Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes

Abstract

IntroductionThis study aimed to assess the association between fasting serum C-peptide levels and the presence of impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes.Research design and methodsWe performed a cross-sectional study among 509 individuals with type 1 diabetes (diabetes duration 5–65 years). Extensive clinical data and fasting serum C-peptide concentrations were collected and related to the presence or absence of IAH, which was evaluated using the validated Dutch version of the Clarke questionnaire. A multivariable logistic regression model was constructed to investigate the association of C-peptide and other clinical variables with IAH.ResultsIn 129 (25%) individuals, residual C-peptide secretion was detected, while 75 (15%) individuals reported IAH. The median (IQR) C-peptide concentration among all participants was 0.0 (0.0–3.9) pmol/L. The prevalence of severe hypoglycemia was lower in people with demonstrable C-peptide versus those with absent C-peptide (30% vs 41%, p=0.025). Individuals with IAH were older, had longer diabetes duration, more frequently had macrovascular and microvascular complications, and more often used antihypertensive drugs, antiplatelet agents and cholesterol-lowering medication. There was a strong association between IAH and having a severe hypoglycemia in the preceding year. In multivariable regression analysis, residual C-peptide, either continuously or dichotomous, was associated with lower prevalence of IAH (p=0.040–0.042), while age at diabetes onset (p=0.001), presence of microvascular complications (p=0.003) and body mass index (BMI) (p=0.003) were also independently associated with the presence of IAH.ConclusionsHigher BMI, the presence of microvascular complications and higher age at diabetes onset were independent risk factors for IAH in people with type 1 diabetes, while residual C-peptide secretion was associated with lower risk of this complication.

N-3 PUFA and Pregnancy Preserve C-Peptide in Women with Type 1 Diabetes Mellitus

“…A lower prevalence of severe hypoglycemia and a decline in required total insulin units during pregnancy were associated with increased endogenous insulin secretion. C-peptide serves as the mediator in the correlation between the duration of type 1 diabetes and the required total insulin dose [42,43] (Table 1). Hypoglycemia in pregnant women with type 1 diabetes most often occurs due to insulin overdose or untimely insulin delivery, missed or reduced (insufficient) meals, emesis or hyperemesis in the first trimester of pregnancy, gastroparesis, or increased glucose consumption during and immediately after exercise [8].…”

Fall in prevalence of impaired awareness of hypoglycaemia in individuals with type 1 diabetes

“…In accordance with previous findings, individuals with IAH in the present cohort were significantly older than individuals with NAH and had a longer duration of diabetes, higher frequency of (severe) hypoglycaemia and more microvascular complications compared to individuals with NAH. Also, the level of glucose control, reflected for instance by the HbA 1c level, did not show any association with the hypoglycaemia awareness state 5,7,8,26 . It is worth mentioning that more than 82% of individuals with NAH at one point were found to preserve normal awareness at a later timepoint, reflecting the persistence of normal awareness.…”

“…The proportion of participants reporting a history of severe hypoglycaemia based on the modified Clarke questionnaire 25,26 was 21.2% in 2006, 46.7% in 2010, 49.8% in 2016 and 13.1% in 2020 ( p ‐value for trend 0.010). In fact, both questions of the modified Clarke questionnaire relating to severe hypoglycaemia were positively answered by fewer individuals in 2020 as compared to those in 2010 and 2016 ( p ‐value for trend <0.001) (Table 4).…”

Multi-Faceted Influence of Obesity on Type 1 Diabetes in Children – From Disease Pathogenesis to Complications

“…Likewise, while residual C-peptide secretion was proved to be correlated with lower risk of severe hypoglycaemia in T1D,people with higher BMI present this complication more often, presumably due to the fact that excessive weight impacts on impaired awareness of hypoglycaemia. The causes of this phenomenon are not completely understood, so it requires further investigation ( 104 ).…”