Type 1 diabetes

May combine two claims.

Recent data suggest that although most patients with longstanding type 1 diabetes have few β cells, if any, there is evidence for β-cell regeneration in infants and very young children, but not in adolescents or adults.

“Recent data suggest that although most patients with longstanding type 1 diabetes have few β cells, if any, there is evidence for β-cell regeneration in infants and very young children (but not in adolescents or adults).51,52”

• cites [51] Gregg, 2012, Formation of a human beta-cell population within pancreatic islets is set early in life, J Clin Endocrinol Metab sourcePartly supported

  The paper reports a burst of β-cell proliferation in the first two years of normal life, with little growth thereafter (Abstract; page unavailable). It does not establish regeneration in patients with longstanding type 1 diabetes or address how many β cells those patients retain. It also reports rare β-cell neogenesis in adolescents and adults, so the claim’s categorical exclusion of those ages is not supported. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [52] Keenan, 2010, Residual insulin production and pancreatic ß-cell turnover after 50 years of diabetes: Joslin Medalist Study, Diabetes sourceDisputed

  The Discussion (page unavailable in our copy) says β-cells can be replenished despite prolonged autoimmune stress and reports evidence of β-cell proliferation in people with type 1 diabetes for over 50 years. That is contrary to the claim that regeneration does not occur in adults. The paper does not establish the claimed contrast with infants and very young children. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Type 1 diabetes is one of the most common chronic diseases of childhood.

“Although type 1 diabetes can be diagnosed at any age, it is one of the most common chronic diseases of childhood.4”

• cites [4] Gale, 2005, Type 1 diabetes in the young: the harvest of sorrow goes on, Diabetologia sourceCould not verify

  The paper’s main text (page unavailable) discusses childhood-onset type 1 diabetes and reports rising incidence in Europe. It does not say whether type 1 diabetes is among the most common chronic diseases of childhood; searches for that phrase and for childhood disease prevalence found no comparison with other diseases. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

May combine two claims.

Not all patients with type 1 diabetes have immunological characteristics, leading to proposed classifications of type 1A (autoimmune) diabetes and type 1B (idiopathic) diabetes.

“However, not all patients with type 1 diabetes have these characteristics, leading to proposed classifications of type 1A (autoimmune) diabetes,41 for the 70–90% of patients with type 1 disease that have immunological, self-reactive autoantibodies, and type 1B (idiopathic) diabetes, representing the remainder whose specific pathogenesis remains unclear.42”

• cites [41] Eisenbarth, 2007, Update in type 1 diabetes, J Clin Endocrinol Metab sourceSupported
• cites [42] Gianani, 2010, Dimorphic histopathology of long-standing childhood-onset diabetes, Diabetologia sourcePartly supported

  The Introduction reports that about 15% of children presenting with new-onset diabetes produce no islet autoantibodies, and the Discussion says the causes of some other forms of childhood-onset diabetes need further study. The paper does not identify this entire remainder as type 1B (idiopathic) diabetes; it also discusses other possible forms, including type 2 and monogenic diabetes. No page numbers are available in our copy. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Age at symptomatic onset of type 1 diabetes is no longer a restricting factor.

“Historically, type 1 diabetes was largely considered a disorder in children and adolescents, but this opinion has changed over the past decade, so that age at symptomatic onset is no longer a restricting factor.3”

• cites [3] Leslie, 2010, Predicting adult-onset autoimmune diabetes: clarity from complexity, Diabetes sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

A 2011 study of adult-onset type 1 diabetes suggested that autoimmune type 1 diabetes in children and adults differs by just a few age-dependent genetic effects.

“A 2011 study of adult-onset type 1 diabetes suggested that autoimmune type 1 diabetes in children and adults differs by just a few age-dependent genetic effects;48”

• cites [48] Howson, 2011, Genetic analysis of adult-onset autoimmune diabetes, Diabetes sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

In 2009, the American Diabetes Association modified their guidelines for diabetes diagnosis to include glycated haemoglobin (HbA1C) of 6·5% or higher.

“In 2009, the American Diabetes Association modified their guidelines for diabetes diagnosis to include glycated haemoglobin (HbA1C; a test that averages blood glucose concentrations over 3 months) of 6·5% or higher.35”

• cites [35] 2009, International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes, Diabetes Care sourcePartly supported

  The Recommendations and conclusions section recommends diagnosing diabetes at A1C ≥6.5%. But the opening section says the report represents the International Expert Committee’s views, not necessarily those of the American Diabetes Association, and invites professional organizations to consider its recommendations. It does not establish that the ADA modified its guidelines in 2009. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

If 5-15% of adults diagnosed with type 2 diabetes actually have type 1 disease, perhaps as many as 50% of actual type 1 diabetes cases are misdiagnosed as type 2, meaning that the number of cases of type 1 disease is vastly underestimated.

“if this is the case, perhaps as many as 50% of actual type 1 diabetes cases are misdiagnosed as type 2, meaning that the number of cases of type 1 disease is vastly underestimated.”

• cites [36] Tuomi, 2005, Type 1 and type 2 diabetes: what do they have in common?, Diabetes sourcePartly supported

  The ‘Latent Autoimmune Diabetes in Adults’ section (pp. S40–S45) reports LADA in some adults diagnosed with type 2 diabetes, including prevalence estimates of 4.2–13.2% in specified Caucasian populations. It does not estimate that 50% of actual type 1 cases are diagnosed as type 2 or conclude that type 1 case counts are vastly underestimated. Its discussion also treats LADA as heterogeneous, rather than equating every LADA case with type 1 diabetes. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Incidence of type 1 diabetes in Estonia is less than one-third of the incidence in Finland, although the two countries are separated by less than 120 km.

“For example, incidence in Estonia is less than one-third of the incidence in Finland, although the two countries are separated by less than 120 km.17”

• cites [17] Podar, 2001, Increasing incidence of childhood-onset type I diabetes in 3 Baltic countries and Finland 1983–1998, Diabetologia sourcePartly supported

  The Results report mean childhood-onset type 1 diabetes incidence of 11.2 in Estonia and 37.7 in Finland during 1983–1998, making Estonia’s rate less than one-third of Finland’s. The passages found do not state that the countries are separated by less than 120 km. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Both the concept of autoimmune destruction and the concept that remaining β cells are incapable of regeneration have been debated.

“Both of these concepts of pathogenesis of type 1 diabetes have been debated.50,51”

• cites [50] Butler, 2007, The replication of beta cells in normal physiology, in disease and for therapy, Nat Clin Pract Endocrinol Metab sourceNot checked — no full text of the source
• cites [51] Gregg, 2012, Formation of a human beta-cell population within pancreatic islets is set early in life, J Clin Endocrinol Metab sourcePartly supported

  The passage labeled Abstract (page unavailable) reports occasional β-cell neogenesis in adults, which bears on the idea that β cells cannot regenerate. But the study examined normal human pancreases, not remaining β cells in type 1 diabetes, and our copy does not address whether autoimmune destruction is debated. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

May combine two claims.

Genetic changes or more children being born from mothers with type 1 diabetes cannot solely explain the rapid rates of increased incidence of type 1 diabetes.

“Genetic changes or more children being born from mothers with type 1 diabetes cannot solely explain such rapid rates of increased incidence.22”

• cites [22] Soltesz, 2007, Worldwide childhood type 1 diabetes incidence—what can we learn from epidemiology?, Pediatr Diabetes sourcePartly supported

  The 'Temporal trends in incidence' section reports rising childhood type 1 diabetes incidence, and 'Childhood type 1 diabetes' offers environmental and lifestyle factors as potential explanations. This supports the broader point that genetics alone need not explain the increase, but the paper does not address whether an increase in births to mothers with type 1 diabetes could explain it. Page numbers were unavailable in our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In many countries, the rise in incidence of type 1 diabetes has fluctuated, although Sweden has recently seen incidence rates plateau.

“In many countries, the rise in incidence of type 1 diabetes has fluctuated, although Sweden has recently seen incidence rates plateau.12”

• cites [12] Berhan, 2011, Thirty years of prospective nationwide incidence of childhood type 1 diabetes: the accelerating increase by time tends to level off in Sweden, Diabetes sourcePartly supported

  The Results (Generalized additive models; page unavailable) report that Swedish childhood type 1 diabetes incidence leveled off during the last seven years studied. The paper also describes rising incidence in many countries and short-term variation, but it does not establish that the rise fluctuated in many countries. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Type 1 diabetes is generally thought to be precipitated by an immune-associated, if not directly immune-mediated, destruction of insulin-producing pancreatic β cells.

“Type 1 diabetes is generally thought to be precipitated by an immune-associated, if not directly immune-mediated, destruction of insulin-producing pancreatic β cells.1,2”

• cites [1] Todd, 2010, Etiology of type 1 diabetes, Immunity sourceSupported
• cites [2] Bluestone, 2010, Genetics, pathogenesis and clinical interventions in type 1 diabetes, Nature sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Type 1B (idiopathic) diabetes represents the remainder of type 1 diabetes cases whose specific pathogenesis remains unclear.

“and type 1B (idiopathic) diabetes, representing the remainder whose specific pathogenesis remains unclear.42”

• cites [42] Gianani, 2010, Dimorphic histopathology of long-standing childhood-onset diabetes, Diabetologia sourcePartly supported

  The Introduction (page unavailable) says most childhood-onset diabetes is immune-mediated type 1A and identifies other, less well-characterised forms. The Discussion (page unavailable) calls for further study of the causes of a distinct histological pattern. Neither passage identifies those cases as type 1B (idiopathic) or says they constitute the remainder of type 1 diabetes cases. (LLM, conf=0.79)

  Experimental — accuracy not yet measured

May combine two claims.

Increases in incidence of type 1 diabetes have not occurred equally across all age groups; in Europe, the most substantial increases have been in children younger than 5 years of age.

“Increases in incidence have not occurred equally across all age groups; in Europe, the most substantial increases have been noted in children younger than 5 years of age.5,21”

• cites [5] Harjutsalo, 2008, Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study, Lancet sourceNot checked — no full text of the source
• cites [21] 2006, Incidence and trends of childhood type 1 diabetes worldwide 1990–1999, Diabet Med sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Type 1 diabetes is most common in Finland (>60 cases per 100 000 people each year) and Sardinia (around 40 cases per 100 000 people each year).

“Type 1 diabetes is most common in Finland (>60 cases per 100 000 people each year) and Sardinia (around 40 cases per 100 000 people each year).16”

• cites [16] Patterson, 2009, Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study, Lancet sourcePartly supported

  The Results table (page not available in our copy) shows high childhood type 1 diabetes incidence in two Finnish regions, but its highest reported rate is 52.6 per 100,000, not over 60. The paper does not report a rate for Sardinia, and its rates concern children aged 0–14 rather than people of all ages. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Subtypes of type 2 diabetes in children are poorly characterised, particularly in minority populations in the USA.

“similarly, subtypes of type 2 diabetes in children are poorly characterised, particularly in minority populations in the USA.44”

• cites [44] Dabelea, 2007, Incidence of diabetes in youth in the United States, JAMA sourcePartly supported

  The Comment section reports that some US youth clinically diagnosed with type 2 diabetes had positive autoantibodies and says their role among minority youth requires further exploration. This supports uncertainty about one aspect of type 2 diabetes in minority children, but does not establish the broader claim that its subtypes generally are poorly characterised. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

Other factors that complicate diagnosis of type 1 diabetes include the growing problem of obesity, difficulties in health-care provider recognition of disease, and increasingly diverse genetic admixtures due to migration and social changes.

“Other factors that complicate diagnosis of type 1 diabetes include the growing problem of obesity (both childhood and adult), difficulties in health-care provider recognition of disease, and increasingly diverse genetic admixtures due to migration and social changes.45–47”

• cites [45] Wilkin, 2009, The accelerator hypothesis: a review of the evidence for insulin resistance as the basis for type I as well as type II diabetes, Int J Obes (Lond) sourceNot checked — no full text of the source
• cites [46] Soderstrom, 2012, Being born in Sweden increases the risk for type 1 diabetes—a study of migration of children to Sweden as a natural experiment, Acta Paediatr sourceNot checked — no full text of the source
• cites [47] Puett, 2012, Neighborhood context and incidence of type 1 diabetes: the SEARCH for Diabetes in Youth study, Health Place sourceCould not verify

  The Introduction discusses type 1 diabetes incidence, genetics and environmental factors, while the Study design describes how cases were identified and validated; neither addresses obstacles to diagnosis. Searches for obesity, provider recognition and genetic admixture due to migration found no passage linking them to diagnostic difficulty in our copy. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

A plethora of environmental influences have been purported to affect the epidemiology of type 1 diabetes, with infant and adolescent diets, vitamin D and vitamin D pathway constituents, and viruses receiving the most focus.

“A plethora of environmental influences have been purported to affect the epidemiology of type 1 diabetes,25 with infant and adolescent diets,26 vitamin D and vitamin D pathway constituents,27–29 and viruses receiving the most focus.30,31”

• cites [25] Maclaren, 1992, Is insulin-dependent diabetes mellitus environmentally induced?, N Engl J Med sourceNot checked — no full text of the source
• cites [26] Knip, 2010, Infant feeding and the risk of type 1 diabetes, Am J Clin Nutr sourceNot checked — no full text of the source
• cites [27] Svoren, 2009, Significant vitamin D deficiency in youth with type 1 diabetes mellitus, J Pediatr sourcePartly supported

  The Methods and Results (page unavailable) show that this study measured vitamin D status in youth who already had type 1 diabetes, supporting vitamin D as a topic of research in this population. It does not examine whether vitamin D or its pathway constituents influence the incidence or epidemiology of type 1 diabetes; the diet and virus portions have separate citations. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [28] Blanton, 2011, Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes, Diabetes sourceSupported
• cites [29] Cooper, 2011, Inherited variation in vitamin D genes is associated with predisposition to autoimmune disease type 1 diabetes, Diabetes sourceSupported

May combine two claims.

Disease heterogeneity is an important aspect of type 1 diabetes, and suggests a role for genetics, age at disease onset, and intensity of disease management on the ability to retain β-cell function.

“Thus, disease hetero geneity is an important asp of type 1 diabetes, and suggests a role for genetics, age at disease onset, and intensity of disease management on the ability to retain β-cell”

• cites [84] Keenan, 2010, Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study, Diabetes sourcePartly supported

  The Results and Discussion (page unavailable in our copy) show substantial variation in residual C-peptide and associate higher levels with HLA genotype, later age at onset, and better glycemic control. They do not assess the intensity of disease management or establish that management intensity affects retention of β-cell function; glycemic control is not the same measure. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In Mozambique, the life expectancy for a newly diagnosed child with type 1 diabetes is 7 months.

“For example, in Mozambique, the life expectancy for a newly diagnosed child with type 1 diabetes is 7 months.123”

• cites [123] Beran, 2005, Access to care for patients with insulin-requiring diabetes in developing countries: case studies of Mozambique and Zambia, Diabetes Care sourcePartly supported

  In “Estimates of prevalence and prognosis” (Table 2; page not specified), the paper estimates 0.6 years—about seven months—for a child aged 0–14 with insulin-requiring diabetes in rural Mozambique. The claim omits the rural restriction: the paper’s national estimate for that age group is 3.5 years. The table also does not specify newly diagnosed children with type 1 diabetes. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

These autoantibodies can appear as early as 6 months of age, with a peak incidence before 2 years of age in genetically susceptible individuals; thus, they are present months to years before symptomatic onset.

“These autoantibodies can appear as early as 6 months of age, with a peak incidence before 2 years of age in genetically susceptible individuals;66 thus, they are present months to years before symptomatic onset.”

• cites [66] Ziegler, 2012, Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes, Diabetologia sourcePartly supported

  The Results and Discussion report peak autoantibody incidence from 9 months to 2 years in genetically at-risk children. The claim that autoantibodies can appear as early as 6 months is not established by this study: the Discussion reports no seroconversion at 3 or 6 months in the BABYDIET cohort, while cautioning that its size cannot rule out occurrence then. The citation precedes the sentence’s concluding inference about symptomatic onset, so that inference is not part of the attributed claim. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

A trial comparing a sensor-augmented pump with multiple daily injection therapy showed significant improvement in HbA1C reduction with less hypoglycaemia in the sensor-augmented pump cohort.

“A trial comparing a sensor-augmented pump with multiple daily injection therapy showed significant improvement in HbA1C reduction with less hypoglycaemia in the sensor-augmented pump cohort.88,94”

• cites [88] Bergenstal, 2010, Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes, N Engl J Med sourcePartly supported

  The Results report a significantly greater HbA1c reduction with sensor-augmented pump therapy. But the Adverse Events section says hypoglycemia measures were similar between groups, and the Results report no significant difference in severe hypoglycemia rates; the claim of less hypoglycaemia is not supported. Page numbers were unavailable in our copy. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [94] 2011, Sensor-augmented pump therapy for A1C reduction (STAR 3) study: results from the 6-month continuation phase, Diabetes Care sourcePartly supported

  The Abstract Conclusions report greater A1C reductions with sensor-augmented pump therapy than with multiple daily injections. The Results do not support the claim of less hypoglycaemia: in the continuation phase, severe hypoglycaemia rates were not significantly different between the continuing-pump and crossover groups. Our copy does not establish a lower hypoglycaemia rate for the pump cohort versus the injection cohort. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

A study in Finland identified 230 infants with a first-degree relative with type 1 diabetes, and randomly assigned infants to receive a hydrolysed infant formula or conventional formula whenever breast milk was not available during the first 6-8 months of life.

“A study in Finland128 identified 230 infants with a first-degree relative with type 1 diabetes, and randomly assigned infants to receive a hydrolysed infant formula or conventional formula whenever breast milk was not available during the first 6–8 months of life.”

• cites [128] Knip, 2010, Dietary intervention in infancy and later signs of beta-cell autoimmunity, N Engl J Med sourceSupported

May combine two claims.

When comparing the safety and efficacy of overnight closed-loop delivery of insulin with conventional insulin-pump therapy in adults with type 1 diabetes, closed-loop delivery improved overnight control of glycaemia and reduced the risk of nocturnal hypoglycaemia.

“when comparing the safety and efficacy of overnight closed-loop delivery of insulin with conventional insulin-pump therapy in adults with type 1 diabetes, closed-loop delivery improved overnight control of glycaemia and reduced the risk of nocturnal hypoglycaemia.98,99”

• cites [98] Garg, 2012, Reduction in duration of hypoglycemia by automatic suspension of insulin delivery: the in-clinic ASPIRE study, Diabetes Technol Ther sourceNot checked — no full text of the source
• cites [99] Buckingham, 2010, Prevention of nocturnal hypoglycemia using predictive alarm algorithms and insulin pump suspension, Diabetes Care sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Lipid and metabolite profiles can serve as markers for impending type 1 diabetes; these markers include decreased phosphatidylcholine at birth, and reduced triglycerides and antioxidant ether phospholipids followed by increased proinflammatory lysophosphatidylcholine several months before seroconversion to autoantibody positivity.

“Lipid and metabolite profiles can also serve as markers for impending type 1 diabetes; these markers include decreased phosphatidylcholine at birth, and reduced triglycerides and antioxidant ether phospholipids followed by increased proinflammatory lysophosphatidylcholine several months before seroconversion to auto antibody positivity.70”

• cites [70] Oresic, 2008, Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes, J Exp Med sourceSupported

May combine two claims.

A randomised controlled trial in adults with type 1 diabetes reported lower HbA1C concentrations with sensor-augmented pump therapy than with injection therapy, and a greater proportion of patients reaching the targeted levels of HbA1C.

“A randomised controlled trial in adults with type 1 diabetes reported lower HbA1C concentrations with sensor-augmented pump therapy than with injection therapy, and a greater proportion of patients reaching the targeted levels of HbA1C.88”

• cites [88] Bergenstal, 2010, Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes, N Engl J Med sourceSupported

May combine two claims.

Metabolic changes in the natural history of type 1 diabetes are marked by decreased early C-peptide response at least 2 years before onset, increased glucose fluctuations as an individual approaches onset, and an overall linear rise, with a last-minute surge, in plasma glucose in the months before onset.

“Metabolic changes in the natural history of type 1 diabetes are marked by decreased early C-peptide response at least 2 years before onset,80 increased glucose fluctuations as an individual approaches onset,81 and an overall linear rise, with a last-minute surge, in plasma glucose in”

• cites [80] Sosenko, 2010, Trends of earlier and later responses of C-peptide to oral glucose challenges with progression to type 1 diabetes in diabetes prevention trial-type 1 participants, Diabetes Care sourcePartly supported

  Split into 3 atoms — 1 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [81] Sosenko, 2010, Glucose excursions between states of glycemia with progression to type 1 diabetes in the diabetes prevention trial-type 1 (DPT-1), Diabetes sourceSupported
• cites [82] Ferrannini, 2010, Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset, Diabetes sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

HLA class II show the strongest association with type 1 diabetes, where haplotypes DRB1*0401-DQB1*0302 and DRB1*0301-DQB1*0201 confer the greatest susceptibility, and DRB1*1501 and DQA1*0102-DQB1*0602 provide disease resistance.

“Of the many HLA types, HLA class II show the strongest association with type 1 diabetes, where haplotypes DRB1*0401-DQB1*0302 and DRB1*0301-DQB1*0201 confer the greatest susceptibility, and DRB1*1501 and DQA1*0102-DQB1*0602 provide disease resistance.74”

• cites [74] Erlich, 2008, HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families, Diabetes sourcePartly supported

  The Results (page not provided) place both named susceptibility haplotypes among the most susceptible and identify DRB1*1501-DQA1*0102-DQB1*0602 as highly protective. But DRB1*0405-DQA1*0301-DQB1*0302 has a higher reported odds ratio than either named susceptibility haplotype, so the claim that those two confer the greatest susceptibility overstates the risk ranking. The passages also do not compare the strength of class II associations with other HLA classes. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Leptin might benefit type 1 diabetes therapy via its ability to reverse a catabolic state through suppression of hyperglucagonaemia.

“Leptin, the adipocyte hormone, might also benefit type 1 diabetes therapy via its ability to reverse a catabolic state through suppression of hypergluca-gonaemia.103”

• cites [103] Oral, 2012, Leptin for type 1 diabetes: coming onto stage to be (or not?), Pediatr Diabetes sourceSupported

May combine two claims.

GLP-1 might prove beneficial, with studies noting that this incretin decreased peak postprandial glucose by 45% regardless of residual β-cell function.

“GLP-1 might also prove beneficial, with studies noting that this incretin decreased peak postprandial glucose by 45% regardless of residual β-cell function.101”

• cites [101] Kielgast, 2011, Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual beta-cell function, Diabetes sourceSupported

May combine two claims.

Not all individuals with anti-β-cell autoimmunity progress to overt disease; less than 5% who express a single type 1 diabetes-associated autoantibody progress.

“Not all individuals with anti-β-cell autoimmunity progress to overt disease (less than 5% who express a single type 1 diabetes-associated autoantibody progress41), for reasons unknown.”

• cites [41] Eisenbarth, 2007, Update in type 1 diabetes, J Clin Endocrinol Metab sourcePartly supported

  The Prediction section (page unavailable) says that having at least two islet autoantibodies is highly predictive of progression, supporting the distinction between autoantibody expression and overt diabetes. It does not give a progression rate for people with a single autoantibody, so the claimed figure of less than 5% is unsupported. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Two studies have provided cost estimates specifically for type 1 diabetes, proposing an annual figure of $14·4-14·9 billion in the USA.

“However, two studies have provided cost estimates specifically for type 1 diabetes, proposing an annual figure of $14·4–14·9 billion in the USA.104,105”

• cites [104] Dall, 2009, Distinguishing the economic costs associated with type 1 and type 2 diabetes, Popul Health Manag sourceNot checked — no full text of the source
• cites [105] Tao, 2010, Estimating the cost of type 1 diabetes in the US: a propensity score matching method, PLoS One sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

A recent report found that after myocardial infarction, patients with type 1 diabetes express antibodies to cardiac proteins, whereas patients with type 2 diabetes do not.

“a finding that might be explained by a recent report that, after myocardial infarction, patients with type 1 diabetes express antibodies to cardiac proteins, whereas patients with type 2 diabetes do not.111”

• cites [111] Gottumukkala, 2012, Myocardial infarction triggers chronic cardiac autoimmunity in type 1 diabetes, Sci Transl Med sourcePartly supported

  The Results section ('Discovery of a PIA syndrome in human T1D patients'; page not provided) reports cardiac autoantibodies in 15/18 post-MI patients with type 1 diabetes, supporting that part of the claim. It also reports them in 3/20 post-MI patients with type 2 diabetes, so the assertion that those patients do not express such antibodies is too absolute. (LLM, conf=0.92)

  Experimental — accuracy not yet measured

May combine two claims.

Although it is often stated that symptoms occur when 90-95% of β cells are lost, diagnosis of type 1 diabetes can occur when roughly two-thirds of the islets are devoid of insulin-producing cells.

“Although it is often stated that symptoms occur when 90–95% of β cells are lost, diagnosis of type 1 diabetes can occur when roughly two-thirds of the islets are devoid of insulin-producing cells.61,62”

• cites [61] Foulis, 1984, The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue, Diabetologia sourcePartly supported

  The Patients section says nine children died within 24 hours of diagnosis, and the Results and Discussion report many insulin-deficient islets in their pancreases. But the available Table 1 text does not provide usable counts, and no passage establishes that roughly two-thirds of islets lacked insulin-producing cells at diagnosis. The Discussion’s separate “two-thirds” figure describes the A-cell composition of insulin-deficient islets, not the proportion of islets affected. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [62] Willcox, 2009, Analysis of islet inflammation in human type 1 diabetes, Clin Exp Immunol sourceNot checked — no full text of the source

May combine two claims.

Pramlintide has been shown to reduce postprandial hyperglycaemia, bodyweight, insulin dosage, and HbA1C concentrations, and to reduce postprandial glucagon and glucose excursions and slow gastric emptying.

“The hormone pramlintide has been shown to reduce postprandial hyperglycaemia, bodyweight, insulin dosage, and HbA1C concentrations, and to reduce postprandial glucagon and glucose excursions and slow gastric emptying.102”

• cites [102] Ryan, 2009, Review of pramlintide as adjunctive therapy in treatment of type 1 and type 2 diabetes, Drug Des Devel Ther sourceSupported

May combine two claims.

Although endogenous insulin secretion is typically low, maintenance is important since it is associated with less retinopathy and less severe hypoglycaemia at later stages of the disease.

“Although this endogenous secretion is typically low, maintenance is important since it is associated with less retinopathy and less severe hypoglycaemia at later stages of the disease.86”

• cites [86] Steffes, 2003, Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial, Diabetes Care sourcePartly supported

  The paper reports that sustained C-peptide (and thus insulin) secretion was associated with less retinopathy and fewer episodes of severe hypoglycemia in DCCT participants with type 1 diabetes (p. 1). It does not establish those associations specifically at later stages of disease; its discussion notes that most patients eventually lose β-cell function (p. 4). (LLM, conf=0.80)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Individuals with type 1 diabetes have a ten-times higher risk for cardiovascular events than age-matched non-diabetic populations.

“Individuals with type 1 diabetes have a ten-times higher risk for cardiovascular events (eg, myocardial infarction, stroke, angina, and the need for coronary-artery revascularisation) than age-matched non-diabetic populations.107”

• cites [107] Orchard, 2006, Type 1 diabetes and coronary artery disease, Diabetes Care sourcePartly supported

  In “The Magnitude of the Problem” (page not available), the review reports a tenfold or greater increase in coronary heart disease mortality compared with U.S. national data. It also reports elevated coronary-event rates in people with type 1 diabetes, but does not establish a tenfold risk for the broader set of cardiovascular events listed in the citing sentence compared with age-matched people without diabetes. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

This mechanism might help explain the differing rates of progression to type 1 diabetes in adults versus children, where only minor variations in genetic susceptibility have been noted.

“This mechanism might help explain the differing rates of progression to type 1 diabetes in adults versus children, where only minor variations in genetic susceptibility have been noted.48”

• cites [48] Howson, 2011, Genetic analysis of adult-onset autoimmune diabetes, Diabetes sourceSupported

May combine two claims.

Islet-cell transplantation depends on overcoming recurrent autoimmunity and averting alloimmunity.

“Similarly, islet-cell transplantation depends on overcoming recurrent autoimmunity and averting alloimmunity.153”

• cites [153] Vendrame, 2010, Recurrence of type 1 diabetes after simultaneous pancreas-kidney transplantation, despite immunosuppression, is associated with autoantibodies and pathogenic autoreactive CD4 T-cells, Diabetes sourcePartly supported

  The Conclusions and Discussion describe recurrent autoimmunity as a cause of graft loss despite immunosuppression. The Results also document rejection of a second pancreas graft, supporting the need to avert alloimmune rejection. However, the patients received pancreas-kidney transplants, not islet-cell transplants, so the claim extends the clinical finding to a different transplant setting. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Islet transplantation remains an experimental procedure, with ongoing research focusing on new methods using biomaterials, immune modulation, site of delivery, improved vascularisation, and more.

“Therefore, islet transplantation remains an experimental procedure, with ongoing research focusing on new methods using biomaterials (eg, encapsulation), immune modulation, site of delivery, improved vascularisation, and more.151”

• cites [151] Gibly, 2011, Advancing islet transplantation: from engraftment to the immune response, Diabetologia sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Despite decades of investigation, the mechanisms by which β cells are eliminated or selectively destroyed (apart from antigen-specific immune responses) remain unclear.

“Despite decades of investigation, the mechanisms by which β cells are eliminated or selectively destroyed (apart from antigen-specific immune responses) remain unclear.55”

• cites [55] Atkinson, 2011, How does type 1 diabetes develop?: the notion of homicide or beta-cell suicide revisited, Diabetes sourcePartly supported

  The section on β-cell ‘suicide’ describes several possible contributors to selective destruction, including cytokine sensitivity and ER stress, while the section on immune-mediated destruction says multiple elimination pathways may operate together. The paper supports the idea that the process is not fully resolved, but it does not say that mechanisms apart from antigen-specific immune responses are simply unknown. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In the past 5 years, interest in reversal of type 1 diabetes has grown.

“In the past 5 years, interest in reversal of type 1 diabetes has grown.134”

• cites [134] Greenbaum, 2011, Persistence is the twin sister of excellence: an important lesson for attempts to prevent and reverse type 1 diabetes, Diabetes sourcePartly supported

  The main text (page unavailable) describes expanding therapeutic approaches and pharmaceutical involvement, and Table 1 lists large trials seeking to reverse type 1 diabetes. This supports growing interest, but the paper describes developments over roughly a decade rather than establishing the claimed five-year period. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

To achieve progress with islet-cell transplantation, investigators are focusing on xenotransplantation, encapsulation, novel sites for cell delivery, and development of surrogate insulin-producing cells.

“To achieve progress with islet-cell transplantation, investigators are focusing on xenotransplantation, encapsulation, novel sites for cell delivery (eg, eye), and development of surrogate insulin-producing cells.151”

• cites [151] Gibly, 2011, Advancing islet transplantation: from engraftment to the immune response, Diabetologia sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The terms type 1A and type 1B diabetes are not commonly used.

“Despite knowledge gains that could allow for adopting this new set of terminologies for subgrouping cases of type 1 diabetes, the terms type 1A and type 1B diabetes are not commonly used;”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Diagnosis of diabetes has historically included fasting blood glucose higher than 7 mmol/L (126 mg/dL), any blood glucose of 11·1 mmol/L (200 mg/dL) or higher with symptoms of hyperglycaemia, or an abnormal 2-hour glucose-tolerance test.

“Diagnosis of diabetes has historically included fasting blood glucose higher than 7 mmol/L (126 mg/dL), any blood glucose of 11·1 mmol/L (200 mg/dL) or higher with symptoms of hyperglycaemia, or an abnormal 2 horal glucose-tolerance test.34”

• cites [34] 2012, Diagnosis and classification of diabetes mellitus, Diabetes CareNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly regarding disease prediction and heterogeneity, pancreatic pathology, and epidemiology.

“Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly with regard to disease prediction and heterogeneity, pancreatic pathology, and epidemiology.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Despite efforts to standardise diagnosis of type 1 diabetes, the causes and typology remain unclear.

“Despite efforts to standardise diagnosis of type 1 diagnosis, the causes and typology remain unclear.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Another dogma is that in patients with longstanding type 1 diabetes, the pancreas is devoid of insulin-producing cells and the remaining β cells are incapable of regeneration.

“Another dogma is that in patients with longstanding disease, the pancreas is devoid of insulin-producing cells and the remaining β cells are incapable of regeneration.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Globally, the quality of diabetes management remains uneven.

“and, globally, the quality of diabetes management remains uneven.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage lifelong insulin administration.

“Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage the challenge of lifelong insulin administration.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

An immediate need for exogenous insulin replacement is a hallmark of type 1 diabetes, for which lifetime treatment is needed.

“An immediate need for exogenous insulin replacement is also a hallmark of type 1 diabetes, for which lifetime treatment is needed.”

May combine two claims.

The incidence of type 1 diabetes varies with seasonal changes and birth month.

“The incidence of type 1 diabetes varies with seasonal changes and birth month.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Type 1 diabetes is uncommon in China, India, and Venezuela (around 0·1 cases per 100 000 people each year).

“By contrast, the disorder is uncommon in China, India, and Venezuela (around 0·1 cases per 100 000 people each year).”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Polydipsia, polyphagia, and polyuria along with overt hyperglycaemia remain diagnostic hallmarks in children and adolescents, and to a lesser extent in adults.

“Polydipsia, polyphagia, and polyuria (the classic trio of symptoms associated with disease onset) along with overt hyperglycaemia remain diagnostic hallmarks in children and adolescents, and to a lesser extent in adults.”

Classified as probably not a substantial claim.

No means for preventing or curing type 1 diabetes exists.

“However, despite broad organisational, intellectual, and fiscal investments, no means for preventing or curing type 1 diabetes exists”

May combine two claims.

Most cases of type 1 diabetes represent an immune, if not autoimmune-mediated disorder, meaning patients often show features of an immunological contribution to disease pathogenesis.

“Most cases of type 1 diabetes represent an immune, if not autoimmune-mediated disorder, meaning patients often show features of an immunological contribution to disease pathogenesis (eg, autoantibodies or genetic associations with genes controlling immune responses).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Type 1 diabetes is slightly more common in boys and men.

“Whereas most autoimmune disorders disproportionately affect women, type 1 diabetes is slightly more common in boys and men.6”

• cites [6] Ostman, 2008, Gender differences and temporal variation in the incidence of type 1 diabetes: results of 8012 cases in the nationwide Diabetes Incidence Study in Sweden 1983–2002, J Intern Med sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Type 1 diabetes can be diagnosed at any age.

“Although type 1 diabetes can be diagnosed at any age, it is one of the most common chronic diseases of childhood.4”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Agents that show promise for averting debilitating disease-associated complications have been identified.

“Agents that show promise for averting debilitating disease-associated complications have also been identified.”

May combine two claims.

CD8+ T cells are the most predominant population within the insulitis lesion, followed by macrophages (CD68+), CD4+ T cells, B lymphocytes (CD20+), and plasma cells (CD138+).

“In terms of potential pathogenic mechanisms, CD8+ T cells are the most predominant population within the insulitis lesion, followed by (in declining order) macrophages (CD68+), CD4+ T cells, B lymphocytes (CD20+), and plasma cells (CD138+).62”

• cites [62] Willcox, 2009, Analysis of islet inflammation in human type 1 diabetes, Clin Exp Immunol sourceNot checked — no full text of the source

May combine two claims.

Insulin degludec might improve basal insulin administration in patients with type 1 diabetes, since it provides effective glycaemic control and reduces the risk of nocturnal hypoglycaemia.

“Examples include insulin degludec (recently approved for use in the EU, although approval declined by the US Food and Drug Administration), an analogue that might improve basal insulin administration in patients with type 1 diabetes, since it provides effective glycaemic control and reduces the risk of nocturnal hypoglycaemia.100”

• cites [100] Heller, 2012, Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial, Lancet sourceNot checked — no full text of the source

May combine two claims.

A meta-analysis has shown that insulin pumps lower HbA1C concentrations more than multiple daily injections in adults with type 1 diabetes, with similar rates of hypoglycaemia.

“A meta-analysis has also shown that insulin pumps lower HbA1C concentrations more than multiple daily injections in adults with type 1 diabetes, with similar rates of hypoglycaemia.89”

• cites [89] Yeh, 2012, Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis, Ann Intern Med sourceNot checked — no full text of the source

May combine two claims.

FOXP3+ cells (regulatory T cells) and natural killer cells are rare in the insulitis lesion.

“Surprisingly, FOXP3+ cells (ie, regulatory T cells; a population of intense research interest2) and natural killer cells are rare in this lesion.”

• cites [62] Willcox, 2009, Analysis of islet inflammation in human type 1 diabetes, Clin Exp Immunol sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Organisations such as the International Diabetes Federation, Life for a Child, Insulin for Life, and others are developing means to alleviate the disparity in insulin access.

“Fortunately, organisations such as the International Diabetes Federation, Life for a Child, Insulin for Life, and others are developing means to alleviate this disparity.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Low-glucose suspend systems are currently available for clinical use in Europe, but remain in clinical trial testing in the USA.

“Low-glucose suspend systems are currently available for clinical use in Europe, but remain in clinic trial testing in the USA.”

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

The discovery of insulin in 1921-22 was clearly the most significant therapeutic event in the history of type 1 diabetes.

“The discovery of insulin in 1921–22 was clearly the most significant therapeutic event in the history of type 1 diabetes;”

Probably not a substantial claim: may not pass S3 (load-bearing).

Nearly three decades have passed since the first immune-based therapies, using ciclosporin, were attempted to reverse type 1 diabetes.

“Nearly three decades have passed since the first immune-based therapies, using ciclosporin, were attempted to reverse type 1 diabetes.125”

• cites [125] Bach, 2011, A historical view from thirty eventful years of immunotherapy in autoimmune diabetes, Semin Immunol sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The physical, social, and economic costs of type 1 diabetes are difficult to calculate, and attempts to quantify these variables typically do not distinguish between type 1 and type 2 disease.

“The physical, social, and economic costs of type 1 diabetes are difficult to calculate, and attempts to quantify these variables typically do not distinguish between type 1 and type 2 disease.”

Classified as probably not a substantial claim. May combine two claims.

Continuous glucose monitoring is most appropriate for highly motivated patients with type 1 diabetes who are willing to wear the monitoring device, and those with continuous poor control during intensive insulin therapy.

“Therefore, continuous glucose monitoring is most appropriate for highly motivated patients with type 1 diabetes who are willing to wear the monitoring device, and those with continuous poor control during intensive insulin therapy.93”

• cites [93] Ahmet, 2011, Prevalence of nocturnal hypoglycemia in pediatric type 1 diabetes: a pilot study using continuous glucose monitoring, J Pediatr sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

Since type 1 diabetes is now a predictable disease, several large trials are investigating methods to prevent or delay the onset of disease.

“Since type 1 diabetes is now a predictable disease, several large trials are investigating methods to prevent or delay the onset of disease.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Efforts are underway to combine insulin pumps and continuous glucose monitors with a computer algorithm-ie, an integrated closed-loop system, or artificial pancreas.

“Efforts are underway to combine insulin pumps and continuous glucose monitors with a computer algorithm—ie, an integrated closed-loop system, or artificial pancreas (figure 5).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The nPOD effort attempts to extend investigations to the entire pancreas, rather than be limited by use of a biopsy sample.

“Additionally, the nPOD effort attempts to extend investigations to the entire pancreas, rather than be limited by use of a biopsy sample.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Current sensor-augmented pump therapy uses each device independently, but integration of both systems is being investigated.

“Although current sensor-augmented pump therapy uses each device independently, integration of both systems is being investigated.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Once a critical mass (not well defined) of β cells is destroyed, symptomatic onset occurs, and the need for exogenous insulin replacement begins.

“Once a critical mass (not well defined) of β cells is destroyed, symptomatic onset occurs, and the need for exogenous insulin replacement begins.”

The quote only partly states this claim.

Of the remaining loci, only those for the insulin VNTR, PTPN22, CTLA4, and IL2RA are associated with odds ratios greater than 1·1.

“Of the remaining loci, only those for the insulin VNTR, PTPN22, CTLA4, and IL2RA are associated with odds ratios greater than 1·1.75”

• cites [75] Polychronakos, 2011, Understanding type 1 diabetes through genetics: advances and prospects, Nat Rev Genet sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Cardiovascular disease is becoming a more common macrovascular complication as individuals with type 1 diabetes live longer.

“Cardiovascular disease is becoming a more common macrovasular complication as individuals with in type 1 diabetes live longer.106”

• cites [106] Melendez-Ramirez, 2010, Complications of type 1 diabetes, Endocrinol Metab Clin North Am sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Inequalities in the availability of technologies to reduce complications, improve quality of life, and improve diabetes management raise ethical concerns.

“Inequalities in the availability of technologies to reduce complications, improve quality of life, and improve diabetes manage ment (eg, HbA1C testing and blood-glucose monitoring) also raise ethical concerns.”

Probably not a substantial claim: may not pass S2 (checkable).

This classification seems appropriate in view of the ongoing disease processes and the near certainty that such individuals will eventually become symptomatic (insulin dependent).

“This classification seems appropriate in view of the ongoing disease processes and the near certainty that such individuals will eventually become symptomatic (insulin dependent).”

May combine two claims.

A model originally posed in 1986, updated in 2001, and modified subsequently, poses that individuals are born with various degrees of genetic susceptibility for type 1 diabetes.

“A model originally posed in 1986,77 updated in our 2001 article,78 and modified subsequently, poses that individuals are born with various degrees of genetic susceptibility for type 1 diabetes.”

• cites [77] Eisenbarth, 1986, Type I diabetes mellitus. A chronic autoimmune disease, N Engl J Med sourceNot checked — no full text of the source
• cites [78] Atkinson, 2001, Type 1 diabetes: new perspectives on disease pathogenesis and treatment, Lancet sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

This model has stood the test of time, but some modifications should be considered due to knowledge gains.

“Although this model has stood the test of time, some modifications should be considered due to knowledge gains (figure 4).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Many practical and intellectual advances have been made since the first immune-based therapies, including improved metabolic testing, better understanding of disease pathogenesis, and availability of immune markers.

“Many practical and intellectual advances have been made since then, including improved metabolic testing, better understanding of disease pathogenesis, and availability of immune markers.126”

• cites [126] van Belle, 2011, Type 1 diabetes: etiology, immunology, and therapeutic strategies, Physiol Rev sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The risk for microvascular complications, including retinopathy, nephropathy, and neuropathy, decreases with intensive insulin therapy.

“The risk for microvascular complications, including retinopathy, nephropathy, and neuropathy, decreases with intensive insulin therapy.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Over the past 5 years, several large clinical trials have advanced the prediction and prevention of microvascular complications.

“Over the past 5 years, several large clinical trials have advanced the prediction and prevention of microvascular complications (table 1).”

May combine two claims.

Preserving insulin secretion after disease onset is increasingly a therapeutic goal, and can involve intensive insulin therapy, mechanical technologies, or immune intervention to disrupt β-cell destruction.

“Therefore, preserving insulin secretion after disease onset is increasingly a therapeutic goal, and can involve intensive insulin therapy, mechanical technologies, or, as in several trials, immune intervention to disrupt β-cell destruction.”

May combine two claims.

Symptomatic onset happens after a silent phase that lasts for months to many years, which could, in genetically susceptible individuals with multiple autoantibodies, be considered asymptomatic type 1 diabetes.

“This symptomatic onset happens after a silent phase that lasts for months to many years, that could, in genetically susceptible individuals with multiple autoantibodies, be considered asymptomatic type 1 diabetes.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Efforts to prevent or cure type 1 diabetes are now done via large collaborative networks, with rigorous mechanistic assays and uniform protocols.

“Efforts to prevent or cure type 1 diabetes are now done via large collaborative networks (eg, NIH TrialNet, Immune Tolerance Network, and Islet Cell Transplantation Consortium), with rigorous mechanistic assays and uniform protocols.”

May combine two claims.

Type 1 diabetes is clearly a polygenic disorder, with nearly 40 loci (so far) known to affect disease susceptibility.

“Type 1 diabetes is clearly a polygenic disorder, with nearly 40 loci (so far) known to affect disease susceptibility.72”

• cites [72] Concannon, 2009, Genetics of type 1A diabetes, N Engl J Med sourceNot checked — no full text of the source

May combine two claims.

Tamborlane and colleagues reported that a real-time continuous glucose monitoring system decreased the amount of time spent in hypoglycaemia (<4 mmol/L [70 mg/dL]) and lowered HbA1C when used by patients an average of 6 days a week.

“Tamborlane and colleagues91 reported that a real-time continuous glucose monitoring system decreased the amount of time spent in hypoglycaemia (<4 mmol/L [70 mg/dL]) and lowered HbA1C when used by patients an average of 6 days a week.”

• cites [91] Tamborlane, 2008, Continuous glucose monitoring and intensive treatment of type 1 diabetes, N Engl J Med sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The Pittsburgh Epidemiology of Diabetes Complications study of type 1 diabetes reported cardiovascular events in adult patients younger than 40 years of age to be 1% per year, and three times higher in individuals older than 55 years.

“The Pittsburgh Epidemiology of Diabetes Complications study108 of type 1 diabetes reported cardiovascular events in adult patients younger than 40 years of age to be 1% per year, and three times higher in individuals older than 55 years.”

• cites [108] Maser, 1991, Cardiovascular disease and arterial calcification in insulin-dependent diabetes mellitus: interrelations and risk factor profiles. Pittsburgh Epidemiology of Diabetes Complications Study-V, Arterioscler Thromb sourceNot checked — no full text of the source

May combine two claims.

These results imply that single-agent immunosuppression alone might be insufficient to completely control the autoimmune destruction of β cells, or that more specific and targeted therapies are needed.

“These results imply that single-agent immunosuppression alone might be insufficient to completely control the autoimmune destruction of β cells, or that more specific and targeted therapies are needed.”

Classified as probably not a substantial claim. May combine two claims.

In addition to preserving production of C-peptide, a key goal is to induce immune tolerance against β cells and thereby halt autoimmune destruction.

“In addition to preserving production of C-peptide, a key goal is to induce immune tolerance against β cells and thereby halt autoimmune destruction.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Despite the advances in type 1 diabetes research and therapy, some researchers and clinicians are disappointed by a perceived lack of progress.

“Despite the advances in type 1 diabetes research and therapy, some researchers and clinicians are disappointed by a perceived lack of progress.”

Probably not a substantial claim: may not pass S2 (checkable).

Combination therapies that target several pathogenic pathways and improve β-cell viability might be needed to preserve endogenous insulin production in patients with type 1 diabetes.

“Combination therapies that target several pathogenic pathways and improve β-cell viability might be needed to preserve endogenous insulin production in patients with type 1 diabetes.”

May combine two claims.

Other phase 2 studies of immune modulators showed evidence of therapeutic efficacy in settings of recent-onset type 1 diabetes; however, even with continued use, most did not show durable effects.

“Other phase 2 studies of immune modulators showed evidence of therapeutic efficacy in settings of recent-onset type 1 diabetes; however, even with continued use, most did not show durable effects.”

Probably not a substantial claim: may not pass S2 (checkable).

Knowledge voids that have long existed for type 1 diabetes remain today.

“Knowledge voids that have long existed for type 1 diabetes, unfortunately, remain today.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Efforts are underway to assign specific phenotypes to genotypes and to improve understanding of the genetic risk for type 1 diabetes by genotyping at multiple susceptibility loci.

“Efforts are underway to assign specific phenotypes to genotypes, and to improve understanding of the genetic risk for type 1 diabetes by genotyping at multiple susceptibility loci.154”

• cites [154] Winkler, 2012, A strategy for combining minor genetic susceptibility genes to improve prediction of disease in type 1 diabetes, Genes Immun sourceNot checked — no full text of the source

• AssumptionRests on an assumption: Although many genotypic associations with type 1 diabetes exist, the specific phenotypes resulting from these genetic influences are largely unknown.

May combine two claims.

Nicotinamide and intranasal insulin have not been shown to delay or prevent diabetes onset.

“Other agents used for secondary prevention, nicotinamide and intranasal insulin, have not been shown to delay or prevent diabetes onset.132,133”

• cites [132] Gale, 2004, European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes, Lancet sourceNot checked — no full text of the source
• cites [133] Näntö-Salonen, 2008, Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial, Lancet sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Many of the limitations for islet transplantation hold true for another promising area, the use of stem cells as insulin-producing surrogates for β cells.

“Many of the limitations for islet transplantation hold true for another promising area, the use of stem cells as insulin-producing surrogates for β cells.”

May combine two claims.

A post-hoc analysis suggested that individuals with high titre insulin autoantibodies benefited from oral insulin treatment-it was estimated that diabetes onset was delayed as much as 5 years.

“but a post-hoc analysis suggested that individuals with high titre insulin autoantibodies benefited from treatment—it was estimated that diabetes onset was delayed as much as 5 years.131”

• cites [131] Skyler, 2005, Effects of oral insulin in relatives of patients with type 1 diabetes: the Diabetes Prevention Trial—Type 1, Diabetes Care sourceNot checked — no full text of the source