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.     

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.     

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.     

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.     

Contribution of glimepiride to basal-prandial insulin therapy in patients with type 2 diabetes

Aim

To investigate the efficacy of continuing glimepiride in combination with basal-prandial insulin therapy in type 2 diabetes.

Methods

An open crossover study was performed with arms of discontinuation and continuation of glimepiride in 25 subjects with mean diabetes duration of 17 years and 5 years of insulin treatment combined with glimepiride plus metformin. At entry and at the end of each 3-month arm, meal tolerance tests were performed for measurements of blood glucose and C-peptide.

Results

In terms of between-treatment differences (discontinuation vs. continuation arm of glimepiride) during meal tolerance tests performed at the ends of arms, significant increases in plasma glucose were seen on the discontinuation arm at 0-, 30-, and 60-min, while significant decreases in serum C-peptide were observed at 60- and 120-min. A1C values of the discontinuation arm significantly increased (from 6.6 ± 0.6 at baseline to 7.7 ± 0.8 at 3-months, p < 0.0001). Increases in A1C were closely correlated with decreases in area under the curve of meal-stimulated serum C-peptide (r = −0.61, p < 0.0001).

Conclusions

Since endogenous insulin secretion is more physiological than subcutaneous insulin injection, continuing glimepiride may remain beneficial, partly through enhancing insulin secretion, in individuals with a long duration of diabetes and basal-prandial insulin therapy.     

Association of VKORC1 −1639 G > A polymorphism with carotid intima-media thickness in type 2 diabetes mellitus

Aims

Media calcification is a predictor of cardiovascular mortality in type 2 diabetes mellitus (T2DM). Undercarboxylation of some vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1, can lead to calcification. We examined a potential association between VKORC1 −1639 G > A polymorphism and T2DM and, also, the association of this polymorphism with carotid intima-media thickness (cIMT).

Methods

VKORC1 −1639 G > A polymorphism was determined in 299 T2DM patients and 328 controls of Caucasian origin using PCR-RFLP. cIMT was measured in a subgroup of 118 T2DM patients.

Results

The frequency of VKORC1 genotypes between diabetic and nondiabetic subjects differed significantly (p = 0.01). VKORC1 genotype was associated with T2DM in an adjusted model (OR 1.36, p = 0.009). A statistically significant difference was observed in the maximum value of cIMT among different genotypes. VKORC1 −1639 G > A polymorphism was an independent predictor of cIMT (p = 0.029) after adjusting for established risk factors.

Conclusions

The association between VKORC1 −1639 G > A polymorphism and risk of T2DM could be due to the higher prevalence of calcification in T2DM patients. This is supported by the independent association between VKORC1 −1639 G > A polymorphism and maximum cIMT in T2DM patients which is likely due to atherosclerosis characterized by increased calcification.     

Educational attainment moderates the effect of a brief diabetes self-care intervention

Aims

Those with less education are at increased risk for developing diabetes and have a poorer prognosis. Intensive diabetes self-care interventions have been more effective at improving glycemic control in those with lower educational attainment. Due to limited resources, the focus has shifted to brief, cost-effective health interventions. This study examined whether educational attainment moderates the effect of a brief, telephone delivered self-care intervention on glycemic control in people with type 2 diabetes.

Methods

Randomized clinical trial. Participants (N = 62) were assigned to receive treatment as usual or treatment as usual plus a brief telephone intervention. The primary outcome measure was hemoglobin A1c.

Results

A significant education by intervention group interaction effect indicated that participants with higher educational attainment had greater improvement in glycemic control (A1c) than those with less educational attainment; whereas, educational attainment was unrelated to change in glycemic control (A1c) within the control group.

Conclusions

People with higher educational attainment may benefit to a greater extent from brief self-care interventions for diabetes, while those with lower educational attainment may require more intensive treatment.     

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.     

Risk factor associations with clinical distal symmetrical polyneuropathy and various neuropathy screening instruments and protocols in type 1 diabetes

Objective

To determine whether DSP and neuropathy-assessment instruments used by non-physicians have similar risk factors.

Research design and methods

Analyses were cross-sectional (n = 176).

Results

Risk factors were similar for DSP and screening devices.

Conclusions

These data support the clinical utility of neuropathy screening devices used by non-physician personnel.     

Effect of pharmacist intervention on glycemic control in diabetes

Aim

To conduct a meta-analysis evaluating the effect of pharmacist intervention on glycemic control.

Methods

A systematic search of Medline and CENTRAL was conducted from the earliest possible date through June 2010. Trials were included if they were randomized controlled trials in a diabetic population, evaluated any form of pharmacist intervention and reported data on hemoglobin A1C (A1C). A random-effects model was used to calculate weighted mean differences (WMDs) and 95% confidence intervals.

Results

Fourteen trials (n = 2073) evaluating the effect of pharmacist intervention on glycemic control were identified. Pharmacist intervention significantly lowered A1C (n = 14 trials, WMD −0.76%, 95%CI −1.06 to −0.47) and fasting blood glucose (FBG) (n = 4 trials, WMD −29.32 mg/dL, 95%CI −39.54 to −19.10). A moderate to high degree of statistical heterogeneity was observed in these analyses (I² ≥ 44.1% for both).

Conclusions

Our findings demonstrate statistically and clinically significant associations between pharmacist intervention and improvement in glycemic control.     

The achievement of target cholesterol level differs between coronary heart disease and diabetic patients

Background

Guidelines recommend that LDL-C level should be < 100 mg/dl among diabetes mellitus (DM) and coronary heart disease (CHD) patients.

Objective

To evaluate how patients with DM and CHD differ in attaining the target level and to examine the association between goal achievement, demographic and clinical parameters.

Methods

The study was conducted in Maccabi Healthcare Services, the second largest health maintenance organization in Israel. All patients with DM (n = 54,261), CHD (n = 24,083) or DM and CHD (n = 15,370) who were listed in the computerized database and had at least one LDL-C level measurement between January 1, 2007 and July 15, 2008 were eligible. The percentage of patients who attained LDL-C level < 100 mg/dl and its association with demographic and clinical parameters were analyzed.

Results

The rate of reaching the LDL-C target level was higher among the CHD and CHD and DM patients than DM ones (67% vs. 57% vs. 50%, p < 0.001, respectively). Male gender; 5th socioeconomic status quintile; underlying disease i.e. CHD, CHD and DM; high statins compliance; and revascularization by percutaneous coronary intervention predicted for reaching target level. DM; absence of renal function evaluation; hospitalizations; HbA1C > 7% or missing its measurements had a negative predictive value.

Conclusions

The rate of reaching LDL-C target level should be increased in all high risk patients, mainly diabetic ones. Efforts should include educational programs to physicians and patients regarding the importance, the need to adhere and to intensify the cholesterol lowering treatment.     

Type 2 diabetes and universal health care for low-income groups: a case-control study

Purpose

In 2007 in France, type 2 diabetes involved 2.5 million people, and 4.5 million patients received free healthcare coverage under the universal healthcare coverage program (CMU) for low-income households. An optimal glycemic control and adequate diabetes monitoring can reduce the incidence of complications. The objective of this study was to compare the diabetes care of low-income patients (as defined by CMU coverage) with the rest of the population.

Methods

A retrospective case-control study (non-CMU and CMU) over a one-year period of glycemic control for both populations through private laboratory data (number and values of HbA1c) and of individuals monitoring through data from the regional health insurance public institute.

Results

Regarding glycemic control, 154 patients were included. The number of annual HbA1c tests was similar between CMU and non-CMU patients. The mean HbA1c value was higher for CMU patients (8.7% versus 8%; P < 0.01). Regarding monitoring, 1254 patients were included. Over a one-year period, the number of HbA1c tests, lipid profile tests, serum creatinine measures and cardiology consultations were similar across groups. However, CMU patients benefited from less microalbuminuria testing (P < 0.001), ophthalmologic monitoring visits (P < 0.01), endocrinology consultations (P < 0.01), and from more general physician consultations (P < 0.001).

Conclusions

Receiving CMU health coverage was associated with a poorer glycemic control and lesser specialized monitoring than that was observed in control patients. Across the population, follow-up recommendations are far from being implemented satisfactorily.     

Predictors of microvascular complications in type 1 diabetic patients at onset: the role of metabolic memory

Background

Several epidemiological studies showed a close association between metabolic control and microvascular complications in type 1 Diabetes Mellitus (T1DM). The aim of our longitudinal observational study was to evaluate the predictive role of the main clinical and biochemical parameters in determining microvascular complications.

Methods

376 T1DM patients, hospitalized in our division from 1991 to 2005 (mean follow-up = 10.93 ± 4.26 years) were studied. Stepwise Cox regression analysis was used to identify the influence of residual ß-cell function, ß-cell autoimmunity, HbA1c levels and other clinical and laboratory parameters in the development of microalbuminuria and retinopathy.

Results

The probability of developing microalbuminuria was higher in males than in females (HR 1.82; 95% CI 1.01-3.28; p = 0.044), in patients with higher mean HbA1c values (HR 2.80; 95% CI 1.63-4.83; p < 0.001), longer duration of disease (HR 1.98; 95% CI 1.10-3.57; p = 0.022) and younger age of diabetes onset (HR 0.53; 95% CI 0.03-0.92; p = 0.026). An increased probability of developing retinopathy was found in patients with higher mean HbA1c levels during follow-up (HR 2.35; 95% CI 1.34-4.12, p = 0.003), as well as at onset (HR 1.85; 95% CI 1.06-3.24; p = 0.030).

Conclusions

Our study suggests that among the clinical, metabolic, immunological and biochemical factors evaluated at onset, only HbA1c is predictive for the microangiopathy development in T1DM.     

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.     

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.     

Key elements for successful intensive insulin pump therapy in individuals with type 1 diabetes

Objective

Clinical trials have demonstrated that in individuals with type 1 diabetes the use of CSII pump resulted in better glucose control. Advantages of pumps therapy include many features such as the bolus calculators (wizard). These features are optional and therefore it is important to determine whether their use is associated with better glucose control. Thus, the aim of this analysis was to assess which features and parameters of insulin pump use are associated with better glucose control.

Methods

Data regarding consecutive patients with type 1 diabetes treated with an insulin pump and attending a tertiary referral for intensive glucose control was included in this analysis. The relationship between glycemic indices and treatment parameters (number of insulin units, number of glucose readings, bolus calculator use etc.) was assessed.

Results

A statistically significant relationship was found between glycemic indices and wizard use. Thus, individuals that used the wizard function in 50% of their boluses had an A1C, mean blood glucose values that were 0.6% (p = 0.008) and 25 mg/dL (p = 0.000) lower respectively.

Conclusion

The use of the bolus calculator feature was associated with better glucose control. Larger prospective clinical trials are needed in order to further validate this finding.     

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.     

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.     

Psychological screening in adolescents with type 1 diabetes predicts outcomes one year later

Aims

Adolescents with type 1 diabetes are at increased risk for depression and anxiety, which can adversely affect diabetes management, glycemic control, and quality of life (QOL). However, systematic psychological screening is rarely employed. We hypothesized that higher depression and anxiety screener scores would predict higher HbA1c, less frequent blood glucose monitoring (BGM), and poorer QOL one year later. Raw screener scores were expected to be more robust predictors than cutoff scores.

Methods

150 adolescents age 13-18 with type 1 diabetes completed depression and anxiety screeners. One year later, blood glucose meters were downloaded to assess BGM frequency, HbA1c values were obtained, and caregivers rated the participants’ QOL. Separate regressions were conducted for each outcome, including demographic and medical covariates.

Results

Higher depression scores predicted less frequent BGM (b = −0.05, p < .05) and poorer QOL (b = −0.71, p < .01), and higher state anxiety scores predicted higher HbA1c (b = 0.07, p < .05). Continuous screener scores identified risk for 12-month outcomes more robustly than clinical cut-off scores.

Conclusions

Psychological screeners predict diabetes outcomes one year later. Future clinical research studies should explore whether psychological screening and referral for appropriate intervention can prevent deteriorations in diabetes management and control commonly seen during adolescence.     

Level of serum IL-12 and its correlation with endothelial dysfunction, insulin resistance, proinflammatory cytokines and lipid profile in newly diagnosed type 2 diabetes

Aim

This study was an attempt to evaluate and correlate serum interleukin-12 (IL-12) with different circulating markers in newly diagnosed type-2 diabetes mellitus (T2DM) for possible progression of atherosclerosis.

Methods

For this study, we recruited 1968 family members of diabetics and 349 had abnormal glucose. Out of 349 subjects, 197 were T2DM as per American Diabetes Association guidelines and further investigated for cardiovascular abnormalities. 63 T2DM have high sensitive C-reactive protein (hsCRP) > 3.0 mg/l and cardiovascular complications. Overall, 150 subjects, 50 healthy, 50 T2DM (D1) and 50 T2DM with cardiovascular complications (D2) were enrolled and investigated for soluble markers.

Results

The levels of serum glucose, proinflammatory cytokines (IL-6, IL-12, tumor necrosis factor), endothelial dysfunction markers [vascular cell adhesion molecule-1 (VCAM-1), inter-cellular adhesion molecule-1 (ICAM-1), nitric oxide] and lipid abnormality were highest in D2 group. Correlation and regression study showed that IL-12 was dependent on hsCRP, insulin resistance, VCAM-1, ICAM-1 and lipids. The multivariate stepwise regression analysis demonstrates that hsCRP contributes significantly for variance of IL-12.

Conclusion

This study reveals that, even first-time diagnosis of T2DM, subjects with higher insulin resistance and abnormal lipids have elevated IL-12, endothelial dysfunction and proinflammatory markers. Further increased hsCRP enhance IL-12 which up-regulate cardiovascular disease progression.