Control In Type 2 Diabetes Mellitus Patients Research Articles

Factors Associated with Improved Glycemic Control by Direct-Acting Antiviral Agent Treatment in Egyptian Type 2 Diabetes Mellitus Patients with Chronic Hepatitis C Genotype 4.

BackgroundThe association of chronic hepatitis C virus (HCV) infection with type 2 diabetes mellitus (T2DM) was first reported in 1994. Little is known about the effect of direct-acting antiviral agents (DAAs) on glycemic control in T2DM patients. The aim of the present study was to evaluate the factors associated with improved glycemic control (IGC) by DAA treatment in Egyptian T2DM patients with chronic HCV genotype 4 infection.MethodsThis study included 460 T2DM patients with chronic HCV genotype 4 infection. Four hundred patients received DAAs and 60 patients did not receive DAAs. Patients with sustained virological response after 3 months of DAAs (378 patients) were allocated into two groups: first group included 292 patients (77.2%) with IGC and second group included 86 patients (22.8%) with non-improved glycemic control (NIGC).ResultsIn IGC group, 78 patients (26.7%) needed to decrease the dose of antidiabetic treatment. There were no significant differences between IGC and NIGC groups as regards age, sex, and body mass index. The percentage of patients with positive family history of T2DM, those with Child B class and duration of T2DM were significantly higher in NIGC group compared to IGC.ConclusionDiabetic patients receiving DAAs should be closely monitored for reduction of antidiabetic drugs especially insulin and sulfonylurea to avoid hypoglycemic events. Improvement of glycemic control with DAAs is more in patients without family history of T2DM, short duration of diabetes mellitus, and mild liver disease.

Impact of Endurance Exercise Training in the Fasted State on Muscle Biochemistry and Metabolism in Healthy Subjects: Can These Effects be of Particular Clinical Benefit to Type2 Diabetes Mellitus and Insulin-Resistant Patients?

Exercise trainingintervention is a cornerstone in the care of type2 diabetes mellitus (T2DM) and insulin resistance (IR), and it is pursued in order to optimize exercise interventions for these patients. In this regard, the nutritional state of patients during exercise (being in the fed or fasted state) can be of particular interest. The aim of the present review is to describe the impact of endurance exercise (training) in the fasted versus fed state on parameters of muscle biochemistry and metabolism linked to glycemic control or insulin sensitivity in healthy subjects. From these data it can then be deduced whether exercise training in the fasted state may be relevant to patients with T2DM or IR. In healthy subjects, acute endurance exercise in the fasted state is accompanied by lower blood insulin and elevated blood free fatty acid concentrations, stable blood glucose concentrations (in the first 60-90min), superior intramyocellular triacylglycerol oxidation and whole-body lipolysis, and muscle glycogen preservation. Long-term exercise training in the fasted state in healthy subjects is associated with greater improvements in insulin sensitivity, basal muscle fat uptake capacity, and oxidation. Therefore, promising results of exercise (training) in the fasted state have been found in healthy subjects on parameters of muscle biochemistry and metabolism linked to insulin sensitivity and glycemic control. Whether exercise training intervention in which exercise sessions are organized in the fasted state may be more effective in improving insulin sensitivity or glycemic control in T2DM patients and insulin-resistant individuals warrants investigation.

The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Worse Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels. Design and Methods. The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed. Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels. Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed.

Is Urinary NGAL Determination Useful for Monitoring Kidney Function and Assessment of Cardiovascular Disease? A 12-Month Observation of Patients with Type 2 Diabetes.

Background. Diabetic kidney disease (DKD) may start as glomerular or tubular damage. We assessed kidney function during one-year-long observation of patients with type 2 diabetes mellitus (T2DM) after initiation of nephroprotective treatment, with emphasis on the changes in urinary neutrophil gelatinase-associated lipocalin (uNGAL), and evaluated the association between tubular damage and cardiovascular complications of T2DM. Materials and Methods. Adult T2DM patients (55) were assessed initially and 30 patients after 1 year. Albumin and uNGAL and creatinine were measured in first morning urine. Albumin/creatinine (uACR) and uNGAL/creatinine (uNCR) ratios were calculated. Results. In logistic regression, both uACR above 30 mg/g and uNCR the median (21.3 μg/g) were associated with cardiovascular complications, independently of classical risk factors and diabetes duration. One year after initiation of treatment, a significant reduction in HbA1c was observed. BMI and lipid profiles did not change. Increase in serum creatinine and reduction in eGFR occurred, along with decrease in uNGAL and uNCR. Increasing uNCR and uACR were associated with higher control HbA1c. The increase in uNCR was more frequent in patients with hypertension. Conclusions. Better glycemic control in T2DM patients results in improved tubular function, as reflected by reduced uNCR and uNGAL. First morning urine uNGAL and uNCR may be useful to assess renal function and cardiovascular risk, along with albuminuria and eGFR.

New Therapeutic Approaches to Prevent or Delay Beta-Cell Failure in Diabetes

Abstract Background and aims: The most recent estimates of International Diabetes Federation indicate that 382 million people have diabetes, and the incidence of this disease is increasing. While in type 1 diabetes mellitus (T1DM) beta-cell death is autoimmunemediated, type 2 diabetes mellitus (T2DM) results from an interaction between genetic and environmental factors that impair beta-cell function and insulin action. Many people with T2DM remain unaware of their illness for a long time because symptoms may take years to appear or be recognized, while the body is affected by excess blood glucose. These patients are often diagnosed only when diabetes complications have already developed. The aim of this article was to perform a review based on literature data on therapeutic modalities to prevent/delay beta cell function decline. Material and Methods: We searched MEDLINE from 2000 to the present to identify the therapeutic approaches to prevent or delay beta-cell failure in patients with T2DM. Results and conclusions: Several common polymorphisms in genes linked to monogenic forms of diabetes appear to influence the response to T2DM pharmacotherapy. Recent studies report the role of the G protein coupled receptor 40 (GPR40), also known as Free Fatty Acids Receptor 1 (FFAR1) in the regulation of beta-cell function- CNX-011-67 (a GPR40 agonist) has the potential to provide good and durable glycemic control in T2DM patients.

Glycemic control and antidiabetic drugs in type 2 diabetes mellitus patients with renal complications.

BackgroundGood glycemic control can delay the progression of kidney diseases in type 2 diabetes mellitus (T2DM) patients with renal complications. To date, the association between antidiabetic agents and glycemic control in this specific patient population is not well established.PurposeThis study aimed to identify antidiabetic regimens as well as other factors that associated with glycemic control in T2DM patients with different stages of chronic kidney disease (CKD).Patients and methodsThis retrospective, cross-sectional study involved 242 T2DM inpatients and outpatients with renal complications from January 2009 to March 2014 and was conducted in a tertiary teaching hospital in Malaysia. Glycated hemoglobin (A1C) was used as main parameter to assess patients’ glycemic status. Patients were classified to have good (A1C <7%) or poor glycemic control (A1C ≥7%) based on the recommendations of the American Diabetes Association.ResultsMajority of the patients presented with CKD stage 4 (43.4%). Approximately 55.4% of patients were categorized to have poor glycemic control. Insulin (57.9%) was the most commonly prescribed antidiabetic medication, followed by sulfonylureas (43%). Of all antidiabetic regimens, sulfonylureas monotherapy (P<0.001), insulin therapy (P=0.005), and combination of biguanides with insulin (P=0.038) were found to be significantly associated with glycemic control. Other factors including duration of T2DM (P=0.004), comorbidities such as anemia (P=0.024) and retinopathy (P=0.033), concurrent medications such as erythropoietin therapy (P=0.047), α-blockers (P=0.033), and antigouts (P=0.003) were also correlated with A1C.ConclusionIdentification of factors that are associated with glycemic control is important to help in optimization of glucose control in T2DM patients with renal complication.

Improved glycemic control with teneligliptin in patients with type 2 diabetes mellitus on hemodialysis: Evaluation by continuous glucose monitoring

AimsRecent reports suggest that appropriate glycemic control without hypoglycemia could decrease mortality in patients with diabetes mellitus (DM) and end-stage renal disease (ESRD). However, an indication of oral anti-diabetic drugs is limited in this population. The aim of this study was to evaluate efficacy of teneligliptin, a novel DPP-4 inhibitor, by continuous glucose monitoring (CGM) in patients with type 2 DM (T2DM) on hemodialysis (HD). MethodsThis 4-week, open label, single arm, intervention trial included 10 diabetic patients undergoing HD and with glycated albumin (GA) level of ≥18.3%. Teneligliptin treatment was administered on days with HD sessions (HD day) and on days without HD sessions (NHD day); blood glucose values were measured by CGM. The primary endpoint was improvement of glycemic control evaluated by area under the curve (AUC). As secondary endpoints, changes in GA, HbA1c and fasting plasma glucose (FPG) were evaluated. ResultsTeneligliptin improved blood glucose AUC on both HD days (p=0.004), and NHD days (p=0.004). This was accompanied by a significant reduction in GA, HbA1c, and FPG, without severe hypoglycemia. ConclusionsTeneligliptin is one of the useful options for glycemic control in T2DM patients undergoing HD.

Depressive Symptoms, Age at Diagnosis and A Clinically Defined Metabolic Syndrome as Independent Correlates of Glycemic Control in Patients with Type 2 Diabetes Mellitus

Objective: The findings concerning the association of metabolic syndrome (MetS) and depression with glycemic control are controversial. Recently, age at type 2 diabetes mellitus (T2DM) diagnosis has attracted particular attention but the relevant findings are limited. This study aimed to further assess the association between age at T2DM diagnosis, depressive symptoms and MetS with glycemic control in T2DM patients. Methods: In 116 T2DM patients we assessed disease-related and MetS-related variables as well as depressive symptom severity (Center for Epidemiological Studies-Depression scale - CES-D). Glycemic control, as assessed by glycated hemoglobin (HBA1c) levels, was the dependent variable. Results: Suboptimal HBA1c levels, i.e. 7% (53 mmol/mol) or higher, were found in 35.3% of the patients. Elevated CES-D scores indicative of clinically relevant depressive symptoms (CES-D≥16) or possible major depression (CES-D>23) where found in 31.9% and 11.2% of the patients, respectively. Younger age at T2DM diagnosis (p=0.004), greater treatment intensity (p=0.009), higher levels of depressive symptoms (p=0.011) and the presence of a clinically defined MetS (p=0.012) were the variables independently associated with glycemic control in multiple regression analysis after adjusting for sex, education, marital status, family history of diabetes and disease duration. Conclusion: In T2DM patients, the linear association found between depressive symptom severity and glycemic control points to the need of depressive symptoms being timely addressed. Younger age at T2DM onset may also be an important correlate of suboptimal glycemic control, independent of disease duration. Finally, classification of MetS in T2DM by clinical severity might help delineate its impact on glycemic control.

IMPACT OF FAMILY HISTORY IN GLYCEMIC CONTROL AMONG TYPE-2 DIABETES MELLITUS PATIENTS IN ASEER DIABETIC CENTER

There is a significant increase in the incidence and prevalence of Diabetes Mellitus (DM) worldwide and in the Kingdom of Saudi Arabia (KSA). Various studies have been shown the relevance of genetic factor in the onset of type-2 diabetes mellitus (T2DM). In this view the study has been conducted to find the correlation between family history and glycemic control among the T2DM patients in Aseer Diabetic Center (ADC), Abha KSA. This is a cross sectional retrospective study. A total of 343 patient's medical records were accessed to evaluate the role of family history in glycemic control. For the purpose of the study patients were randomly selected and divided into four groups (I-without family history; II-with first degree family history; III-with second degree family history and IV-with both first and second degree family history). The HbA1c value was considered as primary outcome measure in each group. In addition to this other factors such as age, duration of DM, BMI (Body Mass Index) were also studied. Among this study population, about 54.81 % of patients had positive 1 degree family history. The mean age for patients without family history is 62.19 (± 9.29) yrs and 59.98 (± 10.39) for patients with family history, which shows that occurring of DM is early in positive family history groups. The HbA1c value in patients without family history and with family history in either sex is not significant (p < 0.39). In our study, HbA1c levels show no significant difference between patients with and without family history. In conclusion the family history plays no significant role in glycemic control in T2DM patients in ADC.

Where does combination therapy with an SGLT2 inhibitor plus a DPP-4 inhibitor fit in the management of type 2 diabetes?

Hyperglycemia is the critical risk factor for diabetic microvascular complications. Several landmark studies, e.g., UK Prospective Diabetes Study (UKPDS) and Diabetes Control and Complications Trial (DCCT), have demonstrated that lowering the HbA1c by 1% decreases microvascular complications by approximately 35% (1,2). Despite the unequivocal evidence for the importance of achieving good glycemic control in patients with type 2 diabetes mellitus (T2DM), approximately half of individuals with T2DM fail to achieve the American Diabetes Association (ADA) goal of glycemic control (HbA1c <7.0%) (3). Thus, novel therapeutic agents and strategies are required to improve glycemic control in T2DM patients. Two novel classes of antihyperglycemic drugs have been developed during the last decade for the treatment of T2DM: dipeptidyl peptidase-4 inhibitors (DPP-4i) (4) and sodium–glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) (5). DPP-4i have been in clinical use for the treatment of T2DM for more than a decade. DPP-4i inhibit the enzyme that degrades the incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and result in elevated plasma GLP-1 and GIP concentrations. The increase in plasma GLP-1 and GIP concentrations stimulates insulin secretion from the β-cell and inhibits glucagon secretion from the α-cell, leading to inhibition of endogenous glucose production (EGP) and reduction in plasma glucose concentration (6). SGLT2i are a novel class of antidiabetes drugs that recently have been approved for the treatment of T2DM. Members of this class reduce the plasma glucose concentration by inhibiting renal glucose reabsorption and producing glucosuria. Urinary glucose loss results in negative energy balance and because SGLT2i also block sodium absorption in the proximal tubule, they cause weight loss (∼2–3 kg) and decrease in blood pressure (4–6/1–2 mmHg systolic/diastolic) (5). Because the pathogenesis of T2DM is complex and involves multiple metabolic defects (7), the …

Abstract 11267: LX4211, a Dual Inhibitor of Sodium-Glucose Cotransporters 1 and 2, Reduces Systolic Blood Pressure in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment

Introduction: Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors target only the kidney, and they have reduced efficacy when patients with type 2 diabetes mellitus (T2DM) have renal impairment (RI). LX4211 blocks sodium and glucose absorption in the gastrointestinal tract by inhibition of SGLT1, and it enhances urinary sodium and glucose excretion in the urine through inhibition of SGLT2. The dual SGLT1/2 action of LX4211 was anticipated to reduce systolic blood pressure (SBP) in addition to improving glucose control in the setting of RI. Methods: This analysis explored the effect of LX4211 on SBP in a clinical trial of patients with T2DM and moderate to severe RI. Patients (N=31) were randomly assigned to be treated with LX4211 (400 mg, N=16) or placebo (N=15) qd for 7 consecutive days. Postprandial glucose levels after a standard high glucose meal served as the primary measure of pharmacodynamic activity. Baseline and Day 8 trough SBP measures were each an average of 3 seated assessments. Results: Mean baseline characteristics included age 66.4 years, estimated glomerular filtration rate (eGFR) 43.4 mL/min/1.73 m 2 , and SBP 130.9 mmHg. Postprandial glucose area under the curve (sampled from pre-dose to 4 hours post meal) was reduced from Baseline to Day 7 by 169.3 mg*hr/dL on LX4211 compared to placebo (p=0.003). Day 8 SBP reductions were 11.4 mmHg on LX4211 and 0.0 mmHg on placebo (p=0.045 for difference between groups). Patients with greater RI (eGFR &lt;45 mL/min/1.73 m2) treated with LX4211 (N=6) had a 10.5 mmHg SBP reduction compared to 0.3 mmHg on placebo (N=9). The difference between seated and standing SBP did not change with LX4211 (0.0 mmHg change, Day 8 vs. Baseline). There were no reports of hypotension, hypovolemia, no serious adverse events, and no patient discontinued due to an adverse event. Mild hypoglycemia was reported in 1 LX4211 patient compared to 2 placebo patients. Conclusions: LX4211 may reduce SBP and enhance glycemic control in T2DM patients with moderate to severe RI.

A Prospective Cohort Study of IRS Genes Polymorphisms in Type 2 Diabetes Mellitus Patients during Severe/Acute Hyperglycemia Phase. 2: Association with Glycemic Control

Purpose: To investigate the genetic polymorphisms that may contribute to the worsening of glycemic control in type 2 diabetes mellitus (T2DM) with severe or acute hyperglycemia.Methods: The prospective cohort study included 156 T2DM patients with severe or acute hyperglycemia from all medical wards of the National University of Malaysia Medical Centre (UKMMC) that were treated with insulin therapy. For the genetic association study, we used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The glycemic control assessment during the acute phase was based on the degree to which the patient achieved the targeted glucose levels. The primary outcome was the influence of IRS gene on glycemic control in T2DM patients with severe/acute phase hyperglycemia.Results: Insulin Receptor Substrate 1 (IRS1) (R2 = -0.023, p = 0.771) and Insulin Receptor Substrate 2 (IRS2) gene polymorphisms (R2 = -0.160, p = 0.046) were not associated with glycemic control in T2DM patients with severe/acute hyperglycemia.Conclusion: The IRS1 and IRS2 genetic factors may not be significant genetic determinant for glycemic control in T2DM patients during severe/acute phase hyperglycemia.Keywords: Insulin receptor substrate, Gene, Polymorphism, Diabetes, Insulin resistance,Hyperglycemia, IRS 1, IRS 2

Lowering low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of β-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy.

Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors in Type 2 Diabetes: A Literature Review of Approved Products

Diabetes mellitus continues to be a major health issue worldwide. Despite all of the treatment options available on the market, many patients with diabetes fail to reach their treatment goals. Novel agents such as the Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors show promise in effectively lowering blood glucose. Objective: To review the scientific literature for efficacy information regarding the use of approved SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin) in the treatment of Type 2 Diabetes Mellitus (T2DM). Methods: A MEDLINE (1950-August 2014) literature review was performed. All of the literature published as an original clinical trial was included in this review. Other pertinent articles published related to the original clinical trial were also included. Meta-analysis type studies were not selected for this review. Conclusions: With an increasing prevalence and incidence of type 2 diabetes mellitus worldwide, there is an apparent need for effective therapeutic strategies to combat this chronic and progressive disease. SGLT2 inhibitors offer this potential. Recently approved agents (canagliflozin, dapagliflozin and empagliflozin) have shown significant promise as mono- and add-on therapy to current glucose-lowering regimens that may not otherwise be providing sufficient glycemic control in T2DM patients.

Glycaemic control and implementation of the ADA/EASD-2006 consensus algorithm in type 2 diabetes mellitus patients in primary care in Spain

In 2006, the American Diabetes Association and the European Association for the Study of Diabetes established a consensus algorithm (ADA/EASD-2006) for the adjustment of drug therapy for type 2 diabetes mellitus (T2DM). To study glycaemic control in T2DM patients and the implementation of the ADA/EASD-2006 recommendations in primary care centres in Spain. Prospective observational study in 1194 patients with T2DM conducted in 250 primary care centres in Spain. Patients were assessed at study inclusion (V0) and at 3 (V1) and 6 months (V2) post baseline. Information was collected at the level of DM control, HbA(1c) < 7% (HbC) and implementation of the ADA/EASD-2006 guidelines. Type 2 diabetes mellitus patients (53% women; mean age 64.9 years) had a mean (SD) HbA(1c) 7.8 (1.4)% and HbC 25.2% at baseline, 95% of them were receiving oral antihyperglycaemic agents (AAs) only. At V1, HbA(1c) was 7.3 (1.1)% and HbC was 38.1%; 65.0% of patients were receiving oral AAs, 5.6% insulin and 27.9% oral AAs plus insulin. At V2, HbA(1c) was 7.1 (0.9)% and HbC was 48.0%; 57.1% of patients were receiving oral AAs, 5.0% insulin and 36.9% oral AAs plus insulin. The ADA/EASD-2006 algorithm was adhered to in 33% patients up to study month 3, vs. 17.2% throughout the entire 6-month period. In patients with T2DM seen in primary care, the HbA1c target was met in 48.0% after adjusting their AAs. However, this is not reflected in greater implementation of the ADA/EASD-2006 guidelines, which are adhered to in only 17%.

Managing diabetic patients with moderate or severe renal impairment using DPP-4 inhibitors: focus on vildagliptin

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors are novel classified oral anti-diabetic drugs for the treatment of type 2 diabetes mellitus (T2DM) that provide important reduction in glycated hemoglobin, with a low risk for hypoglycemia and no weight gain. In T2DM patients with reduced renal function, adequate glycemic control is essential to delay the progress of kidney dysfunction, but they are at a greater risk of experiencing hypoglycemic events, especially with longer-acting sulfonylureas and meglitinides.ObjectiveTo evaluate vildagliptin as an option to achieve glycemic control in T2DM patients with moderate or severe chronic kidney disease (CKD).MethodsA comprehensive search in the literature was performed using the term “vildagliptin.” Original articles and reviews exploring our topic were carefully selected.ResultsVildagliptin provides effective glycemic control in patients with T2DM and CKD. Dose reductions are required for vildagliptin and other DPP-4 inhibitors, except linagliptin, in T2DM patients with moderate-to-severe CKD. Dose of vildagliptin had to be reduced by half (to 50 mg/day) both for moderate (estimated glomerular filtration rate [eGFR] ≥30 to ≤50 mL/min) and severe CKD (eGFR < 30 mL/min). Available results support a favorable efficacy, safety, and tolerability profile for vildagliptin in T2DM with moderate or severe renal failure. Preliminary data may suggest additional benefits beyond improvement of glycemic control.ConclusionVildagliptin can be safely used in T2DM patients with varying degrees of renal impairment. Dose adjustments for renal impairment are required. Potential long-term renal benefit of vildagliptin needs to be further explored.

The A1chieve study - an observational non-interventional study of patients with type 2 diabetes mellitus initiating or switched to insulin analogue therapy: subgroup analysis of the Gulf population

To evaluate the safety and effectiveness of insulin analogues (insulin aspart, insulin detemir and biphasic insulin aspart 30, alone or in combination) in type 2 diabetes mellitus (T2DM) patients in routine clinical practice in the Gulf as a subgroup of the A(1) chieve multi-national study. A total of 10,704 T2DM Gulf patients with uncontrolled T2DM on oral antidiabetics ± insulins other than insulin aspart, insulin detemir or biphasic insulin aspart 30, who initiated or switched to study insulins were included and followed up for 24 weeks in the context of the A(1) chieve study. Baseline HbA(1c) (± SD) was poor: 9.7 ± 1.7%. At Week 24, an improvement in HbA(1c) of -2.3 ± 1.6% was observed in the entire cohort, and -2.4 ± 1.5% and -2.1 ± 1.7% for insulin-naïve patients and prior insulin users respectively. Overall, rates of hypoglycaemia increased in those new to insulin therapy, whereas a reduction was observed in those switching from other insulins. A marginal reduction in body weight (-0.8 ± 4.4 kg) was noted in the entire cohort, whereas the overall lipid profile and systolic blood pressure (-6.2 ± 15.3 mmHg) improved. Initiating or switching to insulin analogues was well tolerated and resulted in significant improvements in glycaemic control in T2DM patients in the Gulf.

Systematic review and meta-analysis of soy products consumption in patients with type 2 diabetes mellitus.

Clinical trials have reported the lipid-lowering effect of consuming soy products, and epidemiological studies have shown that soy intake is associated with decreased risk of type 2 diabetes mellitus (T2DM). The aim of this meta-analysis was to systematically review the effects of soy products consumption on serum lipid profiles and glycaemic control in T2DM patients. Potential papers were initially searched from PubMed (1966 to 2010) and Cochrane Library (1984 to 2010) without language limitations. All randomized controlled trials were included in which soy products supplementation was the only intervention in subjects with type 2 diabetes. Weighted mean effect size was calculated for net changes in serum lipids and fasting glucose concentrations using fixed-effect or random-effect models. Previously defined subgroup analyses were performed to identify the source of heterogeneity. Eight studies were included according to the criteria. The intake of soy products was associated with a significant reduction in serum total cholesterol (by 0.42 mmol/L; 95% confidence interval (CI): -0.70, -0.14; p<0.001), triacylglycerol (by 0.22 mmol/L; 95% CI: -0.38, -0.07; p<0.001) and low-density lipoprotein-cholesterol (by 0.30 mmol/L; 95% CI: -0.60, -0.00; p<0.001), and a significant increase in high-density lipoprotein-cholesterol (0.05 mmol/L; 95% CI: 0.04, 0.06; p=0.89). There were no significant effects on fasting glucose, insulin and glycated hemoglobin. It can be concluded that intake of soy and soy products has beneficial effects in T2DM patients in relation to serum lipids.

Health economic evaluation of dipeptidyl peptidase-4 inhibitors

Sir, The predicted loss of national income from diabetes in India is 336.6 billion International Dollars.[1] Furthermore, studies have demonstrated that the prevalence of diabetes in India is rising with the progression of time.[2] Therefore, this financial burden is bound to increase. About 90-95% of all the diabetes patients are of the type-2 diabetes mellitus (T2DM). A range of classes of oral therapeutic agents exists for the treatment of T2DM. Among these classes, the newest US FDA-approved drug therapeutic class is of the DPP-4 inhibitors. DPP-4 inhibitors offer substantial glycemic control in T2DM patients. However, DPP-4 inhibitors come at increased costs. Thus a systematic review of the health economic evaluation of DPP-4 inhibitors is required. Separately, the PubMed was searched using the following search strategies: (1) (“saxagliptin” [Supplementary Concept]) AND “Economics”[Mesh] 2) (“sitagliptin” [Supplementary Concept]) AND “Economics”[Mesh] 3) (“vildagliptin” [Supplementary Concept]) AND “Economics”[Mesh] 4) (“BI 1356” [Supplementary Concept]) AND “Economics”[Mesh]. The references cited in all the above retrieved publications were also reviewed for relevance and were obtained and included in the search results when applicable. Currently, saxagliptin is approved at once a daily dosage of 2.5 mg and 5 mg in individuals with normal renal functioning and at 2.5 mg in individuals with moderate-to-severe renal insufficiency or end-stage renal disease (ESRD).[3,4] Furthermore, several clinical trials have shown the effectiveness, safety, and tolerability of saxagliptin in terms of HbA1C, FPG, and PPG reductions.[3,4] A total of three studies were obtained when the PubMed was searched for saxagliptin and economics, combined. These searches were examined as follows. The abstracts of these three studies were reviewed for the inclusion criterion of the cost-effectiveness analysis of saxagliptin. This lead to non-inclusion of all three studies, as none of them met the above described inclusion criterion. This indicates that, including India, no health economic evaluation of saxagliptin has been conducted till date in any part of the world. Currently, the recommended daily dosage of sitagliptin is 100 mg once daily which may be taken without regard to food.[4] The efficacy, safety, and tolerability of sitagliptin is well established in several well designed clinical trial studies.[4] A total of 11 studies were obtained when the PubMed was searched for sitagliptin and economics, combined. The articles obtained were examined for the inclusion criterion of the health economic evaluation of sitagliptin. Based on this criterion, only one study evaluating the cost and consequences associated with sitagliptin was found.[5] As per this study, in comparison to glyburide and exenatide, sitagliptin was found cost-effective. Nonetheless, this study was conducted in the United States settings, and, therefore, the results of cost-effectiveness analysis, if conducted in any other country, may differ. No other study evaluating the pharmacoeconomics of sitagliptin was found in the conducted literature search. Vildagliptin is currently not approved by the US FDA, but is in India, European countries, and Japan for the treatment of T2DM patients. Currently, vildagliptin is given 50 mg twice a day in combination with metformin or a thazolidinedione and 50 mg once a day in combination with sulfonylurea.[6] The efficacy, safety, and tolerability of vildagliptin have been established in various clinical trials of durations of 12 to 104 weeks.[6] Only one study was found when PubMed was searched for vildagliptin and economics, combined. The full-text article for this study was retrieved and was reviewed for the health economic evaluation of vildagliptin.[4] On reviewing the full-text article, no health economic evaluation of vildagliptin was found. This indicates that, including India, no health economic evaluation of vildagliptin has been conducted in any part of the world till date. Currently, the recommended dose of linagliptin (BI 1356) is 5 mg once a day, with or without food. No active-comparator clinical trial study of linagliptin monotherapy has been conducted till now. However, in two double-blinded, placebo-controlled clinical trials, the efficacy, safety, and tolerability of linagliptin was established.[7] No studies were found when PubMed was searched for linagliptin (BI 1356) and economics, combined. This indicates that no health economic evaluation of linagliptin has been conducted till date in any part of the world. Sitagliptin, saxagliptin, vildaglitpin, and linagliptin have been approved worldwide including in places such as India, USA, and Europe. However, this literature review demonstrates that, except for sitagliptin, no formal economic evaluation of DPP-4 inhibitors has been conducted till date in any part of the world. For sitagliptin also, only one cost-effectiveness analysis conducted in the US settings was found. Therefore, formal and systematic health economic evaluations for assessing the cost-effectiveness of DPP-4 inhibitors in the treatment of T2DM are required in India as well as in other parts of the world.

The Impact of Training Modalities on the Clinical Benefits of Exercise Intervention in Patients with Cardiovascular Disease Risk or Type 2 Diabetes Mellitus

Exercise training intervention represents an effective means to reduce adipose tissue mass, improve glycaemic control and increase whole-body oxygen uptake capacity (VO(2peak)) in obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM) and heart disease patients. In this manuscript, we review the impact of different exercise training modalities on clinical benefits of prolonged exercise intervention in these patient (sub)populations. By changing training modalities, significantly greater clinical benefits can be obtained. Greater training frequency and longer programme duration is associated with greater reduction in adipose tissue mass in obesity patients. A greater training frequency (up to 2 days/week) and a longer programme duration (up to 38 weeks) seems to be associated with greater improvements in VO(2peak) in heart disease patients. Longer programme duration and addition of resistance-type exercise further improve glycaemic control in T2DM patients. The first line of evidence seems to indicate that high-intensity interval exercise training has a greater impact on VO(2peak) in heart disease patients and insulin sensitivity in subjects with metabolic syndrome, but not on adipose tissue mass in obese subjects. However, it remains unclear whether addition of resistance-type exercise and continuous higher-intensity endurance-type exercise training are accompanied by greater improvements in VO(2peak) in heart disease patients. Furthermore, the impact of training session duration/volume on adipose tissue mass loss and glycaemic control in obesity and T2DM patients, respectively, is currently unknown. The impact of training frequency on glycaemic control remains to be investigated in T2DM patients.