Pre-Diabetes 2

© 2011

A1C between 5.7 and 6.4% as a marker for identifying pre-diabetes, insulin sensitivity and secretion, and cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study (IRAS)

            (Lorenzo, Wagenknecht et al. 2010) Download

OBJECTIVE: A1C is an optional method for diagnosing diabetes and also for detecting individuals at increased risk of the disease. However, how A1C compares with fasting (FPG) and 2-h plasma glucose for detecting at-risk individuals is not well known. RESEARCH DESIGN AND METHODS: A 2-h glucose tolerance test, frequently sampled intravenous glucose tolerance test, and A1C were obtained at the follow-up examination in 855 participants in the Insulin Resistance Atherosclerosis Study (IRAS). For this report, 385 individuals were at increased risk of diabetes as defined by A1C between 5.7 and 6.4%, impaired glucose tolerance (IGT), and/or impaired fasting glucose (IFG). RESULTS: IFG and IGT identified 69.1 and 59.5% of all individuals at increased risk of diabetes, respectively. A1C 5.7-6.4% detected 23.6% of all at-risk individuals, although more African Americans (31.4%) and Hispanics (35.2%) than non-Hispanic whites (9.9%). Relative to A1C, FPG was more strongly related to fasting insulin (r = 0.38 vs. 0.26; P < 0.01), acute insulin response (r = - 0.20 vs. - 0.09; P < 0.01), and waist circumference (r = 0.43 vs. 0.25; P < 0.001) by the Spearman correlation test. Similarly, 2-h plasma glucose was more strongly related to Si (r = - 0.40 vs. - 0.27; P < 0.01) and triglycerides (r = 0.30 vs. 0.08; P < 0.001). CONCLUSIONS: A1C 5.7-6.4% is less sensitive for detecting at-risk individuals than IFG and IGT, particularly among non-Hispanic whites. Single determinations of FPG and 2-h plasma glucose seem to be more precise correlates of insulin resistance and secretion than A1C and, in general, better for other metabolic disorders.

Could pre-diabetes be considered a clinical condition? opinions from an endocrinologist and a cardiologist

            (Magalhaes, Cavalcanti et al. 2010) Download

The prevalence of pre-diabetes is increasing worldwide and may start 7 to 10 years before the clinical diagnosis of diabetes. In this stage the presence and accumulation of risk factors is common and already implies an increase in cardiovascular risk. Likewise, the onset of cardiovascular diseases (CVD), mainly coronary artery disease (CAD), peripheral vascular disease and cerebrovascular disease can also take place, all of which account for high rates of morbidity and mortality worldwide. Considering pre-diabetes as a clinical entity, non-pharmacological and pharmacological treatments are indicated with drugs which have shown clinical benefits related to reduction in morbidity and mortality. However, there is still need for new long-term studies to assess the real benefits of several new therapeutical approaches, as well as its cost-effectiveness.

Impact of A1C screening criterion on the diagnosis of pre-diabetes among U.S. adults

            (Mann, Carson et al. 2010) Download

OBJECTIVE: New clinical practice recommendations include A1C as an alternative to fasting glucose as a diagnostic test for identifying pre-diabetes. The impact of these new recommendations on the diagnosis of pre-diabetes is unknown. RESEARCH DESIGN AND METHODS: Data from the National Health and Nutrition Examination Survey 1999-2006 (n = 7,029) were analyzed to determine the percentage and number of U.S. adults without diabetes classified as having pre-diabetes by the elevated A1C (5.7-6.4%) and by the impaired fasting glucose (IFG) (fasting glucose 100-125 mg/dl) criterion separately. Test characteristics (sensitivity, specificity, and positive and negative predictive values) using IFG as the reference standard were calculated. RESULTS: The prevalence of pre-diabetes among U.S. adults was 12.6% by the A1C criterion and 28.2% by the fasting glucose criterion. Only 7.7% of U.S. adults, reflecting 61 and 27% of those with pre-diabetes by A1C and fasting glucose, respectively, had pre-diabetes according to both definitions. A1C used alone would reclassify 37.6 million Americans with IFG to not having pre-diabetes and 8.9 million without IFG to having pre-diabetes (46.5 million reclassified). Using IFG as the reference standard, pre-diabetes by the A1C criterion has 27% sensitivity, 93% specificity, 61% positive predictive value, and 77% negative predictive value. CONCLUSIONS: Using A1C as the pre-diabetes criterion would reclassify the pre-diabetes diagnosis of nearly 50 million Americans. It is imperative that clinicians and health systems understand the differences and similarities in using A1C or IFG in diagnosis of pre-diabetes.

Functional assessment of pancreatic beta-cell area in humans

            (Meier, Menge et al. 2009) Download

OBJECTIVE: beta-Cell mass declines progressively during the course of diabetes, and various antidiabetic treatment regimens have been suggested to modulate beta-cell mass. However, imaging methods allowing the monitoring of changes in beta-cell mass in vivo have not yet become available. We address whether pancreatic beta-cell area can be assessed by functional test of insulin secretion in humans. RESEARCH DESIGN AND METHODS: A total of 33 patients with chronic pancreatitis (n = 17), benign pancreatic adenomas (n = 13), and tumors of the ampulla of Vater (n = 3) at various stages of glucose tolerance were examined with an oral glucose load before undergoing pancreatic surgery. Indexes of insulin secretion were calculated and compared with the fractional beta-cell area of the pancreas. RESULTS: beta-Cell area was related to fasting glucose concentrations in an inverse linear fashion (r = -0.53, P = 0.0014) and to 120-min postchallenge glycemia in an inverse exponential fashion (r = -0.89). beta-Cell area was best predicted by a C-peptide-to-glucose ratio determined 15 min after the glucose drink (r = 0.72, P < 0.0001). However, a fasting C-peptide-to-glucose ratio already yielded a reasonably close correlation (r = 0.63, P < 0.0001). Homeostasis model assessment (HOMA) beta-cell function was unrelated to beta-cell area. CONCLUSIONS: Glucose control is closely related to pancreatic beta-cell area in humans. A C-peptide-to-glucose ratio after oral glucose ingestion appears to better predict beta-cell area than fasting measures, such as the HOMA index.

Retinal vascular changes in pre-diabetes and prehypertension: new findings and their research and clinical implications

            (Nguyen, Wang et al. 2007) Download

Screening for diabetes and pre-diabetes with proposed A1C-based diagnostic criteria

            (Olson, Rhee et al. 2010) Download

OBJECTIVE: An International Expert Committee (IEC) and the American Diabetes Association (ADA) proposed diagnostic criteria for diabetes and pre-diabetes based on A1C levels. We hypothesized that screening for diabetes and pre-diabetes with A1C measurements would differ from using oral glucose tolerance tests (OGTT). RESEARCH DESIGN AND METHODS: We compared pre-diabetes, dysglycemia (diabetes or pre-diabetes), and diabetes identified by the proposed criteria (A1C >/= 6.5% for diabetes and 6.0-6.4% [IEC] or 5.7-6.4% [ADA] for high risk/pre-diabetes) with standard OGTT diagnoses in three datasets. Non-Hispanic white or black adults without known diabetes who had A1C and 75-g OGTT measurements were included from the prospective Screening for Impaired Glucose Tolerance study (n = 1,581), and from the National Health and Nutrition Examination Survey (NHANES) III (n = 2014), and NHANES 2005-2006 (n = 1,111). RESULTS: OGTTs revealed pre-diabetes in 35.8% and diabetes in 5.2% of combined study subjects. A1C provided receiver operating characteristic (ROC) curve areas for diabetes of 0.79-0.83, but ROC curve areas were </= 0.70 for dysglycemia or pre-diabetes. The proposed criteria missed 70% of individuals with diabetes, 71-84% with dysglycemia, and 82-94% with pre-diabetes. Compared with the IEC criteria, the ADA criteria for pre-diabetes resulted in fewer false-negative and more false-positive result. There were also racial differences, with false-positive results being more common in black subjects and false-negative results being more common in white subjects. With use of NHANES 2005-2006 data, approximately 5.9 million non-Hispanic U.S. adults with unrecognized diabetes and 43-52 million with pre-diabetes would be missed by screening with A1C. CONCLUSIONS The proposed A1C diagnostic criteria are insensitive and racially discrepant for screening, missing most Americans with undiagnosed diabetes and pre-diabetes.

Increased incidence of pre-diabetes mellitus at a department of rheumatology: a retrospective study

            (Origuchi, Yamaguchi et al. 2011) Download

We aimed to retrospectively review the incidence of pre-diabetes mellitus (preDM), one of the factors in metabolic syndrome screening, in patients with rheumatic diseases. We examined the levels of hemoglobin A1c (HbA1c) in a total of 498 patients with rheumatic diseases between April 2007 and March 2008 at the Department of Rheumatology in Nagasaki University Hospital. Of the 498 patients, 409 (82.1%) had HbA1c levels higher than 5.6% (National Glycohemoglobin Standardization Program; NGSP) and were recommended for health guidance with a focus on metabolic syndrome. Serum HbA1c levels higher than 6.0%, a possible indicator of DM, were seen in 227 patients (45.6%). Serum HbA1c levels higher than 6.5%, which constitute a high risk for DM, were found in 115 patients (23.1%). PreDM increased gradually with age. Our results suggest that the incidence of preDM may be higher in patients with rheumatic diseases than in patients with other diseases and that these patients should receive healthcare guidance to prevent metabolic syndrome.

Increased expression of beta-N-acetylglucosaminidase in erythrocytes from individuals with pre-diabetes and diabetes

            (Park, Saudek et al. 2010) Download

OBJECTIVE: O-linked beta-N-acetylglucosamine (O-GlcNAc) plays an important role in the development of insulin resistance and glucose toxicity. O-GlcNAcylation is regulated by O-GlcNAc transferase (OGT), which attaches O-GlcNAc to serine and/or threonine residues of proteins and by O-GlcNAcase, which removes O-GlcNAc. We investigated the expression of these two enzymes in erythrocytes of human subjects with diabetes or pre-diabetes. RESEARCH DESIGN AND METHODS: Volunteers with normal condition, pre-diabetes, and diabetes were recruited through a National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases) study and at the Johns Hopkins Comprehensive Diabetes Center. Erythrocyte proteins were extracted and hemoglobins were depleted. Global O-GlcNAcylation of erythrocyte proteins was confirmed by Western blotting using an O-GlcNAc-specific antibody. Relative OGT and O-GlcNAcase protein amounts were determined by Western blot analysis. Relative expression of O-GlcNAcase was compared with the level of A1C. RESULTS: Erythrocyte proteins are highly O-GlcNAcylated. O-GlcNAcase expression is significantly increased in erythrocytes from both individuals with pre-diabetes and diabetes compared with normal control subjects. Unlike O-GlcNAcase, protein levels of OGT did not show significant changes. CONCLUSIONS: O-GlcNAcase expression is increased in erythrocytes from both individuals with pre-diabetes and individuals with less well-controlled diabetes. These findings, together with the previous study that demonstrated the increased site-specific O-GlcNAcylation of certain erythrocyte proteins, suggest that the upregulation of O-GlcNAcase might be an adaptive response to hyperglycemia-induced increases in O-GlcNAcylation, which are likely deleterious to erythrocyte functions. In any case, the early and substantial upregulation of O-GlcNAcase in individuals with pre-diabetes may eventually have diagnostic utility.

All pre-diabetes is not the same: metabolic and vascular risks of impaired fasting glucose at 100 versus 110 mg/dl: the Screening for Impaired Glucose Tolerance study 1 (SIGT 1)

            (Phillips, Weintraub et al. 2006) Download

Cigarette smoking is associated with conversion from normoglycemia to impaired fasting glucose: the Western New York Health Study

            (Rafalson, Donahue et al. 2009) Download

PURPOSE: To determine whether cigarette smoking is associated with the conversion from normoglycemia to impaired fasting glucose (IFG). METHODS: During the years 2003 and 2004, 1,455 participants (mean age, 56.5 years; range, 35-79 years) from the Western New York Health Study who were free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001) were reexamined (68% response rate). Incident IFG was defined as a subject whose baseline fasting plasma glucose was <100mg/dL (normoglycemic) and between 100 and 125 mg/dL at follow-up. Prevalent IFG (n=528) was excluded. Baseline smoking status was categorized as never, former, or current. RESULTS: Of the 1,455 participants, 924 were normoglycemic at baseline: 101/924 converted to IFG over 6 years. Compared with those who remained normoglycemic, converters to IFG were at baseline older, had a larger body mass index, more likely to be hypertensive, currently smoke, and have a family history of type 2 diabetes mellitus (all p<0.05). Multivariate logistic regression demonstrated that compared with subjects who remained normoglycemic, the odds ratio of incident IFG among former and current smokers (vs. never) was 1.68 (95% confidence interval: 0.99-2.80) and 2.35 (95% confidence interval: 1.17-4.72) (p trend=0.008), respectively. CONCLUSION: Smoking was positively associated with incident IFG after accounting for several putative risk factors.


Glucose intolerance in pregnancy and future risk of pre-diabetes or diabetes

            (Retnakaran, Qi et al. 2008) Download

OBJECTIVE: The purpose of this study was to test the hypothesis that any degree of abnormal glucose homeostasis detected on antepartum screening for gestational diabetes mellitus (GDM) should be associated with an increased risk of postpartum pre-diabetes or diabetes. RESEARCH DESIGN AND METHODS: In this prospective cohort study, 487 women underwent 1) antepartum GDM screening by a glucose challenge test (GCT) and a diagnostic oral glucose tolerance test (OGTT) and 2) postpartum metabolic characterization by OGTT at 3 months after delivery. Four baseline glucose tolerance groups were defined on the basis of the antepartum GCT/OGTT: 1) GDM (n = 137); 2) gestational impaired glucose tolerance (GIGT) (n = 91); 3) abnormal GCT with normal glucose tolerance on an OGTT (abnormal GCT NGT) (n = 166); and 4) normal GCT with NGT on an OGTT (normal GCT NGT) (n = 93). RESULTS: The prevalence of postpartum glucose intolerance (pre-diabetes or diabetes) increased across the groups from normal GCT NGT (3.2%) to abnormal GCT NGT (10.2%) to GIGT (16.5%) to GDM (32.8%) (P(trend) < 0.0001). On logistic regression analysis, all three categories of abnormal glucose homeostasis in pregnancy independently predicted postpartum glucose intolerance: abnormal GCT NGT odds ratio (OR) 3.6 (95% CI 1.01-12.9); GIGT OR 5.7 (1.6-21.1); and GDM OR 14.3 (4.2-49.1). Furthermore, both in pregnancy and at 3 months postpartum, insulin sensitivity (IS(OGTT)) and pancreatic beta-cell function (insulinogenic index/homeostasis model assessment of insulin resistance) progressively decreased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all P(trend) < 0.0001). CONCLUSIONS: Any degree of abnormal glucose homeostasis in pregnancy independently predicts an increased risk of glucose intolerance postpartum.

Many Americans have pre-diabetes and should be considered for metformin therapy

            (Rhee, Herrick et al. 2010) Download

OBJECTIVE: To determine the proportion of the American population who would merit metformin treatment, according to recent American Diabetes Association (ADA) consensus panel recommendations to prevent or delay the development of diabetes. RESEARCH DESIGN AND METHODS: Risk factors were evaluated in 1,581 Screening for Impaired Glucose Tolerance (SIGT), 2,014 Third National Health and Nutrition Examination Survey (NHANES III), and 1,111 National Health and Nutrition Examination Survey 2005-2006 (NHANES 2005-2006) subjects, who were non-Hispanic white and black, without known diabetes. Criteria for consideration of metformin included the presence of both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), with > or =1 additional diabetes risk factor: age <60 years, BMI > or =35 kg/m(2), family history of diabetes, elevated triglycerides, reduced HDL cholesterol, hypertension, or A1C >6.0%. RESULTS: Isolated IFG, isolated IGT, and IFG and IGT were found in 18.0, 7.2, and 8.2% of SIGT; 22.3, 6.4, and 9.4% of NHANES III; and 21.8, 5.0, and 9.0% of NHANES 2005-2006 subjects, respectively. In SIGT, NHANES III, and NHANES 2005-2006, criteria for metformin consideration were met in 99, 96, and 96% of those with IFG and IGT; 31, 29, and 28% of all those with IFG; and 53, 57, and 62% of all those with IGT (8.1, 9.1, and 8.7% of all subjects), respectively. CONCLUSIONS: More than 96% of individuals with both IFG and IGT are likely to meet ADA consensus criteria for consideration of metformin. Because >28% of all those with IFG met the criteria, providers should perform oral glucose tolerance tests to find concomitant IGT in all patients with IFG. To the extent that our findings are representative of the U.S. population, approximately 1 in 12 adults has a combination of pre-diabetes and risk factors that may justify consideration of metformin treatment for diabetes prevention.

Comparison of islet autoantibodies in 'pre-diabetes' and recommendations for screening

            (Riley, Atkinson et al. 1990) Download

(Pre)diabetes, brain aging, and cognition

            (Roriz-Filho, Sa-Roriz et al. 2009) Download

Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy. In fact, diabetes subjects are more prone to develop extense and earlier-than-usual leukoaraiosis (White Matter High-Intensity Lesions - WMHL). WMHL are usually present at different degrees in brain scans of elderly people. People with more advanced WMHL are at increased risk for executive dysfunction, cognitive impairment and dementia. Clinical phenotypes associated with insulin resistance possibly represent true clinical models for brain and systemic aging.

Five-year incidence of cataract in older persons with diabetes and pre-diabetes

            (Saxena, Mitchell et al. 2004) Download

PURPOSE: To investigate longitudinal associations between diabetes and the 5-year incidence of cataract and cataract surgery. (A population-based, cohort study of 2335 persons with baseline ages 49 years or older resident in the Blue Mountains region, west of Sydney, Australia). METHODS: Baseline information on diabetes history was collected during an interviewer-administered questionnaire. Impaired Fasting Glucose (IFG) was defined as venous plasma glucose between 6.0 and 7.0 mmol/L and newly diagnosed diabetes as plasma glucose >7.0 mmol/L, using fasting blood glucose measurements taken at baseline. Retroillumination lens photographs from the baseline and 5-year follow-up examinations were graded for presence of cortical, posterior subcapsular (PSC) and nuclear cataract. RESULTS: We found a 2-fold higher 5-year incidence of cortical cataract in participants with IFG, multivariate adjusted odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1-4.1. Incident PSC cataract was more frequent among persons with diabetes, but this association was statistically significant only for those with newly diagnosed diabetes, multivariate adjusted OR 4.5 (CI 1.5-13.0). There were no statistically significant associations found between incident nuclear cataract or cataract surgery and either diabetes or IFG. CONCLUSIONS: These epidemiological data suggest that IFG, a pre-diabetic condition, may be a risk factor for the development of cortical cataract.


Elevated serum ferritin concentrations in prediabetic subjects

            (Sharifi, Nasab et al. 2008) Download

BACKGROUND: Few data are available on the association of variables of the insulin resistance syndrome and serum ferritin, an indicator of body iron stores. We examined the relationship between serum ferritin levels and impaired fasting glucose, a pre-diabetes stage associated with insulin resistance, in this study. SUBJECTS & METHODS: One hundred and eighty seven people, including 91 subjects with impaired fasting glucose (IFG) and 96 healthy people who were well matched for age and sex, were enrolled. Body mass index (BMI) and blood pressure of the participants were measured and serum cholesterol, triglyceride, white blood cells (WBC) count, C-reactive protein (CRP) and ferritin were evaluated. All the data were analysed by t-test, chi2 test and analysis of variance. RESULTS: The IFG group had higher serum ferritin concentrations (85.5+/-6.6 microg/L vs. 49.4+/-3.7 microg/L, p=0.001). A positive correlation was found between fasting plasma glucose and serum ferritin (r=0.29, p=0.001). Using multiple regression analysis, we found an association between serum ferritin and blood pressure (0.15, p=0.01), FPG (0.29, p=0.001), triglyceride (0.08, p=0.01) and cholesterol (0.07, p=0.03). The odds ratio for the association of IFG in male subjects with a high serum ferritin level was 8.3 (95% CI: 1.2-11.9, p=0.01) and for females was 3.06 (95% CI: 0.58-15, p=0.1). CONCLUSION: Based on the data from our study, aelevation in serum ferritin can be seen in pre-diabetes stage, before the occurrence of an overt diabetes mellitus.

Increased arterial stiffness in healthy subjects with high-normal glucose levels and in subjects with pre-diabetes

            (Shin, Lee et al. 2011) Download

BACKGROUND: Increased fasting plasma glucose (FPG), which includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes, is a risk factor for arterial stiffness. While IFG is widely accepted as a cardiovascular risk factor, recent studies have argued that subjects with high-normal glucose level were characterized by a high incidence of cardiovascular disease. The purpose of this study is to investigate the relationship between FPG and arterial stiffness in non-diabetic healthy subjects. METHODS: We recruited 697 subjects who visited the health promotion center of a university hospital from May 2007 to August 2008. Age, sex, body mass index (BMI), resting heart rate, smoking habits, alcohol intake, exercise, blood pressure, medical history, FPG, lipid profile, high sensitivity C-reactive protein (hs-CRP), and Brachial-ankle pulse wave velocity (ba-PWV) were measured. We performed correlation and multiple linear regression analyses to divide the research subjects into quartiles: Q1(n=172), 65 mg/dL</=FPG<84 mg/dL; Q2(n=188), 84 mg/dL</=FPG<91 mg/dl; Q3(n=199), 91 mg/dL</=FPG<100 mg/dL; Q4(n=138), 100 mg/dL</=FPG<126 mg/dL. RESULTS: FPG has an independent, positive association with ba-PWV in non-diabetic subjects after correcting for confounding variables, including age, sex, BMI, blood pressure, resting heart rate, hs-CRP, lipid profile, and behavioral habits. The mean ba-PWV of the high-normal glucose group (Q3, 1384 cm/s) was higher than that of the low-normal glucose group (1303+/-196 cm/s vs.1328+/-167 cm/s, P<0.05). The mean ba-PWV value in the IFG group (1469+/-220 cm/s) was higher than that in the normoglycemic group (P<0.05, respectively). CONCLUSIONS: An increase in FPG, even within the normal range, was associated with aggravated arterial stiffness. Further research is needed to determine the glycemic target value for the prevention of arterial stiffness in clinical and public health settings.

Increased red cell count in diabetes and pre-diabetes

            (Simmons 2010) Download

The aim of this study was to test whether an increased red cell count (RCC) is present in pre-diabetes, obesity and the metabolic syndrome. The results demonstrate that these diabetes precursor states are associated with an increased RCC. This relationship can be explained, in part, by an increased HbA1c.

Hypomagnesaemia is associated with diabetes: Not pre-diabetes, obesity or the metabolic syndrome

            (Simmons, Joshi et al. 2010) Download

AIMS: The mechanism for the association between diabetes and hypomagnesaemia remains uncertain. This study aimed to test whether hypomagnesaemia is present in pre-diabetes, obesity and the metabolic syndrome. METHODS: 1453 adults from randomly selected households from rural Victoria, Australia, attended for biomedical assessment. Serum magnesium concentrations, hypomagnesaemia defined using local laboratory criteria (<0.70mmol/l), and defined by the bottom quintile of serum magnesium concentrations, were compared in different diabetes pre-cursor states including metabolic syndrome using ATP III criteria. RESULTS: The mean serum magnesium was 0.84+/-0.06mmol/l and 25 (1.7%) had a low magnesium. Mean magnesium was lower among those with known diabetes than those with new diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and normal subjects (0.79 (0.78-0.81) vs 0.83 (0.81-0.86); 0.84 (0.82-0.85); 0.84 (0.82-0.86); 0.85 (0.84-0.85)mmol/l). After adjusting for confounders, and compared with those without diabetes, hypomagnesaemia was 10.51 (1.37-80.60)-fold more common with new diabetes, 8.63 (2.20-33.90)-fold more common with known diabetes, 6.77 (1.75-26.17)-fold more common among those taking anti-hypertensive medication but with no difference to those with IGT/IFG (0.90 (0.10-8.10)). CONCLUSION: Diabetes is associated with hypomagnesaemia, but not its pre-cursor states.

Vascular disease in pre-diabetes: new insights derived from systems biology

            (Sprague and Ellsworth 2010) Download

In many cases vascular disease is present before the clinical onset of type 2 diabetes, that is, during the pre-diabetic period when insulin levels are markedly increased. In pre-diabetes, microvascular dysfunction correlates with plasma insulin levels and not blood glucose. Here we discuss the concept that insulin, at levels found in pre-diabetes, contributes to microvascular disease in skeletal muscle by inhibiting the release of the vasodilator, adenosine triphosphate (ATP), from erythrocytes.

Pre-diabetes essential action: a European perspective

            (Valensi, Schwarz et al. 2005) Download

Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits

            (Zhao, Fritsche et al. 2010) Download

Impaired glucose tolerance (IGT) which precedes overt type 2 diabetes (T2DM) for decades is associated with multiple metabolic alterations in insulin sensitive tissues. In an UPLC-qTOF-mass spectrometry-driven non-targeted metabonomics approach we investigated plasma as well as spot urine of 51 non-diabetic, overnight fasted individuals aiming to separate subjects with IGT from controls thereby identify pathways affected by the pre-diabetic metabolic state. We could clearly demonstrate that normal glucose tolerant (NGT) and IGT subjects clustered in two distinct groups independent of the investigated metabonome. These findings reflect considerable differences in individual metabolite fingerprints, both in plasma and urine. Pre-diabetes associated alterations in fatty acid-, tryptophan-, uric acid-, bile acid-, and lysophosphatidylcholine-metabolism, as well as the TCA cycle were identified. Of note, individuals with IGT also showed decreased levels of gut flora-associated metabolites namely hippuric acid, methylxanthine, methyluric acid, and 3-hydroxyhippuric acid. The findings of our non-targeted UPLC-qTOF-MS metabonomics analysis in plasma and spot urine of individuals with IGT vs NGT offers novel insights into the metabolic alterations occurring in the long, asymptomatic period preceding the manifestation of T2DM thereby giving prospects for new intervention targets. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-010-0203-1) contains supplementary material, which is available to authorized users.


References

Lorenzo, C., L. E. Wagenknecht, et al. (2010). "A1C between 5.7 and 6.4% as a marker for identifying pre-diabetes, insulin sensitivity and secretion, and cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study (IRAS)." Diabetes Care 33(9): 2104-9.

Magalhaes, M. E., B. A. Cavalcanti, et al. (2010). "Could pre-diabetes be considered a clinical condition? opinions from an endocrinologist and a cardiologist." Diabetol Metab Syndr 2: 2.

Mann, D. M., A. P. Carson, et al. (2010). "Impact of A1C screening criterion on the diagnosis of pre-diabetes among U.S. adults." Diabetes Care 33(10): 2190-5.

Meier, J. J., B. A. Menge, et al. (2009). "Functional assessment of pancreatic beta-cell area in humans." Diabetes 58(7): 1595-603.

Nguyen, T. T., J. J. Wang, et al. (2007). "Retinal vascular changes in pre-diabetes and prehypertension: new findings and their research and clinical implications." Diabetes Care 30(10): 2708-15.

Olson, D. E., M. K. Rhee, et al. (2010). "Screening for diabetes and pre-diabetes with proposed A1C-based diagnostic criteria." Diabetes Care 33(10): 2184-9.

Origuchi, T., S. Yamaguchi, et al. (2011). "Increased incidence of pre-diabetes mellitus at a department of rheumatology: a retrospective study." Mod Rheumatol 21(5): 495-9.

Park, K., C. D. Saudek, et al. (2010). "Increased expression of beta-N-acetylglucosaminidase in erythrocytes from individuals with pre-diabetes and diabetes." Diabetes 59(7): 1845-50.

Phillips, L. S., W. S. Weintraub, et al. (2006). "All pre-diabetes is not the same: metabolic and vascular risks of impaired fasting glucose at 100 versus 110 mg/dl: the Screening for Impaired Glucose Tolerance study 1 (SIGT 1)." Diabetes Care 29(6): 1405-7.

Rafalson, L., R. P. Donahue, et al. (2009). "Cigarette smoking is associated with conversion from normoglycemia to impaired fasting glucose: the Western New York Health Study." Ann Epidemiol 19(6): 365-71.

Retnakaran, R., Y. Qi, et al. (2008). "Glucose intolerance in pregnancy and future risk of pre-diabetes or diabetes." Diabetes Care 31(10): 2026-31.

Rhee, M. K., K. Herrick, et al. (2010). "Many Americans have pre-diabetes and should be considered for metformin therapy." Diabetes Care 33(1): 49-54.

Riley, W. J., M. A. Atkinson, et al. (1990). "Comparison of islet autoantibodies in 'pre-diabetes' and recommendations for screening." J Autoimmun 3 Suppl 1: 47-51.

Roriz-Filho, S. J., T. M. Sa-Roriz, et al. (2009). "(Pre)diabetes, brain aging, and cognition." Biochim Biophys Acta 1792(5): 432-43.

Saxena, S., P. Mitchell, et al. (2004). "Five-year incidence of cataract in older persons with diabetes and pre-diabetes." Ophthalmic Epidemiol 11(4): 271-7.

Sharifi, F., N. M. Nasab, et al. (2008). "Elevated serum ferritin concentrations in prediabetic subjects." Diab Vasc Dis Res 5(1): 15-8.

Shin, J. Y., H. R. Lee, et al. (2011). "Increased arterial stiffness in healthy subjects with high-normal glucose levels and in subjects with pre-diabetes." Cardiovasc Diabetol 10: 30.

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