The True Value of HbA1c as a Predictor of Diabetic Complications: Simulations of HbA1c Variables

Aim

The updated mean HbA1c has been used in risk estimates of diabetic complications, but it does not take into account the temporal relationship between HbA1c and diabetic complications. We studied whether the updated mean HbA1c underestimated the risk of diabetic complications.

Method

Continuous HbA1c curves for 10,000 hypothetical diabetes patients were simulated over an average of 7 years. Simulations were based on HbA1c values encountered in clinical practice. We assumed that each short time interval of the continuous HbA1c curves had a long-lasting effect on diabetic complications, as evidenced by earlier studies. We tested several different HbA1c variables including various profiles, e.g. different duration, of such a long-lasting effect. The predictive power of these variables was compared with that of the updated mean HbA1c.

Results

The predictive power of the constructed HbA1c variables differed considerably compared to that of the updated mean HbA1c. The risk increase per standard deviation could be almost 100% higher for a constructed predictor than the updated mean HbA1c.

Conclusions

The importance of good glycemic control in preventing diabetic complications could have been underestimated in earlier hallmark studies by not taking the time-dependent effect of HbA1c into account.     

Diabetes mellitus is associated with shortened activated partial thromboplastin time and increased fibrinogen values

Objective

This study was designed to examine the relationship between shortened activated partial thromboplastin time (APTT) and increased fibrinogen values with diabetes mellitus.

Methods

APTT, prothrombin time (PT), fibrinogen, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) levels were measured in 1,300 patients. Patients were divided into three groups according to their HbA1c and FPG levels.

Results

When participants were grouped according to their HbA1c levels, we found significantly shorter APTT values (26.9±5.6 s) and increased fibrinogen levels (3.1, 1.9–6.3 g/L) in the diabetes group when compared with the other two groups. When participants were grouped according to their FPG levels, we found significantly shorter APTT values (26.9±6.2 s) and increased fibrinogen levels (3.1, 1.8–6.2 g/L) in the diabetes group when compared with the euglycemic group.

Conclusions

Shorter APTT and increased fibrinogen levels might be useful hemostatic markers in patients with diabetes and in patients at high risk for diabetes.     

Dietary fiber, carbohydrate quality and quantity, and mortality risk of individuals with diabetes mellitus

Background

Dietary fiber, carbohydrate quality and quantity are associated with mortality risk in the general population. Whether this is also the case among diabetes patients is unknown.

Objective

To assess the associations of dietary fiber, glycemic load, glycemic index, carbohydrate, sugar, and starch intake with mortality risk in individuals with diabetes.

Methods

This study was a prospective cohort study among 6,192 individuals with confirmed diabetes mellitus (mean age of 57.4 years, and median diabetes duration of 4.4 years at baseline) from the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary intake was assessed at baseline (1992–2000) with validated dietary questionnaires. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality, while adjusting for CVD-related, diabetes-related, and nutritional factors.

Results

During a median follow-up of 9.2 y, 791 deaths were recorded, 306 due to CVD. Dietary fiber was inversely associated with all-cause mortality risk (adjusted HR per SD increase, 0.83 [95% CI, 0.75–0.91]) and CVD mortality risk (0.76[0.64–0.89]). No significant associations were observed for glycemic load, glycemic index, carbohydrate, sugar, or starch. Glycemic load (1.42[1.07–1.88]), carbohydrate (1.67[1.18–2.37]) and sugar intake (1.53[1.12–2.09]) were associated with an increased total mortality risk among normal weight individuals (BMI≤25 kg/m²; 22% of study population) but not among overweight individuals (P interaction≤0.04). These associations became stronger after exclusion of energy misreporters.

Conclusions

High fiber intake was associated with a decreased mortality risk. High glycemic load, carbohydrate and sugar intake were associated with an increased mortality risk in normal weight individuals with diabetes.     

Development of an HbA1c-Based Conversion Equation for Estimating Glycated Albumin in a Korean Population with a Wide Range of Glucose Intolerance

Background

Compared to the golden standard glycation index of HbA1c, glycated albumin (GA) has potentials for assessing insulin secretory dysfunction and glycemic fluctuation as well as predicting diabetic vascular complications. However, the reference ranges of GA and a conversion equation need to be clearly defined. We designed this study to determine the reference ranges in patients with normal glucose tolerance (NGT) based on conventional measures of glycemic status and to devise a conversion equation for calculating HbA1c and GA in a Korean population.

Methodology/Principal Findings

In this multicenter, retrospective, cross-sectional study, we recruited antidiabetic drug-naïve patients with available glycemic variables including HbA1c, GA, and fasting plasma glucose regardless of glucose status. For the reference interval of serum GA, 5^th to 95^th percentile value of GA in subjects with NGT was adopted. The conversion equation between HbA1c and GA was devised using an estimating regression model with unknown break-points method. The reference range for GA was 9.0–14.0% in 2043 subjects. The 95^th percentile responding values for FPG, and HbA1c were approximately 5.49 mmol/l, and 5.6%, respectively. The significant glycemic turning points were 5.868% HbA1c and 12.2% GA. The proposed conversion equation for below and above the turning point were GA (%) = 6.960+0.8963 × HbA1c (%) and GA (%) = −9.609+3.720 × HbA1c (%), respectively.

Conclusions/Significance

These results should be helpful in future studies on the clinical implications of high GA relative to HbA1c and the clinical implementation of diabetes management.     

Association of NT-proBNP and multiple biomarkers with severity of angiographic coronary artery disease in diabetic and pre-diabetic Chinese patients

Background

Little is known about the plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the relationship between the severity of coronary heart disease (CHD) with NT-proBNP and multiple biomarkers in diabetic and pre-diabetic patients, compared to individuals with normal glucose levels.

Methods

Four hundred and fifteen consecutive Chinese patients of both sexes were assigned to three groups on the basis of the new hemoglobin (Hb) A1c (HbA1c) cut-off points for diagnosis of diabetes and pre-diabetes. The three groups were divided into tertiles according to NT-proBNP, hs-CRP, cystatin C, and troponin T levels. Gensini scores were compared among the three groups and biomarker tertiles. Receiver operating characteristic (ROC) curves were used to obtain the angiographic CHD cut-off points for each biomarker. Stepwise multivariate linear correlation analysis was applied to examine the association between the severity of CHD and biomarker levels.

Results

Gensini scores increased with increasing biomarker tertile levels and HbA1c. Gensini scores were significantly different in the middle and upper NT-proBNP tertiles of the diabetic, pre-diabetic and control groups. NT-proBNP had the highest positive and negative predictive values and area under the curve for CHD. Only NT-proBNP was identified as an independent variable for Gensini score.

Conclusions

Plasma NT-proBNP may be an important biomarker to evaluate the severity of CHD and screen for CHD in diabetic or pre-diabetic patients.     

Good glycemic control is associated with better survival in diabetic patients on peritoneal dialysis: a prospective observational study

Background

The effect of glycemic control after starting peritoneal dialysis (PD) on the survival of diabetic PD patients has largely been unexplored, especially in Asian population.

Methods

We conducted a prospective observational study, in which 140 incident PD patients with diabetes were recruited. Patients were divided into tertiles according to the means of quarterly HbA1C levels measured during the first year after starting PD. We examined the association between HbA1C and all-cause mortality using Cox proportional hazards models.

Results

The mean age was 58.7 years, 59.3% were male, and the mean follow-up duration was 3.5 years (range 0.4–9.5 years). The mean HbA1C levels were 6.3%, 7.1%, and 8.5% in the 1^st, 2^nd, and 3^rd tertiles, respectively. Compared to the 1^st tertile, the all-cause mortality rates were higher in the 2^nd [hazard ratio (HR), 4.16; 95% confidence interval (CI), 0.91–18.94; p = 0.065] and significantly higher in the 3^rd (HR, 13.16; 95% CI, 2.67–64.92; p = 0.002) tertiles (p for trend = 0.005), after adjusting for confounding factors. Cardiovascular mortality, however, did not differ significantly among the tertiles (p for trend = 0.682). In contrast, non-cardiovascular deaths, most of which were caused by infection, were more frequent in the 2^nd (HR, 7.67; 95% CI, 0.68–86.37; p = 0.099) and the 3^rd (HR, 51.24; 95% CI, 3.85–681.35; p = 0.003) tertiles than the 1^st tertile (p for trend = 0.007).

Conclusions

Poor glycemic control is associated with high mortality rates in diabetic PD patients, suggesting that better glycemic control may improve the outcomes of these patients.     

Skin Autofluorescence Based Decision Tree in Detection of Impaired Glucose Tolerance and Diabetes

Aim

Diabetes (DM) and impaired glucose tolerance (IGT) detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF) is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE) which are considered to be a carrier of glycometabolic memory. We compared SAF and a SAF-based decision tree (SAF-DM) with fasting plasma glucose (FPG) and HbA1c, and additionally with the Finnish Diabetes Risk Score (FINDRISC) questionnaire±FPG for detection of oral glucose tolerance test (OGTT)- or HbA1c-defined IGT and diabetes in intermediate risk persons.

Methods

Participants had ≥1 metabolic syndrome criteria. They underwent an OGTT, HbA1c, SAF and FINDRISC, in adition to SAF-DM which includes SAF, age, BMI, and conditional questions on DM family history, antihypertensives, renal or cardiovascular disease events (CVE).

Results

218 persons, age 56 yr, 128M/90F, 97 with previous CVE, participated. With OGTT 28 had DM, 46 IGT, 41 impaired fasting glucose, 103 normal glucose tolerance. SAF alone revealed 23 false positives (FP), 34 false negatives (FN) (sensitivity (S) 68%; specificity (SP) 86%). With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM) (S 82%; SP 89%). HbA1c scored 48 FP, 18 FN (S 80%; SP 75%). Using HbA1c-defined DM-IGT/suspicion ≥6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM) (S76%; SP72%), FPG 29 FP, 41 FN (S71%; SP80%). FINDRISC≥10 points as detection of HbA1c-based diabetes/suspicion scored 79 FP, 23 FN (S 69%; SP 45%).

Conclusion

SAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons. SAF-DM’s value for diabetes/IGT screening is further supported by its established performance in predicting diabetic complications.     

The Effect of Periodontal Treatment on Hemoglobin A1c Levels of Diabetic Patients: A Systematic Review and Meta-Analysis

Background

There is growing evidence that periodontal treatment may affect glycemic control in diabetic patients. And several systematic reviews have been conducted to assess the effect of periodontal treatment on diabetes outcomes. Researches of this aspect are widely concerned, and several new controlled trials have been published. The aim of this study was to update the account for recent findings.

Methods

A literature search (until the end of January 2014) was carried out using various databases with language restriction to English. A randomized controlled trial (RCT) was selected if it investigated periodontal therapy for diabetic subjects compared with a control group received no periodontal treatment for at least 3 months of the follow-up period. The primary outcome was hemoglobin A1c (HbA1c), and secondary outcomes were periodontal parameters included probing pocket depth (PPD) and clinical attachment level (CAL).

Results

Ten trials of 1135 patients were included in the analysis. After the follow-up of 3 months, treatment substantially lowered HbA1c compared with no treatment after periodontal therapy (–0.36%, 95%CI, −0.52% to −0.19%, P<0.0001). Clinically substantial and statistically significant reduction of PPD and CAL were found between subjects with and without treatment after periodontal therapy (PPD −0.42 mm, 95%CI: −0.60 to −0.23, P<0.00001; CAL −0.34 mm, 95%CI: −0.52 to −0.16, P = 0.0002). And there is no significant change of the level of HbA1c at the 6-month comparing with no treatment (–0.30%, 95%CI, −0.69% to 0.09%, P = 0.13).

Conclusions

Periodontal treatment leads to the modest reduction in HbA1c along with the improvement of periodontal status in diabetic patients for 3 months, and this result is consistent with previous systematic reviews. And the effect of periodontal treatment on HbA1c cannot be observed at 6-month after treatment.     

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.     

A two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes

Backgrounds

We compared the usefulness of fasting plasma glucose (FPG), or hemoglobin A1c (HbA1c), or both in predicting type 2 diabetes.

Methods

This retrospective cohort study investigated 9,322 Japanese adults (4,786 men and 4,536 women), aged 19–69 yrs, free of diabetes at baseline. Usefulness was assessed by predictive values (PV), sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) maximised under the best cut-off point.

Results

During the average 6 years of follow-up, 221 men (4.6%) and 92 women (2%) developed diabetes. The best cut-off points for FPG (i.e., 5.67 mmol/l for men and 5.5 mmol/l for women) gave excellent AUROC, and the highest positive PV (13% for men and 9% for women) in predicting diabetes. In high risk subjects with FPG 6.1–6.9 mmol/l, 119 men (26.8%) and 39 women (28.3%) developed diabetes. Under the best cut-off points of FPG 6.39 mmol/l and A1c 5.8, AUROC and positive PV for FPG slightly decreased indicating FPG became less useful and were statistically indistinguishable from those for HbA1c in men. In fact, HbA1c was the most useful in women: HbA1c of 6.0% gave the highest positive likelihood ratio of 2.74 and larger AUROC than did FPG. Although AUROC for HbA1c was acceptable and indistinguishable from that for the combined use, HbA1c had higher specificity and positive LR than did the combined use.

Conclusions

This study demonstrated that FPG was the most useful to predict diabetes in the general population. However, in subjects with FPG 6.1–6.9 mmol/l, FPG became less useful and diagnostic performance of FPG was indistinguishable from that of HbA1c in men whereas HbA1c was the most useful in women. Thus, a two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes.     

Impact of Walking on Glycemic Control and Other Cardiovascular Risk Factors in Type 2 Diabetes: A Meta-Analysis

Background

Walking is the most popular and most preferred exercise among type 2 diabetes patients, yet compelling evidence regarding its beneficial effects on cardiovascular risk factors is still lacking. The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the association between walking and glycemic control and other cardiovascular risk factors in type 2 diabetes patients.

Methods

Three databases were searched up to August 2014. English-language RCTs were eligible for inclusion if they had assessed the walking effects (duration ≥8 weeks) on glycemic control or other cardiovascular risk factors among type 2 diabetes patients. Data were pooled using a random-effects model. Subgroup analyses based on supervision status and meta-regression analyses of variables regarding characteristics of participants and walking were performed to investigate their association with glycemic control.

Results

Eighteen studies involving 20 RCTs (866 participants) were included. Walking significantly decreased glycosylated haemoglobin A1c (HbA1c) by 0.50% (95% confidence intervals [CI]: −0.78% to −0.21%). Supervised walking was associated with a pronounced decrease in HbA1c (WMD −0.58%, 95% CI: −0.93% to −0.23%), whereas non-supervised walking was not. Further subgroup analysis suggested non-supervised walking using motivational strategies is also effective in decreasing HbA1c (WMD −0.53%, 95% CI: −1.05% to −0.02%). Effects of covariates on HbA1c change were generally unclear. For other cardiovascular risk factors, walking significantly reduced body mass index (BMI) and lowered diastolic blood pressure (DBP), but non-significantly lowered systolic blood pressure (SBP), or changed high-density or low-density lipoprotein cholesterol levels.

Conclusions

This meta-analysis supports that walking decreases HbA1c among type 2 diabetes patients. Supervision or the use of motivational strategies should be suggested when prescribed walking to ensure optimal glycemic control. Walking also reduces BMI and lowers DBP, however, it remains insufficient regarding the association of walking with lowered SBP or improved lipoprotein profiles.

Trial Registration

PROSPERO CRD42014009515     

Increased Intraocular Pressure and Hyperglycemic Level in Diabetic Patients

Purpose

To determine whether hyperglycemic levels as determined from high hemoglobin A1c (HbA1c) levels influence intraocular pressure (IOP) in patients with non-proliferative diabetic retinopathy (NPDR).

Methods

A retrospective chart review was performed on subjects with a diagnosis of NPDR and a corresponding HbA1c level measured within 90 days before or after an IOP measurement over a two-year period. Exclusion criteria included a diagnosis of glaucoma or treatment with IOP lowering medications or oral or topical steroids.

Results

Using 14.5mmHg as a baseline mean value for IOP, 42 subjects had an IOP < 14.5mmHg and mean HbA1c of 8.1±1.1, while 72 subjects had an IOP ≥ 14.5mmHg and a mean HbA1c of 9.0±2.1. Although there was an overlap in the confidence intervals, a significant difference (P = 0.01) in the mean HbA1c level was observed in regression analysis between the two groups. Importantly, diabetic subjects with elevated HbA1c levels rarely (<1%) exhibited reduced IOP levels.

Conclusions

Diabetic subjects with elevated HbA1c levels exhibited significantly higher IOPs compared to those with lower HbA1c levels. Findings from this study indicate an association between hyperglycemia and elevated IOP and that poor glycemic control may contribute to increased IOP levels in long-term diabetic patients.     

Relationship of Glycated Hemoglobin Levels with Myocardial Injury following Elective Percutaneous Coronary Intervention in Patients with Type 2 Diabetes Mellitus

Background

Glycated hemoglobin (HbA1c) predicts clinical cardiovascular disease or cardiovascular mortality. However, the relationship between HbA1c and myocardial injury following elective percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (DM) has not been investigated.

Objectives

The study sought to assess the relationship between HbA1c and myocardial injury following elective PCI in patients with type 2 DM.

Methods

We studied a cohort of consecutive 994 diabetic patients with coronary artery disease (CAD) undergoing elective PCI. Periprocedural myocardial injury was evaluated by analysis of troponin I (cTnI). The association between preprocedural HbA1c levels and the peak values of cTnI within 24 hours after PCI was evaluated.

Results

Peak postprocedural cTnI >1×upper limit of normal (ULN), >3×ULN and >5×ULN were detected in 543 (54.6%), 337 (33.9%) and 245 (24.6%) respectively. In the multivariate model, higher HbA1c levels were associated with less risk of postprocedural cTnI >1×ULN (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.76–0.95; P = 0.005). There was a trend that higher HbA1c levels were associated with less risk of postprocedural cTnI >3×ULN (OR, 0.90; 95% CI, 0.81–1.02; P = 0.088). HbA1c was not associated with the risk of postprocedural cTnI elevation above 5×ULN (OR, 0.95; 95% CI, 0.84–1.08; P = 0.411).

Conclusions

The present study provided the first line of evidence that higher preprocedural HbA1c levels were associated with less risk of myocardial injury following elective PCI in diabetic patients.     

Effects of age and sex in the diagnosis of type 2 diabetes using glycated haemoglobin in Japan: the Yuport Medical Checkup Centre study

Background

We examined how the prevalence of individuals diagnosed with diabetes differs by age and sex using the diagnostic criteria of fasting plasma glucose (FPG) and/or glycated haemoglobin (HbA1c) in a large Japanese population.

Methods

We conducted a cross-sectional study using a dataset of 33,959 people (16,869 men and 17,090 women) without known diabetes who underwent health checkups from 1998 to 2006. We divided the age range of the participants into six groups of similar numbers. We compared the prevalence of diabetes using the criteria of FPG ≥7.0 mmol/l (126 mg/dl), HbA1c ≥48 mmol/mol (6.5%), or both, in men and women in each age group.

Results

Men had higher prevalence of diabetes than women using the criterion of either FPG or HbA1c (7.5% men vs. 3.4% women, P<0.001), or both (4.3% men vs. 1.8% women, P<0.001). HbA1c increased steadily in women through the six age groups. In the oldest group (≥66 years), the proportion of women among those diagnosed with diabetes was as high as 42.3% (215/508) using the criterion of either FPG or HbA1c, and 41.6% (116/279) using both criteria.

Conclusions

Using either FPG or HbA1c, the prevalence of people diagnosed with diabetes would almost double compared to using the criterion of both scores, and this would include more elderly women than men. The impact of introducing HbA1c for diabetes diagnosis should be considered in terms of age and sex.     

Association between Sleep Duration and Urinary Albumin Excretion in Patients with Type 2 Diabetes: The Fukuoka Diabetes Registry

Objective

Few studies have so far investigated the impact of sleep duration on chronic kidney disease in diabetic patients. The objective of the present study was to examine the relationship between sleep duration and albuminuria in type 2 diabetic patients.

Research Design and Methods

A total of 4,870 Japanese type 2 diabetic patients ≥20 years of age were divided into six groups according to self-reported sleep duration: less than 4.5 hours, 4.5–5.4 hours, 5.5–6.4 hours, 6.5–7.4 hours, 7.5–8.4 hours and more than 8.5 hours. The association between sleep duration and urinary albumin-creatinine ratio (UACR) was examined cross-sectionally.

Results

Both short and long sleep durations were significantly associated with higher UACR levels and higher proportions of patients with albuminuria (≥30 mg/g) and macroalbuminuria (≥300 mg/g) compared with a sleep duration of 6.5–7.4 hours (P for quadratic trend <0.001). A U-shaped association between sleep duration and UACR remained significant even after adjustment for potential confounders, including age, sex, duration of diabetes, current smoking habits, former smoking habits, current drinking habits, regular exercise habits, total energy intake, total protein intake, hypnotic use and estimated glomerular filtration rate. Furthermore, the association remained substantially unchanged after additional adjustment for body mass index, hemoglobin A_1c, systolic blood pressure, renin-angiotensin system inhibitor use and depressive symptoms.

Conclusions

Our findings suggest that sleep duration has a U-shaped association with the UACR levels in type 2 diabetic patients, independent of potential confounders.     

Fluctuation between Fasting and 2-H Postload Glucose State Is Associated with Chronic Kidney Disease in Previously Diagnosed Type 2 Diabetes Patients with HbA1c ≥ 7%

Objective

To investigate how the glucose variability between fasting and a 2-h postload glucose state (2-h postload plasma glucose [2hPG]-fasting plasma glucose [FPG]) is associated with chronic kidney disease (CKD) in middle-aged and elderly Chinese patients previously diagnosed with type 2 diabetes.

Design and Methods

This cross-sectional study included 1054 previously diagnosed type 2 diabetes patients who were 40 years of age and older. First, the subjects were divided into two groups based on a glycated hemoglobin (HbA1c) value of 7%. Each group was divided into two subgroups, with or without CKD. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the glomerular filtration rate (GFR). CKD was defined as eGFR<60 mL/min/1.73 m². Multiple linear regression analysis was used to estimate the association between the 2hPG-FPG and eGFR. The 2hPG-FPG value was divided into four groups increasing in increments of 36 mg/dl (2.0 mmol/L): 0–72, 72–108, 108–144 and ≥144 mg/dl, based on the quartiles of patients with HbA1c levels ≥7%; then, binary logistic regression analysis was used to investigate the association between 2hPG-FPG and the risk of CKD.

Results

In the patients with HbA1c levels ≥7%, the 2hPG-FPG was significantly associated with decreased eGFR and an increased risk of CKD independent of age, gender, body mass index (BMI), systolic blood pressure (BP), diastolic BP, smoking, and drinking, as well as fasting insulin, cholesterol, triglyceride, and HbA1c levels. The patients with 2hPG-FPG values ≥144 mg/dl showed an increased odds ratio (OR) of 2.640 (P = 0.033). Additionally, HbA1c was associated with an increased risk of CKD in patients with HbA1c values ≥7%.

Conclusions

The short-term glucose variability expressed by 2hPG-FPG is closely associated with decreased eGFR and an increased risk of CKD in patients with poor glycemic control (HbA1c≥7%).     

Dietary glycemic load and glycemic index and risk of coronary heart disease and stroke in Dutch men and women: the EPIC-MORGEN study

Background

The associations of glycemic load (GL) and glycemic index (GI) with the risk of cardiovascular diseases (CVD) are not well-established, particularly in men, and may be modified by gender.

Objective

To assess whether high dietary GL and GI increase the risk of CVD in men and women.

Methods

A large prospective cohort study (EPIC-MORGEN) was conducted within the general Dutch population among 8,855 men and 10,753 women, aged 21–64 years at baseline (1993–1997) and free of diabetes and CVD. Dietary intake was assessed with a validated food-frequency questionnaire and GI and GL were calculated using Foster-Powell''s international table of GI. Information on morbidity and mortality was obtained through linkage with national registries. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for incident coronary heart disease (CHD) and stroke, while adjusting for age, CVD risk factors, and dietary factors.

Results

During a mean follow-up of 11.9 years, 581 CHD cases and 120 stroke cases occurred among men, and 300 CHD cases and 109 stroke cases occurred among women. In men, GL was associated with an increased CHD risk (adjusted HR per SD increase, 1.17 [95% CI, 1.02–1.35]), while no significant association was found in women (1.09 [0.89–1.33]). GI was not associated with CHD risk in both genders, while it was associated with increased stroke risk in men (1.27 [1.02–1.58]) but not in women (0.96 [0.75–1.22]). Similarly, total carbohydrate intake and starch intake were associated with a higher CHD risk in men (1.23 [1.04–1.46]; and 1.24 [1.07–1.45]), but not in women.

Conclusion

Among men, high GL and GI, and high carbohydrate and starch intake, were associated with increased risk of CVD.     

Phagocytic activity is impaired in type 2 diabetes mellitus and increases after metabolic improvement

Objective

1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients present an impairment of phagocytic activity; 2) To determine whether the eventual impairment in phagocytic activity is related to glycemic control and can be reversed by improving blood glucose levels.

Methods

21 type 2 diabetic patients and 21 healthy volunteers were prospectively recruited for a case-control study. In addition, those patients in whom HbA1c was higher than 8% (n = 12) were hospitalized in order to complete a 5-day intensification treatment of blood glucose. Phagocytic activity was assessed by using a modified flow cytometry procedure developed in our laboratory based on DNA/RNA viable staining to discriminate erythrocytes and debris. This method is simple, highly sensitive and reproducible and it takes advantage of classic methods that are widely used in flow cytometry.

Results

Type 2 diabetic patients showed a lower percentage of activated macrophages in comparison with non-diabetic subjects (54.00±18.93 vs 68.53±12.77%; p = 0.006) Significant negative correlations between phagocytic activity and fasting glucose (r = −0.619, p = 0.004) and HbA1c (r = −0.506, p = 0.019) were detected. In addition, multiple linear regression analyses showed that either fasting plasma glucose or HbA1c were independently associated with phagocytic activity. Furthermore, in the subset of patients who underwent metabolic optimization a significant increase in phagocytic activity was observed (p = 0.029).

Conclusions

Glycemic control is related to phagocytic activity in type 2 diabetes. Our results suggest that improvement in phagocytic activity can be added to the beneficial effects of metabolic optimization.     

The Association between HbA1c,Fasting Glucose, 1-Hour Glucose and 2-Hour Glucose during an Oral Glucose Tolerance Test and Cardiovascular Disease in Individuals with Elevated Risk for Diabetes

Objective

To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes.

Design

We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study.

Setting

Follow-up of clinical trial.

Participants

504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c.

Main Outcome Measure

Relative risk of CVD.

Results

Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD.

Conclusions and Relevance

Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes.