Search

Aims/hypothesis: Reversion from prediabetes to normoglycaemia is accompanied by an improvement in cardiovascular risk factors, but it is unclear whether this translates into a reduction in risk of cardiovascular disease (CVD) events or death. Hence, we studied the probability of reversion from prediabetes to normoglycaemia and the associated risk of future CVD and death using data from the Whitehall II observational cohort study. Methods: Three glycaemic criteria for prediabetes (fasting plasma glucose [FPG] 5.6–6.9 mmol/l, 2 h plasma glucose [2hPG] 7.8–11.0 mmol/l, and HbA1c 39–47 mmol/mol [5.7–6.4%]) were assessed in 2002–2004 and 2007–2009 for 5193 participants free of known diabetes at enrolment. Among participants with prediabetes in the first examination, we calculated the probability of reversion to normoglycaemia by re-examination according to each glycaemic criterion. Poisson regression analysis was used to estimate and compare incidence rates of a composite endpoint of a CVD event or death in participants with prediabetes who did vs did not revert to normoglycaemia. Analyses were adjusted for age, sex, ethnicity and previous CVD. Results: Based on the FPG criterion, 820 participants had prediabetes and 365 (45%) of them had reverted to normoglycaemia in 5 years. The corresponding numbers were 324 and 120 (37%) for the 2hPG criterion and 1709 and 297 (17%) for the HbA1c criterion. During a median follow-up of 6.7 (interquartile range 6.3–7.2) years, 668 events of non-fatal CVD or death occurred among the 5193 participants. Reverting from 2hPG-defined prediabetes to normoglycaemia vs remaining prediabetic or progressing to diabetes was associated with a halving in event rate (12.7 vs 29.1 per 1000 person-years, p = 0.020). No association with event rate was observed for reverting from FPG-defined (18.6 vs 18.2 per 1000 person-years, p = 0.910) or HbA1c-defined prediabetes to normoglycaemia (24.5 vs 22.9 per 1000 person-years, p = 0.962). Conclusions/interpretation: Most people with HbA1c-defined prediabetes remained prediabetic or progressed to diabetes during 5 years of follow-up. In contrast, reversion to normoglycaemia was frequent among people with FPG- or 2hPG-defined prediabetes. Only reversion from 2hPG-defined prediabetes to normoglycaemia was associated with a reduction in future risk of CVD and death. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA, fasting insulin and HOMA-IR with incident type 2 diabetes mellitus. Methods: The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations. Results: After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA, 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA with incident diabetes were non-linear, rising more steeply at higher values. Conclusions/interpretation: FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA, HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We previously identified the G6PC2 locus as a strong determinant of fasting plasma glucose (FPG) and showed that a common G6PC2 intronic single nucleotide polymorphism (SNP) (rs560887) and two common G6PC2 promoter SNPs (rs573225 and rs13431652) are highly associated with FPG. However, these promoter SNPs have complex effects on G6PC2 fusion gene expression, and our data suggested that only rs13431652 is a potentially causative SNP. Here we examine the effect of rs560887 on G6PC2 pre-mRNA splicing and the contribution of an additional common G6PC2 promoter SNP, rs2232316, to the association signal. Methods: Minigene analyses were used to characterise the effect of rs560887 on G6PC2 pre-mRNA splicing. Fusion gene and gel retardation analyses characterised the effect of rs2232316 on G6PC2 promoter activity and transcription factor binding. The genetic association of rs2232316 with FPG variation was assessed using regression adjusted for age, sex and BMI in 4,220 Europeans with normal FPG. Results: The rs560887-G allele was shown to enhance G6PC2 pre-mRNA splicing, whereas the rs2232316-A allele enhanced G6PC2 transcription by promoting Foxa2 binding. Genetic analyses provide evidence for association of the rs2232316-A allele with increased FPG ( β = 0.04 mmol/l; p = 4.3 × 10) as part of the same signal as rs560887, rs573225 and rs13431652. Conclusions/interpretation: As with rs13431652, the in situ functional data with rs560887 and rs2232316 are in accord with the putative function of G6PC2 in pancreatic islets, and suggest that all three are potentially causative SNPs that contribute to the association between G6PC2 and FPG. [ABSTRACT FROM AUTHOR]

A high but normal fasting plasma glucose level in adults is a risk factor for future development of type 2 diabetes mellitus and cardiovascular disease. We investigated whether normal fasting plasma glucose levels (<5.60 mmol/l) are associated with decreases in insulin sensitivity and beta cell function, as well as an adverse cardiovascular profile in obese youth. We performed a cross-sectional analysis in a multiethnic sample of 1,020 obese youth (614 girls and 406 boys; mean age 12.9 years [CI 95% 12.7–13.1], BMI z score 2.34 [CI 95% 2.31–2.38]) with normal fasting plasma glucose. All participants had a standard OGTT, with calculation of indices of insulin sensitivity and beta cell function. For the analysis, prepubertal and pubertal participants were stratified into quartiles of normal fasting plasma glucose. We observed a significant increase in fasting insulin and AUC 2 h glucose across quartiles. Pronounced changes were observed in insulin sensitivity and secretion, particularly in the pubertal group. Moreover, the odds of presenting with impaired glucose tolerance increased by 4.5% with each 0.06 mmol/l increase in fasting plasma glucose. No significant differences in cardiovascular indices were seen across quartiles. These data suggest that in obese youth, independent of age, BMI z score, sex, family history and ethnicity, insulin sensitivity and secretion decline when moving from low to high normal fasting plasma glucose. The simple measure of fasting plasma glucose could assist clinicians in identifying children for targeted diabetes screening and subsequent lifestyle management. [ABSTRACT FROM AUTHOR]

To test fasting glucose association at four loci recently identified or verified by genome-wide association (GWA) studies of European populations, we performed a replication study in two Asian populations. We genotyped five common variants previously reported in Europeans: rs1799884 ( GCK), rs780094 ( GCKR), rs560887 ( G6PC2–ABCB11) and both rs1387153 and rs10830963 ( MTNR1B) in the general Japanese ( n = 4,813) and Sri Lankan ( n = 2,319) populations. To identify novel variants, we further examined genetic associations near each locus by using GWA scan data on 776 non-diabetic Japanese samples. Fasting glucose association was replicated for the five single nucleotide polymorphisms (SNPs) at p < 0.05 (one-tailed test) in South Asians (Sri Lankan) as well as in East Asians (Japanese). In fine-mapping by GWA scan data, we identified in the G6PC2–ABCB11 region a novel SNP, rs3755157, with significant association in Japanese ( p = 2.6 × 10-8) and Sri Lankan ( p = 0.001) populations. The strength of association was more prominent at rs3755157 than that of the original SNP rs560887, with allelic heterogeneity detected between the SNPs. On analysing the cumulative effect of associated SNPs, we found the per-allele gradients ( β = 0.055 and 0.069 mmol/l in Japanese and Sri Lankans, respectively) to be almost equivalent to those reported in Europeans. Fasting glucose association at four tested loci was proven to be replicable across ethnic groups. Despite this overall consistency, ethnic diversity in the pattern and strength of linkage disequilibrium certainly exists and can help to appreciably reduce potential causal variants after GWA studies. [ABSTRACT FROM AUTHOR]

Variation in fasting plasma glucose (FPG) within the normal range is a known risk factor for the development of type 2 diabetes. Several reports have shown that genetic variation in the genes for glucokinase ( GCK), glucokinase regulatory protein ( GCKR), islet-specific glucose 6 phosphatase catalytic subunit-related protein ( G6PC2) and melatonin receptor type 1B ( MTNR1B) is associated with FPG. In this study we examined whether these loci also contribute to type 2 diabetes susceptibility. A random selection from the Dutch New Hoorn Study was used for replication of the association with FGP (2,361 non-diabetic participants). For the genetic association study we extended the study sample with 2,628 participants with type 2 diabetes. Risk allele counting was used to calculate a four-gene risk allele score for each individual. Variants of the GCK, G6PC2 and MTNR1B genes but not GCKR were associated with FPG (all, p ≤ 0.001; GCKR, p = 0.23). Combining these four genes in a risk allele score resulted in an increase of 0.05 mmol/l (0.04–0.07) per additional risk allele ( p = 2 × 10−13). Furthermore, participants with less than three or more than five risk alleles showed significantly different type 2 diabetes susceptibility compared with the most common group with four risk alleles (OR 0.77 [0.65–0.93], p = 0.005 and OR 2.05 [1.50–2.80], p = 4 × 10−6 respectively). The age at diagnosis was also significantly associated with the number of risk alleles ( p = 0.009). A combined risk allele score for single-nucleotide polymorphisms in four known FPG loci is significantly associated with FPG and HbA1c in a Dutch population-based sample of non-diabetic participants. Carriers of low or high numbers of risk alleles show significantly different risks for type 2 diabetes compared with the reference group. [ABSTRACT FROM AUTHOR]

Recently, FTO was identified as a candidate gene contributing to both childhood and severe adult obesity. We tested the hypothesis that mRNA expression of FTO and/or of the neighbouring RPGRIP1L in adipose tissue correlates with measures of obesity and fat distribution. We also investigated whether the FTO obesity risk alleles might explain variability in FTO and RPGRIP1L mRNA expression. In paired samples of visceral and subcutaneous adipose tissue from 55 lean and obese participants, we investigated whether FTO and RPGRIP1L mRNA expression is fat depot-specific, altered in obesity and related to measures of fat accumulation, insulin sensitivity and glucose metabolism. All participants were genotyped for the obesity-associated rs8050136 FTO variant. FTO mRNA expression was threefold higher in subcutaneous than in visceral adipose tissue. Subcutaneous FTO expression correlated with visceral FTO expression. FTO gene expression in both depots correlated with age and was negatively correlated to BMI and per cent body fat. FTO mRNA levels were not related to measures of insulin sensitivity and glucose metabolism. RPGRIP1L mRNA expression was 1.6-fold higher in visceral than in subcutaneous adipose tissue, but did not correlate with anthropometric and metabolic characteristics. There was no association between rs8050136 and FTO or RPGRIP1L mRNA expression in adipose tissue. Expression of adipose tissue FTO mRNA is fat depot-specific and negatively correlates with measures of obesity. However, the direction of this relationship still needs to be elucidated. [ABSTRACT FROM AUTHOR]

This 52-week multinational, randomised, open-label, parallel-group, non-inferiority trial compared clinical outcomes following supplementation of oral glucose-lowering drugs with basal insulin analogues detemir and glargine in type 2 diabetic patients. Insulin-naive adults ( n = 582, HbA1c 7.5–10.0%, BMI ≤ 40.0 kg/m2) were randomised 1:1 to receive insulin detemir or glargine once daily (evening) actively titrated to target fasting plasma glucose (FPG) ≤ 6.0 mmol/l. An additional morning insulin detemir dose was permitted if pre-dinner plasma glucose (PG) was >7.0 mmol/l after achieving FPG < 7.0 mmol/l. Due to labelling restrictions, no second glargine dose was allowed. Baseline HbA1c decreased from 8.6 to 7.2 and 7.1% (NS) with detemir and glargine, respectively. FPG improved from 10.8 to 7.1 and 7.0 mmol/l (NS), respectively. With detemir, 45% of participants completed the study on once daily dosing and 55% on twice daily dosing, with no difference in HbA1c. Overall, 52% of participants achieved HbA1c ≤ 7.0%: 33% (detemir) and 35% (glargine) without hypoglycaemia. Within-participant variability for self-monitored FPG and pre-dinner PG did not differ by insulin treatment, nor did the relative risk of overall or nocturnal hypoglycaemia. Modest reductions in weight gain were seen with detemir vs glargine in completers (3.0 vs 3.9 kg, p = 0.01) and in the intention-to-treat population (2.7 vs 3.5 kg, p = 0.03), primarily related to completers on once-daily detemir. Mean daily detemir dose was higher (0.78 U/kg [0.52 with once daily dosing, 1.00 U/kg with twice daily dosing]) than glargine (0.44 IU/kg). Injection site reactions were more frequent with detemir (4.5 vs 1.4%). Supplementation of oral agents with detemir or glargine achieves clinically important improvements in glycaemic control with low risk of hypoglycaemia. Non-inferiority was demonstrated for detemir using higher insulin doses (mainly patients on twice daily dosing); weight gain was somewhat reduced with once daily insulin detemir. ClinicalTrials.gov ID no.: NCT00283751. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: An increase in endogenous glucose production (EGP) is a major contributor to fasting morning hyperglycaemia in type 2 diabetes. This increase is dissipated with fasting, later in the day. To understand its origin, EGP, gluconeogenesis and hormones that regulate metabolism were measured over 24 h. We hypothesised that EGP, and therefore glycaemia, would demonstrate a centrally mediated circadian rhythm in type 2 diabetes. Subjects and methods: Seven subjects with type 2 diabetes and six age- and BMI-matched control subjects, fasting after breakfast (08.00 h), underwent a further 24-h fast, with the infusion of [U-13C] glucose and [3-14C]lactate, starting at 14.00 h. The MCR and production of total and gluconeogenic glucose were determined from the tracer concentrations using compartmental analysis. Results: MCR was near constant: 1.73± 0.10 in control and 1.40±0.14 ml kg-1 min-1 in diabetic subjects (p=0.04). EGP in diabetes rose gradually overnight from 8.2±0.7 to 11.3±0.5 µmol kg-1 min-1 at 06.00 h (p<0.05). Glucose utilisation lagged EGP, rising from 8.5±0.6 to 10.5±0.4 µmol kg-1 min-1 (p<0.05), inducing a fall in glycaemia from a peak of 8.0±0.5 mmol/l to 6.3±0.4 mmol/l (p<0.05). Cortisol and melatonin showed diurnal variations, whereas insulin, glucagon and leptin did not. Melatonin was most closely related to EGP, but its secretion was attenuated in diabetes (p<0.05). Conclusions/interpretation: In type 2 diabetes, EGP and gluconeogenesis display diurnal rhythms that drive the fasting hyperglycaemia and are absent in healthy control subjects. The rise in EGP may be related to a deficit in suprachiasmatic nucleus activity in diabetes, or result from non-linear behaviour plus a transition from a normal steady state to a limit cycle pattern in diabetes, or both. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this study was to evaluate differences in insulin sensitivity, insulin secretion and risk factors for cardiovascular disease between sub- jects with a 2-h plasma glucose (2hPG) level within the normal range (NPG) and subjects with IGT, following a 75-g OGTT. We also aimed to determine the respective contributions made by 2hPG and fasting plasma glucose to the metabolic risk profile. Methods: We compared cardiovascular risk factors and insulin sensitivity and insulin secretion by using several indices calculated using measurements obtained during an OGTT. Subjects (n=643, age 18-71 years) were participants in the Québec Family Study and were categorised according to 2hPG as having low NPG (2hPG <5.6 mmol/l, the group median for normal values), high NPG (2hPG 5.6-7.7 mmol/l) or IGT (2hPG 7.8-11.0 mmol/l). Subjects with type 2 diabetes were excluded from all analyses. Results: Beta cell function and insulin sensitivity progressively decreased with increasing 2hPG. Compared with subjects with low NPG, subjects with high NPG were more insulin-resistant (p<0.05) and had reduced insulin secretion (adjusted for insulin resistance) (p<0.001). They also had higher plasma triglyceride concentrations (p<0.01) and cholesterol:HDL cholesterol ratios (p'c0.05). These differences remained even after adjustment for age, sex, BMI and waist circumference. Multivariate analyses showed that 2hPG was closely associated with risk factors for diabetes and with cardiovascular variables, including triglycerides (p<0.0001) and apolipoprotein B (p'cO .01). Conclusions/interpretation: These results show that deteriorations in glucose-insulin metabolism, which may predispose individuals to type 2 diabetes and cardiovascular disease, are already present in subjects with 2hPG concentrations within the high normal range. Independently of obesity, 2hPG was found to explain, in part, the variance observed in cardiovascular and diabetes risk factors. In addition, elevated 2hPG was associated with metabolic alterations that appear to be the most detrimental to metabolic health. Thus, 2hPG values within the high normal range may be an important marker for the identification of people at risk of complications related to type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. The aims of this study were to compare the ability of tests measuring fasting plasma glucose, 2-h plasma glucose and HbA1c levels in predicting specific diabetic retinopathy, and to determine the cut-off level of each measurement for diagnosing diabetes in a Japanese population. Methods. In a total of 1637 subjects, fasting plasma glucose, 2-h plasma glucose and HbA1c levels were measured in a 75-g oral glucose tolerance test, and diabetic retinopathy was assessed by ophthalmic examination. We calculated receiver operating characteristic (ROC) curves as well as the prevalence of diabetic retinopathy by deciles of the distribution of these glycaemic measurements. Results. Of the subjects, 37 (2.3%) had diabetic retinopathy. The prevalence of retinopathy dramatically increased in the tenth decile of each variable. Analysis with ROC curves showed that the optimal cut-off levels for diagnosis of diabetes were 6.4 mmol/l for fasting plasma glucose, 11.1 mmol/l for 2-h plasma glucose, and 5.7% for HbA1c. The sensitivities for the cut-off point of the three measurements were identical (86.5%), and the specificities were similar (fasting plasma glucose 87.3%; 2-h plasma glucose 89.6%; HbA1c 90.1%). The area under the ROC curve for 2-h plasma glucose (96.1%) was slightly but not significantly larger than that for fasting plasma glucose (90.0%) and that for HbA1c (94.5%). Conclusions/interpretation. Our findings suggest that measuring fasting plasma glucose or HbA1c is just as useful as measuring 2-h plasma glucose for the diagnosis of diabetes, and that the cut-off point for diagnostic fasting plasma glucose level is lower than that of the current diagnostic criteria. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Our aim was to define the level of glycaemia at which pancreatic insulin secretion, particularly first-phase insulin release, begins to decline. Methods. Plasma glucose and insulin concentrations were measured during an IVGTT in 553 men with non-diabetic fasting plasma glucose concentrations. In 466 of the men C-peptide was also estimated. IVGTT insulin secretion in first and late phases was assessed by: (i) the circulating insulin response; (ii) population parameter deconvolution analysis of plasma C-peptide concentrations; and (iii) a combined model utilising both insulin and C-peptide concentrations. Measurements of insulin sensitivity and elimination were also derived by modelling analysis. Results. As fasting plasma glucose (FPG) increased, IVGTT first-phase insulin secretion declined by 73%, 71% and 68% for the three methods respectively. The FPG values at which this decline began, determined by change point regression, were 4.97, 5.16 and 5.42 mmol/l respectively. The sensitivity of late-phase insulin secretion to glucose declined at FPG concentrations above 6.0 mmol/l. Insulin elimination, but not insulin sensitivity, varied with FPG. Conclusions/interpretation. The range of FPG over which progressive loss of the first-phase response begins may be as low as 5.0 to 5.4 mmol/l, with late-phase insulin responses declining at FPG concentrations above 6.0 mmol/l. [ABSTRACT FROM AUTHOR]

We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male ( n = 120) and female subjects ( n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40–70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, proinsulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A1 c, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia. [Diabetologia (1998) 41: 706–712] [ABSTRACT FROM AUTHOR]

The current classification and diagnostic criteria for diabetes mellitus were introduced by the United States National Data Group in 1979 and endorsed by the World Health Organization in 1980, with modifications in 1985 and 1994. The criteria, chosen to reflect the risk of complications, were the synthesis of considerable thought and expertise and represented a consensus which, it was hoped, would prove helpful to all those involved with diabetes – practising clinician, research scientist and epidemiologist alike. The inconvenience, variability and nonphysiological nature of the oral glucose tolerance test (OGTT) are well-recognised. In spite of these limitations the 2-h post-load plasma glucose has remained the standard against which all other tests have been evaluated. This article reviews the original justification for the OGTT, and in the light of more recent epidemiological research seeks to place the current diagnostic criteria for diabetes into a pathophysiological, diagnostic and prognostic perspective. [Diabetologia (1997) 40: 247–255] [ABSTRACT FROM AUTHOR]

A multi-centre, prospective randomised study of the therapy of maturity-onset diabetes has been started, and we report progress of the first 286 patients with 1-year followup. Newly presenting patients (aged 25-65 years inclusive) were initially treated by diet and divided into three categories. (1) Forty-one patients (14%) were 'primary diet failure' in that they continued to have symptoms or their fasting plasma glucose remained >15 mmol/l. Their therapy was allocated randomly to insulin, chlorpropamide or glibenclamide, and doses adjusted to try to maintain a fasting plasma glucose <6 mmol/l. Insulin produced a similar decrease in fasting plasma glucose to sulphonylurea therapy (median fasting plasma glucose fell from 15.4 to 8.0 mmol/l and from 15.5 to 8.6 mmol/l, respectively). (2) After 3-4 months diet, 161 patients (56%) were asymptomatic but had a fasting plasma glucose >6 mmol/l. In the 'main randomisation' their therapy was allocated to diet only, or diet plus chlorpropamide, glibenclamide or a basal insulin supplement from ultralente insulin. On diet alone, fasting plasma glucose remained constant over 1-year follow-up (from 7.7 to 7.6 mmol/l), whereas it was reduced significantly by insulin (from 8.0 to 6.4 mmol/l), chlorpropamide (8.6 to 6.1 mmol/l) and glibenclamide (7.8 to 6.5 mmol/l). On diet alone, weight remained unchanged over 1 year but increased significantly on insulin, chlorpropamide or glibenclamide (median change ideal body weight +3.5%, +4% and +4%, respectively). Obese patients (>20% over ideal weight) did not differ from normal weight diabetic subjects in either fasting plasma glucose or weight changes. Insulin therapy was associated with few hypoglycaemic episodes, with 8% of patients on ultralente insulin alone reporting an episode compared with 7% on chlorpropamide. Fifty-one patients (86%) randomised to insulin remain on it lyear later. (3) After 3-4 months on diet, 84 patients (30%) after dieting had a fasting plasma glucose <6 mmol/l. During the following year on diet alone 34 patients were less well controlled with a fasting plasma glucose >6 mmol/l and were included in a 'delayed randomisation'. Thus 83% of all patients entered into the study had their therapy randomised by 1 year. Insulin and sulphonylurea therapy are equally effective in reducing glycaemia, and the study is being extended to determine if either therapy will prevent the complications of diabetes or have untoward long-term side effects. [ABSTRACT FROM AUTHOR]

A Southern California community study of 4,541 men and women (aged 20-79 years) showed significant seasonal variation in fasting plasma glucose. There was a mean 0.6 mmol/l difference between highest levels in winter and lowest levels in spring. This difference was consistent over a two-year period, similar at all ages and seen in both men and women. Fasting plasma glucose levels correlated directly with percentage possible sunshine ( p= 0.03) and inversely with temperature ( p= 0.04). Adjustment for the level of measured obesity did not alter the observed association, but a history of recent weight gain corresponded to the season of maximum fasting plasma glucose level. [ABSTRACT FROM AUTHOR]

To examine the temporal relationship between Hb A values and various indices of blood glucose control, 38 diabetic and 28 nondiabetic youth counsellors employed at two summer camps for diabetic children took part in an eight-week study. Each week fasting determinations were made of Hb A, Hb A, serum cholesterol, triglyceride and growth hormone and plasma glucose. Total daily urine glucose excretion was measured approximately two times per week, capillary glucose values were measured fasting and at 11 a. m. and 3 p. m. on two days per week, and urine glucose was measured semi-quantitatively four times per day. As Hb A was correlated highly with Hb A (r = 0.997), it was used as the primary index of glycosylated haemoglobin. The mean values of Hb A, serum cholesterol and triglycerides and fasting plasma glucose were all significantly elevated in the diabetic group but only Hb A values provided total separation of the two groups. Within the diabetic group the Week 8 Hb A values showed a significant correlation with the Week 8 mean capillary glucose concentrations, the proportion of urine tests showing 2% and 0% glycosuria, and mean serum triglycerides. Correlations of Week 8 Hb A with the mean values of these glycaemic parameters for each week of the study demonstrated low order correlations with the glycaemic measures of Week 1, and a progressive increase in the degree of correlation reaching a plateau with the glycaemic measures of Week 4 to 8. Similar correlation analysis using the Hb A values from Week 4 confirmed these findings. Therefore, while Hb A provides an index of the control of diabetes, it appears to be more acutely responsive to blood glucose alteration than generally recognized. [ABSTRACT FROM AUTHOR]

The frequency distributions of both the fasting and two-hour post-load plasma glucose levels were bimodal in the Pima Indian population aged 25 years and over. The hyperglycaemic component of this distribution represents those with diabetes mellitus, as some 30 percent of this group had evidence of the specific vascular complications of the disease, whereas these abnormalities were virtually absent in those with lower glucose levels. The bimodal characteristics of the frequency distributions were utilized to define optimal criteria to separate those with and without diabetes. The sensitivity and specificity of these criteria for fasting and two-hour glucose levels were compared and were found to be similar. The fasting glucose determination, however, was more reproducible and stable, as well as being easier to obtain, indicating that it is the better measurement for diagnostic purposes. The optimal level for diagnosis of 7.5 mmol/l (136 mg/dl) for the fasting glucose and the equivalent two-hour value of 14 mmol/l (250 mg/dl), were higher than many previously recommended diagnostic levels. Nevertheless, there was no evidence that subjects with lower levels were at appreciable risk of developing the specific complications of diabetes. Subjects with impaired glucose tolerance (IGT), but without fasting hyperglycaemia, should not be diagnosed as having diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. We examined the prevalence of diabetes and investigated the characteristics of subjects diagnosed by the American Diabetes Association and the World Health Organization criteria. Methods. A total of 1235 Japanese-Americans living in Hawaii and Los Angeles was studied. Of the subjects 114 were classified as previously diagnosed as having diabetes. A 75-g glucose tolerance test was given to the rest of the subjects. Results. When abnormal glucose tolerance was diagnosed by the American Diabetes Association criteria, it was possible to identify only 40 % of diabetic subjects who had not been previously diagnosed compared with the current World Health Organization criteria based on a glucose tolerance test. In addition, the subjects identified by the American Diabetes Association criteria had higher glucose concentrations and had less insulin secretory capacity and they were in need of intensive treatment for diabetes. On the other hand, the subjects not diagnosed by the American Diabetes Association criteria alone were those whose glucose tolerance would be more likely to improve with lifestyle modification. Conclusion/interpretation. It might be better to use the fasting plasma glucose criterion advocated by the American Diabetes Association in combination with a glucose tolerance test after taking a detailed medical history. To reduce the number of subjects requiring the glucose tolerance test, priority should be given to subjects with impaired fasting glucose (6.1 ≤ fasting plasma glucose < 7.0 mmol/l). [Diabetologia (1999) 42: 1168–1170] [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA 1c , fasting insulin and HOMA-IR with incident type 2 diabetes mellitus., Methods: The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations., Results: After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA 1c , 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA 1c with incident diabetes were non-linear, rising more steeply at higher values., Conclusions/interpretation: FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA 1c , HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.