Blood glucose overestimation in diabetic patients on continuous ambulatory peritoneal dialysis for end-stage renal disease.

AIMS: Diabetic patients on continuous ambulatory peritoneal dialysis (CAPD) for renal failure depend on glucose analysers for regular monitoring of glycaemic control. We aim to inform health professionals of the potentially dangerous overestimation of blood glucose values by some analysers in patients using Icodextrin for dialysis. METHODS: Twenty-five patients on continuous ambulatory peritoneal dialysis (10 patients on an 8-12-h nocturnal exchange of Icodextrin) had random glucose analysis performed on venous blood using standardized reference laboratory (lab) technique (glucose oxidase GOD-PAP), and simultaneously on capillary blood using the Precision Q.I.D System (glucose oxidase method) and the Advantage meter (glucose dehydrogenase method). RESULTS: The Precision Q.I.D System agreed with the lab results in both the Icodextrin group and the non-Icodextrin group (80-90% of values fell within 20% of the corresponding lab result). In contrast, the Advantage meter agreed with the lab results only in the non-Icodextrin group (95% of values within 20% of the corresponding lab value), and not in the Icodextrin group, where only 5% of the analyser values fell within 20% of the corresponding lab value. CONCLUSIONS: The Precision Q.I.D System, which utilizes glucose oxidase reaction, is safe for use in diabetic patients treated with Icodextrin. All analysers must be cross-checked with the laboratory reference method before use in these patients.     

Performance assessment of the Medtronic-MiniMed Continuous Glucose Monitoring System and its use for measurement of glycaemic control in Type 1 diabetic subjects.

AIMS: To assess the accuracy, reliability and measurement of glycaemic control associated with the Medtronic-MiniMed Continuous Glucose Monitoring System (CGMS) in comparison with blood glucose self-monitoring (BGSM) in Type 1 diabetic patients. METHODS: Type 1 diabetic patients (n = 18) underwent glucose monitoring by the CGMS for up to 3 days, when control was also assessed by BGSM performed eight times daily. RESULTS: Ninety-five per cent of paired non calibration samples were in the clinically acceptable zones of the Clarke error grid, and 97% in a consensus grid. The median bias was 0.1 mmol/l and relative bias 15%. The failure rate of sensors was 28% of those initially inserted. The CGMS detected significantly more hypoglycaemia and post-prandial hyperglycaemia, but total duration of hyperglycaemia, blood glucose oscillations and day-to-day variability were similarly assessed by CGMS and BGSM. CONCLUSIONS: The CGMS has acceptable clinical accuracy. Detection by the CGMS of more hypoglycaemia and post-prandial hyperglycaemia than BGSM promises a valuable tool for control assessment and optimization of treatment.     

Assessment of hypoglycaemia awareness using continuous glucose monitoring.

AIMS: To investigate the possibility of assessing hypoglycaemia awareness in patients with Type 1 diabetes using continuous glucose monitoring. METHODS: Twenty patients with Type 1 diabetes were investigated. Ten patients with Type 1 diabetes and strongly impaired hypoglycaemia awareness were compared with 10 patients with intact hypoglycaemia awareness regarding quality of hypoglycaemia perception (number of undetected hypoglycaemic episodes per 24 h, glucose level < 3.3 mmol/l). Hypoglycaemia detection was assessed using the event function of the Continuous Glucose Monitoring System (CGMS; Medtronic MiniMed, Northridge, CA, USA). Patients were instructed to enter an event upon suspecting being hypoglycaemic. RESULTS: Satisfactory CGMS performance could be achieved [mean r = 0.893 between calibration measurements and CGMS data, mean absolute difference (MAD) = 20.6%], although artefacts were observable and had to be controlled. Hypoglycaemia unaware patients showed a significantly higher total number of hypoglycaemic episodes (P < 0.05), number of undetected hypoglycaemic episodes (P < 0.01), and mean glucose levels (P < 0.05). Even in aware patients, undetected hypoglycaemia was observable. No significant differences regarding occurrence of nocturnal hypoglycaemia were observable. CONCLUSIONS: The possibility of direct assessment of hypoglycaemia awareness using continuous glucose monitoring was demonstrated. Its application in clinical practice could be of use for assessing hypoglycaemia perception and evaluating the impact of treatment changes on hypoglycaemia awareness.     

由血清甘油三酯和血糖所得简易指数用于评估胰岛素抵抗的临床研究

目的 在不同体重指数和糖耐量状态受试者中,比较由血甘油三酯和血糖所得简易胰岛素抵抗指数与两种传统方法稳态模型和静脉葡萄糖耐量试验(FSIGT)所得胰岛素抵抗指数(HOMA -IR和FSIGT-ISI)用于评估胰岛素抵抗的敏感性和特异性.方法 共收集1024名受试者.其中,正常对照组240名,单纯性肥胖组335例,糖调节受损组312例及初发2型糖尿病组137例,均进行口服75 g葡萄糖耐量试验及胰岛素释放试验,检测空腹血脂谱和其他重要生化指标.所有受试者中540名进行FSIGT.甘油三酯与空腹血糖所得简易指数为TyG,甘油三酯与餐后2h血糖所得简易指数为TyG2.结果 Pearson相关分析结果显示,TyG与HOMA-IR(r=0.427,P＜0.01)和FSIGT-ISI(r=-0.100,P=0.024)均显著相关.TyG2与HOMA-IR(r=0.455,P＜0.01)和FSIGT-ISI(r=-0.162,P＜0.01)亦显著相关.与HOMA-IR相比,TyG用于诊断胰岛素抵抗的敏感性和特异性分别为68.5％和63.5％,TyG2分别为81.7％和51.5％.与FSIGT-ISI相比,TyG用于诊断胰岛素抵抗的敏感性和特异性分别为68.5％和49.5％,TyG2分别为75.7％和48.2％.结论 在中国人群中,TyG和TyG2可以作为胰岛素抵抗的简易评价指数.但由于其存在敏感性高而特异性低的特点,限制了其在大规模流行病学筛查中的应用.     

Oral glucose tolerance test‐based calculation identifies different glucose intolerance phenotypes within the impaired fasting glucose range

Aims/Introduction

The conventional oral glucose tolerance test (OGTT) cannot detect future diabetics among isolated impaired fasting glucose (is‐IFG) nor normal glucose tolerant (NGT) groups. By analyzing the relationship between fasting (FPG) and 2‐h plasma glucose (2hPG), the present study identifies is‐IFG subjects liable to worsening glucose homeostasis.

Materials and Methods

Oral glucose tolerance test was carried out in 619 patients suffering from obesity, hypertension or dyslipidemia, whose FPG was in the 100–125 mg/dL range. We calculated the percentage increment of 2hPG with respect to FPG (PG%) in these patients using the formula: ([2hPG − FPG] / FPG) × 100. Differences in β‐cell function within is‐IFG patients were assessed by estimated insulin sensitivity index (EISI), first‐phase insulin release (1stPH) and 1stPH/1/EISI (1stPH_corrected).

Results

Diabetes was diagnosed in 69 patients (11.2%), combined IFG/impaired glucose tolerance (IGT) in 185 patients (29.9%) and is‐IFG in 365 patients (58.9%). Is‐IFG was subdivided into PG% tertile groups: the percentage of females increased from 25% in the lowest to 45.2% in the highest tertile (χ² = 18.7, P < 0.001). Moving from the lowest to the highest PG% tertile group, insulin and 2hPG concentrations rose, whereas FPG, EISI, and 1stPH_corrected decreased progressively and significantly. Furthemore, PG% correlated inversely with EISI (r = −0.44, P < 0.0001) and 1stPH_corrected (r = −0.38, P < 0.0001).

Conclusions

Oral glucose tolerance test does differentiate the great heterogeneity in metabolic disorders of patients with FPG 100–125 mg/dL. Furthermore, PG% can expand the diagnostic power of OGTT in the is‐IFG range by distinguishing metabolic phenotypes very likely to herald different clinical risks.     

Relative contribution of glycogenolysis and gluconeogenesis to hepatic glucose production in control and diabetic rats. A re-examination in the presence of euglycaemia

Summary Several studies have suggested that, in non-insulin-dependent diabetes mellitus, augmented gluconeogenesis is responsible for increased endogenous glucose production (EGP) and in the end determines fasting hyperglycaemia. However, human and animal studies have been conducted by comparing euglycaemic control subjects to hyperglycaemic diabetic probands. We measured EGP and hepatic gluconeogenesis comparing control and diabetic rats in the fasting state (with diabetic animals in hyperglycaemia), re-examining them in the presence of identical euglycaemia (with diabetic rats made acutely euglycaemic through i. v. phloridzin) or during a hyperinsulinaemic clamp. All rats were infused with [3-³H]-glucose and [U-¹⁴C]-lactate; the ratio between ¹⁴C-uridine-diphosphoglucose (reflecting ¹⁴C-glucose 6-phosphate) and 2 ·¹⁴C-phosphoenolpyruvate specific activities (both purified by high performance liquid chromatography from liver) measured hepatic gluconeogenesis. In diabetic animals, although overall EGP ( ∼ 19.5 mg · kg^–1· min^–1) remained unaffected by experimental euglycaemia, the contribution of glycogenolysis largely increased (from 5.4 to 11.7 mg · kg^–1· min^–1, hyper- vs euglycaemia) while gluconeogenesis decreased (from 14.0 to 8.1 mg · kg^–1? min^–1); both were responsible for the augmented EGP (control rats, EGP: 12.7 mg · kg^–1· min^–1; gluconeogenesis: 5.9 mg · kg^–1· min^–1; glycogenolysis: 6.7 mg · kg^–1· min^–1). Finally, during insulin clamp, gluconeogenesis and glycogenolysis were similarly decreased, and both contributed to the hepatic insulin-resistance of diabetic animals. We conclude that, in this model of non-insulin-dependent diabetes, augmented gluconeogenesis is not primarily responsible for fasting hyperglycaemia and hepatic insulin resistance. Finally, failure to accurately match the experimental conditions in which diabetic and control humans or animals are compared affects gluconeogenesis, overestimating its role in determining hyperglycaemia. [Diabetologia (1998) 41: 307–314] Received: 10 September 1997 and in revised form: 13 November 1997     

Impact of differing glucose‐lowering regimens on the pattern of association between glucose control and survival

Aims

To characterize survival in relation to achieved glycated haemoglobin (HbA1c) level within alternative glucose‐lowering regimens with differing risks of hypoglycaemia.

Methods

Data were extracted from the UK Clinical Practice Research Datalink and the corresponding Hospital Episode Statistics. Patients with type 2 diabetes prescribed glucose‐lowering therapy in monotherapy or dual therapy with metformin between 2004 and 2013 were identified. Risk of all‐cause mortality within treatment cohorts was evaluated using the Cox proportional hazards model, introducing mean HbA1c as a quarterly updated, time‐dependent covariable.

Results

There were 6646 deaths in a total follow‐up period of 374 591 years. Survival for lower (<7%) vs moderate HbA1c levels (≥7%, <8.5%) differed by cohort: metformin, adjusted hazard ratio (aHR) 1.03 (95% confidence interval [CI] 0.95‐1.12); sulphonylurea, aHR 1.11 (95% CI 0.99‐1.25); insulin, aHR 1.47 (95% CI 1.25‐1.72); combined regimens with low hypoglycaemia risk, aHR 1.02 (95% CI 0.94‐1.10); and combined regimens with higher hypoglycaemia risk excluding insulin, aHR 1.24 (95% CI 1.13‐1.35) and including insulin, aHR 1.28 (95% CI 1.18‐1.37). Higher HbA1c levels were associated with increased mortality in regimens with low hypoglycaemia risk. Post hoc analysis by HbA1c deciles revealed an elevated risk of all‐cause mortality for the lowest deciles across all cohorts, but particularly in those regimens associated with hypoglycaemia. High HbA1c was associated with no difference, or a small increase in mortality risk in regimens with increased risk of hypoglycaemia.

Conclusions

The pattern of mortality risk across the range of HbA1c differed by glucose‐lowering regimen. Lower HbA1c was associated with increased mortality risk compared with moderate control, especially in those regimens associated with hypoglycaemia. High levels of HbA1c were associated with the expected elevated mortality risk in regimens with low hypoglycaemia risk.     

A proficiency score for assessing the reliability of self blood glucose monitoring

The reliability of self blood glucose analysis was studied in 83 insulin-treated diabetic patients. Reliability was assessed by laboratory analysis of capillary blood samples collected simultaneously on filter paper. Patient and laboratory results were compared using a scoring system which produces an easily understood Proficiency Score. The score was designed to highlight unreliable performance in measuring glucose concentrations in the euglycaemic as well as hypo- and hyperglycaemic ranges. Only 17% of patients achieved acceptable Proficiency Scores by maintaining adequate performance on five occasions.     

The introduction of a quality assessment scheme for extra-laboratory blood glucose analysis

An external quality assessment scheme is described for on-ward testing of blood glucose by nursing staff using the Glucometer II/Glucostix system. This involved the distribution of two concentrations of glucose solutions to the wards at 2-week intervals. Initially, results were examined prior to the introduction of a formal training programme for use of the blood glucose meters when the hospital CV was 25% (low glucose) and 19% (high glucose). Some improvement was shown after 6 months, with CVs of 13 and 8%, and a greater improvement after 12 months with CVs of 6 and 8%, respectively. A ward report was designed to allow easy interpretation of performance by the participants in the scheme. The introduction of this report was well received and generated enthusiasm among the ward staff.     

Strong association of C-reactive protein with body mass index and 2-h post-challenge glucose in non-diabetic, non-smoker subjects without hypertension.

AIMS: Increases in C-reactive protein (CRP) levels have been shown to be associated with cardiovascular diseases as well as asymptomatic atherosclerosis and to be closely related to traditional cardiovascular risk factors. The aim of this study was to determine the clinical and biochemical characteristics associated with CRP in non-diabetic, non-smoker subjects without hypertension. METHODS: A 75-g oral glucose tolerance test was performed on 305 Japanese subjects aged 40-70 years who were undergoing health examinations. We recruited non-diabetic, non-smoker subjects without hypertension. Subjects with known cardiovascular diseases, chronic or acute inflammation, malignant diseases, or autoimmune disorders were excluded. Plasma high-sensitivity CRP was measured in 125 subjects who satisfied the admission criteria. RESULTS: Plasma CRP levels were significantly higher in the 28 subjects with impaired glucose tolerance (IGT) than that in the 97 subjects with normal glucose tolerance (NGT) (median 0.53, range 0.18-1.10 mg/l vs. median 0.32, range 0.17-0.49 mg/l; P = 0.032). There was a positive correlation of CRP with body mass index (BMI), triglycerides, uric acid, fasting glucose, oral glucose tolerance test (OGTT) 1-h glucose, OGTT 2-h glucose, and a negative correlation with HDL cholesterol. Multivariate regression analysis identified BMI (F = 8.57, P = 0.004) and OGTT 2-h glucose (F = 5.96, P = 0.016) as independent predictors for CRP. CONCLUSIONS: BMI and OGTT 2-h glucose are the most important predictors for plasma CRP in non-diabetic, non-smoker subjects without hypertension.     

Post-challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima-media thickness: the RIAD Study. Risk Factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes.

AIMS: Only scarce information exists on the distribution and atherosclerosis risk in different types of hyperglycaemia at diabetes detection. This study aimed to analyse the occurrence of isolated fasting (IFH), isolated post-challenge (IPH) and combined hyperglycaemia (FH/PH) among subjects detected to have diabetes and the association of these types of hyperglycaemia with cardiovascular risk factors and carotid intima-media thickness (IMT). METHODS: A total of 785 middle-aged subjects of the Risk Factors in Impaired Glucose Tolerance (IGT) for Atherosclerosis and Diabetes (RIAD) study underwent a 75-g oral glucose tolerance test and examination of various atherosclerosis risk factors. IMT was measured by B-mode ultrasound. RESULTS: One hundred and nineteen (15.2%) asymptomatic diabetic subjects were detected: of these, 35.3% with IFH, 26% with IPH and 38.7% with FH/PH. The level of risk factors was higher in diabetic vs. non-diabetic subjects. HbA1c and cardiovascular risk factors were in the same range for IFH and IPH except for active plasminogen activator inhibitor (PAI)-1 which was significantly higher in IFH. A higher risk burden was found in the FH/PH group vs. both IFH and IPH. IMT was as follows: non-diabetic subjects 0.85 +/- 0.18 mm, IFH 0.91 +/- 0.20 mm, IPH 0.94 +/- 0.18 mm, FH/PH 0.98 +/- 0.17 mm (P < 0.05 vs. non-diabetes). 2 h post-challenge glucose (2hPG) correlated more closely (r = 0.23, P < 0.001) to IMT than fasting plasma glucose (FPG) (r = 0.14, P = 0.004). The importance of 2hPG was confirmed by the direct comparison of FPG and 2hPG in a three dimensional analysis. A significant increase of IMT was only observed in the subgroups with abnormal post-challenge hyperglycaemia for both combinations with normal FPG and IFG. FPG category did not significantly add to IMT in either group of post-challenge hyperglycaemia. Regression analysis in the whole sample revealed 2hPG but not FPG as a significant determinant of IMT. Further significant risk factors were age, male sex, total cholesterol, HDL-cholesterol and hypertension. CONCLUSIONS: The RIAD study population at high risk for Type 2 diabetes mellitus, post-challenge hyperglycaemia was found to relate more strongly than fasting hyperglycaemia with carotid IMT.     

Concordance between fasting and 2-h post-glucose challenge criteria for the diagnosis of diabetes mellitus and glucose intolerance in high risk individuals.

AIMS: To compare the new fasting with the 2-h post glucose challenge diagnostic criteria for diabetes mellitus in a high-risk Central European population. METHODS: The results of the 75-g oral glucose tolerance tests (OGTT) performed between 1st January 1990 and 31st December 1998 in patients at high risk of glucose metabolism disturbance were analysed. RESULTS: From 1554 patients with OGTT results available for the study, 1360 (759 women and 601 men, aged 65.5+/-6.9 years, body mass index 28.2 +/- 4.5 kg/m2) were included into the study. With the use of the post-challenge criteria, 41.3% of the analysed population had diabetes or impaired diabetes tolerance (IGT), whereas with the new fasting system only 16.6% would have been diagnosed with any type of glucose intolerance. Diabetes was significantly more often diagnosed with the post-challenge criteria than with the fasting ones: 16.2 vs. 5.3% (P < 0.0001). The subjects with diabetes diagnosed upon fasting glucose value were significantly younger than the subjects with diabetes diagnosed according to the 2-h glucose challenge: 65.7 +/- 6.2 vs. 68.8 +/- 7.0 years, respectively (P < 0.01). The sensitivity of the new criteria for the diagnosis of diabetes was 18.2%, and specificity 97.2%. A total of 77.8% of IGT cases would have been diagnosed as having normal glucose metabolism according to the fasting glucose. The sensitivity of the new criteria for the diagnosis of impaired glucose tolerance (IGT or impaired fasting glucose) was 14.6%, and specificity 89.8%. The overall kappa statistic (k) was low; 0.211 (95% confidence interval 0.149-0.27). CONCLUSIONS: The new lower fasting criteria might be too insensitive to identify a large proportion of individuals with diabetes or impaired glucose intolerance, particularly in a high-risk population.     

A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals

Glucosamine (GlcN) is a widely utilized dietary supplement that is used to promote joint health. Reports that oral GlcN supplementation at usual doses adversely affects glucose metabolism in subjects with impaired glucose tolerance have raised concerns that GlcN should be contraindicated in individuals with diabetes and those at risk for developing it. This review addresses its potential, when used at typical doses, to affect glucose metabolism and insulin sensitivity in healthy individuals and those with diabetes or 'pre-diabetes'. Publicly available scientific information and data on GlcN were systematically compiled using the electronic search tool, Dialog , and reviewed with special emphasis on human studies. In long-term clinical trials, including those containing subjects with type 2 diabetes or 'pre-diabetes', GlcN produced a non-significant lowering of fasting blood glucose concentrations in all groups of subjects treated for periods of up to 3 years. Owing to limitations in study design, conclusions based on studies that report adverse affects of GlcN on insulin sensitivity and glucose tolerance in pre-diabetic subjects are suspect. However, no definitive long-term studies of GlcN use for individuals with pre-diabetes are available. Nevertheless, based on available evidence, we conclude that GlcN has no effect on fasting blood glucose levels, glucose metabolism, or insulin sensitivity at any oral dose level in healthy subjects, individuals with diabetes, or those with impaired glucose tolerance.     

Diurnal blood glucose profiles in women with gestational diabetes with or without hypertension.

AIM: The aim of the study was to establish whether diurnal blood glucose profiles differed in women with gestational diabetes (GDM) with different forms of hypertensive complications. METHODS: The subjects were patients diagnosed at 26-32 gestational weeks as having GDM (n = 178). They were classified as being normotensive, having chronic hypertension (with or without superimposed pre-eclampsia on chronic hypertension) or pregnancy-induced hypertension (with or without proteinuria). We compared diurnal blood glucose profiles (blood glucose taken every 4 h over 24 h) in these three groups. RESULTS: Hypertension complicated 43% of the women with GDM. The glucose profiles were similar between the three groups, except that in early morning hours (from 04:00 to 08:00 h) blood glucose concentrations increased in mothers with chronic hypertension, whereas they decreased in the normotensive women. In univariate regression analysis, both obesity (BMI > or = 28 kg/m(2)) and chronic hypertension showed significant association with blood glucose rise from 04:00 to 08:00 h, but in a multiple regression model neither showed significant independent effect. CONCLUSIONS: The rise in blood glucose levels during the early morning hours in women with GDM and chronic hypertension could reflect greater insulin resistance and sympathetic overactivity.     

Impaired glucose metabolism and health related quality of life

AimsWe aimed at investigating whether different categories of glucose tolerance have any effect on a person's HRQoL.MethodsPopulation-based cross-sectional study conducted as a community sample of apparently healthy middle-aged individuals living in Western Finland. The subjects of the study, 1383 individuals, aged 45–70 years, had at least one cardiovascular risk factor but no previous diagnoses of either diabetes or cardiovascular disease. They completed health related quality of life (HRQoL) questionnaire before the oral glucose tolerance test (OGTT) was performed to diagnose the gategories of glucose tolerance.ResultsPersons with newly diagnosed type 2 diabetes (NDM) had lower scores for physical functioning, general health and emotional role than subjects with normal glucose tolerance.ConclusionThe results of the HRQoL questionnaire demonstrated that NDM is negatively associated with HRQoL, but prediabetes – IFG or IGT – does not.     

Use of an alpha-glucosidase inhibitor to maintain glucose homoeostasis during postprandial exercise in intensively treated Type 1 diabetic subjects.

AIM: We evaluated the effects of an alpha-glucosidase inhibitor, acarbose, on glucose homoeostasis during postprandial exercise in Type 1 diabetic subjects. METHODS: Seven Type 1 diabetic subjects with good glycaemic control on ultralente-regular insulin were randomized in a single blind cross-over study to acarbose 100 mg or placebo taken with a mixed meal (600 kcal, 75 g carbohydrates), followed 90 min later by 30 min of exercise at 50% maximum aerobic capacity. Glucose turnover was measured by tracer (d-[6,6,2H2]glucose) methodology, and intestinal glucose absorption was quantified using carbohydrate polymers labelled with [13C]glucose. RESULTS: Acarbose resulted in a significant decrease in the postprandial glycaemic rise (mean +/- SEM 2.9 +/- 0.6 vs. 5.0 +/- 0.7 mmol/l; P < 0.005) and in the glycaemic nadir during exercise (- 0.8 +/- 0.6 vs. 0.9 +/- 1.3 mmol/l below baseline; P < 0.05). Total glucose appearance increased similarly under the two treatments during the postprandial (27.0 vs. 27.9 micromol per kg per min) and exercise (33.9 vs. 33.5 micromol per kg per min) periods. Mean glucose absorption was significantly delayed by acarbose (7.8 vs. 10.2 micromol per kg per min; P < 0.02), but was compensated by the lack of postprandial suppression of hepatic glucose production (106% of basal hepatic glucose production vs. 81%; P < 0.006). Episodes of hypoglycaemia were no different (three vs. six). CONCLUSION: These results indicate that, in Type 1 diabetic subjects, acarbose results in a better glycaemic profile during postprandial exercise and suggest that it could lead to a lower risk of exercise-induced hypoglycaemia due to delayed glucose absorption and less suppression of hepatic glucose production.