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may include infection with a certain
virus , exposure to a dietary element , changes in the microbiome or perinatal factors . 7 There is no evidence that immunisation modulates the risk of type 1 diabetes .
RISK FACTORS
IT is not currently possible to
pre-emptively identify individuals who will develop type 1 diabetes . 5 Even when a family member or close relative has the condition , the risk of other family members developing it is less than one in ten ( see box 1 ). 8 It is recommended to measure autoantibodies only in those suspected of having type 1 diabetes . 6 It is not justified to test family members of individuals with type 1 diabetes for either
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Adapted from Rogers et al 2017 4 |
Box 1 . The association between family history and future risk of type 1 diabetes
• No family history : 0.4 %.
• Offspring of an affected individual : 2-9 %.
• Sibling of an affected individual : about 6 %.
• Dizygotic twin of an affected individual : about 8 %.
• Identical twin of an affected individual : 30-70 %. Source : DiMeglio LA et al 2018 8
Box 2 . A diagnosis of diabetes is made in any symptomatic patient with any one of these features
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their genetic haplotype or screen for the presence of autoantibodies . 5 Even if an individual tests positive for one islet-directed autoantibody , the likelihood of that individual developing type 1 diabetes still remains low .
INITIAL PRESENTATION
TYPE 1 diabetes usually presents in
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Figure 1 . Age of onset of type 1 diabetes . |
• A fasting venous blood glucose concentration of 7.0mmol / L or greater .
• A random blood glucose level of 11.1mmol / L or greater .
• An HbA1c of 6.5 % ( 48mmol / mol ) or greater .
Source : Holt RIG et al 2021 5
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adults as an acute illness that evolves over 1 – 4 weeks and is associated with the classical symptomatic triad of |
Box 3 . Features suggestive of type 1 diabetes |
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polydipsia , polyuria and unintentional weight loss . 8 , 9 A diagnosis of diabetes can be made in any symptomatic patient with corroborating evidence of an elevated blood glucose level ( see box 2 ).
Acute diabetic ketoacidosis ( DKA ) is the first presenting feature in at least a quarter of cases . DKA is often misdiagnosed as infection as it is associated with non-specific symptoms , such as nausea , vomiting , abdominal pain , shortness of breath and confusion . 8 Such a misdiagnosis can be life threatening . However , evidence of markedly elevated blood glucose levels ( see box 2 ) can quickly lead to a correct diagnosis and facilitate appropriate emergency treatment .
More than 40 % of cases of adult-onset type 1 diabetes pres-
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• A younger age at diagnosis ( under 35 ).
• Not overweight ( eg , BMI less than 25kg / m2 [ Caucasian ] or less than 23kg / m2 [ Asian ]).
• Experiencing rapid and unintentional weight loss .
• Ketoacidosis at first presentation .
• Very high blood glucose ( eg , greater than 20mmol / L ) at first presentation .
• Rapid progression to insulin requirements ( less than three years ).
• Personal or family history of autoimmune disorders ( eg , autoimmune thyroid disease , coeliac disease , type 1 diabetes in another family member ).
Source : Holt RIG et al 2021 5
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ent with mild symptoms and only |
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modestly elevated glucose levels . Such cases are often initially , and effectively , managed as type 2 diabetes . 10-12 This is completely understandable given the far higher prevalence of type 2 diabetes in adults and the fact that most adults are now overweight or obese and so at increased risk .
Moreover , substantial , although inadequate β-cell function may still be retained in many adults with type
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Figure 2 . Pancreatic islets . |
Box 4 . Indications for urgent referral to ED
• Signs of ketosis or dehydration .
• Severe hyperglycaemia accompanied by vomiting .
• Symptoms or signs of an underlying infection .
• Altered level of consciousness , confusion or delirium .
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1 diabetes at their first presentation , |
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meaning that insulin injections may |
autoantibody testing and / or revisit |
and most such patients can continue to |
1 diabetes — such that , after three or |
with the goal of safely maintain- |
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not initially be required provided that |
the diagnosis at subsequent clinical |
be managed as having type 1 diabetes . |
more years of diabetes , any individ- |
ing glucose levels as close to optimal |
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insulin requirements can be reduced — |
reviews . |
In autoantibody-negative individuals , |
uals with C-peptide levels less than |
for the individual . The way insulin |
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for example , by improving insulin sensitivity through diet , weight loss and / or oral medication . 13 As β-cell loss may be slowly progressive in adult-onset |
DIAGNOSIS
A DIAGNOSIS of type 1 diabetes is suggested by the presence of islet cell
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where a diagnosis of type 1 diabetes is still suspected , additional testing for non-fasting plasma C-peptide can be undertaken , with concurrent plasma |
200pmol / L may be effectively diagnosed with type 1 diabetes if the diagnosis was ever in doubt . 4 , 16
Note that many adults with type 2
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is started plays an important role in determining future adherence , glycaemic control and outcomes . In all cases , insulin therapy should be carefully |
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type 1 diabetes , there may be a latent period between the onset of hyperglycaemia and absolute insulin deficiency necessitating insulin therapy . 8 Consequently , initially identifying whether an adult has type 1 or type 2 diabetes may not be straightforward . |
autoantibodies in patients presenting with significant hyperglycaemia ( see figure 4 ). More than 90 % of new cases of type 1 diabetes will be positive for anti-glutamic acid decarboxylase ( anti-GAD65 ) antibody . 14 If anti-GAD65 is negative , additional tests for islet |
glucose , within five hours of eating . Insulin is co-secreted with C-peptide from β-cells . If insulin production is damaged , as occurs in type 1 diabetes , circulating C-peptide levels fall to a similar extent . A value of less than 200 pmol / L is consistent with a diagnosis of |
diabetes are also positive for anti-GAD antibody . 8 These patients may have been misdiagnosed with type 1 diabetes and effectively managed with insulin . These patients can be screened for C-peptide , after three or more years of diabetes . Some will retain insulin and |
individualised , culturally appropriate and titrated , accompanied by patient education , training and support .
Initial management of an extremely elevated blood glucose concentration ( greater than 20mmol / L ) in an unwell adult is a medical emer-
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Some clinical features suggestive |
tyrosine phosphatase 2 ( IA2 ) and / or |
type 1 diabetes , and elevated C-peptide |
C-peptide secretion at this point , and |
gency and requires immediate spe- |
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of type 1 diabetes are listed in box 3 . |
zinc transporter 8 ( ZnT8 ) can be under- |
values greater than 600pmol / L are con- |
may be able to come off insulin therapy |
cialist assessment and management . |
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However , each of these features may |
taken ; the latter two are often tested |
sistent with type 2 diabetes . 4 |
or access other mediations — for exam- |
Indications for urgent referral to hos- |
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be seen in some adults with type 2 dia- |
for together with anti-GAD65 as part |
However , C-peptide is not a perfect |
ple , SGLT2 inhibitors — for the manage- |
pital appear in box 4 . |
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betes . Equally , many older adults pre- |
of a screening panel , reducing the |
indicator either . At least one in every |
ment of their type 2 diabetes . |
For adults diagnosed with type 1 |
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senting with type 1 diabetes do not have these features . Therefore , it is important to retain a degree of suspicion in all adults presenting with diabetes ; where appropriate , initiate |
false-negative rate .
About 5-10 % of adults with features of type 1 diabetes have negative islet antibodies . 15 This does not exclude a diagnosis of type 1 diabetes ,
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three adults with type 1 diabetes initially retain some C-peptide and insulin secretion at diagnosis . 16 Ultimately , both insulin and C-peptide production will be lost in people with type |
INITIAL INSULIN TREATMENT
ALL adults with type 1 diabetes
require lifelong treatment with insulin
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diabetes who are not severely unwell , treatment with multiple daily injection basal – bolus insulin regimens can be safely initiated , starting at doses of 0.3-0.4 units / kg .
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