Non-diabetic Hyperglycaemia Research Articles

Performance of the UK Prospective Diabetes Study Risk Engine and the Framingham Risk Equations in Estimating Cardiovascular Disease in the EPIC- Norfolk Cohort

OBJECTIVEThe purpose of this study was to examine the performance of the UK Prospective Diabetes Study (UKPDS) Risk Engine (version 3) and the Framingham risk equations (2008) in estimating cardiovascular disease (CVD) incidence in three populations: 1) individuals with known diabetes; 2) individuals with nondiabetic hyperglycemia, defined as A1C ≥6.0%; and 3) individuals with normoglycemia defined as A1C <6.0%.RESEARCH DESIGN AND METHODSThis was a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40–79 years recruited from U.K. general practices attended a health examination (1993–1998) and were followed for CVD events/death until April 2007. CVD risk estimates were calculated for 10,137 individuals.RESULTSOver 10.1 years, there were 69 CVD events in the diabetes group (25.4%), 160 in the hyperglycemia group (17.7%), and 732 in the normoglycemia group (8.2%). Estimated CVD 10-year risk in the diabetes group was 33 and 37% using the UKPDS and Framingham equations, respectively. In the hyperglycemia group, estimated CVD risks were 31 and 22%, respectively, and for the normoglycemia group risks were 20 and 14%, respectively. There were no significant differences in the ability of the risk equations to discriminate between individuals at different risk of CVD events in each subgroup; both equations overestimated CVD risk. The Framingham equations performed better in the hyperglycemia and normoglycemia groups as they did not overestimate risk as much as the UKPDS Risk Engine, and they classified more participants correctly.CONCLUSIONSBoth the UKPDS Risk Engine and Framingham risk equations were moderately effective at ranking individuals and are therefore suitable for resource prioritization. However, both overestimated true risk, which is important when one is using scores to communicate prognostic information to individuals.

Three years follow-up of screen-detected diabetic and non-diabetic subjects: who is better off? The ADDITION Netherlands study

BackgroundPeople with non-diabetic hyperglycaemia might be at risk of lacking adequate control for cardiovascular risk factors. Our aim was to determine the extent of health care utilization and provision in primary care and to evaluate the risk of cardiovascular disease in persons with an elevated risk score in a stepwise diabetes screening programme.MethodsA total of 56,978 non-diabetic patients, aged 50–70 years, from 79 practices in the Netherlands were invited to participate in a screening programme starting with a questionnaire. Those with an elevated score, underwent further glucose testing. Screened participants with type 2 diabetes (n = 64), impaired glucose tolerance (IGT) (n = 62), impaired fasting glucose (IFG) (n = 86), and normal glucose tolerance (NGT) (n = 142) were compared after three years regarding use of medication, care provider encounters and occurrence of CVD.ResultsIn all glucose regulation categories cardiovascular medication was prescribed more frequently during follow-up with the strongest increase in diabetic patients. Number of practice visits was higher in diabetic patients compared to those in the other categories. Glucose, lipids, and blood pressure were measured most frequently in diabetic patients. Numbers of cardiovascular events in participants with NGT, IFG, IGT and diabetes were 16.7, 32.6, 17.3 and 15.7 per 1,000 person-years (non significant), respectively.ConclusionAfter three years of follow-up, screened non-diabetic participants with an elevated risk score had cardiovascular event rates comparable with diabetic patients. Screened non-diabetic persons are at risk of lacking optimal control for cardiovascular risk factors while screen-detected diabetic patients were controlled adequately.

Abstract P62: Derangements in Blood Glucose Following Initial Resuscitation from In-Hospital Cardiac Arrest: A Report from the American Heart Association National Registry of Cardiopulmonary Resuscitation

BACKGROUND: Hyperglycemia is associated with poor outcomes in a variety of critically-ill patient populations; however, little is known about the role of hyperglycemia in determining outcomes following in-hospital cardiac arrest (IHCA). METHODS: We performed a retrospective analysis of 17,800 adult in-hospital cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Minimum and maximum blood glucose values during the first 24 hours following return of spontaneous circulation (ROSC) were examined. RESULTS: Glucose data from 3,226 patients were available for analysis. Post-ROSC maximum blood glucose values were markedly elevated in diabetic (median, 226 mg/dL, [IQR, 165 – 307 mg/dL)] as well as non-diabetic patients (176 mg/dL, 135 – 239 mg/dL). Survival to hospital discharge was higher in non-diabetics than diabetics (45.5% [95% CI, 43.3 – 47.6%] vs. 41.7% [95% CI, 38.9 –44.5%], p = 0.037). In non-diabetics, survival to hospital discharge varied significantly when stratified by glucose value with optimal survival odds occurring across a broad range of minimum (71 – 170 mg/dL) and maximum (111 – 240 mg/dL) glucose values. Cardiac arrest duration quartile was identified as a significant factor associated with the development of post-ROSC hypo- and hyperglycemia in non-diabetics. CONCLUSIONS: Derangements in blood glucose are common following IHCA in both diabetic and non-diabetic patients. Optimal survival odds occur across a relatively broad range of glucose values in non-diabetics; however, both hypo- and hyperglycemia are associated with worse outcomes and associated with longer arrest durations.

Non-diabetic maternal hyperglycaemia was associated with adverse pregnancy outcomes

Source Citation The HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358:1991-2002. 18463375

Nondiabetic maternal hyperglycemia was associated with adverse pregnancy outcomes

ACP Journal Club19 August 2008Nondiabetic maternal hyperglycemia was associated with adverse pregnancy outcomesAnna P. Kenyon, MBChB, MD, Andrew H. Shennan, MBBS, MDAnna P. Kenyon, MBChB, MDKings College, London, United Kingdom (A.P.K., A.H.S.)Search for more papers by this author, Andrew H. Shennan, MBBS, MDKings College, London, United Kingdom (A.P.K., A.H.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-4-200808190-02006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationThe HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358:1991-2002. https://pubmed.ncbi.nlm.nih.gov/18463375Clinical Impact RatingsGIM/FP/GP: Endocrinology: References1 Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005;352:2477-86. [PMID: 15951574] Google Scholar2 Antenatal care: routine care for the healthy pregnant woman. NICE Clinical Guideline 62; 2008. www.nice.org.uk/nicemedia/pdf/CG062QuickRefGuide.pdf. Google Scholar3 Moses R, Griffiths R, Davis W. Gestational diabetes: Do all women need to be tested? Aust NZ J Obstet Gynaecol. 1995;35:387-9. [PMID: 8717560] Google Scholar Author, Article, and Disclosure InformationAffiliations: Kings College, London, United Kingdom (A.P.K., A.H.S.)This article was published at Annals.org on 5 August 2008. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMetformin (alone or with insulin) was as effective as insulin for preventing perinatal complications in gestational diabetes Anna P. Kenyon and Andrew H. Shennan Metrics 19 August 2008Volume 149, Issue 4Page: JC2-6KeywordsBlood plasmaCesarean sectionGestational diabetesGlucoseHyperglycemiaInsulinMedical risk factorsPopulation statisticsPregnancy ePublished: 19 August 2008 Issue Published: 19 August 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Diabetes and hyperglycemia: Strict glycemic control

To critically review recent evidence on pathophysiology, diagnosis, and control of acute and chronic hyperglycemia in medical and surgical intensive care unit (ICU) patients. A MEDLINE/PubMed search (1966 through February 2006) with manual cross-referencing was conducted, including all relevant articles published on blood glucose control in intensive care patients. An emphasis was placed on more recent clinical trials investigating the effects of tight glycemic control in ICU patients and on basic science studies investigating the pathophysiology and systemic effects of transient hyperglycemia in nondiabetic patients. Original articles, selected reviews, letters to the editor, and chapters of selected textbooks were extracted. The reviewed information was then analyzed with respect to the prevalence of hyperglycemia in ICU patients, the pathophysiology of hyperglycemia in nondiabetics, and evidence on glycemic control in various subgroups of ICU patients. The risk of iatrogenic hypoglycemia in the ICU and potential future research directions are discussed at the end of the review. Recent evidence shows direct improvements in patient mortality and in-hospital morbidity with strict control of even short-term elevations of glucose levels in certain subgroups of ICU patients. However, precisely defined target glucose levels, subgroup analyses of different patient populations and treatment interventions, and the avoidance of hypoglycemic episodes during insulin therapy remain incompletely resolved and warrant future investigation.

Registro continuo de glucosa en sujetos con alto riesgo de diabetes tipo 2

To assess the relevance of unrecognised hyperglycaemia among high-risk subjects for developing type 2 diabetes. Cross-sectional multicentre study in primary care. Subjects aged 40 to 75 years with previous evidence of impaired glucose metabolism were screened according to the World Health Organization rules by means of an oral glucose tolerance test (OGTT). Those with diabetes diagnostic criteria were excluded. An individualized 48-h ambulatory continuous glucose monitoring (CGM) calibrated by plasma values (Glucoday) was performed. Data from biosensor activity were computerized in order to identify hyperglycaemic records. 50 out of 64 screened subjects were included and evaluated; there were 30 female (60%). Mean age was 59 years; body mass index, 30.9; HbA1c, 5.3%, and HOMA, 2.8. Regarding the CGM results, 9 whole registers (18%) were rejected because of technical problems and 41 continuous profiles (72%) were analysed, corresponding to 17 (41.5%) subjects with normal OGTT and 24 (58.5%) with non-diabetic hyperglycaemia on OGTT. Mean CGM time with hyperglycaemia (fasting > or = 6.1 mmol/l or non-fasting > or = 7.8 mmol/l) accounted for 5.8 h, a 17.2% of the effective register per subject (33.8 h). Both groups matched the World Health Organization diabetes diagnostic interval (fasting > or = 7 mmol/l or non-fasting > or = 11.1 mmol/l): 1.1 h of effective register (3.6%) and 1.2 h (3.3%), respectively. The CGM evidenced a high degree of unrecognised hyperglycaemia among high-risk individuals. Therefore, casual plasma glucose measurements should be recommended to achieve early screening.

The threshold for diagnosing impaired fasting glucose: a position statement by the European Diabetes Epidemiology Group

The category of IFG was introduced in the late 1990s to denote a state of non-diabetic hyperglycaemia defined by a fasting plasma glucose (FPG) concentration between 6.1 and 6.9 mmol/l. In 2003 the American Diabetes Association recommended that this diagnostic threshold be lowered to 5.6 mmol/l. The justification for lowering the threshold has been questioned. This simple change in cut-off value creates a pandemic of IFG, with a two- to five-fold increase in the prevalence of IFG across the world. Such a change in threshold has far-reaching public health implications. The European Diabetes Epidemiology Group (EDEG) has reviewed the evidence for this lower cut-off point for the definition of IFG and concludes that the previous definition should not be altered. EDEG further recommends that the value of all categorical definitions of non-diabetic hyperglycaemia should be reconsidered.

Diabetic and nondiabetic hyperglycemia in the ICU

Summary Hyperglycemia is a common feature in critically ill patients, whether they are diabetic or not, and it is associated with unfavorable outcome. The more severe the underlying disease, the more important the hyperglycemia appears to be although, we still cannot define whether hyperglycemia is just a marker of the severity of the acute illness or rather an active contributor to poor outcome. The review of the literature on this subject published from 2001 up today conveys a massive amount of information the interpretation of which is equivocal, due to the heterogeneity of patients (nondiabetic vs. diabetic, medical intensive care unit (ICU) pts vs. surgical ICU pts) and of interventions (dose and modality of insulin infusion). The association between high glucose level and mortality is strong in critically ill patients without a previous history of diabetes. Admission hyperglycemia seems to be an independent risk factor of in-hospital mortality in patients both with and without diabetes in cardiac, cardiothoracic and neurosurgical ICUs. No data are still available on general surgical ICU patients. Tight control of blood glucose levels has been demonstrated to improve outcome in both diabetic and nondiabetic critically ill patients. In surgical ICUs, tight glucose control improves mortality and reduces morbidity only among patients admitted in ICU for more than 5 days, while outcome is not improved in patients who stay in ICU for less than 3 days. However, it is not yet understood if such favorable effect is secondary to glucose control itself or if insulin plays a part, by means of its nonglucose, anabolic effects. More randomized controlled trials are needed, addressing specific issues—such as the optimal target glucose concentration and the most effective insulin regimen—especially in the general surgical patient.

Is Nondiabetic Hyperglycemia a Risk Factor for Cardiovascular Disease?

Although hyperglycemia increases the risk of cardiovascular disease (CVD) in diabetic patients, the risk associated with blood glucose levels in the nondiabetic range remains unsettled. We identified 38 reports in which CVD incidence or mortality was an end point, blood glucose levels were measured prospectively, and the relative risk (RR) and information necessary to calculate the variance were reported comparing groups of nondiabetic people. These reports were prospective studies, published in English-language journals. First author, publication year, participant age and sex, study duration, CVD end points, glucose assessment methods, control for confounding, range of blood glucose levels, RR, and confidence intervals (CIs) or P values were extracted. Using a random effects model, we calculated pooled RRs and 95% CIs. The group with the highest postchallenge blood glucose level (midpoint range, 150-194 mg/dL [8.3-10.8 mmol/L]) had a 27% greater risk for CVD compared with the group with the lowest level (midpoint range, 69-107 mg/dL [3.8-5.9 mmol/L]) (RR, 1.27 [95% CI, 1.09-1.48]). The results were similar when combining studies regardless of type of blood glucose assessment (RR, 1.36 [95% CI, 1.23-1.52]) and when using strict criteria for exclusion of diabetic subjects (RR, 1.26 [95% CI, 1.11-1.43]). Adjustment for CVD risk factors attenuated but did not abolish this relationship (RR, 1.19 [95% CI, 1.07-1.32]). The RR was greater in cohorts including women than in cohorts of men (RR, 1.56 vs 1.24 [P = .03]). Blood glucose level is a risk marker for CVD among apparently healthy individuals without diabetes.

Correlation between extracellular glucose and seizure susceptibility in adult rats.

In adult diabetic patients, periods of hyperglycemia may be associated with exacerbation of focal seizures. Our objective was to determine in the adult rats the correlation between seizure susceptibility and extracellular glucose concentration in two models of seizures. Male rats were injected with two doses of streptozocin (40 mg/kg IP) on 2 consecutive days to induce diabetic hyperglycemia. Controls either received vehicle or were not injected. After 2 weeks, blood glucose concentration was measured, and the rats were subjected to flurothyl seizure test. Another group of rats received glucose solution (20%, 5 ml IP) 30 minutes before testing to induce nondiabetic hyperglycemia. Thresholds for flurothyl-induced clonic and tonic-clonic seizures were determined. Finally, in vitro epileptiform activity was induced in the entorhinal cortex-hippocampal slices from naive rats by perfusing with magnesium-free medium with various glucose concentrations. In additional slices, paired-pulse paradigm was determined in the perforant path. Susceptibility to clonic and tonic-clonic flurothyl-induced seizures positively correlated with blood glucose concentrations as the increased glucose concentration was associated with proconvulsant effects. Similarly, in the in vitro experiments, epileptiform activity was promoted by increased and suppressed by decreased glucose concentrations. Data indicate that, in the adult rats, high glucose concentrations are associated with proconvulsant effects.

Vitamin C and Glycohemoglobin Revisited

Blood glucose (BG) concentrations averaged over a 2- to 3-month period are represented by blood glycohemoglobin (GHb) as a percentage of total hemoglobin. Strict glycemic control is important to the successful outcome of diabetic pregnancy and in avoiding development of many diabetic complications (1). Hyperglycemia in nondiabetics is a major risk factor in cardiovascular disease and cancer (2). Thus, knowledge of an individual’s true GHb value is vital. This need has prompted continuing investigations of potential interferences in GHb assays (3)(4), including conflicting reports on the effect of vitamin C on GHb (5)(6)(7). …

Prevalence and atherosclerosis risk in different types of non-diabetic hyperglycemia. Is mild hyperglycemia an underestimated evil?

So far little is known about the importance of different types of non-diabetic hyperglycemia for the development of macrovascular disease. The aim of this work was to examine the intima-media thickness (IMT) of the common carotid artery (CCA), a well-accepted marker of atherosclerosis, as well as various risk factors for atherosclerosis in non-diabetic subjects with isolated fasting (IFH; n=67), isolated postchallenge (IPH; n=82) and combined hyperglycemia (CH; n=88) in comparison to normoglycemic (NG; n=265) controls. Subjects were participants of the RIAD study (Risk Factors in IGT for Atherosclerosis and Diabetes). IMT in the IPH (IMTmean: 0.89+/-0.02 mm; IMTmax: 1.01+/-0.02 mm; mean+/-SEM) and CH group (IMTmean: 0.91+/-0.02 mm; IMTmax: 1.03+/-0.02 mm) was significantly increased vs. the NG (IMTmean: 0.82+/-0.01 mm; IMTmax: 0.94+/-0.01 mm) and IFH group (IMTmean: 0.81+/-0.02 mm; IMTmax: 0.90+/-0.03 mm). IMT of the IFH group was similar to the normoglycemic controls. Subjects in the first and second tertile for postchallenge plasma glucose have similar carotid IMT irrespective of the level of fasting plasma glucose. The individuals of the third tertile for 2 h plasma glucose, whether in the first, second or third tertile of fasting plasma glucose, showed the same carotid IMT, which was significantly higher than all other groups, except for the one with lowest tertile for fasting and postchallenge plasma glucose. Except for total cholesterol and von Willebrand factor the levels of all other risk parameters were significantly higher in the hyperglycemic groups in comparison to the normoglycemic controls. Among the hyperglycemic subjects the CH group was at the highest risk for atherosclerosis with significantly increased levels of plasma triglycerides, fibrinogen, PAI-1, albuminuria, HDL-triglycerides, free fatty acids, insulin and proinsulin, and significantly reduced HDL-cholesterol in comparison to the normoglycemic controls. In summary, postchallenge hyperglycemia within the non-diabetic range is associated with atherosclerosis, as measured by the increased intima-media thickness of the common carotid artery. Furthermore, cardiovascular risk factors are significantly raised in all types of non-diabetic hyperglycemia.

Hypertension, serum insulin, obesity and the metabolic syndrome.

In recent years it has been proposed that hypertension is part of a cluster of metabolic risk factors (syndrome X) involving hyperlipidaemia and hyperglycaemia, with hyperinsulinaemia as the common link. This study has investigated: (1) the prevalence of the metabolic syndrome and its component variables and their relationship to body mass index (BMI) and non-fasting insulin levels in a general population; and (2) the distribution and clustering of metabolic variables in normotensives and hypertensives. Cross-sectional study of 5222 men aged 40-59 years with no history of coronary heart disease (CHD), diabetes mellitus or stroke drawn from general practices in 18 British towns. The men were a subgroup of the 7735 men in the British Regional Heart Study (BRHS) cohort whose baseline non-fasting serum was analysed for insulin, using a specific ELISA method. Hyperinsulinaemia, hyperglycaemia, high serum total cholesterol, high triglyceride and hyperuricaemia were defined as the top 20% of the distribution in the 5222 men. Low HDL-cholesterol was defined as the bottom 20%. BMI and non-fasting insulin were both significantly and strongly associated with non-diabetic hyperglycaemia, lipid abnormalities (HDL-cholesterol, triglyceride and total cholesterol) and hyperuricaemia. BMI was strongly associated with hypertension whereas non-fasting insulin showed a much weaker relationship which was abolished after adjustment for BMI. However, only 2.9% of men showed the 'full metabolic syndrome' (hypertension, hyperglycaemia and dyslipidaemia) and a large proportion of these men were hyperinsulinaemic (65%) or obese (47%). Dyslipidaemia (any one of low-HDL-cholesterol, high triglyceride or high cholesterol) was common in both normotensives and hypertensives (40.5% vs 46.4%). Hypertensives showed significantly higher levels of total cholesterol, triglyceride, blood glucose, urate and more clustering of hyperglycaemia and dyslipidaemia than normotensives even after adjustment for BMI. Hypertensives were more likely to have lipid abnormalities and clustering of risk factors than normotensives even after adjustment for BMI. The metabolic syndrome is more strongly associated with hyperinsulinaemia than with obesity but it is relatively uncommon in men with no history of cardiovascular disease or diabetes. Given the weak relationship between hypertension and hyperinsulinaemia, the latter is unlikely to explain the higher levels of lipid abnormalities and clustering seen in hypertensives. Overweight/obesity may be primarily involved in the pathways to hypertension and lipid abnormalities but the unravelling of these relationships require more specific measures of adipose tissue distribution, composition and function.

Does non-diabetic hyperglycemia predict future ihd? Evidence from the caerphilly and speedwell studies

We have examined the risk of subsequent ischemic heart disease (IHD) in men according to their initial fasting plasma glucose level in a prospective cohort study (Caerphilly Collaborative Study) of 4860 middle aged men from South Wales and Bristol, U.K. Ninety-four men reported themselves to be diabetic at initial screening and fasting venous plasma glucose levels were determined in these men and in a further 4519 non-diabetic men. At follow-up new IHD events occurred twice as commonly in diabetics compared to non-diabetics and overall mortality was increased 4-fold. Among non-diabetics however, increased IHD events only occurred in men with fasting values at the upper end of the distribution of baseline plasma glucose values [at 6.8 mmol/l (122 mg/dl) or more]. This association was reduced, but remained statistically significant, after adjusting for factors associated with plasma glucose levels; body mass index, plasma triglyceride, smoking habit and pre-existing IHD. In conclusion there is no evidence of a consistent, graded increase in risk of IHD by initial fasting plasma glucose level although the risk is significantly increased in men with baseline plasma values at 6.8 mmol/l (122 mg/dl) or more, and also in diabetics. This study suggests that such levels probably represent a pre-diabetic state in many individuals. Appropriate non-pharmacological intervention may be useful in halting the progression to the diabetic state, although this should be tested in experimental studies.

Impaired Glucose Homeostasis in Adult Rats From Hyperglycemic Mothers

The purpose of our study was to investigate whether nondiabetic gestational hyperglycemia during fetal life could have additional effects on glucose homeostasis and insulin secretion in the adult rat. Hyperglycemia without the main other metabolic disorders and vascular injuries associated with diabetes was produced in unrestrained pregnant rats by continuous glucose infusion during the last week of pregnancy. Control rats were infused with distilled water. Compared with controls, the newborns from hyperglycemic rats were hyperglycemic and hyperinsulinemic. When studied longitudinally up to 3 mo, they showed slightly but significantly increased basal plasma glucose levels and normal basal insulin concentrations compared with controls. Glucose tolerance and insulin secretion in response to a glucose load (0.5 mg/kg, i.v.) were altered: Plasma glucose values were more increased at 5 min and remained higher 90 min after glucose injection; incremental plasma insulin values and the insulinogenic indexes (delta IRI/delta G) were always lower in rats from hyperglycemic mothers than in controls. These alterations were more and more marked with advancing age (1-3 mo). These data show that gestational hyperglycemia may lead to persistent impairment of glucose homeostasis and insulin secretion in the adult rat.

Transient Hyperglycemia and Aketotic Hyperosmolar Acidosis with Heat Stroke

Five children are described with aketotic, hyperosmolar, and non-diabetic hyperglycemia. Four of the children were suffering from heat stroke, the etiology was undetermined in the fifth. The cases of heat stroke were managed by reduction of the elevated temperature and fluid replacement. No insulin was used and the elevated blood sugars returned promptly to normal. A possible mechanism is discussed.