<h2 style="text-align: center;">WHY TO SCREEN</h2>
Proactive screening reduces the likelihood of a medical emergency and enables a smoother transition to life with Stage 3 autoimmune T1D.7,8,27,28

<h2>SCREENING AND MONITORING PROGRAMMES CAN REDUCE RATES OF DKA BY UP TO APPROXIMATELY 90%, PREVENTING SEVERE COMPLICATIONS AND REDUCING HOSPITALISATION27</h2>
Studies show that screening can lower rates of DKA at onset of Stage 3 autoimmune T1D.34–40 
 High reductions of DKA rates were observed in the following studies:

DKA, diabetic ketoacidosis; HLA, human leukocyte antigen; T1D, type 1 diabetes; TEDDY, The Environmental Determinants of Diabetes in the Young; US, United States. *Public health screening that screened 90,632 children for autoimmune T1D islet autoantibodies in Bavaria, Germany, of the 62 children with presymptomatic autoimmune T1D who developed Stage 3 of the condition, 2 (3.2%) were diagnosed in the laboratory with mild or moderate DKA without clinical symptoms, while 60 (96.8%) did not have DKA.34&nbsp; †The previously reported prevalence of DKA in unscreened children is over 20% in Germany.34 
 ‡A study that screened 424,788 children for autoimmune T1D HLA risk at birth and enrolled 8,677 children between 2004 and 2010. Of those children aged &lt;5 years at autoimmune T1D diagnosis, 9 of 79 (11%) experienced DKA at diagnosis.35

<h2>ENABLE A SMOOTHER TRANSITION INTO LIFE WITH AUTOIMMUNE T1D7,8,27,28,47,48</h2>
An abrupt Stage 3 autoimmune T1D diagnosis can feel like a crash-landing for individuals and their families.49,50

TIME TO PREPARE

LESS DISTRESS

A SMOOTHER TRANSITION

FAMILY EDUCATION

TYPE-1-DIABETES

DIABETES

DKA, diabetic ketoacidosis; T1D, type 1 diabetes. *Diabetes distress refers to the emotional burden and stress resulting from the ongoing demands of managing diabetes daily.51 †Qualitative studies reveal that while maternal anxiety levels initially spike after learning of their child’s high-risk status, this anxiety typically subsides to normal levels within 4–12 months.48

References

Why to screen for Autoimmune T1D

INTEGRATED-DIABETES-CARE

Unveiling Significance of Time in Range: Value as key Glycemic Biomarker

Join Dr. Battelino as he explores the crucial role of ‘Time in Range’ as a glycemic biomarker, illuminating its value in diabetes management and overall health outcomes. This insightful discussion offers a comprehensive understanding of this key metric in diabetes care. Don’t miss out on this opportunity to enhance your knowledge and improve patient care.

<h2>Beyond HbA1C, It is time to think Time-in-Range</h2>

<h3>Glycemic variability is a common challenge for people with diabetes and has a range of serious consequences1- 9</h3>
It is known today that two people with identical HbA1c&nbsp;level of 8.0% can have&nbsp;markedly different degrees of glycemic variability10*

<h3>Beyond HbA1c, rise of Time-in-Range as a new key metric for Glycemic control</h3>

Evaluating TIR can aid understanding&nbsp;whether hypoglycemia (time-below-range) or hyperglycemia (time-above-range) are improving with treatment over time12,13

As per the latest International Consensus on Time-in-Range,&nbsp;TIR is identified as a metric of glycemic control that provides&nbsp;more actionable information than HbA1C&nbsp;alone11

<h3>Optimizing HbA1c&nbsp;to &lt;7.0%12,14&nbsp;and reducing Glycemic variability: TIR&gt;70% and %CV≤36%6,12,13&nbsp;helps achieve better patient outcomes9,13-16</h3>

Which Time-in-Range target should you aim for?
International guidelines recommend&nbsp;a target of&gt;70% TIR&nbsp;(70-80 mg/dL) for most adult patients with T1DM or T2DM11,13†

<h4>Optimizing Time-in-Range</h4>
<ul>
 <li>A fundamental aspect to effective diabetes management11</li>
</ul>

*15-day glucose traces of two patients who had identical HbA1c of 8.0% but different degrees of GV. High GV in patient 1 was reflected by numerous episodes of both hypo- and hyper- glycemia, whereas low GV in patient 2 resulted in no such episodes.1

†It is recommended that most adult patients spend &lt;1 hour per day with blood glucose &lt;70 mg/dL (&lt;3.9 mmol/L); &lt;15 minutes per day with blood glucose &lt;54 mg/dL (&lt;3.0 mmol/L); &lt;1 hour 12 minutes per day with blood glucose &gt;250 mg/dL (&gt;13.9 mmol/L); and &lt;6 hours per day with blood glucose &gt;180 mg/dL (&gt;10.0 mmol/L), although CGM-based targets vary for different diabetes populations. For people with T1DM aged &lt;25 years, if the HbA1c&nbsp;goal is 7.5%, then the TIR target should be set to approximately 60%. For older patients or those at high risk, the TIR target is 50% although individualized decision making is recommended. There is insufficient data to allow recommendation of TIR target for pregnant women.11,13

# Includes percentage of values &lt;54 mg/dL (3.0 mmol/L).11
**Includes percentage of values &gt;250 mg/dL (13.9 mmol/L).11

Abbreviations

Understanding Time-in-Range: Assessment, Targets, and Benefits for Optimal Glycemic Control

A trigger initiates an autoimmune attack on the beta cells of the pancreas through autoreactive T cells&nbsp;10

T1D is an autoimmune disease caused by an autoimmune response against pancreatic beta cells3

T1D is not primarily a metabolic disease; in T1D, the immune system&nbsp;attacks&nbsp;pancreatic beta cells,&nbsp;hindering their ability to produce insulin3

The body is&nbsp;no longer able to produce insulin&nbsp;once beta cells have been destroyed by the immune system3

Lack of production of insulin leads to&nbsp;hyperglycaemia3

A criticial deficiency of insulin causes&nbsp;DKA&nbsp;to occur8, a traumatic event which can have a lasting negative impact on brain function&nbsp;1,9

DKA,diabetic ketoacidosis; T1D, type 1 diabetes.

<h2>AUTOIMMUNE T1D CAN START LONG BEFORE SYMPTOMS ARISE1</h2>
The rate of autoimmune T1D progression varies significantly; it can take months to decades for symptoms to develop.1,6

70% of children with multiple autoantibodies progress to symptomatic autoimmune T1D within 10 years.*10

5-year risk&nbsp;of progressing to symptomatic autoimmune T1D (Stage 3)6:

From Stage 1

From Stage 2

The&nbsp;lifetime risk&nbsp;of progressing to symptomatic autoimmune T1D (Stage 3) from Stages 1 and 2 approaches&nbsp;100%.&nbsp;6

Screening can transform lives by detecting the condition before symptoms develop.6,8,9

IQR, interquartile range; T1D, type 1 diabetes. *In a pooled analysis of three prospective cohort studies including children from Colorado, Finland and Germany, progression to autoimmune T1D at 10-year follow-up after autoantibody seroconversion in 585 children with multiple autoantibodies was 69.7% (95% CI, 65.1%-74.3%).10

Autoimmune T1D is a progressive condition; the decline of beta cell function can begin months to years before symptoms appear.1,5,6
People with autoimmune T1D progress through three clinically distinct stages as their beta cells are progressively destroyed.4,6,7

The lifetime risk of progressing to symptomatic autoimmune T1D (Stage 3) from Stages 1 and 2 approaches&nbsp;100%.&nbsp;6

Screening can transform lives by detecting the condition before symptoms develop.6,8,9

T1D, type 1 diabetes. 
 *Reversion to single autoantibody or negative status can occur in some people with previously confirmed multiple autoantibody positivity.4

Understanding Autoimmune T1D disease & Different Stages

Time-in-Range: A Key Determinant of Quality of Life

Tune in to Dr. Battelino’s enlightening talk on the profound impact of ‘Time in Range’ on the quality of life for diabetes patients. Gain valuable insights into how optimizing this crucial metric can significantly improve patient well-being and life satisfaction. A must-watch for all physicians striving for excellence in diabetes care.

The value of Time-in-range

Insights from Prof. Tadej Battelino on the value of Time-in-range as a Glycemic biomarker.

The Evolving Role of Treatment and Technology in Diabetes Care

Join Dr. Robert Rizzel as he navigates the transformative role of treatment and technology in diabetes care. This video provides a detailed overview of how these innovations are reshaping diabetes management, offering medical practitioners a deeper insight into contemporary diabetes care. Step into this enlightening journey to understand the future trajectory of diabetes treatment.

<h2>DKA IS A MEDICAL EMERGENCY ASSOCIATED WITH HIGH MORBIDITY3</h2>
Prevalence of DKA at diagnosis varies, but can be up to 70% across Europe and North America. DKA at diagnosis is often due to diagnostic error and treatment delay.3

DKA is responsible for approximately half of all hospitalisations in people with autoimmune T1D.29,30

DKA can have serious neurocognitive effects31; even a single severe episode has been shown to impair memory and IQ.*32

DKA is associated with a sustained negative effect on glycaemic control over time,†&nbsp;increasing morbidity and mortality.33

By approximately how much can screening and monitoring programmes reduce DKA rates?
DKA, diabetic ketoacidosis; FLUID, Fluid Therapies Under Investigation in Diabetic Ketoacidosis; IQ, intelligence quotient; PECARN, Pediatric Emergency Care Applied Research Network; T1D, type 1 diabetes. *In a prospective study including 758 children who presented with DKA in a randomised multisite clinical trial evaluating fluid protocols for DKA treatment (PECARN FLUID trial). DKA status was associated with lower scores in overall IQ, memory for item-colour associations and forward digit span recall.32†Independent of other variables.33

<h2>AVOIDING DKA AT DIAGNOSIS CAN IMPROVE HEALTH OUTCOMES1,41–44</h2>
Screening can facilitate prompt and effective glycaemic management, reducing the risk of severe macrovascular and microvascular complications.1,41–44
Avoiding DKA at diagnosis is associated with better long-term HbA1c levels.7,33

Preventing chronic hyperglycaemia can help reduce the risk of:

including stroke and cardiovascular disease

MACROVASCULAR COMPLICATIONS45

including eye, kidney and nervous system

MICROVASCULAR COMPLICATIONS45

An average of up to ~18 life-years lost in those diagnosed before age 10

A REDUCED LIFE EXPECTANCY*†46

Of ~40% of adults with autoimmune T1D initially misdiagnosed,&nbsp;77% were misdiagnosed with T2D‡; this can delay proper insulin replacement therapy, prolong hyperglycaemia and increase the risk of DKA.20
CI, confidence interval; DKA, diabetic ketoacidosis; HbA1c, haemoglobin A1c; T1D, type 1 diabetes; US, United States. *Compared to matched controls, according to a nationwide, register-based cohort study including 27,195 individuals with autoimmune T1D in Sweden, using data from the Swedish National Diabetes Register46&nbsp;†Men diagnosed with autoimmune T1D before 10 years of age lost a median of 14.2 life-years (95% CI 12.1, 18.2). Females diagnosed at the same age lost a median of 17.7 life-years (95% CI 14.5, 20.4). People diagnosed after 20 years of age lost approximately 10 life-years.46&nbsp;‡In a retrospective online survey of people with autoimmune T1D and caregivers of people with autoimmune T1D in the US, a diagnosis of autoimmune T1D was missed in 38.6% of those diagnosed at ≥18 years of age. Of those people, 76.8% were initially diagnosed with type 2 diabetes.20

The burden of Autoimmune T1D

<h2>Beyond HbA1C, It is time to think Time-in-Range</h2>
Optimizing Time-in-range is fundamental to effective Diabetes management and to help reduce the risk of the negative consequences for your patients1-5

Each&nbsp;1‌0‌% drop in Time-in-Range (TIR)&nbsp;was associated with increased frequency of

<h4 style="text-align: center;">Retinopathy2*</h4>
<img alt="" src="/dam/jcr:b196a16d-2dec-4c07-a138-242cc1bf3cc0/encadres-1.png">

<h4 style="text-align: center;">Microalbuminuria2*</h4>
<h4><img alt="" src="/dam/jcr:6f5f7f10-64e8-48c5-aa14-2dd071b9d7fb/encadres-2.png"></h4>

<h4 style="text-align: center;">Neuropathy3†</h4>
<img alt="" src="/dam/jcr:72b8750b-f8cc-4d4f-b6a4-ad32a7c56277/encadres-3.png">

<h4 style="text-align: center;">Mortality4☨</h4>
<img alt="" src="/dam/jcr:73077044-5ded-40bc-ac02-3cabb06f421a/encadres-4.png">

More TIR was associated with reduced&nbsp;risk of severe hypoglycemia, MACE and microvascular complications&nbsp;vs&nbsp;less TIR5#&nbsp;

In people with T2DM
Risk of a severe hypoglycemia event decreased by up to:

<div>
 <table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="text-align: center;">Time-in-range is an important physical and emotional measure of success for people with T1DM and T2DM6,7</td>
 </tr>
 </tbody>
 </table>
 Up to 5‌7‌% of people with T1‌DM and T2‌DM ranked TIR as the measurable therapy outcome that had the biggest impact on daily life with diabetes6†† Up to 5‌4‌% ranked TIR as the highest driver of a positive mindset6‡‡&nbsp;
</div>

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="text-align: center;">ADA and the International Consensus on TIR&nbsp;recommend reducing glycemic variability and&nbsp;optimizing TIR&nbsp;as a key aspect of effective diabetes management in people with T1DM and T2DM&nbsp;8,9</td>
 </tr>
 </tbody>
</table>

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="text-align: center;">Optimizing HbA1c to &lt;7‌.0‌%8,10&nbsp;and reducing glycemic variability: 
 TIR&gt;7‌0‌% and %CV≤3‌6‌%8,10&nbsp;helps achieve better patient outcomes2,4,5,7,8</td>
 </tr>
 </tbody>
</table>

*Post hoc analysis using the DCCT dataset to evaluate the association of TIR of 7‌0‌–1‌8‌0‌ mg/dL (3‌.9‌–1‌0‌ mmol/L) with the development or progression of retinopathy and microalbuminuria to validate TIR as a metric. Criteria for the retinopathy outcome were met by n=2‌7‌1‌/1‌,4‌4‌0‌ (1‌9‌%), and for the microalbuminuria outcome were met by n=1‌1‌6‌/1‌,2‌8‌3‌ (9‌%). Mean TIR for 7‌-point profiles for 1‌,4‌4‌0‌ people was 4‌1‌ ± 1‌6‌%. Adjusted HR (9‌5‌% CI) for retinopathy: 1‌.6‌4‌ (1‌.5‌1‌ to 1‌.7‌8‌); adjusted HR (9‌5‌% CI) for microalbuminuria: 1‌.4‌0‌ (1‌.2‌5‌ to 1‌.5‌6‌). From discrete Cox proportional hazards regression models using a time-dependent version of each glucose metric stratified by the ETDRS level of retinopathy at baseline and adjusted for the pre-DCCT glycemic exposure represented by the pre-existing duration of diabetes separately for the primary and secondary cohorts; p&lt;0‌.0‌0‌1‌.2

†&nbsp;Data from a prospective observational cohort study which evaluated the association of TIR of 7‌0‌–1‌8‌0‌ mg/dL (3‌.9‌–1‌0‌ mmol/L) with microvascular diabetes outcomes, including peripheral neuropathy; 6‌2‌ out of 1‌0‌5‌ participants with a total MNSI questionnaire score ≥2‌ were defined as having distal peripheral neuropathy, including 5‌1‌ with CKD and 1‌1‌ controls; CKD patients defined as having eGFR &lt;6‌0‌mL/min/1‌.7‌3‌m2. Odds ratio (9‌5‌% CI): 1‌.2‌5‌ (1‌.0‌2‌ to 1‌.5‌2‌). Adjusted for age, sex and race.3

‡&nbsp;A prospective cohort study (N=6‌,2‌2‌5‌) evaluating the link between TIR of 7‌0‌–1‌8‌0‌ mg/dL (3‌.9‌–1‌0‌ mmol/L) with all-cause and cardiovascular mortality, with the objective of validating TIR as surrogate marker of long-term adverse clinical outcomes. Adjusted HR (9‌5‌% CI) for all-cause mortality: 1‌.0‌8‌ (1‌.0‌5‌ to 1‌.1‌2‌); adjusted HR (9‌5‌% CI) for CV mortality: 1‌.0‌5‌ (1‌.0‌0‌ to 1‌.1‌1‌). From restricted cubic spline nested in time-dependent Cox model. Adjusted for age, sex, smoking, diabetes duration, BMI, systolic blood pressure, triglycerides, HDL cholesterol, LDL cholesterol, history of cancer, history of CVD, and using antihypertensive drugs, aspirin, and statins.4

#Post hoc study using data from the devote&nbsp;study from 5‌,6‌4‌4‌ people with T2‌DM who had an 8‌-point glucose profile. Individual TIR was derived as the proportion of the 8‌-point glucose profile within range (derived TIR). A Cox model was used to estimate the association between derived TIR and time to first MACE, severe hypoglycaemic episode and microvascular event (retinopathy and CKD). HRs (9‌5‌% CI) for MACE: 0‌.6‌9‌ (0‌.5‌2‌ to 0‌.9‌1‌) for TIR&gt;7‌0‌% vs TIR ≤5‌0‌%; 0‌.9‌1‌ (0‌.6‌6‌ to 1‌.2‌4‌) for TIR &gt;7‌0‌% vs TIR &gt;5‌0‌–≤7‌0‌% (overall association p&lt;0‌.0‌1‌). HR (9‌5‌% CI) for microvascular event: 0‌.6‌0‌ (0‌.4‌3‌ to 0‌.8‌5‌) for TIR&gt;7‌0‌% vs TIR ≤5‌0‌%; 0‌.7‌3‌ (0‌.4‌9‌ to 1‌.0‌9‌) for TIR &gt;7‌0‌% vs TIR &gt;5‌0‌–≤7‌0‌% (overall association p&lt;0‌.0‌1‌9‌). Hazard ratios were consistent when analyses were adjusted for baseline characteristics.5

**TIR &gt;7‌0‌% vs ≤5‌0‌%. HR (9‌5‌% CI) vs TIR ≤5‌0‌% for time to first severe hypoglycemia: 0‌.5‌4‌ (0‌.4‌0‌ to 0‌.7‌3‌).5

††Online survey of 3‌,4‌6‌1‌ people with T1‌DM (n=1‌,0‌2‌6‌) or T2‌DM (n=1‌,1‌5‌4‌ on insulin; n=1‌,2‌8‌1‌ not on insulin). The survey presented respondents with 2‌5‌ questions investigating patients’ perceptions of the success of current diabetes drugs and devices; which factors have the biggest impact on patients’ daily lives and which changes would have the biggest positive impact on diabetes management and mindset; and mental well-being, QoL, desired improvements for future therapies, relationships with health care providers, and the concerns of loved ones. The survey was conducted from 1‌7‌–2‌2‌ August.6

‡‡Food choices were rated by all groups (range 6‌3‌% to 6‌7‌% of the groups) as the greatest factor having an impact on daily life with diabetes, but TIR emerged as the measurable therapy outcome that had the biggest impact on daily life with diabetes for all groups of respondents (range 4‌1‌% to 5‌7‌%).6

##Including intra-day mean glucose, glycemic variability, and glucose levels after meals and overnight. Based on a multicentre, randomised, crossover trial in adults with T1‌DM (n=8‌2‌) and T2‌DM (n=3‌0‌6‌). Participants received basal-bolus regimen of insulin glargine plus premeal insulin glulisine (n=1‌9‌2‌) or premix analogue insulin (n=1‌9‌6‌). Participants were then crossed over to the other treatment at 1‌2‌ weeks and continued for another 1‌2‌ weeks.7

Impact of Time-In-Range on Diabetes Management

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