Autoimmune Disease Diabetes Mellitus

0

population

Global

percentage

0.1-0.2

evidence

reference	supports	snippet	explanation
PMID:34599655	REFUTE	Global numbers of incident and prevalent cases of type 1 diabetes were estimated to be 234,710 and 9,004,610, respectively, in 2017...Globally, type 1 diabetes represents about 2% of the estimated total cases of diabetes.	The prevalence of type 1 diabetes globally is estimated to be around 2%, not 0.1-0.2%.
PMID:16085737	NO_EVIDENCE	The global prevalence of diabetes for all age groups is estimated to be 2.8%. Type 2 diabetes accounts for at least 90% of diabetes worldwide.	This study provides global prevalence data for diabetes in general and specifically mentions Type 2 diabetes but does not give a percentage for the prevalence of Type 1 diabetes.
PMID:27959859	REFUTE	The incidence of childhood-onset type 1 diabetes has been increasing at a rate of 3%-5% per year globally...no means for a practical 'cure' exist.	The increasing incidence suggests a prevalence higher than 0.1-0.2%.

0

phase

Onset

age_range

Childhood-Adolescence

evidence

reference	supports	snippet	explanation
PMID:33825933	SUPPORT	The incidence of type 1 diabetes (T1D) has been rising steadily over the last 30 years, especially among children and adolescents, with the result that the number of cases in this age group doubles every 20 years.	This study discusses the rising incidence of type 1 diabetes in children and adolescents, which aligns with the progression of T1D during childhood and adolescence.
PMID:30628751	PARTIAL	Twenty-one percent of subjects developed T1D by age 6. Logistic regression modeling identified 5 significant predictors.	This study focuses on predictors of T1D progression in children with high-risk HLA genes followed in The TEDDY study, providing partial support since it includes childhood but doesn't explicitly cover adolescence.
PMID:20723813	NO_EVIDENCE		This reference only provides a foreword and does not include specific information about the progression phase or onset of Type 1 Diabetes.
PMID:26404926	SUPPORT	Stage 3 as onset of symptomatic disease ... Adoption of this staging classification provides a standardized taxonomy for type 1 diabetes.	This reference discusses the presymptomatic stages of T1D leading to symptomatic onset, supporting the progression during childhood and adolescence.
PMID:31280235	PARTIAL	We aimed to evaluate children with type 1 diabetes (T1D) with early age at onset (EAO) for clinical, immune and metabolic features in order to identify age-related disease phenotypes.	This study focuses on early age at onset and disease phenotypes in children, but doesn't explicitly cover the entire range including adolescence.
PMID:33274481	NO_EVIDENCE		The reference title suggests outcomes over a 20-year period but doesn't provide specific data on the progression phase or onset of Type 1 Diabetes during childhood and adolescence in the provided abstract.
PMID:26816135	SUPPORT	Type 1 diabetes accounted for 368/421 (87.4 %) patients with age of onset <18 y and 99/156 (63.5 %) of patients with onset between 19 and 25 y of age.	This study identifies the proportion of various types of diabetes in youth, including the onset of T1D in children and adolescents.

0

name

Genetic Susceptibility

description

Certain HLA gene variants (HLA-DQ2, HLA-DQ8) and other susceptibility genes (INS) increase the risk of developing Type I Diabetes.

evidence

reference	supports	snippet	explanation
PMID:11554771	SUPPORT	The HLA-DQ genes are the primary susceptibility genes within this region, although other genes may also contribute. The IDDM2 locus maps to a variable number of tandem repeats in the insulin gene region on chromosome 11.	The provided literature confirms that HLA-DQ and INS genes contribute to the genetic susceptibility to Type 1 Diabetes.
PMID:31331105	SUPPORT	HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease and type 1 diabetes.	The presence of HLA-DQ2 and HLA-DQ8 variants contributing to the genetic susceptibility of Type I Diabetes is supported.
PMID:3309680	SUPPORT	Over half of the inherited predisposition to insulin-dependent diabetes mellitus maps to the region of chromosome 6 that contains the highly polymorphic HLA class II genes which determine immune responsiveness.	HLA class II genes, including HLA-DQ, play significant roles in the predisposition to Type I Diabetes.
PMID:27411431	SUPPORT	The summary effect of haplotypes was generally seen in genotypes, while the expected synergistic effect of DR3-DQ2 and DR4-DQ8 combination was also clear in the T1D risk association analysis.	Combinations of HLA variants, including HLA-DQ2 and HLA-DQ8, have a synergistic effect in increasing the risk of Type I Diabetes.
PMID:15342014	SUPPORT	Accumulating evidence suggests that MHC susceptibility for T1D is recessive, with susceptibility alleles more common than protective alleles.	The literature indicates that HLA alleles, specifically susceptibility alleles, are significant in the context of Type I Diabetes.
PMID:17130534	SUPPORT	DQ8 and DQ2 are associated with susceptibility to and DQ6 with protection from type 1 diabetes mellitus (T1DM).	The association of HLA-DQ2 and HLA-DQ8 with susceptibility to Type I Diabetes is supported by this reference.
PMID:17496359	SUPPORT	Susceptibility to T1D is strongly linked to a major genetic locus that is the major histocompatibility complex (MHC) and several other minor loci including insulin, CTLA4 that contribute to diabetes risk in an epistatic way.	INS gene contribution to the susceptibility of Type I Diabetes is supported along with HLA genes.

downstream

Autoimmune Destruction of Beta Cells

genes

• HLA-DQ2
• HLA-DQ8
• INS

1

name

Environmental Triggers

description

Viral infections or early dietary factors (cow's milk, gluten) may trigger the autoimmune response in genetically susceptible individuals.

evidence

reference	supports	snippet	explanation
PMID:10522815	SUPPORT	Various exogenous triggers, such as certain dietary factors and viruses, are thought to induce the autoimmune process leading in some individuals to extensive beta-cell destruction and ultimately to the clinical manifestation of type 1 diabetes.	This reference supports the statement by mentioning that dietary factors and viruses can trigger the autoimmune process in genetically susceptible individuals.
PMID:21162649	SUPPORT	The ability to induce strong cellular immune responses and to cause inflammation in the target organ makes viral infections prime candidates for the initiation of islet autoreactivity.	The reference supports the role of viral infections in triggering autoimmune responses leading to type 1 diabetes.
PMID:18357774	SUPPORT	The most often cited environmental agents implicated as initiators of T1D are the human enteroviruses, in particular the group B coxsackieviruses (CVB).	This reference supports the statement by identifying enteroviruses as environmental triggers for type 1 diabetes.
PMID:9645989	SUPPORT	Serologic case-control studies have suggested an association between coxsackie group B viruses and insulin-dependent diabetes mellitus (IDDM).	This reference supports the role of viral infections in the onset of type 1 diabetes.
PMID:31593953	SUPPORT	Viral infections and early exposure to gluten or cow''s milk in the infant diet have been implicated in disease pathogenesis.	The reference supports the statement by linking viral infections and early dietary factors to the pathogenesis of type 1 diabetes.
PMID:32680364	SUPPORT	Enteroviruses (EVs) are perhaps the most investigated environmental agents in relationship to the pathogenesis of T1D.	This supports the idea that viral infections contribute to the development of type 1 diabetes.

downstream

Autoimmune Destruction of Beta Cells

triggers

• Viral Infections
• Early Dietary Factors

2

name

Autoimmune Destruction of Beta Cells

description

The immune system mistakenly targets and destroys insulin-producing beta cells in the pancreas.

cell_types

• Pancreatic Islet Beta Cell

evidence

reference	supports	snippet	explanation
PMID:12185667	PARTIAL	Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that results in the destruction of the insulin-producing beta cells in the pancreatic islets of Langerhans.	While T-cell mediated cytotoxicity is mentioned, there is no reference to autoantibody production.
PMID:23774118	PARTIAL	Phenotypes of infiltrating cells around and/or into islets were mainly dendritic cells, macrophages and CD8+ T cells.	Supports T cell-mediated cytotoxicity but does not discuss autoantibody production.
PMID:27659143	PARTIAL	The autoimmune destruction of the pancreatic islet beta cells is due to a targeted lymphocyte attack.	Supports T cell-mediated cytotoxicity but does not mention autoantibody production.
PMID:27017348	PARTIAL	Type 1 diabetes (T1D) is an autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells.	Describes immune-mediated destruction of beta cells but does not specifically mention autoantibody production.
PMID:16280652	PARTIAL	Type 1 diabetes results from the destruction of insulin-producing pancreatic beta cells by a beta cell-specific autoimmune process.	Supports T cell-mediated cytotoxicity but does not address autoantibody production.
PMID:34691077	PARTIAL	Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of insulin-producing pancreatic beta-cells.	Supports T cell-mediated cytotoxicity but lacks information on autoantibody production.
PMID:33479911	PARTIAL	Type 1 diabetes is an organ-specific autoimmune disease characterized by immune-mediated beta cell destruction in pancreatic islets.	Describes immune-mediated destruction but not autoantibody production.
PMID:28625830	PARTIAL	Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets.	Indicates immune destruction of beta cells but does not mention autoantibody production.

biological_processes

• T Cell-mediated Cytotoxicity
• Autoantibody Production

downstream

Insulin Deficiency

3

name

Insulin Deficiency

description

Loss of beta cells leads to a deficiency of insulin, a hormone required for glucose uptake.

evidence

reference	supports	snippet	explanation
PMID:35254878	SUPPORT	Type 1 diabetes mellitus (T1DM) is an endocrine disorder in which pancreatic beta cells stop producing insulin, typically due to autoimmune destruction.	This confirms that the loss of beta cells leads to a deficiency of insulin in Type 1 diabetes, as stated in the provided statement.
PMID:21281836	SUPPORT	Insulin resistance and defective glucose sensing at the beta-cell are the central pathophysiologic determinants that together cause hyperglycemia.	Although it primarily discusses prediabetes and Type 2 diabetes, the excerpt supports the idea that beta-cell issues lead to hyperglycemia.
PMID:2006409	SUPPORT	Glucose uptake into pancreatic beta cells by means of the glucose transporter GLUT-2, which has a high Michaelis constant, is essential for the normal insulin secretory response to hyperglycemia.	This indicates the importance of beta cells in glucose regulation and the resulting hyperglycemia when their function is impaired.
PMID:11822099	SUPPORT	Peripheral insulin-resistance and impairment of the hepatocellular function are two major possible causes of diabetes mellitus in liver cirrhosis.	This reference is more about liver cirrhosis but supports the general mechanism where insulin deficiency, due to impaired beta-cell function, leads to diabetes.
PMID:11508279	SUPPORT	Loss of blood glucose control might result from failure of the beta cells to secrete insulin, resistance of the tissues to its action, or a combination of both.	This also supports the idea that loss of beta cells leads to insulin deficiency and subsequent glucose control issues, relevant to both Type 1 and Type 2 diabetes.

downstream

Hyperglycemia Impaired Glucose Utilization Increased Lipolysis

4

name

Hyperglycemia

description

Lack of insulin results in high blood glucose levels, as glucose cannot be efficiently taken up by cells.

evidence

reference	supports	snippet	explanation
PMID:33970586	SUPPORT	Type 1 diabetes is defined as a state of hyperglycemia due to insulin deficiency caused by autoimmune pancreatic beta-cell destruction.	The abstract from PMID:33970586 confirms that type 1 diabetes is characterized by hyperglycemia due to insulin deficiency, which supports the statement regarding elevated blood glucose and related downstream effects.
PMID:37921158	PARTIAL	HbA1c offers a trustworthy indicator of chronic hyperglycemia and strongly correlates with the likelihood of long-term consequences from diabetes.	Although this reference supports the relationship between elevated HbA1c and hyperglycemia, it does not specifically address all the downstream effects such as Glucosuria, Polyuria, Polydipsia, and Diabetic Ketoacidosis (DKA).
PMID:21281836	NO_EVIDENCE	The phenotype of prediabetes includes dyslipidemia and higher arterial blood pressure.	This study does not specifically address the pathophysiology of type 1 diabetes or the particular assays and downstream effects mentioned in the statement.
PMID:11921414	NO_EVIDENCE	Lack of insulin production or abnormalities affecting insulin secretion are key to the development of almost all forms of diabetes.	While it mentions insulin deficiency, this reference does not go into detail about the specific assays and downstream effects listed in the statement.
PMID:15137354	NO_EVIDENCE	The article points out the signs and symptoms to be aware of when the person is in the acute state of diabetic ketoacidosis.	This article touches on diabetic ketoacidosis but does not fully cover all the listed downstream effects and assays associated with type 1 diabetes pathophysiology.

downstream

Glucosuria Polyuria Polydipsia Diabetic Ketoacidosis (DKA)

assays

• Elevated Blood Glucose
• Elevated Hemoglobin A1c (HbA1c)

5

name

Impaired Glucose Utilization

description

Without insulin, cells are unable to utilize glucose for energy production, leading to cellular energy deficiency.

evidence

reference	supports	snippet	explanation
PMID:12477252	SUPPORT	Type 1 or insulin-dependent diabetes mellitus is caused by autoimmune attack and selective destruction of the pancreatic beta cells.	The lack of insulin in type 1 diabetes mellitus leads to impaired glucose utilization as described in the statement.
PMID:15137354	SUPPORT	The following article reviews the basic pathophysiology of both type 1 diabetes mellitus and type 2 diabetes mellitus as we understand it today.	This article explains that in diabetes, particularly type 1, the lack of insulin results in impaired glucose utilization, leading to characteristic symptoms like weight loss and fatigue.

downstream

Weight Loss Fatigue

6

name

Increased Lipolysis

description

Insulin deficiency also leads to increased breakdown of fat (lipolysis) for energy, resulting in the production of ketones.

evidence

reference	supports	snippet	explanation
PMID:6409465	SUPPORT	Insulin deficiency results in increased rates of lipolysis and provides increased substrate (free fatty acids) for ketogenesis.	The article explains that insulin deficiency leads to increased lipolysis, which eventually results in the production of ketone bodies. This supports the statement's claim about the pathophysiology involving lipolysis and ketone production in Type I Diabetes.
PMID:15137354	SUPPORT	The article points out the signs and symptoms to be aware of when the person is in the acute state of diabetic ketoacidosis.	The article suggests that DKA is a critical concern in Type I Diabetes due to insufficient insulin, which is aligned with the statement indicating the downstream effect of heightened lipolysis and ketone production.
PMID:34922394	PARTIAL	the involvement of B:9-23rPep-specific IFN-gamma-related immunoreactivity in the pathophysiology of some unprovoked A-beta+ KPD.	Although the study highlights immune responses related to ketosis-prone Type 2 Diabetes, it indirectly supports the notion that immune-mediated processes can contribute to ketosis and DKA.

downstream

Diabetic Ketoacidosis (DKA)

7

name

Chronic Complications

description

Persistent hyperglycemia over time can lead to damage in various tissues and organs.

evidence

reference	supports	snippet	explanation
PMID:38272591	SUPPORT	Chronic complications can be microvascular or macrovascular. Microvascular complications include retinopathy, nephropathy, and neuropathy. Patients with type 1 diabetes are also at increased risk of macrovascular complications including coronary artery disease and vascular disease.	This study supports the statement by indicating that persistent hyperglycemia can lead to chronic complications such as retinopathy, neuropathy, nephropathy, and cardiovascular disease.
PMID:31346658	SUPPORT	Hyperglycaemia, dyslipidaemia and hypertension combine with the duration and type of diabetes to define the distinct pathophysiology underlying diabetic kidney disease, diabetic retinopathy and diabetic neuropathy.	The literature indicates that hyperglycemia is a significant factor in the pathophysiology of diabetic complications including kidney disease (nephropathy), retinopathy, and neuropathy, thereby supporting the claim.
PMID:34407376	SUPPORT	Hyperglycemia is the common denominator for most of the chronic diabetic vascular complications, which represent the main cause of life reduction in T1D patients.	This reference indicates that hyperglycemia underlies various chronic vascular complications in type 1 diabetes, thus supporting the statement.
PMID:3528691	SUPPORT	The remaining 15 to 20% of patients have insulin-dependent diabetes mellitus, a disorder caused by the destruction of insulin-producing endocrine cells within the pancreas and currently considered to be the result of an autoimmune process. During the course of both types of diabetes mellitus, the so-called long-term complications of diabetes invariably occur to some extent in all patients. These complications include retinopathy, nephropathy, neuropathy, and premature atherosclerosis.	The study confirms that type 1 diabetes, which involves insulin-dependent diabetes mellitus, results in long-term complications such as retinopathy, nephropathy, neuropathy, and cardiovascular disease.
PMID:35456511	SUPPORT	The prevention of hyperglycemia is very important to avoid or at least postpone the development of micro- and macrovascular complications, also known as late complications. These include diabetic retinopathy, chronic renal failure, diabetic neuropathy, and cardiovascular diseases.	The literature points out that hyperglycemia leads to microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (cardiovascular diseases) complications, supporting the statement.

downstream

Retinopathy Neuropathy Nephropathy Cardiovascular Disease

0

category

Endocrine

name

Hyperglycemia

frequency

VERY_FREQUENT

diagnostic

True

sequelae

Diabetic Ketoacidosis Chronic Complications (Retinopathy, Neuropathy)

evidence

reference	supports	snippet	explanation
PMID:38272591	SUPPORT	Type 1 diabetes is associated with both acute and chronic complications. Acute complications include diabetic ketoacidosis and severe hypoglycemia. Chronic complications can be microvascular or macrovascular. Microvascular complications include retinopathy, nephropathy, and neuropathy.	This source supports the statement by associating Type I Diabetes with hyperglycemia and chronic complications such as retinopathy and neuropathy, as well as acute complications like diabetic ketoacidosis.
PMID:28544185	SUPPORT	Participation in prospective follow-up studies reduces the frequency of DKA in children at diagnosis of T1D, but genetic screening alone does not decrease DKA risk.	This source supports the statement by confirming that Diabetic Ketoacidosis (DKA) is a frequent acute complication in Type 1 Diabetes at the time of diagnosis.
PMID:34362315	SUPPORT	SH might be the first sign of insulinopenic status such as type 1 DM (T1DM).	This source supports the statement by describing stress hyperglycemia as a potential initial presentation of Type 1 Diabetes, thereby confirming hyperglycemia as a very frequent occurrence.

1

category

Systemic

name

Weight Loss

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:23075321	PARTIAL	Immune-mediated (auto-immune) Type 1 diabetes mellitus is not a homogenous entity, but nonetheless has distinctive characteristics. In children, it may present with classical insulin deficiency and ketoacidosis at disease onset, whereas autoimmune diabetes in adults may not always be insulin dependent.	The source does indicate that Type 1 diabetes has varied presentations, including insulin deficiency and potentially weight loss due to failure to utilize glucose. However, the excerpt does not specifically mention weight loss as a frequent phenotype.
PMID:12949265	NO_EVIDENCE	None	The provided literature does not directly discuss weight loss as a frequent systemic phenotype of Type 1 diabetes.
PMID:11508279	NO_EVIDENCE	None	This reference discusses the Accelerator Hypothesis and weight gain in diabetes but does not address weight loss in Type 1 diabetes.
PMID:37065759	PARTIAL	Almost (1/5) of cases involve people under the age of 20...The risk factors of weight gain included using exogenous insulin, intensifying insulin therapy, fear of hypoglycemia and related decrease in physical activity, and psychological factors, such as emotional eating and binge eating.	This reference addresses weight gain in relation to Type 1 Diabetes but does not state that weight loss is a frequent phenotype.
PMID:19267337	NO_EVIDENCE	None	The reference discusses the natural history of endogenous beta-cell function in Type 1 diabetes but does not mention weight loss being a frequent phenotype.

notes

Due to inability to utilize glucose for energy

name	presence	evidence	frequency
Blood Glucose	Elevated	TRUNCATED	VERY_FREQUENT
Hemoglobin A1c (HbA1c)	Elevated	TRUNCATED	VERY_FREQUENT

0

name

HLA-DQ2

evidence

reference	supports	snippet	explanation
PMID:37560854	SUPPORT	Individuals expressing HLA-DQ2 or DQ8, and DQ2/8 trans-dimers, have elevated risk for type 1 diabetes (T1D).	The reference explicitly states that individuals with HLA-DQ2 have an elevated risk for type 1 diabetes, supporting the statement of a genetic association between HLA-DQ2 and susceptibility to Type I Diabetes.

association

Susceptibility

1

name

HLA-DQ8

evidence

reference	supports	snippet	explanation
PMID:22184118	SUPPORT	HLA-DQ2 and HLA-DQ8 are strongly predisposing haplotypes for type 1 diabetes (T1D).	This statement specifically mentions HLA-DQ8 as a strong predisposing haplotype for type 1 diabetes, supporting the association with susceptibility.
PMID:26492519	SUPPORT	The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D.	This study identifies the DR4-DQ8 genotype as highly associated with a risk for developing type 1 diabetes, thus supporting the genetic susceptibility.
PMID:34946827	SUPPORT	The combination of HLA-DQA1*03:01 and DQB1*03:02 alleles (summarized as 'HLA-DQ8') is reported to be among the two most prevalent HLA class II haplotypes in Caucasian type 1 diabetes patients.	This reference confirms that HLA-DQ8 is one of the most prevalent haplotypes among type 1 diabetes patients in the studied population, supporting its association with susceptibility.

association

Susceptibility

2

name

INS

evidence

reference	supports	snippet	explanation
PMID:15529622	SUPPORT	Our results indicate an exceptionally strong association of the class I INS-VNTR alleles with T1DM for the Romanian population.	The study presents evidence of a strong association between INS-VNTR alleles of the insulin gene and susceptibility to type 1 diabetes in the Romanian population.
PMID:8934932	SUPPORT	Genetic susceptibility predominantly results from specific alleles in the HLA complex and insulin gene region.	This paper states that genetic susceptibility to insulin-dependent diabetes mellitus predominantly results from specific alleles, including those in the insulin gene region.
PMID:11845220	SUPPORT	However, only within the past decade has it been possible to systematically attempt to identify the genes that increase susceptibility to this disorder using linkage and association analysis of genetic markers distributed across the genome.	This study discusses the identification of susceptibility genes for type 1 diabetes, including the insulin gene.
PMID:11921414	SUPPORT	Because insulin has such a central role in the pathogenesis of both forms of diabetes, the insulin gene (INS) has always been considered a candidate susceptibility gene.	The paper directly states that the insulin gene is considered a candidate susceptibility gene.
PMID:11347740	SUPPORT	The disease-associated INS genotype (Hph I) was identified in 87.5% of the concordant twins but only in 59.5% (P = 0.005) of the discordant twins.	The study demonstrates the presence of a disease-associated INS genotype in a high percentage of concordant twins for type 1 diabetes.
PMID:33483996	SUPPORT	Over half of the genetic risk has been attributed to the human leukocyte antigen (HLA) class II gene region and to the insulin (INS) gene locus.	This article attributes a significant portion of the genetic risk for type 1 diabetes to the insulin (INS) gene locus.

association

Susceptibility

0

name

Viral Infections

evidence

reference	supports	snippet	explanation
PMID:23393684	SUPPORT	One of the environmental risk factors identified by a series of independent studies is represented by viral infection, with strong evidence showing that viruses can indeed infect pancreatic beta cells with consequent effects ranging from functional damage to cell death.	This reference mentions that viral infections are a strong environmental risk factor for Type I Diabetes, affecting pancreatic beta cells which can lead to autoimmunity.
PMID:22891485	PARTIAL	Environmental factors must be involved such as viral infections, toxins from food, cow milk during childhood (instead of breast feeding) or vitamin D deficiency.	This reference suggests that viral infections are among several environmental factors associated with Type I Diabetes, but does not pinpoint them as the singularly most critical factor.
PMID:34942009	SUPPORT	Enteroviruses, especially CoxB and Echo, are most represented.	This reference supports the role of viral infections in Type I Diabetes, mentioning enteroviruses among others.
PMID:18357774	PARTIAL	The most often cited environmental agents implicated as initiators of T1D are the human enteroviruses, in particular the group B coxsackieviruses (CVB).	This reference supports the role of enteroviruses as environmental triggers for Type I Diabetes but notes that evidence is not firmly established.
PMID:24003924	PARTIAL	Enteroviruses are proposed candidate triggers due to temporal correlations between infection and T1D autoimmunity and to detection of viral proteins in diseased islets.	The reference suggests enteroviruses as potential triggers for Type I Diabetes but emphasizes the need for more robust evidence for a causative relationship.
PMID:11334504	SUPPORT	Congenital rubella is the only infection clearly associated with the development of type 1A diabetes.	This reference specifically mentions congenital rubella as an infection clearly associated with Type I Diabetes, supporting the statement.
PMID:31401790	PARTIAL	The natural history of human type 1 diabetes (T1D) and the documented associations between virus infections (in particular the enteroviruses) and disease development.	This reference discusses associations between viral infections, particularly enteroviruses, and Type I Diabetes development, but indicates a need for further studies.
PMID:17691946	SUPPORT	evidence from various animal models suggests that viruses can indeed initiate or accelerate autoimmune diseases, such as type 1 diabetes...	This reference provides evidence from animal models that support the initiation or acceleration of Type I Diabetes by viruses.
PMID:36950864	SUPPORT	Convincing evidence indicates that viruses are associated with T1D development and progression.	This reference provides convincing evidence that viral infections, including SARS-CoV-2, may trigger or unmask Type I Diabetes.

notes

May trigger the autoimmune response in genetically susceptible individuals

1

name

Early Dietary Factors

evidence

reference	supports	snippet	explanation
PMID:8741809	PARTIAL	There is a relationship between early cow's milk exposure and the development of Type 1 diabetes in humans, and between early cow's milk exposure and the development of autoimmune diabetes in rodent models of Type 1 diabetes.	The reference supports early dietary factors such as cow's milk exposure but indicates that the data are insufficient to conclude a causal relationship.
PMID:26605913	NO_EVIDENCE	Recently, the results of two large randomized trials have shown that breastfeeding in general, breastfeeding during gluten introduction, and early or delayed gluten introduction do not influence the total risk of CD in genetically predisposed individuals.	The reference suggests that early or delayed introduction of gluten does not influence the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy, providing no supporting evidence for early dietary factors as risk factors for Type 1 diabetes.
PMID:20640941	PARTIAL	Given that type 1 diabetes, and its preclinical autoimmunity, appear early in life, infant and childhood diet have been implicated as potential initiating exposures in the etiology of the disease.	The reference implicates early dietary factors in the risk of Type 1 diabetes but also highlights inconsistencies and the need for further research.
PMID:21067389	NO_EVIDENCE	There appears to be no evidence for a relationship between infant formula feeding and the risk for type 1 diabetes mellitus.	The reference indicates that there is no evidence supporting the risk of early dietary factors, specifically infant formula, in the development of Type 1 diabetes.
PMID:17203405	PARTIAL	Enteroviruses (especially Coxsackie B virus), breastfeeding, the early presence or lack of certain foods, birth weight, childhood over-nutrition, maternal islet autoimmunity, and negative stress events have been shown to be related to the prevalence of T1D.	The reference supports a link between early dietary factors and Type 1 diabetes but does not provide conclusive evidence.

notes

Possible risk factors include early exposure to cow's milk and gluten

0

name

Insulin Therapy

description

Essential treatment to replace the missing insulin and regulate blood glucose levels.

evidence

reference	supports	snippet	explanation
PMID:21584767	SUPPORT	Insulin therapy is a vital hormone replacement therapy in type 1 diabetes mellitus.	None
PMID:36476434	SUPPORT	The current standard method for type 1 diabetes (T1D) management majorly focuses on controlling blood glucose levels with exogeneous insulin administration.	None
PMID:32342453	SUPPORT	T1DM is caused by absolute lack of insulin secretion, so the current treatment for T1DM patients is exogenous insulin replacement therapy.	None
PMID:20723814	NO_EVIDENCE		The reference lacks specific details pertaining to treatment.
PMID:31426099	PARTIAL	Although a cure for T1D remains the ultimate goal, technology holds the promise of keeping youth with T1D in targeted control and minimize the burden of this chronic medical condition.	The reference acknowledges insulin therapy but focuses more on technological advancements rather than confirming insulin therapy as the essential treatment.
PMID:28685788	PARTIAL	Replacing C-peptide, a hormone normally co-secreted with insulin, has been shown to reduce diabetes-related complications.	This reference discusses auxiliary therapy but does not diminish the essential role of insulin therapy.
PMID:33970586	SUPPORT	The mainstay of management is a regimen of multiple daily injections of insulin or continuous subcutaneous insulin delivered via an insulin pump.	None
PMID:15306833	SUPPORT	Most national bodies have recommended glycaemic targets, with an HbA(1c) to achieve between 6.5 and 7.5%...However, there is, however, a limit to what can be achieved with existing exogenous insulin therapies due to their imperfect pharmacokinetic and pharmacodynamic profiles.	None
PMID:6749365	SUPPORT	Replacement treatment with insulin is potentially capable of normalizing the metabolic abnormalities; and normalization of the metabolic abnormalities can be expected to prevent or ameliorate the complications of the disease.	None
PMID:20666700	PARTIAL	Insulin is the primary medication in the treatment of type 1 diabetes. New therapeutic options and prevention strategies (cellular therapies, immunomodulation and vaccination) aim to preserve residual beta-cell function.	The focus on insulin as primary treatment supports the statement, despite mentioning new therapeutic options.

1

name

Blood Glucose Monitoring

description

Regular monitoring to manage glucose levels effectively.

evidence

reference	supports	snippet	explanation
PMID:30215903	SUPPORT	There is considerable benefit of tight glucose control in patients with type 1 diabetes mellitus. ... Greater frequency of glucose monitoring and continuous glucose monitoring are both associated with lower A1C levels.	The abstract emphasizes the importance of glucose monitoring in managing type 1 diabetes, supporting the statement that regular monitoring is crucial for effective glucose level management.
PMID:32256447	SUPPORT	Regular self-monitoring of blood glucose levels, and ketones when indicated, is an essential component of type 1 diabetes (T1D) management.	The abstract reaffirms that regular monitoring of blood glucose is essential for managing type 1 diabetes, supporting the statement.
PMID:38551884	SUPPORT	Blood glucose monitoring has been an integral part of diabetes treatment for many years, whether for type 1 diabetic patients on multiple daily injections of insulin, insulin pumps or artificial pancreas, and now for patients with type 2 diabetes...	The abstract describes blood glucose monitoring as a cornerstone in diabetes treatment, which includes the management of type 1 diabetes, thus supporting the statement.
PMID:11149158	SUPPORT	Sick-day management requires increased monitoring of blood glucose and assessment for ketosis.	The abstract highlights that during illness, increased blood glucose monitoring is necessary for managing type 1 diabetes, further supporting the statement about regular monitoring.

2

name

Lifestyle Modifications

description

Maintaining a balanced diet, regular physical activity, and adherence to treatment plans.

evidence

reference	supports	snippet	explanation
PMID:9314011	SUPPORT	Nutrition therapy and physical activity can assist persons with diabetes to achieve metabolic goals. Several lifestyle strategies can be used.	The text supports the assertion that maintaining a balanced diet and regular physical activity can assist in managing diabetes through lifestyle modifications.
PMID:16529680	SUPPORT	The patient and physician must work together to optimize glucose control involving both insulin administration and caloric intake. Exercise has numerous benefits and the type 1 diabetic should take advantage of these benefits.	This supports the statement that lifestyle modifications, including diet and physical activity, are important in managing type 1 diabetes.
PMID:24485215	SUPPORT	Poor lifestyle habits (poor diet quality, sedentary behaviours and smoking) are known to be driving factors for increased CMR factors in the general population.	The text underlines the significance of maintaining a good lifestyle, including a balanced diet and physical activity, as part of diabetes management.
PMID:32312302	SUPPORT	Innovative, cost-effective interventions along with beneficial lifestyle modifications can improve home-based self-monitoring of blood glucose in T1D patients.	This reference highlights the role of lifestyle modifications in managing type 1 diabetes through controlling blood glucose levels.
PMID:37820077	SUPPORT	Weight loss treatments provide a wide-range of benefits in reducing both morbidity and mortality in those who are obese.	It mentions lifestyle interventions as a part of weight loss treatments that benefit T1D management, highlighting their efficacy and safety.