The association between glycemia and endothelial function in nondiabetic individuals: the importance of body weight

The aim of this study was to examine the association between glycemia and markers of early atherosclerosis in healthy nondiabetic individuals. In 309 individuals without diabetes or symptomatic cardiovascular disease, we assessed long-term glycemia by glycosylated hemoglobin (HbA1c) and endothelial function by flow-mediated dilatation (FMD) in the brachial artery. HbA1c was negatively associated with FMD (r = -0.162, P = 0.004). Multivariate linear regression analysis after adjusting for common risk factors of cardiovascular disease showed that BMI was an effect modifier of the association between HbA1c and FMD (P = 0.034 for the HbA1c x BMI interaction). We stratified the FMD outcome data into two groups separated by the median BMI (group 1: BMI < or = 26.1 kg/m(2) and group 2: BMI > 26.1 kg/m(2)). In the lower BMI group, HbA1c was an independent predictor of FMD even when adjusted for confounding factors associated with impaired glucose metabolism (r = -0.215, P = 0.009), but in the higher BMI group HbA1c was not associated with FMD (r = -0.051, P = 0.5). In a nondiabetic population, long-term glycemia was associated with endothelial dysfunction only in lean individuals. In the overweight individuals, this association was not apparent, possibly because some of the mechanisms that mediate the effect of glycemia on vascular function are shared by obesity.     

Variables Involved in the Discordance between HbA1c and Fructosamine: The Glycation Gap Revisited

Aims

Glycation gap (GG) is defined as the difference between the measured level of HbA1c and the level that would be predicted from its regression on the fructosamine level. The aims of the study were: 1) To determine the reproducibility and consistency of GC; 2) To discover factors related to GG value. Given that metformin might increase glucose transport through the erythrocyte membrane, this treatment was also considered in the analyses of the results.

Methods

GG was calculated in two blood samples separated 30.6 (SD 7.3) weeks, obtained in 508 type 2 diabetic patients. The following variables were considered: HbA1c, fructosamine, glucose, creatinine, hematological parameters and treatment with metformin. Multivariate and logistic regression analyses were performed to explore the variables independently related to CG.

Results

GG was reproducible and consistent over time. Creatinine, mean corpuscular hemoglobin concentration (MCHC), and glycemia (inverse relationship); and HbA1c and treatment with metformin (direct relationship) were independently related to GG. Patients treated with metformin showed higher HbA1c values, despite similar fructosamine concentrations, than patients not treated with the drug.

Conclusions

GG is independently related to serum levels of creatinine, MCHC and treatment with metformin. The spurious effect of metformin on Hb glycation could have serious clinical implications and should be considered when interpreting the results of clinical trials.     

Impact of variation in the FTO gene on whole body fat distribution, ectopic fat, and weight loss

Polymorphisms in the fat mass- and obesity-associated (FTO) gene have been identified to be associated with obesity and diabetes in large genome-wide association studies. We hypothesized that variation in the FTO gene has an impact on whole body fat distribution and insulin sensitivity, and influences weight change during lifestyle intervention. To test this hypothesis, we genotyped 1,466 German subjects, with increased risk for type 2 diabetes, for single-nucleotide polymorphism rs8050136 in the FTO gene and estimated glucose tolerance and insulin sensitivity from an oral glucose tolerance test (OGTT). Distribution of fat depots was quantified using whole body magnetic resonance (MR) imaging and spectroscopy in 298 subjects. Two-hundred and four subjects participated in a lifestyle intervention program and were examined after a follow-up of 9 months. In the cross-sectional analysis, the A allele of rs8050136 in FTO was associated with a higher BMI, body fat, and lean body mass (all P < 0.001). There was a significant effect of variation in the FTO gene on subcutaneous fat (P < or = 0.05) and a trend for liver fat content, nonvisceral adipose tissue, and visceral fat (all P < or = 0.1). However, the single-nucleotide polymorphism was not associated with insulin sensitivity or secretion independent of BMI (all P > 0.05). During lifestyle intervention, there was also no influence of the FTO polymorphism on changes in body weight or fat distribution. In conclusion, despite an association with BMI and whole body fat distribution, variation in the FTO locus has no effect on the success of a lifestyle intervention program.     

Serum fructosamine concentrations in patients with type II (non-insulin-dependent) diabetes mellitus during changes in management.

The serum fructosamine concentration was examined as a new means to monitor metabolic control in non-insulin-dependent diabetes during changes in management. Weekly fructosamine estimations were compared with glycosylated haemoglobin (HbA1c), 24 hour urinary glucose, and fasting plasma glucose concentrations in a 17 week study entailing withdrawal and reinstitution of oral treatment. The serum fructosamine concentration was more sensitive than the other measurements in detecting a deterioration in diabetic control after stopping oral hypoglycaemic drugs. The response to reinstitution of treatment was not significant in the first three weeks (p = 0.266), despite a highly significant reduction in fasting plasma glucose (p = 0.001) and 24 hour urinary glucose concentrations (p = 0.012). Compared with HbA1c, concentrations of fructosamine appeared more useful in monitoring short term (three to six weeks) changes after alterations in management of diabetes. Additional advantages were lower cost and technical simplicity of measurement.     

Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults.

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007) but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.     

Circulating Adipocyte Fatty Acid Binding Protein (FABP4) Levels Are Associated with Irisin in the Middle-Aged General Chinese Population

Background

Adipocyte fatty acid binding protein (FABP4) has been recently characterized as an adipokine that is closely associated with obesity and metabolic syndrome. Irisin, a novel myokine, activates thermogenesis by increasing the transformation of white adipocytes to brown, and it has improved glucose homeostasis in animal models. In this study, we aimed to explore the relationship between serum FABP4 and irisin in middle-aged Chinese subjects.

Methods

A total of 111 normal residents (56 men and 55 women) of Fengxian District who were 40 to 60 years of age were recruited. Circulating FABP4 and irisin were determined by enzyme-linked immunosorbent assay. Anthropometric parameters, oral glucose tolerance test results, hemoglobin A1C (HbA1C), blood lipids, homeostasis model assessment of insulin resistance, homeostasis model assessment-β and body fat composition were also determined.

Results

All participants were categorized by FABP4 tertiles. There were significant differences in blood pressure, body fat percentage, 2-h plasma glucose, and skeletal muscle mass among the three groups (P<0.05). Furthermore, FABP4 levels in the women were significantly higher than in the men (P<0.05). However, there was no sexual dimorphism in serum irisin (P>0.05). To exclude the effect of sex difference, partial correlations analysis showed that FABP4 was positively correlated with diastolic blood pressure (P<0.05) and body fat percentage (P<0.05) negatively correlated with skeletal muscle mass (P<0.05) and irisin (P<0.05), while irisin was positively correlated with HbA1c (P<0.05) and negatively correlated with creatinine (P<0.05). Multivariate regression analysis demonstrated that serum FABP4 was independently associated with skeletal muscle mass (P<0.001), diastolic blood pressure (P<0.05) and irisin (P<0.05) after adjustment for age, body mass index, body fat percentage, total cholesterol and HbA1C.

Conclusions

Elevated FABP4 levels increase the risks of obesity-related metabolic disorders and hypertension. Serum irisin might exert antagonistic effects on FABP4 in the middle-aged Chinese population.     

Parameters of glucose and lipid metabolism in the male Göttingen minipig: influence of age, body weight, and breeding family

The pig is useful as a model for human physiology and pathophysiology and could be an important supplement to the many available rodent models of diabetes mellitus. Due to their small size, G?ttingen minipigs are especially suitable for long-term studies. The aim of the study reported here was to establish reference values for a range of glucose and lipid homeostasis parameters of interest that could be used to identify possible diabetes-prone male G?ttingen minipig individuals, families, or age groups. Plasma samples from nonfed animals were analyzed for glucose, leptin, fructosamine, insulin, C-peptide, triglyceride, free fatty acids, and total cholesterol values. Breeding family had significant effects only on plasma triglyceride concentrations (P < 0.001). Plasma concentrations of glucose (P = 0.012), fructosamine (P < 0.001) and triglycerides (P < 0.001) increased significantly with age, whereas total cholesterol concentration decreased significantly (P = 0.001) with age. Age did not influence other parameters. In conclusion, glycemia and insulinemia increased with age and body weight, possibly indicating a small deterioration in insulin sensitivity with age. It is, therefore, hypothesized that older, compared to younger animals may be more useful in the development of a model of type-2 diabetes mellitus. Furthermore, on the basis of decrease in cholesterol concentration with age, animals fed ad libitum with possibly a high calorie diet might be even more useful in the development of a type-2 diabetes mellitus model.     

Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease

Obese adolescents are at risk of developing NAFLD and type 2 diabetes. We measured noninvasively the IHF content of obese adolescents to ascertain whether it is associated with insulin resistance and abnormal energy homeostasis. IHF content, whole body energy homeostasis, insulin sensitivity, and body composition were measured using localized hepatic (1)H-MRS, indirect calorimetry, fasting-derived and 3-h-OGTT-derived surrogate indexes (HOMA2 and WBISI), and DEXA, respectively, in 54 obese adolescents (24 female and 30 male, age 13 +/- 2 yr, BMI >99th percentile for their age and sex). NAFLD (defined as IHF content >5% wet weight) was found in 16 individuals (30%) in association with higher ALT (P < 0.006), Hb A(1c) (P = 0.021), trunk fat content (P < 0.03), and lower HDL cholesterol (P < 0.05). Individuals with NAFLD had higher fasting plasma glucose (89 +/- 8 vs. 83 +/- 9 mg/dl, P = 0.01) and impaired insulin sensitivity (HOMA2 and WBISI, P < 0.05). Meanwhile, parameters of insulin secretion were unaffected. Their reliance on fat oxidation in the fasting state was lower (RQ 0.83 +/- 0.08 vs. 0.77 +/- 0.05, P < 0.01), and their ability to suppress it during the oral glucose challenge was impaired (P < 0.05) vs. those with normal IHF content. When controlling for trunk fat content, the correlation between IHF content and insulin sensitivity was weakened, whereas the correlation with fasting lipid oxidation was maintained. In conclusion, NAFLD is common in childhood obesity, and insulin resistance is present in association with increased trunk fat content. In contrast, the rearrangement of whole body substrate oxidation in these youngsters appeared to be an independent feature.     

Glycosylated Hemoglobin and Albumin-Corrected Fructosamine Are Good Indicators for Glycemic Control in Peritoneal Dialysis Patients

Purpose

Diabetes mellitus (DM) is the most common cause of end-stage renal disease and is an important risk factor for morbidity and mortality after dialysis. However, glycemic control among such patients is difficult to assess. The present study examined glycemic control parameters and observed glucose variation after refilling different kinds of fresh dialysate in peritoneal dialysis (PD) patients.

Methods

A total of 25 DM PD patients were recruited, and continuous glucose monitoring system (CGMS) was applied to measure interstitial fluid (ISF) glucose levels at 5-min intervals for 3 days. Patients filled out diet and PD fluid exchange diaries. The records measured with CGMS were analyzed and correlated with other glycemic control parameters such as fructosamine, albumin-corrected fructosamine (AlbF), glycosylated hemoglobin (HbA1c), and glycated albumin levels.

Results

There were significant correlations between mean ISF glucose and fructosamine (r = 0.45, P<0.05), AlbF (r = 0.54, P<0.01), and HbA1c (r = 0.51, P<0.01). The ISF glucose levels in glucose-containing dialysate increased from approximately 7–8 mg/dL within 1 hour of exchange in contrast to icodextrin dialysate which kept ISF glucose levels unchanged.

Conclusion

HbA1c and AlbF significantly correlated with the mean ISF glucose levels, indicating that they are reliable indices of glycemic control in DM PD patients. Icodextrin dialysate seems to have a favorable glycemic control effect when compared to the other glucose-containing dialysates.     

Effect of Diabetes Mellitus Type 2 on Salivary Glucose – A Systematic Review and Meta-Analysis of Observational Studies

Background

Early screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM.

Methods and Findings

We conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge''s g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37).

Conclusions

Our systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients.     

Birth weight and body composition in overweight Latino youth: a longitudinal analysis

To examine the associations between birth weight and BMI, and total body composition, in overweight Latino adolescents. Two hundred and forty-two overweight Latino children (baseline age = 11.1 +/- 1.7 years; BMI >or= 85th percentile) were measured annually for up to 6 years (2.6 +/- 1.4 observations/child, total 848 visits). Birth weight and history of gestational diabetes were obtained by parental interview. Visceral fat and subcutaneous abdominal fat were assessed by magnetic resonance imaging, while total body fat, total lean tissue mass (LTM), trunk fat, and lean tissue trunk mass were measured by dual-energy X-ray absorptiometry. BMI and BMI percentile were calculated using the Centers for Disease Control and Prevention age appropriate cutoffs. Longitudinal linear mixed effects (LME) modeling was used to evaluate the influence of birth weight on subsequent changes in body composition and distribution of fat across puberty. Birth weight significantly predicted BMI (P < 0.001), total trunk fat (P < 0.001), total trunk LTM (P < 0.001), total fat mass (FM) (P < 0.001), and total LTM (P < 0.001), but not subcutaneous (P = 0.534) or visceral fat (P = 0.593) at age 11 years. Longitudinally, as participants transitioned into puberty, birth weight did not significantly predict any of the body composition or fat distribution measures (P > 0.05). Birth weight is significantly associated with increased adiposity and LTM and negatively associated with trunk fat mass and trunk lean mass at baseline; however these relationships did not predict rate of change of any of the variables as the children progress through adolescence.     

Association of serum adiponectin concentration to lipid and glucose metabolism in healthy humans.

BACKGROUND: Adiponectin is a recently discovered plasma protein with many associations to glucose and lipid metabolism. Due to its central role in cardiovascular diseases and insulin resistance, we studied the relationship between serum adiponectin and factors reflecting glucose and lipid metabolism. METHODS AND RESULTS: Thirty healthy participants (20M/10F, age 32.0 +/- 2.1 years, BMI 25.8 +/- 0.9 kg/m (2) and HbA (1c) 5.2 +/- 0.1 %) were studied four times at approximately one week intervals. The effects of a 4-hour euglycemic hyperinsulinemia (40 mU/m (2)/min), saline infusion (control), oral glucose, and oral fat load on serum adiponectin were studied. No significant correlation was found between serum adiponectin and insulin sensitivity before (r = 0.25) or after adjustment for age, BMI and gender (r = 0.04). Adiponectin concentration correlated inversely with HbA (1c) (r = - 0.43, p < 0.05), insulin concentration (r = - 0.38, p < 0.05) and triglyceride concentration (r = - 0.42, p < 0.05) but positively with HDL cholesterol (r = 0.38, p < 0.05). Metabolic procedures had no effect on serum adiponectin. CONCLUSIONS: Our findings favor the interpretation that adiponectin is not causally related to insulin sensitivity in healthy participants. The strongest associations of adiponectin in healthy participants are to be found to lipid metabolism. Serum levels of adiponectin are very stable and not acutely affected by hyperinsulinemia, oral glucose or fat load.     

The Normal Limits,Subclinical Significance,Related Metabolic Derangements and Distinct Biological Effects of Body Site-Specific Adiposity in Relatively Healthy Population

Background

The accumulation of visceral adipose tissue that occurs with normal aging is associated with increased cardiovascular risks. However, the clinical significance, biological effects, and related cardiometabolic derangements of body-site specific adiposity in a relatively healthy population have not been well characterized.

Materials and Methods

In this cross-sectional study, we consecutively enrolled 608 asymptomatic subjects (mean age: 47.3 years, 27% female) from 2050 subjects undergoing an annual health survey in Taiwan. We measured pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue volumes by 16-slice multi-detector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA) and related these to clinical characteristics, body fat composition (Tanita 305 Corporation, Tokyo, Japan), coronary calcium score (CCS), serum insulin, high-sensitivity C-reactive protein (Hs-CRP) level and circulating leukocytes count. Metabolic risk was scored by Adult Treatment Panel III guidelines.

Results

TAT, PCF, and total body fat composition all increased with aging and higher metabolic scores (all p<0.05). Only TAT, however, was associated with higher circulating leukocyte counts (ß-coef.:0.24, p<0.05), serum insulin (ß-coef.:0.17, p<0.05) and high sensitivity C-reactive protein (ß-coef.:0.24, p<0.05). These relationships persisted after adjustment in multivariable models (all p<0.05). A TAT volume of 8.29 ml yielded the largest area under the receiver operating characteristic curve (AUROC: 0.79, 95%CI: 0.74–0.83) to identify metabolic syndrome. TAT but not PCF correlated with higher coronary calcium score after adjustment for clinical variables (all p<0.05).

Conclusion

In our study, we observe that age-related body-site specific accumulation of adipose tissue may have distinct biological effects. Compared to other adiposity measures, peri-aortic adiposity is more tightly associated with cardiometabolic risk profiles and subclinical atherosclerosis in a relatively healthy population.     

Relations among measures of body composition, age, and sex in the common marmoset monkey (Callithrix jacchus)

Few studies of body composition have been done in New World primates. In the study reported here, four methods of assessing body composition (body weight, anthropometry, labeled-water dilution, and total body electroconductivity) were compared in 20 marmosets, aged 0.96 to 7.97 years. Males and females did not differ in any measure (P > 0.05). Body weight ranged from 272 to 466 g, and body fat estimates varied from 1.6 to 19.5%. Strong positive correlations were observed between total body water and total body electroconductivity (R2 = 0.77), body weight and fat-free mass (males R2 = 0.95; females R2 = 0.91), and body weight and fat mass (males R2 = 0.86; females R2 = 0.85; P < 0.01). Male and female slopes were equivalent (P > 0.05) for the regressions of fat and fat-free mass against body weight. Positive correlations also were observed between girth measures and fat-free mass (R2 = 0.48 to 0.78) and fat mass (R2 = 0.60 to 0.74; P < 0.01). A good second- order polynomial relationship was observed between age and fat-free mass for the combined sample (R2 = 0.64). Results indicated that: subjects were lean; there was no sexual dimorphism relative to measures; body weight provided a reliable estimate of fat and fat-free mass; and within-subject body weight changes reflected a similar relationship between body weight and fat-free mass as did that across subjects.     

Hemoglobin A1c Levels and Aortic Arterial Stiffness: The Cardiometabolic Risk in Chinese (CRC) Study

Objective

The American Diabetes Association (ADA) recently published new clinical guidelines in which hemoglobin A1c (HbA1c) was recommended as a diagnostic test for diabetes. The present study was to investigate the association between HbA1c and cardiovascular risk, and compare the associations with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT).

Research Design and Methods

The study samples are from a community-based health examination survey in central China. Carotid-to-femoral pulse wave velocity (cfPWV) and HbA1c were measured in 5,098 men and women.

Results

After adjustment for age, sex, and BMI, the levels of HbA1c were significantly associated with an increasing trend of cfPWV in a dose-dependent fashion (P for trend <0.0001). The associations remained significant after further adjustment for blood pressure, heart rate, and lipids (P = 0.004), and the difference in cfPWV between the highest and the lowest quintiles of HbA1c was 0.31 m/s. Fasting glucose and 2 h OGTT were not associated with cfPWV in the multivariate analyses. HbA1c showed additive effects with fasting glucose or 2 h OGTT on cfPWV. In addition, age and blood pressure significantly modified the associations between HbA1c and cfPWV (P for interactions <0.0001 for age; and  = 0.019 for blood pressure). The associations were stronger in subjects who were older (≥60 y; P for trend = 0.004) and had higher blood pressure (≥120 [systolic blood pressure]/80 mmHg [diastolic blood pressure]; P for trend = 0.028) than those who were younger and had lower blood pressure (P for trend >0.05).

Conclusions

HbA1c was related to high cfPWV, independent of conventional cardiovascular risk factors. Senior age and high blood pressure might amplify the adverse effects of HbA1c on cardiovascular risk.     

Normal insulin sensitivity and IMCL content in overweight humans are associated with higher fasting lipid oxidation

Intramyocellular lipid (IMCL) storage is considered a local marker of whole body insulin resistance; because increments of body weight are supposed to impair insulin sensitivity, this study was designed to assess IMCL content, lipid oxidation, and insulin action in individuals with a moderate increment of body fat mass and no family history of diabetes. We studied 14 young, nonobese women with body fat <30% (n = 7) or >30% (n = 7) and 14 young, nonobese men with body fat <25% (n = 7) or >25% (n = 7) by means of the euglycemic-insulin clamp to assess whole body glucose metabolism, with indirect calorimetry to assess lipid oxidation, by localized (1)H NMR spectroscopy of the calf muscles to assess IMCL content, and with dual-energy X-ray absorptiometry to assess body composition. Subjects with higher body fat had normal insulin-stimulated glucose disposal (P = 0.80), IMCL content in both soleus (P = 0.22) and tibialis anterior (P = 0.75) muscles, and plasma free fatty acid levels (P = 0.075) compared with leaner subjects in association with increased lipid oxidation (P < 0.05), resting energy expenditure (P = 0.046), resting oxygen consumption (P = 0.049), and plasma leptin levels (P < 0.01) in the postabsorptive condition. In conclusion, in overweight subjects, preservation of insulin sensitivity was combined with increased lipid oxidation and maintenance of normal IMCL content, suggesting that abnormalities of these factors may mutually determine the development of insulin resistance associated with weight gain.     

The role of serum fructosamine as a screening test for gestational diabetes mellitus

The serum fructosamine concentration indicates the degree of glycation of serum proteins, particularly albumin, and reflects an average blood glucose level over the previous 1-3 weeks. Serum fructosamine, glycated haemoglobin (HbA1c), total serum protein, serum albumin, fasting plasma glucose and oral glucose tolerance test (OGTT) have been measured in 127 healthy control subjects, 102 type 1 and 152 type 2 diabetes mellitus patients and 106 nondiabetic pregnant women. Fructosamine concentration of 2.24 +/- 0.16 and 3.21 +/- 0.41 mmol/l (mean +/- S.D.) has been found in control subjects and diabetics respectively (P less than 0.001). During the second trimester a significantly lower fructosamine level (1.92 +/- 0.21 mmol/l) has been found in pregnant women, most likely due to the low serum albumin concentration (31.35 +/- 3.97 g/l). None of them had a fructosamine level above the normal limit of 2.55 mmol/l. On the other hand, 12 pregnant women showed a disturbed OGTT with normal fructosamine. If the serum fructosamine concentration was adjusted for 40 g/l albumin, then a mean fructosamine of 2.16 +/- 0.24 mmol/l was found in patients with gestational diabetes. Our results show that serum fructosamine has a similar diagnostic value as HbA1c for non-pregnant adults, but neither can replace OGTT for the diagnosis of gestational diabetes.     

Osteocalcin and vitamin D status are inversely associated with homeostatic model assessment of insulin resistance in Canadian Aboriginal and white women: the First Nations Bone Health Study

ObjectiveOsteocalcin, a protein synthesized by osteoblasts, and vitamin D status have independently been implicated in energy metabolism and glucose regulation. This study was conducted to simultaneously explore the relationships among osteocalcin, vitamin D status and indicators of glucose metabolism and adiposity in a mixed-ethnicity cohort of adult women.DesignCross-sectional.MethodsAboriginal and white women (n=368) over 25 years of age (45.3±13.6 years) were studied for measures of osteocalcin and 25-hydroxy vitamin D [25(OH)D] plus glucose metabolism including glucose, insulin, C-peptide, hemoglobin A1c (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR). Measures of adiposity included body mass index (BMI) plus total body fat and trunk fat from dual-energy X-ray absorptiometry.ResultsAboriginal women had higher BMI, fat and markers of dysglycemia. Osteocalcin was not different between groups, but 25(OH)D was lower in Aboriginal women. Osteocalcin was inversely related to all five parameters of glucose metabolism, whereas 25(OH)D was inversely related to insulin, C-peptide and HOMA-IR. After accounting for age, ethnicity or adiposity using regression analyses, glucose, HbA1c and HOMA-IR were inversely related to both osteocalcin and 25(OH)D. However, only 25(OH)D was inversely related to C-peptide, and neither osteocalcin nor 25(OH)D was related to insulin.ConclusionsThese data from a unique mixed Aboriginal and white population suggest that both vitamin D and osteocalcin are involved in glucose control.     

Involvement of Helicobacter pylori infection and impaired glucose metabolism in the increase of brachial-ankle pulse wave velocity

BACKGROUND: The role of Helicobacter pylori in the pathogenesis of atherosclerosis remains controversial. The present study was designed to elucidate the pathogenic role of H. pylori in the early stages of atherosclerosis by measurement of brachial-ankle pulse wave velocity (baPWV) in relation to glucose metabolism. MATERIALS AND METHODS: baPWV level, anti-H. pylori antibody, fasting blood glucose (FBG), and glycosylated hemoglobin A1c (HbA1c) and other conventional risk factors for cardiovascular diseases were measured in 947 subjects who attended their annual medical check-up. RESULTS: Multiple regression analyses indicated that age, gender (male), body mass index, FBG, systolic blood pressure, and smoking habits were each independently related to baPWV values. In younger subjects (30-49 years), H. pylori seropositivity was significantly correlated with an increase of baPWV levels (r = 0.100, p = .0445). baPWV values in the H. pylori-positive subjects with impaired glucose metabolism (IG: FBG >or= 110 mg/dL and/or HbA1c >or= 5.9%) were significantly greater than those in the H. pylori-negative subjects with IG (p = .0078). Furthermore, H. pylori-positive subjects with IG were at higher risk for increase of baPWV, in younger (r = 0.203, p < .0001) as well as in older subjects (50-69 years, r = 0.099, p = .0009). CONCLUSIONS: These results suggest that H. pylori seropositivity is a potential risk factor for increased baPWV levels, and that H. pylori infection accelerates the effect of IG on an increase of baPWV, especially in younger subjects. Thus, the possible interaction between H. pylori infection and IG may contribute to the early development of atherosclerosis.     

Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy

Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique (80 mU x m(-2) x min(-1)) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous (SAT) and visceral adipose tissue (VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[18F]fluoro-D-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT (3.8 +/- 0.4 vs. 2.3 +/- 0.5 micromol x kg tissue(-1) x min(-1), P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal (r2 = 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area (r = -0.75, P = 0.008), and whole body glucose disposal (r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process.