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Background: Obstructive sleep apnea (OSA) is a frequent comorbid condition in patients with type 2 diabetic (T2DM). Concomitant OSA is associated with a detrimental impact on metabolic control. Both OSA and T2DM independently lead to increased cardiovascular disease and mortality. The impact of OSA on the acceleration of organ dysfunction leading to increased healthcare utilization is unknown., Methods: This is a retrospective case-control cohort study, a secondary analysis utilizing a nationwide dataset. Patients who underwent elective surgical procedures from 2009 to 2014 were identified. Among these patients, we compared patients with obstructive sleep apnea and those without obstructive sleep apnea. Exact 1:1 matching was performed based on similar characteristics such as age, sex, geographic location, surgical facility environment, performing surgeon, and severity of illness during hospitalization. The subgroup of patients with T2DM with or without OSA was analyzed for post-discharge hospital admissions, intensive care unit (ICU) admissions, emergency room (ER) visits, and outpatient visits., Results: Among 47,719 matched patients of the initial study, this subgroup included 4,567 patients with diabetes and OSA and 3,842 patients with diabetes but no OSA. In the presence of comorbid OSA, patients with T2DM had higher odds of increased healthcare utilization among all the outcomes: inpatient visits increased with an odds ratio of 2.50 (confidence interval (CI) 2.28-2.74) and ICU admissions 1.96 (CI 1.73-2.25) ER 1.93 **(CI 1.75-2.12) and outpatient visits 2.18 (CI 2.00-2.38). Future healthcare utilization per 100 patient-years was also increased significantly among all outcomes (p < 0.0001)., Conclusions: In patients with diabetes undergoing elective surgery, the presence of OSA was associated with higher future healthcare utilization., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Purpose: Impaired red blood cell (RBC) deformability impedes tissue perfusion. This study aims to investigate RBC biomechanics in type 2 diabetes mellitus (DM) patients with different grades of diabetic retinopathy (DR) and to correlate RBC deformability with hematological and serum biochemical markers., Methods: This cross-sectional study included 86 type 2 DM patients (31 with no DR, 31 with non-proliferative DR [NPDR] and 24 with proliferative DR [PDR]) and 32 control subjects. RBC deformability was measured by a microfluidic cross-slot channel (elongation index, EI). Venous blood samples were taken for assessment of hematological and serum biochemical markers., Results: RBC deformability showed significant reduction in diabetic patients, being lowest in the PDR group, followed by NPDR and DM with no DR groups, and highest in control group (P = .018). RBC deformability was not affected by age or gender but showed significant associations with certain hematological and serum biochemical markers. In the regression analysis controlling for DM status, urea concentration and reticulocyte count were shown to be negatively associated with EI., Conclusion: Impaired RBC deformability measured by a microfluidic cross-slot channel in DM patients with different grades of DR underscores the contribution of RBC rheological properties to the pathogenesis and progression of DM related microangiopathy., (© 2020 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

Diabetes-associated organ fibrosis, marked by elevated cellular senescence, is a growing health concern. Intriguingly, the mechanism underlying this association remained unknown. Moreover, insulin alone can neither reverse organ fibrosis nor the associated secretory phenotype, favoring the exciting notion that thus far unknown mechanisms must be operative. Here, we show that experimental type 1 and type 2 diabetes impairs DNA repair, leading to senescence, inflammatory phenotypes, and ultimately fibrosis. Carbohydrates were found to trigger this cascade by decreasing the NAD + /NADH ratio and NHEJ-repair in vitro and in diabetes mouse models. Restoring DNA repair by nuclear over-expression of phosphomimetic RAGE reduces DNA damage, inflammation, and fibrosis, thereby restoring organ function. Our study provides a novel conceptual framework for understanding diabetic fibrosis on the basis of persistent DNA damage signaling and points to unprecedented approaches to restore DNA repair capacity for resolution of fibrosis in patients with diabetes., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Aim: This study aimed to assess efficacy and safety of evogliptin versus sitagliptin, when added to background metformin therapy in Indian patients with uncontrolled type 2 diabetes., Method: Overall, 184 patients with uncontrolled type 2 diabetes (7% ≤ HbA 1c  < 10%) receiving ≥8 weeks of stable metformin monotherapy (≥1 g/day), were randomized to receive add-on treatment (evogliptin 5 mg or sitagliptin 100 mg) for 24 weeks. Primary endpoint was change in HbA 1c from baseline to 12 weeks (non-inferiority margin: <0.35)., Results: Mean reductions in HbA1c at 12 weeks in evogliptin- and sitagliptin-treated patients were -0.37 (1.06) and -0.32 (1.14), respectively. The adjusted mean difference between treatment groups was -0.022 (95% CI: -0.374, 0.330; P = 0.901), that demonstrated non-inferiority. Reductions in FPG and PPG were similar between evogliptin and sitagliptin at 12 and 24 weeks. Changes in body weight were comparable between the treatment groups. Patients achieving target HbA 1c  < 7.0% (evogliptin, 26.7% vs. sitagliptin, 20%) was almost equal in both groups. Treatment-emergent adverse events occured in 52 patients (evogliptin, 25% and sitagliptin, 31.5%) and were generally mild., Conclusions: Evogliptin was non-inferior to sitagliptin in HbA 1c reduction. It effectively improved glycemic control and was well tolerated in type 2 diabetes patients inadequately controlled by metformin alone., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Diabetic nephropathy (DN) remains the most common cause of end stage renal disease (ESRD) as the burden of diabetes increases worldwide. Only 25 to 40% of patients with type 2 diabetes mellitus (T2DM) develop diabetic nephropathy irrespective of glycemic control so there should be a specific genetic basis for the development of diabetic nephropathy., Methods: We have collected venous blood samples from 50 cases (Diabetic nephropathy) and 20 controls (T2DM without nephropathy) diagnosed by spot urine albumin creatinine ratio (ACR). DNA was isolated from processed samples. PCR study and sequencing was done to detect polymorphism of rs2237897 in KCNQ1 gene., Results: Statistically significant difference was found when the allelic frequencies between the two groups were compared (p=0.03), with the C allele having a 2.4 fold higher risk of having diabetic nephropathy (risk ratio, RR )= 1.16, 95%CI of RR = 1.01 to 1.3, Odds Ratio (OR) =2.4; 95% CI of OR =1.06 to 4.6). Chi-square analysis showed a significant difference in genotype frequency of rs2237897 (χ2 = 4.63, p=0.03) in Diabetic nephropathy subjects, compared with that of controls., Conclusions: This study suggested that, KCNQ1 being an established type 2 diabetes gene, genetic variation in this gene may contribute to susceptibility to diabetic nephropathy and the C allele is the risk allele for diabetic nephropathy, which is different from Japanese population where the T allele was the risk allele., (© Journal of the Association of Physicians of India 2011.)

Objective: Diabetes mellitus has been claimed to be a risk factor for the development of pancreatic carcinoma. CA 19-9 has a great sensitivity in detection of pancreatic adenocarcinoma. Metformin exhibits a strong and consistent antiproliferative action on several cancer cell lines including pancreatic cancer. We aim to determine the influence of metformin on CA 19-9 levels in type 2 diabetes mellitus patients., Methods: Total 193 patients with type 2 diabetes mellitus were registered for a single centre, cross-sectional study. On the basis of treatment modalities, patients were divided into metformin group (93 patients) and non-metformin group (100 patients). Detailed history, clinical examination, anthropometric measurements, serum CA 19-9 level, glucose and lipid metabolic profiles were determined. Results were presented as mean±SD. Association between CA 19-9 level and other variables were assessed with Pearson correlation and multiple stepwise regression analysis., Results: Mean CA 19-9 level was 18.99±4.30 U/ml in the metformin group as compared to 30.49±5.61 U/ml in non-metformin group (p<0.001). Mean value of CA 19-9 was found highest among all i.e. 37.05±4.94 U/ml in patients taking insulin. Patients having lifestyle modification for the management of diabetes had their mean CA 19-9 level of 21.39±5.62 U/ml. CA 19-9 level is positively correlated with age, duration of diabetes, BMI, 2-hour Plasma Glucose level, HbA1C, VLDL cholesterol, triglyceride, total cholesterol, LDL cholesterol (p<0.005) and negatively correlated with HDL cholesterol (p<0.001)., Conclusion: Metformin is associated with lower level of CA 19-9 in type 2 diabetes mellitus patients. It may have a protective role in preventing pancreatic damage and pancreatic cancer in diabetic individuals. CA 19-9 level could be an effective indicator of glycemic control, disease progression and lipid metabolism in patients with type 2 diabetes mellitus., (© Journal of the Association of Physicians of India 2011.)

Objectives: Type-2 diabetes mellitus (DM) has considerable prevalence in India. A noninvasive diagnostic tool will be more appropriate in conditions like DM. In this study, we intend to find a difference in cytomophometric values, and glycogen accumulation (if any) in buccal mucosa exfoliated cells of type-2 DM patients when compared to nondiabetic healthy individuals, and establish its diagnostic role., Methodology: In the present study, 36 known DM patients with at least 1-year history (case group) and 36 healthy, age- (5 year interval) -matched patients (control group) were included in the study. Patients with any other systemic disease were excluded from the study. Buccal mucosa exfoliative cytology smears were prepared from all 72 patients and stained with Papanicolaou (PAP) stain. The cytomorphometric analysis was performed to evaluate nuclear area (NA), cytoplasmic area (CA), and cytoplasm to nuclear area ratio (CNR) of cells in the smear. The data were tabulated and statistically analyzed using Chi-square test, Student's t-test, Karl Pearson's correlation coefficient and significance (two tailed) test., Results: Statistically significant difference was found in NA and CNR in exfoliative cytology of DM patient group when compared to control group. Fasting blood sugar of DM patients was significantly correlated with NA and CNR of buccal mucosa exfoliated cells., Conclusion: The cytomorphometric changes in exfoliated buccal mucosa cells of type-2 DM patients can have a diagnostic value which needs to be explored further., Competing Interests: There are no conflicts of interest.

Importance: Optical coherence tomographic angiography (OCT-A) is able to visualize retinal microvasculature without the need for injection of fluorescein contrast dye. Nevertheless, it is only able to capture a limited view of macula and does not show leakage., Objectives: To evaluate the retinal microvasculature using OCT-A in patients with type 2 diabetes as well as the association of OCT-A characteristics with diabetic retinopathy (DR) and systemic risk factors., Design, Setting, and Participants: A prospective, observational study was conducted from January 1 to June 30, 2016, at medical retina clinics at the Singapore National Eye Center among 50 patients with type 2 diabetes with and without DR (n = 100 eyes). We examined the retinal microvasculature with swept-source OCT-A and a semiautomated software to measure the capillary density index (CDI) and fractal dimension (FD) at the superficial vascular plexus (SVP) and deep retinal vascular plexus (DVP). We collected data on histories of patients' glycated hemoglobin A1c, hypertension, hyperlipidemia, smoking, and renal impairment., Main Outcomes and Measures: The CDI and FD at the SVP and DVP for each severity level of DR and the association of systemic risk factors vs the CDI and FD., Results: The mean (SD) glycated hemoglobin A1c of the 50 patients (26 men and 24 women; 35 Chinese; mean [SD] age, 59.5 [8.9] years) was 7.9% (1.7%). The mean (SD) CDI at the SVP decreased from 0.358 (0.017) in patients with no DR to 0.338 (0.012) in patients with proliferative DR (P < .001) and at the DVP decreased in patients with no DR from 0.361 (0.019) to 0.345 (0.020) in patients with proliferative DR (P = .04). The mean (SD) FD at the SVP increased from 1.53 (0.05) in patients with no DR to 1.60 (0.05) in patients with proliferative DR (P < .01) and at the DVP increased from 1.55 (0.06) in patients with no DR to 1.61 (0.05) in patients with proliferative DR (P = .02). For systemic risk factors, hyperlipidemia (odds ratio [OR], 9.82; 95% CI, 6.92-11.23; P < .001), smoking (OR, 10.90; 95% CI, 8.23-12.34; P < .001), and renal impairment (OR, 3.72; 95% CI, 1.80-4.81; P = .05) were associated with reduced CDI, while increased glycated hemoglobin A1c (≥8%) (OR, 8.77; 95% CI, 5.23-10.81; P < .01) and renal impairment (OR, 10.30; 95% CI, 8.21-11.91; P < .001) were associated with increased FD., Conclusions and Relevance: Optical coherence tomographic angiography is a novel imaging modality to quantify the retinal capillary microvasculature in patients with diabetes. It can be potentially used in interventional trials to study the effect of systemic risk factors on the microvasculature that was previously not accessible in a noninvasive manner. The relevance of these findings relative to visual acuity, however, remains largely unknown at this time.

Background: Increase in prolactin during pregnancy has been identified as a major stimulus for β cells. These effects have been demonstrated in both in-vitro and in-vivo non-pregnant animal models. Recently, bromocriptine has also been approved for the therapy of type 2 diabetes, regardless of the baseline prolactin level, with its mechanism of action poorly understood. Hence, this study was planned to assess whether prolactin levels within normal range associates with prediabetes and diabetes., Methods: A total of 300 participants, 180 males and 120 females, with equal number of subjects in the prediabetes, diabetes and normal group were analyzed. The participants were categorized into sex-specific quartiles of serum prolactin, with the first quartile representing subjects with the lowest prolactin levels and the fourth quartile having the highest levels. In addition, multinomial logit analyses were performed to evaluate the odds ratio and 95% confidence interval of having prediabetes & diabetes for each quartile., Results: Prolactin levels in the normal group were 10.99 ± 3.65 ng/ml for the males and 12.25 ± 3.67 ng/ml for the post-menopausal females. The prolactin levels for the males in prediabetes group were 9.46 ± 3.43 ng/ml and for diabetes group were 8.98 ± 3.43 ng/ml (p value = 0.005). In females, the prolactin levels were 10.20 ± 3.99 ng/ml for the prediabetes group and 9.60 ± 3.85 ng/ml for the diabetes group (p value = 0.007). The mean fasting plasma glucose for the four male quartiles in their numerical order were 135 mg/dl, 128 mg/dl, 120 mg/dl and 110 mg/dl (p value = 0.04) and the mean HbA1c in the same order for the quartiles were 7%, 6.4%, 6.1% and 5.9% (p value = 0.01). Similarly, the mean fasting plasma glucose for the four female quartiles in their numerical order were 138 mg/dl, 131 mg/dl, 124 mg/dl and 107 mg/dl (p value = 0.03) and the mean HbA1c in the same order for the quartiles were 7.2%, 6.7%, 6.3% and 5.8% (p value = 0.01). The age adjusted odds ratio for 2nd, 3rd and 4th quartiles as compared to the 1st quartile for prediabetes in men were 0.82, 0.72 and 0.61 and for diabetes were 0.84, 0.65 and 0.55, respectively. Risk for diabetes in females ranged from 0.04 to 0.72 for the 3rd quartile and 0.03 to 0.56 for the 4th quartile as compared to 1st quartile. The risk for prediabetes in females ranged from 0.06 to 0.95 for 3rd quartile and 0.04 to 0.74 for the 4th quartile as compared to 1st quartile., Conclusions: Mean prolactin levels in both males and females were lower in prediabetics and lowest in diabetics. Prolactin, on quartile based analysis, associated with better HbA1c and fasting plasma glucose. Decreasing relative risk trends for both prediabetes and diabetes were found with increasing serum prolactin concentrations. No association was found with obesity and dyslipidemia.

Objective: Vitamin D deficiency may be responsible for endothelial dysfunction which in turn affects the onset and progression of vascular disease including coronary artery disease and its risk factor, directly or indirectly through various mechanisms. This study was undertaken to find out association between vitamin D and endothelial dilatation of brachial artery, which may help to suggest possible underlying mechanisms and may be of clinical importance in planning preventive and therapeutic strategies., Material and Methods: 50 cases of type 2 diabetes mellitus aged 40-60 years were taken. 50 cases without type 2 diabetes mellitus matched for confounding factors were taken as controls. Venous blood samples were collected for the investigations including vitamin D levels. Then Participants were subjected to ultrasound examination for measurement of flow mediated dilatation (FMD) and endothelial independent dilatation after ingestion of glyceryl tri-nitrate (GTN). Unpaired student T test and correlation coefficient analysis were used to find out association between different variables., Results: The mean values of FMD were 18.85 ± 5.39% and 10.29 ± 4.91% in controls and cases respectively (p<0.001). The dilatation after GTN was observed to be 26.16 ± 4.25% and 18.74 ± 5.72% in controls and cases respectively (p<0.001). The mean levels of vitamin D among controls and cases were 25.41 ± 12.18 and 14.52 ± 8.28 ng/ml respectively. The correlation between endothelial dependent dilatation (FMD), endothelial independent dilatation (after GTN) and vitamin D was found to be more positive in cases (r=0.870, r=0.798) than controls (r=0.079, r=0.158)., Conclusions: Vitamin D deficiency state is higher among cases of type 2 DM. Endothelial dependent dilatation (FMD) was found to be lower among the patients of type 2 DM. The study gives us an insight to identify the diabetics with vitamin D deficiency which may be at higher risk of vascular complications including coronary artery disease.

A pilot cross sectional study was conducted to investigate the role of red blood cells (RBC) deformability in type 2 diabetes mellitus (T2DM) without and with diabetic retinopathy (DR) using a dual optical tweezers stretching technique. A dual optical tweezers was made by splitting and recombining a single Nd:YAG laser beam. RBCs were trapped directly (i.e., without microbead handles) in the dual optical tweezers where they were observed to adopt a "side-on" orientation. RBC initial and final lengths after stretching were measured by digital video microscopy, and a Deformability index (DI) calculated. Blood from 8 healthy controls, 5 T2DM and 7 DR patients with respective mean age of 52.4 yrs, 51.6 yrs and 52 yrs was analysed. Initial average length of RBCs for control group was 8.45 ± 0.25 μm, 8.68 ± 0.49 μm for DM RBCs and 8.82 ± 0.32 μm for DR RBCs (p < 0.001). The DI for control group was 0.0698 ± 0.0224, and that for DM RBCs was 0.0645 ± 0.03 and 0.0635 ± 0.028 (p < 0.001) for DR group. DI was inversely related to basal length of RBCs (p =  .02). DI of RBC from DM and DR patients was significantly lower in comparison with normal healthy controls. A dual optical tweezers method can hence be reliably used to assess RBC deformability.

Aim: Diabetes is a well known risk factor for carotid atherosclerosis. However, screening of all diabetics by carotid ultrasonography is cumbersome and cost-effective. Search for anthropometric measures related to severity of disease has been relentless. It's a proposal for waist-calf ratio as a better marker of carotid atherosclerosis than traditional measurements as it is cost-effective and non-invasive., Methods: This was a cross-sectional observational study. 100 patients were included. Detailed history, clinical examination, biochemical indices and anthropometric measurements were recorded. Carotid atherosclerosis was measured using a high resolution USG system with 10 MHz linear transducer. The carotid intima-media thickness (CIMT) was measured at 3 points on far wall of mid and distal CCA and 1 cm proximal to dilation of carotid bulb. Mean value of six measurements from right and left CCA was used. CIMT → Distance between media-adventitia interface and lumen intima interface. Carotid Plaque → distinct area of hyperechogenicity and or protrusion into the lumen of vessel with at least 50% greater thickness than the surrounding area. Carotid atherosclerosis → Focal plaque or CIMT > 1.1 mm., Results: Mean CIMT in quartiles of WCR in females and males are 1st (0.740, 0.674); 2nd (0.833, 0.726); 3rd (0.902, 0.814); 4th (1.005, 0.910) as well as mean WCR in quartiles of CIMT in males and females are 1st (2.292, 2.302); 2nd (2.473,2.443 ); 3rd (2.641, 2.671); 4th (3.177, 2.967). All the quartiles are statistically highly significant with p<0.001. Out of 100 patients 17 patients with carotid plaques, 12 had CIMT >1 and 14 had WCR >2.5. The difference was statistically significant with p<0.01., Conclusions: waist-calf ratio is a stronger anthropometric marker of carotid atherosclerosis and can be used in screening of high risk patients in diabetic population.

Introduction: An increased prevalence of rheumatological manifestations is recognised in diabetes and is a common source of disability. The relationship with other risk factors and glycaemic control is uncertain. We designed this study to find out the prevalence of rheumatological manifestations, association with various risk factors and to assess differences between type 1 and type 2 diabetes., Material and Methods: The study was conducted from Jan 2010 to Dec 2011 at tertiary care hospital. We recorded type of diabetes, various risk factors viz age, duration of diabetes, glycaemic control (HbA1C) and BMI and noted prevalence of various rheumatological manifestations by clinical examination, X-ray and if needed CT scan/MRI. We explored correlation between rheumatological manifestations and these variables using logistic regression., Results: The prevalence of rheumatological manifestations was estimated at 570 per 1000 population. The manifestations were more common in type 1 diabetes (62.7%). The various complications observed in the present study were DISH (13%), Frozen Shoulder (20%), Dupuytren's Contracture (7.2%), Osteoarthritis (36.1%), Neuroarthropathy (2.9%), Chieroarthropathy (22.6%) and Flexor Tenosynovitis (8.1%). Among various risk factors, duration of diabetes (odd ratio: 5.127), BMI (odd ratio: 7.429) and age (odd ratio: 4.731) were common risk factors. Poor glycaemic control was also associated with increased prevalence of rheumatological manifestations., Conclusion: Rheumatologic manifestations are very common in diabetics and are associated with poor glycaemic control, BMI, duration of diabetes and age of the patients.

The rising prevalence of type-2 diabetes is becoming a pressing issue based on emerging reports that T2DM can also adversely impact mental health. We have utilized the UCD-T2DM rat model in which the onset of T2DM develops spontaneously across time and can serve to understand the pathophysiology of diabetes in humans. An increased insulin resistance index and plasma glucose levels manifested the onset of T2DM. There was a decrease in hippocampal insulin receptor signaling in the hippocampus, which correlated with peripheral insulin resistance index along the course of diabetes onset (r=-0.56, p<0.01). T2DM increased the hippocampal levels of 4-hydroxynonenal (4-HNE; a marker of lipid peroxidation) in inverse proportion to the changes in the mitochondrial regulator PGC-1α. Disrupted energy homeostasis was further manifested by a concurrent reduction in energy metabolic markers, including TFAM, SIRT1, and AMPK phosphorylation. In addition, T2DM influenced brain plasticity as evidenced by a significant reduction of BDNF-TrkB signaling. These results suggest that the pathology of T2DM in the brain involves a progressive and coordinated disruption of insulin signaling, and energy homeostasis, with profound consequences for brain function and plasticity. All the described consequences of T2DM were attenuated by treatment with the glucagon-like peptide-1 receptor agonist, liraglutide. Similar results to those of liraglutide were obtained by exposing T2DM rats to a food energy restricted diet, which suggest that normalization of brain energy metabolism is a crucial factor to counteract central insulin sensitivity and synaptic plasticity associated with T2DM., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: To determine the prevalence of micro and macrovascular complications in type-2 diabetes in Northwest India and its correlation with various risk factors., Methods: In this study, total 11,157 subjects (M:F 6661:4496), attending the diabetic clinic, were analysed. The study sample resembles the population sample in anthropometric, age and socioeconomic factors. All patients had undergone the test for retinopathy by fundus examination, nephropathy by microalbuminuria, serum creatinine and blood urea, neuropathy by monofilament and biothesiometer, peripheral vascular disease (PVD) by colour doppler and cardiovascular disease by ECG., Results: Among 11,157 subjects, retinopathy was diagnosed in 32.5%, nephropathy was present in 30.2%, peripheral neuropathy was present in 26.8%, coronary heart disease (CHD) was present in 25.8% and peripheral vascular disease (PVD) was present in 28% of the subjects. Multiple logistic regression analyses showed that age had a significant association with retinopathy, neuropathy, coronary heart disease (CHD) and peripheral vascular diseases (PVD). Duration of diabetes had significant association with the neuropathy, nephropathy and PVD. Higher HbA1C increases the risk of retinopathy, neuropathy and nephropathy. Hypertension was associated with nephropathy and coronary heart disease., Conclusion: The study highlights the high prevalence of vascular complications in type-2 diabetes in Northwest India. Retinopathy and nephropathy were the commonest complications of diabetes in our study.

The new chemical entity (NCE) has been knocked as novel antidiabetic agent, e.g. Saroglitazar. Saroglitazar is a drug for the treatment of Type II diabetes. Saroglitazar is marketed under the trade name Lipaglyn, developed by the Zydus Cadila. Lipaglyn is the first indigenously developed NCE by any Indian pharmaceutical company, ever. Lipaglyn has been approved for the treatment of Type II diabetes by the Drug Controller General of India in June 2013. Lipaglyn is indicated for the patients suffering from diabetes dyslipidemia. It also provides the option of a once-daily oral therapy. Saroglitazar regulates the lipid parameters as well as glycemic control. The present article describes Saroglitazar with its chemical synthesis and patent status with its summary of clinical studies.

Aim: Non-alcoholic steatohepatitis (NASH) patients are at increased risk for progression to cirrhosis. The aim of this study was to assess all-cause and liver-specific mortality in a cohort of non-alcoholic fatty liver disease (NAFLD) patients., Methods: Biopsy-proven NAFLD patients with and without NASH from two historic databases were included. Clinico-demographic information from the time of biopsy was available. Mortality data were obtained from National Death Index-Plus and used for estimating overall and cause-specific mortality. The non-parametric Kaplan-Meier method with log-rank test and multivariate analyses with Cox proportional hazard model were used to compare cohorts., Results: Two hundred eighty-nine NAFLD patients were included (50.3 ± 14.5 years old, 39.4 % male, 78.6 % Caucasian, 46.0 % obese, 26.0 % diabetic, 5.9 % with family history of liver diseases). Of these, 59.2 % had NASH whereas 40.8 % had non-NASH NAFLD. NASH patients were predominantly female, had higher aspartate aminotranserase, alanine aminotransferase and fasting serum glucose. During follow-up (median 150 months, maximum 342 months), patients with NASH had higher probability of mortality from liver-related causes than non-NASH NAFLD patients (p value = 0.0026). In the entire NAFLD cohort, older age [aHR = 1.07 (95 % CI = 1.05-1.10)] and presence of type II diabetes [aHR = 2.09 (1.39-3.14)] were independent predictors of overall mortality. However, in addition to age [aHR = 1.06 (1.02-1.10)] having histologic NASH [aHR = 9.16 (2.10-9.88)] was found to be an independent predictor of liver-related mortality. Additionally, presence of type II diabetes was associated with liver-related mortality [aHR = 2.19 (1.00-4.81)]., Conclusions: This long-term follow-up of NAFLD patients confirms that NASH patients have higher risk of liver-related mortality than non-NASH. Additionally, patients with NAFLD and type II diabetes are at highest risk for overall and liver-related mortality.

Context: The roots of Aerva lanata Linn. (Amaranthaceae) (AL) are employed traditionally as an antihyperglycaemic in the Ayurvedic system of medicine., Objective: The present investigation is focus for identification and isolation of the bioactive compound from methanol roots extract of AL against streptozocin-nicotinamide induced elevated serum glucose level in rats., Materials and Methods: The methanol extract of the roots was fractionated using different solvents. The partially purified alkaloid basified toluene fraction (PPABTF) showed the presence of alkaloids. The fraction (10 and 20 mg/kg) was tested for oral glucose tolerance test (OGTT) and in non-insulin-dependent diabetes mellitus (NIDDM)-induced elevated serum glucose level in rats. The fraction was also subjected to high performance thin layer chromatography (HPTLC) for the determination of content of individual alkaloids., Results: Single oral administration of PPABTF (10 and 20 mg/kg) after 20 h caused a significant (p < 0.01) reduction in the serum glucose level (mg/dl). On other hand, PPABTF normalised plasma glucose levels after 2 weeks of repeated oral administration in diabetic rats (p < 0.01). HPTLC analysis on PPABTF showed the presence of three known alkaloids. The fraction was further subjected to column chromatography and the compounds identified by ultraviolet, infrared, mass spectroscopy and nuclear magnetic resonance, as canthin-6-one derivatives., Conclusion and Discussion: The PPABTF in the dose of 20 mg/kg showed significant effects on streptozotocin-nicotinamide induced type-II NIDDM in rats. The activity may be due to the presence of alkaloids like canthin-6-one derivatives.

Chemically, methylxanthine nucleus based Linagliptin (BI-1356, BI-1356-BS) is a dipeptidyl peptidase-IV inhibitor, which has been developed by Boehringer Ingelheim in association with Lilly for the treatment of Type-II Diabetes. Linagliptin was marketed by Lilly under the trade name Tradjenta and Trajenta. Linagliptin was approved as the once-daily dose by USFDA on 2 May 2011, for the treatment of Type-II Diabetes. Linagliptin 5mg once daily dose was approved based on a clinical trial program, which was conducted on approximately 4,000 adults with Type-II Diabetes. Linagliptin demonstrated statistically significant mean difference in HbA1c from placebo of up to 0.72 percent, when it was used monotherapically. In patients, who were not adequately controlled on metformin or metformin plus sulphonylurea, the addition of Linagliptin resulted in a statistically significant mean difference in HbA1c from placebo of -0.6 percent. Linagliptin was observed to produce significant reduction in fasting plasma glucose (FPG) compared to placebo, when used as a monotherapy in combination with metformin, sulfonylurea and/or pioglitazone. Linagliptin demonstrated significant reduction post-prandial glucose (PPG) levels in two hours as compared with placebo in monotherapy as well as in combination with metformin. In vitro assays also anticipated that Linagliptin is a potent DPPIV inhibitor as well as it exhibits good selectivity for DPP-IV as compared with other DPPs. The in-vivo studies also demonstrated same anticipation with respect to Linagliptin. Consequently, increasing the GLP-1 levels so far improved glucose tolerance in both healthy animals. X-ray crystallography anticipates that Linagliptin complexes with human DPPIV enzyme, e.g. butynyl substituent occupies the S1 hydrophobic pocket of the enzyme; the aminopiperidine substituent in the xanthine scaffold occupies the S2 subsite and its primary amine interacts with the key amino acid residues, which involves in the recognition of peptide substrates. In the present review, we have tried to cover comparative study of DPPIV inhibitors, chemistry, physical properties, commercial synthesis, patent portfolio, crystalline polymorphic forms of Linagliptin and its receptor interaction, Pharmacophore rational, mechanism, clinical studies, preclinical, adverse effect, available formulations, dose regimen, co-therapy of Linagliptin, giving emphasis on the medicinal chemistry aspects.

Background/objectives: Hypoglycemic effect of camel milk supplementation in experimental rat model and significant reduction in doses of insulin in type 1 diabetic patients have been observed in our previous studies. This long-term study was undertaken to assess the efficacy, safety and acceptability of camel milk as an adjunct to insulin therapy in type 1 diabetics., Subjects/methods: In this 2-year randomized clinical, parallel design study, 24 type 1 diabetics were enrolled and divided into two groups. Group I (n=12) received usual care, that is, diet, exercise and insulin and Group II (n=12) received 500 ml camel milk in addition to the usual care. Insulin requirement was titrated weekly by blood glucose estimation. Results were analyzed by using the regression technique., Results: In camel milk group, there was decrease in mean blood glucose (118.58±19-93.16±17.06 mg/dl), hemoglobin A1c levels (7.81±1.39-5.44±0.81%) and insulin doses (32.50±9.99-17.50±12.09 U/day, P<0.05). Out of 12 subjects receiving camel milk, insulin requirement in 3 subjects reduced to zero. There was nonsignificant change in plasma insulin and anti-insulin antibodies in both the groups., Conclusion: It may be stated that camel milk is safe and efficacious in improving long-term glycemic control, with a significant reduction in the doses of insulin in type 1 diabetic patients.

A cross-sectional case-control study was conducted in 80 diabetic patients, to evaluate the incidence of gastropathy by endoscopy in type 2 diabetes mellitus. An association between Helicobacter pylori infection and non-gastrointestinal complication of diabetes mellitus was also looked into. Gastric biopsies were subjected to rapid urease test for demonstration of Helicobacter pylori. The fasting blood glucose levels among Helicobacter pylori positive diabetes were 175 +/- 36.5 mg %, and in Helicobacter pylori negative diabetics were 138 +/- 39.4 mg %. The prevalence of endoscopically detectable gastro-intestinal complications were higher in Helicobacter pylori infected diabetics (odd's ratio 4:2; p < 0.05). The total prevalence of Helicobacter pylori positive in diabetics by rapid urease test was statistically significant (p < 0.05). Coronary heart disease was more prevalent in diabetics with Helicobacter pylori infection than those without Helicobacter pylori (57%). The prevalence of H. pylori positivity in other complications such as peripheral vascular diseases, cerebrovascular diseases was not significant. The association between nephropathy, retinopathy and neuropathy with Helicobacter pylori, was also observed and the strong association was seen in diabetic retinopathy (p < 0.001), diabetic neuropathy (p < 0.01) and nephropathy (p < 0.001).

The aim of this study was to evaluate relationship between serum magnesium and course of diabetes mellitus and also to find out, if there is any relation between serum magnesium and various complications of diabetes mellitus. A cross-sectional study was conducted to examine the relationship between serum magnesium in 50 type 1 and type 2 diabetic patients with or without complications and 40 normal healthy persons. Serum magneisum estimation was done using calmagite dye method using autoanalyser (Beckman DU clin systems). Serum magnesium levels in diabetic population was significantly low (1.93 +/- 0.282 meq/l) in comparison to control (2.25 +/- 0.429 meq/l). It was statistically significant (+3.84; p < 0.005). Serum magnesium was significantly low in diabetes with complication than without complications (p < 0.001). Duration of diabetes and serum magnesium were inversely related. Poor glycaemic control was associated with hypomagnesaemia (-2.623; p < 0.05). There was strong association between hypomagnesaemia and retinopathy (1.76 +/- 0.26), obesity (1.878 +/- 0.326) and hypertension (1.75 +/- 0.071) and it was statistically significantly (p < 0.005, 0.042, 0.000 respectively). Hence it is concluded that the change in serum magnesium level may have a bearing on the complication and morbidity in patients of diabetes mellitus.

Aim: Type 2 diabetes is not only associated with hyperglycemia but also with disorders of lipid metabolism. The aim of this study was to investigate the association of dyslipedemia with micro and macro vascular complications of diabetes., Methods: Population based cross sectional study included 4067 diabetic patients who visited hospital during January 2000 to December 2002. Lipid profile was estimated by semi autoanalyser, Retinopathy was assessed by fundoscopy, Nephropathy by microalbuminurea, coronary artery disease (CAD) by electro cardiogram (ECG) changes, peripheral vascular disease (PVD) by doppler study and neuropathy by clinical examinations. The association of dyslipedemia with micro and macro vascular complications was assessed by regression analysis., Results: The prevalence of dyslipedemia is high in diabetic population with high serum cholesterol >240mg/dl was seen in 15%, serum triglycerides >160mg/dl was seen in 42.41%, raised LDL >130mg/dl in 45.26%, VLDL >40mg/dl in 24.09% and low levels of HDL-C <40mg/dl were seen in 52.27%. On regression analysis, CAD had strong correlation with high levels of VLDL (0.76), triglycerides (0.82), LDL (0.23) and low HDL (-0.81). Similar association was seen with PVD. Diabetic retinopathy and nephropathy were found to have significant correlation with low HDL (-0.43) and raised LDL (0.37), respectively. Neuropathy was not found to have any significant correlation with lipid profile abnormalities., Conclusion: Lipid profile abnormalities are very common in type 2 diabetes and it has great influence on CAD and PVD. Hence, appropriate preventive and treatment strategies should be considered timely.

Objective: Angiotensin-converting enzyme inhibitors plus dihydropyridine calcium channel blockers or low-dose thiazide diuretics are considered first-line therapies in hypertensive diabetic patients as glucose metabolism is not relevantly affected. Most diabetic patients require at least two different drug classes to achieve the recommended target blood pressure of 130/85 mmHg. This controlled clinical trial investigated the calcium channel blocker lercanidipine versus hydrochlorothiazide (HCTZ) as add-on in diabetic patients with uncontrolled hypertension on enalapril monotherapy., Methods: Overall, 174 patients (18-80 years old, well-controlled diabetes type 1 or 2, mild to moderate hypertension) were included in a 2-week placebo run-in followed by 4 weeks on enalapril 20 mg. Subsequently, 135 non-responders (90 mmHg < or = mean sitting diastolic blood pressure < or = 109 mmHg) were randomized to 20 weeks of double-blind add-on therapy to enalapril with either lercanidipine 10 mg (n = 69) or HCTZ 12.5 mg (n = 66). The primary study objective was to prove non-inferiority of lercanidipine add-on versus HCTZ add-on in reducing sitting diastolic blood pressure; response rates and tolerability data were also observed., Results: Both add-on treatments clearly decreased diastolic blood pressure to a greater extent than enalapril monotherapy (mean +/- SD changes at study end: lercanidipine, -9.3 mmHg; HCTZ, -7.4 mmHg); non-inferiority of lercanidipine versus HCTZ was formally proven. Blood pressure response rates reached 69.6% on enalapril plus lercanidipine as compared with 53.6% on enalapril plus HCTZ (difference between treatments, P > 0.05). Blood pressure of 130/85 mmHg or less was achieved in 30.4% of patients on lercanidipine add-on and in 23.2% of those randomized to HCTZ add-on (P > 0.05). Both treatment regimens were well tolerated., Conclusion: Lercanidipine add-on showed comparable efficacy to HCTZ add-on in diabetic patients with hypertension badly controlled on angiotensin-converting enzyme inhibitor monotherapy. The blood pressure response rates seemed to be somewhat higher following enalapril plus lercanidipine than enalapril plus HCTZ.

Objective: To evaluate the safety and effectiveness of Inolter in achieving glycemic control and changes in lipid profile of newly diagnosed type 2 diabetics., Study Design: A randomized, placebo-controlled double blind. Sixty newly diagnosed patients of type-2 diabetes were randomized. Of these, 30 were put on Inolter monotherapy and 30 patients on placebo. Efficacy of Inolter was determined by observing glycemic control by estimating glycosylated haemoglobin (HbA1c) and fasting blood sugar (FBS), alteration of lipid profile by serum cholesterol, LDL, VLDL, HDL and triglycerides., Statistical Methods: Student's unpaired 't' test., Results: Patients compliance was satisfactory and no adverse effects were observed. Better hypoglycemic effect was observed with Inolter both respect to fasting blood sugar (mean 65.4 +/- 63.72 mg/dl) compared to placebo (mean 26.45 +/- 38.3 mg/dl) (p < 0.001). The mean change, with Inolter, in serum cholesterol (21.33 +/- 26.05 mg/dl), serum triglyceride (30.36 +/- 32.62 mg/dl), VLDL (8.85 +/- 3.25 mg/dl), LDL (10.00 +/- 4.48 mg/dl) and HDL (-2.33 +/- 5.66 mg/dl) was also significantly different (p < 0.001) from those given placebo, where it was 15.7 +/- 20.14 mg/dl, 8.70 +/- 13.24, 0.10 +/- 4.10 mg/dl, -0.70 +/- 4.58 mg/dl and 0.65 +/- 0.00 mg/dl, respectively., Conclusion: Inolter appears to be an useful adjunctive therapy to exercise and diet control in newly diagnosed type 2 diabetes mellitus.