ABSTRACT
AIMS: To evaluate risk factors for severe hypoglycaemia (SH) in patients with type 1 diabetes (T1DM). METHODS AND RESULTS: Retrospective observational and comparative study. All SH occurring between 2007 and 2014 in a German population (Lippe-Detmold) were captured. Characteristics of patients with T1DM and SH were compared with a control group being equivalent concerning age, diabetes duration, HbA1c, comorbidity, and ß-blocker treatment. SH was defined as a symptomatic event requiring treatment with intravenous glucose or glucagon administration and being confirmed by a blood glucose measurement of <2.8 mmol/l. Predictive factors for SH were analysed by a multivariable regression model. As many as 405 cases of SH in T1DM occurred in 206 subjects; 50% of episodes were related to 31 patients who experienced ≥3 SH. Need for nursing care (OR 4.88), treatment with NPH (OR 3.68), and impaired hypoglycaemia awareness (OR 2.06) were the strongest risk factors for SH (all p < 0.05, all pFDR-adjusted < 0.10; false discovery rate (FDR)). Depression (OR 0.14), treatment with CSII (OR 0.39) and short-acting insulin analogues (OR 0.31) appeared to be protective (all p < 0.10; FDR-adjusted). The probability of SH onset was significantly higher in patients who had previously experienced recurrent SH episodes. ß-Blocker treatment did not appear to be a risk factor. CONCLUSION: The complex risk for SH in people with T1DM can be reduced by treatment with CSII and short-acting analogues. Future structures of diabetes care will be challenged by the need of treating increasingly geriatric subjects with T1DM having a high risk of SH.
Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemia/chemically induced , Hypoglycemia/prevention & control , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Adult , Age Factors , Aged , Biomarkers/blood , Blood Glucose/metabolism , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/diagnosis , Drug Administration Schedule , Drug Compounding , Female , Germany , Glycated Hemoglobin/metabolism , Home Health Nursing , Humans , Hypoglycemia/blood , Hypoglycemia/diagnosis , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Multivariate Analysis , Nursing Homes , Odds Ratio , Proportional Hazards Models , Protective Factors , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: Severe hypoglycaemia (SH) induced by sulfonylureas is a life-threatening condition. We hypothesized that recently identified polymorphisms associated with insulin secretion in GCKR, GIPR, ADCY5 and VPS13C genes affect the response to sulfonylureas in patients with type 2 diabetes (T2D) and so, result in reduced risk for SH. RESEARCH DESIGN AND METHODS: We assessed the prevalence of GCKR, GIPR, ADCY5 and VPS13C polymorphisms in a case-control study including 111 patients with SH and 100 patients with T2D but without a history of SH. All patients were treated with the sulfonylurea drugs glimepiride, glibenclamide or gliquidon. SH was defined as a symptomatic event with blood glucose of <50 mg/dl requiring treatment with intravenous glucose. RESULTS: In logistic regression analyses, a low HbA(1c) and a higher sulfonylurea dose appeared to be the only predictors of SH (P=0.001 and P=0.04, respectively). There was no significant difference in the genotype distribution between the control group and the cases with SH for any of the investigated polymorphisms (OR and 95% confidence intervals - 0.90 (0.59-1.38) for GCKR; 1.11 (0.67-1.85) for GIPR; 0.75 (0.48-1.17) for ADCY5; 1.43 (0.95-2.15) for VPS13C; all P-values >0.05). Also, there was no significant effect of the examined genetic variants on HbA1c levels (all P-values >0.05 adjusted for age, sex, BMI, diabetes duration, sulfonylurea dose). CONCLUSIONS: We found no detectable effect (with an OR >2.1) of the variants in GCKR, GIPR, ADCY5 and VPS13C on the response to sulfonylurea treatment, indicating that these variants are not significantly contributing to the risk of SH in patients with T2D.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Adenylyl Cyclases/genetics , Diabetes Mellitus, Type 2 , Hypoglycemia , Hypoglycemic Agents , Polymorphism, Genetic , Proteins/genetics , Receptors, Gastrointestinal Hormone/genetics , Sulfonylurea Compounds , Aged , Aged, 80 and over , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Female , Humans , Hypoglycemia/chemically induced , Hypoglycemia/genetics , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Male , Middle Aged , Risk Factors , Severity of Illness Index , Sulfonylurea Compounds/administration & dosage , Sulfonylurea Compounds/adverse effectsABSTRACT
OBJECTIVE: To assess the number and sex ratio of children in individuals with Type 1 diabetes mellitus and the influence of parental diabetes on age at onset of Type 1 diabetes in our cohort. METHODS: In a cross-sectional study in a German region comprising 350,000 inhabitants, 697 subjects with Type 1 diabetes (364 women, 333 men) underwent a standardized assessment regarding the number and sex of their children and the family history of diabetes. RESULTS: Compared with 1.36 children per woman in the German background population, the total fertility rate in the calendar year of 2010 in our female cohort with Type 1 diabetes (age 18-49 years) was 0.88. Men with Type 1 diabetes had a fertility rate of 0.65. More men (51.1%) than women (35.7%; P < 0.0001) were childless. Twenty per cent of all women aged 41-45 years in the background population were childless compared with 36.2% of all women and 52% of all men in this specific age group from our cohort. The sex ratio of female vs. male offspring of individuals with Type 1 diabetes did not differ significantly from the expected 1:1 ratio. Maternal Type 1 or Type 2 diabetes increased the age at onset of Type 1 diabetes from 22.9 ± 13.7 (no maternal diabetes) to 28.6 ± 16.8 and 30.1 ± 15.1 years (p < 0.0001), respectively. CONCLUSIONS: Compared with the German reference population, individuals with Type 1 diabetes had significantly fewer children and were more often childless. The sex ratio female vs. male offspring of women and men with Type 1 diabetes was unaffected. Maternal history of Type 1 and Type 2 diabetes was associated with a significant later onset of Type 1 diabetes.
