ABSTRACT
We aimed to assess the prevalence of diabetic retinopathy (DR) in adult patients with GCK-MODY and HNF1A-MODY in Poland and to identify biochemical and clinical risk factors associated with its occurrence.We examined 74 GCK mutation carriers, 51 with diabetes and 23 with prediabetes, respectively, and 63 patients with HNF1A-MODY. Retinal photographs, 12 for each patient, were done by a fundus camera. Signs of DR were graded according to the DR disease severity scale. Statistical tests were performed to assess differences between the groups and logistic regression was done for the association with DR.The mean age at examination was 34.5±14.8 and 39.9±15.2 in the GCK-MODY and HNF1A-MODY groups, respectively. Mild nonproliferative DR (NPDR) was found in one patient with the GCK mutation and likely concomitant type 1 diabetes, whereas DR was diagnosed in 15 HNF1A-MODY patients: 9 with proliferative, 3 with moderate NPDR and 2 with mild NPDR. In univariate logistic regression analysis in the HNF1A-MODY group, significant results were found for diabetes duration, fasting glycemia, HbA1c, arterial hypertension, age at the examination, and eGFR. The strongest independent predictors of DR in HNF1A-MODY were markers of glucose control: HbA1c (OR: 2.05, CL%95: 1.2-3.83, p=0.01) and glucose (p=0.006, OR: 1.40, CL%95: 1.12-1.83) analyzed in 2 separated models. Additionally, arterial hypertension independently predicted DR (OR: 9.06, CL%95: 1.19-98.99, p=0.04) in the model with HbA1c as glycaemic control marker.In conclusion, DR of any degree was not present in our GCK-MODY group, while in spite of young age almost every fourth subject with HNF1A-MODY showed signs of this complication.
Subject(s)
Diabetic Retinopathy , Hepatocyte Nuclear Factor 1-alpha , Protein Serine-Threonine Kinases , Adult , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Female , Germinal Center Kinases , Hepatocyte Nuclear Factor 1-alpha/genetics , Hepatocyte Nuclear Factor 1-alpha/metabolism , Humans , Male , Middle Aged , Poland/epidemiology , Prevalence , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolismABSTRACT
AIMS/HYPOTHESIS: Most pregnant women with type 1 diabetes mellitus achieve HbA1c targets; however, macrosomia remains prevalent and better pregnancy glycaemic markers are therefore needed. 1,5-Anhydroglucitol (1,5-AG) is a short-term marker of glycaemia, reflecting a period of 1 to 2 weeks. Its excretion rate depends on the renal glucose threshold and thus it is unclear whether it may be used in pregnant type 1 diabetes women. We evaluated 1,5-AG as a glycaemic marker and birthweight predictor in pregnant women with type 1 diabetes, and compared its performance with HbA1c. METHODS: 1,5-AG and HbA1c were measured in 82 pregnant women with type 1 diabetes. In addition, 58 continuous glucose monitoring system (CGMS) records were available. Macrosomia was defined as birthweight >90th centile. The data were analysed with Pearson's correlations, and linear and logistic regression models. Receiver operating characteristic (ROC) analysis was used to evaluate third trimester 1,5-AG as a predictor of macrosomia. RESULTS: Unlike HbA1c, 1,5-AG strongly correlated with CGMS indices: the AUC above 7.8 mmol/l (r = -0.66; p < 0.001), average maximum glucose (r = -0.58; p < 0.001) and mean glucose (r = -0.54; p < 0.001). In the third trimester, 1,5-AG was the strongest predictor of macrosomia, with ROC AUC 0.81 (95% CI 0.70, 0.89). In contrast, HbA1c in the third trimester had a ROC AUC of 0.69 (95% CI 0.58, 0.81). The best discrimination was achieved when both markers were used jointly, yielding a ROC AUC of 0.84 (95% CI 0.76, 0.93). CONCLUSIONS/INTERPRETATION: In pregnant women with type 1 diabetes, 1,5-AG is a better glycaemic marker than HbA1c, as assessed by CGMS. A decreased third trimester 1,5-AG level, either singly or with HbA1c, is a strong predictor of macrosomia.
Subject(s)
Deoxyglucose/blood , Diabetes Mellitus, Type 1/blood , Pregnancy in Diabetics/blood , Adult , Birth Weight , Blood Glucose/metabolism , Female , Glucose/metabolism , Glycated Hemoglobin/metabolism , Humans , Infant, Newborn , Maternal Age , Pregnancy , Pregnancy Trimester, Third , ROC Curve , Regression AnalysisABSTRACT
Mutations in the glucokinase (GCK) gene result in maturity-onset diabetes of the young (MODY). Pharmacotherapy is not effective in GCK MODY. Thus, nutritional intervention seems to be the only therapeutic option. This study evaluated the effect of the quantity of dietary carbohydrate on glucose levels in 10 GCK mutation carriers: seven with MODY and three with prediabetes. All patients were exposed to high-carbohydrate diets for 2 days and then switched to low-carbohydrate diets (60% versus 25% of the daily calorie intake) for another 2 days, after a 1-day washout. Glucose levels were assessed by continuous blood glucose monitoring. In patients with GCK MODY on high-carbohydrate diets, glucose levels were significantly higher, and more hyperglycaemic episodes occurred, compared with patients on low-carbohydrate diets. This short-term observational study suggested that diets with a modestly limited carbohydrate content may improve glycaemic control in patients with GCK MODY.