Prospective association between late evening food consumption and risk of prediabetes and diabetes: the Whitehall II cohort study.

AIMS: We examined whether late evening food consumption was prospectively associated with the risk of developing prediabetes or diabetes in a large observational study of individuals with normoglycaemia. METHODS: Participants were 2642 men and women with normoglycaemia (HbA1c < 39 mmol/mol; < 5.7%) from the Whitehall II study. Time of last eating episode (TLEE) before the examination day was assessed at baseline. We studied the associations of TLEE with 5-year changes in HbA1c and risk of developing prediabetes or diabetes (HbA1c ≥ 39 mmol/mol; ≥ 5.7%). Potential heterogeneity in the association between TLEE and prediabetes or diabetes was examined using recursive partitioning modelling for time-to-event outcomes. RESULTS: There was a tendency of an overall association of TLEE with change in HbA1c but with little effect size [ß per 1-h increase in TLEE = 0.2 mmol/mol, 95% CI -0.0 to 0.3 (0.01%, -0.00 to 0.03); P = 0.055] and no association with the risk of developing prediabetes/diabetes (risk ratio per 1-h increase in TLEE = 1.03, 95% CI 0.94 to 1.13; P = 0.511). According to the recursive partitioning modelling, women with HbA1c ≤ 36 mmol/mol and TLEE after 21:00 had a 1.51 times (95% CI 1.16 to 1.93) higher 5-year risk of developing prediabetes or diabetes than those having their TLEE between 16:00 and 21:00 (35.4% vs. 23.5%; P = 0.003). CONCLUSIONS: There was no overall association of TLEE with the development of prediabetes or diabetes in the Whitehall II population. However, explorative analyses suggested that eating late in the evening was associated with increased risk of developing prediabetes/diabetes among women with good glycaemic control. Whether restricting late evening food consumption is effective and feasible for the prevention of Type 2 diabetes needs testing in randomized controlled trials.

Is there a connection between postprandial hyperglycemia and IGT related sensory nerve dysfunction?

BACKGROUND AND AIMS: To assess the risk factors for sensory nerve dysfunction in subjects with isolated impaired glucose tolerance (IGT). METHODS AND RESULTS: Seventy-two people with isolated IGT (WHO 1999 criteria) and 39 gender and age-matched healthy volunteers underwent detailed clinical and neurological assessment including quantitative sensory testing using the Neurometer device (current perception threshold measurement on four limbs at three different frequencies). Sensory nerve dysfunction was defined as at least two abnormalities on any frequencies on the upper or lower limbs. Sensory nerve dysfunction was more prevalent among subjects with IGT compared to controls (58.3 vs. 10.3%, OR: 11.23, 95%CI: 3.57-35.35). This association was not influenced by BMI, systolic and diastolic blood pressure, heart rate and autonomic neuropathy (multiple adjusted OR: 13.87, 95%CI: 3.18-60.58), but further adjustment for glycaemic measures abolished the association (OR: 1.58, 95%CI: 0.07-35.68). Assessing the components of glycaemic measures separately, the association between sensory nerve dysfunction and IGT was not affected by HbA1c (OR: 13.94, 95%CI: 1.84-105.5). It was, however, substantially attenuated by fasting plasma glucose (OR: 6.75, 95%CI: 1.33-34.27) while the significance was lost after adjustment for 120 min postload glucose level (OR: 3.76, 95%CI: 0.26-54.10). In the pooled population assessed, independent determinants of sensory nerve dysfunction were older age, 120 min glucose, higher height and cardiovascular autonomic neuropathy at near significance. CONCLUSIONS: Sensory nerve dysfunction amongst subjects with IGT was not explained by cardiovascular covariates, only by glycaemic measures. In addition to 120 min glucose, cardiovascular autonomic neuropathy at borderline significance, age, and height were the independent determinants of sensory nerve dysfunction.

The effect of steroid pulse therapy on carbohydrate metabolism in multiple myeloma patients: a randomized crossover observational clinical study.

BACKGROUND: Hyperglycemia is a common, but not well-characterized side effect of glucocorticoid treatment. AIM: To study the effect of pulse dexamethasone treatment on carbohydrate metabolism among multiple myeloma patients. MATERIAL/SUBJECTS AND METHODS: A randomized crossover observational study in a teaching hospital with nine myeloma patients (one male, two with known type 2 diabetes (KDM), mean age 69.0 ± 6.7 years) were investigated using a standard 75 g Oral Glucose Tolerance Test (patients without KDM) and a 3-day continuous glucose monitoring (CGM--all patients) during and between dexamethasone cycles. RESULTS: During dexamethasone treatment patients had elevated 2-h postload glucose (12.8 ± 4.7 vs. 8.7 ± 3.2 mmol/L, P = 0.024) but similar fasting glucose (6.3 ± 1.4 vs. 5.1 ± 0.5 mmol/L, P = 0.112). Estimated hourly mean interstitial glucose values based on linear mixed models showed an increase of 0.03 [SE 0.01] mmol/L per hour from 5.0 [0.4] in patients without KDM and followed a quadratic curve from 5.0 [0.4] mmol/L at midnight to 7.5 [0.5] mmol/L at 12:00 h in patients with KDM during control periods. During dexamethasone treatment glucose was similar to control periods between 02:00 and 12:00 h in the non-KDM group, where they followed a cubic trajectory from 5.3 [0.4] mmol/L at 04:00 h to 7.3 [0.4] mmol/L at 18:00 h. In contrast, interstitial glucose was increased by at least 7.9 [0.3] mmol/L throughout the day in KDM patients during dexamethasone treatment and increased from 13.6 [0.5] mmol/L at midnight to 17.5 [0.5] mmol/L at 17:00 h. CONCLUSIONS: During pulse steroid therapy of myeloma patients without KDM afternoon and evening glucose measurements may be the optimal tools to characterize glucose metabolism.

Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance.

AIMS: To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. METHODS: Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. RESULTS: Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. CONCLUSION: Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

Effect of time of day and fasting duration on measures of glycaemia: analysis from the Whitehall II Study.

AIMS/HYPOTHESIS: We aimed to study diurnal variation in glucose regulation by examining the effects of time of day and fasting duration on fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG) and HbA(1c) levels. METHODS: We analysed data from 5,978 non-diabetic white men and women from the prospective Whitehall II Study. All studied participants fasted for at least 8 h before a clinical examination, which included an OGTT and anthropometric measurements. We fitted mixed-effects models for FPG, 2hPG and HbA(1c) as outcome variables, and time of day and/or fasting duration as explanatory variables. Models were adjusted for age, BMI and study phase. RESULTS: Time of day and fasting duration were associated inversely with FPG and positively with 2hPG. The mean difference between measures at 08:00 and 15:00 hours in men/women was -0.46 (95% CI -0.50, -0.42) mmol/l/-0.39 (95% CI -0.46, -0.31) mmol/l and 1.39 (95% CI 1.25, 1.52) mmol/l/1.19 (95% CI 0.96, 1.42) mmol/l for FPG and 2hPG, respectively. HbA(1c) levels were independent of either time. Time of day and fasting duration were independently associated with 2hPG. In contrast, the effect of fasting duration on FPG was markedly attenuated with adjustment for time of day. Ageing, but not obesity, was associated with increased diurnal variation in glucose tolerance. CONCLUSIONS/INTERPRETATION: Both time of day and fasting duration should be considered in clinical practice and epidemiological studies, since they have clinically relevant effects on FPG and 2hPG levels. As biochemically expected, HbA(1c) levels are independent of time of blood sampling and fasting duration.

Relationship between body mass index and mortality among Europeans.

BACKGROUND/OBJECTIVES: To investigate the relationship between body mass index (BMI) and mortality from various causes. SUBJECTS/METHODS: Data of 72,947 European men and 62,798 women aged 24-99 years at baseline were collaboratively analyzed. Both absolute and relative mortality risks were estimated within each BMI categories. The hazard ratio was estimated using Cox regression analysis adjusting for age, cohort and smoking status. RESULTS: Over a median follow-up of 16.8 years, 29,071 participants died, 13,502 from cardiovascular disease (CVD) and 8748 from cancers of all types. All-cause and cancer mortality showed a U-shaped relationship: decreased first, leveled off, and then increased with increasing BMI with the lowest mortality risk approximately between 23.0 and 28.0 kg/m(2) of BMI in men and 21.0 and 28.0 kg/m(2) in women. The U-shaped relationship held for all-cause mortality but disappeared for cancer mortality among non-smokers. The CVD mortality was constant until a BMI of approximately 28.0 kg/m(2) and then increased gradually in both men and women, which was independent of age, cohort and smoking status. CONCLUSIONS: A U-shaped relationship of BMI with all-cause mortality but a graded relationship with CVD mortality at BMI >28.0 kg/m(2) was detected. The relationship between cancer mortality and BMI largely depended on smoking status, and need to be further investigated with site-specific cancers.

The prevalence and predictors of gestational diabetes mellitus in Hungary.

There are conflicting results regarding the frequency of gestational diabetes (GDM) in Hungary. The aim of this study was to estimate the prevalence of GDM and to clarify the association between selected maternal characteristics and GDM risk. In a population-based screening program of GDM in Tolna County, Hungary, 75 g OGTTs were offered to all pregnant women between 24-28 weeks of gestation and evaluated according to WHO criteria in 2000 (WHO GDM). Women were also classified based on the IADPSG criteria (IADPSG GDM). Selected risk factors were recorded by district nurses. OGTT results were available for 1,835 (81.2%) pregnancies out of 2,261. Altogether 159 (8.7%) were diagnosed as WHO GDM and 304 (16.6%) as IADPSG GDM. Gestational diabetes was related to older age, higher BMI, and an increasing number of deliveries (all p<0.005). The risk of IADPSG GDM monotonously increased with age, -pre-pregnancy BMI and number of deliveries. The risk of WHO GDM increased linearly with age, however, women with the highest BMI (≥ 29.2 kg/m2) had decreased risk compared to women with a BMI of 26.1-29.1 kg/m2 (p<0.05). There was an inverse U-shaped association between GDM risk and number of deliveries with the highest risk observed in those with 3 deliveries (p quadratic term=0.008). We found a high prevalence of GDM in this Caucasian Hungarian population. Our results suggest that pre-pregnancy BMI and previous deliveries elevate the risk of WHO GDM only to a certain level, above which the risk decreases.

Selenium status and blood lipids: the cardiovascular risk in Young Finns study.

BACKGROUND: Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. OBJECTIVES: To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. METHODS: Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). RESULTS: Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1); 95% CI: 30.3 to 34.3, P < 0.0001). In univariate and multivariable cross-sectional models in 1980 and 1986, increased serum selenium levels were consistently associated with increased total, HDL and Low-density lipoprotein (LDL) cholesterol. However, the average longitudinal changes in lipids were -0.20 mmol L(-1) (95% CI: -0.30 to -0.10, P < 0.0001) for total cholesterol, 0.06 mmol L(-1) (95% CI: 0.03 to 0.10, P < 0.0001) for HDL cholesterol, and -0.23 mmol L(-1) (95% CI: -0.31 to -0.14, P < 0.0001) for LDL cholesterol. Selenium measured in 1986 was not associated with lipids assessed in 2001 and 2007. CONCLUSIONS: Cross-sectional findings from the Young Finns study corroborate positive associations of selenium status with serum lipids. However, longitudinal evidence does not support the causality of this link.

The Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) update of the Finnish diabetes risk score for prediction of incident type 2 diabetes.

AIMS/HYPOTHESIS: The Finnish diabetes risk questionnaire is a widely used, simple tool for identification of those at risk for drug-treated type 2 diabetes. We updated the risk questionnaire by using clinically diagnosed and screen-detected type 2 diabetes instead of drug-treated diabetes as an endpoint and by considering additional predictors. METHODS: Data from 18,301 participants in studies of the Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project with baseline and follow-up information on oral glucose tolerance status were included. Incidence of type 2 diabetes within 5 years was used as the outcome variable. Improvement in discrimination and classification of the logistic regression model was assessed by the area under the receiver-operating characteristic (ROC) curve and by the net reclassification improvement. Internal validation was by bootstrapping techniques. RESULTS: Of the 18,301 participants, 844 developed type 2 diabetes in a period of 5 years (4.6%). The Finnish risk score had an area under the ROC curve of 0.742 (95% CI 0.726-0.758). Re-estimation of the regression coefficients improved the area under the ROC curve to 0.766 (95% CI 0.750-0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity. CONCLUSIONS/INTERPRETATION: The predictive value of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid populations.

Changes in C-reactive protein levels before type 2 diabetes and cardiovascular death: the Whitehall II study.

OBJECTIVE: Prospective studies show that high C-reactive protein (CRP) levels predict diabetes and cardiovascular disease (CVD), but changes in this marker preceding disease onset are not well characterized. This study describes CRP trajectories prior to type 2 diabetes onset and fatal CVD. METHODS: In a prospective cohort of 7350 British civil servants (70% male, mean age 51 years), 558 incident type 2 diabetes cases (75-g oral glucose tolerance test, doctor's diagnosis, or self-report) and 125 certified fatal cardiovascular events were observed during a median follow-up of >14 years. Trajectories of logarithmically transformed CRP levels prior to incident diabetes or fatal cardiovascular event (cases), or the end of follow-up (controls) were calculated using multilevel modeling. RESULTS: Baseline CRP levels were higher among participants who developed diabetes (median (interquartile range) 1.44 (2.39) vs 0.78 (1.21) mg/l) or fatal CVD (1.49 (2.47) vs 0.84 (1.30) mg/l) compared with controls (both P<0.0001). In models adjusted for age, sex, body mass index, ethnicity, and employment grade, CRP levels increased with time among both incident diabetes cases and controls (P<0.0001), but this increase was less steep for cases group (P<0.05). CRP levels followed increasing linear trajectories in fatal cardiovascular cases and controls (P<0.0001) with no slope difference between the groups. CONCLUSIONS: CRP levels were higher among those who subsequently developed diabetes or died from CVD. For type 2 diabetes, age-related increase in CRP levels was less steep in the cases group than in controls, whereas for fatal CVD these trajectories were parallel.

The effect of paternal and maternal history of diabetes mellitus on the development of gestational diabetes mellitus.

BACKGROUND: There is an ongoing debate whether maternal diabetes is a more important risk factor for gestational diabetes (GDM) development than paternal diabetes. AIM: To describe the risk of GDM associated with paternal and maternal diabetes, and to further characterise GDM women with maternal diabetes. SUBJECTS AND METHODS: Case-control study within a population-based GDM screening program in an urban area of Hungary in 2002-2003. All GDM women (no.=133) and an age-matched control group (no.=135) with a mean age of 31 years was evaluated. Blood pressure, anthropometric data, and blood glucose values from a 75 g Oral Glucose Tolerance Test (OGTT) were recorded at 24-28 weeks of gestation. Family history data were by self-report. RESULTS: Known paternal diabetes was not related to GDM risk [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.35-2.00]. Known maternal diabetes (OR 2.90, 95% CI 0.99-8.49) and diabetes in the maternal line (OR 2.83, 95% CI 1.16-6.89) were both related to GDM after adjustment for body mass index (BMI). GDM women with known maternal diabetes had a higher BMI, 31.6 [9.1] kg/m2 median [interquartile range], than GDM women with or without diabetes in the maternal line, 26.1 [4.9] and 26.3 [6.1] kg/m2, respectively, while figures for fasting glucose during OGTT were 5.2 [0.7] vs 4.4 [1.1] vs 4.9 [0.8] mmol/l respectively (all p<0.05). CONCLUSIONS: Maternal history of diabetes and history of diabetes in the maternal line seems to be a stronger predictor of GDM than paternal history.

Low serum adiponectin predicts 10-year risk of type 2 diabetes and HbA1c independently of obesity, lipids, and inflammation: Whitehall II study.

Our aim of the present work was to study the effect of serum adiponectin on incident diabetes and HbA1c values. We measured baseline serum adiponectin levels in a nested case-control selection (n=140) of the Whitehall II Cohort. Participants (mean [SD] age 50.9 [6.3] years) had no prevalent diabetes or CHD at baseline. Cases (n=55) had incident diabetes according to an oral glucose tolerance test during follow-up (mean: 11.5+/-3.0 years). Adiponectin levels were lower among cases (9.3 microg/ml, 3.2 [median; IQR] vs. 10.5; 3.6, p=0.01). The risk of incident diabetes decreased by 11% (p=0.03) for 1 microg/ml higher adiponectin levels. Higher adiponectin levels were associated with lower HbA1c at follow-up (p<0.05). Both associations were stable to adjustment for age, sex, body mass index, systolic blood pressure, and serum lipids, and for the case of HbA1c, also for C-reactive protein (all p<0.05). The observed robust, prospective associations support that adiponectin is an independent predictor of diabetes and the degree of glycaemic impairment.

Targets and reality: a comparison of health care indicators in the U.S. (Pittsburgh Epidemiology of Diabetes Complications Study) and Hungary (DiabCare Hungary).

OBJECTIVE: In the U.S., both primary care and specialist physicians share in the care of type 1 diabetic patients, often in an informal collaboration. In Hungary, however, type 1 diabetic patients are generally managed in special centralized diabetes units. These different treatment settings may lead to different health care practices and outcomes. To determine if this is true, diabetes care indicators and complications were compared across representative study populations from the 2 countries. RESEARCH DESIGN AND METHODS: The Pittsburgh Epidemiology of Diabetes Complications Study (EDC) is a prospective cohort of childhood-onset type 1 diabetic patients. DiabCare Hungary, a multicenter cross-sectional study, was developed for quality control purposes and provides a nationwide data set of diabetic patients. We identified 2 comparable populations (EDC, n = 416; DiabCare, n = 405) in terms of age (> or =14 years) and age at onset (<17 years). RESULTS: EDC patients were less likely to receive diabetes education (P<0.0001), see an ophthalmologist (P<0.0001), be treated by diabetologists (P<0.0001), or perform self-monitoring of blood glucose (P<0.0001). They were more likely to use conservative insulin regimens (i.e., 1-2 injections/day, P<0.0001) and have a higher glycated hemoglobin (P< 0.0001). DiabCare patients more often experienced severe hypoglycemia (P<0.01) and had a lower prevalence of proliferative retinopathy (P<0.0001), legal blindness (P<0.05), and albuminuria (> or =30 mg/day P<0.01). No significant differences in macrovascular complications were seen, although rates were generally low CONCLUSIONS: These data suggest that the 2 populations differ by their diabetes care practices, degree of glycemic control, and microvascular complication status.