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

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

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

Peer reviewedPublisher PD

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

Glucose Monitoring During Pregnancy

Self-monitoring of blood glucose in women with mild gestational diabetes has recently been proven to be useful in reducing the rates of fetal overgrowth and gestational weight gain. However, uncertainty remains with respect to the optimal frequency and timing of self-monitoring. A continuous glucose monitoring system may have utility in pregnant women with insulin-treated diabetes, especially for those women with blood sugars that are difficult to control or who experience nocturnal hypoglycemia; however, continuous glucose monitoring systems need additional study as part of larger, randomized trials

Monocyte Derived Microvesicles Deliver a Cell Death Message via Encapsulated Caspase-1

Apoptosis depends upon the activation of intracellular caspases which are classically induced by either an intrinsic (mitochondrial based) or extrinsic (cytokine) pathway. However, in the process of explaining how endotoxin activated monocytes are able to induce apoptosis of vascular smooth muscle cells when co-cultured, we uncovered a transcellular apoptosis inducing pathway that utilizes caspase-1 containing microvesicles. Endotoxin stimulated monocytes induce the cell death of VSMCs but this activity is found in 100,000 g pellets of cell free supernatants of these monocytes. This activity is not a direct effect of endotoxin, and is inhibited by the caspase-1 inhibitor YVADcmk but not by inhibitors of Fas-L, IL-1β and IL-18. Importantly, the apoptosis inducing activity co-purifies with 100 nm sized microvesicles as determined by TEM of the pellets. These microvesicles contain caspase-1 and caspase-1 encapsulation is required since disruption of microvesicular integrity destroys the apoptotic activity but not the caspase-1 enzymatic activity. Thus, monocytes are capable of delivering a cell death message which depends upon the release of microvesicles containing functional caspase-1. This transcellular apoptosis induction pathway describes a novel pathway for inflammation induced programmed cell death

Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Several recent studies have shown that angiotensin type 1 receptor (AT1) antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ). PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions.</p> <p>Methods</p> <p>We have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers) provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662.</p> <p>Results</p> <p>We observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co-administration of GW9662.</p> <p>Conclusion</p> <p>The results suggest that telmisartan provides effective neuroprotection against dopaminergic cell death and that the neuroprotective effect is mediated by PPAR-γ activation. However, the results in AT1-deficient mice show that blockage of AT1, unrelated to the pharmacological properties of AT1 blockers, also protects against dopaminergic cell death and neuroinflammation. Furthermore, the results show that PPAR-γ activation is involved in the anti-inflammatory and neuroprotective effects of AT1 deletion.</p