Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women

OBJECTIVE: To investigate the association of retinopathy with the risk of all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in type 2 diabetic subjects in a population-based 18-year follow-up study with particular emphasis on sex differences. RESEARCH DESIGN AND METHODS: Our study cohort comprised 425 Finnish type 2 diabetic men and 399 type 2 diabetic women who were free of CVD at baseline. The findings were classified based on standardized clinical ophthalmoscopy to categories of no retinopathy, background retinopathy, and proliferative retinopathy. The study end points were all-cause, CVD, and CHD mortality. RESULTS: Adjusted Cox model hazard ratios (95% CIs) of all-cause, CVD, and CHD mortality in men were 1.34 (0.98-1.83), 1.30 (0.86-1.96), and 1.18 (0.74-1.89), respectively, for background retinopathy and 3.05 (1.70-5.45), 3.32 (1.61-6.78), and 2.54 (1.07-6.04), respectively, for proliferative retinopathy and in women 1.61 (1.17-2.22), 1.71 (1.17-2.51), and 1.79 (1.13-2.85), respectively, for background retinopathy and 2.92 (1.41-6.06), 3.17 (1.38-7.30), and 4.98 (2.06-12.06), respectively, for proliferative retinopathy. CONCLUSIONS: Proliferative retinopathy in both sexes and background retinopathy in women predicted all-cause, CVD, and CHD death. These associations were independent of current smoking, hypertension, total cholesterol, HDL cholesterol, glycemic control of diabetes, duration of diabetes, and proteinuria. This suggests the presence of common background pathways for diabetic microvascular and macrovascular disease other than those included in the conventional risk assessment of CVD. The sex difference observed in the association of background retinopathy with macrovascular disease warrants closer examination.     

Transient loss of consciousness as reason for admission to primary health care emergency room

OBJECTIVE: To study the occurrence and main causes of transient loss of consciousness in primary health care. DESIGN: A 4-month prospective survey. SETTING: Primary health care emergency room of the City of Tampere, Finland. SUBJECTS: Consecutive patients, aged over 15 years, admitted to the emergency room. MAIN OUTCOME MEASURES: The overall prevalence of loss of consciousness divided into three subgroups: seizure, syncope and uncertain, and their distribution by gender and age. The prevalence of epilepsy, coronary heart disease and alcohol abuse among these diagnostic subgroups. RESULTS: Of all emergency room visits, 1.2% were for loss of consciousness. Of these, 53% were diagnosed as seizures, 33% as syncope attacks and 14% as uncertain. In the seizure group, 75% of patients were men and 67% had a history of alcohol abuse. In the syncope group, 44% of patients had coronary heart disease and 68% were women. CONCLUSION: Loss of consciousness is a fairly frequent problem for the primary health care emergency room. A history of alcohol abuse is commonly associated with seizures.     

Importance of obtaining independent measures of insulin secretion and insulin sensitivity during the same test: results with the Botnia clamp

OBJECTIVE: To validate and apply a method for independent assessment of insulin secretion and insulin sensitivity (S(I)) during the same test; that is, an intravenous glucose tolerance test followed by a euglycemic-hyperinsulinemic clamp, also called the Botnia clamp. This test was then applied to nondiabetic subjects with (FH+) and without (FH-) a first-degree family history of diabetes. RESEARCH DESIGN AND METHODS: The Botnia clamp measures the first-phase insulin response (FPIR) to 0.3g/kg glucose i.v. and insulin sensitivity (M-value) from a 2-h euglycemic clamp begun 60 min after the glucose bolus. The M-value obtained during the Botnia clamp was compared with M-values obtained during a regular euglycemic clamp without prior glucose bolus. Repeated tests were performed in random order in subjects with normal and abnormal glucose tolerance. Finally, the test was applied to subjects with and without a family history of type 2 diabetes. RESULTS: S(I) and insulin secretion from this test showed a high degree of reproducibility, and the M-value obtained with the Botnia clamp correlated strongly with the M-value from a euglycemic clamp without prior glucose bolus (r = 0.953, P < 0.005). FH+ subjects showed decreased S(I) (P = 0.02), but similar FPIR, compared with FH- subjects. However, insulin secretion adjusted for the degree of insulin resistance was significantly impaired (P = 0.04). CONCLUSIONS: In conclusion, the Botnia clamp provides reliable and independent measures of S(I) and beta-cell function during the same test. As illustrated above, knowledge of the degree of S(I) is mandatory when presenting data on insulin secretion.     

The associations of daylight and melatonin receptor 1B gene rs10830963 variant with glycemic traits: the prospective PPP-Botnia study

Background: Seasonal variation in glucose metabolism might be driven by changes in daylight. Melatonin entrains circadian regulation and is directly associated with daylight. The relationship between melatonin receptor 1B gene variants with glycemic traits and type 2 diabetes is well established. We studied if daylight length was associated with glycemic traits and if it modified the relationship between melatonin receptor 1B gene rs10830963 variant and glycemic traits.Materials: A population-based sample of 3422 18–78-year-old individuals without diabetes underwent an oral glucose tolerance test twice, an average 6.8 years (SD = 0.9) apart and were genotyped for rs10830963. Daylight data was obtained from the Finnish Meteorological Institute.Results: Cross-sectionally, more daylight was associated with lower fasting glucose, but worse insulin sensitivity and secretion at follow-up. Longitudinally, individuals studied on lighter days at follow-up than at baseline showed higher glucose values during the oral glucose tolerance test and lower Corrected Insulin Response at follow-up. GG genotype carriers in the rs10830963 became more insulin resistant during follow-up if daylight length was shorter at follow-up than at baseline.Conclusions: Our study shows that individual glycemic profiles may vary according to daylight, MTNR1B genotype and their interaction. Future studies may consider taking daylight length into account.

Key messages

• In Western Finland, the amount daylight follows an extensive annual variation ranging from 4 h 44 min to 20 h 17 min, making it ideal to study the associations between daylight and glycemic traits. Moreover, this allows researchers to explore if the relationship between the melatonin receptor 1B gene rs10830963 variant and glycemic traits is modified by the amount of daylight both cross-sectionally and longitudinally.
• This study shows that individuals, who participated in the study on lighter days at the follow-up than at the baseline, displayed to a greater extent worse glycemic profiles across the follow-up.
• Novel findings from the current study show that in the longitudinal analyses, each addition of the minor G allele of the melatonin receptor 1B gene rs10830963 was associated with worsening of fasting glucose values and insulin secretion across the 6.8-year follow-up.
• Importantly, this study shows that in those with the rs10830963 GG genotype, insulin sensitivity deteriorated the most significantly across the 6.8-year follow-up if the daylight length on the oral glucose tolerance testing date at the follow-up was shorter than at the baseline.
• Taken together, the current findings suggest that the amount of daylight may affect glycemic traits, especially fasting glucose and insulin secretion even though the effect size is small. The association can very according to the rs10830963 risk variant. Further research is needed to elucidate the mechanisms behind these associations.

     

Dietary fat predicts coronary heart disease events in subjects with type 2 diabetes

OBJECTIVE: To investigate whether quantity or quality of dietary fat predicts coronary heart disease (CHD) events in middle-aged type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: The dietary habits of 366 type 2 diabetic men and 295 women, aged 45-64 years and free from CHD, were assessed with a 53-item food frequency questionnaire. They were followed up for 7 years. RESULTS: Men in the highest tertile of the polyunsaturated/saturated fat (P/S) ratio (>0.28) had a significantly lower risk for CHD death than men in the two lowest tertiles (5.0 vs. 14.2%, P = 0.009). The risk for all CHD events was 14.2 vs. 23.2%, respectively (P = 0.044). P/S ratio did not predict CHD events in women. In Cox multiple regression analyses taking into account other cardiovascular risk factors, the highest P/S ratio tertile was associated with the lowest rate of CHD death in men (P = 0.048). CONCLUSIONS: Low P/S ratio in men predicted future CHD events in type 2 diabetic subjects independently of conventional CHD risk factors.     

ERP denoising in multichannel EEG data using contrasts between signal and noise subspaces

In this paper, a new method intended for ERP denoising in multichannel EEG data is discussed. The denoising is done by separating ERP/noise subspaces in multidimensional EEG data by a linear transformation and the following dimension reduction by ignoring noise components during inverse transformation. The separation matrix is found based on the assumption that ERP sources are deterministic for all repetitions of the same type of stimulus within the experiment, while the other noise sources do not obey the determinancy property. A detailed derivation of the technique is given together with the analysis of the results of its application to a real high-density EEG data set. The interpretation of the results and the performance of the proposed method under conditions, when the basic assumptions are violated – e.g. the problem is underdetermined – are also discussed.Moreover, we study how the factors of the number of channels and trials used by the method influence the effectiveness of ERP/noise subspaces separation. In addition, we explore also the impact of different data resampling strategies on the performance of the considered algorithm. The results can help in determining the optimal parameters of the equipment/methods used to elicit and reliably estimate ERPs.     

Continuous glucose monitoring versus self-monitoring of blood glucose in the treatment of gestational diabetes mellitus

OBJECTIVE: To compare Continuous Glucose Monitoring System (CGMS) with self-monitoring of plasma glucose (SM) in detecting patients with gestational diabetes mellitus (GDM) needing antidiabetic drug treatment. RESEARCH DESIGN AND METHODS: Pregnant women at 22-34 gestational weeks had at least two abnormal high values out of three in OGTT. Patients were randomly allocated to have CGMS) (n=36) or SM (n=37). Dietary counselling was similar in both groups. Patients tested their plasma glucose 5 times per day. Need of antidiabetic treatment was determined using the following cut-off values: fasting plasma glucose >5.5mmol/L twice or >5.5mmol/l once and postprandial value>7.8mmol/l, or postprandial value at least twice above 7.8mmol/l. RESULTS: In 11 out of 36 patients (31%) monitored with CGMS) antihyperglycemic drug therapy was introduced (8/36 insulin only, 2/36 metformin only, 1/36 insulin+metformin) whereas only 3/37 (8%) in the self-monitoring group were drug-treated (difference between groups, p=0.0149). There were no statistically significant differences between the groups regarding maternal age, pre-pregnancy BMI, HbA1c, gestational weeks at delivery, rate of pregnancy-induced hypertension, rate of caesarean section, infant birth weight or neonatal hypoglycaemia. CONCLUSIONS: Continuous glucose monitoring system detects a markedly higher proportion of GDM mothers needing antihyperglycemic medication compared with self-monitoring of plasma glucose. Further large-scale studies are needed to evaluate whether CGMS) guided initiation of antihyperglycemic therapy results in less macrosomia and perinatal complications related to GDM.     

Polymorphisms in the gene encoding the voltage-dependent Ca<Superscript>2+</Superscript> channel Ca<Subscript>V</Subscript>2.3 (<Emphasis Type="Italic">CACNA1E</Emphasis>) are associated with type 2 diabetes and impaired insulin secretion

Aims/hypothesis Glucose-stimulated insulin secretion is dependent on the electrical activity of beta cells; hence, genes encoding beta cell ion channels are potential candidate genes for type 2 diabetes. The gene encoding the voltage-dependent Ca²⁺ channel Ca_V2.3 (CACNA1E), telomeric to a region that has shown suggestive linkage to type 2 diabetes (1q21-q25), has been ascribed a role for second-phase insulin secretion. Methods Based upon the genotyping of 52 haplotype tagging single nucleotide polymorphisms (SNPs) in a type 2 diabetes case–control sample (n = 1,467), we selected five SNPs that were nominally associated with type 2 diabetes and genotyped them in the following groups (1) a new case–control sample of 6,570 individuals from Sweden; (2) 2,293 individuals from the Botnia prospective cohort; and (3) 935 individuals with insulin secretion data from an IVGTT. Results The rs679931 TT genotype was associated with (1) an increased risk of type 2 diabetes in the Botnia case–control sample [odds ratio (OR) 1.4, 95% CI 1.0–2.0, p = 0.06] and in the replication sample (OR 1.2, 95% CI 1.0–1.5, p = 0.01 one-tailed), with a combined OR of 1.3 (95% CI 1.1–1.5, p = 0.004 two-tailed); (2) reduced insulin secretion [insulinogenic index at 30 min p = 0.02, disposition index (D _I) p = 0.03] in control participants during an OGTT; (3) reduced second-phase insulin secretion at 30 min (p = 0.04) and 60 min (p = 0.02) during an IVGTT; and (4) reduced D _I over time in the Botnia prospective cohort (p = 0.05). Conclusions/interpretation We conclude that genetic variation in the CACNA1E gene contributes to an increased risk of the development of type 2 diabetes by reducing insulin secretion. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Association studies of BMI and type 2 diabetes in the neuropeptide Y pathway: a possible role for NPY2R as a candidate gene for type 2 diabetes in men

The neuropeptide Y (NPY) family of peptides and receptors regulate food intake. Inherited variation in this pathway could influence susceptibility to obesity and its complications, including type 2 diabetes. We genotyped a set of 71 single nucleotide polymorphisms (SNPs) that capture the most common variation in NPY, PPY, PYY, NPY1R, NPY2R, and NPY5R in 2,800 individuals of recent European ancestry drawn from the near extremes of BMI distribution. Five SNPs located upstream of NPY2R were nominally associated with BMI in men (P values = 0.001-0.009, odds ratios [ORs] 1.27-1.34). No association with BMI was observed in women, and no consistent associations were observed for other genes in this pathway. We attempted to replicate the association with BMI in 2,500 men and tested these SNPs for association with type 2 diabetes in 8,000 samples. We observed association with BMI in men in only one replication sample and saw no association in the combined replication samples (P = 0.154, OR = 1.09). Finally, a 9% haplotype was associated with type 2 diabetes in men (P = 1.73 x 10(-4), OR = 1.36) and not in women. Variation in this pathway likely does not have a major influence on BMI, although small effects cannot be ruled out; NPY2R should be considered a candidate gene for type 2 diabetes in men.