Longitudinal relationship of particulate matter and metabolic control and severe hypoglycaemia in children and adolescents with type 1 diabetes.

BACKGROUND: Evidence for the metabolic impact of long-term exposure to air pollution on diabetes is lacking. We investigated the association of particulate matter <10 µm (PM10) and <2.5 µm (PM2.5) with yearly averages of HbA1c, daily insulin dose (IU/kg) and rates of severe hypoglycaemia in type 1 diabetes (T1D). METHODS: We studied data of 44,383 individuals with T1D < 21 years which were documented in 377 German centres within the diabetes prospective follow-up registry (DPV) between 2009 and 2018. Outcomes were aggregated by year and by patient. PM10-and PM2.5-yearly averages prior to the respective treatment year were linked to individuals via the five-digit postcode areas of residency. Repeated measures linear and negative binomial regression were used to study the association between PM-quartiles (Q1 lowest, Q4 highest concentration) and yearly averages of HbA1c, daily insulin dose and rates of severe hypoglycaemia (confounders: sex, time-dependent age, age at diabetes onset, time-dependent type of treatment, migratory background, degree of urbanisation and socioeconomic index of deprivation). RESULTS: Adjusted mean HbA1c increased with PM10 (Q1: 7.96% [95%-CI: 7.95-7.98], Q4: 8.03% [8.02-8.05], p-value<0.001) and with PM2.5 (Q1: 7.97% [7.95-7.99], Q4: 8.02% [8.01-8.04], p < 0.001). Changes in daily insulin dose were inversely related to PM (PM10 and PM2.5: Q1 0.85 IU/kg [0.84-0.85], Q4: 0.83 IU/kg [0.82-0.83], p < 0.001). Adjusted rates of severe hypoglycaemia increased with PM-quartile groups (PM10 Q1:11.2 events/100 PY [10.9-11.5], PM10 Q4: 15.3 [14.9-15.7], p < 0.001; PM2.5 Q1: 9.9 events/100 PY [9.6-10.2], PM2.5 Q4: 14.2 [13.9-14.6], p < 0.001). DISCUSSION: Air pollution was associated with higher HbA1c levels and increased risk of severe hypoglycaemia in people with T1D, consequently indicating a higher risk of diabetes complications. Further studies are needed to explore causal pathways of the observed associations.

Comparison of BMI and HbA1c changes before and during the COVID-19 pandemic in type 1 diabetes: a longitudinal population-based study.

Purpose: To compare the changes in body weight and glycemic control before and during the COVID-19 pandemic in people with type 1 diabetes (T1D). Methods: In 47,065 individuals with T1D from the German Diabetes Prospective Follow-up Registry (DPV), we compared the adjusted mean changes in BMI-Z-scores and HbA1c as well as the distribution of individual changes between four periods from March 2018 to February 2022, by sex and age group (4- < 11, 11- < 16, 16-50 years). Results: At population level, the only significant pandemic effects were a slight increase in BMI Z-score in prepubertal children (girls: + 0.03 in the first COVID year vs. before, P < 0.01; boys: + 0.04, P < 0.01) as well as a stabilization of HbA1c in all subgroups or even improvement in women (- 0.08%, P < 0.01). At individual level, however, heterogeneity increased significantly (p < 0.01), especially in children. More prepubertal children gained weight (girls: 45% vs. 35% before COVID; boys: 39% vs. 33%). More pubertal girls lost weight (30% vs. 21%) and fewer gained weight (43% vs. 54%). More children had a decreasing HbA1c (prepubertal group: 29% vs. 22%; pubertal girls: 33% vs. 28%; pubertal boys: 32% vs. 25%) and fewer had increasing values. More women had stable HbA1c and fewer had increasing values (30% vs. 37%). In men, no significant changes were observed. Conclusion: This real-world analysis shows no detrimental consequences of the two first COVID years on weight and HbA1c in T1D on average, but reveals, beyond the mean trends, a greater variability at the individual level.

Identification of novel GCK and HNF1A/TCF1 mutations and polymorphisms in German families with maturity-onset diabetes of the young (MODY).

Maturity-onset diabetes of the young is a genetically heterogeneous autosomal dominant form of diabetes mellitus, characterized by an early age at onset and a primary defect in beta-cell function. Forty families with a clinical presentation suggestive of MODY were screened for the most common MODY subtypes caused by mutations in the genes encoding glucokinase (GCK, MODY2) and hepatocyte nuclear 1-alpha (HNF1A/TCF1, MODY3). Overall, 14 mutations were found (35%) giving a relative frequency of 22.5% and 12.5% for MODY2 and MODY3, respectively. Five of the nine GCK mutations identified were novel and included two deletions, two nonsense, and one splice site mutation. The GCK splice donor mutation was shown to result in an aberrant transcript owing to the recruitment of a cryptic splice site. The translated protein is predicted to contain an in frame insertion of nine amino acids. Among the five HNF1A mutations identified, three were novel comprising one missense mutation, one deletion, and one insertion. In addition, several novel polymorphisms within GCK were identified and their allele frequencies estimated. Knowledge of the genetic cause of MODY has significant impact on therapeutic decision making and may help to identify family members at risk for diabetes.