Tiinamaija Tuomi

Fasting versus postload plasma glucose concentration and the risk for future type 2 diabetes: results from the Botnia Study.

OBJECTIVE—The purpose of this study was to assess the efficacy of the postload plasma glucose concentration in predicting future risk of type 2 diabetes, compared with prediction models based on measurement of the fasting plasma glucose (FPG) concentration. RESEARCH DESIGN AND METHODS—A total of 2,442 subjects from the Botnia Study, who were free of type 2 diabetes at baseline, received an oral glucose tolerance test (OGTT) at baseline and after 7–8 years of follow-up. Future risk for type 2 diabetes was assessed with area under the receiver-operating characteristic curve for prediction models based up measurement of the FPG concentration 1) with or without a 1-h plasma glucose concentration during the OGTT and 2) with or without the metabolic syndrome. RESULTS—Prediction models based on measurement of the FPG concentration were weak predictors for the risk of future type 2 diabetes. Addition of a 1-h plasma glucose concentration markedly enhanced prediction of the risk of future type 2 diabetes. A cut point of 155 mg/dl for the 1-h plasma glucose concentration during the OGTT and presence of the metabolic syndrome were used to stratify subjects in each glucose tolerance group into low, intermediate, and high risk for future type 2 diabetes. CONCLUSIONS—The plasma glucose concentration at 1 h during the OGTT is a strong predictor of future risk for type 2 diabetes and adds to the prediction power of models based on measurements made during the fasting state. A plasma glucose cut point of 155 mg/dl plus the Adult Treatment Panel III criteria for the metabolic syndrome can be used to stratify nondiabetic subjects into low-, intermediate-, and high-risk groups.

High frequency of mutations in MODY and mitochondrial genes in Scandinavian patients with familial early-onset diabetes.

Aims/hypothesis. To investigate the contribution of mutations in maturity-onset diabetes of the young (MODY) and mitochondrial genes to early-onset diabetes with a strong family history of diabetes in a cohort with a high prevalence of Type I (insulin-dependent) diabetes mellitus. Methods. Screening for sequence variants in the hepatocyte nuclear factor (HNF)–4α (MODY1), glucokinase (MODY2), HNF-1α (MODY3) genes and mitochondrial DNA was carried out in 115 Finnish and Swedish patients with early-onset ( ≤ 40 years) diabetes using the single strand conformation polymorphism (SSCP) technique and direct sequencing. Allele frequencies were compared with 118 patients with onset of diabetes Type II (non-insulin-dependent) diabetes mellitus after the age of 40 and 92 non–diabetic control subjects without a family history of diabetes. Results. In total 52 sequence variants were found in the HNF-1α, HNF-4α and glucokinase genes, 12 of which were considered as MODY mutations. Three families had the A3243G mutation in the mitochondrial tRNALeu gene, which resulted in an overall prevalence of these mutations of 13 %. Conclusion/interpretation. Among 115 Scandinavian families, mutations in the HNF-1α gene represented the most common cause of familial early-onset ( ≤ 40 years) diabetes: MODY3 (5.2 %) more than MODY2 (3.5 %) more than MIDD (2.6 %) more than MODY1 (1.7 %). [Diabetologia (1999) 42: 1131–1137]

Non-insulin-dependent Diabetes Mellitus - A Collision between Thrifty Genes and an Affluent Society

Non-insulin-dependent diabetes mellitus (NIDDM) is one of the most common non-communicable diseases in the world. It has become obvious that NIDDM is the result of a collision between thrifty genes and an affluent society. Genes predisposing to NIDDM might have been survival genes for our ancestors, helping them to store energy during long periods of starvation. When these genes are exposed to a sedentary lifestyle and high caloric intake typical to the Western world, they predispose to obesity and insulin resistance. NIDDM results when beta cells cannot compensate for insulin resistance by increasing insulin secretion. Therefore, at least two inherited defects can be expected in NIDDM, one causing obesity and insulin resistance and the other inability to increase insulin secretion. In reality there may be more inherited defects. It has become quite clear that diabetes cannot simply be divided into NIDDM and insulin-dependent diabetes mellitus (IDDM). The disease is more heterogeneous; unmasking this heterogeneity and identifying new subgroups of diabetes presents a challenge to modern molecular biology.

The shape of plasma glucose concentration curve during OGTT predicts future risk of type 2 diabetes

The aim of the study is to assess the relationship between the shape of plasma glucose concentration during the OGTT and future risk for T2DM.

Minimal Contribution of Fasting Hyperglycemia to the Incidence of Type 2 Diabetes in Subjects With Normal 2-h Plasma Glucose

OBJECTIVE To assess the relative contribution of increased fasting and postload plasma glucose concentrations to the incidence of type 2 diabetes in subjects with a normal 2-h plasma glucose concentration. RESEARCH DESIGN AND METHODS A total of 3,450 subjects with 2-h plasma glucose concentration <140 mg/dl at baseline were followed up in the San Antonio Heart Study (SAHS) and the Botnia Study for 7–8 years. The incidence of type 2 diabetes at follow-up was related to the fasting, 1-h, and 2-h plasma glucose concentrations. RESULTS In subjects with 2-h plasma glucose <140 mg/dl, the incidence of type 2 diabetes increased with increasing fasting plasma glucose (FPG) and 1-h and 2-h plasma glucose concentrations. In a multivariate logistic analysis, after adjustment for all diabetes risk factors, the FPG concentration was a strong predictor of type 2 diabetes in both the SAHS and the Botnia Study (P < 0.0001). However, when the 1-h plasma glucose, but not 2-h plasma glucose, concentration was added to the model, FPG concentration was no longer a significant predictor of type 2 diabetes in both studies (NS). When subjects were matched for the level of 1-h plasma glucose concentration, the incidence of type 2 diabetes markedly increased with the increase in 1-h plasma glucose, but the increase in FPG was not associated with a significant increase in the incidence of type 2 diabetes. CONCLUSIONS An increase in postload glycemia in the normal range is associated with an increase in the incidence of type 2 diabetes. After controlling for 1-h plasma glucose concentration, the increase in FPG concentration is not associated with an increase in the incidence of type 2 diabetes.

Alcohol and the risk for latent autoimmune diabetes in adults: results based on Swedish ESTRID study

Objective Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design A population-based case–control study was carried out to investigate the association of alcohol consumption and the risk of LADA. Methods We used data from the ESTRID case–control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged ≥35. Logistic regression was used to estimate the odds ratios (ORs) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Results Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92–0.99 for every 5-g increment in daily intake). Similar results were observed for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA levels (OR 0.85, 95% CI 0.76–0.94/5 g alcohol per day), whereas no association was observed with LADA having high GADA levels (OR 1.00, 95% CI 0.94–1.06/5 g per day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in homeostasis model assessment of insulin resistance (P=0.0418). Conclusions Our findings indicate that alcohol intake may reduce the risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.

Type 1 Diabetes in Autoimmune Syndromes

Two fundamentally different autoimmune polyendocrine syndromes (APSs) are generally recognized, and type 1 diabetes mellitus is common in both (see Table 1). APS type 1 (APS-1) or autoimmune polyendocrinopathy—candidiasis—ectodermal dystrophy (APECED) is an autosomal recessive disease. It can often be diagnosed by clinical criteria (presence of mucocutaneous candidiasis and/or hypoparathyroidism, which do not occur in APS-2) or by DNA analysis.