Insulin and Insulin Antibody: What a Family Physician should Know ?

Antibodies develop to injected insulin frequently. The development of anti-insulin antibodies is maximum to conventional bovine insulin compared to the porcine variety. The immunogenicity of the insulin is not only due to the species from which the insulin is prepared but also the impurities that are present in the preparation like proinsulin and other islet ceil hormones. Hence the purified insulins produce lesser amount of antibodies and among the purified insulins, the least is produced by human insulin. The production of these antibodies depends on the insulin preparation, the route of administration, age and sex and the genetic status of the individuals. These antibodies produce various complications. They include allergy, lipoatrophy, insulin resistance, alteration of metabolic control, hypoglycemia, reduction in the duration of remission period and fetal hypoglycemia when given during the gestational period. These can be overcome by the use of purified insulins

The burden of diabetes mellitus during pregnancy in low- and middle-income countries : a systematic review

Peer reviewedPublisher PD

BNP AND NT-PRO BNP AS INDEPENDENT DIAGNOSTIC BIOMARKERS FOR CARDIOVASCULAR DISEASE IN TYPE 2 DIABETES MELLITUS

The risk of developing heart failure (HF) with a reduced and preserved ejection fraction is known to increase with pre-diabetes and diabetic mellitus (DM). Natriuretic peptides (NPs) have been shown to be an important tool for assessing the risk of cardiovascular diseases (CVD) in people with pre-diabetes and Type 2 diabetes (T2DM), regardless of HF characteristics. Elevated levels of NPs were associated with an increased risk of readmission for HF, all-cause mortality, CVD mortality, HF progression, and readmission due to HF, according to earlier clinical investigations. In pre-diabetes and T2DM populations, the discriminative power of NPs for CVD death and HF-related clinical events has not been established beyond conventional CVD risk variables. The purpose of the review is to gather details regarding the predictive value of circulating NPs based on pre-diabetes and established T2DM presentation. Researchers have found that HFrEF or HFpEF in T2DM patients may necessitate a change in NP cutoff values to diagnose primary HF and identify HF-related risks. The relationship between clinical outcomes and the dynamic of circulating levels of NPs in diabetics treated with glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors has to be clarified in big clinical trials in the future

Efficacy of early versus late postpartum DIPSI test in gestational diabetes mellitus women for follow up

Background: The present study aimed to evaluate if postpartum gestational diabetes mellitus (GDM) screening can be performed during immediate post-delivery 72 hrs instead of six weeks postpartum for follow-up. Methods: Total 150 GDM patients were included. The sample size was calculated as 150 with Nimaster2.0 software. GDM patients are enrolled after meeting the exclusion criteria for the study. The GDM diagnosis was made by DIPSI test and treated as per guidelines. After delivery, the Dipsi test was done on PND-3 (PP1). Furthermore, all were kept on LSM irrespective of the glycaemic level DIPSI test was repeated in all Patients after 45 days (PP2). Results: All 150 patients had a DIPSI test on 3rd day post-partum (PP1) and repeat test at 45 days (PP2)., Of these, 60 patients (40%) showed negative DIPSI test on P1 and all remained in Group 1, with 63 patients having negative DIPSI test on PP2. 50 patients (33.3%) had blood glucose between 140-199 mg (Group 2) on PP1 and increased to 53 patients in PP2 in 45 days. 40 patients had diabetic (26.6%) value (Group 3) in PP1, and out of them 34 (22.6%) remained in group 3 in PP2 after 45 days post-partum. Conclusions: This pilot study shows that nearly 60% of the GDM patient have either IGT or diabetic value following delivery on 3rd day of PP1 and almost similar results in PP2. Hence, we can do the postpartum screening on the postpartum 3rd day and need not wait for 6 wks when more than 50% is lost for follow-up. This study shows among GDM 60% of them have underlying beta cell dysfunction

"If I Don't Eat Enough, I Won't Be Healthy":Women's Experiences with Gestational Diabetes Mellitus Treatment in Rural and Urban South India

Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes as well as increased risk of future type 2 diabetes and cardiovascular disease. In India, 10%–35% of pregnant women develop GDM. In this study, we investigated women’s experiences with the dietary and pharmaceutical treatment for GDM in rural and urban Tamil Nadu, India. Semi-structured interviews were conducted with 19 women diagnosed with GDM. Data were analyzed using qualitative content analysis. Three overall aspects were discovered with several sub-aspects characterizing women’s experiences: emotional challenges (fear and apprehension for the baby’ health and struggling to accept a treatment seen as counterintuitive to being safe and healthy), interpersonal challenges (managing treatment in the near social relations and social support, and coordinating treatment with work and social life), and health system-related challenges (availability and cost of treatment, interaction with health care providers). Some aspects acted as barriers. However, social support and positive, high-quality interactions with health care providers could mitigate some of these barriers and facilitate the treatment process. Greater efforts at awareness creation in the social environment and systemic adjustments in care delivery targeting the individual, family, community and health system levels are needed in order to ensure that women with GDM have the opportunity to access treatment and are enabled and motivated to follow it as well

The effect of peri-conception hyperglycaemia and the involvement of the hexosamine biosynthesis pathway in mediating oocyte and embryo developmental competence

The environment that the oocyte is exposed to during the peri-conception period can have a significant impact on oocyte developmental competence (the ability of the oocyte to support fertilisation and subsequent embryo development) and the long-term health of the resulting offspring. This is particularly true for maternal hyperglycaemia. While maternal hyperglycaemia during early pregnancy through term development has been extensively studied, the effects on the oocyte itself, and the underlying mechanisms, remain largely unknown. There is increasing evidence, however, for the role of the fuel-sensing hexosamine biosynthesis pathway in mediating the effects of hyperglycaemia in many different cell types. In this review, we will focus on the reproductive consequences of maternal hyperglycaemia during the peri-conceptual period and the role of the hexosamine pathway in mediating these processes.Laura A. Frank, Melanie L. Sutton-McDowall, Robert B. Gilchrist, and Jeremy G. Thompso

Molecular bases of diabetic nephropathy

The determinant of the diabetic nephropathy is hyperglycemia, but hypertension and other genetic factors are also involved. Glomerulus is the focus of the injury, where mesangial cell proliferation and extracellular matrix occur because of the increase of the intra- and extracellular glucose concentration and overexpression of GLUT1. Sequentially, there are increases in the flow by the poliol pathway, oxidative stress, increased intracellular production of advanced glycation end products (AGEs), activation of the PKC pathway, increase of the activity of the hexosamine pathway, and activation of TGF-beta1. High glucose concentrations also increase angiotensin II (AII) levels. Therefore, glucose and AII exert similar effects in inducing extracellular matrix formation in the mesangial cells, using similar transductional signal, which increases TGF-beta1 levels. In this review we focus in the effect of glucose and AII in the mesangial cells in causing the events related to the genesis of diabetic nephropathy. The alterations in the signal pathways discussed in this review give support to the observational studies and clinical assays, where metabolic and antihypertensive controls obtained with angiotensin-converting inhibitors have shown important and additive effect in the prevention of the beginning and progression of diabetic nephropathy. New therapeutic strategies directed to the described intracellular events may give future additional benefits.O principal determinante da nefropatia diabética é a hiperglicemia, mas hipertensão e fatores genéticos também estão envolvidos. O glomérulo é o foco de lesão, onde proliferação celular mesangial e produção excessiva de matriz extracelular decorrem do aumento da glicose intracelular, por excesso de glicose extracelular e hiperexpressão de GLUT1. Seguem-se aumento do fluxo pela via dos polióis, estresse oxidativo intracelular, produção intracelular aumentada de produtos avançados da glicação não enzimática (AGEs), ativação da via da PKC, aumento da atividade da via das hexosaminas e ativação de TGF-beta1. Altas concentrações de glicose também aumentam angiotensina II (AII) nas células mesangiais por aumento intracelular da atividade da renina (ações intrácrinas, mediando efeitos proliferativos e inflamatórios diretamente). Portanto, glicose e AII exercem efeitos proliferativos celulares e de matriz extracelular nas células mesangiais, utilizando vias de transdução de sinais semelhantes, que levam a aumento de TGF-beta1. Nesse estudo são revisadas as vias que sinalizam os efeitos da glicose e AII nas células mesangiais em causar os eventos-chaves relacionados à gênese da glomerulopatia diabética. As alterações das vias de sinalização implicadas na glomerulopatia, aqui revisadas, suportam dados de estudos observacionais/ensaios clínicos, onde controle metabólico e anti-hipertensivo, especificamente com inibidores do sistema renina-angiotensina, têm-se mostrado importantes - e aditivos - na prevenção do início e progressão da nefropatia. Novas estratégias terapêuticas dirigidas aos eventos intracelulares descritos deverão futuramente promover benefício adicional.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)HC Instituto do Coração Unidade de HipertensãoUSP FMUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Laboratório de NefrologiaFundação Universitária de Cardiologia Instituto de Cardiologia Laboratório de Cardiologia Molecular e CelularUNIFESP, EPM, Laboratório de NefrologiaSciEL

AUTONOMIC NEUROPATHY AND DIABETIC FOOT SYNDROME

Introduction Autonomic Neuropathy in diabetics, contrary to the general belief that it is a late complication, can occur not only early in the natural course of the disease but even precede the diagnosis of diabetes, the best example being impotence. The assessment of autonomic neural involvement is usually done by evaluating cardiac autonomic reflex functions. The current evidence suggests that these tests reflect autonomic nervous damage not only in the heart but also elsewhere in the body. In the present study ninety six diabetic patients were screened for cardiovascular autonomic dysfunction using the four standard tests of cardiac autonomic functions namely (1) The heart rate response to Valsalva manoeuvre, (2) Heart rate variation during deep breathing (3) Blood pressure response to sustained hand grip and (4) immediate blood pressure response to standing from lying. The results of the study were correlated with the clinical symptoms of autonomic neuropathy and peripheral neuropathy in the patients tested. Materials and Methods Ninety six diabetic patients attending the Diabetic Clinic of the Govt. General Hospital, Madras formed the subjects of this study. Out of these ninety six subjects ten were insulin dependent diabetics and the rest were non-insulin dependent diabetics. The age group of the study subjects ranged from 20-60 years and the duration of diabetes from one year to 23 years. All were subjected to a careful clinical assessment, particular attention being given to the presence of clinical evidence of peripheral and autonomic neuropathy. A routine resting twelve lead ECG was done and detailed fundus examination was carried out. Patients with ECG evidence of IHD and those who had proliferative diabetic retinopathy were excluded from this study. Twenty age matched healthy controls were also assessed for the presence of cardiac autonomic neural dysfunction. Department of Diabetology, Madras Medical College & Govt. General Hospital, Madras-3. January, 1988 90 Study Protocol: All the ninety six subjects were subjected to the tests in the morning hours between 10 AM and 12 Noon. No smoking was allowed on the morning of the study and subjects were instructed not to take medications like aspirin, vitamins or anti-histamines for atleast 48 hours before the test. The results of the four tests were categorised and depending on it the subjects were put into one of the following four groups