Degree Of Glucose Intolerance Research Articles

糖尿病者の血糖コントロール及び耐糖能異常の指標としてのGlycosylated Hemoglobin (HbA1) の意義

糖尿病者の血糖コントロール及び耐糖能異常の指標としてのGlycosylated Hemoglobin (HbA1) の意義

Insulin therapy in patients with cystic fibrosis related diabetes mellitus: benefit, timing of initiation and hypoglycaemia

AbstractPancreatic endocrine dysfunction in patients with cystic fibrosis heralds declining pulmonary function and a six‐fold rise in mortality. Insulin therapy increases weight and reduces decline in lung function. Optimal timing of initiation remains contentious but early intervention may maximise benefit. We explored the optimal timing of initiation of therapy and characterised the frequency and usual symptoms of hypoglycaemia.Fifty‐four patients with cystic fibrosis treated with insulin were compared up to five years pre and post insulin initiation with respect to weight gain and lung function. Frequency and usual symptoms of hypoglycaemia were assessed using the Hypoglycemia Symptoms Awareness Questionnaire.Mean age was 27.6(16–52) years. In the five years preceding insulin therapy, FEV1 declined from 2.6±0.14L to 1.78±0.12L (p<0.001). In the group as a whole, rate of decline was arrested with insulin initiation; the mean five‐year post insulin FEV1 was 1.74±0.20L (p=0.15). When stratified according to oral glucose tolerance testing at initiation the rate of decline was significant in patients with impaired glucose tolerance (p=0.02) but not normal glucose tolerance nor overt cystic fibrosis diabetes mellitus. Insulin therapy increased weight from 53.08±1.53kg to 56.22±2.08kg (p=0.05). Hypoglycaemia was common and 75% of respondents scored results indicative of hypoglycaemia unawareness.This study confirms that the favourable effect of insulin upon lung function in patients with cystic fibrosis correlates with the degree of glucose intolerance at baseline. Hypoglycaemia is an important clinical issue. Copyright © 2011 John Wiley & Sons.

Isolated abnormal value during the 3-hour glucose tolerance test: which value is associated with macrosomia?

Objective. The aim of this retrospective review was to evaluate obstetric outcomes in patients with an isolated abnormal value on the oral glucose tolerance test (OGTT) at 0, 1, 2, and 3 h.Methods. From January 2003 through June 2009, all consecutive pregnant women who presented to Baskent University were screened for gestational diabetes mellitus (GDM). Patients with one abnormal value based on findings of the OGTT were grouped according to increased levels of glucose at 0, 1, 2, and 3 h (Group 1 > 95 mg/dl for fasting glucose concentration, Group 2 > 180 mg/dl for the serum glucose concentration in the first hour, Group 3 > 155 mg/dl for the serum glucose concentration in the second hour, Group 4 > 140 mg/dl for serum glucose concentration in the third hour). The four groups were compared for classic GDM risk factors. The primary outcome measures were large for gestational age (LGA) (birthweight >95th percentile for gestational age using population birth weight centile charts) and macrosomia.Results. The incidence of LGA baby (Group 1, 10%; Group 2, 3.8%; Group 3 20.3%; Group 4, 13.2%; p = 0.008) was significantly highest in Group 3 and macrosomia (Group 1, 30%; Group 2, 5.1%; Group 3, 18.6%; Group 4, 15.8%; p = 0.039) was significantly higher in Groups 1 and 3.Conclusions. Our results suggest that even with relatively mild degrees of glucose intolerance at 2 h, no treatment is associated with LGA babies.

Glucagon suppression during OGTT worsens while suppression during IVGTT sustains alongside development of glucose intolerance in patients with chronic pancreatitis

Aims To examine plasma glucagon responses to oral and intravenous ( iv) glucose in patients with chronic pancreatitis (CP) and either normal glucose tolerance (NGT), secondary impaired glucose tolerance (IGT) or secondary diabetes mellitus (DM). Methods Eleven patients with CP and NGT, 6 patients with CP and secondary IGT, 7 patients with CP and secondary non-insulin requiring DM, and 8 healthy subjects were examined with an oral glucose tolerance test (OGTT) and an iv glucose tolerance test (IVGTT). Results In the CP groups, significant differences (increasing with the degree of glucose intolerance) in glucagon responses during the first hour of OGTT compared to IVGTT were observed (CP + NGT: − 13 ± 22 vs. − 88 ± 17, p = 0.02; CP + IGT: 3 ± 17 vs. − 87 ± 19, p = 0.01; CP + DM: 94 ± 27 vs. − 78 ± 16 1 h × pmol/l (mean ± SEM), p < 0.001). Glucagon was suppressed equally following OGTT and IVGTT in the healthy subjects (− 103 ± 22 vs. − 131 ± 19 1 h × pmol/l; p = NS). IVGTT suppressed glucagon similarly in all groups except for a slightly impaired suppression in the CP + DM-group compared to healthy subjects. Conclusions These results suggest that along with the development of secondary glucose intolerance in patients with CP, the suppression of glucagon by oral glucose is gradually lost and substituted by a paradoxical stimulation of secretion, while the suppression by iv glucose is maintained. This might indicate a glucagon stimulatory mechanism of gastrointestinal origin in CP patients.

Gestational Diabetes Mellitus and Obesity

This is the sixth of a series of articles based on presentations at the American Diabetes Association (ADA) Scientific Sessions held 5–9 June 2009 in New Orleans, Louisiana. ### Gestational diabetes mellitus In a symposium on advances in the understanding of obesity and weight gain during pregnancy, Teresa A. Hillier (Portland, OR) discussed the implications that pregnancy weight gain in gestational diabetes mellitus (GDM) has for the fetus. Much of the discussion following her lecture and those of the other speakers concerned the May 2009 guidelines of the Institute of Medicine (IOM) for weight gain during pregnancy (www.iom.edu/pregnancyweightgain), which suggest that recommendations to patients be based on prepregnancy BMI. For BMI levels 30 kg/m2, weight gain ranges are suggested at 28–40, 25–35, 15–25, and 11–20 pounds, respectively, and the recommended rates of weight gain are 1–1.3, 0.8–1, 0.5–0.7, and 0.4–0.6 pounds/week. GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Hillier noted the lack of consensus on screening and diagnostic criteria for GDM. In the U.S. two steps are used, a 1-h 50-g glucose challenge followed by a 75- or 100-g oral glucose tolerance test (OGTT); outside the U.S., a 2-h 75-g OGTT is recommended. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study of providers blinded to GDM status reported correlations between fasting, 1-h, and 2-h glucose levels and adverse outcomes, including Caesarian section (1). The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) was a randomized controlled trial of 1,000 women with normal fasting glucose not having GDM by World Health Organization criteria (2-h glucose 140–199 mg/dl) assigned to treatment with dietary advice, self-monitoring, and insulin as required or to routine care (2). There was gestational weight gain of 8.1 vs. 9.8 kg, and adverse fetal outcomes occurred in 7 …

New Insights on Glucose Pathophysiology in Gestational Diabetes and Insulin Resistance

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition of GDM does not preclude the possibility that unrecognized glucose intolerance may have existed before the pregnancy, and the definition applies whether insulin, oral antidiabetic agents, or dietary modification is used for treatment. Approximately 7% of all pregnancies in the United States are complicated by gestational diabetes resulting in more than 200,000 cases annually, but the prevalence ranges from 1% to 14% of all pregnancies depending on the population studied and the diagnostic tests used. Despite the better detection of GDM and recognition of its adverse consequences for mother and baby in many countries, there is still no consensus regarding GDM pathophysiology; as a result, diagnosis and treatment of GDM remain controversial. A better understanding of obesity along with new studies in GDM has identified the intra-abdominal metabolically active adipose tissue as a major factor in the pathophysiology of GDM. This review examines recent research regarding the link between obesity and glucose intolerance and highlights studies in the areas of genetics, glucose transport, and adipokines.

Gestational Diabetes — Whom Do We Treat?

In 1964, O'Sullivan and Mahan1 proposed glucose-tolerance-test criteria to define gestational diabetes mellitus — that is, any degree of glucose intolerance that first occurs or is first identified during pregnancy. Women whose glucose levels exceeded these thresholds during an index pregnancy were recognized to be at increased risk for developing nongestational diabetes 8 years later. Subsequently, considerable data indicated that lowering glucose levels in women who were diagnosed with gestational diabetes mellitus was associated with reduced rates of perinatal complications and death. However, many considered these data to be insufficient evidence to support treatment for gestational diabetes2,3; most . . .

Establishing diagnosis of gestational diabetes mellitus: Impact of the hyperglycemia and adverse pregnancy outcome study

The diagnosis of gestational diabetes mellitus (GDM) remains controversial, without universal acceptance of a particular set of diagnostic criteria, and, in fact, a lack of consensus as to whether this is an entity worth diagnosis. Some of the debate derives from differences of opinion about what degree of glucose intolerance should be labeled as GDM. Therefore, it is to be expected that there are different viewpoints on how to detect and screen for GDM. It is believed that early diagnosis will result in a significant improvement in perinatal outcome in these patients. In this review, we discuss the current data concerning screening for GDM and new strategies for GDM diagnosis in light of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Effect of different degrees of glucose intolerance on maternal and perinatal outcomes

Objective. To evaluate the effect of markedly elevated 50-g glucose loading test (GLT) (≥200 mg/dL) and equivocal 100-g GLT (one abnormal value) results on maternal and perinatal outcomes.Methods. Retrospective analysis of 2029 singleton pregnancies screened for gestational diabetes mellitus (GDM). Maternal and perinatal outcomes in five different groups with different degrees of glucose intolerance were compared. First group consisted of patients with normal 50-g test, second group was formed by patients with abnormal 50-g glucose test but a normal 100-g test. Third group included patients with one abnormal value after 100-g test. Patients in the fourth group were diagnosed to have GDM after an abnormal 100-g test. Patients in the fifth group had a value ≥200 mg/dL after 50-g test and were diagnosed to have GDM.Results. Macrosomia and large for gestational age incidence were highest in the group with one elevated glucose tolerance test (GTT) value. Hospitalisation rates, hypoglycemia, hyperbilirubinemia and polycythemia were more common in neonates born to mothers with one elevated GTT value and to mothers with a GLT > 200 mg/dL.Conclusion. Adverse maternal and perinatal outcomes in patients with one elevated GTT value and in patients with a GLT value > 200 mg/dL warrant close glucose monitoring and treatment in these groups even in the absence of a diagnostic abnormal GTT.

Usefulness of Fasting Plasma Glucose to Predict Mortality or Coronary Heart Disease in Persons ≥60 Years of Age Without Diabetes Mellitus or in Those With Undiagnosed Diabetes Mellitus (from The Dubbo Study)

The role of fasting plasma glucose (FPG) levels below diabetes "thresholds" in predicting mortality or coronary heart disease (CHD) is unclear. This study examines whether FPG predicts mortality or CHD in subjects without diabetes (historical or undiagnosed) or in those with undiagnosed diabetes (or lesser degrees of glucose intolerance). We have analyzed all-causes mortality and CHD incidence from a 16-year follow-up in a cohort of Australian senior citizens, 60 years and older, first examined in 1988-89. Diabetes was defined on historical grounds or by use of medication; undiagnosed diabetics were those without history but with FPG >124 mg/dl. Hazard ratio and 95% confidence intervals of the specified outcomes were obtained from Cox models, with FPG being entered as a continuous variable. Mortality and CHD incidence rates in subjects with previous cardiovascular disease (CVD) and diabetes were substantially higher than in nondiabetics, but CHD rates were disproportionately higher in diabetic women. FPG did not significantly predict any outcome in men in the absence of diabetes. In women, FPG was a significant predictor of death (hazard ratio = 1.30, 95% confidence interval 1.09 to 1.56) and CHD (hazard ratio 1.24, confidence interval 1.02 to 1.51) in the cohort, which included previous CVD but excluded all diabetes. In women with undiagnosed diabetes, FPG predicted death independently of previous CVD presence but did not predict CHD. In conclusion, FPG in the range of 95 to 108 mg/dl in a nondiabetic woman is still of prognostic importance for survival or CHD if she has previous CVD, whereas FPG is of prognostic importance for survival if she has undiagnosed diabetes. No similar findings were made in men.

Eficacia de los hipoglicemiantes orales en el control metabólico de pacientes con diabetes mellitus gestacional

Gestational Diabetes is characterized by different degrees of glucose intolerance that produce a series of fetal and perinatal alterations. During many years, in those cases of gestational diabetes that did not respond to nutritional interventions, the use of insulin was a proven treatment to achieve metabolic control and thus a better perinatal outcome. At present, some new oral hypoglycemic drugs, from the family of sulfonylureas and biguanides, have been shown to be safe, of low cost, and apparently effective in the metabolic control of this disease. We review the publications that propose the use of oral hypoglycemic drugs for the metabolic control of gestational diabetes that does not respond to nutritional measures.

Effectiveness of oral hypoglycemic drugs in the metabolic control of patients with gestational diabetes

Gestational Diabetes is characterized by different degrees of glucose intolerance that produce a series of fetal and perinatal alterations. During many years, in those cases of gestational diabetes that did not respond to nutritional interventions, the use of insulin was a proven treatment to achieve metabolic control and thus a better perinatal outcome. At present, some new oral hypoglycemic drugs, from the family of sulfonylureas and biguanides, have been shown to be safe, of low cost, and apparently effective in the metabolic control of this disease. We review the publications that propose the use of oral hypoglycemic drugs for the metabolic control of gestational diabetes that does not respond to nutritional measures.

Management of Hyperglycemia in Gestational Diabetes Mellitus

Gestational diabetes mellitus is a common disorder which is defined as any degree of glucose intolerance with onset at, or first recognized during pregnancy. Women with gestational diabetes are at greater risk for many adverse pregnancy outcomes and maternal or fetal mortality. We tried to conduct the cumulative experience regarding the management of the disease, especially emphasizing the novel therapeutic approaches like new types of insulin preparations, oral hypoglycemic agents and herbal drugs or supplements. In this review important recent patents are also discussed.

Could mean platelet volume be a predictive marker for gestational diabetes mellitus?

Background: Gestational diabetes mellitus is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Early diagnosis of this complication and appropriate treatment aimed at tight control over maternal glucose levels may positively influence the perinatal outcome. There are studies, which suggest platelets play a role in the pathogenesis of gestational diabetes mellitus.Aim: The aim of this study is to compare the platelet count and other platelet parameters in gestational diabetic and normal pregnant women and to investigate whether these parameters have a predictive significance in gestational diabetes mellitus.Materials and methods: Thirty four women with gestational diabetes mellitus and 45 normal pregnant women were enrolled into the study.Results: Women with gestational diabetes mellitus had lower platelet counts and higher mean platelet volume (MPV) values which were statistically significant (p <0·006 and p <0·0001), respectively.Conclusion: Our results indicate that platelet count and MPV play an important predictive role in gestational diabetes mellitus.

Detection of small dense LDL-cholesterol: is it necessary to determine particle size?

Evaluation of: Julius U, Dittrich M, Pietzsch J: Factors influencing the formation of small dense low-density lipoprotein particles in dependence on the presence of the metabolic syndrome and on the degree of glucose intolerance. Int. J. Clin. Pract. 61(11), 1798–1804 (2007). Samples from the Familial Metabolic Syndrome Study in Saxony were used to assess the determinants of small dense LDL levels. After correction for degree of hyperglycemia, hyperinsulinemia, age, gender and BMI the strongest correlates of particle size were the levels of VLDL triglyceride (r = -0.598) or plasma triglycerides (r = -0.623). The study reviewed has highlighted the great utility of triglycerides as a simple practical surrogate for the detection of small dense LDL particles, but has also suggested that significant quantities of small dense LDL may occur at far higher HDL-cholesterol concentrations than previously suspected, suggesting that formal measurement of levels of small dense particles may be necessary. However it sti...

478: Women with gestational diabetes or lesser degrees of glucose intolerance have a greater risk of preeclampsia

INTOLERANCE HAVE A GREATER RISK OF PREECLAMPSIA DARCY CARR, KATHERINE NEWTON, KRISTINA UTZSCHNEIDER, MIRJAM FAULENBACH, STEVEN KAHN, SUSAN HECKBERT, THOMAS EASTERLING, University of Washington, Seattle, Washington, Group Health Center for Health Studies, Seattle, Washington, VA Puget Sound Health Care System, Seattle, Washington OBJECTIVE: Preeclampsia and type 2 diabetes are both associated with obesity and insulin resistance. We hypothesized that women who have higher glucose levels on the 50 gm, 1-hr oral glucose challenge test (OGCT), one abnormal value on the 100 gm, 3-hr oral glucose tolerance test (OGTT), or gestational diabetes mellitus (GDM) would have a greater frequency of preeclampsia. STUDY DESIGN: We performed a retrospective cohort study among 26,105 women who delivered between 1985 and 2002 at Group Health in Washington state who received care for 1 year before delivery, had an OGCT or OGTT, and did not have preexisting hypertension or diabetes. Preeclampsia was defined by ICD-9 codes. RESULTS: The women were 30.3 6.2 years old. Preeclampsia developed in 1,809 (6.9%) women. The risk of preeclampsia increased across 1-hr OGCT quartiles adjusting for age, primigravidity, and GDM compared to the reference group (OGCT 97 mg/dl; Table 1). Among the 6,222 women with a 3-hr OGTT, 3,639 had a normal OGTT and 6.5% developed preeclampsia; 1,253 had one abnormal value and 8.7% developed preeclampsia; and 1,330 had GDM (2 abnormal values by Carpenter and Coustan criteria) and 9.2% developed preeclampsia. Women with abnormal OGTT values had a higher risk of preeclampsia compared to those with normal values adjusting for age and primigravidity (Table 2).

Factors influencing the formation of small dense low-density lipoprotein particles in dependence on the presence of the metabolic syndrome and on the degree of glucose intolerance

Small dense low-density lipoprotein (LDL) particles are known to be especially atherogenic. Several mechanisms are involved in this atherogenicity. We wanted to look for the presence of small dense LDL particles depending on gender, metabolic syndrome (MS) and different degrees of glucose intolerance. Moreover, we looked for anthropometric factors and factors of lipid and carbohydrate metabolism that are associated with changes in the LDL size. We studied 752 persons (330 males, 422 females; age 40 +/- 17 years). LDL particle size was estimated with polyacrylamide gel electrophoresis. Males had smaller LDL particles than females. Probands with the MS had smaller LDL particles than those without this syndrome. With rising plasma triglyceride (TG) levels more small dense LDL particles were seen. The highest proportion of these small dense LDL particles was observed in the subgroup of type 2 diabetic patients. In the whole material, the mean LDL diameter was correlated negatively with plasma TG and very low-density lipoprotein components (TG, cholesterol and proteins) and positively with high-density lipoprotein cholesterol. In a linear stepwise regression analysis different significant factors influencing the LDL size were found in the whole population, in normoglycaemic probands, in persons with impaired glucose tolerance, in type 2 diabetic patients and in type 2 diabetic patients injecting insulin. Our data point to different mechanisms of the formation of small dense LDL particles in dependence on the degree of glucose intolerance. Moreover, the target values for plasma TG should be set lower.

The Role of Continuous Glucose Monitoring in Clinical Decision-Making in Diabetes in Pregnancy

Numerous studies have shown that improved glucose control in pregnancy will lessen both maternal and fetal complications, but adverse outcomes remain more frequent in diabetic than in nondiabetic pregnancies. Complications increase with the degree of glucose intolerance. The continuous glucose monitoring system (CGMS) can provide a glucose profile over 72 hours. It consists of a disposable glucose-sensing device that is placed just beneath the skin and connects by cable to a pager-size glucose monitor. Interstitial-fluid glucose levels are estimated at 10-second intervals and averaged every 5 minutes. Pregnant women with diabetes were offered the CGMS in the setting of standard diabetes care. Its accuracy was determined by comparing the readings with patient's finger-prick glucose readings. Sixty-eight CGMS traces were obtained in 55 pregnant women: 37 with gestational diabetes, 10 with type 2 diabetes, and 8 with type 1 diabetes. Forty-two CGMS traces, 62% of the total, provided information beyond that available from the patients' home glucose monitoring diary. Examples include undetected postprandial hyperglycemia and overnight hypoglycemia. The CGMS was generally most helpful in women with type 1 diabetes, in whom all but 2 of 18 studies yielded additional information. More than three-fourths of women responding to a questionnaire expressed a belief that the benefits of the CGMS outweigh its inconvenience. All but 4 of 48 participants found the CGMS to be easy to use. In addition, 90% of respondents felt that they had a better understanding of how to control blood glucose since using the CGMS. In this community-based cohort study, these investigators found the CGMS to be of substantial help in managing preexisting and gestational diabetes in pregnant women. By adding information to that available from finger-prick monitoring, it may help clinicians to optimize glycemic control and prevent hypoglycemia.

Comparison of 11 Human Insulin Assays: Implications for Clinical Investigation and Research

The American Diabetes Association task force on standardization of insulin assays in 1996 showed wide variation in assay bias. Newer assays are specific for insulin, with several now available on automated immunoassay analyzers. In 2004, we compared 11 commercially available insulin assays by analyzing 150 serum samples (99 fasting/51 postprandial) from study participants with various degrees of glucose intolerance (exclusions being type 1 diabetes, insulin treatment, or presence of insulin antibodies). All assays were calibrated against International Reference Preparation 66/304. One assay was not specific for insulin and another was an RIA; 10 assays used enzyme/chemiluminescent labels. Bland-Altman difference plots were modified to use the mean insulin from all assays on the x-axis as a common comparator. As in the 1996 study, insulin values from the different assays varied by a factor of 2, with the nonspecific assay ranking in the middle of the distribution. Spearman rank correlation coefficients, for ranking samples vs the mean, were 0.983-0.997. Both offsets and concentration-dependent differences were seen in the modified difference plots. Imprecision (mean CV) for automated assays (3%) was not significantly different from manual assays (5%). Similar values were obtained when one automated assay was run in laboratories in both the UK and the US. Results of 1 assay showed lower insulin concentrations in heparinized plasma than in serum. Assay performance must be considered before comparing insulin results. The 2-fold variation in insulin results may be related to specificity, manufacturers' calibration procedures or conversion factors.

ApoB/apoA-I ratio is related to femoral artery plaques in 64-year-old women also in cases with low LDL cholesterol

Introduction The apolipoproteinB (apoB)/apolipoproteinA-I (apoA-I) ratio mirrors the number of pro-atherogenic and anti-atherogenic lipoprotein particles. This ratio may carry more information on risk for atherosclerosis than LDL in cohorts with impaired glucose tolerance. The aim was to examine the association between the apoB/apoA-I ratio and ultrasound-assessed atherosclerosis in the carotid and femoral arteries in women with varying degrees of glucose tolerance. Methods Plaque occurrence, and intima-media thickness in the carotid and femoral arteries were examined by B-mode ultrasound in a random sample of 64-year-old women ( n = 646) living in Gothenburg, Sweden, representing different degrees of glucose intolerance (diabetes ( n = 234), impaired ( n = 212) and normal glucose tolerance ( n = 200)). Traditional risk factors and serum concentrations of apolipoproteins were analysed. Results For subjects in the lowest LDL tertile, the risk of having a plaque in the femoral artery was three times greater for subjects in the highest apoB/apoA-I tertile compared to subjects in the lowest tertile (OR: 3.0, 95% CI: 1.2–7.5). A clear increase in the occurrence of femoral plaque was observed already at a cut-off value of 0.63 (OR: 1.8, 95% CI: 1.2–2.6). ApoB/apoA-I was also related to femoral plaque occurrence in women with low HbA1c. ApoB/A-I ratio was associated with carotid and femoral IMT but not carotid plaques. Conclusion The apoB/apoA-I ratio improved the identification of cases with femoral artery atherosclerosis in a cohort of women with varying degrees of glucose tolerance. Such cases could also be identified in women with normal LDL and HbA1c levels. The results indicate that an apoB/apoA-I ratio above 0.63 should be used as a marker of increased risk.