condition but in whom the diagnosis has yet to be made. 3In the USA, the situation appears to be even more serious with some commentators predicting that one in every three Americans born in the year 2000 will go on to develop diabetes during their lifetime, bringing unprecedented costs in terms of healthcare dollars as well as human morbidity and mortality. 4The majority (w90%) of these cases will be type 2 in origin, reflecting a trend towards obesity and more sedentary lifestyles as the 'norm' rather than the exception in 'developed' societies.Indeed, the face of T2DM is changing, as a condition that was once considered the preserve of middle/old age is increasingly diagnosed in young adults and even children, reflecting the high rates of obesity (and, in particular, visceral adiposity) in these populations."
            },
            {
                "document_id": "770beab7-59a4-4bbe-94a5-79a965ab696a",
                "section_type": "main",
                "text": "\n\nType 2 diabetes is the most common type of diabetes with prevalence in the United Kingdom of around 4%.It is most commonly diagnosed in middle-aged adults, although more recently the age of onset is decreasing with increasing levels of obesity (Pinhas-Hamiel and Zeitler, 2005).Indeed, although development of the disease shows high hereditability, the risk increases proportionally with body mass index (Lehtovirta et al., 2010).Type 2 diabetes is associated with insulin resistance, and a lack of appropriate compensation by the beta cells leads to a relative insulin deficiency.Insulin resistance can be improved by weight reduction and exercise (Solomon et al., 2008).If lifestyle intervention fails, there are a variety of drugs available to treat type 2 diabetes (Krentz et al., 2008), which can be divided into five main classes: drugs that stimulate insulin production from the beta cells (e.g.sulphonylureas), drugs that reduce hepatic glucose production (e.g.biguanides), drugs that delay carbohydrate uptake in the gut (e.g.a-glucosidase inhibitors), drugs that improve insulin action (e.g.thiazolidinediones) or drugs targeting the GLP-1 axis (e.g.GLP-1 receptor agonists or DPP-4 inhibitors)."
            },
            {
                "document_id": "45cdaf79-d881-43e6-8555-ff47f04ae3d4",
                "section_type": "main",
                "text": "Background\n\nThe past few decades have shown a marked increase in the number of patients with diabetes rising from 151 million (4.6% of the global population) in 2000 to 463 million (9.3%) in 2019 [1].The risk of type 2 diabetes (T2DM), the most common type of diabetes, is modified by a strong interaction between environmental and genetic factors [2,3].T2DM is a multifactorial disease with a population-specific heritability (26% in the European population) [4].A number of common variants implicated in the pathogenesis and genetic architecture of T2DM have been identified so far, some of them also capable of modifying the pharmacologic response to antidiabetic drugs [5,6]."
            },
            {
                "document_id": "b3fa4d11-72b9-4e6f-9c28-39efdaded492",
                "section_type": "main",
                "text": "Introduction\n\nDiabetes is one of the most prevalent complex disorders with type 2 diabetes accounting for more than 90% of all diabetic cases.Hyperglycemia is the characteristic feature of this syndrome, which results from defective insulin secretion or action.The disease itself may not lead to death of the affected individual but being the major risk factor of macrovascular complications like coronary artery disease, cerebrovascular events and peripheral vascular disease, diabetes is an indirect cause of deaths due to such diseases.It is also responsible for disabilities such as diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, skin complications, eye complications as well as mental illness.The International Diabetes Federation (IDF) 2015 reported an estimate of 415 million adults (20-79 years of age) worldwide to have diabetes in the year 2015, which is projected to reach 642 million by the year 2040.Diabetes has been a major public health concern in the 21st century (IDF 2015) among the worldwide countries/territories, particularly in China, India and USA, which show the alarmingly increasing prevalence (figure 1).India, in particular, is expected to have doubled its prevalence by 2040."
            },
            {
                "document_id": "3548bb7f-727c-4ccb-acc7-a97553b89992",
                "section_type": "main",
                "text": "\n\nTHE GLOBAL BURDEN OF TYPE 2 DIABETES-The dynamics of the diabetes epidemic are changing rapidly.Once a disease of the West, type 2 diabetes has now spread to every country in the world.Once \"a disease of affluence,\" it is now increasingly common among the poor.Once an adult-onset disease almost unheard of in children, rising rates of childhood obesity have rendered it more common in the pediatric population, especially in certain ethnic groups.According to the International Diabetes Federation (1), diabetes affects at least 285 million people worldwide, and that number is expected to reach 438 million by the year 2030, with two-thirds of all diabetes cases occurring in low-to middle-income countries.The number of adults with impaired glucose tolerance will rise from 344 million in 2010 to an estimated 472 million by 2030."
            },
            {
                "document_id": "9c9cc0b3-5dde-4077-ae41-1410db9aeb24",
                "section_type": "main",
                "text": "\n\nThere is a high degree of variability for prevalence of type 2 diabetes across the globe.East Asia, South Asia, and Australia have more adults with diabetes than any other region (153 million).North America and the Caribbean have the highest prevalence rate, with one in eight affected (8)."
            },
            {
                "document_id": "988d55c7-f831-4adb-94c0-6de4ebf4727b",
                "section_type": "main",
                "text": "\n\nIn Germany, type 2 diabetes shows increasing prevalence with 5-8 million people having some form of diabetes (prevalence: 6-10%).In an effort to identify causative genetic factors, we report here results of linkage studies in which we identified two type 2 diabetes loci.We elucidated potentially interacting regions by conditioning our sample on the positive linkage signals identified.Taken together, our results and the findings of other studies provide evidence for a complex metabolic syndrome locus on chromosome 1p36.13."
            },
            {
                "document_id": "a7bad429-5f6a-464f-a666-f9cb1be60338",
                "section_type": "main",
                "text": "\n\nof those initially classified may require revision [7] .The classical classification of diabetes as proposed by the American Diabetes Association (ADA) in 1997 as type 1, type 2, other types, and gestational diabetes mellitus (GDM) is still the most accepted classification and adopted by ADA [1] .Wilkin [8] proposed the accelerator hypothesis that argues \"type 1 and type 2 diabetes are the same disorder of insulin resistance set against different genetic backgrounds\" [9] .The difference between the two types relies on the tempo, the faster tempo reflecting the more susceptible genotype and earlier presentation in which obesity, and therefore, insulin resistance, is the center of the hypothesis.Other predictors of type 1 diabetes include increased height growth velocity [10,11] and impaired glucose sensitivity of β cells [12] .The implications of increased free radicals, oxidative stress, and many metabolic stressors in the development, pathogenesis and complications of diabetes mellitus [13-18] are very strong and well documented despite the inconsistency of the clinical trials using antioxidants in the treatment regimens of diabetes [19][20][21] .The female hormone 17-β estradiol acting through the estrogen receptor-α (ER-α) is essential for the development and preservation of pancreatic β cell function since it was clearly demonstrated that induced oxidative stress leads to β-cell destruction in ER-α knockout mouse.The ER-α receptor activity protects pancreatic islets against glucolipotoxicity and therefore prevents β-cell dysfunction [22] ."
            },
            {
                "document_id": "2e317f9d-c028-41b7-a99e-28da61db9970",
                "section_type": "main",
                "text": "Introduction\n\nDiabetes impacts approximately 200 million people worldwide [1], with microvascular and cardiovascular disease being the primary complications.Approximately 10% of cases are type 1 diabetes (T1D) sufferers, with ,3% increase in the incidence of T1D globally per year [2].It is expected that the incidence is 40% higher in 2010 than in 1998 [3].T1D is a clear example of a complex trait that results from the interplay between environmental and genetic factors.There are many lines of evidence that there is a strong genetic component to T1D, primarily due to the fact that T1D has high concordance among monozygotic twins [4] and runs strongly in families, together with a high sibling risk [5]."
            },
            {
                "document_id": "b9c9912f-0344-4945-adb1-fd038bed90ab",
                "section_type": "main",
                "text": "Introduction\n\nType 2 diabetes is a common complex disease characterised by deficient insulin secretion and decreased insulin sensitivity.In 2010, 285 million people worldwide were affected by type 2 diabetes [1], with 60% of them located in Asia [2,3].China now has the largest number of patients with diabetes in the world, with an estimated 92 million affected individuals, and an additional 150 million with impaired glucose tolerance [4]."
            },
            {
                "document_id": "f44149e0-d183-48c1-a937-729e7abd87f5",
                "section_type": "main",
                "text": "Background\n\nType 2 diabetes mellitus (T2D) is a phenotypic and genetically heterogeneous chronic disease [1] that represents 90% to 95% of all diabetes types; given its magnitude, it has become an increasingly important public health problem worldwide, occurring in ever-younger individuals [2].In México, the National Health Survey 2000 (ENSA 2000) showed a T2D prevalence of 7.5% in individuals 20 years and older [3]."
            },
            {
                "document_id": "15b5c53c-d153-4932-9d24-9864e92a601d",
                "section_type": "main",
                "text": "INTRODUCTION\n\nType 2 diabetes (T2D) is a complex disease characterized by insulin resistance and b-cell dysfunction.An estimated 630 million adults are expected to have T2D by 2045, 1 making it one of the fastest growing global health challenges of the 21st century.Genome-wide association studies (GWASs) have successfully identified more than 500 genomic loci to be associated with T2D, 2 although the majority of these are driven by common variants with small individual effects on T2D risk."
            },
            {
                "document_id": "a7bad429-5f6a-464f-a666-f9cb1be60338",
                "section_type": "main",
                "text": "TYPE 2 DIABETES MELLITUS\n\nThe global prevalence of diabetes in adults (20-79 years old) according to a report published in 2013 by the IDF was 8.3% (382 million people), with 14 million more men than women (198 million men vs 184 million women), the majority between the ages 40 and 59 years and the number is expected to rise beyond 592 million by 2035 with a 10.1% global prevalence.tissues.In addition to insulin resistance, the increased demand for insulin could not be met by the pancreatic β cells due to defects in the function of these cells [18] .On the contrary, insulin secretion decreases with the increased demand for insulin by time due to the gradual destruction of β cells [57] that could transform some of type 2 diabetes patients from being independent to become dependent on insulin.Most type 2 diabetes patients are not dependent on insulin where insulin secretion continues and insulin depletion rarely occurs."
            },
            {
                "document_id": "251d15dc-e1ec-4fea-8c29-b000f51a62cd",
                "section_type": "main",
                "text": "INTRODUCTION\n\nType 2 diabetes (T2D) is a complex metabolic disorder that accounts for 85%-95% of all cases of diabetes and afflicts hundreds of millions of people worldwide (http://www.diabetesatlas.org/content/diabetes).It is a leading cause of substantial morbidity and is characterized by defects in insulin sensitivity and secretion resulting from the progressive dysfunc-tion and loss of b cells in the pancreatic islets of Langerhans (Butler et al., 2007;Muoio and Newgard, 2008).Both genetic predisposition and environmental factors contribute to these islet defects.Islets constitute 1%-2% of human pancreatic mass (Joslin and Kahn, 2005) and are composed of five endocrine cell types that secrete different hormones: a cells (glucagon), b cells (insulin), d cells (somatostatin), PP cells (pancreatic polypeptide Y), and 3 cells (ghrelin).These cells sense changes in blood glucose concentration and respond by modulating the activity of multiple pathways, including insulin and glucagon secretion, to maintain glucose homeostasis (Joslin and Kahn, 2005).Several key transcription factors (TFs) that regulate these responses are known (Oliver-Krasinski and Stoffers, 2008).However, efforts to identify cis-regulatory elements upon which these and other factors act have been restricted primarily to promoter regions at specific loci (e.g., INS, PDX1) (Brink, 2003;Ohneda et al., 2000)."
            },
            {
                "document_id": "3675ae2a-18d5-4f2b-97e1-1827eddc0f6f",
                "section_type": "main",
                "text": "\n\nType 2 diabetes affects more than 200 million individuals worldwide, and its prevalence is continuously increasing in many countries, including Japan.Although the precise mechanisms underlying the development and progression of type 2 diabetes have not been fully elucidated, a combination of multiple genetic and environmental factors is considered to contribute to the pathogenesis of the disease 1 ."
            },
            {
                "document_id": "ff69cd83-ab79-4c24-8bc5-fd9009aa259b",
                "section_type": "main",
                "text": "Background & Summary\n\nDiabetes is one of the fastest-growing health challenges of the 21 st century.The most common form of diabetes, type 2 diabetes (T2D), is a complex multifactorial disease which can lead to further severe health consequences such as cardiovascular diseases and premature death.In 2019, 463 million people worldwide were living with diabetes according to the International Diabetes Federation, and this number is expected to rise to 700 million by 2045 1 .Genome-wide association studies (GWAS) have made considerable progress in identifying genetic risk factors and in providing evidence for more in-depth understanding of the biological and pathological pathways underlying T2D.A recent study performed a meta-analysis of T2D across 32 GWAS of European ancestry participants and identified 243 genome-wide significant loci (403 distinct genetic variants) associated with T2D risk 2 .The summary statistics from this meta-analysis are publicly available; however, the GWAS results for each participating study, including EPIC-InterAct, cannot be acquired easily."
            },
            {
                "document_id": "41ba5319-e77d-4838-8f50-e59fe86b94f8",
                "section_type": "main",
                "text": "\n\nDIABETES EPIDEMIC-The latest estimates from the Center for Disease Control and Prevention indicate that in 2010 approximately 26 million American adults had diabetes and 79 million had prediabetes (1).African Americans and other ethnic groups continue to suffer higher rates of diabetes than whites.Worldwide, diabetes affects 285 million adults (2).Type 2 diabetes accounts for ;95% of all cases.The exact reasons for the diabetes epidemic, and its predilection for certain ethnic groups, are unknown.However, interactions between genetic predisposition and environmental triggers (or accelerants) are generally presumed to underlie the etiology of diabetes (3-5) (Fig. 1).The best known environmental risk factors are dietary habits, physical inactivity, and obesity; interventions that ameliorate these risk factors prevent the development of type 2 diabetes (6,7)."
            },
            {
                "document_id": "d15b3490-241d-4766-8e3e-feb683503d1b",
                "section_type": "main",
                "text": "\n\nType 2 diabetes is one of the leading health problems in the United States, affecting approximately 21 million persons or almost 10% of the US adult population (1).Type 2 diabetes is nearly twice as prevalent among African Americans as among Caucasians (1)."
            },
            {
                "document_id": "7d4a197e-3774-40a4-9897-ed7c71f213b6",
                "section_type": "main",
                "text": "Introduction\n\nDiabetes impacts the lives of approximately 200 million people worldwide [1], with chronic complications including accelerated development of cardiovascular disease.Over 90% of cases are of type 2 diabetes (T2D), with the bulk of the remainder presenting with type 1 diabetes (T1D)."
            },
            {
                "document_id": "6a2d9ea5-7018-42fe-bed9-2c9c508531cb",
                "section_type": "main",
                "text": "Introduction\n\nType 2 diabetes mellitus (T2D) is a major chronic disease worldwide, affecting more than 300 million people.The greatest increase in the prevalence of T2D in the coming years is likely to be in Asia, home to half of the world's population with 3 billion people [1][2].It is estimated that in China alone, there are 100 million people with T2D [3]."
            },
            {
                "document_id": "961f88ba-2090-4904-942c-f0e014bbe53f",
                "section_type": "main",
                "text": "Classification of Diabetes\n\nOn the basis of insulin deficiency, diabetes can be classified into the following types as follows."
            },
            {
                "document_id": "ad88aed6-75ba-469d-b96b-7be4a65be8fc",
                "section_type": "main",
                "text": "Introduction\n\nType 2 diabetes (T2D) is a common disease with substantial and rapidly increasing global impact.While prevalence varies with age, sex and population, the global age-standardized adult diabetes prevalence is >9.2%, and an estimated >347 million adults have diabetes (1).Diabetes can be diagnosed based on the level of blood glucose after fasting or 2 h after an oral glucose challenge (2hGlu), or based on hemoglobin A1c (HbA1c), which provides a 3month average of blood glucose (2).In many individuals with T2D, insulin resistance coexists with obesity, adverse lipid profiles, high blood pressure and a proinflammatory state, each likely influenced by genetic and environmental factors (3).Progression to T2D is characterized by abnormalities in pancreatic islet β-cell function in the presence of insulin resistance (4), although these biological processes are only partially defined.Strong evidence for a genetic component exists for T2D risk, insulin secretion and insulin action (5,6)."
            },
            {
                "document_id": "ee21529b-bf7d-49ec-a21e-c52c9c7ff7e1",
                "section_type": "main",
                "text": "Symptomatic T1DM\n\nAccording to the International Diabetes Federation, 8.8% of the adult population worldwide has diabetes 14 .Of all individuals with diabetes, only 10-15% have T1DM; type 2 diabetes mellitus (T2DM) is the most common form.However, T1DM is the most com mon form of diabetes in children (<15 years of age), and >500,000 children are currently living with this condition globally."
            },
            {
                "document_id": "8857153e-a7be-45ee-84dd-14911bdd064a",
                "section_type": "main",
                "text": "Introduction\n\nType 2 diabetes (T2D) affects at least 6% of the world's population; the worldwide prevalence is expected to double by 2025 [1].T2D is a complex disorder that is characterized by hyperglycemia, which results from impaired pancreatic b cell function, decreased insulin action at target tissues, and increased glucose output by the liver [2].Both genetic and environmental factors contribute to the pathogenesis of T2D.The disease is considered to be a polygenic disorder in which each genetic variant confers a partial and additive effect.Only 5%-10% of T2D cases are due to single gene defects; these include maturity-onset diabetes of the young (MODY), insulin resistance syndromes, mitochondrial diabetes, and neonatal diabetes [3][4][5].Inherited variations have been identified from studies of monogenic diabetes, and have provided insights into b cell physiology, insulin release, and the action of insulin on target cells [6]."
            }
        ],
        "document_id": "DF2A84CC99BAED8C3168AE12F76252A2",
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        "keywords": [
            "type&1&diabetes",
            "type&2&diabetes",
            "gestational&diabetes",
            "LADA",
            "MODY",
            "insulin&resistance",
            "pancreatic&beta&cells",
            "autoimmune&destruction",
            "insulin&deficiency",
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        "metadata": [
            {
                "object": "rs2059806 of INSR was associated with both type 2 diabetes mellitus and type 2 diabetic nephropathy, while rs7212142 of mTOR was associated with type 2 diabetic nephropathy but not type 2 diabetes mellitus in a Chinese Han population.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab687817"
            },
            {
                "object": "The genotype EE/EK/KK frequencies % for the CTRL group 38.2/50.2/11.6, Type 1 Diabetes 34.3/52.0/13.7, and Type 2 Diabetes 38.2/48.9/12.9 were in Hardy-Weinberg equilibrium and there were no significant differences. The minor allele frequencies MAF; K for CTRL 37.0%, Type 1 Diabetes 39.7%, and Type 2 Diabetes 37.4% were not different among the groups",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab818180"
            },
            {
                "object": "Data suggest that secretion of insulin by beta-cells is related to insulin resistance in complex manner; insulin secretion is associated with type 2 diabetes in obese and non-obese subjects, but insulin resistance is associated with type 2 diabetes only in non-obese subjects. Chinese subjects were used in these studies.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab210958"
            },
            {
                "object": "Data suggest IGT10 mice, diabetes type 2 model, exhibit 2 genetic defects: haploinsufficiency heterozygosity for null allele of insulin receptor Insr; splice-site mutation in protein phosphatase 2 regulatory subunit B alpha Ppp2r2a. Inheritance of either allele results in insulin resistance but not overt diabetes. Double heterozygosity leads to insulin resistance and diabetes type 2 without increase in body weight.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab203476"
            },
            {
                "object": "Sfrp5 may be concurrently associated with COPD [ chronic obstructive pulmonary disease ] and insulin resistance; insulin resistance may be associated with airway inflammation and airflow limitation. Sfrp5 may be involved in the development of COPD and may be the key link by which insulin resistance exerts its effects on airway inflammation.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab702425"
            },
            {
                "object": "Data suggest a novel pathophysiological role of CD163 in type 2 diabetes; monocyte surface CD163 levels are significantly associated with insulin resistance in patients with type 2 diabetes; the association of insulin resistance with soluble CD163 levels is less significant. This study was conducted in Japan.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab202739"
            },
            {
                "object": "Decreased plasma ghrelin significantly associated with abdominal adiposity, hyperinsulinemia and insulin resistance in type 2 diabetic patients. Hyperinsulinemia with insulin resistance may suppress plasma ghrelin in type 2 diabetes mellitus.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab218455"
            },
            {
                "object": "results show an association between the AGER -374 T/A polymorphism & type 1 diabetes; the polymorphism was associated with diabetic nephropathy in both type 1 & type 2 diabetes & with sight-threatening retinopathy in type 1 diabetic patients",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab660185"
            },
            {
                "object": "polymorphism of IAPP gene in nondiabetic subjects and type 2 diabetes is associated with lower levels of LDL cholesterol; abnormalities of coding regions or 5'-UTR not associated with type 2 diabetes or gestational diabetes mellitus in Spanish population.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab604559"
            },
            {
                "object": "The association of variants in IRS1 with type 2 diabetes and type 2 diabetes-related phenotypes and the differential expression of IRS1 in adipocytes and skeletal muscle suggest a role of this gene in the pathogenesis of type 2 diabetes in Pima Indians.",
                "predicate": "http://www.w3.org/2000/01/rdf-schema#comment",
                "subject": "ndd791caee50643ad90a986f563d2a0dab782328"
            }
        ],
        "question": "How many types of diabetes exist?",
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