Mette K Andersen, Virve Lundgren, Bo Isomaa, Leif Groop and Tiinamaija Tuomi
Previously, we observed an association between family history of type 1 diabetes and development of non-insulin-dependent diabetes. The aims of this study were to assess whether type 1 diabetes susceptibility gene variants explain this association and investigate the effect of the variants on insulin secretion and presence of glutamic acid decarboxylase autoantibodies (GADA) in nondiabetic adults.
Design and methods
Polymorphisms in INS (rs689), PTPN22 (rs2476601), CTLA4 (rs3087243), and the HLA-DQA1-DQB1 regions (rs2187668 and rs7454108 tagging HLA-DQ2.5 and HLA-DQ8 respectively) were genotyped in the Botnia Prospective Study (n=2764), in which initially nondiabetic participants were followed for a mean of 8.1 years.
The variants did not explain the association between family history of type 1 diabetes and development of non-insulin-dependent diabetes. In these nondiabetic adults, HLA-DQ and PTPN22 risk genotypes were associated with GADA (HLA-DQ2.5/HLA-DQ8 or HLA-DQ8: OR (95% CI): 1.7 (1.3–2.3), P=0.0004; PTPN22 CT/TT: OR: 1.6 (1.2–2.2), P=0.003; P values were adjusted for sex, age, BMI, and follow-up time). A higher genetic risk score was associated with lower insulin secretion (insulinogenic index: 13.27 (16.27) vs 12.69 (15.27) vs 10.98 (13.06), P=0.02) and better insulin sensitivity index (risk score of 0–1 vs 2–3 vs 4–6: 142 (111) vs 144 (118) vs 157 (127), P=0.01) at baseline and a poorer capacity to compensate for the increased insulin demand after follow-up.
In nondiabetic adults, HLA-DQ2.5/HLA-DQ8 and PTPN22 CT/TT genotypes were associated with GADA.
Josefin E Löfvenborg, Tomas Andersson, Per-Ola Carlsson, Mozhgan Dorkhan, Leif Groop, Mats Martinell, Tiinamaija Tuomi, Alicja Wolk and Sofia Carlsson
Sweetened beverage intake is associated with increased risk of type 2 diabetes, but its association with autoimmune diabetes is unclear. We aimed to investigate sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA); autoimmune diabetes with features of type 2 diabetes.
Data from a Swedish population-based study was used, including incident cases of LADA (n = 357) and type 2 diabetes (n = 1136) and randomly selected controls (n = 1371). Diabetes classification was based on onset age (≥35), glutamic acid decarboxylase autoantibodies (GADA) and C-peptide. Sweetened beverage intake information was derived from a validated food frequency questionnaire. ORs adjusted for age, sex, family history of diabetes, education, lifestyle, diet, energy intake and BMI were estimated using logistic regression.
Daily intake of >2 servings of sweetened beverages (consumed by 6% of participants) was associated with increased risk of LADA (OR: 1.99, 95% CI: 1.11–3.56), and for each 200 mL daily serving, OR was 1.15 (95% CI: 1.02–1.29). Findings were similar for sugar-sweetened (OR: 1.18, 95% CI: 1.00–1.39) and artificially sweetened beverages (OR: 1.12, 95% CI: 0.95–1.32). Similarly, each daily serving increment in total sweetened beverage conferred 20% higher type 2 diabetes risk (95% CI: 1.07–1.34). In type 2 diabetes patients, high consumers displayed higher HOMA-IR levels (4.5 vs 3.5, P = 0.0002), but lower HOMA-B levels (55 vs 70, P = 0.0378) than non-consumers. Similar tendencies were seen in LADA.
High intake of sweetened beverages was associated with increased risk of LADA. The observed relationship resembled that with type 2 diabetes, suggesting common pathways possibly involving insulin resistance.
Barbara Di Camillo, Liisa Hakaste, Francesco Sambo, Rafael Gabriel, Jasmina Kravic, Bo Isomaa, Jaakko Tuomilehto, Margarita Alonso, Enrico Longato, Andrea Facchinetti, Leif C Groop, Claudio Cobelli and Tiinamaija Tuomi
Type 2 diabetes arises from the interaction of physiological and lifestyle risk factors. Our objective was to develop a model for predicting the risk of T2D, which could use various amounts of background information.
Research design and methods
We trained a survival analysis model on 8483 people from three large Finnish and Spanish data sets, to predict the time until incident T2D. All studies included anthropometric data, fasting laboratory values, an oral glucose tolerance test (OGTT) and information on co-morbidities and lifestyle habits. The variables were grouped into three sets reflecting different degrees of information availability. Scenario 1 included background and anthropometric information; Scenario 2 added routine laboratory tests; Scenario 3 also added results from an OGTT. Predictive performance of these models was compared with FINDRISC and Framingham risk scores.
The three models predicted T2D risk with an average integrated area under the ROC curve equal to 0.83, 0.87 and 0.90, respectively, compared with 0.80 and 0.75 obtained using the FINDRISC and Framingham risk scores. The results were validated on two independent cohorts. Glucose values and particularly 2-h glucose during OGTT (2h-PG) had highest predictive value. Smoking, marital and professional status, waist circumference, blood pressure, age and gender were also predictive.
Our models provide an estimation of patient’s risk over time and outweigh FINDRISC and Framingham traditional scores for prediction of T2D risk. Of note, the models developed in Scenarios 1 and 2, only exploited variables easily available at general patient visits.