#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Hemoglobin A1c Levels and Risk of Severe Hypoglycemia in Children and Young Adults with Type 1 Diabetes from Germany and Austria: A Trend Analysis in a Cohort of 37,539 Patients between 1995 and 2012


Background:
Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years.

Methods and Findings:
We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4±3.8 y, range 1–20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels were assessed by multivariable regression analysis. From 1995 to 2012, the relative risk (RR) for severe hypoglycemia and coma per 1% HbA1c decrease declined from 1.28 (95% CI 1.19–1.37) to 1.05 (1.00–1.09) and from 1.39 (1.23–1.56) to 1.01 (0.93–1.10), respectively, corresponding to a risk reduction of 1.2% (95% CI 0.6–1.7, p<0.001) and 1.9% (0.8–2.9, p<0.001) each year, respectively. Risk reduction of severe hypoglycemia and coma was strongest in patients with HbA1c levels of 6.0%–6.9% (RR 0.96 and 0.90 each year) and 7.0%–7.9% (RR 0.96 and 0.89 each year). From 1995 to 2012, glucose monitoring frequency and the use of insulin analogs and insulin pumps increased (p<0.001). Our study was not designed to investigate the effects of different treatment modalities on hypoglycemia risk. Limitations are that associations between diabetes education and physical activity and severe hypoglycemia were not addressed in this study.

Conclusions:
The previously strong association of low HbA1c with severe hypoglycemia and coma in young individuals with type 1 diabetes has substantially decreased in the last decade, allowing achievement of near-normal glycemic control in these patients.

Please see later in the article for the Editors' Summary


Vyšlo v časopise: Hemoglobin A1c Levels and Risk of Severe Hypoglycemia in Children and Young Adults with Type 1 Diabetes from Germany and Austria: A Trend Analysis in a Cohort of 37,539 Patients between 1995 and 2012. PLoS Med 11(10): e32767. doi:10.1371/journal.pmed.1001742
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001742

Souhrn

Background:
Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years.

Methods and Findings:
We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4±3.8 y, range 1–20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels were assessed by multivariable regression analysis. From 1995 to 2012, the relative risk (RR) for severe hypoglycemia and coma per 1% HbA1c decrease declined from 1.28 (95% CI 1.19–1.37) to 1.05 (1.00–1.09) and from 1.39 (1.23–1.56) to 1.01 (0.93–1.10), respectively, corresponding to a risk reduction of 1.2% (95% CI 0.6–1.7, p<0.001) and 1.9% (0.8–2.9, p<0.001) each year, respectively. Risk reduction of severe hypoglycemia and coma was strongest in patients with HbA1c levels of 6.0%–6.9% (RR 0.96 and 0.90 each year) and 7.0%–7.9% (RR 0.96 and 0.89 each year). From 1995 to 2012, glucose monitoring frequency and the use of insulin analogs and insulin pumps increased (p<0.001). Our study was not designed to investigate the effects of different treatment modalities on hypoglycemia risk. Limitations are that associations between diabetes education and physical activity and severe hypoglycemia were not addressed in this study.

Conclusions:
The previously strong association of low HbA1c with severe hypoglycemia and coma in young individuals with type 1 diabetes has substantially decreased in the last decade, allowing achievement of near-normal glycemic control in these patients.

Please see later in the article for the Editors' Summary


Zdroje

1. The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 329: 977–986.

2. NathanDM, ZinmanB, ClearyPA, BacklundJY, GenuthS, et al. (2009) Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983–2005). Arch Intern Med 169: 1307–1316.

3. The Diabetes Control and Complications Trial Research Group (1994) Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. J Pediatr 125: 177–188.

4. DavisEA, KeatingB, ByrneGC, RussellM, JonesTW (1997) Hypoglycemia: incidence and clinical predictors in a large population-based sample of children and adolescents with IDDM. Diabetes Care 20: 22–25.

5. MortensenHB, HougaardP (1997) Comparison of metabolic control in a cross-sectional study of 2,873 children and adolescents with IDDM from 18 countries. The Hvidøre Study Group on Childhood Diabetes. Diabetes Care 20: 714–720.

6. BulsaraMK, HolmanCD, DavisEA, JonesTW (2004) The impact of a decade of changing treatment on rates of severe hypoglycemia in a population-based cohort of children with type 1 diabetes. Diabetes Care 27: 2293–2298.

7. de BeaufortCE, SwiftPG, SkinnerCT, AanstootHJ, AmanJ, et al. (2007) Continuing stability of center differences in pediatric diabetes care: do advances in diabetes treatment improve outcome? The Hvidoere Study Group on Childhood Diabetes. Diabetes Care 30: 2245–2250.

8. RosenbauerJ, DostA, KargesB, HungeleA, StahlA, et al. (2012) Improved metabolic control in children and adolescents with type 1 diabetes: a trend analysis using prospective multicenter data from Germany and Austria. Diabetes Care 35: 80–86.

9. JacobsonAM, MusenG, RyanCM, SilversN, ClearyP, et al. (2007) Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 356: 1842–1852.

10. FeltbowerRG, BodanskyHJ, PattersonCC, ParslowRC, StephensonCR, et al. (2008) Acute complications and drug misuse are important causes of death for children and young adults with type 1 diabetes: results from the Yorkshire Register of diabetes in children and young adults. Diabetes Care 31: 922–926.

11. RewersA, ChaseHP, MackenzieT, WalravensP, RobackM, et al. (2002) Predictors of acute complications in children with type 1 diabetes. JAMA 287: 2511–2518.

12. SämannA, MühlhauserI, BenderR, KloosC, MüllerUA (2005) Glycaemic control and severe hypoglycaemia following training in flexible, intensive insulin therapy to enable dietary freedom in people with type 1 diabetes: a prospective implementation study. Diabetologia 48: 1965–1970.

13. CryerPE (2008) The barrier of hypoglycemia in diabetes. Diabetes 57: 3169–3176.

14. HellerSR (2008) Minimizing hypoglycemia while maintaining glycemic control in diabetes. Diabetes 57: 3177–3183.

15. DavisEA, KeatingB, ByrneGC, RussellM, JonesTW (1998) Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus. Arch Dis Child 78: 111–115.

16. SvenssonJ, JohannesenJ, MortensenHB, NordlyS, Danish Childhood DiabetesRegistry (2009) Improved metabolic outcome in a Danish diabetic paediatric population aged 0–18 yr: results from a nationwide continuous registration. Pediatr Diabetes 10: 461–467.

17. O'ConnellSM, CooperMN, BulsaraMK, DavisEA, JonesTW (2011) Reducing rates of severe hypoglycemia in a population-based cohort of children and adolescents with type 1 diabetes over the decade 2000–2009. Diabetes Care 34: 2379–2380.

18. BlasettiA, Di GiulioC, ToccoAM, VerrottiA, TuminiS, et al. (2011) Variables associated with severe hypoglycemia in children and adolescents with type 1 diabetes: a population-based study. Pediatr Diabetes 12: 4–10.

19. KatzML, VolkeningLK, AndersonBJ, LaffelLM (2012) Contemporary rates of severe hypoglycaemia in youth with type 1 diabetes: variability by insulin regimen. Diabet Med 29: 926–932.

20. CengizE, XingD, WongJC, WolfsdorfJI, HaymondMW, et al. (2013) Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D Exchange clinic registry. Pediatr Diabetes 14: 447–454.

21. SvorenBM, VolkeningLK, ButlerDA, MorelandEC, AndersonBJ, et al. (2007) Temporal trends in the treatment of pediatric type 1 diabetes and impact on acute outcomes. J Pediatr 150: 279–285.

22. KargesB, MeissnerT, IcksA, KapellenT, HollRW (2012) Management of diabetes mellitus in infants. Nat Rev Endocrinol 8: 201–211.

23. KargesB, KapellenT, NeuA, HoferSE, RohrerT, et al. (2010) Long-acting insulin analogs and the risk of diabetic ketoacidosis in children and adolescents with type 1 diabetes: a prospective study of 10,682 patients from 271 institutions. Diabetes Care 33: 1031–1033.

24. American Association of Diabetes Workgroup on Hypoglycemia (2005) Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 28: 1245–1249.

25. The Diabetes Control and Complications Trial Research Group (1991) Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT Research Group. Am J Med 90: 450–459.

26. ClarkeW, JonesT, RewersA, DungerD, KlingensmithGJ (2009) Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatr Diabetes 10 (Suppl 12)134–145.

27. KnerrI, WolfJ, ReinehrT, StachowR, GrabertM, et al. (2005) The ‘accelerator hypothesis’: relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9,248 German and Austrian children with type 1 diabetes mellitus. Diabetologia 48: 2501–2504.

28. Fiallo-ScharerR, ChengJ, BeckRW, BuckinghamBA, ChaseHP, et al. (2011) Factors predictive of severe hypoglycemia in type 1 diabetes: analysis from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized control trial dataset. Diabetes Care 34: 586–590.

29. JohnsonSR, CooperMN, JonesTW, DavisEA (2013) Long-term outcome of insulin pump therapy in children with type 1 diabetes assessed in a large population-based case-control study. Diabetologia 56: 2392–2400.

30. TupolaS, RajantieJ, MäenpääJ (1998) Severe hypoglycaemia in children and adolescents during multiple-dose insulin therapy. Diabet Med 15: 695–699.

31. ShalitinS, PhillipM (2008) Hypoglycemia in type 1 diabetes: a still unresolved problem in the era of insulin analogs and pump therapy. Diabetes Care 31 (Suppl 2)S121–S124.

32. ZieglerR, HeidtmannB, HilgardD, HoferS, RosenbauerJ, et al. (2011) Frequency of SMBG correlates with HbA1c and acute complications in children and adolescents with type 1 diabetes. Pediatr Diabetes 12: 11–17.

33. BrunelleBL, LlewelynJ, AndersonJH, GaleEA, KoivistoVA (1998) Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes. Diabetes Care 21: 1726–1731.

34. RossettiP, PorcellatiF, BolliGB, FanelliCG (2008) Prevention of hypoglycemia while achieving good glycemic control in type 1 diabetes: the role of insulin analogs. Diabetes Care 31 (Suppl 2)S113–S120.

35. BottS, BottU, BergerM, MühlhauserI (1997) Intensified insulin therapy and the risk of severe hypoglycaemia. Diabetologia 40: 926–932.

36. CryerPE, DavisSN, ShamoonH (2003) Hypoglycemia in diabetes. Diabetes Care 26: 1902–1912.

Štítky
Interné lekárstvo

Článok vyšiel v časopise

PLOS Medicine


2014 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#