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Förbättrad prognos för T1DM i Sverige. NDR. The Lancet

Förbättrad prognos för personer med typ 1 diabetes – men stor variation inom gruppen

NY STUDIE.

Sedan början av 2000-talet är det allt färre personer med typ 1 diabetes som insjuknar i hjärt- kärlsjukdomar eller avlider. Men variationen i prognos är stor inom patientgruppen och vården kan i linje med det behöva differentieras mera.

Det visar en studie från Göteborgs universitet som nyligen publicerades i tidskriften The Lancet Regional Health – Europe.

Historiskt sett har personer med typ 1 diabetes haft en högre risk att dö i hjärt- kärlsjukdomarän människor i allmänhet. Och även om risken fortfarande är tre till fem gånger högre, har risken för den här gruppen stadigt minskat de senaste decennierna. Men skillnader i prognos inom gruppen är stor.

Om en njurpåverkan från diabetessjukdomen föreligger, även i mindre grad, hade det stor betydelse för dödlighet och hjärtsjukdom i den aktuella studien.

Sara Hallström, en av forskarna bakom studien.
Foto: Ingrid Hallström

– För dem utan njurkomplikationer eller tidigare hjärtsjukdomar – vilka utgör knappt hälften av dem vi studerat – är dödligheten inte större än inom normalbefolkningen i stort, säger Sara Hallström på Sahlgrenska akademin vid Göteborgs universitet som är en av forskarna bakom studien.

Stora register

I studien har forskarna gått igenom NDR data i nationella register för över 45 000 personer med typ 1 diabetes, och jämfört uppgifterna med en kontrollgrupp på över 220 000 personer. Utöver trenden med minskad risk för hela gruppen kunde de även se att variationen inom patientgruppen var ett av de viktigaste resultaten.

– Det här innebär att vården vid typ 1 diabetes behöver differentieras än mer i hög- och lågriskpatienter med tanke på högt blodsocker, njursjukdom eller hjärtsjukdom, säger Sara Hallström.

Dessutom behöver behandlingen av högriskpatienterna bli mer intensiv än idag för att uppnå minskad dödlighet även i den gruppen.

Fortsatt uppåt

Forskarna förväntar sig att prognosen kommer förbättras ytterligare i framtiden.

– Med dagens diabetesvård kommer många barn och unga vuxna med typ 1 diabetes sannolikt ha en god prognos i framtiden eftersom allt större grupper når en god blodsockerkontroll och har fler riskfaktorer välbehandlade vilket resulterar i relativt låg risk för utveckling av njur- och hjärtsjukdom.

Studien är utförd av Göteborgs universitet i samarbete med forskare vid Linköpings universitet och Harvard Medical School.

Studien är publicerad i The Lancet Regional Health – Europe

https://www.sciencedirect.com/science/article/pii/S266677622200165X?via%3Dihub

Lars-Olof Karlssson Press release Göteborgs Universitet

Nyhetsinfo

www red DiabetologNytt

Läs hel studien pdf free

https://www.sciencedirect.com/science/article/pii/S266677622200165X?via%3Dihub

Risk factors, mortality trends and cardiovasuclar diseases in people with Type 1 diabetes and controls: A Swedish observational cohort study

Author links open overlay panelSaraHallström^a^bMagnus OlofWijkman^cJohnnyLudvigsson^dPerEkman^eMarc AlanPfeffer^fHansWedel^gAnnikaRosengren^bMarcusLind^a^b^h

Cite

https://doi.org/10.1016/j.lanepe.2022.100469 Get rights and content

Under a Creative Commons license

Open access

Summary

Background

Historically, the incidence of cardiovascular disease and mortality in persons with Type 1 diabetes (T1D) has been increased compared to the general population. Contemporary studies on time trends of mortality and cardiovascular disease are sparse.

Methods

In this observational study, T1D persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141). Incidence rates from 2002 to 2019 were estimated with respect to mortality and cardiovascular disease in persons with T1D overall and when stratified for prevalent cardiovascular and renal disease relative to controls.

Findings

Mean age in persons with T1D was 32.4 years and 44.9% (20,446/45,575) were women. Age- and sex- adjusted mortality rates declined over time in both groups but remained significantly higher in those with T1D compared to controls during 2017–2019, 7.62 (95% CI 7.16; 8·08) vs. 2.23 (95% CI 2.13; 2.33) deaths per 1,000 person years. Myocardial infarction, heart failure and stroke decreased over time in both groups, with persistent excess risks in the range of 3.4–5.0 times from 2017 to 2019 in those with T1D. T1D persons ≥45 years without previous renal or cardiovascular complications had standardized mortality rates similar or even lower than controls 5.55 (4.51; 6.60) vs.7.08 (6.75; 7.40) respectively in the last time period.

Interpretation

Excess mortality persisted over time in persons with T1D, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on individualized treatment is needed to close the gap in mortality for individuals with T1D.

Research in context

Evidence before this study

We searched PubMed and Google Scholar for articles published until December 20, 2021 with the search terms “Type 1 diabetes” and “mortality” in the title or the abstract. We found no recent studies evaluating mortality rates in persons with Type 1 diabetes. We found a few earlier studies stratifying persons with Type 1 diabetes on diabetes complications evaluating prognosis over time.

Added value of this study

Excess risk of mortality, myocardial infarction, heart failure and stroke remain for persons with Type 1 diabetes and rates are 3.4–5.8 times higher when evaluated over 20 years until December 31, 2019.

Type 1 diabetes is a cardiovascular equivalent with respect to future risk of myocardial infarction.

Contemporary mortality rates in persons ≥45 years are lower in people with Type 1 diabetes free from cardiorenal complications than for controls without diabetes at the same age and sex.

Type 1 diabetes persons free from cardiorenal complications but with hyperglycemia have excess risk of myocardial infarction, but the risk attenuates for patients with mean Hba1c≤58 mmol/mol (7.5%) over time and converges to incidence rates in controls.

Implications of all the available evidence

Excess mortality remains in people with Type 1 diabetes, but prognosis needs to be individualized and diversified since large groups without cardiorenal complications show low mortality rates and cardiovascular incidences.

To reduce the overall gap in mortality for persons with Type 1 diabetes, improved secondary prevention in patients with cardiorenal complications is urgently needed.

From the Discussion

Discussion

In this population-based study of persons with T1D over two decades, mortality rates and incidences of AMI, HF, and stroke decreased over time.

However, the gap between T1D persons and controls did not converge due to improvements in prognosis in the general population. By contrast, people with T1D ≥45 years of age without previous cardiovascular or renal complications (constituting approximately 50% of this group over time) had mortality rates similar to persons ≥45 years without diabetes, as well as low risks of AMI, HF, and stroke.

Previous studies have evaluated excess risks of mortality and CVD over time for persons with diabetes in different geographic regions showing excess risks on a group level but only a few studies have distinguished patients by cardiorenal complications or other risk factors.15, 16, 17, 18^,21, 22, 23 Whether diabetes is a cardiovascular risk equivalent has been debated, i.e., whether persons with diabetes free from coronary artery disease have similar risk of myocardial infarction as persons in the general population with established coronary disease.²⁴

This has primarily been evaluated in persons with type 2 diabetes (T2D) and has been an important basis for whether they should receive more aggressive primary preventive treatment. We found T1D to be a cardiovascular risk equivalent with respect to AMI highlighting the need for aggressive CVD prevention in this patient group. For HF, the impact of renal complications was even stronger than when AMI was evaluated.

Renal complications

Renal complications are a marker of past elevated glucose levels and a key explanatory variable for excess mortality in persons with T1D.¹^,15, 16, 17, 18 The gap in mortality between persons with T1D and the general population would likely converge if mortality and cardiovascular risk could be reduced in patients with renal complications. In the current study, renal complications had a marked impact on mortality, implying that aggressive prevention is needed at early stages of renal complications.

Lower blood pressure and treatment with RAAS-inhibitors are recommended for patients with renal complications to reduce further renal progression. Moreover, persons at high risk of AMI, stroke, and HF likely benefit from very strict blood pressure control, although this has been debated among people with T2D.²⁵ Lower blood lipid targets than the overall targets of LDL 2.5 mmol/l (97 mg/dl) may be warranted for individuals with T1D and renal complications who are not yet on dialysis.

SGLT2-inhibitors have shown a preventive effect regarding advanced renal complications, HF, and cardiovascular mortality not only in patients with T2D but also in people without diabetes.26, 27, 28, 29, 30 Similar preventive effects, not acting via the glucose-lowering effect, but among other mechanisms via reduction of intraglomerular pressure are likewise beneficial for patients with T1D.³¹

Future studies are needed to evaluate the effect of SGLT-2 inhibitors in T1D persons with cardiovascular and cardiorenal disease. As in T2D guidelines, clinicians ought to characterize T1D patients as at high- or low-risk to a greater extent.³² Moreover, other cardiorenal preventive treatments need further investigation, including finerenone which has shown beneficial effects in persons with T2D and renal complications.³³^,³⁴

Risk factors and cardiorenal complications

Persons with T1D free from cardiovascular and renal complications showed slightly increased risk of AMI compared with persons without diabetes. Hence, some patients seem to convert from low-risk to high-risk via AMI. When exploring traditional risk factors the strongest association existed with glucose control.

Patients with historical mean HbA1c ≤7.5% (58 mmol/mol) without cardiorenal complications had no excess risk of AMI. The strong association between AMI and HbA1c may be explained by other risk factors (hypertension and LDL cholesterol levels) that were well-treated overall whereas HbA1c 60–65 mmol/mol were nearly double compared to levels in the general population in Sweden with mean HbA1c 34 mmol/mol.³⁵

The importance of glucose control to prevent a patient from converting to a high-risk profile is supported by the fact that hyperglycemia is a prerequisite for diabetic nephropathy.³ Continuous glucose monitoring (CGM) and advanced insulin pumpsconnecting CGM with an insulin pump for adjusting insulin delivery may reduce cardiorenal complications by improving glucose control. In a recent study including patients from four countries, renal complications were still common in patients with diabetes onset over the last 20 years, and the majority of patients had glucose levels above target.³⁶

Hence, improved prevention in people with T1D and cardiorenal complications should be the focus of attention in clinical practice and research to reduce the gap in mortality over time.

Strengths and limitations

A strength of the current study is the population-based design comprising nearly all persons with T1D in Sweden over 2 decades including information on diabetes complications and risk factors.

This study has several limitations. First, due to the registry-based study design, it is inevitable that some data are missing, for example information on renal complications was less comprehensive during the first 3 years of follow-up.

Moreover, coverage of the NDR in the first time periods was lower but improved over time to include almost all persons with T1D during the last decade. It should also be acknowledged that the NDR does not contain data regarding race and ethnicity, so these variables were not accounted for in the analyses.

Second, information on CVD in age- and sex-matched controls was available but levels of blood pressure, blood lipids, BMI, and smoking were not.

Third, information about renal complications was not available in controls, although renal complications are known to be relatively rare in persons without diabetes.

Fourth, information on use of medication to prevent and treat renal complications and hyperlipidemia were not considered in the analysis. This may be of interest in future analyses, especially in high risk patients.

Finally, in real-life evaluations as the current, data registration depends on when examinations are performed in clinical practice and not evaluated at specific predefined time points.

Conclusions

Mortality and cardiovascular disease prognosis is improving in persons with T1D but clear excess risks remain overall compared with individuals without diabetes.

With respect to mortality, the prognosis of persons with T1D and without cardiorenal complications is similar to persons without diabetes. Increased focus on prevention in patients with renal complications, and improved glucose control in the T1D population overall, are likely key factors to reducing the overall gap in mortality for persons with T1D compared with the general population.

Accordingly, a differentiated treatment focus is needed in future care of T1D patients.

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