Type 2 diabetes risk in persons with dysglycemia: the Framingham Offspring Study

Aims

Detection of risk of type 2 diabetes mellitus (T2DM) among adults with dysglycemia.

Methods

We used a nested case-cohort prospective design to estimate risk of new diabetes (diabetes treatment or FPG ≥7.0 mmol/L) among 1004 Framingham Heart Study Offspring with baseline dysglycemia [fasting plasma glucose (FPG) 5.4-6.9 mmol/L and/or 2-h post glucose load level 7.8-11.0 mmol/L]. Using clinical characteristics previously shown to predict incident T2DM, we used logistic regression to estimate odds ratios (OR), p-values for predictors, and assessment of model discrimination.

Results

At the end of 7 years follow-up there were 118 incident T2DM cases. In a model that included age, sex, elevated blood pressure or blood pressure treatment, lipid-lowering treatment and elevated triglycerides, we found the following additional characteristics to be independently associated with new T2DM: parental history of diabetes (OR 2.28, p = 0.004); excess adiposity (BMI ≥ 30 kg/m² or waist circumference ≥101.6 cm) (OR 2.04, p = 0.0005), and low HDL-C [<1.0 (men) or <1.3 mmol/L (women)] (OR 2.77, p < 0.0001). The multivariable C-statistic for this model was 0.701, and with glycemic category information included, c = 0.751.

Conclusions

The key non-glycemic traits that predicted later T2DM in adults with dysglycemia were parental history of diabetes, excess adiposity and low HDL-C.     

Retinal microvascular calibre and risk of incident diabetes: the multi-ethnic study of atherosclerosis

Aim

To prospectively examine the association of retinal microvascular signs with incident diabetes and impaired fasting glucose (IFG) in a multi-ethnic population-based cohort.

Methods

The multi-ethnic study of atherosclerosis comprised Caucasians, African-Americans, Hispanics and Chinese aged 45-84 years. Retinal vascular calibre and retinopathy were quantified from baseline retinal photographs. Incident diabetes and IFG were ascertained prospectively.

Results

After a median follow-up of 3 years, 243 (4.9%) people developed diabetes and 565 (15.0%) developed IFG. After adjusting for known risk factors, participants with wider retinal arteriolar calibre had a higher risk of developing diabetes [HR: 1.60; 95% CI: 1.12-2.29, p = 0.011 comparing highest with lowest arteriolar calibre tertile]. In ethnic subgroup analysis, the association between wider retinal arteriolar calibre and incident diabetes was stronger and statistically significant only in Caucasians [HR: 2.78; 95% CI: 1.37-5.62, p = 0.005]. Retinal venular calibre and retinopathy signs were not related to risk of diabetes or IFG.

Conclusion

Wider retinal arteriolar calibre is independently associated with an increased risk of diabetes, supporting a possible role for early arteriolar changes in diabetes development. This effect was largely seen in Caucasians, and not in other ethnic groups, and may reflect ethnic differences in susceptibility to diabetes from microvascular pathways.     

Changes in serum adiponectin concentrations and endothelial function after intensive insulin treatment in people with newly diagnosed type 2 diabetes: a pilot study

Aims

We aimed to assess changes in serum adiponectin and endothelial function after intensive insulin treatment in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Methods

Patients with newly diagnosed T2DM were randomly assigned to Group A (intensive insulin treatment) or Group B (conventional insulin treatment). Before treatment and 2 weeks after plasma glucose concentrations had been maintained at the specified concentrations, blood samples were obtained to measure serum adiponectin and nitric oxide (NO) concentrations. A total of 21 patients were randomized to each Group.

Results

Adiponectin, NO, endothelium-dependent vasodilation (EDD), and endothelium-independent vasodilation (EID) measures were significantly higher post-treatment than pre-treatment in Group A (all P < 0.05). Only EID was significantly higher in Group B (P < 0.05). Post-treatment adiponectin and NO concentrations, and EDD were significantly higher in Group A compared with Group B (all P < 0.05). Both treatment regimens were well tolerated (all patients completed the study). The most common adverse event was hypoglycemia. Thus, early intensive insulin therapy can increase serum adiponectin and NO concentrations and improve endothelial function in patients with newly diagnosed T2DM.

Conclusions

These effects may underlie the reduced incidence of microvascular and macrovascular in patients who receive early intensive hypoglycemic therapy.     

Serum visfatin is associated with type 2 diabetes mellitus independent of insulin resistance and obesity

Objective

The aim of this study was to evaluate the association of serum visfatin, adiponectin and leptin with 2 diabetes mellitus (T2DM) in the context of the role of obesity or insulin resistance, which is not well understood.

Methods

A total of 76 newly-diagnosed T2DM patients and 76 healthy control subjects, matched for age, body mass index (BMI) and sex ratio, were enrolled. Anthropometric parameters, glycemic and lipid profile, insulin resistance (measured by homeostasis model assessment of insulin resistance index [HOMA-IR]), leptin, adiponectin, and visfatin were assessed.

Results

On the contrary to adiponectin, serum leptin and visfatin levels were higher in T2DM patients compared with controls (10.07 ± 4.5, 15.87 ± 16.4, and 5.49 ± 2.4 vs. 12.22 ± 4.9 μg/ml, 8.5 ± 7.8 ng/ml and 3.58 ± 2.2 ng/ml, respectively, P < 0.01). Waist circumference and BMI were correlated with leptin and adiponectin but not with visfatin. Leptin, adiponectin and visfatin all were associated with T2DM following adjusting for obesity measures. After controlling for HOMA-IR, visfatin remained as an independent predictor of T2DM (odds ratio = 1.32, P < 0.05). In a multiple regression analysis to determine visfatin only triglycerides and fasting glucose remained in the model (P < 0.05).

Conclusion

Elevation of visfatin in T2DM is independent of obesity and insulin resistance and is mainly determined by fasting glucose and triglycerides.     

Effects of the long-acting human glucagon-like peptide-1 analog liraglutide on plasma omentin-1 levels in patients with type 2 diabetes mellitus

Objective

Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue, which increases insulin sensitivity in human adipocytes. However, its pathophysiologic role in humans remains largely unknown. The objective of this study is to assess plasma omentin-1 levels in patients with type 2 diabetes mellitus (T2DM) and matched control subjects and to investigate the effects of liraglutide on plasma omentin-1 levels in patients with T2DM.

Patients and methods

Thirty T2DM patients with poor glycemic control after more than 3 months of treatment with one or two OHA(s) (T2DM), and 30 matched normal glycaemic controls (NGT) participated in the study. The T2DM group was given an injection of liraglutide once-daily for 16 weeks. Plasma omentin-1 levels were measured by enzyme-linked immunosorbent assay and the relationship between plasma omentin-1 levels and metabolic parameters was also analyzed.

Results

Plasma omentin-1 levels were lower in T2DM than in the control (19.3 ± 4.0 μg/L vs. 26.4 ± 6.0 μg/L, P < 0.01). Plasma omentin-1 levels increased significantly in T2DM patients after treatment with liraglutide compared with pre-treatment (19.3 ± 4.0 μg/L vs. 21.2 ± 3.9 μg/L, P < 0.01). In all diabetic patients, multiple regression analysis showed that FINS and HOMA-IR were independently associated with plasma omentin-1 levels.

Conclusions

In T2DM patients, plasma omentin-1 levels decreased, but significantly increased after the treatment with liraglutide and metformin. These data suggest that liraglutide may play a role in increasing omentin-1 levels in T2DM patients.     

An elevated apolipoprotein B/AI ratio is independently associated with microalbuminuria in male subjects with impaired fasting glucose

Background and aims

The ratio of apolipoprotein B/AI (apo B/AI) has been used as a marker to predict the risk of coronary artery disease. Recent studies have suggested an association between apolipoprotein B level and microalbuminuria in diabetic subjects. This study was performed to assess a possible association between the apo B/AI ratio and microalbuminuria in male subjects with impaired fasting glucose (IFG).

Methods and results

In 1266 patients with fasting serum glucose level in the pre-diabetic range, urine albumin-to-creatinine ratio (UACR, μg mg⁻¹) was measured from single morning voided urine. The presence of microalbuminuria was defined as a UACR between 30 and 299 μg mg⁻¹. Participants were stratified into four groups by apo B/AI quartiles, from the lowest to the highest. Apo B/AI was higher with increasing body mass index, higher serum triglyceride and serum low-density lipoprotein cholesterol, systolic and diastolic blood pressure values, but lower with higher high-density lipoprotein cholesterol concentrations. After adjusting for these and other confounding factors, an increased apo B/AI ratio was independently associated with the presence of microalbuminuria. In receiver operating characteristic (ROC) curve analyses, apo B/AI ratio showed the highest correlation with the presence of microalbuminuria among the variables, although statistically not different.

Conclusion

These findings indicate that apo B/AI ratio shows significant association with microalbuminuria in Korean male subjects with IFG.     

Serum FGF21 levels are increased in newly diagnosed type 2 diabetes with nonalcoholic fatty liver disease and associated with hsCRP levels independently

Objective

Fibroblast growth factor (FGF21) has beneficial effects on lipolysis. Highly sensitive C-reactive protein (hs-CRP) is a predictor of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the levels of serum FGF21 and hs-CRP in newly diagnosed type 2 diabetes patients with and without NAFLD, and further explored the correlation between FGF21 with hs-CRP in newly diagnosed type 2 DM.

Research design and methods

69 patients with newly diagnosed type 2 DM and 30 normal subjects were included in the study. FGF21 and hs-CRP were measured by ELISA kits. The severity of NAFLD was measured by ultrasound.

Results

Serum FGF21 in newly diagnosed type 2 DM with NAFLD group were significantly increased (p < 0.01). There was no difference for the FGF21 level in normal control group and newly diagnosed type 2 DM without NFALD group. In type 2 DM group, the FGF21 level was positively correlated with hsCRP (r = 0.417, p < 0.001). In multiple stepwise regression models, only hsCRP was a significantly independent determinant for serum FGF21.

Conclusions

Serum levels of FGF21 are closely related to liver steatosis in newly diagnosed type 2 DM patients.     

Likelihood of obstructive coronary disease in metabolic syndrome patients with abnormal stress echocardiography

Background

Metabolic syndrome (MetSx) encompasses several risk factors for macrovascular coronary artery disease. An association between MetSx and coronary syndrome X has also been reported, suggesting that patients with MetSx are more likely to have endothelial dysfunction in the setting of angiographically normal coronary arteries. It remains unknown whether MetSx patients with abnormal stress echocardiography (SE) are more likely to have obstructive coronary disease (CAD) compared to patients without MetSx.

Methods

We identified symptomatic patients without known CAD and abnormal SE who underwent coronary angiography within 4 weeks after the SE. Patients were grouped according to their MetSx and impaired fasting glucose (IFG) status. We compared the proportion of patients with obstructive CAD in each subgroup using the x² test. Multivariate regression analysis was used to adjust for the pre-test probability of underlying coronary artery disease.

Results

Among 583 consecutive symptomatic patients who had an abnormal SE and were referred for angiography, 158 (36%) met the NCEP definition of MetSx. MetSx patients had a trend towards having more obstructive CAD than those without MetSx (OR 1.44, p = 0.07). After adjusting for pre-test probability of coronary disease, smoking and LDL-C, MetSx/IFG combination was an independent predictor of obstructive CAD (OR 2.06 [1.24-3.44], p < 0.001) but MetSx with normal fasting blood glucose was not (OR 0.91 [0.47-1.70], p 0.09).

Conclusion

Symptomatic patients with MetSx and IFG are more likely to have angiographically significant CAD after abnormal SE than patients without MetSx or those with normal fasting blood glucose.     

Short-term metabolic changes achieved by weight loss in hypertensive patients

Introduction

Glucose and lipid metabolism abnormalities of hypertensive patients are highly relevant due to its increase in cardiovascular risk; moreover, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have a high risk of new-onset diabetes mellitus (DM) development. The objective of the study was to describe glucose metabolism abnormalities and the impact of mid-term weight loss.

Methods

A six-month prospective, observational and multicentre study of patients with hypertension was conducted. Clinical antecedents, physical examination, blood test and treatments were collected in two separated visits; conventional advice was the only intervention planned.

Results

A total of 1957 patients were included, mean age 66.3 (10.9) years and 59.9% males. A previous diagnosis of glucose metabolism alteration was present in 43.9% (25.5% type-2 DM, 14.8% IFG, 1.6% IFG and IGT, 1.0% IGT and 1.0% type-1 DM). An increasing pattern of cardiovascular risk and target organ damage was observed according to the categories of fasting glucose. Oral glucose tolerance test (OGTT) was carried out in 234 patients (11.9%) patients and yielded the diagnosis of IGT in 44.7% or DM in 22.4% of patients with fasting glucose > 100 mg/dl. Six months follow-up was achieved in 85.9% patients. A slight reduction in fasting glucose was observed in the whole cohort and patients who achieved ≥ 5% weight loss experienced the highest reduction in fasting glucose, LDL-c and triglycerides; moreover, 15.8% normalized their IFG.

Conclusions

Glucose and lipid metabolism abnormalities are highly prevalent in hypertensive patients and improve with 5% of weight lost at 6 months follow-up. OGTT is not currently extended in daily clinical practise.     

Association of diabetes mellitus with myocardial collagen accumulation and relaxation impairment in patients with dilated cardiomyopathy

Aims

To assess the effects of diabetes mellitus (DM) on myocardial collagen accumulation, myocardial relaxation, and prognosis in patients with dilated cardiomyopathy (DCM).

Methods

A total of 102 consecutive DCM patients with a New York Heart Association functional class of I or II were enrolled. Patients were allocated to two groups on the basis of the presence (DCM + DM group, n = 30) or absence (DCM − DM group, n = 72) of DM. Cardiac catheterization performed and left ventricular pressure were measured in all patients. The pressure half-time (T_1/2) was determined as an index of myocardial relaxation function. Endomyocardial specimens were subjected to histological analysis.

Results

The T_1/2 was significantly longer (P < 0.001) and the collagen volume fraction was significantly greater (P = 0.018) in the DCM + DM group than in the DCM − DM group. Multivariate analysis showed that DM was significantly associated with increased incidence of cardiac events (hazard ratio, 3.7; 95% confidence interval, 1.05 to 13.16; P = 0.03).

Conclusions

The prognosis of DCM patients with DM was worse than that of those without DM. Impairment of myocardial relaxation, increased myocardial fibrosis, and mitochondrial degeneration associated with DM may underlie this difference.     

Microangiopathy is independently associated with presence, severity and composition of carotid atherosclerosis in type 2 diabetes

Background and aims

Common mechanisms for the development of micro- and macroangiopathic diabetic complications have been suggested. We aimed to cross-sectionally investigate strength and characteristics of the association between carotid atherosclerosis and microangiopathy in type 2 diabetic patients.

Methods and results

Common carotid artery intima-media thickness (cIMT), carotid plaque (CP) type and degree of stenosis were evaluated by ultrasound, along with the determination of anthropometric parameters, HbA1c, lipid profile, assessment of diabetic retinopathy and nephropathy, in 662 consecutive patients with type 2 diabetes mellitus (T2DM). Patients were divided according to high/low cIMT, presence/absence of CP and of retinopathy and nephropathy. Patients with CP were older, more prevalently males, past smokers, had longer diabetes duration, significantly lower HDL cholesterol and more prevalent ischemic heart disease (all p < 0.05) as compared to those with cIMT < 1 mm. Microangiopathies were more prevalent in patients with CP than in those without. At multivariate logistic regression, factors independently associated with the presence of CP were age, past smoke, HDL cholesterol, retinopathy and retinopathy plus nephropathy. A significant independent correlation of CP stenosis with stage of retinopathy and nephropathy was found. Finally, echolucent CPs were associated with a lower prevalence of proliferative retinopathy than CP containing calcium deposits.

Conclusion

In T2DM, retinopathy, alone or in combination with nephropathy, is independently associated to CP, and severity of microangiopathy correlates with severity of carotid atherosclerosis. These observations, together with the different prevalence of proliferative retinopathy according to CP types, point to possible common pathogenic mechanisms in micro- and macrovascular complications.     

Association between rs13266634 C/T polymorphisms of solute carrier family 30 member 8 (SLC30A8) and type 2 diabetes, impaired glucose tolerance, type 1 diabetes--a meta-analysis

Aims

To investigate the association of solute carrier family 30 member 8 (SLC30A8) rs13266634 C/T polymorphism with type 2 diabetes (T2DM), impaired glucose tolerance (IGT), and type 1 diabetes (T1DM).

Methods

We searched all the publications about the association between SLC30A8 and diabetes from PubMed, and evaluated the association between SLC30A8 rs13266634 C/T polymorphism and T2DM, IGT and T1DM, respectively, by meta-analysis of all the validated studies. Allelic and genotypic comparisons between cases and controls were evaluated.

Results

Thirty six studies were included in the meta-analysis: 31 studies were analysed for rs13266634 C/T polymorphism with T2DM, 3 studies with IGT and 4 studies with T1DM. The pooled odds ratios (ORs) for allelic and genotypic comparisons (including additive model, co-dominant model, dominant model and recessive model) showed that rs13266634 C/T polymorphism was significantly associated with increased T2DM risk: OR = 1.15, 95% confidence interval (CI) = 1.13-1.17, P < 0.001, P_{heterogeneity} = 0.041, OR = 1.34, 95% CI = 1.26-1.41, P < 0.001, P_{heterogeneity} = 0.908, OR = 1.20, 95% CI = 1.16-1.24, P < 0.001, P_{heterogeneity} = 0.699, and OR = 1.23, 95% CI = 1.17-1.30, P < 0.001, P_{heterogeneity} = 0.801, respectively. In subgroup analyses, we found that rs13266634 C/T polymorphism was associated with T2DM risk both in Asian and European subgroup (P < 0.001), but not in African (P > 0.05). And the pooled odds ratio (OR) for allelic frequency comparison showed that rs13266634 C/T polymorphism was also significantly associated with IGT: OR = 1.15, 95% CI = 1.06-1.26, P < 0.001, P_{heterogeneity} = 0.364. Meanwhile, our meta-analysis did not suggest that rs13266634 C/T polymorphism was associated with T1DM risk (P > 0.05): OR = 1.02, 95% CI = 0.98-1.06, P = 0.328, P_{heterogeneity} = 0.488 for allelic frequency comparison.

Conclusions

Our meta-analysis results revealed the significant association between rs13266634 C/T polymorphism and T2DM and IGT, but did not support the association between this polymorphism and T1DM.     

Hepcidin expression and iron parameters change in Type 2 diabetic patients

Aim

Iron may contribute to the pathogenesis of Type 2 diabetes mellitus (DM). The aim of this study was to determine iron regulator hepcidin and iron metabolic parameters in Type 2 DM patients, the relationships among them were evaluated in this specific sub-groups.

Materials and methods

The study included sixty-four people: 34 cases of diabetes and 30 age-matched controls. Serum hepcidin, IL-6, hsCRP, ferritin, sTfR, EPO as well as other clinical parameters were detected, and the associations between hepcidin levels and iron/inflammatory parameters were analyzed in diabetes and the controls.

Results

Serum ferritin and hepcidin levels in diabetic patients were significant higher than the controls (p < 0.001 respectively). A positive correlation between hepcidin and ferritin, as well as between ferritin and IL-6 levels was existed in diabetes and the control groups (p < 0.001 respectively).

Conclusion

All of these data demonstrated that the higher hepcidin levels in diabetic patients may be due to those higher ferritin and IL-6 levels, the elevated hepcidin might have adaptive value through down-regulated iron absorb and play an important role in pathogenesis of Type 2 DM.     

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.     

Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease

Aims

Patients with diabetes mellitus (DM) are prone to atherosclerosis. Atherosclerosis activates platelets; activated platelets release serotonin, and therefore, evaluation of serotonin levels in blood could be a valuable biomarker for future risk of cardiovascular events.

Methods

Plasma serotonin levels obtained from patients with DM complicated with chronic kidney disease were measured using HPLC and were compared to serotonin levels of healthy control subjects. Patients with DM were classified into 2 subgroups of mildly (group 1) and moderately/severely (group 2) impaired renal function.

Results

Serotonin concentration in platelet-poor plasma for group 1 was significantly higher than that of healthy control subjects (p < 0.01), and was significantly higher than that of patients from group 2 (p < 0.05). The concentration of serotonin in whole blood for group 2 patients was significantly lower than that measured from healthy control subjects (p < 0.01). The ratio of the plasma to whole blood level was significantly elevated in both groups 1 and 2 compared with healthy controls (p < 0.01).

Conclusions

Our results indicate that platelets are activated to release serotonin into plasma in diabetic patients with mildly impaired renal function. When renal damage is advanced, platelets are over-activated to release serotonin.     

Contrasting cardiovascular risk profiles and prescribed cardio-protective therapies in newly-diagnosed type 2 diabetes identified through screening and standard practice

Aims

Screening for Type 2 diabetes mellitus (T2DM) may improve long-term outcomes by managing cardiovascular risk at an earlier stage of the disease. The cardiovascular risk profile of screen-detected (SD) T2DM is ill defined and has not been compared to conventional newly diagnosed (CD) cases.

Methods

Baseline data from SD (n = 337) and CD (n = 824) cohorts were compared. SD adopted mixed approaches to screening, population based (n = 214) and cardiovascular-risk factor targeted (n = 123). CD reflected UK primary care practice with cases referred within four weeks of diagnosis.

Results

People with SD T2DM were leaner, had a lower HbA1c(%) and lower triglyceride but were more hypertensive compared to people with CD T2DM. Fewer SD were on blood pressure lowering (46% vs. 60%, p < 0.0001), statin (30% vs. 41%, p < 0.0001) or anti-platelet (15% vs. 27%, p < 0.0001) therapies. Modelled 10 year cardiovascular disease (CVD) risk was actually greater in the SD group compared to CD (CVD: 20.8 vs. 17.2, p = 0.0001).

Conclusion

Individuals with SD T2DM are at high risk of CVD as a result of untreated hyperglycaemia, hypertension and dyslipidaemia. Those prescribed antihypertensive or lipid-lowering therapies frequently still had inadequate control. Identifying vascular risk by screening for latent glucose disease provides therapeutic opportunities for earlier intervention.     

Relative utility of 1-h Oral Glucose Tolerance Test as a measure of abnormal glucose homeostasis

Background and aims

Impaired glucose tolerance based on 2-h glucose levels is more predictive of future cardiovascular disease and more sensitive in detecting earlier diabetes compared to impaired fasting glucose. However, the 1-h OGTT may be even more sensitive than the 2-h. We assessed the relative value of 1-h OGTT by exploring its relationship with adiposity and other measures of glucose homeostasis.

Methods and results

Ninety four overweight/obese individuals free of diabetes and major cardiovascular conditions were included in the analyses. We adjusted for age, gender, smoking status and physical activity. One-h OGTT showed similar partial correlations with fasting glucose and 2-h OGTT (r = 0.60 and 0.64 respectively). Fasting glucose, fasting insulin and HOMA correlated better with 1-h OGTT (r = 0.60, 0.47 and 0.52) than with 2-h OGTT (r = 0.50, 0.41, and 0.45). BMI and waist circumference also showed stronger correlation with 1-h (r = 0.31, 0.29), compared to 2-h OGTT (r = 0.16, 0.16) or fasting glucose (r = 0.23, 0.22). Metabolic syndrome was associated similarly with 1-h and 2-h OGTT.

Conclusions

The 1-h OGTT correlates well with both fasting glucose and 2-h OGTT and shows similar or higher associations with obesity measures. The 1-h OGTT has potential utility in epidemiologic studies.     

Impairment of insulin action in non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients

Aims

To investigate first-phase insulin release and peripheral insulin sensitivity of non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients.

Methods

12 euglycemic first-degree relatives of type 2 diabetic patients (ERDM), 12 newly diagnosed type 2 diabetic patients (DM-2) and 12 healthy individuals (control) participated in the study. All subjects were non-obese (BMI < 25 kg/m²). Intravenous glucose tolerance test and euglycemic hyperinsulinemic clamp test were performed to evaluate first-phase insulin release and quantify insulin sensitivity, respectively.

Results

The first-phase insulin release did not differ between the ERDM and control subjects (p = 0.532), while the acute insulin response was absent in the DM-2 patients (p = 0.001). Peripheral glucose deposit rate (GDR) was significantly lower in the ERDM (10.6 ± 2.1 mg/kg·min, p = 0.000) and DM-2 (9.6 ± 1.1 mg/kg·min, p = 0.000) groups than that in the control group (13.2 ± 1.2 mg/kg·min). There was no statistical difference in GDR between the ERDM and DM-2 groups (p = 0.110). Fasting FFA levels of the ERDM (p = 0.007) and DM-2 (p = 0.000) subjects were significantly higher than those of the controls.

Conclusions

Non-obese, first-degree relatives of type 2 diabetic patients with normal glucose tolerance (NGT) exhibit remarkable impairment of insulin sensitivity and increased FFA levels. Insulin resistance is independent of obesity and blood glucose level. Progression from NGT to type 2 diabetes may mainly be attributed to deterioration of early insulin secretion.     

Potential celiac disease in type 1 diabetes: a multicenter study

Aims

To describe the prevalence of potential celiac disease (pot-CD) in young patients with type 1 diabetes mellitus (T1DM) and characterize their clinical features.

Methods

This cross-sectional multicenter study involved 8717 T1DM patients from 31 Italian centers. Information was collected on the total number of T1DM patients, CD patients and pot-CD patients. The following data were collected on pot-CD patients: gender, age at T1DM diagnosis, age at the first CD serological positivity, presence of CD-related symptoms, presence of other autoimmune disorders and treatment with gluten free diet (GFD). One thousand-three-hundred-sixty-one patients who were positive for CD serology were the control group.

Results

CD serological positivity was found in 7.2% T1DM patients. Prevalence of pot-CD was 12.2% (n = 77) among CD positive patients: symptoms were present in 12/77; a third autoimmune disorder was found in 15 patients. Prevalence of pot-CD in the control population was 8.4% (n = 114; p = 0.005). No difference was found with regard to clinical features. Only few symptomatic patients were on GFD both in T1DM and control patients.

Conclusions

A higher prevalence of pot-CD was found in T1DM patients, that may be ascribed to the routine screening, although the influence of genetic factors cannot be excluded.     

Efficacy and safety of saxagliptin added to metformin in Asian people with type 2 diabetes mellitus: a randomized controlled trial

Aim

To assess efficacy and safety of saxagliptin added to metformin versus placebo plus metformin in Asian patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin alone.

Methods

Adults (HbA_1c 7.0-10.0%, on stable metformin ≥1500 mg/day) were randomized 1:1 to saxagliptin 5 mg daily plus metformin (n = 283) or placebo plus metformin (n = 287). The primary end point was HbA_1c change from baseline to Week 24.

Results

Saxagliptin plus metformin provided significant adjusted mean decreases versus placebo plus metformin (p ≤ 0.0052) in HbA_1c (−0.78% versus −0.37%), fasting plasma glucose (−1.14 mmol/L versus −0.58 mmol/L), and postprandial glucose area under the curve from 0 to 180 min (−315 mmol min/L versus −160 mmol min/L). Significantly more saxagliptin-treated patients achieved a therapeutic glycemic response (HbA_1c < 7.0%) (46.5% versus 30.5%; p = 0.0001). The proportion of patients experiencing adverse events (excluding hypoglycemia) was similar for saxagliptin plus metformin (42.8%) versus placebo plus metformin (40.8%). Hypoglycemic events were reported in 1.4% of patients in each group.

Conclusion

Saxagliptin added to metformin significantly improved glycemic control and was well tolerated in Asian patients with T2DM who had inadequate glycemic control with metformin and diet and lifestyle modification.