Novel Compounds as GIPR Agonists for Treating Type 2 Diabetes Mellitus and Obesity.

Background: It is evident that the metabolism of some trace metals is altered in diabetes mellitus and these micronutrients may have specific roles in the pathogenesis and progression of the disease. The aim of this study was to determine the status of trace elements; iron, copper, selenium and lead in obese diabetic patients. Method: The study was carried out on two hundred and four (204) subjects, aged 20-68yrs which comprised of fifty nine (59) obese diabetic subjects, forty five (45) obese non-diabetic patients, forty (40) non-obese diabetic patients and sixty (60) non-obese non-diabetics (apparently healthy volunteers) as control. The trace metals (Fe, Cu, Se and Pb) studied were analyzed using atomic absorption spectrophotometer. Results: The mean levels of Se and Pb were decreased significantly when obese diabetics were compared with control. The Se level was also decreased significantly when obese diabetic was compared with each of obese non diabetic and non obese diabetic. The mean levels of other trace metals studied were decreased when obese diabetics were compared with non obese non diabetics (normal control) although not significant. Values in obese only (OND) subjects were higher than even the controls but this decreased with complication-diabetes mellitus although not statistically significant. In the obese diabetic group, Cu and Se negatively correlated with BMI and this was significant. All trace metals studied significantly correlated positively with BMI in both obese only (OND) and control groups. Conclusion: this study showed that essential trace elements (Fe, Cu and Se) and the toxic trace metal Pb studied were depleted in obese diabetics. It is therefore recommended that Fe, Cu and Se supplementation and therapeutic strategies that will enhance Fe, Cu and Se availability in the body been instituted in obese diabetics.

The aim of the study was to determine the association of lipid profile with high sensitivity C-reactive protein (hs-CRP), obese, hypertensive in type 2 diabetes in north Chennai area, Tamil Nadu, India. Nearly 300 blood sample were collected from patients in JPM diagnostic centre, north Chennai, Tamil Nadu and grouped them into diabetic (n=150) and non diabetic (n=150). Behavioral characters were calculated by using the data from the questionnaire like age, sex, height, weight, food habits, obesity, blood pressure (BP), family history, alcohol and smoking habits were correlated for interpretation. The systolic and diastolic blood pressure was measured by using standard mercury sphygmomanometer. Hypertension was diagnosed as per the criteria provided by the WHO (1959&1978). The body weight was calculated by taking weight in kg and height was measured in cms. The body mass index was calculated from the formula BMI = weight in kg/(height in meters) 2 Patients were taken as obese if their body mass index was 29.9. All biochemical analyses were done on a semi autoanalyser (RA 50). hs-CRP levels were measured with Elisa reader (Star Fax 325). The lipid concentration level was significantly higher in diabetic patients compared with non diabetic patients, serum total cholesterol mean ± SD 209.57±26.56 (P<0.001), serum triglycerides mean ± SD 184.78±49.10 (P<0.001), serum LDL - cholesterol mean ± SD 165.27±29.43,(P<0.001) and decrease in serum HDL-cholesterol levels mean ± SD 42.30±7.12, (P<0.001), and total cholesterol/HDL ratio, mean ± SD 5.13±1.27 (P<.001), Regression analysis revealed obese to be strongly associated with diabetes observed. BMI mean±SD 26.93-3.10 (P<0.001). hs-CRP values increased with increase of obese mean ± SD 6.71±2.78 (ANOVA P<0.001) and HbA1c mean± SD 8.54±1.07 (ANOVA P<0.001). Lipid concentration is elevated in hypertensive with diabetes serum total cholesterol mean ± SD 211.61±26.21 (P<0.001) and compared with hypertensive with non diabetic subjects. Lipid concentration level increased (Total cholesterol, LDL, TGL&VLDL) and decreased (HDL) in diabetes subjects. Lipoprotein particles significantly higher in diabetic female, compared to diabetic male. hs-CRP, increased in obese diabetes when compared with non obese diabetics, and obese non diabetics. hs-CRP strongly associated in obese with diabetes. Lipid concentration elevated in hypertensive with diabetes. The risk factors such as obesity, smoking, alcohol consumption, hypertension, food habits and family history were found to promote the development of type 2 diabetes.

Background: Several studies have highlighted the high prevalence of low Total Testosterone (TT) and Free Testosterone (FT) in men with type 2 diabetes and demonstrated links with visceral adiposity, insulin resistance and HbA₁C. The aim of this study is to evaluate the role of diabetes alone and the association of diabetes and obesity on prevalence of infertility in Iraqi male. Subjects and Methods: This case-control study was carried out at Al-Amam Ali Hospital and The Specialized Center For Diseases of Endocrines & Diabetes, Baghdad- Iraq, during the period from December 2011 to April 2012. It consisted of 63 male patients with type 2 Diabetes Mellitus (DM) and 25 healthy controls . Diabetic patients were further subdivided into the three groups according to their BMI as: 1. Diabetic Normo BMI group(n=28, BMI18 -25 kg/m² ), 2. Diabetic Overweight group(n=11 BMI 25 - 30 kg/m² ),and 3. Diabetic Obese group(n=24; BMI was over than 30 kg/m²). Investigations included serum measurements of fasting serum glucose, HbA₁C(using spectrophotometric technique), follicle stimulating hormone FSH, lutilizing hormone LH, prolactin, free testosterone by using ELISA technique in patient groups and healthy controls. Results: The mean(±SD) values of HbA₁C of diabetic obese, diabetic overweight, and diabetic normoBMI patients were higher than that of healthy controls(for all; P<0.0001). Also, the mean values of HbA₁C of diabetic normoBMI was significntly increased compared to that of diabetic obese(P<0.025). However, there was no significant difference in mean value of HbA₁C between diabetic overweight and diabetic obese. Serum levels of FSH, LH, and prolactin did not differ significantly among the patient groups and controls. Serum mean value of free testosterone of diabetic obese patients was significantly lower than that of diabetic overweight (P<0.016) and healthy controls (P<0.001), but did not differ significantly between the diabetic overweight and diabetic normoBMI with control group. The results also showed that there was significant negative correlation between the serum free testosterone levels and the HbA₁C values in diabetic obese group(r=-0.455, P<0.025). Conclusion: This study revealed that association of diabetes mellitus and obesity but not diabetes alone have significant impact on deficiency of free testosterone and consequent sub fertility in male not suffering from primary or secondary causes of infertility.

Objectives:Type 2 diabetes mellitus (DM) and obesity are an independent risk factor for cardiovascular diseases, so early prediction of LV dysfunction carries better prognosis. So our aim was to assess the subclinical LV dysfunction in type 2 diabetic obese and non-obese patients using two-dimensional speckle tracking echocardiography (2DSTE).Materials and Methods:We studied 93 patients, including two groups of 31 each with type 2 diabetes mellitus (T2DM), divided by body mass index (BMI), and 31 non-diabetic non-obese controls. All these subjects underwent two-dimensional Echo (2DE) imaging with analysis of conventional parameters of systolic and diastolic function, as well as speckle tracking echocardiography s (STE) analysis of LV global and regional longitudinal strain.Results:We reported significant inter-group differences in parameters of diastolic function, but no significant differences in ejection fraction or fractional shortening. Nevertheless, we found significant differences in strain, which we interpreted as evidence of subclinical systolic dysfunction.Conclusion:2DSTE is better than basic echocardiographic measurements in assessment of subclinical LV dysfunction in type 2 diabetic obese and non-obese patients which can be used to predict cardiomyopathic changes in the earlier course of type 2 DM and start earlier treatment with better prognosis.

Attribution of Nonalcoholic Steatohepatitis as an Etiology of Cirrhosis for Clinical Trials Eligibility: Recommendations From the Multi-stakeholder Liver Forum

Provided herein are novel substituted 1,1'-biphenyl compounds as glucagon receptor agonists, pharmaceutical compositions, use of such compounds in treating type 2 diabetes mellitus and obesity, and processes for preparing such compounds.

Provided herein are novel compounds as glucagon receptor agonists, pharmaceutical compositions, use of such compounds in treating type 2 diabetes mellitus and obesity, and processes for preparing such compounds.

Background:Both hyperglycemia and obesity are known to cause oxidative stress, which leads to many complications associated with diabetes mellitus. A large number of diabetic patients are obese. Glutathione peroxidase (GPx) is an important indicator of level of oxidative stress.Materials and Methods:In the present study, we assessed GPx levels in 20 healthy controls, obese, and nonobese diabetic patients (n=20 each) and analyzed the effect of insulin treatment for 24 and 48 weeks on GPx activity. GPx activity was measured using biochemical method. The GPx activity was also correlated with glycemic status of obese and nonobese diabetic patients [fasting plasma glucose (FPG) levels] after insulin therapy. Statplus software was used for statistical analysis.Results:We found that there is suppression of GPx activity in diabetic patients as compared to healthy controls (70.9 ± 9.6 U/mg protein) and suppression is more in case of obese (23.4 ± 3.8 U/mg protein) than nonobese diabetics (41.5 ± 3.5 U/mg protein). Both obese (26.05 ± 4.03 U/mg protein) and nonobese (48.7 ± 4.8 U/mg protein) diabetics had increase in GPx activity after 24 weeks of insulin treatment. Further, insulin treatment led to improvement in oxidative stress after 48 weeks in both obese (28.4 ± 6.4) as well as nonobese diabetics (51.8 ± 5.4). The nonobese group showed extremely significant (P<0.001) increase in GPx activity after 24 and 48 weeks both, while obese group showed significant (P value<0.05) increase in GPx activity with insulin treatment only after 48 weeks. A negative correlation was found between postinsulin GPx levels and FPG of obese and nonobese diabetics. The correlation was more strong in case of nonobese than obese diabetics.Conclusion:Higher levels of oxidative stress in obese diabetics even after control of hyperglycemia by insulin treatment reflect the importance of obesity in contributing to oxidative stress.

Fatty liver is commonly associated with insulin-resistant conditions, often related to increased abdominal visceral fat. Our objective was to elucidate the specific roles of obesity, type 2 diabetes mellitus, insulin-resistance and abdominal fat distribution. The study population comprised 13 diabetic obese (DO), 10 nondiabetic obese (NDO), and nine normal-weight control (C) men aged 28-65 years, with normal plasma triglyceride levels. DO were in good glycaemic control (HbA1c = 6·8 ± 0·8%) (M ± SD) with diet (n = 8) or diet + metformin (n = 5). Liver fat content was measured by (1) H-magnetic resonance spectroscopy, abdominal fat distribution by magnetic resonance imaging and insulin sensitivity by hyperinsulinaemic euglycaemic clamp. DO and NDO subjects had similar whole-body insulin resistance, BMI and waist circumference, higher than those of C subjects (P < 0·001). DO had more liver fat (11·9 ± 7·0%) than NDO (5·2 ± 2·8%, P < 0·05) and C (1·6 ± 1·0%, P < 0·001). Abdominal fat was greater in DO and NDO than in C (visceral: DO 3184 ± 843, NDO 2843 ± 1378 vs. C 1212 ± 587 cm(3), P < 0·001; subcutaneous: DO 4029 ± 362, NDO 5197 ± 1398 vs. C 2312 ± 626 cm(3), P < 0·001), visceral fat being not significantly different between the two obese groups, and subcutaneous fat significantly less in DO than in NDO (P < 0·05). Type 2 diabetes is associated with increased fat accumulation in the liver, independent of obesity and whole-body insulin resistance. The increased liver fat in DO patients may be part of an altered regional fat distribution that includes an inadequate subcutaneous fat storing capacity, rather than simply being a consequence of increased abdominal visceral content.

Hyperoxaluria can cause kidney disease through multiple mechanisms, including tubular obstruction from calcium oxalate crystals, sterile inflammation, and tubular epithelial cell injury. Hyperoxaluria is also observed in individuals with diabetes mellitus and obesity, which are in turn risk factors for chronic kidney disease (CKD). Whether hyperoxaluria is a potential mediator of increased risk of CKD in diabetes mellitus and obesity is unknown. Individuals with diabetes have increased levels of plasma glyoxal (a protein glycation product) and glyoxylate, both of which are precursors for oxalate. Increased gut absorption of oxalate in obesity may be because of obesity-associated inflammation. A recent study in individuals with CKD found that higher 24 h urinary oxalate excretion was independently associated with increased risk of kidney disease progression, especially in individuals with diabetes and obesity. Both diabetes mellitus and obesity are associated with higher urinary oxalate excretion through distinct mechanisms. Hyperoxaluria could be a mechanism by which kidney disease develops in individuals with diabetes mellitus or obesity and could also contribute to progressive loss of renal function. Future research on pharmacologic or dietary measures to limit oxalate absorption or generation are required to test whether lowering urinary oxalate excretion is beneficial in preventing kidney disease development and progression in diabetes mellitus and obesity.

Type 2 diabetes mellitus (T2D) and obesity already represent 2 of the most prominent risk factors for cardiovascular disease, and are destined to increase in importance given the global changes in lifestyle. Ten years have passed since the first round of genome-wide association studies for T2D and obesity. During this decade, we have witnessed remarkable developments in human genetics. We have graduated from the despair of candidate gene-based studies that generated few consistently replicated genotype-phenotype associations, to the excitement of an exponential harvest of loci robustly associated with medical outcomes through ever larger genome-wide association study meta-analyses. As well as discovering hundreds of loci, genome-wide association studies have provided transformative insights into the genetic architecture of T2D and other complex traits, highlighting the extent of polygenicity and the tiny effect sizes of many common risk alleles. Genome-wide association studies have also provided a critical starting point for discovering new biology relevant to these traits. Expectations are high that these discoveries will foster development of more effective strategies for intervention, through optimization of precision medicine approaches. In this article, we review current knowledge and provide suggestions for the next steps in genetic research for T2D and obesity. We focus on four areas relevant to precision medicine: genetic architecture, pharmacogenetics and other gene-environment interactions, mechanistic inference, and drug development. As we describe, the genetic architecture of complex traits has major implications for the prospects of precision medicine, rendering some anticipated approaches decidedly unrealistic. We highlight obstacles to the translation of human genetic findings into mechanism inference but are optimistic that, as these are overcome, there is untapped potential for novel drugs and more effective strategies for treating and preventing T2D and obesity.

Background: Non-Communicable Disease is a disease that is considered unable to transmit or spread from one person to another but is a cause of death globally, especially diabetes mellitus and obesity. According to WHO, the number of deaths due to PTM in 2016 was 40.5 million (71%) worldwide. Diet is one of the risk factors for Diabetes Mellitus and Obesity. This study aims to analyze the effect of diet as a risk factor for diabetes mellitus and obesity. Subjects and Method: This study was a syste­matic review and meta-analysis using a cross-sectional design. The articles used in this stu­dy were obtained from several databases, including PubMed, Google Scholar, Spring­er­link, and ScienceDirect. The articles used in this study were those published from 2011-2020. The article search was carried out by consi­dering the eligibility criteria defined using the PICO model. P: adults, I: unhealthy eating patterns, C: healthy eating patterns, and O: Diabetes Mellitus and Obesity. The keywords to search for articles were "dietary pattern", "risk", "obesity", and "diabetes mellitus," and "adjus­ted odds ratio". The articles included in this study were full-text articles with cross-sectional study design. Articles were collected using PRISMA flow diagrams. Articles were analyzed using the Review Manager 5.3 application. Results: A total of 15 articles were reviewed in this study. The meta-analysis showed that an unhealthy diet increased the risk of Diabetes (aOR= 1.65; 95% CI= 1.29 to 2.11; p &lt;0.001). The meta-analysis of 9 articles also showed that an unhealthy diet increased the risk of obesity (aOR= 1.42; 95% CI= 1.21 to 2.66; p &lt;0.001). This meta-analysis combines primary studies from Swaziland, China, Ethiopia, Kenya, Ame­rica, Malaysia, Ghana, Romania, Nepal, Ire­land, and Korea. Conclusion: Unhealthy diet is a risk factor for diabetes mellitus and obesity. Keyword s : dietary pattern, diabetes mellitus, obesity, cross-sectional Correspondence: Linda Wahyu Septiananwati. Masters Program in Public Health, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126, Central Java. Email: lindatian81@gmail.com. Indonesian Journal of Medicine (2021), 06(01): 82-94 https://doi.org/10.26911/theijmed.2021.06.01.09.

The main goal of nursing care should be to increase health-related quality of life as well as improve the medical status of patients with chronic disease. For this reason, this study aims to evaluate and compare the health-related quality of life of patients with diabetes mellitus, hypertension and obesity in Gaziantep, a south-eastern city in Turkey. Diabetes mellitus, hypertension and obesity are the most decisive factors in terms of adversely affecting health-related quality of life. A cross-sectional, descriptive design was used. In this study, the research population included a total of 1601 diabetes mellitus, hypertension and obesity patients. To evaluate health-related quality of life of patients, Short Form-36 (SF-36) was used. Student's t-test, one-way anova and chi-square analyses were used for comparisons between groups. In total, 18·1% of patients had combined obesity, hypertension and diabetes mellitus; 16·1% had hypertension and diabetes mellitus. Approximately 16·1% had only hypertension; 15·4% had obesity and hypertension; 13·3% had diabetes mellitus; 12·7% had obesity and diabetes mellitus; and 8·4% had obesity. The health-related quality of life physical component mean scores of patients with combined obesity and hypertension were lower than that of the other groups (p < 0·05). Health-related quality of life physical component mean scores were determined as 34·5 (SD 0·4), and mental component mean scores were determined as 43·9 (SD 4·4). Health-related quality of life physical component mean scores of moderately active patients were higher, while older age and lower educational and income levels had a negative effect on health-related quality of life (p < 0·05). Diabetes, hypertension and obesity decrease patient health-related quality of life while physical activity increases it. The coexistence of obesity and hypertension, in particular, has a more negative effect on health-related quality of life. Patients with hypertension, obesity and diabetes mellitus need professional support from nurse. Frequent health-related quality of life evaluation and support is required for chronic patients, especially for those who are older, have lower educational and income levels and those with more than one chronic disease.

AimsPopulation surveys of Type 2 diabetes mellitus and obesity conducted in Samoa over three decades have used varying methodologies and definitions. This study standardizes measures, and trends of Type 2 diabetes mellitus and obesity for 1978–2013 are projected to 2020 for adults aged 25–64 years.MethodsUnit records from eight surveys (n = 12 516) were adjusted to the previous census for Division of residence, sex and age to improve national representativeness. Type 2 diabetes mellitus is defined as a fasting plasma glucose ≥ 7.0 mmol/l and/or on medication. Obesity is defined as BMI ≥ 30 kg/m2. Random effects meta‐regression was employed to assess time trends following logit transformation. Poisson regression from strata was used to assess the effects of mean BMI changes on Type 2 diabetes mellitus period trends.ResultsOver 1978–2013, Type 2 diabetes mellitus prevalence increased from 1.2% to 19.6% in men (2.3% per 5 years), and from 2.2% to 19.5% in women (2.2% per 5 years). Obesity prevalence increased from 27.7% to 53.1% in men (3.6% per 5 years) and from 44.4% to 76.7% (4.5% per 5 years) in women. Type 2 diabetes mellitus and obesity prevalences increased in all age groups. From period trends, Type 2 diabetes mellitus prevalence in 2020 is projected to be 26% in men and women. Projected obesity prevalence is projected to be 59% in men and 81% in women. Type 2 diabetes mellitus period trends attributable to BMI increase are estimated as 31% (men) and 16% (women), after adjusting for age.ConclusionThis is the first study to produce trends of Type 2 diabetes mellitus and obesity in Samoa based on standardized data from population surveys. Type 2 diabetes mellitus is equally prevalent in both sexes, and obesity is widespread. Type 2 diabetes mellitus prevalence in Samoa is likely to continue to increase in the near future.

Background:Obesity and diabetes mellitus are two major factors related with the risk of metabolic syndrome and cardiovascular diseases. Co-existing hypertension with diabetes mellitus and obesity has poor prognosis for cardiovascular diseases. Ambulatory blood pressure monitoring (ABPM) correlates more closely to target organ damage than clinic blood pressure.Objectives:The objective of the study is to assess and compare ABPM pattern among obese and nonobese diabetes mellitus patients.Materials and Methods:A cross-sectional study was conducted among fifty obese and fifty nonobese diabetic patients who were classified based on their body mass index as per the WHO criterion. The clinical blood pressure measurements were measured on each subject using a digital sphygmomanometer, and 24 h ABPM was done and ABPM parameters such as dipping pattern, 24 h systolic blood pressure (SBP), diastolic blood pressure (DBP), Mean SBP, mean DBP, diurnal variability of SBP, DBP, Mean arterial pressure, pulse pressure, SD systole (Standard Deviation systole), SD diastole, white coat hypertension was derived and compared between the two groups.Results:Around 37 (74%) obese and 18 (36%) nonobese showed non dipping pattern in SBP and 28 (66.7%) of obese and 14 (33.3%) of nonobese showed a nondipping pattern in DBP and was found to be statistically significant (P < 0.001). On comparison between normotensive obese and normotensive nonobese, it was found that SBP non dipping pattern18 (67%) versus 9 (29%) and DBP nondipping pattern 12 (45%) versus 5 (16%) was statistically significant with P = 0.004, 0.016, respectively.Conclusion:Obese diabetes mellitus subjects had altered ABPM parameters and increased prevalence of nondipping status. In addition, obese diabetic patients who did not give prior history of hypertension were also found to have higher nondipping SBP and DBP patterns.