Ageing and associations of fasting plasma glucose and 2 h plasma glucose with HbA(1C) in apparently healthy population. "FIN-D2D" study

Objective

In this FIN-D2D cross-sectional survey the relationship of age with HbA_1c and fasting and 2 h glucose in the oral glucose tolerance test (OGTT) was explored in apparently randomly selected healthy population.

Patients and methods

The glycaemic parameters were measured in 1344 men and 1482 women (aged 45–74 years), and among them we excluded all subjects with known diabetes, hypertension or dyslipidaemia. The final analyses for HbA_1c and the ratios of fasting glucose/HbA_1c and 2 h glucose/HbA_1c included 649 men and 804 women.

Results

Mean age was 57 years and BMI 26.1 kg/m² for both genders. HbA_1c increased in both genders with age (p < 0.001). For a particular fasting glucose level HbA_1c level was higher in older age groups (p < 0.001 for linearity). By contrast, a particular 2 h plasma glucose value in OGTT implied significantly lower HbA_1c in the elderly (p < 0.001 for linearity).

Conclusion

In apparently healthy population, screened with OGTT, in older individuals compared with younger ones a particular HbA_1c value implies slightly lower fasting glucose, but relatively higher 2 h glucose. These results need to be verified in different populations. The effects of age on relation between HbA_1c and plasma glucose should be taken into account in classifying people into different dysglycaemia categories.     

The relative merits of haemoglobin A1c and fasting plasma glucose as first-line diagnostic tests for diabetes mellitus in non-pregnant subjects

HbA_1c was measured by high-performance ion-exchange chromatography in 401 non-pregnant patients undergoing oral glucose tolerance tests (OGTT). All those with HbA_1c>6.2 % (reference range 3.8–5.5 %) had diabetic OGTT (sensitivity 41 %, specificity 100 %). Although a fasting plasma glucose (FPG) cut-off ≥7.0 mmol l⁻¹, as recommended by the American Diabetes Association (ADA), had greater sensitivity (78 %), false positives (12 %) limited its usefulness, so more diagnostic confidence could be placed in a positive HbA_1c. In agreement with the ADA, we found FPG gave only slightly lower diabetes prevalence than the OGTT, but this masked a significant number of individual discrepancies (false positives and negatives) cancelling out each other. The new ADA category of impaired fasting glucose did not correlate well with impaired glucose tolerance. HbA_1c is insufficiently sensitive as a direct substitute for the OGTT. A third of subjects diabetic on OGTT had normal HbA_1c values, so it cannot exclude diabetes as currently defined, but HbA_1c screening could make sufficient positive diagnoses to reduce our non-pregnant OGTTs by one-fifth. If a ‘risk threshold’ for diabetic complications could be applied to HbA_1c, it could replace the OGTT as a more pragmatic diagnostic/prognostic test. © 1998 John Wiley & Sons, Ltd.     

β-Cell function in type 2 diabetes

Different in vivo tests explore different aspects of β-cell function. Because intercorrelation of insulin secretion indices is modest, no single in vivo test allows β-cell function to be assessed with accuracy and specificity comparable to insulin sensitivity. Physiologically-based mathematical modeling is necessary to interpret insulin secretory responses in terms of relevant parameters of β-cell function. Models can be used to analyze intravenous glucose tests, but secretory responses to intravenous glucose may be paradoxical in subjects with diabetes. Use of oral glucose (or mixed meal) data may be preferable not only for simplicity but also for physiological interpretation.     

Indexes of β-cell function from the oral glucose tolerance test can modestly predict pancreatic β-cell area in Korean

Aims

Pancreatic β-cell function indexes have been suggested using the oral glucose tolerance test (OGTT). Here, we investigated whether β-cell function index from the OGTT reflects pancreatic β-cell area in Korean patients.

Methods

The study consisted of 45 patients who underwent pancreatectomies. Before operation, a 75-g OGTT was performed. Immunohistochemical staining was performed, and indexes of β-cell function from the OGTT data were compared with the pancreatic β-cell area.

Results

The β-cell area of the pancreas was 1.07 ± 0.33% in the normal glucose tolerance group, 1.71 ± 0.85% in the pre-diabetes group (impaired glucose tolerance and impaired fasting glucose), and 1.08 ± 0.57% in the diabetes group. The β-cell area of the pre-diabetes group was significantly higher than that of the diabetes group. Pancreatic β-cell area showed a significant correlation with a homeostasis model assessment of β-cell function (r = 0.358, P = 0.016), disposition index (r = 0.336, P = 0.024), fasting glucose (r = −0.359, P = 0.015), and the C-peptide/glucose 30 min ratio (r = 0.319, P = 0.035).

Conclusions

Some parameters of β-cell function from the OGTT showed a significant relationship with the β-cell area of pancreas.     

2型糖尿病患者糖化血红蛋白水平与内皮功能评估指数的相关性

目的 探讨糖化血红蛋白(HbA1c)与反应性充血指数(RHI)的相关性.方法 入选2017年1月至2019年2月南京医科大学第一附属医院内分泌科收治的2型糖尿病患者608例,住院期间所有患者均使用Endo-PAT无创血管内皮功能检测技术计算出评估指数RHI.根据RHI结果分组,RHI≥1.67为对照组,RHI<1.67...     

糖化血红蛋白与血浆致动脉粥样硬化指数对中老年2型糖尿病发生风险的联合预测价值

目的:探讨糖化血红蛋白（HbA 1c）和血浆致动脉粥样硬化指数（AIP）对中老年2型糖尿病（T2DM）发生风险的联合预测价值。 方法:本研究依托中国T2DM患者肿瘤发生风险的流行病学研究（REACTION）,对2011至2014年在大连社区40周岁及以上人群中开展的流行病学调查资料进行回顾性分析,...     

Hypertriglyceridaemia either in isolation or in combination with abdominal obesity is strongly associated with atherogenic dyslipidaemia in Asian Indians

Aim

To assess the prevalence of isolated hypertriglyceridaemia (iHTG) and hypertriglyceridaemic waist phenotype (HTWP) in urban adult Asian Indian population and to study their associations with atherogenic dyslipidaemia.

Methods

Data of an epidemiological survey (n = 2117, M:F 1007:1110) was used. Prevalences of iHTG (fasting triglycerides (TG) ≥ 1.7 mmol/l) and HTWP (waist circumference male ≥ 90 cm and female ≥ 80 cm and TG ≥ 1.7 mmol/l), were assessed. Their prevalences in relation to glucose intolerance were also studied. Associations of iHTG and HTWP with the occurrence of atherogenic dyslipidaemia indicated by elevated LDL-C/HDL-C ratio of ≥ 2.5 were assessed using multiple logistic regression analyses.

Results

iHTG, and HTWP were present in 13.4% and 17.8% respectively. Prevalence of HTWP was significantly higher among women. Prevalence of HTWP progressively increased with glucose intolerance. Nearly 60% of the subjects with iHTG or HTWP had atherogenic dyslipidaemia and prevalence was similar in both groups.

Conclusions

Hypertriglyceridaemia, present either as iHTG or HTWP was strongly associated with atherogenic dyslipidaemia. Dyslipidaemia occurred more frequently in glucose intolerance since the prevalence of both forms of hypertriglyceridaemia increased with glucose intolerance.     

A short message service (SMS) intervention to prevent diabetes in Chinese professional drivers with pre-diabetes: A pilot single-blinded randomized controlled trial

Aim

To determine the efficacy of delivering short-message service (SMS) to provide diabetes-related information in reducing the risk of developing diabetes in Chinese professional drivers with pre-diabetes.

Methods

A pilot single-blinded randomized controlled trial was conducted in Hong Kong between 05/2009 and 04/2012. Professional drivers with impaired glucose tolerance (IGT) were randomly allocated to either a SMS group receiving messages comprising knowledge and lifestyle modification on diabetes or to a control group with usual care. Primary outcomes were the incidence rate of diabetes mellitus over 12 and 24 months period.

Results

Fifty-four, out of 104 professional drivers recruited, were randomly allocated to intervention group. Fewer subjects developed diabetes at 12 months in intervention group (5.56%) compared to control group (16.00%). Relative risk (RR) of diabetes onset was 0.35 (95%CI: 0.10–1.24) and the number needed to treat (NNT) for preventing one diabetes was 9.57. At 24 months, RR increased to 0.62 (95%CI: 0.24–1.61) with a NNT of 10.58. Logistic regression showed a significant odds ratio of 0.04 (P = 0.021) for intervention group compared to control group at 12-month follow-up for completers and a non-significant odds ratio of 0.34 (P = 0.303) at 24-month follow-up.

Conclusions

The SMS program proved to have potential to reduce the risk of developing diabetes at 12 months but additional measures should be integrated to prevent or delay disease progression.     

Association of serum fibroblast growth factor 19 levels with visceral fat accumulation is independent of glucose tolerance status

Background and aims

Recent studies suggested that circulating fibroblast growth factor (FGF) 19 levels might be associated with the fat content and distribution, and varied with different glucose tolerance status. This study aimed to investigate the association of serum FGF19 levels with obesity and visceral fat accumulation in a Chinese population with differing glucose tolerance status.

Hemoglobin A1c,frequency of glucose testing and social disadvantage: Metrics of racial health disparity in youth with type 1 diabetes

Introduction

Black youth with type 1 diabetes (T1D) have higher HbA1c than whites. To understand HbA1c differences, we examined the relationship of psycho-social factors and glucose testing with HbA1c.

Eight weeks of treatment with long-acting GLP-1 analog taspoglutide improves postprandial insulin secretion and sensitivity in metformin-treated patients with type 2 diabetes

Objective

Loss of pancreatic function is pivotal to the deterioration of fasting and postprandial glycemic control in type 2 diabetes (T2D). We evaluated the effects of a long-acting, human glucagon-like peptide-1 analog, taspoglutide, added to metformin, on pancreatic function and peripheral insulin sensitivity.

Materials/methods

We studied 80 T2D patients inadequately controlled [glycosylated hemoglobin (HbA_1c), 7.0%–9.5%] receiving stable metformin for ≥ 12 weeks. They were a subset of participants to a phase 2 trial that received also a 240-min mixed-meal tolerance test (MTT) at baseline and study end. Patients received once weekly (QW) sc injection of taspoglutide 5, 10, or 20 mg (n = 21, 19, or 19), or placebo (n = 21), plus metformin, for 8 weeks. We measured postprandial plasma glucose (PPG) and insulin profiles, insulin secretion rate (ISR), oral glucose insulin sensitivity (OGIS) index; β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios, and insulin sensitivity-to-insulin resistance (or disposition) index.

Results

After 8 weeks of treatment, taspoglutide 5, 10, and 20 mg QW doses vs. placebo improved mean PPG_{0–240 min} (relative change from baseline: − 22.1%, − 25.9%, and − 22.9% vs. − 8.1%; P < 0.005) and mean postprandial ISR_{0–240 min} (+ 14%, + 18%, and + 23% vs. + 1%; P < 0.005 vs dose). Taspoglutide at 20 mg QW dose also resulted in improvements from baseline in OGIS, β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios and the disposition index during the MTT.

Conclusion

Taspoglutide QW significantly improved pancreatic function in patients with T2D treated with metformin.     

Lactation intensity and fasting plasma lipids,lipoproteins, non-esterified free fatty acids,leptin and adiponectin in postpartum women with recent gestational diabetes mellitus: The SWIFT cohort

Objectives

Lactation may influence future progression to type 2 diabetes after gestational diabetes mellitus (GDM). However, biomarkers associated with progression to glucose intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy independent of obesity, socio-demographics and insulin resistance.

Methods

The Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective cohort study that recruited 1035 women diagnosed with GDM by the 3-h 100 g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008–2011. Research staff conducted 2-h 75 g OGTTs, and assessed lactation intensity, anthropometry, lifestyle behaviors and socio-demographics at 6–9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored samples obtained at 6–9 weeks postpartum in 1007 of the SWIFT participants who were free of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models.

Results

Increasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5%–8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20%–28% lower fasting triglycerides, 15%–21% lower leptin (all trend P-values < 0.01), and with 6% lower adiponectin, but only after adjustment for insulin resistance (trend P-value = 0.04).

Conclusion

Higher lactation intensity was associated with more favorable biomarkers for type 2 diabetes, except for lower plasma adiponectin, after GDM delivery. Long-term follow-up studies are needed to assess whether these effects of lactation persist to predict progression to glucose intolerance.     

Plasma polyunsaturated fatty acid profile and delta-5 desaturase activity are altered in patients with type 2 diabetes

Objective

The association between imbalance of polyunsaturated fatty acids (PUFAs), especially low plasma n-3 to n-6 PUFA ratio, and risk of cardiovascular diseases is well known. A balance of plasma PUFAs is determined not only by dietary fatty acid intake, but also by the endogenous fatty acid metabolism, which could be dysregulated by diabetes. In this study, we investigated the plasma n-3 and n-6 PUFA profile and fatty acid desaturase activity in patients with type 2 diabetes (T2D).

Materials/Methods

The subjects were 396 patients with T2D and 122 healthy controls. Plasma eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA) levels were measured by capillary gas chromatography.

Results

Plasma DHA, AA, and DGLA levels were significantly higher, and EPA levels tended to be lower in patients with T2D than in the controls. Patients with T2D also exhibited significantly lower EPA/AA, DHA/AA, and (EPA + DHA)/AA ratios, and a higher AA/DGLA ratio than the controls. Multiple regression analyses, including age, sex, body mass index, and metabolic parameters in the total population, revealed that the presence of T2D was independently associated with elevated plasma DHA, AA, and DGLA levels and decreased EPA/AA, DHA/AA, and (EPA + DHA)/AA ratios. Furthermore, T2D was independently and positively related to the AA/DGLA ratio, which serves as an estimate of delta (Δ)-5 desaturase activity.

Conclusions

Elevated plasma AA levels and decreased n-3 PUFA/AA ratios in T2D are attributable, at least partly, to Δ5 desaturase activation.     

Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: A 4 year retrospective longitudinal study

Objective

Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men.

Materials and Methods

This 4 year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method.

Results

During a 4 year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend < 0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30–2.00 mg/dl) than in the lowest bilirubin quartile category (i.e., ≤ 0.90 mg/dl), even after adjustment for confounding variables (RR = 0.69, 95% confidence interval 0.48–0.99, P for trend = 0.041).

Conclusions

The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects.     

The one year exercise and lifestyle intervention program KLAKS: Effects on anthropometric parameters,cardiometabolic risk factors and glycemic control in childhood obesity

Objective

Regular physical exercise within structured lifestyle programs may improve weight status and minimize metabolic risk factors in childhood obesity. The aim of this study was to evaluate the effect of the one-year combined physical exercise/lifestyle program KLAKS on anthropometric and metabolic parameters and glycemic control in childhood obesity.

Materials and Methods

142 overweight/obese (BMI > 90th percentile) candidates (7–18 years) were enrolled, 115 participants completed the program. Anthropometrics and biochemical parameters were obtained at beginning and completion. An oral glucose tolerance test (OGTT) was performed in a subgroup of participants. Course of glucose and insulin levels within OGTT was correlated with several parameters and is reported here for those who completed the program.

Results

The mean standard deviation scores (SDS) decreased significantly for BMI, waist circumference, waist-to-height ratio (WHtR) and percentage body fat (all p ≤ 0.01). Improved metabolic risk markers included mean glucose levels within an OGTT at follow-up compared to baseline (p < 0.0001) and HbA1c (p = 0.05) as well as indications of improvement for gamma-glutamyl-transferase and free fatty acids.

Conclusions

The one-year combined exercise/lifestyle program KLAKS significantly improves markers of obesity and glycemic control. Impaired cardiometabolic risk markers, even subclinical, are also favorably influenced by program participation.     

Low circulating insulin-like growth factor-1 levels are associated with high serum uric acid in nondiabetic adult subjects

Background and aimsLow insulin-like growth factor-1 (IGF-1) levels and high uric acid concentrations are associated with cardio-metabolic disorders. Acute IGF-1 infusion decreases uric acid concentration in healthy individuals. In this study, we aimed to examine the relationship between IGF-1 and uric acid levels.Methods and results1430 adult non diabetic subjects were stratified into quartiles according to their circulating IGF-1 values. Significant differences in uric acid concentration, measured by the URICASE/POD method were observed between low (quartile 1), intermediate (quartile 2 and 3), and high (quartile 4) IGF-1 levels groups after adjusting for age, gender, and body mass index (P = 0.02). These differences remained significant after adjustment for blood pressure, total cholesterol, high density lipoprotein, triglycerides, fasting and 2 h post-load glucose levels, HOMA-IR index (P = 0.005), liver enzymes (P = 0.03), glucose tolerance status (P = 0.02), growth hormone levels (GH) (P = 0.05), anti-hypertensive treatments (P = 0.04) or diuretics use (P = 0.04)). To clarify the molecular links between IGF-1 and uric acid, we performed an in vitro study, incubating human hepatoma cells with uric acid for 24 or 48 h in the presence of GH and observed a 21% and 26% decrease, respectively, in GH-stimulated IGF-1 mRNA expression (P = 0.02 and P = 0.012, respectively). This effect appears to be mediated by uric acid ability to down regulate GH intracellular signaling; in fact we observed a significant decrease of GH activated JAK2 and Stat5 phosphorylation.ConclusionsThese data demonstrate an inverse relationship between IGF-1 and uric acid levels in adults and suggest that uric acid might affect hepatic IGF-1 synthesis.     

Changes in adiposity mediate the associations of diet quality with insulin sensitivity and beta-cell function

Background and aimsTo examine the mediating role of adiposity on the associations of diet quality with longitudinal changes in insulin sensitivity and beta-cell function.Methods and resultsAdults at-risk for type 2 diabetes (T2D) in the PROMISE cohort had 4 assessments over 9 years (n = 442). Alternate Healthy Eating Index (AHEI) scores were used to assess diet quality. Generalized Estimating Equations (GEE) evaluated the associations between the AHEI and longitudinal changes in insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI/HOMA-IR and ISSI-2). The proportion of the mediating effect of waist circumference changes was estimated using the difference method. In the primary longitudinal analysis, AHEI was positively associated with insulin sensitivity and beta-cell function over time (% difference per standard deviation increase of AHEI for HOMA2-%S (β = 11.0, 95%CI 5.43–17.0), ISI (β = 10.4, 95%CI 4.35–16.8), IGI/HOMA-IR (β = 7.12, 95%CI 0.98–13.6) and ISSI-2 (β = 4.38, 95%CI 1.05–7.80), all p < 0.05). There was no significant association between AHEI and dysglycemia incidence (OR = 0.95, 95%CI 0.77–1.17). Adjustments for longitudinal changes in waist circumference substantially attenuated all associations of AHEI with insulin sensitivity and beta-cell function. Mediation analysis indicated that waist circumference mediated 73%, 70%, 83% and 81% of the association between AHEI and HOMA2-%S, ISI, IGI/HOMA-IR, and ISSI-2, respectively (all p < 0.01).ConclusionIn a Canadian population at-risk for T2D, AHEI score was positively associated with changes in insulin sensitivity and beta-cell function. These associations were substantially mediated by waist circumference, suggesting that changes in adiposity may represent an important pathway linking diet quality with risk phenotypes for T2D.