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.     

Role of omentin 1 and IL-6 in type 2 diabetes mellitus patients with diabetic nephropathy

Aims

Diabetic nephropathy (DN) is one of the major chronic vascular complication of T2DM and leading cause of end-stage renal disease. Inflammation is one of the proposed pathway which explains microvascular complications in T2DM but exact mechanism is still unclear. Omentin-1 is an anti-in?ammatory adipokine which promotes insulin signaling. IL-6 is a multifunctional cytokine having role in immune and inflammatory responses. The present study was conducted to elucidate the role of omentin-1 and IL-6 in the pathogenesis of DN and its association with insulin resistance. We aimed to assess and compare the serum levels of omentin-1 and IL-6 in T2DM patients with and without DN.

Physical activity energy expenditure is associated with 2-h insulin independently of obesity among Inuit in Greenland

Aims

Indigenous populations throughout the Arctic are experiencing a rapid increase in the prevalence of obesity and type 2 diabetes. The role of physical activity in relation to glucose metabolism in Arctic populations is not well studied. We examined the association between objectively measured physical activity energy expenditure (PAEE) and glucose metabolism in a population-based study of adult Inuit in Greenland.

Methods

Cross-sectional data were collected by combined accelerometry and heart rate monitoring (ACC + HR) among Inuit (18+ years) in Greenland during 2005–2010 (n = 1545). PAEE was calculated and the associations with fasting glucose, 2-h glucose, fasting insulin, 2-h insulin concentrations and body composition were analysed by linear regression.

Results

An inverse association between PAEE and fasting insulin, 2-h insulin, 2-h glucose, fat percentage, BMI and waist circumference (WC) was found after adjustments by age and sex. Only the association between PAEE and 2-h insulin remained significant after adjustment by WC (P = 0.01), most pronounced at low levels of PAEE indicating a threshold around 35–40 kJ/kg/day. No overall linear trend was found for fasting glucose and 2-h glucose.

Conclusions

This population-based study showed that PAEE was associated with 2-h insulin independently of obesity in an inverse dose-response relation. Insufficient physical activity may contribute to impaired glucose tolerance through a pathway including alterations in obesity and fat distribution. Both obesity and low levels of PAEE may be important contributing risk factors for the increasing prevalence of type 2 diabetes mellitus among Inuit in Greenland, but additional risk factors should be examined in this indigenous population.     

Assessment of adiponectin and its isoforms in Polish centenarians

Background

The physiological mechanisms that promote longevity remain unclear. It has been suggested that insulin sensitivity is preserved in centenarians, whereas typical aging is accompanied by increasing insulin resistance. The oldest-old individuals display raised total adiponectin levels, despite the potential correlation between enhanced adiponectin and all-cause and cardiovascular mortality.

Aim

To evaluate the level of adiponectin and its isoforms in sera of centenarians and to assess associations between adiponectin and metabolic parameters.

Participants

A group of 58 Polish centenarians (50 women and 8 men, mean age 101 ± 1.34 years) and 68 elderly persons (55 women and 13 men, mean age 70 ± 5.69 years) as controls.

Measurements

Serum samples were analyzed to evaluate the following parameters: adiponectin array (total adiponectin, HWM-, MMW- and LMW-adiponectin; all by ELISA methods), insulin (by IRMA methods), glucose and lipid profiles. HOMA-IR was calculated. Clinical data were collected. Statistical analyses were performed.

Results

The concentrations of all adiponectin isoforms were significantly higher in the oldest-old participants. In the centenarian group, total adiponectin positively correlated with age and HDL-cholesterol, and HMW-adiponectin was negatively associated with insulin and triglycerides. The long-lived participants had a lower incidence of hypertension, type 2 diabetes, overweight and obesity, with lower concentrations of serum glucose and insulin, and reduced HOMA-IR.

Conclusion

Our findings support the thesis that centenarians possess a different adiponectin isoform pattern and have a favorable metabolic phenotype in comparison with elderly individuals. However, additional work is necessary to understand the relevance of these findings to longevity.     

Effect of folic acid supplementation on biochemical indices in overweight and obese men with type 2 diabetes

Aims

This study performed to determine the effects of folate supplementation on indices of glycemic control, insulin resistance and lipid profile in overweight and obese men with type 2 diabetes under metformin (at least 1500 mg daily) treatment.

Methods

The study was a double-blind randomized controlled clinical trial. Forty-eight overweight and obese men (aged 58.2 ± 8.9 years; BMI = 28.6 ± 2.9 kg/m²) with type 2 diabetes participated in the study. Patients were divided randomly into two groups of folic acid (5 mg/d) and placebo. All patients received the tablets for eight weeks.

Results

Supplementation with folic acid led to 8% decrease in HbA1C (p = 0.048), 7.5% in fasting blood glucose (p = 0.051), 16.2% in serum insulin (p = 0.021), 20.5% in insulin resistance (p = 0.041) and 21.2% in plasma homocysteine (p = 0.000). A significant increase in serum folate and B12 levels (19% and 17.3%, p = 0.000, respectively) were observed in the folic acid group, whereas no significant changes occurred in the placebo group. Also, in the folic acid and placebo groups, there were no significant changes in body weight.

Conclusions

Folic acid supplementation lowered plasma level of homocysteine, improved glycemic control and insulin resistance in patients with type 2 diabetes.     

Insulin detemir in the management of type 2 diabetes in non-Western countries: Safety and effectiveness data from the A1chieve observational study

Aims

This subgroup analysis of the A₁chieve study examined data from 15,545 people who started treatment with insulin detemir ± oral glucose-lowering drugs in routine clinical care.

Methods

A₁chieve was a 24-week, international, prospective, non-interventional study of people with type 2 diabetes from non-Western nations starting treatment with basal insulin detemir, bolus insulin aspart or biphasic insulin aspart 30, alone or in combination, to evaluate their safety and effectiveness in routine clinical practice.

Results

HbA_1c for the global cohort improved after 24 weeks from 9.5 ± 1.6% by −2.0 ± 1.6% [80 ± 17 by −22 ± 17 mmol/mol] (−2.1 ± 1.6% [−23 ± 17 mmol/mol] for insulin-naïve participants; −1.6 ± 1.7% [−17 ± 19 mmol/mol] for prior insulin users). Fasting plasma glucose and postprandial plasma glucose were also significantly reduced (p < 0.001), irrespective of prior therapy or geographical region. The incidence of major hypoglycaemia decreased significantly over 24 weeks in both the insulin-naïve and insulin-experienced groups (p < 0.0001). Mean body weight decreased overall by −0.4 ± 4.0 kg and blood pressure, lipid profiles, and self-reported quality of life improved over 24 weeks for all people starting treatment with insulin detemir.

Conclusion

People with type 2 diabetes in poor glycaemic control starting treatment with insulin detemir reported significant improvements in glycaemic control with improved treatment tolerability, irrespective of prior treatment and geographical region, after 24 weeks.     

Prevalence of insulin resistance and cardiometabolic risk in Korean children and adolescents: A population-based study

Aims

We aimed to establish normal reference values of serum insulin and the homeostasis model assessment of insulin resistance (HOMA-IR). We also aimed to verify HOMA-IR “cut-off values” in predicting cardiometabolic risk among Korean children and adolescents.

Methods

Data from 2716 Korean subjects (1421 male and 1295 female, aged 10–20 years) were evaluated. Insulin resistance was defined as HOMA-IR >95th percentile. The odds ratios of cardiometabolic risk were assessed based on the state of insulin resistance.

Results

Reference values of insulin and HOMA-IR were determined according to sex and age, based on data obtained from normal-weight subjects with normal fasting glucose levels. HOMA-IR values appeared to peak at the age of 14–15 years in male subjects and at the age of 12–13 years in female subjects. The prevalence of insulin resistance in the subjects was 9.8% (male = 10.9%, female = 8.6%). The prevalence of insulin resistance in normal-weight, overweight, and obese subjects were 4.7%, 25.6%, and 47.1% respectively. Subjects with insulin resistance had a higher prevalence of metabolic syndrome (odds ratios = 18.33; 95% confidence interval, 9.62–34.94) and its components, especially hyperglycemia and hypertriglyceridemia.

Conclusion

We established reference values of serum insulin and HOMA-IR according to age and sex. Obesity is the most important risk factor for insulin resistance and metabolic syndrome. However, insulin resistance independently increases cardiometabolic risk. This information may be useful for Korean as well as other Asian in planning programs for the prevention of type 2 diabetes.     

The impact of insulin type on severe hypoglycaemia events requiring inpatient and emergency department care in patients with type 2 diabetes

Aims

To evaluate the risk from different insulin types on severe hypoglycaemia (SHG) events requiring inpatient (IP) or emergency department (ED) care in patients with type 2 diabetes.

Methods

Type 2 diabetes patients newly started on insulin in a large commercial claims database were evaluated for SHG events. Patients were classified into an insulin group based on their most frequently used insulin type. Multivariable Cox models assessed the association between insulin type and the risk of SHG events.

Results

We identified 8626 patients (mean age 53.5 years; 55% female) with type 2 diabetes followed for an average of 4.0 years after insulin initiation. Of these, 161 (1.9%) had a SHG event at an average of 3.1y after insulin initiation. Patients with SHG events were slightly older (56.4 vs. 53.4 years), used a similar number of OADs (1.1 vs. 1.2) but had more co-morbidities compared with those without SHG events. In multivariate Cox models, premixed insulin (HR 2.12; p < 0.01), isophane insulin (NPH) (HR 2.02; p < 0.01), and rapid acting insulin (HR 2.75; p < 0.01) had significantly higher risks of SHG events compared with glargine. No statistically significant difference in SHG events was seen with detemir (HR 1.20; p = 0.73).

Conclusions

Among patients with type 2 diabetes, the use of newer basal insulin analogues was associated with lower rates of SHG events requiring IP or ED care compared with users of other insulin formulations. Future research should examine the impact of hypoglycaemia events of different severity levels.     

Evidence of male hypogonadism at an early age as a familial risk of type 2 diabetes

Objective

Previous investigations provide evidence of an association of hypogonadism with type 2 diabetes in men, and low testosterone levels have been regarded a risk factor for the disease. Since a strong genetic predisposition to type 2 diabetes has been demonstrated, here we investigate a possible tendency towards hypogonadism in young male offspring of diabetic parents.

Material and methods

The study compares 32 male offspring of diabetic parents with 31 male offspring of nondiabetic parents matched by age. The subjects comprised boys (9–17 years) and young adults (19–25 years). Anthropomorphic measurements were made in all subjects. Fasting blood samples were analyzed for glucose and serum concentrations of testosterone (T), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), insulin and leptin were measured by ELISA. Free testosterone (FT) was calculated using T and SHBG levels.

Results

Serum T, FT and bioavailable T (BAT) levels in offspring of diabetic parents were significantly lower than those of offspring of nondiabetic parents across all age groups. Mean serum LH levels were also lower in offspring of diabetic parents compared to the controls. Although LH levels in young adults with diabetic parents, tended to be lower than those of age-matched controls but the difference was not statistically significant. Serum insulin and leptin, and insulin resistance measured by HOMA-IR were significantly raised in older offspring of diabetic parents but were within the normal range.

Conclusion

Whereas hypogonadism was the only indicator of a possible predisposition to metabolic dysfunction in peripubertal children of diabetic parents, a significant change in other metabolic markers becomes apparent at a more advanced age.     

Poorer glycaemic control in type 1 diabetes is associated with reduced self-management and poorer perceived health: A cross-sectional study

Aims

Many people with type 1 diabetes do not achieve optimal treatment targets despite high patient and professional input. To investigate the reasons underlying suboptimal control we have studied clinical characteristics and self-management behaviours in adults with type 1 diabetes attending a large treatment centre.

Methods

A questionnaire-based enquiry into self-care behaviours of 380 patients with type 1 diabetes (mean age: 48 (±15) years and mean duration of diabetes: 26 (±15) years), linked with validated measures of impact of treatment on perceived health and hypoglycaemia recognition (Insulin Treatment Satisfaction Questionnaire; and EuroQoL EQ-5D, Gold score) and retrospective case note review of biomedical parameters. The data were analysed using chi-square test, ANOVA, ANCOVA and post-hoc procedures (Tukey's-b) in SPSS-version 18. The minimum significance level was accepted as 0.05.

Results

Sixty three percent of participants used multiple daily injections; 36% continuous subcutaneous insulin infusion. Mean HbA_1c was 7.7% (±1.2) [61 ± −10 mmol/mol]; 30% had impaired hypoglycaemia awareness (IHA). Factors significantly related to poor glycaemic control with IHA were longer duration of diabetes (p = 0.01); less frequent glucose self-monitoring (p = 0.05); and low level of patient-set glucose targets (p < 0.001). Patients with IHA and poorer control had significantly lower insulin treatment satisfaction (p < 0.001); and perceived health (p < 0.001).

Conclusions

Suboptimal biomedical outcomes in adults with type 1 diabetes attending a specialist intensified insulin therapy clinic are associated with longer duration of diabetes, fewer self-management behaviours and a trend towards poorer perceived health. These data suggest a need for greater emphasis on integration of psychological and self-management support with intensive medical management of type 1 diabetes.     

Comparison of insulin sensitivity measures in South Asians

Objective

South Asians have increased visceral adiposity, insulin resistance and greater prevalence of type 2 diabetes and cardiovascular disease when compared to Caucasians of European origin. Surrogate markers of insulin resistance such as the composite insulin sensitivity (Matsuda) index correlate with glucose clamps in other populations, but ethnicity can affect these indices. We compared the Matsuda index, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and triglyceride/HDL ratio to insulin sensitivity derived from euglycemic clamps in healthy South Asians and Caucasians.

Materials/Methods

Twenty-three healthy South Asians and 18 Caucasians matched for age (mean ± SE = 33.6 ± 2.1 vs. 36.0 ± 3.0 years) and BMI (25.2 ± 1.1 vs. 24.6 ± 0.9 kg/m²) underwent 75 g oral glucose tolerance test (OGTT), 2-h euglycemic hyperinsulinemic clamp (240 pmol · m^− 2 · min^− 1), fasting lipid profile, and anthropometric measures.

Results

South Asians had higher fasting insulin (41 ± 5 vs. 21 ± 2 pmol/l; p = 0.002) and lower HDL-C (1.25 ± 0.06 vs. 1.56 ± 0.10 mmol/l; p = 0.010), but similar fasting glucose (5.0 ± 0.1 vs. 4.9 ± 0.1 mmol/l) levels vs. Caucasians. South Asians had significantly decreased measures of insulin sensitivity derived from both the euglycemic clamp (24.9 ± 1.3 vs. 41.4 ± 1.9 μmol · kg^− 1 · min^− 1; p < 0.0001) and OGTT (Matsuda Index 7.60 ± 0.99 vs. 13.60 ± 1.79; p = 0.004). The Matsuda index correlated highly with clamp insulin sensitivity in South Asians (r = 0.50; p = 0.014) and Caucasians (r = 0.47; p = 0.046). HOMA-IR, QUICKI, and triglyceride/HDL ratio correlated with clamp values in South Asians, but not in Caucasians.

Conclusions

In South Asians, Matsuda index, HOMA-IR, QUICKI, and triglyceride/HDL ratio offer simple and valid surrogate measures of insulin sensitivity that can be employed in larger clinical or epidemiological studies in this ethnic group.     

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.     

Alexithymia impact on type 1 and type 2 diabetes: A case-control study

Objectives

This paper focus on studying the prevalence of alexithymia in diabetes type 1 and type 2 and its impact on diabetes's clinical and therapeutic characteristics. We also studied the relationship between alexithymia and emotional disorders in diabetics.

Materials and methods

The study involved a sample of 125 diabetic patients, among whom 50 had type 1 and 75 had type 2 diabetes mellitus compared with respectively 70 and 52 control subjects matched for age and sex. Alexithymia was assessed using the Toronto Alexithymia Scale, while emotional disorders were evaluated using the Hospital Anxiety and Depression Scale.

Results

Type 1 diabetics were more alexithymic than controls while type 2 diabetics had higher cognitive component score than control subjects. Alexithymic type 1 diabetics had a higher average of fasting blood sugar than non-alexithymic patients did (P = 0.021). Moreover, with type 1 diabetes, erectile dysfunction was associated with difficulties in identifying feelings (P = 0.012). We found that the presence of depression was a predictor of alexithymia in type 1 diabetes (β = 1.78, P = 0.04) and the presence of psychiatric history was indicative of the presence of alexithymia in type 2 diabetes (β = 2.09, P = 0.042).

Conclusion

Given the impact of alexithymia on diabetes types 1 and 2, the detection and treatment of alexithymic subjects are important for a better prognosis of diabetic disease.     

Coffee and green tea consumption is associated with insulin resistance in Japanese adults

Objective

Higher coffee and green tea consumption has been suggested to decrease risk of type 2 diabetes, but their roles in insulin resistance (IR) and insulin secretion remain unclear. This study examined the association between habitual consumption of these beverages and markers of glucose metabolism in a Japanese working population.

Materials/Methods

Participants were 1440 Japanese employees (1151 men and 289 women) aged 18–69 years. Consumption of coffee and green tea was ascertained via a validated brief diet history questionnaire. Multilevel linear regression was used to estimate means (95% confidence intervals) of fasting insulin, fasting plasma glucose, homeostatic model assessment of IR (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β) and glycated hemoglobin (HbA1c) with adjustment for potential confounding variables.

Results

Coffee consumption was significantly, inversely associated with HOMA-IR (P for trend = 0.03), and the association appeared to be confined to overweight subjects (BMI ≥ 25 kg/m²) (P for trend = 0.01, P for interaction = 0.08). Unexpectedly, green tea consumption was positively associated with HOMA-IR (P for trend = 0.02), though there was no dose–response relationship among daily consumers of green tea. Neither coffee nor green tea consumption was associated with HOMA-β and HbA1c.

Conclusions

Our findings indicate that coffee consumption may be associated with decreased IR, but not with insulin secretion. The positive association between green tea consumption and IR warrants further investigation.     

Non-diabetic renal disease in Croatian patients with type 2 diabetes mellitus

Aim

Our study aimed to examine the prevalence of non-diabetic renal disease in selected patients with type 2 diabetes mellitus and to determine important risk factors for non-diabetic renal disease.

Methods

We conducted retrospective analysis of clinical, laboratory and pathohistological data of type 2 diabetes mellitus patients in whom renal biopsies were performed from January 2004 to February 2013 at Dubrava University Hospital Zagreb Croatia (n = 80).

Results

According to renal biopsy findings, isolated diabetic nephropathy was found in 46.25%, non-diabetic renal disease superimposed on diabetic nephropathy in 17.5% and isolated non-diabetic renal disease in 36.25% of the patients. The most common non-diabetic renal diseases found were: membranous nephropathy, followed by IgA nephropathy and focal segmental glomerulosclerosis. In univariate analysis shorter duration of diabetes, independence of insulin therapy, lower levels of HbA1c and absence of diabetic retinopathy were found to be significant clinical predictors of non-diabetic renal disease. In multivariate analysis only independence of insulin therapy (OR 4.418, 95%CI = 1.477–13.216) and absence of diabetic retinopathy (OR 5.579, 95%CI = 1.788–17.404) were independent predictors of non-diabetic renal disease.

Conclusions

This study confirmed usefulness of renal biopsy in patients with type 2 diabetes mellitus, due to the high prevalence of non-diabetic renal disease found. Since non-diabetic renal disease are potentially curable, we should consider renal biopsy in selected type 2 diabetes mellitus patients with renal involvement, especially in those with absence of diabetic retinopathy and independence of insulin therapy.     

Beneficial effects of liraglutide on adipocytokines,insulin sensitivity parameters and cardiovascular risk biomarkers in patients with Type 2 diabetes: A prospective study

Aims

To evaluate the effects of liraglutide after 14 weeks of treatment on serum adipokines, insulin resistance index and cardiovascular risk biomarkers in overweight or obese T2DM patients unable to achieve glycemic control with metformin alone or in association with a sulfonylurea in daily clinical practice.

Methods

Prospective study in 59 consecutive overweight or obese (BMI ≥ 25 kg/m²) T2DM patients unable to achieve glycemic control (HbA1c > 7%, 53 mmol/mol) with metformin alone or in association with sulfonylurea that require initiation of liraglutide in progressive dose increase up to 1.8 mg/day subcutaneously. Weight, body composition, blood pressure, glucose, HbA1c, C-peptide, insulin, plasma lipids, adipokines (leptin, adiponectin, resistin and visfatin) as well as cardiovascular biomarkers (IL-6 and TNF-a) levels were measured fasting at baseline and 14 weeks after liraglutide initiation.

Results

14 weeks of liraglutide treatment significantly reduced HbA1c, BMI and total body fat mass by 0.9%, 1.4 kg/m² and 0.5% respectively. Statistically significant lower insulin resistance and higher insulin secretion was found by HOMA-IR 8.4 (1.6) vs 4.6 (0.9) mol m IU/L² and HOMA-B 48.2 (9.0) vs 87.6 (16.3) μIU/mmol. Statistically significantly higher levels of visfatin 6.3 (2.1) vs 6.8 (2.1) ng/ml and resistin 3.6 (2.0) vs 4.3 (2.3) ng/ml were also observed after treatment. Baseline visfatin was negatively correlated with basal fasting plasma glucose r = −0.360 (p < 0.05).

Conclusions

Liraglutide treatment for 14 weeks in daily clinical practice led to reduction of BMI and improvement of glucose control and insulin sensitivity and resistance parameters. Additionally, circulating levels of adipokines and pro-inflammatory factors could play an important role in GLP-1 treatment response.     

Effect of gender on treatment outcomes in type 2 diabetes mellitus

Aim

To evaluate the effect of gender on clinical outcomes in people with type 2 diabetes mellitus (T2DM) receiving antidiabetes therapy.

Methods

This is a pooled analysis from nine similarly designed phase 3 and 4 randomized, controlled studies evaluating insulin glargine and an active comparator (NPH insulin, insulin lispro, premixed insulin, oral antidiabetes drugs, dietary intervention) in adults with T2DM. Impact of gender on outcomes including HbA1c, fasting plasma glucose (FPG), weight-adjusted insulin dose, and hypoglycemia incidence was evaluated after 24 weeks of treatment.

Results

Overall, 1651 male and 1287 female individuals were included; 49.8% and 50.2% were treated with insulin glargine or comparators, respectively. Females receiving insulin glargine were less likely than males to achieve a glycemic target of HbA1c ≤ 7.0% (53 mmol/mol) (54.3% vs 60.8%, respectively, p = 0.0162); there was no difference between females and males receiving comparators (52.7% vs 51.3%, respectively, p = 0.4625). Females had significantly greater reductions in FPG (3.1 mg/dL, p = 0.0458), required significantly higher insulin doses (0.03 IU/kg, p = 0.0071), and had significantly higher annual rates of symptomatic (p < 0.0001), glucose-confirmed (<50 and <70 mg/dL) symptomatic (p = 0.0005 and p < 0.0001), and severe hypoglycemia (p = 0.0020) than males.

Conclusions

Females in this analysis had smaller reductions in HbA1c and were less likely to reach glycemic goals despite higher insulin doses and more hypoglycemic events than males. Differences in gender responses to therapy should be considered when individualizing treatment for people with T2DM.     

Glucometabolic responses during Glucose Tolerance Test: A comparison between known diabetes and newly detected diabetes after acute myocardial infarction

Background

Glucose Tolerance Test (GTT) newly detects diabetes (new diabetes) in a substantial number of patients without a history of diabetes (known diabetes) after acute myocardial infarction (AMI). Patients with new diabetes have poor outcomes, despite their lower HbA1c levels.

Methods

This study consisted of 53 patients with new diabetes and 47 patients with known diabetes who underwent GTT 1 week after AMI. Sixty-eight patients with normal GTT and 78 patients with impaired glucose tolerance served as control. Plasma glucose and insulin were measured at fasting, 30 m, 60 m and 120 m after glucose load. Peak glucose-fasting glucose was used as a measure of glucose fluctuation. Homeostasis model assessment of insulin resistance and the Stumvoll's equations were used to assess insulin sensitivity and ß-cell function, respectively.

Results

Fasting glucose (115 ± 20 mg/dl versus 129 ± 41 mg/dl, p = 0.02) and hemoglobin A1C (5.7 ± 0.5% versus 6.7 ± 1.4%, p < 0.001) in new diabetes were significantly lower than known diabetes. Insulin sensitivity was similarly impaired in both new diabetes and known diabetes (3.2 ± 2.2 versus 3.0 ± 1.9, p = 0.58). Impairment of insulin secretion was less severe in new diabetes than in known diabetes. Peak glucose-fasting glucose was significantly greater in diabetic patients than inpatients with normal GTT (75 ± 30 mg/dl, p < 0.001) and impaired glucose tolerance (95 ± 24 mg/dl, p < 0.001), with no difference between new diabetes and known diabetes (156 ± 36 mg/dl versus 165 ± 57 mg/dl, p = 0.36).

Conclusions

These findings suggested that insulin resistance and exaggerated glucose fluctuation could be attributable to poor outcomes after AMI in patients with new diabetes.