Variants in MTNR1B influence fasting glucose levels.

To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance. The Australian Diabetes, Obesity and Lifestyle Study (AusDiab)

Background--Diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. The relationship between milder elevations of blood glucose and mortality is less clear. This study investigated whether impaired fasting glucose and impaired glucose tolerance, as well as diabetes mellitus, increase the risk of all-cause and CVD mortality.

Methods and Results--In 1999 to 2000, glucose tolerance status was determined in 10 428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). After a median follow-up of 5.2 years, 298 deaths occurred (88 CVD deaths). Compared with those with normal glucose tolerance, the adjusted all-cause mortality hazard ratios (HRs) and 95% confidence intervals (CIs) for known diabetes mellitus and newly diagnosed diabetes mellitus were 2.3 (1.6 to 3.2) and 1.3 (0.9 to 2.0), respectively. The risk of death was also increased in those with impaired fasting glucose (HR 1.6, 95% CI 1.0 to 2.4) and impaired glucose tolerance (HR 1.5, 95% CI 1.1 to 2.0). Sixty-five percent of all those who died of CVD had known diabetes mellitus, newly diagnosed diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance at baseline. Known diabetes mellitus (HR 2.6, 95% CI 1.4 to 4.7) and impaired fasting glucose (HR 2.5, 95% CI 1.2 to 5.1) were independent predictors for CVD mortality after adjustment for age, sex, and other traditional CVD risk factors, but impaired glucose tolerance was not (HR 1.2, 95% CI 0.7 to 2.2).

Conclusions--This study emphasizes the strong association between abnormal glucose metabolism and mortality, and it suggests that this condition contributes to a large number of CVD deaths in the general population. CVD prevention may be warranted in people with all categories of abnormal glucose metabolism.

Dysglycaemia and other predictors for progression or regression from impaired fasting glucose to diabetes or normoglycaemia

Aims. Diabetes mellitus is a growing health problem worldwide. This study aimed to describe dysglycaemia and determine the impact of body composition and clinical and lifestyle factors on the risk of progression or regression from impaired fasting glucose (IFG) to diabetes or normoglycaemia in Australian women. Methods. This study included 1167 women, aged 20-94 years, enrolled in the Geelong Osteoporosis Study. Multivariable logistic regression was used to identify predictors for progression to diabetes or regression to normoglycaemia (from IFG), over 10 years of follow-up. Results. At baseline the proportion of women with IFG was 33.8% and 6.5% had diabetes. Those with fasting dysglycaemia had higher obesity-related factors, lower serum HDL cholesterol, and lower physical activity. Over a decade, the incidence of progression from IFG to diabetes was 18.1 per 1,000 person-years (95% CI, 10.7-28.2). Fasting plasma glucose and serum triglycerides were important factors in both progression to diabetes and regression to normoglycaemia. Conclusions. Our results show a transitional process; those with IFG had risk factors intermediate to normoglycaemics and those with diabetes. This investigation may help target interventions to those with IFG at high risk of progression to diabetes and thereby prevent cases of diabetes.

Comparison between 100-g glucose tolerance test and two other screening tests for gestational diabetes: combined fasting glucose with risk factors and 50-g glucose tolerance test

CONTEXTO E OBJETIVO: A falta de consenso sobre os protocolos de rastreamento e diagnóstico do diabetes gestacional, associada às dificuldades na realização do teste oral simplificado do diabete gestacional (o teste de tolerância a 100 g de glicose, considerado padrão-ouro) justificam a comparação com alternativas. O objetivo deste trabalho é comparar o teste padrão-ouro a dois testes de rastreamento: associação de glicemia de jejum e fatores de risco (GJ + FR) e o teste oral simplificado de tolerância a 50 g de glicose (TTG 50 g), com o teste de tolerância a 100 g de glicose (TTG 100 g). TIPO DE ESTUDO E LOCAL: Estudo de coorte longitudinal, prospectivo, realizado no Serviço de Ginecologia e Obstetrícia do Hospital Universitário da Universidade Federal de Mato Grosso do Sul. MÉTODOS: 341 gestantes foram submetidas aos três testes. Calcularam-se os índices de sensibilidade (S), especificidade (E), valores preditivos (VPP e VPN), razões de probabilidade (RPP e RPN) e resultados falsos (FP e FN), positivos e negativos da associação GJ + FR e do TTG 50 g em relação ao TTG 100 g. Compararam-se as médias das glicemias de uma hora pós-sobrecarga (1hPS) com 50 e 100 g. Na análise estatística, empregou-se o teste t de Student, com limite de significância de 5%. RESULTADOS: A associação GJ + FR encaminhou mais gestantes (53,9%) para a confirmação diagnóstica que o TTG 50 g (14,4%). Os dois testes foram equivalentes nos índices de S (86,4 e 76,9%), VPN (98,7 e 98,9%), RPN (0,3 e 0,27) e FN (15,4 e 23,1%). As médias das glicemias 1hPS foram semelhantes, 106,8 mg/dl para o TTG 50 g e 107,5 mg/dl para o TTG 100 g. CONCLUSÕES: Os resultados da eficiência diagnóstica associados à simplicidade, praticabilidade e custo referendaram a associação GJ + FR como o mais adequado para o rastreamento. A equivalência das glicemias de 1hPS permitiram a proposição de um novo protocolo de rastreamento e diagnóstico do diabete gestacional, com menores custo e desconforto.

Daily intake of pasteurized orange juice decreases serum cholesterol, fasting glucose and diastolic blood pressure in adults

Previous studies have shown that fresh squeezed orange juice or juice from reconstituted concentrate can help prevent the development of atherosclerosis. Pasteurized orange juice presently represents the major orange juice available in the market, and because of this, it becomes necessary to determine the healthy benefits associated with this product. In this study we investigated the effect of regular consumption of pasteurized orange juice on the nutritional status, biochemical profile, and arterial blood pressure in healthy men and women. Men and women volunteered to consume pasteurized orange juice (500 mL·d–1 and 750 mL·d–1, respectively), for 8 weeks. Anthropometric, biochemical, hemodynamic, and dietary assessments were evaluated at baseline and at the end of the experimental period. Total cholesterol and LDL-C significantly decreased in both men and women after the consumption of orange juice, and an increase in HDL-C level was detected exclusively in women. Fasting glucose, diastolic blood pressure, and triglyceride levels dropped in men after the consumption of orange juice. Anthropometric variables did not change with orange juice consumption, only waist circumference decreased significantly in women. Consumption of orange juice increased the energy and carbohydrate intake for women; however, vitamin C and folate increased after the orange juice period for both men and women. Regular consumption of pasteurized orange juice by men (750 mL·d–1) and women (500 mL·d–1) reduced the risk of developing atherosclerosis, and increased the nutritional quality of their diets.

Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose - Results from the LIPID trial

OBJECTIVE- Diabetes, a major health problem worldwide, increases the risk of cardiovascular disease and its associated mortality. Evidence of the overall benefits of lipid modification in this area is needed. RESEARCH DESIGN AND METHODS- The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that cholesterol-lowering treatment with pravastatin reduced mortality and coronary heart disease (CHD) events in 9,014 patients aged 31-75 years with CHD and total cholesterol 4.0-7.0 mmol/l. We measured the effects of pravastatin therapy, 40 mg/day over 6.0 years, on the risk of CHD death or nonfatal myocardial infarction and other cardiovascular outcomes in 1,077 LIPID patients with diabetes and 940 patients with impaired fasting glucose (IFG). RESULTS- in patients allocated to placebo, the risk of a major CHD event was 61% higher in patients with diabetes and 23% higher in the IFG group than in patients with normal fasting glucose, and the risk of any cardiovascular event was 37% higher in the diabetic group and 19% higher in the IFG group. Pravastatin therapy reduced the risk of a major CHD event overall from 15.9 to 12.3% (relative risk reduction [RRR] 24%, P < 0.001) and from 23.4 to 19.6% in the diabetic group (19%, P = 0.11); in the diabetic group, the reduction was not significantly different from the reductions in the other groups. Pravastatin reduced the risk of any cardiovascular event from 52.7 to 45.2% (21%, P < 0.008) in patients With diabetes and from 45.7 to 37.1% (26%, P = 0.003) in the IFG group. Pravastatin reduced the risk of stroke from 9.9 to 6.3% in the diabetic group (RRR 39%, Cl 7-61%, P = 0.02) and from 5.4 to 3.4% in the IFG group (RRR 42%, Cl -9 to 69%, P = 0.09). Pravastatin did not reduce the incidence of diabetes. Over 6 years, pravastatin therapy prevented one major,CHD event (CHD death or nonfatal myocardial infarction) in 23 patients with IFG and 18 patients with diabetes. A meta-analysis of other major trials confirmed the high absolute risks of diabetes and IFG and the absolute benefits of statin therapy in these patients. CONCLUSIONS- Cholesterol-lowering treatment with pravastatin therapy prevents cardiovascular events, including stroke, in patients with diabetes or IFG and established CHD.

Hyperinsulinism, Insulin Resistance and Impaired Fasting Glucose Revealing an Insulin Autoimmune Syndrome

We report a case of a 55-year-old woman who was evaluated for multiple episodes of late postprandial hypoglycaemia. We diagnosed her condition as insulin autoimmune syndrome (Hirata disease) because of a high insulin autoantibody (IAA) titre in association with high levels of plasmatic insulin and hypoglycaemia in a patient with no history of exogenous insulin administration and the exclusion of other causes of late postprandial hypoglycaemia.

Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia

Abstract Objective: Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia. Methods: Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t=0 min) and lunch (t=330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples. Results: MetS subjects with 3 or 4 components were subdivided into those without (n=34) and with (n=23) fasting hyperglycaemia (≥ 5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (P<0.001). Following the test meals, there was a higher maximum concentration (maxC), area under the curve (AUC) and incremental AUC (P≤0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (P<0.001) and insulin maxC (P=0.010) was also observed in these individuals after the test meals. Multivariate regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response. Conclusion: Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia.

Association of television viewing with fasting and 2-h postchallenge plasma glucose levels in adults without diagnosed diabetes

OBJECTIVE—We examined the associations of television viewing time with fasting plasma glucose (FPG) and 2-h postchallenge plasma glucose (2-h PG) levels in Australian adults.

RESEARCH DESIGN AND METHODS—A total of 8,357 adults aged >35 years who were free from diagnosed diabetes and who attended a population-based cross-sectional study (Australian Diabetes, Obesity and Lifestyle Study [AusDiab]) were evaluated. Measures of FPG and 2-h PG were obtained from an oral glucose tolerance test. Self-reported television viewing time (in the previous week) was assessed using an interviewer-administered questionnaire. Homeostasis model assessment (HOMA) of insulin sensitivity (HOMA-%S) and ß-cell function (HOMA-%B) were calculated based on fasting glucose and insulin concentrations.

RESULTS—After adjustment for confounders and physical activity time, time spent watching television in women was positively associated with 2-h PG, log fasting insulin, and log HOMA-%B and inversely associated with log HOMA-%S (P < 0.05) but not with FPG. No significant associations were observed with glycemic measures in men. The ß-coefficients across categories of average hours spent watching television per day (<1.0, 1.0–1.9, 2.0–2.9, 3.0–3.9, and ≥4.0) for 2-h PG in women were 0 (reference), 0.009, 0.047, 0.473, and 0.501, respectively (P for trend = 0.02).

CONCLUSIONS—Our findings highlight the unique deleterious relationship of sedentary behavior (indicated by television viewing time) and glycemic measures independent of physical activity time and adiposity status. These relationships differed according to sex and type of glucose measurement, with the 2-h PG measure being more strongly associated with television viewing. The findings suggest an important role for reducing sedentary behavior in the prevention of type 2 diabetes and cardiovascular disease, especially in women.

Gender differences in the prevalence of impaired fasting glycaemia and impaired glucose tolerance in Mauritius. Does sex matter?

Objective: To examine gender differences in the characteristics and prevalence of various categories of glucose tolerance in a population study in Mauritius.

Research design and methods: In 1998, a community-based cross-sectional survey was conducted in Mauritius. Categories of glucose metabolism were determined in 5388 adults, with an oral glucose tolerance test given to those who did not have previously diagnosed diabetes (n = 4036). Other cardiovascular risk factors were assessed among those without known diabetes.

Results: For men and women the prevalence of diabetes (22.0 vs. 21.8%, respectively) and the prevalence of coexisting impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (3.2 vs. 2.9%) were similar. However, men were twice as likely as women to have isolated IFG [5.1% (4.2–6.0) vs. 2.9% (2.3–3.5)], despite being younger, thinner and with lower plasma insulin but higher lipids. Conversely, the prevalence of isolated IGT was lower in men [9.0% (7.9–10.2) vs. 13.9% (12.6–15.1)]. Among non-diabetic individuals, fasting glucose was higher in men than women, whereas 2-h glucose was higher in women. In people without diabetes, women had significantly higher body mass index, beta cell function (HOMA-B), fasting and 2-h insulin than men and significantly lower waist-hip ratios, waist circumference, insulin sensitivity (HOMA-S) and triglycerides.

Conclusion: In Mauritius, the distribution of impaired glucose metabolism differs by sex. The observation that IFG is more prevalent in men and IGT more prevalent in women raises important questions about their underlying aetiology and the ability of the current glucose thresholds to equally identify men and women at high-risk of developing diabetes. IFG should be seen as a complimentary category of abnormal glucose tolerance, rather than a replacement for IGT.

Fasting plasma glucose predicts survival and angiographic progression in high-risk postmenopausal women with coronary artery disease

BACKGROUND: We studied the association of baseline fasting plasma glucose (FPG) levels with survival and coronary artery disease (CAD) progression among postmenopausal women without unstable angina. METHODS: Women were recruited from seven centers in the Women's Angiographic Vitamin and Estrogen Trial (WAVE) (n = 423). Event follow-up was available for 400 women (65.1 +/- 8.5 years, 66% white, 92% hypertensive, 19% smokers, 67% hypercholesterolemic). Thirty-eight percent of the women had diabetes or FPG > 125 mg/dL, and 21% had a fasting glucose 100-125 mg/dL. Follow-up angiography was performed in 304 women. Cox regression was used to model survival from a composite outcome of death or myocardial infarction (D/MI, 26 events; median follow-up 2.4 years). Angiographic progression was analyzed quantitatively using linear regression accounting for baseline minimum lumen diameter (MLD), follow-up time, and intrasubject correlations using generalized estimating equations. Regression analyses were adjusted for follow-up time, baseline age, treatment assignment, and Framingham risk (excluding diabetes). RESULTS: Women with impaired fasting glucose/diabetes mellitus (IFG/DM) had a relative risk (RR) of D/MI of 4.2 ( p = 0.009). In all women, each 10 mg/dL increase in FPG was associated with an 11% increase ( p < 0.001) in the hazard of D/MI. Each 10 mg/dL increase in FPG was associated with a 6.8 mum decrease in MLD over the follow-up period ( p = 0.005). CONCLUSIONS: Higher FPG is associated with increased risk of D/MI and greater narrowing of the coronary lumen in women with CAD. Aggressive monitoring of glucose levels may be beneficial for secondary CAD prevention.